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35070298

The application of next-generation sequencing (NGS) in routine clinical analysis is still limited. The significance of NGS in the identification of pathogens of lower respiratory tract infection should be assessed as part of routine clinical bacterial examinations and chest imaging results. In the present study, the alveolar lavage fluid samples of 30 patients (25 males and 5 females, aged 19-92 years old, with a median age of 62) were examined by routine bacterial culture and NGS, and the results of pathogen detection and identification were compared. Chest imaging showed consolidation in all 30 patients (100%), and pleural effusion in 13 of the 30 patients (43.33%). The routine bacterial culture of the lavage solution was only positive in 14 of the 30 patients (46.6%), and negative in 16 patients (53.33%). However, the positive rate of NGS test results of the lavage fluid was 100%. A total of 12 cases (40%) were completely consistent with the routine bacterial culture test, with 56 other pathogens of mixed infection detected, accounting for the short comings of the routine bacterial examination. Although NGS cannot distinguish between live and dead bacteria, it is still a useful detection technology for accurate diagnosis of clinical infectious diseases. It is worthy of adaptation in the clinic for more effective clinical management and treatment of the lower respiratory airway infection in addition to the routine bacterial culture testing.

35046399

The onset of colorectal cancer (CRC) is often attributed to gut bacterial dysbiosis, and thus gut microbiota are highly relevant in devising treatment strategies. Certain gut microbes, like Enterococcus spp., exhibit remarkable anti-neoplastic and probiotic properties, which can aid in silver nanoparticle (AgNPs) induced reactive oxygen species (ROS)-based CRC treatment. However, the effects of AgNPs on gut microbial metabolism have not been reported thus far. In this study, a detailed systems-level understanding of ROS metabolism in Enterococcus durans (E. durans), a representative gut microbe, was gained using constraint-based modeling, wherein, the critical association between ROS and folate metabolism was established. Experimental studies involving low AgNP concentration treatment of E. durans cultures confirmed these modeling predictions (an increased extracellular folate concentration by 52%, at the 9^th h of microbial growth, was observed). Besides, the computational studies established various metabolic pathways involving amino acids, energy metabolites, nucleotides, and SCFAs as the key players in elevating folate levels on ROS exposure. The anti-cancer potential of E. durans was also studied through MTT analysis of HCT 116 cells treated with microbial culture (AgNP treated) supernatant. A decrease in cell viability by 19% implicated the role of microbial metabolites (primarily folate) in causing cell death. The genome-scale modeling approach was then extended to extensively model CRC metabolism, as well as CRC-E. durans interactions in the context of CRC treatment, using tissue-specific metabolic models of CRC and healthy colon. These findings on further validation can facilitate the development of robust and effective cancer therapy.

35031039

<h4>Background</h4>The role of dietary branched chain amino acids (BCAAs) and their effect on metabolic health is complex. How dietary BCAA levels and their interaction with background nutrition affect health is unclear. Here, we used meta-analysis and meta-regression, together with the nutritional modelling, to analyse the results of rodent studies that increased the level of dietary BCAAs and measured circulating levels, outcomes related to metabolic health, body mass and food intake.<h4>Results</h4>Across all studies, increasing dietary BCAAs resulted in increased levels of circulating BCAAs. These effects, however, were heavily moderated by background dietary levels whereby on high BCAA diets, further increases were not reflected in the blood. Impaired glucose tolerance was associated with elevated dietary BCAAs, with the greatest effect occurring with a simultaneous increase in total protein intake. Effects of dietary BCAAs on plasma glucose, insulin, or HOMA emerged only when dietary macronutrient background was considered. We found that elevated dietary BCAAs increases % body fat, with largest increases in adiposity occurring when BCAAs are increased on a high protein, low carbohydrate dietary background. Finally, we found that increased dietary BCAAs were associated with increased food intake when the background diet was low in BCAAs.<h4>Conclusion</h4>Our data highlights the interaction between BCAAs and background nutrition. We show that the effects of BCAAs on metabolic health cannot be studied in isolation but must be considered as part of complex mixture of dietary components.

34402639

A central paradigm in microbiome data analysis, which we term the genome-centric paradigm, is that a linear (non-branching) DNA sequence is the ideal representation of a microbial genome. This representation is natural, as microbes indeed have non-branching genomes. Tremendous discoveries in microbiology were made under this paradigm, but is it always optimal for microbiome research? In this Commentary, we claim that the realization of this paradigm in metagenomic assembly, a fundamental step in the "metagenomics analysis pipeline," suboptimally models the extensive genomic variability present in the microbiome. We outline our efforts to address these issues with a "genome-free" approach that eschews linear genomic representations in favor of a pan-metagenomic graph.

35163976

The effects of copper addition, from various adsorbents, on the accumulation ability and glucosinolate content of cultivated rocket were studied. Different adsorbents (zeolite NaX, egg shells, substrate, fly ash) were treated with copper(II) solution with an adsorption efficiency of 98.36, 96.67, 51.82 and 39.13%, respectively. The lowest copper content and the highest total glucosinolate content (44.37 μg/g DW and 4269.31 µg/g DW, respectively) were detected in the rocket grown in the substrate with the addition of a substrate spiked with copper(II) ions. Rocket grown in the fly ash-substrate mixture showed an increase in copper content (84.98 μg/g DW) and the lowest total glucosinolate content (2545.71 µg/g DW). On the other hand, when using the egg shells-substrate mixture, the rocket copper content increased (113.34 μg/g DW) along with the total GSLs content (3780.03 µg/g DW), indicating the influence of an adsorbent type in addition to the copper uptake. The highest copper content of 498.56 μg/g DW was detected in the rocket watered with copper(II) solution with a notable decrease in the glucosinolate content, i.e., 2699.29 µg/g DW. According to these results rocket can be considered as a copper accumulator plant.

34638398

The complexity of head and neck cancers (HNC) mandates a multidisciplinary approach and radiation therapy (RT) plays a critical role in the optimal management of patients with HNC, either as frontline or adjuvant treatment postoperatively. The advent of both definitive and post-operative RT has significantly improved the outcomes of patients with HNC. Herein, we discuss the role of postoperative RT in different subtypes of HNC, its side effects, and the importance of surveillance. The treatment regions discussed in this paper are the oral cavity, nasopharynx, paranasal sinus cavity, oropharynx, larynx and hypopharynx. Multiple studies that demonstrate the importance of definitive and/or postoperative RT, which led to an improved outlook of survival for HNC patients will be discussed.

34970241

Plant secondary metabolites (SMs) play a crucial role in plant defense against pathogens and adaptation to environmental stresses, some of which are produced from medicinal plants and are the material basis of clinical efficacy and vital indicators for quality evaluation of corresponding medicinal materials. The influence of plant microbiota on plant nutrient uptake, production, and stress tolerance has been revealed, but the associations between plant microbiota and the accumulation of SMs in medicinal plants remain largely unknown. Plant SMs can vary among individuals, which could be partly ascribed to the shift in microbial community associated with the plant host. In the present study, we sampled fine roots and rhizosphere soils of <i>Sophora flavescens</i> grown in four well-separated cities/counties in China and determined the taxonomic composition of rhizosphere bacterial communities using Illumina 16S amplicon sequencing. In addition, the association of the rhizosphere bacterial microbiota with the accumulation of alkaloids in the roots of <i>S. flavescens</i> was analyzed. The results showed that <i>S. flavescens</i> hosted distinct bacterial communities in the rhizosphere across geographic locations and plant ages, also indicating that geographic location was a larger source of variation than plant age. Moreover, redundancy analysis revealed that spatial, climatic (mean annual temperature and precipitation), and edaphic factors (pH and available N and P) were the key drivers that shape the rhizosphere bacterial communities. Furthermore, the results of the Mantel test demonstrated that the rhizosphere bacterial microbiota was remarkably correlated with the contents of oxymatrine, sophoridine, and matrine + oxymatrine in roots. Specific taxa belonging to Actinobacteria and Chloroflexi were identified as potential beneficial bacteria associated with the total accumulation of matrine and oxymatrine by a random forest machine learning algorithm. Finally, the structural equation modeling indicated that the Actinobacteria phylum had a direct effect on the total accumulation of matrine and oxymatrine. The present study addresses the association between the rhizosphere bacterial communities and the accumulation of alkaloids in the medicinal plant <i>S. flavescens</i>. Our findings may provide a basis for the quality improvement and sustainable utilization of this medicinal plant thorough rhizosphere microbiota manipulation.

34725401

The mosquito Aedes aegypti is the major vector of arboviruses like dengue, Zika and chikungunya viruses. Attempts to reduce arboviruses emergence focusing on Ae. aegypti control has proven challenging due to the increase of insecticide resistances. An emerging strategy which consists of releasing Ae. aegypti artificially infected with Wolbachia in natural mosquito populations is currently being developed. The monitoring of Wolbachia-positive Ae. aegypti in the field is performed in order to ensure the program effectiveness. Here, the reliability of the Matrix‑Assisted Laser Desorption Ionization‑Time Of Flight (MALDI‑TOF) coupled with the machine learning methods like Convolutional Neural Network (CNN) to detect Wolbachia in field Ae. aegypti was assessed for the first time. For this purpose, laboratory reared and field Ae. aegypti were analyzed. The results showed that the CNN recognized Ae. aegypti spectral patterns associated with Wolbachia-infection. The MALDI-TOF coupled with the CNN (sensitivity = 93%, specificity = 99%, accuracy = 97%) was more efficient than the loop-mediated isothermal amplification (LAMP), and as efficient as qPCR for Wolbachia detection. It therefore represents an interesting method to evaluate the prevalence of Wolbachia in field Ae. aegypti mosquitoes.

35053105

Fulminant myocarditis causes impaired cardiac function, leading to poor prognosis and heart failure. Cell sheet engineering is an effective therapeutic option for improving cardiac function. Naïve blood mononuclear cells (MNCs) have been previously shown to enhance the quality and quantity of cellular fractions (QQMNCs) with anti-inflammatory and vasculogenic potential using the one culture system. Herein, we investigated whether autologous cell sheet transplant with QQMNCs improves cardiac function in a rat model with experimental autoimmune myocarditis (EAM). Fibroblast sheets (F-sheet), prepared from EAM rats, were co-cultured with or without QQMNCs (QQ+F sheet) on temperature-responsive dishes. QQ+F sheet induced higher expression of anti-inflammatory and vasculogenic genes (Vegf-b, Hgf, Il-10, and Mrc1/Cd206) than the F sheet. EAM rats were transplanted with either QQ+F sheet or F-sheet, and the left ventricular (LV) hemodynamic analysis was performed using cardiac catheterization. Among the three groups (QQ+F sheet, F-sheet, operation control), the QQ+F sheet transplant group showed alleviation of end-diastolic pressure-volume relationship on a volume load to the same level as that in the healthy group. Histological analysis revealed that QQ+F sheet transplantation promoted revascularization and mitigated fibrosis by limiting LV remodeling. Therefore, autologous QQMNC-modified F-sheets may be a beneficial therapeutic option for EAM.

34811848

A high-fat diet (HFD) leads to long-term exposure to gut microbial metabolite secondary bile acids, such as deoxycholic acid (DCA), in the intestine, which is closely linked to colorectal cancer (CRC). Evidence reveals that vasculogenic mimicry (VM) is a critical event for the malignant transformation of cancer. Therefore, this study investigated the crucial roles of DCA in the regulation of VM and the progression of intestinal carcinogenesis. The effects of an HFD on VM formation and epithelial-mesenchymal transition (EMT) in human CRC tissues were investigated. The fecal DCA level was detected in HFD-treated Apc^min/+ mice. Then the effects of DCA on VM formation, EMT, and vascular endothelial growth factor receptor 2 (VEGFR2) signaling were evaluated in vitro and in vivo. Here we demonstrated that compared with a normal diet, an HFD exacerbated VM formation and EMT in CRC patients. An HFD could alter the composition of the gut microbiota and significantly increase the fecal DCA level in Apc^min/+ mice. More importantly, DCA promoted tumor cell proliferation, induced EMT, increased VM formation, and activated VEGFR2, which led to intestinal carcinogenesis. In addition, DCA enhanced the proliferation and migration of HCT-116 cells, and induced EMT process and vitro tube formation. Furthermore, the silence of VEGFR2 reduced DCA-induced EMT, VM formation, and migration. Collectively, our results indicated that microbial metabolite DCA promoted VM formation and EMT through VEGFR2 activation, which further exacerbated intestinal carcinogenesis.

34468309

Infection of wMel Wolbachia in Aedes aegypti imparts two signature features that enable its application for biocontrol of dengue. First, the susceptibility of mosquitoes to viruses such as dengue and Zika is reduced. Second, a reproductive manipulation is caused that enables wMel introgression into wild-type mosquito populations. The long-term success of this method relies, in part, on evolution of the wMel genome not compromising the critical features that make it an attractive biocontrol tool. This study compared the wMel Wolbachia genome at the time of initial releases and 1-7 years post-release in Cairns, Australia. Our results show the wMel genome remains highly conserved up to 7 years post-release in gene sequence, content, synteny and structure. This work suggests the wMel genome is stable in its new mosquito host and, therefore, provides reassurance on the potential for wMel to deliver long-term public-health impacts.

32432696

Comparing ecological communities across environmental gradients can be challenging, especially when the number of different taxonomic groups in the communities is large. In this setting, community-level summaries called diversity indices are widely used to detect changes in the community ecology. However, estimation of diversity indices has received relatively little attention from the statistical community. The most common estimates of diversity are the maximum likelihood estimates of the parameters of a multinomial model, even though the multinomial model implies strict assumptions about the sampling mechanism. In particular, the multinomial model prohibits ecological networks, where taxa positively and negatively co-occur. In this article, we leverage models from the compositional data literature that explicitly account for co-occurrence networks and use them to estimate diversity. Instead of proposing new diversity indices, we estimate popular diversity indices under these models. While the methodology is general, we illustrate the approach for the estimation of the Shannon, Simpson, Bray-Curtis, and Euclidean diversity indices. We contrast our method to multinomial, low-rank, and nonparametric methods for estimating diversity indices. Under simulation, we find that the greatest gains of the method are in strongly networked communities with many taxa. Therefore, to illustrate the method, we analyze the microbiome of seafloor basalts based on a 16S amplicon sequencing dataset with 1425 taxa and 12 communities.

34830706

Type 2 diabetes mellitus (T2DM) is a growing public health challenge for Thailand (current prevalence ~10.0%). Amino acids offer novel biomarkers to predict risk of T2DM and indicate sub-optimal disease management, which could facilitate earlier treatment. We studied amino acid profiles in a Thai cohort comprising of individuals with T2DM (n = 65 single-drug-treated; n = 38 multi-drug-treated) compared to healthy controls (n = 104) using liquid chromatography-mass spectrometry. Age and BMI were significantly lower in the healthy controls compared to the single or multi-treated T2DM groups. The BCAA (leucine and valine) were significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p < 0.001) and isoleucine was significantly lower in the single-treated compared to the healthy controls (p = 0.014). These findings beg the question whether BCAAs supplementation be beneficial in T2DM patients treated with single or multi-drug therapy? Tyrosine was significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p = 0.002), whereas phenylalanine was significantly higher in the multi-treated T2DM group compared to the single treated T2DM group (p = 0.045). We provide novel insights into the effects of diabetes treatments on these amino acids in insulin resistant states such as T2DM in a unique but understudied Thai population.

35098260

<h4>Background</h4>Cardiovascular disease (CVD) remains the leading cause of death in the US. Although physical activity (PA) has been inversely associated with the risk of CVD, few studies have examined whether sedentary behaviors modify such association. Our goal was to examine associations of leisure time PA with risk of CVD and mortality and the role of sedentary behavior as potential effect modifier among US veterans.<h4>Methods</h4>We analyzed self-reported data on leisure time PA, television watching, and time spent on the computer among 438,364 participants of the Veterans Affairs Million Veteran Program from 2011 to 2018. We calculated metabolic equivalent of task-hours per week (MET-h/week) for each person and used electronic health record data to ascertain CVD.<h4>Results</h4>Mean age was 64.6 ± 12.6 years and 92% were men. During a mean follow up of 3.3 years, we observed 22,942 new cases of CVD and 48,325 deaths. There was an inverse relation of leisure time PA with CVD and total mortality [HR: 0.96 (0.95-0.97) and 0.91 (0.90-0.92) per 2 MET-h/week increment for CVD and total mortality, respectively]. The associations of PA with both incident CVD and mortality were stronger in participants who spent more time watching television or on computer (all p values for interaction < 0.01). No interaction of PA with time spent on video game was observed (p>0.05).<h4>Conclusions</h4>Leisure time PA is inversely associated with risk of CVD and mortality among US veterans and such relations were stronger in participants who spent more time watching television or on computer.

34884730

The search of substrates for solute carriers (SLCs) constitutes a major issue, owing notably to the role played by some SLCs, such as the renal electrogenic organic cation transporter (OCT) 2 (SLC22A2), in pharmacokinetics, drug-drug interactions and drug toxicity. For this purpose, substrates have been proposed to be identified by their cis-inhibition and trans-stimulation properties towards transporter activity. To get insights on the sensitivity of this approach for identifying SLC substrates, 15 various exogenous and endogenous OCT2 substrates were analysed in the present study, using 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (DiASP) as a fluorescent OCT2 tracer substrate. All OCT2 substrates cis-inhibited DiASP uptake in OCT2-overexpressing HEK293 cells, with IC50 values ranging from 0.24 µM (for ipratropium) to 2.39 mM (for dopamine). By contrast, only 4/15 substrates, i.e., acetylcholine, agmatine, choline and metformin, trans-stimulated DiASP uptake, with a full suppression of the trans-stimulating effect of metformin by the reference OCT2 inhibitor amitriptyline. An analysis of molecular descriptors next indicated that trans-stimulating OCT2 substrates exhibit lower molecular weight, volume, polarizability and lipophilicity than non-trans-stimulating counterparts. Overall, these data indicated a rather low sensitivity (26.7%) of the trans-stimulation assay for identifying OCT2 substrates, and caution with respect to the use of such assay may therefore be considered.

34759670

<h4>Purpose</h4>Certain ocular resident or pathogenic microbes may remain viable in the presence of multi-purpose disinfectant solutions (MPDSs), subsequently developing biofilms inside contact lens storage cases (CLSCs) which pose a risk of infection to wearers. This study evaluated the formation of ocular microbiota biofilms exposed to three top selling MPDS.<h4>Methods</h4>Crystal violet assay was carried out for the verification of biofilm formation. The <i>in vitro</i> assays evaluated <i>Pseudomonas aeruginosa</i> UFPEDA 416 and <i>Staphylococcus aureus</i> UFPEDA 02 exposure of 48 h to MPDS, as well as the use of 40 KHz ultrasound at the beginning and with 24 h immersion in the MPDS. Subsequently, <i>in vivo</i> assays evaluated the formation of microbial biofilms on the CLSC walls containing silicone-hydrogel contact lenses immersed in MPDS from 15 healthy volunteer patients, who had been wearing the lenses for 7 days.<h4>Results</h4>Biofilms were inhibited by 26%-98% in the <i>in vitro</i> assays, with a statistically significant difference only for <i>P. aeruginosa</i> UFPEDA 416 exposed to diluted MPDS. Most inhibitions occurred moderately and weakly. In addition, adherent cells were detected in more than 90% of the tests. Biofilm was not inhibited in more than one third of the results, nor was it disturbed, especially with the ultrasound treatments. The average of obtained optical densities at 590 nm was between 0.6 and 0.8 in the <i>in vivo</i> assays. The results were similar between the CLSC right and left wells. There was a correlation between microbial biofilm formation and the type of MPDS tested, with statistical difference between the three treatments.<h4>Conclusion</h4>MPDS promoted a partial inhibition of microbial biofilm formation but only one MPDS proved to be more effective <i>in vitro</i> and <i>in vivo</i>. This study, however, could not distinguish the effect of possible errors in the good hygiene practices of the users.

34844659

<h4>Absract</h4>BACKGROUND: To describe the course and intervention of an hospital-wide IMI-Producing Enterobacter ludwigii outbreak.<h4>Methods</h4>This was an outbreak interventional study, done at a tertiary care center in Tel-Aviv, Israel. Data was collected on the course of the outbreak and the demographic and clinical characteristics of all patients involved in the outbreak. The intervention measures included patients' cohorting, contact isolation precautions, environmental cleaning and screening of contacts. The molecular features and phylogeny of outbreak-related isolates were studied by whole-genome based analysis.<h4>Results</h4>The outbreak included 34 patients that were colonized by IMI-Producing E. ludwigii and were identified in 24 wards throughout the hospital. Colonization was identified in the first 72 h of admission in 13/34 patients (38.2%). Most patients (91.2%) were admitted from home and had relatively low level of comorbidities. The majority of them (88%) had no recent use of invasive catheters and none had previous carriage of other multi-drug resistant bacteria. All available isolates harbored the bla_IMI-17 allele and belonged to Sequence-Type 385. With the exception of two isolates, all isolates were closely related with less than a 20-SNP difference between them.<h4>Conclusions</h4>This outbreak had most likely originated in the community and subsequently disseminated inside our institution. More studies are required in order to elucidate the epidemiology of IMI-Producing E. ludwigii and the possible role of environmental sources in its dissemination.

34959936

Recent interest in the gut-brain-axis has highlighted the potential of prebiotics to impact wellbeing, and to affect behavioral change in humans. In this clinical trial, we examined the impact of four-weeks daily supplementation of galacto-oligosaccharides (GOS) on self-reported nutrient intake and relationships on gut microbiota in a four-week two-armed parallel double-blind placebo controlled GOS supplement trial in young adult females. Food diaries and stool samples were collected prior to and following 28 days of supplement consumption. It was found that four weeks of GOS supplementation influenced macronutrient intake, as evident by reduced carbohydrate and sugars and increased fats intake. Further analysis showed that the reduction in carbohydrates was predicted by increasing abundances of Bifidobacterium in the GOS group in comparison to the placebo group. This suggests that Bifidobacterium increase via GOS supplementation may help improve the gut microbiota composition by altering the desire for specific types of carbohydrates and boosting Bifidobacterium availability when fiber intake is below recommended levels, without compromising appetite for fiber from food.

34532031

Docosahexaenoic acid (DHA) is the predominant omega-3 long-chain polyunsaturated fatty acid found in human brain and eyes. There are a number of studies in the literature showing the health benefits of DHA. It is critical throughout all life stages from the need for fetal development, the prevention of preterm birth, and the prevention of cardiovascular disease to the improvements in the cognitive function and the eye health of adults and elderly. These benefits might be related to the modulation of gut microbiota by DHA. In addition, there are some discrepancies in the literature regarding certain health benefits of DHA, and this review is intended to explore and understand these discrepancies. Besides the variations in the DHA contents of different supplement sources, bioavailability is crucial for the efficacy of DHA supplements, which depends on several factors. For example, DHA in phospholipid and triglyceride forms are more readily to be absorbed by the body than that in ethyl ester form. In addition, dietary lipids in meals and emulsification of DHA oil can increase the bioavailability of DHA. Estrogens stimulated the biosynthesis of DHA, whereas testosterone stimulus induced a decrease in DHA. The roles of DHA through human lifespan, the sources, and its recommended daily intake in different countries are also discussed to provide a better understanding of the importance of this review.

35277080

The composition of the gut microbiota and their metabolites are associated with cardiometabolic health and disease risk. Intake of dietary fibers, including resistant starch (RS), has been shown to favorably affect the health of the gut microbiome. The aim of this research was to measure changes in the gut microbiota and fecal short-chain fatty acids as part of a randomized, crossover supplemental feeding study. Fifty participants (68% female, aged 40 ± 13 years, BMI 24.5 ± 3.6 kg/m²) completed this study. Potato dishes (POT) contained more RS than refined grain dishes (REF) (POT: 1.31% wet basis (95% CI: 0.94, 1.71); REF: 0.73% wet basis (95% CI: 0.34, 1.14); <i>p</i> = 0.03). Overall, potato dish consumption decreased alpha diversity, but beta diversity was not impacted. Potato dish consumption was found to increase the abundance of <i>Hungatella xylanolytica</i>, as well as that of the butyrate producing <i>Roseburia faecis</i>, though fecal butyrate levels were unchanged. Intake of one potato-based side dish per day resulted in modest changes in gut microbiota composition and diversity, compared to isocaloric intake of refined grains in healthy adults. Studies examining foods naturally higher in RS are needed to understand microbiota changes in response to dietary intake of RS and associated health effects.

34917123

Chimonanthus of Calycanthaceae is a small endemic genus in China, with unusual winter-blooming sweet flowers widely cultivated for ornamentals and medicinal uses. The evolution of Chimonanthus plastomes and its phylogenetic relationships remain unresolved due to limited availability of genetic resources. Here, we report fully assembled and annotated chloroplast genomes of five Chimonanthus species. The chloroplast genomes of the genus (size range 153,010 - 153,299 bp) reveal high similarities in gene content, gene order, GC content, codon usage, amino acid frequency, simple sequence repeats, oligonucleotide repeats, synonymous and non-synonymous substitutions, and transition and transversion substitutions. Signatures of positive selection are detected in atpF and rpoB genes in C. campanulatus. The correlations among substitutions, InDels, and oligonucleotide repeats reveal weak to strong correlations in distantly related species at the intergeneric levels, and very weak to weak correlations among closely related Chimonanthus species. Chloroplast genomes are used to reconstruct a well-resolved phylogenetic tree, which supports the monophyly of Chimonanthus. Within Chimonanthus, C. praecox and C. campanulatus form one clade, while C. grammatus, C. salicifolius, C. zhejiangensis, and C. nitens constitute another clade. Chimonanthus nitens appears paraphyletic and is closely related to C. salicifolius and C. zhejiangensis, suggesting the need to reevaluate the species delimitation of C. nitens. Chimonanthus and Calycanthus diverged in mid-Oligocene; the radiation of extant Chimonanthus species was dated to the mid-Miocene, while C. grammatus diverged from other Chimonanthus species in the late Miocene. C. salicifolius, C. nitens (a), and C. zhejiangensis are inferred to have diverged in the Pleistocene of the Quaternary period, suggesting recent speciation of a relict lineage in the subtropical forest regions in eastern China. This study provides important insights into the chloroplast genome features and evolutionary history of Chimonanthus and family Calycanthaceae.

35058973

Advances in next-generation sequencing (NGS) have revolutionized microbial studies in many fields, especially in clinical investigation. As the second human genome, microbiota has been recognized as a new approach and perspective to understand the biological and pathologic basis of various diseases. However, massive amounts of sequencing data remain a huge challenge to researchers, especially those who are unfamiliar with microbial data analysis. The mathematic algorithm and approaches introduced from another scientific field will bring a bewildering array of computational tools and acquire higher quality of script experience. Moreover, a large cohort research together with extensive meta-data including age, body mass index (BMI), gender, medical results, and others related to subjects also aggravate this situation. Thus, it is necessary to develop an efficient and convenient software for clinical microbiome data analysis. EasyMicroPlot (EMP) package aims to provide an easy-to-use microbial analysis tool based on R platform that accomplishes the core tasks of metagenomic downstream analysis, specially designed by incorporation of popular microbial analysis and visualization used in clinical microbial studies. To illustrate how EMP works, 694 bio-samples from Guangdong Gut Microbiome Project (GGMP) were selected and analyzed with EMP package. Our analysis demonstrated the influence of dietary style on gut microbiota and proved EMP package's powerful ability and excellent convenience to address problems for this field.

34859110

<h4>Background</h4>Febrile neutropenia (FN) is a frequent complication in immunocompromised patients. However, causative microorganisms are detected in only 10% of patients. This study aimed to detect the microorganisms that cause FN using next-generation sequencing (NGS) to identify the genome derived from pathogenic microorganisms in the bloodstream. Here, we implemented a metagenomic approach to comprehensively analyze microorganisms present in clinical samples from patients with FN.<h4>Methods</h4>FN is defined as a neutrophil count <500 cells/µL and fever ≥37.5°C. Plasma/serum samples of 112 pediatric patients with FN and 10 patients with neutropenia without fever (NE) were sequenced by NGS and analyzed by a metagenomic pipeline, PATHDET.<h4>Results</h4>The putative pathogens were detected by NGS in 5 of 10 FN patients with positive blood culture results, 15 of 87 FN patients (17%) with negative blood culture results, and 3 of 8 NE patients. Several bacteria that were common in the oral, skin, and gut flora were commonly detected in blood samples, suggesting translocation of the human microbiota to the bloodstream in the setting of neutropenia. The cluster analysis of the microbiota in blood samples using NGS demonstrated that the representative bacteria of each cluster were mostly consistent with the pathogens in each patient.<h4>Conclusions</h4>NGS technique has great potential for detecting causative pathogens in patients with FN. Cluster analysis, which extracts characteristic microorganisms from a complex microbial population, may be effective to detect pathogens in minute quantities of microbiota, such as those from the bloodstream.

34711536

35023778

Magnetosome gene clusters (MGCs), which are responsible for magnetosome biosynthesis and organization in magnetotactic bacteria (MTB), are the key to deciphering the mechanisms and evolutionary origin of magnetoreception, organelle biogenesis, and intracellular biomineralization in bacteria. Here, we report the development of MagCluster, a Python stand-alone tool for efficient exploration of MGCs from large-scale (meta)genomic data.

34947853

Forensic microbiomics is a promising tool for crime investigation. Geolocation, which connects an individual to a certain place or location by microbiota, has been fairly well studied in the literature, and several applications have been found. The aim of this review is to highlight the main findings in this field, including the current sample storage, DNA extraction, sequencing and data analysis techniques that are being used, and its potential applications in human trafficking and ancient DNA studies. Second, the challenges and limitations of forensic microbiomics and geolocation are emphasised, providing recommendations for the establishment of this tool in the forensic science community.

35008983

Alzheimer's disease (AD) is a progressive neurodegenerative disease with a multifactorial etiology. A multitarget treatment that modulates multifaceted biological functions might be more effective than a single-target approach. Here, the therapeutic efficacy of combination treatment using anti-Aβ antibody NP106 and curcumin analog TML-6 versus monotherapy was investigated in an APP/PS1 mouse model of AD. Our data demonstrate that both combination treatment and monotherapy attenuated brain Aβ and improved the nesting behavioral deficit to varying degrees. Importantly, the combination treatment group had the lowest Aβ levels, and insoluble forms of Aβ were reduced most effectively. The nesting performance of APP/PS1 mice receiving combination treatment was better than that of other APP/PS1 groups. Further findings indicate that enhanced microglial Aβ phagocytosis and lower levels of proinflammatory cytokines were concurrent with the aforementioned effects of NP106 in combination with TML-6. Intriguingly, combination treatment also normalized the gut microbiota of APP/PS1 mice to levels resembling the wild-type control. Taken together, combination treatment outperformed NP106 or TML-6 monotherapy in ameliorating Aβ pathology and the nesting behavioral deficit in APP/PS1 mice. The superior effect might result from a more potent modulation of microglial function, cerebral inflammation, and the gut microbiota. This innovative treatment paradigm confers a new avenue to develop more efficacious AD treatments.

34680623

Stink bugs (Hemiptera: Pentatomidae) are polyphagous pests that cause significant economic losses to a variety of crops. Although many species have been documented to aggregate within agricultural fields, much less is known regarding the timing and distribution of adults and nymphs within and between surrounding non-crop habitat. Therefore, we explored the spatiotemporal distribution of Euschistus servus (Say), Euschistus tristigmus (Say), and Chinavia hilaris (Say), three species of North American origin, and examined whether distribution patterns varied between species according to habitat. Stink bugs were monitored weekly for three years within an 18 km2 grid of pheromone-baited traps. We tested whether habitat affected distribution patterns, used spatial analysis by distance indices (SADIE) to identify aggregations, and visualized distributions with interpolated maps. Overall, E. servus adults were captured in crops, whereas E. tristigmus adults and nymphs were mainly captured in forests. Accordingly, distribution patterns of E. tristigmus were relatively stable over time, whereas aggregations of adult E. servus varied over space, and the timing of aggregations reflected the phenology of major crops. Chinavia hilaris was most often captured in forest, followed by crop habitat. Pest management strategies for stink bugs may require an area-based management approach that accounts for movement in agricultural fields and surrounding habitat.

34723959

The study of microbial communities and their interactions has attracted the interest of the scientific community, because of their potential for applications in biotechnology, ecology and medicine. The complexity of interspecies interactions, which are key for the macroscopic behavior of microbial communities, cannot be studied easily experimentally. For this reason, the modeling of microbial communities has begun to leverage the knowledge of established constraint-based methods, which have long been used for studying and analyzing the microbial metabolism of individual species based on genome-scale metabolic reconstructions of microorganisms. A main problem of genome-scale metabolic reconstructions is that they usually contain metabolic gaps due to genome misannotations and unknown enzyme functions. This problem is traditionally solved by using gap-filling algorithms that add biochemical reactions from external databases to the metabolic reconstruction, in order to restore model growth. However, gap-filling algorithms could evolve by taking into account metabolic interactions among species that coexist in microbial communities. In this work, a gap-filling method that resolves metabolic gaps at the community level was developed. The efficacy of the algorithm was tested by analyzing its ability to resolve metabolic gaps on a synthetic community of auxotrophic Escherichia coli strains. Subsequently, the algorithm was applied to resolve metabolic gaps and predict metabolic interactions in a community of Bifidobacterium adolescentis and Faecalibacterium prausnitzii, two species present in the human gut microbiota, and in an experimentally studied community of Dehalobacter and Bacteroidales species of the ACT-3 community. The community gap-filling method can facilitate the improvement of metabolic models and the identification of metabolic interactions that are difficult to identify experimentally in microbial communities.

34970712

We investigated the prevalence of coronaviruses in 44 bats from four families in northeastern Eswatini using high-throughput sequencing of fecal samples. We found evidence of coronaviruses in 18% of the bats. We recovered full or near-full-length genomes from two bat species: Chaerephon pumilus and Afronycteris nana, as well as additional coronavirus genome fragments from C. pumilus, Epomophorus wahlbergi, Mops condylurus, and Scotophilus dinganii. All bats from which we detected coronaviruses were captured leaving buildings or near human settlements, demonstrating the importance of continued surveillance of coronaviruses in bats to better understand the prevalence, diversity, and potential risks for spillover.

34688270

<h4>Background</h4>Bacterial vaginosis (BV) is associated with a higher risk of preterm delivery and spontaneous abortion. Yet little data on BV prevalence exist for sub-Saharan countries. The aim of this study was to estimate the prevalence of bacterial vaginosis and associated risk factors among pregnant women in Senegal.<h4>Methods</h4>From October 2013 to December 2018, pregnant women in their third trimester were recruited in two primary health centers (one suburban, one rural) in Senegal. Healthcare workers interviewed women and collected a lower vaginal swab and a blood sample. Vaginal flora were classified into four categories using vaginal smear microscopic examination and Gram's coloration. In our study, BV was defined as vaginal flora with no Lactobacillus spp. Variables associated with BV were analyzed using STATA® through univariate and multivariate analysis.<h4>Results</h4>A total of 457 women provided a vaginal sample for analysis. Overall, BV prevalence was 18.6% (85/457) [95% CI 15.4-22.6]) and was similar in suburban and rural areas (18.9% versus 18.1%, p = 0.843). Multivariate analysis showed that primigravidity was the only factor independently associated with a lower risk of BV (aOR 0.35 [95% CI 0.17-0.72]).<h4>Conclusions</h4>Our study showed significant BV prevalence among pregnant women in Senegal. Although the literature has underscored the potential consequences of BV for obstetric outcomes, data are scarce on BV prevalence in sub-Saharan African countries. Before authorities consider systematic BV screening for pregnant women, a larger study would be useful in documenting prevalence, risk factors and the impact of BV on pregnancy outcomes.

35050030

Many plants adapted to harsh environments have evolved low seed mass ('light seeds') with specific dispersal strategies, primarily either by wind (anemochory) or water (hydrochory). However, the role of their seed microbiota in their survival, and their seed microbial abundance and structure, remain insufficiently studied. Herein, we studied the light seed microbiome of eight anemochores and two hydrochores (as controls) collected from four provinces in China, using qPCR and metagenomic sequencing targeting both bacteria and fungi. Substantial variations were found for seed endophytic fungi (9.9 × 1010~7.3 × 102 gene copy numbers per seed) and bacteria (1.7 × 1010~8.0 × 106). Seed microbial diversity and structure were mainly driven by the plant genotype (species), with weak influences from their host plant classification level or dispersal mode. Seed microbial composition differences were clear at the microbial phylum level, with dominant proportions (~75%) for Proteobacteria and Ascomycota. The light seeds studied harbored unique microbial signatures, sharing only two Halomonas amplicon sequence variants (ASVs) and two fungal ASVs affiliated to Alternaria and Cladosporium. A genome-level functional profile analysis revealed that seed bacterial microbiota were enriched in amino acid, nucleoside, and nucleotide biosynthesis, while in fungal communities the generation of precursor metabolites and respiration were more highly represented. Together, these novel insights provide a deeper understanding of highly diversified plant-specific light seed microbiota and ecological strategies for plants in harsh environments.

34977651

<h4>Purpose</h4>To analyze recent trends in orthopaedic surgery consolidation and quantify these changes temporally and geographically from 2012 to 2020.<h4>Methods</h4>We performed a retrospective cross-sectional analysis of orthopaedic surgeon practice size in the United States using 2012 and 2020 data obtained from the Physician Compare database.<h4>Results</h4>Although we observed an increase from 21,216 unique orthopaedic surgeons in 2012 to 21,553 in 2020 (1.6% increase), the number of practices experienced a large decrease from 7,299 practices in 2012 to 5,829 in 2020 (20.1% decrease). The proportion of orthopaedic surgeons working in solo practices decreased from 13.2% (2,790) in 2012 to 7.4% (1,595) in 2020, and the proportion of orthopaedic surgeons working in groups sized 2 to 24 decreased from 35.3% (7,482) in 2012 to 22.2% (4,775) in 2020. In contrast, groups sized 25 to 99 have grown from 20.7% (4,387) of all orthopaedic surgeons to 23.4% (5,048) in 2020. Groups sized 100 to 499 have increased from 16.9% (3,593) in 2012 to 24.1% (5,190) in 2020, whereas groups sized 500 or greater have grown from 14% (2,964) in 2012 to 22.9% (4,945) in 2020. The number of unique group practices showed a significant decrease in the number of solo groups, which comprised 43.8% (3,200) of the total number of individual practices in 2012, decreasing to 32% (1,886) in 2020. All other groups increased in number and proportionally from 2012 to 2020.<h4>Conclusions</h4>This study shows that over the period from 2012 to 2020, there has been a substantial trend of orthopaedic surgeons shifting to increasing practice sizes, potentially indicating that more orthopaedic surgeons are working for large health care organizations rather than small independent practices.<h4>Clinical relevance</h4>The impact of these changes should be examined to determine large-scale effects on patient care, payment models, access, and outcomes, along with physician compensation, lifestyle, and satisfaction.

35139102

Mechanisms promoting coexistence between closely related species are fundamental for maintaining species diversity. Mechanisms of niche differentiation include allochrony which offsets the peak timing of resource utilisation between species. Many studies focus on spatial and temporal niche partitioning during the breeding season, few have investigated the role allochrony plays in influencing interspecific segregation of foraging distribution and ecology between congeneric species during the non-breeding season. We investigated the non-breeding migrations of Snares (Eudyptes robustus) and Fiordland penguins (Eudyptes pachyrhynchus), closely related species breeding between 100-350 km apart whose migration phenology differs by two months. Using light geolocation tracking, we examined the degree of overlap given the observed allochrony and a hypothetical scenario where the species commence migration simultaneously. We found that Fiordland penguins migrated to the Sub-Antarctic Frontal Zone and Polar Frontal Zone in the austral autumn whereas Snares penguins disperse westwards staying north of the Sub-Tropical Front in the austral winter. Our results suggest that allochrony is likely to be at the root of segregation because the relative profitability of the different water masses that the penguins forage in changes seasonally which results in the two species utilising different areas over their core non-breeding periods. Furthermore, allochrony reduces relatively higher levels of spatiotemporal overlap during the departure and arrival periods, when the close proximity of the two species' colonies would cause the birds to congregate in similar areas, resulting in high interspecific competition just before the breeding season. Available evidence from other studies suggests that the shift in phenology between these species has arisen from adaptive radiation and phenological matching to the seasonality of local resource availability during the breeding season and reduced competitive overlap over the non-breeding season is likely to be an incidental outcome.

34832406

Angulated screw channels (ASC) allow the clinician to reposition the access hole of screw-retained restorations, improving the design of the rehabilitation and the esthetic outcome. Few clinical studies are available on the efficacy of these restorations, especially at longer follow-ups and with a large number of subjects. The objective of this study was therefore to retrospectively evaluate patients rehabilitated with screw-retained restorations using ASC. The time of delivery and their adherence to the maintenance program was obtained, as well as the characteristics of the restoration and of the patient's occlusion; a Kaplan-Meier survival curve was then built to investigate the success rate of these restorations and the effects of several variables were evaluated with a Cox model. A total of 105 subjects and 162 implants were enrolled in this study; after 42 months a success rate (92%) similar to what is reported for conventional screw-retained restorations was encountered. Monolithic zirconia restorations (n = 52) had a higher success rate (95%) when compared to partially veneered restorations (n = 53), which suffered a higher number of complications (90%). The other variables had no statistically significant effect. Implant supported prostheses adopting ASC provide a favorable outcome both in the posterior and anterior regions and can therefore be adopted to treat cases where the implant angulation is unfavorable for a conventional screw-retained prosthesis.

35186190

Diabetes mellitus (DM) is a group of metabolic diseases, and there is an urgent need to develop new therapeutic DM oral drugs with fewer side effects and sound therapeutic efficacy. In this study, a <i>β</i> cell expansion factor A (BefA) production strain of <i>Escherichia coli</i> (BL21-pet 28C-BefA) was constructed, and the antidiabetes effect of BefA was evaluated using type 1 DM (T1DM) and type 2 DM (T2DM) mice models. The T1DM mice results indicated that BefA significantly reduced blood glucose levels; exerted a protective effect on islet <i>β</i> cell morphology; downregulated the expressions of TLR-4, p-NF<i>κ</i>B/NF<i>κ</i>B, and Bax/Bcl-2, and the secretion levels of IL-1<i>β</i> and TNF-<i>α</i>; increased the expression of PDX-1 protein and insulin secretion in a concentration-dependent manner; and restored the disturbed microbial diversity to normal levels. Similarly with the T1DM mice, BefA obviously increased islet <i>β</i> cells and reduced the inflammatory reaction and apoptosis in T2DM mice, as well as improved liver lipid metabolism by downregulating the expressions of CEBP-<i>α</i>, ACC, and Fasn; inhibited the synthesis of triglycerides; and induced Cpt-1, Hmgcs2, and Ppar<i>α</i> in a concentration-dependent manner. In conclusion, BefA alleviates diabetes via increasing the number of islet <i>β</i> cells, reducing the inflammatory reaction and apoptosis, improving liver lipid metabolism, and restoring microbial diversity to normal levels, which provides a new strategy for a DM oral drug.

34957410

Entomopathogenic nematodes (EPN) are excellent biocontrol agents against various insect pests. Novel biotechnological approaches can enhance their utility against insects above-ground, opening a new venue for selecting superior EPN against certain insects. We hypothesize that different populations of the same species but from different origins (habitat, ecoregion) will differ in their virulence. This study aimed to evaluate the virulence of various EPN populations against two pests of worldwide incidence and damage to high value crops: Frankliniella occidentalis (Thysanoptera: Thripidae) and Tuta absoluta (Lepidoptera: Gelechiidae). We tested 10 EPN populations belonging to three EPN species: Heterorhabditis bacteriophora (Koppert, MG-618b, AM-203, RM-102), Steinernema feltiae (Koppert, RS-5, AM-25, RM-107), and Steinernema carpocapsae (Koppert, MG-596a). Each EPN population was tested at two concentrations. Frankliniella occidentalis was tested at 160 and 80 IJs/cm2 and T. absoluta at 21 and 4 IJs/cm2. Control treatments followed the same experimental procedure but only adding distilled water. Overall, whenever different, higher IJs concentration resulted in lower adult emergence, higher larval mortality, and shorter time to kill the insects. Considering the low concentration, S. feltiae provided the best results for both insects and instars investigated, while H. bacteriophora and S. carpocapsae required a high concentration to reach similar or slightly better results. Differences among populations of each of the species were detected, but only the native populations of H. bacteriophora populations showed consistently higher control values against both insects/instar compared with the commercial one. Differences among S. feltiae and S. carpocapsae populations depended on the IJs concentration, insect, and instar. We consider S. feltiae a very promising species for their application against F. occidentalis and T. absoluta, with the Koppert population as the most consistent among the populations tested. Specific EPN-populations of S. carpocapsae and H. bacteriophora were good candidates against certain instar/insects at high concentrations. This study emphasized the importance of intraspecific variability for EPN virulence.

33277629

Short-read metagenomic sequencing and de novo genome assembly of the human gut microbiome can yield draft bacterial genomes without isolation and culture. However, bacterial genomes assembled from short-read sequencing are often fragmented. Furthermore, these metagenome-assembled genomes often exclude repeated genomic elements, such as mobile genetic elements, compromising our understanding of the contribution of these elements to important bacterial phenotypes. Although long-read sequencing has been applied successfully to the assembly of contiguous bacterial isolate genomes, extraction of DNA of sufficient molecular weight, purity and quantity for metagenomic sequencing from stool samples can be challenging. Here, we present a protocol for the extraction of microgram quantities of high-molecular-weight DNA from human stool samples that are suitable for downstream long-read sequencing applications. We also present Lathe ( www.github.com/bhattlab/lathe ), a computational workflow for long-read basecalling, assembly, consensus refinement with long reads or Illumina short reads and genome circularization. Altogether, this protocol can yield high-quality contiguous or circular bacterial genomes from a complex human gut sample in approximately 10 d, with 2 d of hands-on bench and computational effort.

35154044

The multicolored Asian lady beetle (<i>Harmonia axyridis</i>, <i>H. axyridis</i>, Coleoptera, and Coccinellidae) is an effective biocontrol agent against agricultural pests. Previous studies have suggested that amount, type, and the quality of food can directly affect the biological aspects of <i>H. axyridis.</i> In this study, we investigated the influence of the food sources (<i>Acyrthosiphon pisum</i> Harris, <i>Diaphorina citri</i> Kuwayama, and artificial diets) on the gut microbiota diversity and the biology, reproductive variables, and population growth indicators of <i>H. axyridis.</i> Three kinds of diets were considered in this study: (1) HY: the adult of <i>A. pisum</i> Harris (HY group); (2) HM: the adult of <i>D. citri</i> Kuwayama (HM group); (3) HR: artificial diets prepared by blending a portion of fresh homogenized pork liver (15 g), honey (3 g), distilled water (35 ml) (HR group). We found that gut microbiota composition and diversity and the biological parameters differed when <i>H. axyridis</i> was fed with different diets. The abundance of <i>Enterobacteriaceae</i> was the highest in the HM group, followed by HY group, and was the lowest in the HR group. The abundance of <i>Staphylococcaceae</i> was highest in the HR group. Among the gut fungi, <i>Davidiellaceae</i> and <i>Wallemiaceae</i> were the highest and lowest in the HY group; <i>Incertae_sedis</i> were the major gut fungi in the HR group. Meanwhile, the changes of biological parameters may be correlated with the changes of <i>Streptococcaceae</i> abundance, <i>Micrococcaceae</i> abundance, <i>Staphylococcaceae</i> abundance, and <i>Enterobacteriaceae</i> abundance in responds to diet changes. To sum up, these data suggest that different diets can influence the changes in adult <i>H. axyridis</i> gut microbiota, consequently affecting the biological parameters.

23661029

We report information on population density, group size, and habitat preferences of primates along the lower Río Urubamba and in the Río Urubamba-Río Tambo interfluvium, in central-eastern Peruvian Amazonia, an area that has been little explored with regard to its primate fauna. During 425 km of transect walks in October-November 2008 and April-May 2009 totally 174 groups of nine primate species were encountered, the most common being Callicebus brunneus (45 groups), Saguinus imperator (41 groups), and Aotus nigriceps (26 groups). Group sizes were smallest for A. nigriceps and C. brunneus (mean of 2.8 and 2.9, respectively) and largest for Saimiri boliviensis (mean 15.6). Population densities were lowest for Lagothrix cana (3.3 individuals/km(2)) and highest for A. nigriceps (31.1 individuals/km(2)). Groups of C. brunneus, S. imperator, S. boliviensis, Cebus albifrons, and Cebus apella were most frequently (83 % of sightings) encountered in semi-dense or in open primary forest that included stands of bamboo (Guadua sarcocarpa) or where bamboo was a very common species.

35160488

Natural cellulose-based Caesalpinia sappan L. wood fiber (CSWF) has been demonstrated to have significant promise as a new untreated bio-reinforcement of the polybutylene succinate (PBS) composite film. The morphology, mechanical characteristics, and biodegradation were investigated. The morphology, the fiber distribution, and the fiber aggregation has been discussed. The properties of the composite have been improved by the addition of CSWF from 5 phr to 10 phr, while with the addition of 15 phr, the properties were dropped. The result showed that CSWF could be used as a new reinforcement without any treatment, and 10 phr of CSWF was the best formulation of a new biocomposite film. The PBS/CSWF10 composite film had the highest mechanical strength, with a tensile strength of 12.21 N/mm2 and an elongation at break of 21.01%, respectively. It was completely degraded by soil bury in three months. Therefore, the PBS/CSWF10 composite film has the potential to be a green with a promising short-term degradation.

34869737

The giant panda (<i>Ailuropoda melanoleuca</i>) is one of the most endangered mammals in the world; anthropogenic habitat loss and poaching still threaten the survival of wild pandas. Viral infection has become one of the potential threats to the health of these animals, but the available information related to these infections is still limited. In order to detect possible vertebrate viruses, the virome in the fecal samples of seven wild giant pandas from Qinling Mountains was investigated by using the method of viral metagenomics. From the fecal virome of wild giant pandas, we determined six nearly complete genomes belonging to the order <i>Picornavirales</i>, two of which may be qualified as a novel virus family or genus. In addition, four complete genomes belonging to the <i>Genomoviridae</i> family were also fully characterized. This virological investigation has increased our understanding of the gut viral community in giant pandas. Whether these viruses detected in fecal samples can really infect giant panda needs further research.

35033088

<h4>Background</h4>The fasting and stress associated with road transportation contributes to a lack of energy and a decline in the immune system of beef cattle. Therefore, it is essential for beef cattle to enhance energy reserves before transportation. Creatine pyruvate (CrPyr) is a new multifunctional nutrient that can provide both pyruvate and creatine, which are two intermediate products of energy metabolism. To investigate the effects of transport and rumen-protected (RP)-CrPyr on the blood biochemical parameters and rumen fluid characteristics of beef cattle, twenty male Simmental crossbred cattle (659 ± 16 kg) aged 18 months were randomly allocated to four groups (n = 5) using a 2 × 2 factorial arrangement with two RP-CrPyr supplemental levels (0 or 140 g/d) and two transport treatments (5 min or 12 h): T_CrPyr140, T_CrPyr0, NT_CrPyr140, and NT_CrPyr0. After feeding for 30 days, three cattle per treatment were slaughtered.<h4>Results</h4>Compared with nontransport, transport decreased the total antioxidant capacity, catalase activity, contents of IgA, interferon γ, interleukin-1β (IL-1β), and IL-6 in serum, and the amounts of total volatile fatty acids (TVFA), acetate, and butyrate in rumen (P < 0.05); increased the serum lipopolysaccharide (LPS) level, contents of rumen LPS and ammonia nitrogen (P < 0.05). RP-CrPyr supplementation decreased the levels of cortisol and LPS in serum and the butyrate concentration in the rumen of beef cattle compared with those in the unsupplemented groups (P < 0.05). RP-CrPyr and transport interaction had a significant effect on the contents of serum tumour necrosis factor-α, IL-6, LPS, ruminal pH, acetate content, and acetate/propionate (P < 0.05). In terms of ruminal bacterial composition, group T_CrPyr0 increased the Prevotella genus abundance compared with group NT_CrPyr0 (P < 0.05), while group T_CrPyr140 increased Firmicutes phylum abundance and decreased Bacteroidetes phylum and genus Prevotella abundance compared with group T_CrPyr0 (P < 0.05). Moreover, Bacteroidetes was positively correlated with serum LPS.<h4>Conclusions</h4>These results indicated that dietary supplementation with RP-CrPyr might be beneficial to alleviate transport stress by decreasing serum cortisol and LPS levels and promoting the restoration of the rumen natural flora.

34273148

Environmental enteric dysfunction (EED) is a syndrome characterized by impairments of digestion and absorption and intestinal barrier failure in people living in insanitary or tropical environments. There is substantial evidence that it contributes to impaired linear growth of millions of children in low- and middle-income countries, to slowed neurocognitive development, and to diminished responses to oral vaccines. It represents the functional consequences of environmental enteropathy, an asymptomatic inflammatory disorder of the mucosa, and there is considerable overlap with the enteropathy observed in severe clinical malnutrition. The majority of studies of EED have employed functional tests based on lactulose permeation to define the presence of abnormal leak in the gut. However, where intestinal biopsies can safely be collected the opportunity then arises to study the underlying enteropathy in cellular and molecular detail, as well as to measure important functional elements such as enzyme expression. The purpose of this narrative review is to summarize the current understanding of environmental enteropathy obtained from small intestinal biopsies, and prospects for future work. We review histology, electron microscopy, transcription and protein expression, physiological measures, and the microbiome. We conclude that while noninvasive biomarkers of enteropathy and intestinal dysfunction permit large-scale studies of unquestionable value, intestinal biopsies are still required to investigate pathophysiology in depth.

35164860

<h4>Background</h4>Plasma amyloid-β (Aβ) may facilitate identification of individuals with brain amyloidosis. Gut microbial dysbiosis in Alzheimer's disease (AD) is increasingly being recognized. However, knowledge about alterations of gut microbiota in preclinical AD, as well as whether the combination of plasma Aβ and gut microbiota could identify preclinical AD, remains largely unknown.<h4>Methods</h4>This study recruited 34 Aβ-negative cognitively normal (CN-) participants, 32 Aβ-positive cognitively normal (CN+) participants, and 22 patients with cognitive impairment (CI), including 11 patients with mild cognitive impairment (MCI) and 11 AD dementia patients. All participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Meso Scale Discovery (MSD) kits were used to quantify the plasma Aβ₄₀, Aβ₄₂, and Aβ₄₂/Aβ₄₀ in CN- and CN+ participants. Using Spearman's correlation analysis, the associations of global standard uptake value rate (SUVR) with altered gut microbiota and plasma Aβ markers were separately evaluated. Furthermore, the discriminative power of the combination of gut microbiota and plasma Aβ markers for identifying CN+ individuals was investigated.<h4>Results</h4>Compared with the CN- group, the CN+ group showed significantly reduced plasma Aβ₄₂ (p = 0.011) and Aβ₄₂/Aβ₄₀ (p = 0.003). The relative abundance of phylum Bacteroidetes was significantly enriched, whereas phylum Firmicutes and class Deltaproteobacteria were significantly decreased in CN+ individuals in comparison with that in CN- individuals. Particularly, the relative abundance of phylum Firmicutes and its corresponding SCFA-producing bacteria exhibited a progressive decline tendency from CN- to CN+ and CI. Besides, the global brain Aβ burden was negatively associated with the plasma Aβ₄₂/Aβ₄₀ (r = -0.298, p = 0.015), family Desulfovibrionaceae (r = -0.331, p = 0.007), genus Bilophila (r = -0.247, p = 0.046), and genus Faecalibacterium (r = -0.291, p = 0.018) for all CN participants. Finally, the combination of plasma Aβ markers, altered gut microbiota, and cognitive performance reached a relatively good discriminative power in identifying individuals with CN+ from CN- (AUC = 0.869, 95% CI 0.782 ~ 0.955).<h4>Conclusions</h4>This study provided the evidence that the gut microbial composition was altered in preclinical AD. The combination of plasma Aβ and gut microbiota may serve as a non-invasive, cost-effective diagnostic tool for early AD screening. Targeting the gut microbiota may be a novel therapeutic strategy for AD.<h4>Trial registration</h4>This study has been registered in ClinicalTrials.gov (NCT03370744, https://www.clinicaltrials.gov ) in November 15, 2017.

34959967

Overnutrition is one of the risk factors of chronic kidney disease (CKD). The factors related to both obesity and CKD are adiponectin and ghrelin. The aim of the study was to assess if there is a link of nutritional status and selected nutrients intake with adiponectin and ghrelin in patients with diabetic nephropathy (DN). The study involved 55 patients diagnosed with DN in the pre-dialysis period (two groups: GFR < 30 and >30 mL/min/1.73 m2). In all participants standard blood tests, total ghrelin and total adiponectin plasma concentrations and anthropometric measurements (BMI, WHR- waist-hip ratio, body composition analysis) were performed. The evaluation of energy and nutrient intakes was made using the three-day food record method. Excessive body weight was found in 92.80% patients. The average daily energy intake was 1979.67 kcal/day (14.45% protein energy, 28.86% fat, and carbohydrates 56.89%). In the group with eGFR < 30 mL/min/1.73 m2 the analysis showed a negative relationship between ghrelin and WHR value, and the creatine and albumin concentrations. There was a positive correlation between ghrelin concentration and the consumption of carbohydrates and sucrose. In the group of patients with eGFR > 30 mL/min/1.73 m2, a positive correlation was found between the concentration of ghrelin and the consumption of vegetable protein, carbohydrates, and glucose. The study confirms the high prevalence of obesity in patients with DN-Excessive supply of protein was found in the patients' diets, which may contribute to the deterioration of the course of the disease and its prognosis. In patients with eGFR < 30 there was a negative correlation between ghrelin concentration and nutritional status, and in patents with eGFR > 30 between ghrelin concentration and some nutrients intake.

34863264

<h4>Background</h4>Gastrointestinal nematodes are ubiquitous for both domestic and wild ungulates and have varying consequences for health and fitness. They exist as complex communities of multiple co-infecting species, and we have a limited understanding of how these communities vary in different hosts, regions and circumstances or of how this affects their impacts.<h4>Methods</h4>We have undertaken ITS2 rDNA nemabiome metabarcoding with next-generation sequencing on populations of nematode larvae isolated from 149 fecal samples of roe deer of different sex and age classes in the two isolated populations of Chizé and Trois Fontaines in France not co-grazing with any domestic ungulate species.<h4>Results</h4>We identified 100 amplified sequence variants (ASVs) that were assigned to 14 gastrointestinal nematode taxa overall at either genus (29%) or species (71%) level. These taxa were dominated by parasites classically found in cervids-e.g. Ostertagia leptospicularis, Spiculopteragia spp. Higher parasite species diversity was present in the Trois Fontaines population than in the Chizé population including the presence of species more typically seen in domestic livestock (Haemonchus contortus, Bunostomum sp., Cooperia punctata, Teladorsagia circumcincta). No differences in parasite species diversity or community composition were seen in the samples collected from three zones of differing habitat quality within the Chizé study area. Young roe deer hosted the highest diversity of gastrointestinal nematodes, with more pronounced effects of age apparent in Trois Fontaines. The effect of host age differed between gastrointestinal nematode species, e.g. there was little effect on O. leptospicularis but a large effect on Trichostrongylus spp. No effect of host sex was detected in either site.<h4>Conclusions</h4>The presence of some livestock parasite species in the Trois Fontaines roe deer population was unexpected given the isolation of this population away from grazing domestic livestock since decades. Overall, our results illustrate the influence of host traits and the local environment on roe deer nemabiome and demonstrate the power of the nemabiome metabarcoding approach to elucidate the composition of gastrointestinal nematode communities in wildlife.

34995333

Candida albicans is a major opportunistic pathogen of humans. It can grow as morphologically distinct yeast, pseudohyphae and hyphae, and the ability to switch reversibly among different forms is critical for its virulence. The relationship between morphogenesis and innate immune recognition is not quite clear. Dectin-1 is a major C-type lectin receptor that recognizes β-glucan in the fungal cell wall. C. albicans β-glucan is usually masked by the outer mannan layer of the cell wall. Whether and how β-glucan masking is differentially regulated during hyphal morphogenesis is not fully understood. Here we show that the endo-1,3-glucanase Eng1 is differentially expressed in yeast, and together with Yeast Wall Protein 1 (Ywp1), regulates β-glucan exposure and Dectin-1-dependent immune activation of macrophage by yeast cells. ENG1 deletion results in enhanced Dectin-1 binding at the septa of yeast cells; while eng1 ywp1 yeast cells show strong overall Dectin-1 binding similar to hyphae of wild-type and eng1 mutants. Correlatively, hyphae of wild-type and eng1 induced similar levels of cytokines in macrophage. ENG1 expression and Eng1-mediated β-glucan trimming are also regulated by antifungal drugs, lactate and N-acetylglucosamine. Deletion of ENG1 modulates virulence in the mouse model of hematogenously disseminated candidiasis in a Dectin-1-dependent manner. The eng1 mutant exhibited attenuated lethality in male mice, but enhanced lethality in female mice, which was associated with a stronger renal immune response and lower fungal burden. Thus, Eng1-regulated β-glucan exposure in yeast cells modulates the balance between immune protection and immunopathogenesis during disseminated candidiasis.

34523250

<h4>Background</h4>Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia.<h4>Methods</h4>A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed.<h4>Results</h4>A total of 26 pre-clinical and 10 clinical studies were included. For animal studies, three revealed age-related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ-free mice. Seventy-five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short-chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut-muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8 ± 5.6 years, 57.8% female), while 4 studies focused on 244 young adults (29.7 ± 7.8 years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota.<h4>Conclusions</h4>Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age-related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.

35046810

<i>Cancer</i> is a serious disease with an increasing number of reported cases and high mortality worldwide. Gastrointestinal cancer defines a group of cancers in the digestive system, e.g., liver cancer, colorectal cancer, and gastric cancer. <i>Coptidis Rhizoma</i> (<i>C. Rhizoma</i>; Huanglian, in Chinese) is a classical Chinese medicinal botanical drug for the treatment of gastrointestinal disorders and has been shown to have a wide variety of pharmacological activity, including antifungal, antivirus, anticancer, antidiabetic, hypoglycemic, and cardioprotective effects. Recent studies on <i>C. Rhizoma</i> present significant progress on its anticancer effects and the corresponding mechanisms as well as its clinical applications. Herein, keywords related to <i>C. Rhizoma</i>, cancer, gastrointestinal cancer, and omics were searched in PubMed and the Web of Science databases, and more than three hundred recent publications were reviewed and discussed. <i>C. Rhizoma</i> extract along with its main components, berberine, palmatine, coptisine, magnoflorine, jatrorrhizine, epiberberine, oxyepiberberine, oxyberberine, dihydroberberine, columbamine, limonin, and derivatives, are reviewed. We describe novel and classic anticancer mechanisms from various perspectives of pharmacology, pharmaceutical chemistry, and pharmaceutics. Researchers have transformed the chemical structures and drug delivery systems of these components to obtain better efficacy and bioavailability of <i>C. Rhizoma</i>. Furthermore, <i>C. Rhizoma</i> in combination with other drugs and their clinical application are also summarized. Taken together, <i>C. Rhizoma</i> has broad prospects as a potential adjuvant candidate against cancers, making it reasonable to conduct additional preclinical studies and clinical trials in gastrointestinal cancer in the future.

34793539

<h4>Objective</h4>Develop and validate a prognostic model for clinical deterioration or death within days of pulmonary embolism (PE) diagnosis using point-of-care criteria.<h4>Methods</h4>We used prospective registry data from six emergency departments. The primary composite outcome was death or deterioration (respiratory failure, cardiac arrest, new dysrhythmia, sustained hypotension, and rescue reperfusion intervention) within 5 days. Candidate predictors included laboratory and imaging right ventricle (RV) assessments. The prognostic model was developed from 935 PE patients. Univariable analysis of 138 candidate variables was followed by penalized and standard logistic regression on 26 retained variables, and then tested with a validation database (N = 801).<h4>Results</h4>Logistic regression yielded a nine-variable model, then simplified to a nine-point tool (PE-SCORE): one point each for abnormal RV by echocardiography, abnormal RV by computed tomography, systolic blood pressure < 100 mmHg, dysrhythmia, suspected/confirmed systemic infection, syncope, medico-social admission reason, abnormal heart rate, and two points for creatinine greater than 2.0 mg/dL. In the development database, 22.4% had the primary outcome. Prognostic accuracy of logistic regression model versus PE-SCORE model: 0.83 (0.80, 0.86) vs. 0.78 (0.75, 0.82) using area under the curve (AUC) and 0.61 (0.57, 0.64) vs. 0.50 (0.39, 0.60) using precision-recall curve (AUCpr). In the validation database, 26.6% had the primary outcome. PE-SCORE had AUC 0.77 (0.73, 0.81) and AUCpr 0.63 (0.43, 0.81). As points increased, outcome proportions increased: a score of zero had 2% outcome, whereas scores of six and above had ≥ 69.6% outcomes. In the validation dataset, PE-SCORE zero had 8% outcome [no deaths], whereas all patients with PE-SCORE of six and above had the primary outcome.<h4>Conclusions</h4>PE-SCORE model identifies PE patients at low- and high-risk for deterioration and may help guide decisions about early outpatient management versus need for hospital-based monitoring.

35276854

Necrotizing enterocolitis (NEC) is a disease mainly of preterm infants with a 30-50% mortality rate and long-term morbidities for survivors. Treatment strategies are limited and have not improved in decades, prompting research into prevention strategies, particularly with probiotics. Recent work with the probiotic <i>B. infantis</i> EVC001 suggests that this organism may generate a more appropriate microbiome for preterm infants who generally have inappropriate gut colonization and inflammation, both risk factors for NEC. Experimental NEC involving Paneth cell disruption in combination with bacterial dysbiosis or formula feeding was induced in P14-16 C57Bl/6 mice with or without gavaged <i>B. infantis</i>. Following completion of the model, serum, small intestinal tissue, the cecum, and colon were harvested to examine inflammatory cytokines, injury, and the microbiome, respectively. EVC001 treatment significantly decreased NEC in a bacterial dysbiosis dependent model, but this decrease was model-dependent. In the NEC model dependent on formula feeding, no difference in injury was observed, but trending to significant differences was observed in serum cytokines. EVC001 also improved wound closure at six and twelve hours compared to the sham control in intestinal epithelial monolayers. These findings suggest that <i>B. infantis</i> EVC001 can prevent experimental NEC through anti-inflammatory and epithelial barrier restoration properties.

35095783

Functional gastrointestinal disorders (FGIDs) are a common concern during the first year of life. Recognized as gut-brain axis disorders by Rome IV criteria, FGIDs etiology is linked to altered gut-brain interaction, intestinal physiology, and microbiota. In this regard, probiotics have emerged as a promising therapy for infant FGIDs. In this study, we have investigated the probiotic potential of the strains <i>Bifidobacterium longum</i> KABP042 and <i>Pediococcus pentosaceus</i> KABP041-isolated from healthy children's feces-in the treatment of FGIDs. To this scope, genome sequences of both strains were obtained and subjected to <i>in silico</i> analyses. No virulence factors were detected for any strain and only the non-transferable <i>erm(49)</i> gene, which confers resistance to erythromycin and clindamycin, was identified in the genome of <i>B. longum</i> KABP042. Safety of both strains was confirmed by acute oral toxicity in rats. <i>In vitro</i> characterization revealed that the strains tolerate gastric and bile challenges and display a great adhesion capacity to human intestinal cells. The two strains mediate adhesion by different mechanisms and, when combined, synergically induce the expression of Caco-2 tight junction proteins. Moreover, growth inhibition experiments demonstrated the ability of the two strains alone and in combination to antagonize diverse Gram-negative and Gram-positive bacterial pathogens during sessile and planktonic growth. Pathogens' inhibition was mostly mediated by the production of organic acids, but neutralization experiments strongly suggested the presence of additional antimicrobial compounds in probiotic culture supernatants such as the bacteriocin Lantibiotic B, whose gene was detected in the genome of <i>B. longum</i> KABP042. Finally, an exploratory, observational, pilot study involving 36 infants diagnosed with at least one FGID (infant colic and/or functional constipation) showed the probiotic formula was well tolerated and FGID severity was significantly reduced after 14 days of treatment with the 2 strains. Overall, this work provides evidence of the probiotic and synergic properties of strains <i>B. longum</i> KABP042 and <i>P. pentosaceus</i> KABP041, and of their potential to treat pediatric FGIDs. <b>Clinical Trial Registration:</b> [www.ClinicalTrials.gov], [identifier NCT04944628].

35089939

Conventional water quality monitoring has been done for decades in Lake Tanganyika, under different national and international programs. However, these projects utilized monitoring approaches, which were temporally limited, labour intensive and costly. This study examines the use of citizen science to monitor the dynamics of coliform concentrations in Lake Tanganyika as a complementary method to statutory and project-focused measurements. Persons in five coastal communities (Kibirizi, Ilagala, Karago, Ujiji and Gombe) were trained and monitored total coliforms, faecal coliforms and turbidity for one year on a monthly basis, in parallel with professional scientists. A standardized and calibrated Secchi tube was used at the same time to determine turbidity. Results indicate that total and faecal coliform concentrations determined by citizen scientists correlated well to those determined by professional scientists. Furthermore, citizen scientist-based turbidity values were shown to provide a potential indicator for high FC and TC concentrations. As a simple tiered approach to identify increased coliform loads, trained local citizen scientists could use low-cost turbidity measurements with follow up sampling and analysis for coliforms, to inform their communities and regulatory bodies of high risk conditions, as well as to validate local mitigation actions. By comparing the spatial and temporal dynamics of coliform concentrations to local conditions of infrastructure, population, precipitation and hydrology in the 15 sites (3 sites per community) over 12 months, potential drivers of coliform pollution in these communities were identified, largely related to precipitation dynamics and the land use.

34815772

Intestinal microbiota can indirectly modulate airway physiology and immunity through the gut-lung axis. Recent microbiome studies indicate that patients with coronavirus disease 2019 (COVID-19) exhibit a specific intestinal dysbiosis that is closely associated with the disease pathophysiology. Therefore, rebalancing the intestinal microbiome using probiotics may be effective for controlling COVID-19. However, the rationale for using probiotics in COVID-19 remains unclear. In the present study, an <i>in vitro</i> cytokine response assay was conducted, followed by a single-arm, double-blind, prospective trial to evaluate the immunological efficacy of probiotic lactic acid bacteria against COVID-19. The present study focused on <i>Lactobacillus plantarum</i> (<i>L. plantarum</i>), <i>Bifidobacterium longum</i> and <i>Lactococcus lactis</i> ssp. <i>lactis</i>, which exhibit robust protective effects against infection with respiratory RNA viruses. Considering the feasibility of long-term daily intake for prophylactic purposes, healthy uninfected individuals were enrolled as subjects. Our previous pilot trial demonstrated that oral Qingfei Paidu decoction (QFPD), a Chinese herbal medicine formulated specifically against COVID-19, upregulates plasma TNF-α, IL-1β, IL-18 and IL-8. Therefore, the present study utilized the cytokine changes induced by QFPD to define the innate cytokine index QICI [=(TNF-α) x (IL-1β) x (IL-18) x (IL-8)/(IL-6)] as an indicator of the anti-COVID-19 immunomodulatory potential of the lactic acid bacteria. A total of 20 eligible volunteers were enrolled, 18 of whom completed the intervention. <i>L. plantarum</i> demonstrated a strikingly high innate cytokine index in all subjects in the <i>in vitro</i> cytokine response assay. In the subsequent trial, oral intake of <i>L. plantarum</i> significantly increased the innate cytokine index (mean fold change, 17-fold; P=0.0138) and decreased the plasma level of IL-6 (P=0.0128), a key driver of complex immune dysregulation in COVID-19, as compared with the baseline. The cytokine index increased in 16 of 18 subjects (88.9%) with considerable individual differences in the fold change (1- to 128-fold). In line with these innate cytokine changes, <i>L. plantarum</i> ingestion significantly enhanced the activity of natural killer cells. By contrast, oral <i>B. longum</i> failed to induce a significant increase in the innate cytokine index (mean fold change, 2-fold; P=0.474) as compared with the baseline. In conclusion, <i>L. plantarum</i> demonstrated superior QFPD-like immunomodulatory ability and mimicked the blood cytokine environment produced by early immune responses to viral infection. Daily consumption of <i>L. plantarum</i> as an anti-COVID-19 probiotic may be a possible option for preventing COVID-19 during the pandemic. The present study was prospectively registered in the University Hospital Medical Information Network-Clinical Trials Registry under the trial number UMIN000040479 on 22 May 2020 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046202).

34876116

<h4>Background</h4>Oleaginous yeasts are promising microbial platforms for sustainable, bio-based production of biofuels and oleochemical building blocks. Bio-based residues provide sustainable and cost-effective carbon sources for fermentative yeast oil production without land-use change. Considering the regional abundancy of different waste streams, we chose complex biomass residue streams of marine origin; macroalgae hydrolysate, and terrestrial origin; wheat straw hydrolysate in the presence, and absence of corn steep liquor as a complex nitrogen source. We investigated the biomass and lipid yields of an array of well-described oleaginous yeasts; R. glutinis, T. asahii, R. mucilaginosa, R. toruloides, C. oleaginosus growing on these hydrolysates. Furthermore, their sugar utilization, fatty acid profile, and inhibitory effect of the hydrolysates on yeast growth were compared. For correlative reference, we initially performed comparative growth experiments for the strains on individual monomeric sugars separately. Each of these monomeric sugars was a dominant carbon source in the complex biomass hydrolysates evaluated in this study. In addition, we evaluated N-acetylglucosamine, the monomeric building block of chitin, as a low-cost nitrogen and carbon source in yeast fermentation.<h4>Results</h4>C. oleaginosus provided the highest biomass and lipid yields. In the wheat straw and brown algae hydrolysates, this yeast strain gained 7.5 g/L and 3.8 g/L lipids, respectively. Cultivation in algae hydrolysate resulted in a higher level of unsaturated fatty acids in the lipids accumulated by all yeast strains. R. toruloides and C. oleaginosus were able to effectively co-utilize mannitol, glucose, and xylose. Growth rates on wheat straw hydrolysate were enhanced in presence of corn steep liquor.<h4>Conclusions</h4>Among the yeast strains investigated in this study, C. oleaginosus proved to be the most versatile strain in terms of substrate utilization, productivity, and tolerance in the complex media. Various fatty acid profiles obtained on each substrate encourage the manipulation of culture conditions to achieve the desired fatty acid composition for each application. This could be accomplished by combining the element of carbon source with other formerly studied factors such as temperature and oxygen. Moreover, corn steep liquor showed promise for enhancement of growth in the oleaginous strains provided that carbon substrate is available.

35011305

The intestinal absorption of dietary catechins is quite low, resulting in most of them being metabolized by gut microbiota in the colon. It has been hypothesized that microbiota-derived metabolites may be partly responsible for the association between catechin consumption and beneficial cardiometabolic effects. Given the profound differences in gut microbiota composition and microbial load between individuals and across different colon regions, this study examined how microbial (+)-catechin metabolite profiles differ between colon regions and individuals. Batch exploration of the interindividual variability in (+)-catechin microbial metabolism resulted in a stratification based on metabolic efficiency: from the 12 tested donor microbiota, we identified a fast- and a slow-converting microbiota that was subsequently inoculated to SHIME, a dynamic model of the human gut. Monitoring of microbial (+)-catechin metabolites from proximal and distal colon compartments with UHPLC-MS and UPLC-IMS-Q-TOF-MS revealed profound donor-dependent and colon-region-dependent metabolite profiles with 5-(3',4'-dihydroxyphenyl)-γ-valerolactone being the largest contributor to differences between the fast- and slow-converting microbiota and the distal colon being a more important region for (+)-catechin metabolism than the proximal colon. Our findings may contribute to further understanding the role of the gut microbiota as a determinant of interindividual variation in pharmacokinetics upon (+)-catechin ingestion.

35087508

The biodegradation of organic pollutants is the main pathway for the natural dissipation and anthropogenic remediation of polycyclic aromatic hydrocarbons (PAHs) in the environment. However, in the saline soils, the PAH biodegradation could be influenced by soil salts through altering the structures of microbial communities and physiological metabolism of degradation bacteria. In the worldwide, soils from oilfields are commonly threated by both soil salinity and PAH contamination, while the influence mechanism of soil salinity on PAH biodegradation were still unclear, especially the shifts of degradation genes and soil enzyme activities. In order to explain the responses of soils and bacterial communities, analysis was conducted including soil properties, structures of bacterial community, PAH degradation genes and soil enzyme activities during a biodegradation process of PAHs in oilfield soils. The results showed that, though low soil salinity (1% NaCl, <i>w/w</i>) could slightly increase PAH degradation rate, the biodegradation in high salt condition (3% NaCl, <i>w/w</i>) were restrained significantly. The higher the soil salinity, the lower the bacterial community diversity, copy number of degradation gene and soil enzyme activity, which could be the reason for reductions of degradation rates in saline soils. Analysis of bacterial community structure showed that, the additions of NaCl increase the abundance of salt-tolerant and halophilic genera, especially in high salt treatments where the halophilic genera dominant, such as <i>Acinetobacter</i> and <i>Halomonas</i>. Picrust2 and redundancy analysis (RDA) both revealed suppression of PAH degradation genes by soil salts, which meant the decrease of degradation microbes and should be the primary cause of reduction of PAH removal. The soil enzyme activities could be indicators for microorganisms when they are facing adverse environmental conditions.

35163046

Roux-en-Y gastric bypass (RYGB) surgery has been proven successful in weight loss and improvement of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for additional therapeutic approaches. We investigated systemic RYGB surgery effects in a liquid sucrose diet-induced rat obesity model. After consuming a diet supplemented with high liquid sucrose for eight weeks, rats underwent RYGB or control sham surgery. RYGB, sham pair-fed, and sham ad libitum-fed groups further continued on the diet after recovery. Notable alterations were revealed in microbiota composition, inflammatory markers, feces, liver, and plasma metabolites, as well as in brain neuronal activity post-surgery. Higher fecal 4-aminobutyrate (GABA) correlated with higher Bacteroidota and Enterococcus abundances in RYGB animals, pointing towards the altered enteric nervous system (ENS) and gut signaling. Favorable C-reactive protein (CRP), serine, glycine, and 3-hydroxybutyrate plasma profiles in RYGB rats were suggestive of reverted obesity risk. The impact of liquid sucrose diet and caloric restriction mainly manifested in fatty acid changes in the liver. Our multi-modal approach reveals complex systemic changes after RYGB surgery and points towards potential therapeutic targets in the gut-brain system to mimic the surgery mode of action.

35127789

The microbiota-gut-liver axis has emerged as an important player in developing nonalcoholic steatohepatitis (NASH), a type of nonalcoholic fatty liver disease (NAFLD). Higher mushroom intake is negatively associated with the prevalence of NAFLD. This study examined whether lentinan, an active ingredient in mushrooms, could improve NAFLD and gut microbiota dysbiosis in NAFLD mice induced by a high-fat (HF) diet. Dietary lentinan supplementation for 15 weeks significantly improved gut microbiota dysbiosis in HF mice, evidenced by increased the abundance of phylum Actinobacteria and decreased phylum Proteobacteria and Epsilonbacteraeota. Moreover, lentinan improved intestinal barrier integrity and characterized by enhancing intestinal tight junction proteins, restoring intestinal redox balance, and reducing serum lipopolysaccharide (LPS). In the liver, lentinan attenuated HF diet-induced steatohepatitis, alteration of inflammation-insulin (NFκB-PTP1B-Akt-GSK3β) signaling molecules, and dysregulation of metabolism and immune response genes. Importantly, the antihepatic inflammation effects of lentinan were associated with improved gut microbiota dysbiosis in the treated animals, since the Spearman's correlation analysis showed that hepatic LPS-binding protein and receptor (Lbp and Tlr4) and pro- and antiinflammatory cytokine expression were significantly correlated with the abundance of gut microbiota of phylum Proteobacteria, Epsilonbacteraeota and Actinobacteria. Therefore, lentinan supplementation may be used to mitigate NAFLD by modulating the microbiota-gut-liver axis.

34888100

Intermittent hypoxia and sleep fragmentation are pathophysiological processes involved in obstructive sleep apnea (OSA) which affect gut microbiota, sleep architecture, and mTOR signaling pathway. However, the involvement of these elements in the pathogenesis mechanism of OSA-associated hypertension remains unclear. Therefore, this study investigated whether the OSA-associated hypertension mechanism is regulated by the gut microbiota and mTOR signaling pathway. Patients were diagnosed by polysomnography; their fecal samples were obtained and analyzed for their microbiome composition by 16S ribosomal RNA pyrosequencing and bioinformatics analysis. Transcript genes on fasting peripheral blood mononuclear cells (PBMCs) were examined using Illumina RNA-sequencing analysis. Totally, we enrolled 60 patients with severe OSA [without hypertension (<i>n</i> = 27) and with hypertension (<i>n</i> = 33)] and 12 controls (neither OSA nor hypertension). Results revealed that severe-OSA patients with hypertension had an altered gut microbiome, decreased short-chain fatty acid-producing bacteria (<i>P</i> < 0.05), and reduced arginine and proline metabolism pathways (<i>P</i>=0.001), compared with controls; also, they had increased stage N1 sleep and reduced stages N2 and N3 sleep accompanied by repeated arousals (<i>P</i> < 0.05). Analysis of PBMCs using the Kyoto Encyclopedia of Genes and Genomes database showed that the mTOR signaling pathway (<i>P</i>=0.006) was the most important differential gene-enriched pathway in severe-OSA patients with hypertension. Our findings extend prior work and suggest a possibility that the regulation of the mTOR signaling pathway is involved in developing OSA-associated hypertension through its interaction with the disturbance of the gut microbiome and sleep architecture.

34913717

Here, we report the genome sequences of three bacterial isolates, <i>Kinneretia</i> sp. strain XES5, <i>Shinella</i> sp. strain XGS7, and <i>Vogesella</i> sp. strain XCS3, which were cultured from skin of adult female laboratory-bred Xenopus laevis.

34835713

Subwavelength grating (SWG) metamaterials have garnered a great interest for their singular capability to shape the material properties and the propagation of light, allowing the realization of devices with unprecedented performance. However, practical SWG implementations are limited by fabrication constraints, such as minimum feature size, that restrict the available design space or compromise compatibility with high-volume fabrication technologies. Indeed, most successful SWG realizations so far relied on electron-beam lithographic techniques, compromising the scalability of the approach. Here, we report the experimental demonstration of an SWG metamaterial engineered beam splitter fabricated with deep-ultraviolet immersion lithography in a 300-mm silicon-on-insulator technology. The metamaterial beam splitter exhibits high performance over a measured bandwidth exceeding 186 nm centered at 1550 nm. These results open a new route for the development of scalable silicon photonic circuits exploiting flexible metamaterial engineering.

34908523

Clostridioides difficile (formerly Clostridium difficile) colonizes the gastrointestinal tract following disruption of the microbiota and can initiate a spectrum of clinical manifestations ranging from asymptomatic to life-threatening colitis. Following antibiotic treatment, luminal oxygen concentrations increase, exposing gut microbes to potentially toxic reactive oxygen species. Though typically regarded as a strict anaerobe, C. difficile can grow at low oxygen concentrations. How this bacterium adapts to a microaerobic environment and whether those responses to oxygen are conserved amongst strains is not entirely understood. Here, two C. difficile strains (630 and CD196) were cultured in 1.5% oxygen and the transcriptional response to long-term oxygen exposure was evaluated via RNA-sequencing. During growth in a microaerobic environment, several genes predicted to protect against oxidative stress were upregulated, including those for rubrerythrins and rubredoxins. Transcription of genes involved in metal homeostasis was also positively correlated with increased oxygen levels and these genes were amongst the most differentially transcribed. To directly compare the transcriptional landscape between C. difficile strains, a 'consensus-genome' was generated. On the basis of the identified conserved genes, basal transcriptional differences as well as variations in the response to oxygen were evaluated. While several responses were similar between the strains, there were significant differences in the abundance of transcripts involved in amino acid and carbohydrate metabolism. Furthermore, intracellular metal concentrations significantly varied both in an oxygen-dependent and oxygen-independent manner. Overall, these results indicate that C. difficile adapts to grow in a low oxygen environment through transcriptional changes, though the specific strategy employed varies between strains.

33903989

In addition to properly balancing nutritional value in accordance with the needs of a dog, estimating the microbiological quality of dog food is crucial in providing healthy and safe foods. The aim of this study was to examine the quality of dry food for adult dogs, with particular reference to: (1) evaluating the nutritional value and compliance with nutritional guidelines for dogs, (2) comparing the nutritional value of dog foods, with particular emphasis on the division into cereal and cereal-free foods, and (3) evaluating their microbiological safety. All thirty-six evaluated dry dog foods met the minimum European Pet Food Industry FEDIAF requirement for total protein and fat content. The total aerobic microbial count in the analyzed dry dog foods ranged from 2.7 × 10² to above 3.0 × 10⁷ cfu/g. In five (14%) dog foods the presence of staphylococci was detected; however, coagulase positive Staphylococcus (CPS) was not found. Mold presence was reported in one cereal-free dog food and in six cereal foods. In none of the analyzed foods Enterobacteriaceae were found, including coliforms, Escherichia coli and Salmonella spp. Bacteria of the genus Listeria and Clostridium as well as yeasts were also not detected. In conclusion, the evaluated dry dog foods had varied microbiological quality. The detected number of microorganisms may have some implications for long-term consumption of contaminated food. The lack of European Commission standards regarding the permissible amounts of microorganisms in pet food may result in insufficient quality control of these products.

35014873

The composition of microbial communities found in association with plants is influenced by host phenotype and genotype. However, the ways in which specific genetic architectures of host plants shape microbiomes are unknown. Genome duplication events are common in the evolutionary history of plants and influence many important plant traits, and thus, they may affect associated microbial communities. Using experimentally induced whole-genome duplication (WGD), we tested the effect of WGD on rhizosphere bacterial communities in Arabidopsis thaliana. We performed 16S rRNA amplicon sequencing to characterize differences between microbiomes associated with specific host genetic backgrounds (Columbia versus Landsberg) and ploidy levels (diploid versus tetraploid). We modeled relative abundances of bacterial taxa using a hierarchical Bayesian approach. We found that host genetic background and ploidy level affected rhizosphere community composition. We then tested to what extent microbiomes derived from a specific genetic background or ploidy level affected plant performance by inoculating sterile seedlings with microbial communities harvested from a prior generation. We found a negative effect of the tetraploid Columbia microbiome on growth of all four plant genetic backgrounds. These findings suggest an interplay between host genetic background and ploidy level and bacterial community assembly with potential ramifications for host fitness. Given the prevalence of ploidy-level variation in both wild and managed plant populations, the effects on microbiomes of this aspect of host genetic architecture could be a widespread driver of differences in plant microbiomes. <b>IMPORTANCE</b> Plants influence the composition of their associated microbial communities, yet the underlying host-associated genetic determinants are typically unknown. Genome duplication events are common in the evolutionary history of plants and affect many plant traits. Using Arabidopsis thaliana, we characterized how whole-genome duplication affected the composition of rhizosphere bacterial communities and how bacterial communities associated with two host plant genetic backgrounds and ploidy levels affected subsequent plant growth. We observed an interaction between ploidy level and genetic background that affected both bacterial community composition and function. This research reveals how genome duplication, a widespread genetic feature of both wild and crop plant species, influences bacterial assemblages and affects plant growth.

33398160

White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear^1,2. Here we retrospectively categorized 134,529 ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography scans from 52,487 patients, by presence or absence of BAT, and used propensity score matching to assemble a study cohort. Scans in the study population were initially conducted for indications related to cancer diagnosis, treatment or surveillance, without previous stimulation. We report that individuals with BAT had lower prevalences of cardiometabolic diseases, and the presence of BAT was independently correlated with lower odds of type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension. These findings were supported by improved blood glucose, triglyceride and high-density lipoprotein values. The beneficial effects of BAT were more pronounced in individuals with overweight or obesity, indicating that BAT might play a role in mitigating the deleterious effects of obesity. Taken together, our findings highlight a potential role for BAT in promoting cardiometabolic health.

35097319

<h4>Background</h4>Talar body osteonecrosis can be a difficult condition to treat. Recent reports highlight a high rate of failure with the use of femoral head allograft. Additionally, higher rates of failure have been reported in diabetics and smokers. Our institution attempted a novel technique utilizing fresh allograft talus in attempt to improve on a reported 50% nonunion rate.<h4>Methods</h4>Five patients who underwent tibiotalocalcaneal (TTC) fusion utilizing fresh talar allograft were clinically and radiographically reviewed to evaluate fusion rates and functional outcomes.<h4>Results</h4>Our case series of 5 patients had a 100% union rate, including 2 former smokers and 2 diabetic patients. There were no infections or complications. Functional outcomes also improved in our series of patients postoperatively as noted by their FAAM and SF-36 scores.<h4>Conclusion</h4>TTC fusion using fresh allograft talus has a higher union rate than reported with femoral head allograft. This case series requires further study to evaluate whether this technique can be used beyond patients with osteonecrosis of the talus.<h4>Level of evidence</h4>Level IV, case series.

34914785

Endometriosis is an estrogen dependent gynecological disease associated with altered microbial phenotypes. The association among endogenous estrogen, estrogen metabolites, and microbial dynamics on disease pathogenesis has not been fully investigated. Here, we identified estrogen metabolites as well as microbial phenotypes in non-diseased patients (n = 9) and those with pathologically confirmed endometriosis (P-EOSIS, n = 20), on day of surgery (DOS) and ~1-3 weeks post-surgical intervention (PSI). Then, we examined the effects of surgical intervention with or without hormonal therapy (OCPs) on estrogen and microbial profiles of both study groups. For estrogen metabolism analysis, liquid chromatography/tandem mass spectrometry was used to quantify urinary estrogens. The microbiome data assessment was performed with Next generation sequencing to V4 region of 16S rRNA. Surgical intervention and hormonal therapy altered gastrointestinal (GI), urogenital (UG) microbiomes, urinary estrogen and estrogen metabolite levels in P-EOSIS. At DOS, 17β-estradiol was enhanced in P-EOSIS treated with OCPs. At PSI, 16-keto-17β-estradiol was increased in P-EOSIS not receiving OCPs while 2-hydroxyestradiol and 2-hydroxyestrone were decreased in P-EOSIS receiving OCPs. GI bacterial α-diversity was greater for controls and P-EOSIS that did not receive OCPs. P-EOSIS not utilizing OCPs exhibited a decrease in UG bacterial α-diversity and differences in dominant taxa, while P-EOSIS utilizing OCPs had an increase in UG bacterial α-diversity. P-EOSIS had a strong positive correlation between the GI/UG bacteria species and the concentrations of urinary estrogen and its metabolites. These results indicate an association between microbial dysbiosis and altered urinary estrogens in P-EOSIS, which may impact disease progression.

35276979

This review aims to define the effectiveness of the ketogenic diet (KD) for the management of sarcopenic obesity. As the combination of sarcopenia and obesity appears to have multiple negative metabolic effects, this narrative review discusses the effects of the ketogenic diet as a possible synergic intervention to decrease visceral adipose tissue (VAT) and fatty infiltration of the liver as well as modulate and improve the gut microbiota, inflammation and body composition. The results of this review support the evidence that the KD improves metabolic health and expands adipose tissue γδ T cells that are important for glycaemia control during obesity. The KD is also a therapeutic option for individuals with sarcopenic obesity due to its positive effect on VAT, adipose tissue, cytokines such as blood biochemistry, gut microbiota, and body composition. However, the long-term effect of a KD on these outcomes requires further investigations before general recommendations can be made.

34584573

These are the open problems presented at the 13th International Symposium on Orthogonal Polynomials, Special Functions and Applications (OPSFA13), Gaithersburg, Maryland, on June 4, 2015.

35113862

Visual Question Answering (VQA) is a learning task that combines computer vision with natural language processing. In VQA, it is important to understand the alignment between visual concepts and linguistic semantics. In this paper, we proposed a Pre-training Model Based on Parallel Cross-Modality Fusion Layer (P-PCFL) to learn the fine-grained relationship between vision and language. The P-PCFL model is composed of three Encoders: Object Encoder, Language Encoder, and Parallel Cross-Modality Fusion Encoder, with Transformer as the core. We use four different Pre-training missions, namely, Cross-Modality Mask Language Modeling, Cross-Modality Mask Region Modeling, Image-Text Matching, and Image-Text Q&A, to pre-train the P-PCFL model and improve its reasoning and universality, which help to learn the relationship between Intra-modality and Inter-modality. Experimental results on the platform of Visual Question Answering dataset VQA v2.0 show that the Pre-trained P-PCFL model has a good effect after fine-tuning the parameters. In addition, we also conduct ablation experiments and provide some results of Attention visualization to verify the effectiveness of P-PCFL model.

35097332

<h4>Background</h4>Surgical management of patients with acute and chronic ankle instability (CAI) has historically focused on the lateral ligament complex. Recent studies in CAI patients have shown that magnetic resonance imaging (MRI) and arthroscopy demonstrate concomitant injury to the deltoid ligament complex We performed a systematic review to determine if consistent clinical, diagnostic imaging, or arthroscopic findings of deltoid ligament injury in the setting of CAI have been described. In addition, we sought to determine if treatment options and/or clinical outcomes have been described.<h4>Methods</h4>A systematic review was conducted using the PubMed, MEDLINE, and Embase databases. Articles were included if they had a majority of patients 18 years of age or older, focused on deltoid ligament injury in ankle instability, and reported diagnostic and/or treatment methods. Articles were excluded if the study focused on the deltoid ligament in the acute fracture setting. All included articles were assessed for diagnostic criteria, treatments, and patient outcomes.<h4>Results</h4>Our search yielded 157 articles, of which a total of 13 were included in our study. Arthroscopy was described as the gold standard to diagnose and evaluate the severity of deltoid ligament injury, however, little objective data on the arthroscopic diagnosis of deltoid ligament insufficiency was reported. MRI was the imaging modality of choice to evaluate deltoid ligament injury and had a high sensitivity and specificity when compared with arthroscopy. No standard MRI diagnostic criteria for deltoid ligament injury were identified in the literature. Specific treatment techniques and long-term outcomes were not well described in the manuscripts included in this review.<h4>Conclusion</h4>There is limited knowledge on deltoid ligament insufficiency in the setting of chronic ankle instability. Criteria for characterizing deltoid ligament damage with diagnostic imaging appear to be evolving, but there is no standard classification. Only 1 author has described a method to evaluate deltoid ligament competency on arthroscopic examination. There are currently no objective data to guide treatment decisions.<h4>Level of evidence</h4>Level III.

34884379

The gut metabolite trimethylamine N-oxide (TMAO) at admission has a prognostic value in ST-elevation myocardial infarction (STEMI) patients. However, its sequential changes and relationship with long-term infarct-related outcomes after primary percutaneous coronary intervention (PCI) remain elusive. We delineated the temporal course of TMAO and its relationship with infarct size and left ventricular ejection fraction (LVEF) post-PCI, adjusting for the estimated glomerular filtration rate (eGFR). We measured TMAO levels at admission, 24 h and 4 months post-PCI in 379 STEMI patients. Infarct size and LVEF were determined by cardiac magnetic resonance 4 months after PCI. TMAO levels decreased from admission (4.13 ± 4.37 μM) to 24 h (3.41 ± 5.84 μM, p = 0.001) and increased from 24 h to 4 months (3.70 ± 3.86 μM, p = 0.026). Higher TMAO values at 24 h were correlated to smaller infarct sizes (rho = -0.16, p = 0.024). Larger declines between admission and 4 months suggestively correlated with smaller infarct size, and larger TMAO increases between 24 h and 4 months were associated with larger infarct size (rho = -0.19, p = 0.008 and rho = -0.18, p = 0.019, respectively). Upon eGFR stratification using 90 mL/min/1.73 m2 as a cut-off, significant associations between TMAO and infarct size were only noted in subjects with impaired renal function. In conclusion, TMAO levels in post-PCI STEMI patients are prone to fluctuations, and these fluctuations could be prognostic for infarct size, particularly in patients with impaired renal function.

32589957

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

34998377

<h4>Background</h4>Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30-40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear.<h4>Methods</h4>IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total.<h4>Discussion</h4>To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, 'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1.

34769621

Work is a key social determinant of health. Community health and well-being may be impacted in neighborhoods with high proportions of people engaged in precarious work situations compounded by health inequities produced by other social determinants associated with their residential geography. However, little is known about how community residents experience work at the neighborhood level nor how work impacts health at the community-level, particularly in communities with a high proportion of residents engaged in precarious work. We sought to understand, through participatory research strategies, how work is experienced at the community level and to identify community interventions to establish a culture of healthy work. As part of a mixed-methods community health assessment, community researchers conducted focus groups with residents in two high social and economic hardship neighborhoods on Chicago's southwest side. Community and academic researchers engaged in participatory data analysis and developed and implemented member-checking modules to engage residents in the data interpretation process. Twelve focus group discussions (77 community resident participants) were completed. Three major themes emerged: systematic marginalization from the pathways to healthy work situations; contextual and structural hostility to sustain healthy work; and violations in the rights, agency, and autonomy of resident workers. Findings were triangulated with findings from the concept-mapping research component of the project to inform the development of a community health survey focused on work characteristics and experiences. Listening to residents in communities with a high proportion of residents engaging in precarious work allows for the identification of nuanced community-informed intervention points to begin to build a culture of healthy work.

34760228

Fresh-cut fruits and vegetables are becoming particularly popular as healthy fast-food options; however, they present challenges such as accelerated rates of decay and increased risk for contamination when compared to whole produce. Given that food safety must remain paramount for producers and manufacturers, research into novel, natural food preservation solutions which can help to ensure food safety and protect against spoilage is on the rise. In this work, we investigated the potential of using a novel protein hydrolysate, produced by the enzymatic hydrolysis of <i>Pisum sativum</i> (PSH), as a novel bio-preservative and its abilities to reduce populations of <i>Escherichia coli</i> O157:H7 after inoculation on a lettuce leaf. While unhydrolyzed <i>P. sativum</i> proteins show no antimicrobial activity, once digested, and purified, the enzymatically released peptides induced in vitro bactericidal effects on the foodborne pathogen at 8 mg/ml. When applied on an infected lettuce leaf, the PSH significantly reduced the number of bacteria recovered after 2 hr of treatment. PSH may be preferred over other preservation strategies based on its natural, inexpensive, sustainable source, environmentally friendly process, nontoxic nature, good batch to batch consistency, and ability to significantly reduce counts of <i>E. coli</i> both in vitro and in a lettuce leaf.

34674718

<h4>Background</h4>Metabolomics coupled with genome-scale metabolic modeling approaches have been employed recently to quantitatively analyze the physiological states of various organisms, including Saccharomyces cerevisiae. Although yeast physiology in laboratory strains is well-studied, the metabolic states under industrially relevant scenarios such as winemaking are still not sufficiently understood, especially as there is considerable variation in metabolism between commercial strains. To study the potential causes of strain-dependent variation in the production of volatile compounds during enological conditions, random flux sampling and statistical methods were used, along with experimental extracellular metabolite flux data to characterize the differences in predicted intracellular metabolic states between strains.<h4>Results</h4>It was observed that four selected commercial wine yeast strains (Elixir, Opale, R2, and Uvaferm) produced variable amounts of key volatile organic compounds (VOCs). Principal component analysis was performed on extracellular metabolite data from the strains at three time points of cell cultivation (24, 58, and 144 h). Separation of the strains was observed at all three time points. Furthermore, Uvaferm at 24 h, for instance, was most associated with propanol and ethyl hexanoate. R2 was found to be associated with ethyl acetate and Opale could be associated with isobutanol while Elixir was most associated with phenylethanol and phenylethyl acetate. Constraint-based modeling (CBM) was employed using the latest genome-scale metabolic model of yeast (Yeast8) and random flux sampling was performed with experimentally derived fluxes at various stages of growth as constraints for the model. The flux sampling simulations allowed us to characterize intracellular metabolic flux states and illustrate the key parts of metabolism that likely determine the observed strain differences. Flux sampling determined that Uvaferm and Elixir are similar while R2 and Opale exhibited the highest degree of differences in the Ehrlich pathway and carbon metabolism, thereby causing strain-specific variation in VOC production. The model predictions also established the top 20 fluxes that relate to phenotypic strain variation (e.g. at 24 h). These fluxes indicated that Opale had a higher median flux for pyruvate decarboxylase reactions compared with the other strains. Conversely, R2 which was lower in all VOCs, had higher median fluxes going toward central metabolism. For Elixir and Uvaferm, the differences in metabolism were most evident in fluxes pertaining to transaminase and hexokinase associated reactions. The applied analysis of metabolic divergence unveiled strain-specific differences in yeast metabolism linked to fusel alcohol and ester production.<h4>Conclusions</h4>Overall, this approach proved useful in elucidating key reactions in amino acid, carbon, and glycerophospholipid metabolism which suggest genetic divergence in activity in metabolic subsystems among these wine strains related to the observed differences in VOC formation. The findings in this study could steer more focused research endeavors in developing or selecting optimal aroma-producing yeast stains for winemaking and other types of alcoholic fermentations.

35100276

Rhizosphere and endophytic microbiota significantly affect plant growth and development by influencing nutrient uptake and stress tolerance. Herein, root and rhizosphere soil of Acacia species were collected and analyzed to compare the structural differences of the rhizosphere and root endophytic bacterial communities. High-throughput 16S rRNA gene sequencing technology was employed to analyze the rhizosphere and root endophytic bacterial communities. A total of 4249 OTUs were identified following sequence analysis. The rhizosphere soil contained significantly more OTUs than the root soil. Principal component analysis (PCA) and hierarchical cluster analysis indicated that bacterial communities exhibited significant specificity in the rhizosphere and root soil of different Acacia species. The most dominant phylum in the rhizosphere soil was Acidobacteria, followed by Proteobacteria and Actinobacteria, whereas the dominant phylum in the root soil was Proteobacteria, followed by Actinobacteria and Acidobacteria. Among the various Acacia species, specific bacterial communities displayed different abundance. We systematically described the core bacteria in the rhizosphere and root endophytic bacterial communities and predicted their relevant functions. The type and abundance of specific bacteria were correlated with the nutrient absorption and metabolism of the Acacia species. This study addresses the complex host-microbe interactions and explores the rhizosphere and root bacterial community structure of different Acacia species. These results provide new insights into the role of rhizosphere and root endophytic bacterial communities on the growth and reproduction of Acacia, thus informing future efforts towards sustainable development and utilization of Acacia.

21796679

Over the past three decades, the public health landscape in Thailand has shifted remarkably. Currently chronic non-communicable diseases represent the largest cause of mortality in the Thai population. In light of the current situation, this paper synthesizes what is known about the chronic non-communicable disease situation in Thailand and analyzes current policy responses. Relevant contextual factors such as socio-economic transitions, health systems development, and health workforce capacities are also considered. Primary data for this study were collected by a review of policy documents, government statements, and statistics reported by the Thailand Ministry of Public Health. Secondary data were obtained by a thorough review of the existing literature. The paper finds that while current policy responses to chronic non-communicable diseases in the health sector have focused on improving prevention and control of risk factors, a stronger emphasis on chronic disease treatment and management may be needed in the future. The paper concludes with an exploration of the potential for developing and implementing realistic public health responses to the growing burden of chronic non-communicable diseases in a Southeast Asian country context by utilizing existing capacities in research, policy, and health workforce development.

35059326

Colitis, a chronic inflammatory bowel disease, is characterized by bloody diarrhea and inflammation in the colon. <i>Lonicera hypoglauca</i> ("Shanyinhua" in Chinese) and <i>Scutellaria baicalensis</i> ("Huangqin" in Chinese) are two traditional Chinese medicinal plants rich in polyphenols, such as chlorogenic acid (CGA) and baicalin (BA), with the effects of anti-inflammation and antioxidation. However, it remains unknown whether extracts from <i>L. hypoglauca</i> and <i>S. baicalensis</i> (LSEs) could mitigate colonic inflammation. In the present study, ICR mice (22.23 ± 1.65 g) were allocated to three groups treated with chow diet without (CON) or with dextran sulfate sodium (DSS) (CON+DSS) in water or LSE supplementation in diet with DSS (LSE+DSS), and then inflammatory and oxidative parameters and colonic microbiota were detected. The results showed that LSE (500 mg/kg) treatment mitigated DSS-induced colitis symptoms and restored the shortened colon length, the increased disease activity index (DAI), and the damaged intestinal barrier. In serum, LSE supplementation significantly decreased levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and increased IL-10 level. Meanwhile, superoxide dismutase (SOD) and catalase (CAT) were increased, and malondialdehyde (MDA) and reactive oxygen species (ROS) levels were decreased. In the colon tissue, qPCR results showed that LSE supplementation dramatically downregulated the transcriptional expression of <i>IL-1β</i>, <i>IL-6</i>, <i>TNF-α</i>, and <i>MDA</i> and upregulated the expression of <i>SOD1</i>, <i>CAT</i>, and <i>IL-10</i>. Additionally, the damaged gut barriers occludin and zonula occludens-1 (ZO-1) in the CON+DSS group were enhanced with LSE supplementation. Furthermore, LSE treatment regulated the gut microbial communities with higher relative abundance of <i>Dubosiella</i> and <i>Ruminococcus torques</i> group and lower relative abundance of <i>Bacteroides</i> and <i>Turicibacter</i>. Moreover, the contents of short-chain fatty acids (SCFAs) as products of gut microbiota were also increased. Correlation analysis showed that the mRNA expression of <i>SOD1</i> was negatively correlated with <i>TNF-α</i> (r = -0.900, <i>P</i> < 0.05); the mRNA expression of <i>IL-6</i> (r = -0.779, <i>P</i> < 0.05) and <i>TNF-α</i> (r = -0.703, <i>P</i> < 0.05) had a dramatically negative correlation with <i>Dubosiella</i>. In conclusion, LSE supplementation could effectively ameliorate inflammation by modulating oxidative stress and gut microbiota in a colitis mouse model.

34832543

Campylobacter jejuni, a prevalent foodborne bacterial pathogen, is mainly transmitted from poultry with few effective prevention approaches. In this study, we aimed to investigate the role of microbiota on C. jejuni chicken colonization. Microbiota from specific pathogen-free (SPF) mouse stools were collected as SPF-Aerobe and SPF-Anaerobe. Birds were colonized with SPF-Aerobe or SPF-Anaerobe at day 0 and infected with C. jejuni AR101 at day 12. Notably, C. jejuni AR101 colonized at 5.3 and 5.6 log10&nbsp;C. jejuni CFU/g chicken cecal digesta at days 21 and 28, respectively, while both SPF-Aerobe and SPF-Anaerobe microbiota reduced pathogen colonization. Notably, SPF-Aerobe and SPF-Anaerobe increased cecal phylum Bacteroidetes and reduced phylum Firmicutes compared to those in the nontransplanted birds. Interestingly, microbiota from noninfected chickens, SPF-Aerobe, or SPF-Anaerobe inhibited AR101 in vitro growth, whereas microbiota from infected birds alone failed to reduce pathogen growth. The bacterium Enterobacter102 isolated from infected birds transplanted with SPF-Aerobe inhibited AR101 in vitro growth and reduced pathogen gut colonization in chickens. Together, SPF mouse microbiota was able to colonize chicken gut and reduce C. jejuni chicken colonization. The findings may help the development of effective strategies to reduce C. jejuni chicken contamination and campylobacteriosis.

35070042

Pancreatic cancer is the 7^th leading cause of death due to cancer in industrialized countries and the 11^th most common cancer globally, with 458918 new cases (2.5% of all cancers) and 432242 deaths (4.5% of all cancer deaths) in 2018. Unfortunately, 80% to 90% of the patients present with unresectable disease, and the reported 5-year survival rate range between 10% and 25%, even after successful resection with tumor-free margins. Systemic chemotherapy, radiotherapy, and minimally invasive image-guided procedures that have emerged over the past years, are used for the management of non-operable PC. This review focuses on currently available non-surgical options of locally advanced pancreatic cancer.

34876784

<i>Clostridioides difficile</i> (<i>C. difficile</i>) is a gram-positive, anaerobic spore-forming bacterium and a major cause of antibiotic-associated diarrhea. Humans are naturally resistant to <i>C. difficile</i> infection (CDI) owing to the protection provided by healthy gut microbiota. When the gut microbiota is disturbed, <i>C. difficile</i> can colonize, produce toxins, and manifest clinical symptoms, ranging from asymptomatic diarrhea and colitis to death. Despite the steady-if not rising-prevalence of CDI, it will certainly become more problematic in a world of antibiotic overuse and the post-antibiotic era. <i>C. difficile</i> is naturally resistant to most of the currently used antibiotics as it uses multiple resistance mechanisms. Therefore, current CDI treatment regimens are extremely limited to only a few antibiotics, which include vancomycin, fidaxomicin, and metronidazole. Therefore, one of the main challenges experienced by the scientific community is the development of alternative approaches to control and treat CDI. In this Frontier article, we collectively summarize recent advances in alternative treatment approaches for CDI. Over the past few years, several studies have reported on natural product-derived compounds, drug repurposing, high-throughput library screening, phage therapy, and fecal microbiota transplantation. We also include an update on vaccine development, pre- and pro-biotics for CDI, and toxin antidote approaches. These measures tackle CDI at every stage of disease pathology <i>via</i> multiple mechanisms. We also discuss the gaps and concerns in these developments. The next epidemic of CDI is not a matter of if but a matter of when. Therefore, being well-equipped with a collection of alternative therapeutics is necessary and should be prioritized.

35158646

We evaluated the effects of probiotic compounds on the composition of the gut microbiota. Forty newborn calves were random allocated to the lactic acid bacteria + yeast group (LS group), lactic acid bacteria group (L group), yeast group (S group), and control group (D group). Probiotics containing Lactococcus lactis subsp. lactis, Pediococcus pentosaceus, Lactobacillus plantarum, Saccharomyces cerevisiae, and Kluyveromyces marxianus were fed to calves in the three treatment groups for 15 days. The feeding process lasted 15 days. Fecal samples were collected from all calves at the end of the trial and analyzed using high-throughput 16S rRNA sequencing. Totals of 1,029,260 high-quality reads and 420,010,128 bp of sequences were obtained. Among the four groups, the alpha diversity of gut microbes was significantly higher in newborn cattle in the LS group than in those in the L, S, and D groups. Overall, the dominant phyla were Firmicutes, Actinobacteria, and Bacteroidetes, whereas Bifidobacterium was the most abundant phylum in the gut of cattle in the LS group. Newborn calves from the compound probiotic groups had closely clustered gut bacterial communities and had lower rates of diarrhea. Overall, compound probiotics regulated the intestinal microbiota community structure of newborn calves and improved intestinal health. New information relevant to the prevention of diarrhea is provided by our research in newborn calves.

34917357

A safe method to increase the occlusal vertical dimension (OVD) in patients with mild temporomandibular symptoms (such as tenderness upon palpation) is described. After a temporomandibular joint magnetic resonance (MR), an OVD increase was sought, pursuing pure rotational movement without condyle displacement. Prior to definitive rehabilitation, an additional MR confirmed steady and healthy condyle-disc-fossa relationships.

35061828

Fate of biofilm sloughing was assessed in a laboratory-scale (LS) integrated fixed-film sequencing batch reactor (IF-SBR) treating synthetic wastewater and in a full-scale (FS) integrated fixed-film activated sludge (IFAS) system treating municipal wastewater. It was observed that the properties of biofilms and flocs, including sludge volume index (SVI), mixed liquor suspended solids (MLSS), effluent suspended solids (ESS), relative hydrophobicity, and composition of extracellular polymeric substance (EPS) were associated with biofilm sloughing and formation of large granular flocs in the LS IF-SBR. In the FS IFAS system, the changes were studied at the molecular level. For example, the extracted EPS content results (the protein to polysaccharide ratio decreased in the flocs and increased in the biofilms, with biofilm sloughing) were complemented with the confocal laser scanning microscopy (CLSM) coupled with molecular specific staining. CLSM analyses revealed that micro-colonies rich in polysaccharides readily sloughed from the carriers. Live-dead staining revealed areas of the biofilm where the viability of biomass was a contributing factor associated with areas of the biofilm susceptible to sloughing. 16S rRNA gene sequencing (Illumina) of FS IFAS samples revealed greater diversity (α-diversity) in biofilms compared to flocs. Biofilm sloughing resulted in a decrease in diversity in biofilms and a corresponding increase in the flocs during sloughing. Microbial population dynamics revealed that bacteria known for denitrification (for example, Comamonadaceae) detached from the biofilms during sloughing, readily associated with the suspended biomass, and were retained in the bioreactors.

35155528

<h4>Background</h4>Medicinal dendrobiums are used popularly in traditional Chinese medicine for the treatment of diabetes, while their active compounds and mechanism remain unclear. This review aimed to evaluate the mechanism and active compounds of medicinal dendrobiums in diabetes management through a systematic approach.<h4>Methods</h4>A systematic approach was conducted to search for the mechanism and active phytochemicals in Dendrobium responsible for anti-diabetic actions using databases PubMed, Embase, and SciFinder.<h4>Results</h4>Current literature indicates polysaccharides, bibenzyls, phenanthrene, and alkaloids are commonly isolated in <i>Dendrobium</i> genusin which polysaccharides and bibenzyls are most aboundant. Many animal studies have shown that polysaccharides from the species of <i>Dendrobium</i> provide with antidiabetic effects by lowering glucose level and reversing chronic inflammation of T2DM taken orally at 200 mg/kg. <i>Dendrobium</i> polysaccharides protect pancreatic β-cell dysfunction and insulin resistance in liver. <i>Dendrobium</i> polysaccharides up-regulate the abundance of short-chain fatty acid to stimulate GLP-1 secretion through gut microbiota. Bibenzyls also have great potency to inhibit the progression of the chronic inflammation in cellular studies.<h4>Conclusion</h4>Polysaccharides and bibenzyls are the major active compounds in medicinal dendrobiums for diabetic management through the mechanisms of lowering glucose level and reversing chronic inflammation of T2DM by modulating pancreatic β-cell dysfunction and insulin resistance in liver as a result from gut microbita regulation.

34912565

Engineered nanoparticles (NPs) that are released into wastewater are retained by wastewater treatment plants (WWTPs) and accumulate in sewage sludge. Increasing shares of sludge are incinerated and landfilled, especially in industrialized countries. It is debated whether certain types of NPs can outlive the incineration process and subsequently be released from sewage sludge ash (SSA) landfills. To investigate the release of different types of NPs from SSA, we spiked gold (Au), silver (Ag) and cerium dioxide (CeO2) NPs to a pilot WWTP increasing the Au, Ag and Ce concentrations to 30, 43 and 389 mg kg-1 (dry matter basis) in the digested sludge. The spiked sludge was incinerated in a pilot fluidized bed reactor resulting in SSA with Au, Ag and Ce concentrations of 61, 103 and 854 mg kg-1. In addition, two sludge samples from a full-scale WWTP with Au concentrations of 5 and 16 mg kg-1 were incinerated, resulting in SSA with 9 mg kg-1 and 30 mg kg-1 Au. The spiked Au-NPs remain largely unaltered during the wastewater treatment and incineration process, whereas Ag-NPs and CeO2-NPs undergo transformation. During simulated landfill leaching in columns flushed with 400 to 500 pore volumes of artificial rainwater, Ag and Ce were retained in the ash, whereas about 17% of the spiked Au was released, mainly in particulate form. Lower fractions of mostly particulate Au were released from the ashes (3 and 9%) of unspiked SSA. In conclusion, unaltered Au-NPs significantly leach from landfilled SSA, whereas the incorporation of Ag-NPs and CeO2-NPs as transformed species into the SSA matrix limits the leaching of (nano)particulate and dissolved Ag and Ce compounds.

35197949

To understand the relative influences of operational taxonomic units (OTUs) and amplicon sequence variants (ASVs) on patterns of marine microbial diversity and community composition, we examined bacterial diversity and community composition of seawater from 12 sites in the North Atlantic Ocean and Canadian Arctic and sediment from two sites in the North Atlantic. For the seawater analyses, we included samples from three to six zones in the water column of each site. For the sediment analyses, we included over 20 sediment horizons at each of two sites. For all samples, we amplified the V4-V5 hypervariable region of the 16S ribosomal RNA (rRNA) gene. We analyzed each sample in two different ways: (i) by clustering its reads into 97%-similar OTUs and (ii) by assigning sequences to unique ASVs. OTU richness is much higher than ASV richness for every sample, but both OTUs and ASVs exhibit similar vertical patterns of relative diversity in both the water column and the sediment. Bacterial richness is highest just below the photic zone in the water column and at the seafloor in the sediment. For both OTUs and ASVs, richness estimates depend on the number of sequences analyzed. Both methods yield broadly similar community compositions for each sample at the taxonomic levels of phyla to families. While the two methods yield different richness values, broad-scale patterns of relative richness and community composition are similar with both methods.

34636363

<h4>Purpose of review</h4>Antimicrobial resistance is a rising threat to global health and is associated with increased mortality. Intestinal colonisation with multidrug-resistant organisms (MDRO) can precede invasive infection and facilitates spread within communities and hospitals. Novel decolonisation strategies, such as faecal microbiota transplantation (FMT), are being explored. The purpose of this review is to provide an update on how the field of FMT for MDRO decolonisation has developed during the past year and to assess the efficacy of FMT for intestinal MDRO decolonisation.<h4>Recent findings</h4>Since 2020, seven highly heterogenous, small, nonrandomised cohort studies and five case reports have been published. In line with previous literature, decolonisation rates ranged from 20 to 90% between studies and were slightly higher for carbapenem-resistant Enterobacteriaceae than vancomycin-resistant Enterococcus. Despite moderate decolonisation rates in two studies, a reduction in MDRO bloodstream and urinary tract infections was observed.<h4>Summary and implications</h4>Although a number of smaller cohort studies show some effect of FMT for MDRO decolonisation, questions remain regarding the true efficacy of FMT (taking spontaneous decolonisation into account), the optimal route of administration, the role of antibiotics pre and post-FMT and the efficacy in different patient populations. The observed decrease in MDRO infections post-FMT warrants further research.

34974020

During the COVID-19 pandemic, high consumption of antivirals, antibiotics, antiparasitics, antiprotozoals, and glucocorticoids used in the treatment of this virus has been reported. Conventional treatment systems fail to efficiently remove these contaminants from water, becoming an emerging concern from the environmental field. Therefore, the objective of the present work is to address the current state of the literature on the presence and removal processes of these drugs from water bodies. It was found that the concentration of most of the drugs used in the treatment of COVID-19 increased during the pandemic in water bodies. Before the pandemic, Azithromycin concentrations in surface waters were reported to be in the order of 4.3 ng L^-1, and during the pandemic, they increased up to 935 ng L^-1. Laboratory scale studies conclude that adsorption and advanced oxidation processes (AOPs) can be effective in the removal of these drugs. Up to more than 80% removal of Azithromycin, Chloroquine, Ivermectin, and Dexamethasone in aqueous solutions have been reported using these processes. Pilot-scale tests achieved 100% removal of Azithromycin from hospital wastewater by adsorption with powdered activated carbon. At full scale, treatment plants supplemented with ozonation and artificial wetlands removed all Favipiravir and Azithromycin, respectively. It should be noted that hybrid technologies can improve removal rates, process kinetics, and treatment cost. Consequently, the development of new materials that can act synergistically in technically and economically sustainable treatments is required.

34927036

<h4>Background</h4>This study was designed to assess the efficacy of <i>Bifidobacterium animalis</i> ssp. <i>lactis</i> (Bl-04) for prevention of rhinovirus colds and to explore the interactions between the probiotic, the viral infection, the host response and the host microbiome.<h4>Methods</h4>The effect of ingestion of the probiotic Bl-04 was evaluated in a randomized, double-blinded rhinovirus (RV) challenge study. Healthy volunteers recruited from a university community in USA were randomized 1:1 using a computer generated code to ingest either Bl-04 (n=165) or placebo (n=169) for 28 days and were then challenged with RV-A39, and followed for 14 days. All study interactions and sample collection occurred in dedicated clinical research space. The primary analysis was the effect of the probiotic on the incidence of RV-associated illness. (Trial registration: NCT02679807, study complete).<h4>Findings</h4>The first cohort of volunteers was randomized on March 14, 2016 and the last (5^th) cohort was randomized on March 12, 2018. Sixty-three (56%, 95% CI [47%; 66%]) of the 112 subjects in the active group and 60 (50%,95% CI [41%; 59%]) of the 120 subjects in the placebo group had a protocol-defined rhinovirus-associated illness (χ²=0·91, p=0·34). The point estimate of the difference in illness (active-placebo) is 6.3% (95% CI -6.7;19.1). There were no adverse events that were judged as definitely or probably related to the study product.<h4>Interpretation</h4>In this study there was no effect of orally administered Bl-04 on the occurrence of RV-associated illness.<h4>Funding</h4>Danisco Sweeteners Oy (now IFF Health & Biosciences).

34953376

Salmonella Infantis has been the etiological agent of numerous foodborne outbreaks of nontyphoidal Salmonella. Consequently, there is an emergent need to mitigate Salmonella Infantis among poultry. Thus, this study evaluated the efficacy of cetylpyridinium chloride (CPC) versus peroxyacetic acid (PAA), on bone-in, skin-on chicken thighs for the reduction of Salmonella and changes in the microbiota. Exactly 100 skin-on, bone-in chicken thighs (2 trials, 0 and 24 h, k = 5, n = 5, N = 50) were inoculated with 10⁸ CFU/mL of a nalidixic acid resistant strain of S. Infantis for an attachment of 10⁶ CFU/g. Thighs were treated with 20 s part dips (350 mL): a no inoculum, no treatment control (NINTC); no treatment control (NTC); tap water (TW); TW+CPC; TW+PAA. Following treatment, thighs were rinsed in 150 mL of nBPW, and rinsates were collected. Rinsates were spot plated for Salmonella and aerobic bacteria (APC). Log₁₀ transformed counts were analyzed using a mixed-effects model (random effect = trial) with means separated using Tukey's HSD (P ≤ 0.05). The genomic DNA of rinsates was extracted, and the 16S rDNA was sequenced on an Illumina MiSeq. Microbiota data were analyzed using QIIME2, with data considered significant at P ≤ 0.05 (main effects) and Q≤0.05 (pairwise differences). Treatment × time interactions were observed for both Salmonella and APC (P < 0.05). The treatment of thighs with PAA and CPC reduced Salmonella and APC in respect to the controls. Numerically, thighs treated with CPC had less Salmonella (4.29 log₁₀CFU/g) and less APC (4.56 log₁₀CFU/g) at 24 h than all other treatments (P > 0.05). Differences in diversity metrics were not consistently observed between treatments; however, in trial 2, the NTC treated thighs were different than those treated with CPC (P < 0.05; Q < 0.05). In both trials, ANCOM, the analysis of microbiome compositional profiles, revealed shifts at both the phylum and order levels with thighs being different in the relative abundances of Proteobacteria (P < 0.05). In conclusion, treatment of skin-on poultry parts with CPC may reduce the risk of foodborne outbreaks caused by Salmonella Infantis.

34794087

<h4>Background</h4>Foot collapse is primarily diagnosed and monitored using lateral weight-bearing foot x-ray images. There are several well-validated measurements which aid assessment. However, these are subject to inter- and intra-user variability.<h4>Objective</h4>To develop and validate a software system for the fully automatic assessment of radiographic changes associated with foot collapse; automatically generating measurements for calcaneal tilt, cuboid height and Meary's angle.<h4>Methods</h4>This retrospective study was approved by the Health Research Authority (IRAS 244852). The system was developed using lateral weight-bearing foot x-ray images, and evaluated against manual measurements from five clinical experts. The system has two main components: (i) a Random Forest-based point-finder to outline the bones of interest; and (ii) a geometry-calculator to generate the measurements based on the point positions from the point-finder. The performance of the point-finder was assessed using the point-to-point error (i.e. the mean absolute distance between each found point and the equivalent ground truth point, averaged over all points per image). For assessing the performance of the geometry-calculator, linear mixed models were fitted to estimate clinical inter-observer agreement and to compare the performance of the software system to that of the clinical experts.<h4>Results</h4>A total of 200 images were collected from 79 subjects (mean age: 56.4 years ±12.9 SD, 30/49 females/males). There was good agreement among all clinical experts with intraclass correlation estimates between 0.78 and 0.86. The point-finder achieved a median point-to-point error of 2.2 mm. There was no significant difference between the clinical and automatically generated measurements using the point-finder points, suggesting that the fully automatically obtained measurements are in agreement with the manually obtained measurements.<h4>Conclusions</h4>The proposed system can be used to support and automate radiographic image assessment for diagnosing and managing foot collapse, saving clinician time, and improving patient outcomes.

34924799

<h4>Background</h4>The data we present are part of the AGRO-ECOSERVICES project (Assessing ecosystem services and disservices provided by arthropod species in Azorean agroecosystems). The project aims to evaluate the relative importance of native and non-native organisms as ecosystem services (ES) and disservices (ED) providers, by combining novel, direct and quantitative tools for monitoring agro-biodiversity. Ecosystem services include evaluation of natural pest control by predation, seed predation on weed plants, pollination, decomposition and ecosystem disservices, herbivory and seed predation on crop plants. Active Aerial Searching (AAS) (only in maize-fields) and pitfall traps were used to sample the arthropod biodiversity (predatory spiders, true-bugs and beetles and main insect pests) on four agricultural habitats of Terceira Island, namely citrus orchards, low and high elevation maize fields and vineyards.<h4>New information</h4>We provided an inventory of all arthropods recorded in four Azorean agroecosystems (citrus orchards, low and high elevation maize fields and vineyards) from Terceira Island. A total of 50412 specimens were collected, belonging to four classes, 20 orders, 81 families and 200 identified species of arthropods. A total of 127 species are considered introduced (n = 22646) and 69 native non-endemic (n = 24117). Four endemic species were recorded with very few specimens (n = 14) and 3635 specimens belong to unidentified taxa recorded only at genus or family level. Five species are new records for Terceira Island, with <i>Lagriahirta</i> (Linnaeus, 1758) (Coleoptera, Tenebrionidae) being also a new record for the Azores. This publication contributes to a better knowledge of the arthropods communities present in agro-ecosystems of Terceira Island and will serve as a baseline for future monitoring schemes targeting the long-term change in arthropod diversity and abundance.

34978524

The human gastrointestinal tract is home to trillions of microbes. Gut microbial communities have a significant regulatory role in the intestinal physiology, such as gut motility. Microbial effect on gut motility is often evoked by bioactive molecules from various sources, including microbial break down of carbohydrates, fibers or proteins. In turn, gut motility regulates the colonization within the microbial ecosystem. However, the underlying mechanisms of such regulation remain obscure. Deciphering the inter-regulatory mechanisms of the microbiota and bowel function is crucial for the prevention and treatment of gut dysmotility, a comorbidity associated with many diseases. In this review, we present an overview of the current knowledge on the impact of gut microbiota and its products on bowel motility. We discuss the currently available techniques employed to assess the changes in the intestinal motility. Further, we highlight the open challenges, and incorporate biophysical elements of microbes-motility interplay, in an attempt to lay the foundation for describing long-term impacts of microbial metabolite-induced changes in gut motility.

34855380

A physiologically based pharmacokinetic (PBPK) model was developed for daidzein and its metabolite S-equol. Anaerobic in vitro incubations of pooled fecal samples from S-equol producers and nonproducers allowed definition of the kinetic constants. PBPK model-based predictions for the maximum daidzein plasma concentration (<i>C</i>_max) were comparable to literature data. The predictions also revealed that the <i>C</i>_max of S-equol in producers was only up to 0.22% that of daidzein, indicating that despite its higher estrogenicity, S-equol is likely to contribute to the overall estrogenicity upon human daidzein exposure to a only limited extent. An interspecies comparison between humans and rats revealed that the catalytic efficiency for S-equol formation in rats was 210-fold higher than that of human S-equol producers. The described in vitro-in silico strategy provides a proof-of-principle on how to include microbial metabolism in humans in PBPK modeling as part of the development of new approach methodologies (NAMs).

34696323

West Nile virus (WNV, Flaviviridae, Flavivirus) is a mosquito-borne flavivirus introduced to North America in 1999. Since 1999, the Earth's average temperature has increased by 0.6 °C. Mosquitoes are ectothermic organisms, reliant on environmental heat sources. Temperature impacts vector-virus interactions which directly influence arbovirus transmission. RNA viral replication is highly error-prone and increasing temperature could further increase replication rates, mutation frequencies, and evolutionary rates. The impact of temperature on arbovirus evolutionary trajectories and fitness landscapes has yet to be sufficiently studied. To investigate how temperature impacts the rate and extent of WNV evolution in mosquito cells, WNV was experimentally passaged 12 times in Culex tarsalis cells, at 25 °C and 30 °C. Full-genome deep sequencing was used to compare genetic signatures during passage, and replicative fitness was evaluated before and after passage at each temperature. Our results suggest adaptive potential at both temperatures, with unique temperature-dependent and lineage-specific genetic signatures. Further, higher temperature passage was associated with significantly increased replicative fitness at both temperatures and increases in nonsynonymous mutations. Together, these data indicate that if similar selective pressures exist in natural systems, increases in temperature could accelerate emergence of high-fitness strains with greater phenotypic plasticity.