Comparative genomics analysis reveals genetic characteristics and nitrogen fixation profile of Bradyrhizobium.

Bradyrhizobium is a genus of nitrogen-fixing bacteria, with some species producing nodules in leguminous plants. Investigations into Bradyrhizobium have recently revealed its substantial genetic resources and agricultural benefits, but a comprehensive survey of its genetic diversity and functional properties is lacking. Using a panel of various strains (N = 278), this study performed a comparative genomics analysis to anticipate genes linked with symbiotic nitrogen fixation. Bradyrhizobium's pan-genome consisted of 84,078 gene families, containing 824 core genes and 42,409 accessory genes. Core genes were mainly involved in crucial cell processes, while accessory genes served diverse functions, including nitrogen fixation and nodulation. Three distinct genetic profiles were identified based on the presence/absence of gene clusters related to nodulation, nitrogen fixation, and secretion systems. Most Bradyrhizobium strains from soil and non-leguminous plants lacked major nif/nod genes and were evolutionarily more closely related. These findings shed light on Bradyrhizobium's genetic features for symbiotic nitrogen fixation.

Museums and art therapy: A bibliometric analysis of the potential of museum art therapy.

In this paper, the current promotion of art therapy in museum development and the potential value of the combination of museum and art therapy on mental health are explored. Individuals who usually evade any treatment may experience art therapy in a museum setting as a release from their suppressed emotions. Furthermore, art therapy may enable them to discover how to express themselves, thereby reducing anxiety and promoting a sense of social belonging, which may be unattainable in other healing settings. Moreover, this literature review afforded us a preliminary understanding of issues in museum education and art therapy, which require further examination, including implications for China's museum art therapy in practice and future research directions.

Pan-Genome Analysis of Campylobacter: Insights on the Genomic Diversity and Virulence Profile.

The genus Campylobacter contains pathogens that cause bacterial gastroenteritis in humans and animals. Despite large-scale sequencing efforts to raise clinical awareness of Campylobacter, little is known about the diversity and functions of virulence factors. Here, we constructed the pan-genome of Campylobacter using 39 representative genomes, elucidating their genetic diversity, evolutionary characteristics, and virulence and resistance profiles. The Campylobacter pan-genome was open and showed extensive genome variability, with high levels of gene expansion and contraction as the organism evolved. These Campylobacter members had diverse virulence gene content, and six potential core virulence genes (porA, PEB4, cheY, htrB, Cj1135, and kpsF) have been identified. The conserved mechanisms for Campylobacter pathogenicity were related to adherence, motility, and immune modulation. We emphasized the relative importance of variable virulence genes. Many virulence genes have experienced expansion or contraction in specific lineages, which may be one of the factors causing differences in the content of virulence genes. Additionally, these Campylobacter genomes have a high prevalence of the cmeA and cmeC genes, which are linked to the CmeABC pump and contribute to multidrug resistance. The genomic variations, core and variable virulence factors, and resistance genes of Campylobacter characterized in this study would contribute to a better understanding of the virulence of Campylobacter and more effective use of candidates for drug development and prevention of Campylobacter infections. IMPORTANCE Pathogenic members of the genus Campylobacter are recognized as one of the major causative agents of human bacterial gastroenteritis. This study revealed the pan-genome of 39 Campylobacter species, provided the most updated reconstruction of the global virulence gene pool of 39 Campylobacter species, and identified species-related virulence differences. This study highlighted the basic conserved functionality and specificity of pathogenicity that are crucial to infection, which was critical for improving the diagnosis and prevention of Campylobacter infections.

Stage-specific roles of microbial dysbiosis and metabolic disorders in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a progressive disease including four stages, where gut microbiome is associated with pathogenesis. We aimed to investigate stage-specific roles of microbial dysbiosis and metabolic disorders in RA. METHODS: We investigated stage-based profiles of faecal metagenome and plasma metabolome of 76 individuals with RA grouped into four stages (stages I-IV) according to 2010 RA classification criteria, 19 individuals with osteroarthritis and 27 healthy individuals. To verify bacterial invasion of joint synovial fluid, 16S rRNA gene sequencing, bacterial isolation and scanning electron microscopy were conducted on another validation cohort of 271 patients from four RA stages. RESULTS: First, depletion of Bacteroides uniformis and Bacteroides plebeius weakened glycosaminoglycan metabolism (p<0.001), continuously hurting articular cartilage across four stages. Second, elevation of Escherichia coli enhanced arginine succinyltransferase pathway in the stage II and stage III (p<0.001), which was correlated with the increase of the rheumatoid factor (p=1.35×10-3) and could induce bone loss. Third, abnormally high levels of methoxyacetic acid (p=1.28×10-8) and cysteine-S-sulfate (p=4.66×10-12) inhibited osteoblasts in the stage II and enhanced osteoclasts in the stage III, respectively, promoting bone erosion. Fourth, continuous increase of gut permeability may induce gut microbial invasion of the joint synovial fluid in the stage IV. CONCLUSIONS: Clinical microbial intervention should consider the RA stage, where microbial dysbiosis and metabolic disorders present distinct patterns and played stage-specific roles. Our work provides a new insight in understanding gut-joint axis from a perspective of stages, which opens up new avenues for RA prognosis and therapy.

Multi-omics profiling reveals comprehensive microbe-plant-metabolite regulation patterns for medicinal plant Glycyrrhiza uralensis Fisch.

Glycyrrhiza uralensis Fisch is a medicinal plant widely used to treat multiple diseases in Europe and Asia, and its efficacy largely depends on liquiritin and glycyrrhizic acid. The regulatory pattern responsible for the difference in efficacy between wild and cultivated G. uralensis remains largely undetermined. Here, we collected roots and rhizosphere soils from wild (WT) G. uralensis as well as those farmed for 1 year (C1) and 3 years (C3), generated metabolite and transcript data for roots, microbiota data for rhizospheres and conducted comprehensive multi-omics analyses. We updated gene structures for all 40 091 genes in G. uralensis, and based on 52 differentially expressed genes, we charted the route-map of both liquiritin and glycyrrhizic acid biosynthesis, with genes BAS, CYP72A154 and CYP88D6 critical for glycyrrhizic acid biosynthesis being significantly expressed higher in wild G. uralensis than in cultivated G. uralensis. Additionally, multi-omics network analysis identified that Lysobacter was strongly associated with CYP72A154, which was required for glycyrrhizic acid biosynthesis. Finally, we developed a holistic multi-omics regulation model that confirmed the importance of rhizosphere microbial community structure in liquiritin accumulation. This study thoroughly decoded the key regulatory mechanisms of liquiritin and glycyrrhizic acid, and provided new insights into the interactions of the plant's key metabolites with its transcriptome, rhizosphere microbes and environment, which would guide future cultivation of G. uralensis.

Glycyrrhiza uralensis Fisch. Root-associated microbiota: the multifaceted hubs associated with environmental factors, growth status and accumulation of secondary metabolites.

Glycyrrhiza uralensis Fisch. is an important, perennial medicinal plant whose root microbiome is considered to play an important role in promoting accumulation of effective medicinal ingredients (liquiritin and glycrrhizic acid). Here, we report a comprehensive analysis of the microbial community structural composition and metabolite-plant-microbes association of G. uralensis Fisch. We collected both soil and rhizosphere samples of G. uralensis from different environmental conditions (cultivated and wild) and growth years (grown for one year and three years). Our data revealed higher species diversity in the wild group than in the cultivated group. The core rhizosphere microbiome of G. uralensis comprised 78 genera, including Bacillus, Pseudomonas, Rhizobium, some of which were potential plant beneficial microbes. Our results suggest that the growth of G. uralensis has a correlation with the root-associated microbiota assemblage. Integrated analysis among rhizosphere microbial taxa, plant gene expressions, and liquiritin and glycrrhizic acid accumulation showed that the liquiritin and glycrrhizic acid accumulation exhibited associations with the rhizosphere microbial composition at the genus level. The results provide valuable information to guide cultivation of G. uralensis, and potentially to harness the power of the root-associated microbiota to improve medicinal plant production.

Art therapy practices in museum education: A mini review.

This article reviews the potential functions and approaches of museum education in alleviating psychological anxiety, particularly the psychological anxiety experienced by adolescents during the COVID-19 pandemic. We outline the main forms of museum education, highlighting how it supports the potential functions of art therapy for psychological anxiety. Thereafter, we review the representative research on museum art therapy practice for different populations to invite discussion, dialogue, and awareness of future directions for museum education and suggest gaps in the research that require further study.

Understanding of the Site-Specific Microbial Patterns towards Accurate Identification for Patients with Diarrhea-Predominant Irritable Bowel Syndrome.

Fecal microbial community could not fully represent the intestinal microbial community. However, most studies analyzing diarrhea-dominant irritable bowel syndrome (IBS-D) were mainly based on fecal samples. We aimed to characterize the IBS-D microbial community patterns using samples at multiple intestinal sites. This study recruited 74 IBS-D patients and 20 healthy controls (HC). 22.34%, 8.51%, 14.89%, and 54.26% of them contributed to one, two, three, and four sites: duodenal mucosa (DM), duodenal lumen (DL), rectal mucosa (RM), and rectal lumen (RL) of intestinal samples, respectively. Then 16S rRNA gene analysis was performed on these 283 samples. The result showed that IBS-D microbial communities have specific patterns at each intestinal site differing from that of HC. Across hosts and sites, Bacillus, Burkholderia, and Faecalibacterium were the representative genera in duodenum of IBS-D, duodenum of HC, and rectum of HC, respectively. Samples from mucosa and lumen in rectum were highly distinguishable, regardless of IBS-D and HC. Additionally, IBS-D patients have lower microbial co-abundance network connectivity. Moreover, RM site-specific biomarker: Bacteroides used alone or together with Prevotella and Oscillospira in RM showed outstanding performance in IBS-D diagnosis. Furthermore, Bacteroides and Prevotella in RM were strongly related to the severity of abdominal pain, abdominal discomfort, and bloating in IBS-D patients. In summary, this study also confirmed fecal microbial community could not fully characterize intestinal microbial communities. Among these site-specific microbial communities, RM microbial community would be more applicable in the diagnosis of IBS-D. IMPORTANCE Microbial community varied from one site to another along the gastrointestinal tract, but current studies about intestinal microbial community in IBS-D were mainly based on fecal samples. Based on 283 intestinal samples collected from DM, DL, RM, and RL of HC and IBS-D, we found different intestinal sites had their site-specific microbial patterns in IBS-D. Notably, RM site-specific microbes Bacteroides, Prevotella, and Oscillospira could be used to discriminate IBS-D from HC accurately. Our findings could help clinicians realize the great potential of the intestinal microbial community in RM for better diagnosis of IBS-D patients.

Micro-coevolution of host genetics with gut microbiome in three Chinese ethnic groups.

Understanding the micro-coevolution of the human gut microbiome with host genetics is challenging but essential in both evolutionary and medical studies. To gain insight into the interactions between host genetic variation and the gut microbiome, we analyzed both the human genome and gut microbiome collected from a cohort of 190 students in the same boarding college and representing 3 ethnic groups, Uyghur, Kazakh, and Han Chinese. We found that differences in gut microbiome were greater between genetically distinct ethnic groups than those genetically closely related ones in taxonomic composition, functional composition, enterotype stratification, and microbiome genetic differentiation. We also observed considerable correlations between host genetic variants and the abundance of a subset of gut microbial species. Notably, interactions between gut microbiome species and host genetic variants might have coordinated effects on specific human phenotypes. Bacteroides ovatus, previously reported to modulate intestinal immunity, is significantly correlated with the host genetic variant rs12899811 (meta-P = 5.55 × 10-5), which regulates the VPS33B expression in the colon, acting as a tumor suppressor of colorectal cancer. These results advance our understanding of the micro-coevolution of the human gut microbiome and their interactive effects with host genetic variation on phenotypic diversity.

Integrating pan-genome with metagenome for microbial community profiling.

Advances in sequencing technology have led to the increased availability of genomes and metagenomes, which has greatly facilitated microbial pan-genome and metagenome analysis in the community. In line with this trend, studies on microbial genomes and phenotypes have gradually shifted from individuals to environmental communities. Pan-genomics and metagenomics are powerful strategies for in-depth profiling study of microbial communities. Pan-genomics focuses on genetic diversity, dynamics, and phylogeny at the multi-genome level, while metagenomics profiles the distribution and function of culture-free microbial communities in special environments. Combining pan-genome and metagenome analysis can reveal the microbial complicated connections from an individual complete genome to a mixture of genomes, thereby extending the catalog of traditional individual genomic profile to community microbial profile. Therefore, the combination of pan-genome and metagenome approaches has become a promising method to track the sources of various microbes and decipher the population-level evolution and ecosystem functions. This review summarized the pan-genome and metagenome approaches, the combined strategies of pan-genome and metagenome, and applications of these combined strategies in studies of microbial dynamics, evolution, and function in communities. We discussed emerging strategies for the study of microbial communities that integrate information in both pan-genome and metagenome. We emphasized studies in which the integrating pan-genome with metagenome approach improved the understanding of models of microbial community profiles, both structural and functional. Finally, we illustrated future perspectives of microbial community profile: more advanced analytical techniques, including big-data based artificial intelligence, will lead to an even better understanding of the patterns of microbial communities.

Pan-genome study of Thermococcales reveals extensive genetic diversity and genetic evidence of thermophilic adaption.

Thermococcales has a strong adaptability to extreme environments, which is of profound interest in explaining how complex life forms emerge on earth. However, their gene composition, thermal stability and evolution in hyperthermal environments are still little known. Here, we characterized the pan-genome architecture of 30 Thermococcales species to gain insight into their genetic properties, evolutionary patterns and specific metabolisms adapted to niches. We revealed an open pan-genome of Thermococcales comprising 6070 gene families that tend to increase with the availability of additional genomes. The genome contents of Thermococcales were flexible, with a series of genes experienced gene duplication, progressive divergence, or gene gain and loss events exhibiting distinct functional features. These archaea had concise types of heat shock proteins, such as HSP20, HSP60 and prefoldin, which were constrained by strong purifying selection that governed their conservative evolution. Furthermore, purifying selection forced genes involved in enzyme, motility, secretion system, defence system and chaperones to differ in functional constraints and their disparity in the rate of evolution may be related to adaptation to specific niche. These results deepened our understanding of genetic diversity and adaptation patterns of Thermococcales, and provided valuable research models for studying the metabolic traits of early life forms.

Utilizing microbiome approaches to assist source tracking, treatment and prevention of COVID-19: Review and assessment.

COVID-19 has been one of the most serious infectious diseases since the end of 2019. However, the original source, as well as the treatment and prevention of causative agent of COVID-19 (namely SARS-CoV-2) are still unclear nearly a year after its publicly report. The microbiome approach, which has emerged in recent years focusing on human-related microbes, has become one of the promising avenues for source tracking, treatment, and prevention of a variety of infectious diseases including COVID-19. In this review, we summarized the microbiome approach as a supplementary approach for source tracking, treatment, and prevention of SARS-CoV-2 infection. We first provided background information on SARS-CoV-2 and microbiome approaches. Then we illustrated current strategies of microbiome methods to assist three aspects of COVID-19 research, namely source tracking, treatment, and prevention, respectively. Finally, we summarized the microbiome approaches and provided perspectives for future studies on faster and more effective SARS-CoV-2 epidemiology and pathogenesis based on microbiome approaches.

Stratification of athletes' gut microbiota: the multifaceted hubs associated with dietary factors, physical characteristics and performance.

Gut microbial communities of athletes differ from that of sedentary persons in both diversity and the presence of certain taxa. However, it is unclear to what degree elite athletes and non-elite athletes harbor different gut microbial community patterns and if we can effectively monitor the potential of athletes based on microbiota. A team of professional female rowing athletes in China was recruited and 306 fecal samples were collected from 19 individuals, which were separated into three cohorts: adult elite athlete's (AE), youth elite athlete's (YE), and youth non-elite athlete's (YN). The differences in gut microbiome among different cohorts were compared, and their associations with dietary factors, physical characteristics, and athletic performance were investigated. The microbial diversities of elite athletes were higher than those of youth non-elite athletes. The taxonomical, functional, and phenotypic compositions of AE, YE and YN were significantly different. Additionally, three enterotypes with clear separation were identified in athlete's fecal samples, with majority of elite athletes stratified into enterotype 3. And this enterotype-dependent gut microbiome is strongly associated with athlete performances. These differences in athlete gut microbiota lead to establishment of a random forest classifier based on taxonomical and functional biomarkers, capable of differentiating elite athletes and non-elite athletes with high accuracy. Finally, these versatilities of athlete microbial communities of athletes were found to be associated with dietary factors and physical characteristics, which can in concert explain 41% of the variability in gut microbiome.

Comprehensive Analysis Reveals the Evolution and Pathogenicity of Aeromonas, Viewed from Both Single Isolated Species and Microbial Communities.

The genus Aeromonas is a common gastrointestinal pathogen associated with human and animal infections. Due to the high level of cross-species similarity, their evolutionary dynamics and genetic diversity are still fragmented. Hereby, we investigated the pan-genomes of 29 Aeromonas species, as well as Aeromonas species in microbial communities, to clarify their evolutionary dynamics and genetic diversity, with special focus on virulence factors and horizontal gene transfer events. Our study revealed an open pan-genome of Aeromonas containing 10,144 gene families. These Aeromonas species exhibited different functional constraints, with the single-copy core genes and most accessory genes experiencing purifying selection. The significant congruence between core genome and pan-genome trees revealed that core genes mainly affected evolutionary divergences of Aeromonas species. Gene gains and losses revealed a high level of genome plasticity, exhibited by hundreds of gene expansions and contractions, horizontally transferred genes, and mobile genetic elements. The selective constraints shaped virulence gene pools of these Aeromonas strains, where genes encoding hemolysin were ubiquitous. Of these strains, Aeromonas aquatica MX16A seemed to be more resistant, as it harbored most resistance genes. Finally, the virulence factors of Aeromonas in microbial communities were quite dynamic in response to environment changes. For example, the virulence diversity of Aeromonas in microbial communities could reach levels that match some of the most virulent Aeromonas species (such as A. hydrophila) in penetrated-air and modified-air packaging. Our work shed some light onto genetic diversity, evolutionary history, and functional features of Aeromonas, which could facilitate the detection and prevention of infections.IMPORTANCE Aeromonas has long been known as a gastrointestinal pathogen, yet it has many species whose evolutionary dynamics and genetic diversity had been unclear until now. We have conducted pan-genome analysis for 29 Aeromonas species and revealed a high level of genome plasticity exhibited by hundreds of gene expansions and contractions, horizontally transferred genes, and mobile genetic elements. These species also contained many virulence factors both identified from single isolated species and microbial community. This pan-genome study could elevate the level for detection and prevention of Aeromonas infections.

The Seasonal Dynamics and the Influence of Human Activities on Campus Outdoor Microbial Communities.

Large-scale campus resembles a small "semi-open community," harboring disturbances from the exchanges of people and vehicles, wherein stressors such as temperature and population density differ among the ground surfaces of functional partitions. Therefore, it represents a special ecological niche for the study on microbial ecology in the process of urbanization. In this study, we investigated outdoor microbial communities in four campuses in Wuhan, China. We obtained 284 samples from 55 sampling sites over six seasons, as well as their matching climatic and environmental records. The structure of campus outdoor microbial communities which influenced by multiple climatic factors featured seasonality. The dispersal influence of human activities on microbial communities also contributed to this seasonal pattern non-negligibly. However, despite the microbial composition alteration in response to multiple stressors, the overall predicted function of campus outdoor microbial communities remained stable across campuses. The spatial-temporal dynamic patterns on campus outdoor microbial communities and its predicted functions have bridged the gap between microbial and macro-level ecosystems, and provided hints toward a better understanding of the effects of climatic factors and human activities on campus micro-environments.

Agricultural Risk Factors Influence Microbial Ecology in Honghu Lake.

Agricultural activities, including stock-farming, planting industry, and fish aquaculture, can affect the physicochemical and biological characters of freshwater lakes. However, the effects of pollution producing by agricultural activities on microbial ecosystem of lakes remain unclear. Hence, in this work, we selected Honghu Lake as a typical lake that is influenced by agriculture activities. We collected water and sediment samples from 18 sites, which span a wide range of areas from impacted and less-impacted areas. We performed a geospatial analysis on the composition of microbial communities associated with physicochemical properties and antibiotic pollution of samples. The co-occurrence networks of water and sediment were also built and analyzed. Our results showed that the microbial communities of impacted and less-impacted samples of water were largely driven by the concentrations of TN, TP, NO3--N, and NO2--N, while those of sediment were affected by the concentrations of Sed-OM and Sed-TN. Antibiotics have also played important roles in shaping these microbial communities: the concentrations of oxytetracycline and tetracycline clearly reflected the variance in taxonomic diversity and predicted functional diversity between impacted and less-impacted sites in water and sediment samples, respectively. Furthermore, for samples from both water and sediment, large differences of network topology structures between impacted and less-impacted were also observed. Our results provide compelling evidence that the microbial community can be used as a sentinel of eutrophication and antibiotics pollution risk associated with agricultural activity; and that proper monitoring of this environment is vital to maintain a sustainable environment in Honghu Lake.

Pan-genome analyses of 24 Shewanella strains re-emphasize the diversification of their functions yet evolutionary dynamics of metal-reducing pathway.

BACKGROUND: Shewanella strains are important dissimilatory metal-reducing bacteria which are widely distributed in diverse habitats. Despite efforts to genomically characterize Shewanella, knowledge of the molecular components, functional information and evolutionary patterns remain lacking, especially for their compatibility in the metal-reducing pathway. The increasing number of genome sequences of Shewanella strains offers a basis for pan-genome studies. RESULTS: A comparative pan-genome analysis was conducted to study genomic diversity and evolutionary relationships among 24 Shewanella strains. Results revealed an open pan-genome of 13,406 non-redundant genes and a core-genome of 1878 non-redundant genes. Selective pressure acted on the invariant members of core genome, in which purifying selection drove evolution in the housekeeping mechanisms. Shewanella strains exhibited extensive genome variability, with high levels of gene gain and loss during the evolution, which affected variable gene sets and facilitated the rapid evolution. Additionally, genes related to metal reduction were diversely distributed in Shewanella strains and evolved under purifying selection, which highlighted the basic conserved functionality and specificity of respiratory systems. CONCLUSIONS: The diversity of genes present in the accessory and specific genomes of Shewanella strains indicates that each strain uses different strategies to adapt to diverse environments. Horizontal gene transfer is an important evolutionary force in shaping Shewanella genomes. Purifying selection plays an important role in the stability of the core-genome and also drives evolution in mtr-omc cluster of different Shewanella strains.

The Human Gut Virome in Hypertension.

Objectives: Previous studies have reported that the gut microbiome has an important link with the development of hypertension. Though previous researches have focused on the links of gut bacteria with hypertension, little has been known about the linkage of gut viruses to hypertension and the development of hypertension, largely due to the lack of data mining tools for such investigation. In this work, we have analyzed 196 fecal metagenomic data related to hypertension aiming to profile the gut virome and link the gut virome to pre-hypertension and hypertension. Design: Here, we have applied a statistically sound method for mining of gut virome data and linking gut virome to hypertension. We characterized the viral composition and bacterial composition of 196 samples, identified the viral-type of each sample and linked gut virome to hypertension. Results: We stratified these 196 fecal samples into two viral-types and selected 32 viruses as the biomarkers for these groups. We found that viruses could have a superior resolution and discrimination power than bacteria for differentiation of healthy samples and pre-hypertension samples, as well as hypertension samples. Moreover, as to the co-occurrence networks linking viruses and bacteria, we found increasingly pervasive virus-bacteria linkages from healthy people to pre-hypertension people to hypertension patients. Conclusion: Overall, our results have shown ample indications of the link between human gut virome and hypertension, and could help provide microbial solutions toward early diagnoses of hypertension.

Heterogeneous circRNA expression profiles and regulatory functions among HEK293T single cells.

The single-cell analysis is becoming a powerful method for early detection of the abnormal variant in tissues, especially for profiling a small number of heterogeneous cells. With the advancement of sequencing technologies, many types of non-coding elements including miRNAs and lncRNAs which shed light on their heterogeneous patterns and functions among cells, have been profiled at the single-cell level. However, the complete picture of circRNA profile at single-cell level is still lacking. In this study, RNA-Seq data obtained from single HEK293T cells have been used to analyze expressions and functions of heterogeneous circRNA profiles. The enrichment patterns of circRNAs, interactions with miRNAs and pathways such as ErbB signaling pathway and protein processing in endoplasmic reticulum, have also been investigated. The results showed that circRNAs had a specific distribution pattern which was implicated with expression, miRNA and functional profiles at single-cell level. This assessment study of the expressions and functions of circRNAs at single-cell level shed light on heterogeneities among single cells.