The ISME Journal最新文献

{"title":"Akkermansia muciniphila exacerbates acute radiation-induced intestinal injury by depleting mucin and enhancing inflammation","authors":"Yafang Wang, Xusheng Wang, Zhenhui Chen, Jihua Zheng, Xiangqiang Liu, Yilin Zheng, Zhihao Zheng, Zi Xu, Yaowei Zhang, Keli Chen, Yuqin Zhang, Lu Yu, Yi Ding","doi":"10.1093/ismejo/wraf084","DOIUrl":"https://doi.org/10.1093/ismejo/wraf084","url":null,"abstract":"Dysbiosis of gut microbiota plays a crucial role in acute radiation-induced intestinal injury. However, studies on the influence of gut microbiota on acute radiation-induced intestinal injury are inconsistent. In this study, we established an acute radiation-induced intestinal injury mouse model and performed fecal microbiota transplantation to explore the role of the gut microbiota in acute radiation-induced intestinal injury. We observed a significant increase in Akkermansia muciniphila following irradiation, whereas fecal microbiota transplantation effectively reduced Akkermansia muciniphila levels. Contrary to expectations, Akkermansia muciniphila supplementation increased acute radiation-induced intestinal injury and mortality. Mechanistically, post-radiation Akkermansia muciniphila upregulates mucin metabolism genes and consumes mucin, thinning the mucosal barrier and promoting the adhesion and translocation of potential pathogens to epithelial cells, thus exacerbating acute radiation-induced intestinal injury. This enables Akkermansia muciniphila to use mucin as an energy source. Additionally, Akkermansia muciniphila increases the inflammatory macrophage changes and secretion of inflammatory cytokines, leading to a decrease in epithelial stem cell density and inhibition of goblet cell differentiation, further exacerbating acute radiation-induced intestinal injury. Our findings suggest that in certain intestinal environments, the addition of Akkermansia muciniphila may worsen radiation-induced intestinal damage; thus, alternative approaches to reverse the dysbiosis associated with radiotherapy should be explored.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Residence-colonization trade-off and niche differentiation enable coexistence of Escherichia coli phylogroups in healthy humans","authors":"Thibaut Morel-Journel, Sonja Lehtinen, Olivier Cotto, Rafika Amia, Sara Dion, Clarisse Figueroa, Jonathan N V Martinson, Pascal Ralaimazava, Olivier Clermont, Xavier Duval, Forough L Nowrouzian, Seth T Walk, Erick Denamur, François Blanquart","doi":"10.1093/ismejo/wraf089","DOIUrl":"https://doi.org/10.1093/ismejo/wraf089","url":null,"abstract":"Despite abundant literature on pathogenicity and virulence of the opportunistic pathogen Escherichia coli, much less is known about its ecological and evolutionary dynamics as a commensal. Based on two detailed longitudinal datasets on the gut microbiota of healthy adults followed for months to years in France and the USA, we identified a robust trade-off between the ability to establish in a new host (colonization) and to remain in the host (residence). Major E. coli lineages (phylogroups or subgroups) exhibited similar fitness but diverse strategies, from strong colonisers residing few days in the gut to poor colonisers residing for years. Strains with the largest number of extra-intestinal virulence associated genes and highest pathogenicity also resided for longest in hosts. Furthermore, the residence of a strain was more strongly reduced when it competed with other strains from the same phylogroup than from another phylogroup, suggesting niche differentiation between phylogroups. Based on a discrete-state Markov model developed to describe E. coli dynamics in a host population, we found that the trade-off and niche differentiation acted together as equalizing and stabilizing mechanisms allowing phylogroups to coexist over long periods of time. Our model also predicted that external disturbances may disproportionately affect resident strains, such as the extraintestinal pathogenic ones of subgroup B2.3. Our results call for further studies outside high-income countries, where the prevalence of this phylogroup is much lower. More generally, the trade-off between colonization and persistence could play a role in the diversification of other bacterial species of the microbiome.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyhydroxybutyrate production by freshwater SAR11 (LD12)","authors":"Brittany D Bennett, David A O Meier, V Celeste Lanclos, Hasti Asrari, John D Coates, J Cameron Thrash","doi":"10.1093/ismejo/wraf087","DOIUrl":"https://doi.org/10.1093/ismejo/wraf087","url":null,"abstract":"SAR11 bacteria (order Pelagibacterales) are oligotrophs and often the most abundant bacterioplankton in aquatic environments. A subset of sequenced SAR11 genomes, predominantly in the brackish and freshwater SAR11 subclades, contain homologs of pha genes, which in other organisms confer the ability to store carbon and energy via polyhydroxyalkanoate polymers. Here, we investigated the relevance of polyhydroxyalkanoate production to SAR11 biology. Phylogenetics showed that Pha proteins occurred on a long branch and provided evidence for origin at the common ancestor of the brackish IIIa and freshwater LD12 subclades, followed by horizontal transfer within SAR11. Using the LD12 representative “Candidatus Fonsibacter ubiquis” strain LSUCC0530, we found that many LSUCC0530 cells contained a single Nile red-staining granule, confirmed that the cells produced polyhydroxybutyrate, a common form of polyhydroxyalkanoate, and estimated the total polyhydroxybutyrate content in the cells. We heterologously expressed the LSUCC0530 phaCAB locus in Escherichia coli, finding it to be functional and the likely origin of the polyhydroxybutyrate. We also determined that, irrespective of changes to carbon, nitrogen, and phosphorus concentrations, a similar fraction of LSUCC0530 cells generated polyhydroxybutyrate granules and expression of the phaCAB locus remained constant. We suggest that polyhydroxybutyrate synthesis in LSUCC0530 may be constitutively active due to the slow growth dynamics and minimal regulation that characterize SAR11 bacteria. This work characterizes polymer storage in SAR11, providing new insights into the likely fitness advantage for cells harboring this metabolism.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bifidobacterium breve synergizes with Akkermansia muciniphila and Bacteroides ovatus to antagonize Clostridioides difficile.","authors":"Yanan Li,Wen Rui,Xiaoya Sheng,Xilong Deng,Xiaoqian Li,Lingtong Meng,He Huang,Jingpeng Yang","doi":"10.1093/ismejo/wraf086","DOIUrl":"https://doi.org/10.1093/ismejo/wraf086","url":null,"abstract":"The development of ecologically based in vivo microecological formulations for treating Clostridioides difficile infection (CDI) is a current research focus. Here, we selected three microorganisms-Akkermansia muciniphila (AM), Bacteroides ovatus (BO), and Bifidobacterium breve (BB)-to formulate a mixed bacterial formulation (ABB). Subsequently, we evaluated the ecological interactions among these three microorganisms and investigated their therapeutic efficacy in a CDI murine model. Our investigation revealed the presence of a commensalism relationship among AM, BO, and BB. These microorganisms collectively formed a robust and densely packed symbiotic biofilm, with BB being the predominant member in terms of numerical abundance. This phenomenon was concomitant with a marked elevation in the levels of AI-2 and c-di-GMP. ABB exhibits the capability to inhibit crucial biological indicators of C. difficile (CD), such as toxin production, through the secretion of substantial quantities of lactic acid. Additionally, ABB indirectly suppresses CD by activating the NF-κB signaling pathway in Raw 264.7 cells, which stimulates the secretion of significant quantities of IL-6, IL-8, TNF-α, and IL-1β. ABB demonstrated exceptional efficacy in a CDI murine model, as evidenced by a substantial enhancement in survival rates and intestinal short-chain fatty acid (SCFAs) level, the down-regulation of inflammation-associated cytokine secretion, a notable reduction in fecal CD toxin levels, and CD viable bacterial counts. Concurrently, there was an augmentation in the level of gut microbial diversity, accompanied by a rapid reduction in Enterococcus abundance. This ABB formulation holds promise for further development into a novel microecological formulation for the treatment of CDI.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host identity drives the assembly of phytoplankton microbiomes across a continental scale environmental gradient.","authors":"P Signe White,Taryn Y Broe,Mirte C M Kuijpers,Jonathan R Dickey,Sara L Jackrel","doi":"10.1093/ismejo/wraf083","DOIUrl":"https://doi.org/10.1093/ismejo/wraf083","url":null,"abstract":"Host-associated microbiomes often promote host health, yet the key drivers of microbiome assembly and its consequences for host fitness remain unclear. We aimed to determine the relative roles of host identity versus the environment in driving host-microbiome assembly and the consequences of this variation in assembly for host fitness, which may help predict the resilience of host-associated microbiomes and host health amidst fluctuating environmental conditions. Here, we tracked microbiome assembly in association with initially axenic phytoplankton when incubated in seawater originating from four nearshore locations along a continental-scale environmental gradient of North America. Microbiome assembly was highly deterministic. Unexpectedly, host species identity was the overwhelming driver of microbiome community assembly despite continental scale variation in the environment. Although secondary to host identity, the environment was a significant driver of microbiome assembly for each species evaluated, which in turn conferred cascading effects on host fitness as shown by thermal tolerance growth assays. We also found that host-specific microbiomes had host-specific fitness effects, particularly under thermally stressful conditions. Overall, our results advance our understanding of microbiome assembly by empirically demonstrating that although variation among host microbiomes imparted by the local environment has significant implications for host health, the host species is the overwhelming driver of microbiome assembly regardless of wide scale variation in the environment.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proportional relationship between transcript concentrations and carbon biomass for open ocean plankton groups.","authors":"Sacha N Coesel,Shiri Graff van Creveld,Mathilde Dugenne,Fernanda Henderikx-Freitas,Angelicque E White,E Virginia Armbrust","doi":"10.1093/ismejo/wraf079","DOIUrl":"https://doi.org/10.1093/ismejo/wraf079","url":null,"abstract":"Unicellular plankton form the foundation of the marine food web, driving carbon fixation and cycling essential biogeochemical elements in marine ecosystems. Carbon biomass, often measured as a bulk property, serves as a common \"currency\" for ecologists. The increasing availability of metatranscriptomic data presents an opportunity to add taxonomic and functional resolution to ecological models and yet, aligning transcript counts with carbon biomass estimates remains a challenge. Here, we combine 30 quantitative metatranscriptome samples with Imaging FlowCytobot (IFCb)-derived carbon biomass estimates and demonstrate a robust, proportional (log-log scale) relationship between transcript concentration and carbon biomass estimates across abundant protist taxa. Further, we show that dinoflagellates exhibit a transcript-to-biomass ratio ~ 6.4-fold higher than other protist groups, consistent with their known transcriptional divergence. These findings provide a means to address overrepresentation of dinoflagellate transcript levels in metatranscriptome data. Moreover, this study establishes an entrée for integrating metatranscriptomics into carbon biomass-based ecological models, enhancing the interpretability and applicability of transcriptomic data in ecosystem research and modeling.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic microbial community improves chicken intestinal homeostasis and provokes anti-Salmonella immunity mediated by segmented filamentous bacteria","authors":"Meihong Zhang, Suxin Shi, Yimei Feng, Fengwenhui Zhang, Yuxuan Xiao, Xin Li, Xingliang Pan, Yuqing Feng, Dan Liu, Yuming Guo, Yongfei Hu","doi":"10.1093/ismejo/wraf076","DOIUrl":"https://doi.org/10.1093/ismejo/wraf076","url":null,"abstract":"Applying synthetic microbial communities to manipulate the gut microbiota is a promising manner for reshaping the chicken gut microbial community. However, it remains elusive the role of a designed microbial community in chicken physiological metabolism and immune responses. In this study, we constructed a ten-member synthetic microbial community (SynComBac10) that recapitulated the phylogenetic diversity and functional capability of adult chicken intestinal microbiota. We found that early life SynComBac10 exposure significantly enhanced chicken growth performance and facilitated the maturation of both the intestinal epithelial barrier function and the gut microbiota. Additionally, SynComBac10 promoted the pre-colonization and growth of segmented filamentous bacteria, which in turn induced Th17 cell-mediated immune responses, thereby conferring resistance to Salmonella infection. Through metagenomic sequencing, we assembled the genomes of two distinct species of segmented filamentous bacteria from the chicken gut microbiota, which displayed common metabolic deficiency with segmented filamentous bacteria of other host origins. In silico analyses indicated that the SynComBac10-stimulated early establishment of segmented filamentous bacteria in the chicken intestine was likely through SynComBac10-derived metabolite cross-feeding. Our study demonstrated the pivotal role of a designed microbial consortium in promoting chicken gut homeostasis and anti-infection immunity, providing a new avenue for engineering chicken gut microbiota.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fireworms are a reservoir and potential vector for coral-infecting apicomplexans","authors":"Anthony M Bonacolta, Bradley A Weiler, Candace J Grimes, Morelia Trznadel, Mark J A Vermeij, Patrick J Keeling, Javier del Campo","doi":"10.1093/ismejo/wraf078","DOIUrl":"https://doi.org/10.1093/ismejo/wraf078","url":null,"abstract":"Corals (Cnidaria; Anthozoa) play critical roles as habitat-forming species with a wide range, from warm shallow-water tropical coral reefs to cold-water ecosystems. They also represent a complex ecosystem as intricate holobionts made up of microbes from all domains of the Tree of Life that can play significant roles in host health and fitness. The corallicolids are a clade of apicomplexans that infect a wide variety of anthozoans worldwide and can influence the thermal tolerance of habitat-forming corals. Despite their potentially important impacts on reef ecosystems, much of the basic biology and ecology of corallicolids remains unclear. Apicomplexans often have a closed life cycle, with minimal environmental exposure and sometimes multiple hosts. Corallicolids have only been documented in anthozoan hosts, with no known secondary/reservoir hosts or vectors. Here, we show that abundant corallicolid sequences are recovered from bearded fireworms (Hermodice carunculata) in tropical reef habitats off Curaçao and that they are distinct from corallicolids infecting the corals on which the fireworms were feeding at the time of their collection. These data are consistent with a fireworm-specific corallicolid infection, not merely a byproduct of the worms feeding on infected corals. Furthermore, we suggest that H. carunculata is potentially a vector moving corallicolids among coral hosts through its feces. These findings not only expand our understanding of the ecological interactions within coral reef ecosystems but also highlight the potential role of host-associated parasites in shaping the resilience of reef habitats.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of antibiotic-manufacturing wastewater enriches for Aeromonas veronii, a zoonotic antibiotic-resistant emerging pathogen","authors":"Xingshuo Wang, Meilun Wang, Wei Zhang, Hui Li, James M Tiedje, Jizhong Zhou, Edward Topp, Yi Luo, Zeyou Chen","doi":"10.1093/ismejo/wraf077","DOIUrl":"https://doi.org/10.1093/ismejo/wraf077","url":null,"abstract":"Antibiotic-manufacturing wastewater treatment plants primarily target chemical pollutants, but their processes may select for antibiotic-resistant pathogens and antibiotic resistance genes. Here, leveraging the combined strengths of deep metagenomic sequencing, 16S rRNA gene sequencing, qPCR, and bacterial culturing, we investigated bacterial communities and antibiotic resistomes across eleven treatment units in a full-scale antibiotic-manufacturing wastewater treatment plant processing wastewater from a β-lactam manufacturing facility. We demonstrated that both bacterial communities and antibiotic resistance gene compositions varied across the treatment units, but were associated. Certain antibiotic resistance gene persisted through treatment, either carried by identical bacterial species, or linked to mobile genetic elements in different species. Despite the satisfactory performance in chemical removal, the antibiotic-manufacturing wastewater treatment plant continuously enriched zoonotic antibiotic-resistant Aeromonas veronii (an emerging pathogen responsible for substantial economic losses in aquaculture and human health) from influent to effluent, probably due to prolonged β-lactam selection pressure and aquatic nature of A. veronii. This enrichment resulted in a significantly higher abundance of A. veronii in the antibiotic-manufacturing wastewater treatment plant compared to other aquatic samples worldwide. Furthermore, the closest evolutionary relative to the antibiotic-manufacturing wastewater treatment plant derived A. veronii was an isolate obtained from the stool of a local diarrhea patient. These findings highlighted a substantial public health risk posed by antibiotic-manufacturing wastewater treatment plants, underlining their potential role in enriching and disseminating zoonotic antibiotic-resistant pathogens. Beyond chemical monitoring, enhanced surveillance of antibiotic-resistant pathogens and antibiotic resistance genes is needed in antibiotic-manufacturing wastewater treatment plants to avoid creating environmental hotspots of antibiotic resistant pathogens from discharging wastewater effluents.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Climate History Modulates Stress Responses of Common Soil Bacteria Under Experimental Drought","authors":"Nicholas J Bouskill, Stephany S Chacon, Daniela F Cusack, Lee H Dietterich, Liang Chen, Aizah Khurram, Jana Voriskova, Hoi-Ying N Holman","doi":"10.1093/ismejo/wraf075","DOIUrl":"https://doi.org/10.1093/ismejo/wraf075","url":null,"abstract":"Soil drying challenges microbial viability and survival, with bacteria employing various mechanisms to respond to shifts in osmolarity, including dormancy or metabolic upregulation of osmoprotectants. However, the extent to which these responses are shaped by an organism’s phylogeny, or the climate history of a given environment is poorly understood. This study examines the responses of phylogenetically similar bacteria from semi-arid and humid tropical forest soils to osmotic and matric stress using synchrotron radiation-based Fourier Transform Infrared spectromicroscopy. This non-destructive approach depicts the biochemical phenotype for whole cells under control and stress conditions. We observed that, under osmotic stress, bacteria upregulated cell-signaling pathways, rapidly turned over lipid-storage compounds, and increased osmolyte production. In contrast, matric stress induced a more muted response, typically elevating the production of carbohydrate stress compounds, such as glycine betaine and trehalose. Whereas phylogenetically similar bacteria showed comparable biochemistry under control conditions, climate history played an important role in regulating responses to stress, whereby a stronger metabolic response was observed from semi-arid relative to tropical forest isolates. We conclude that bacterial stress response to drought can be more diverse than previously observed and regulated by both phylogeny and climate history.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}