Sheila Gonzalez, Maria G. Noval, Jessica M. Tucker
{"title":"Stress less: Viral mastery of the RNA G-quadruplex","authors":"Sheila Gonzalez, Maria G. Noval, Jessica M. Tucker","doi":"10.1016/j.chom.2024.08.011","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.011","url":null,"abstract":"<p>RNA G-quadruplexes are dynamically regulated during stress and infection. In this issue of <em>Cell Host & Microbe</em>, Schult et al.<span><span><sup>1</sup></span></span> demonstrate that an RNA G-quadruplex conserved across orthoflaviviruses binds hnRNPH1 to mitigate the host stress response, highlighting the potential of this dynamic proviral RNA structure as a pan-flaviviral target.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"9 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sun-Young Kim, Justin R. Randall, Richard Gu, Quoc D. Nguyen, Bryan W. Davies
{"title":"Antibacterial action, proteolytic immunity, and in vivo activity of a Vibrio cholerae microcin","authors":"Sun-Young Kim, Justin R. Randall, Richard Gu, Quoc D. Nguyen, Bryan W. Davies","doi":"10.1016/j.chom.2024.08.012","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.012","url":null,"abstract":"<p>Microcins are small antibacterial proteins that mediate interbacterial competition. Their narrow-spectrum activity provides opportunities to discover microbiome-sparing treatments. However, microcins have been found almost exclusively in <em>Enterobacteriaceae</em>. Their broader existence and potential implications in other pathogens remain unclear. Here, we identify and characterize a microcin active against pathogenic <em>Vibrio cholerae</em>: MvcC. We show that MvcC is reliant on the outer membrane porin OmpT to cross the outer membrane. MvcC then binds the periplasmic protein OppA to reach and disrupt the cytoplasmic membrane. We demonstrate that MvcC’s cognate immunity protein is a protease, which precisely cleaves MvcC to neutralize its activity. Importantly, we show that MvcC is active against diverse cholera isolates and in a mouse model of <em>V. cholerae</em> colonization. Our results provide a detailed analysis of a microcin outside of <em>Enterobacteriaceae</em> and its potential to influence <em>V. cholerae</em> infection.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"48 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charlotte Wallaeys, Natalia Garcia-Gonzalez, Steven Timmermans, Jolien Vandewalle, Tineke Vanderhaeghen, Somara De Beul, Hester Dufoor, Melanie Eggermont, Elise Moens, Victor Bosteels, Riet De Rycke, Fabien Thery, Francis Impens, Serge Verbanck, Stefan Lienenklaus, Sophie Janssens, Richard S. Blumberg, Takao Iwawaki, Claude Libert
{"title":"Paneth cell TNF signaling induces gut bacterial translocation and sepsis","authors":"Charlotte Wallaeys, Natalia Garcia-Gonzalez, Steven Timmermans, Jolien Vandewalle, Tineke Vanderhaeghen, Somara De Beul, Hester Dufoor, Melanie Eggermont, Elise Moens, Victor Bosteels, Riet De Rycke, Fabien Thery, Francis Impens, Serge Verbanck, Stefan Lienenklaus, Sophie Janssens, Richard S. Blumberg, Takao Iwawaki, Claude Libert","doi":"10.1016/j.chom.2024.08.007","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.007","url":null,"abstract":"<p>The cytokine tumor necrosis factor (TNF) plays important roles in limiting infection but is also linked to sepsis. The mechanisms underlying these paradoxical roles are unclear. Here, we show that TNF limits the antimicrobial activity of Paneth cells (PCs), causing bacterial translocation from the gut to various organs. This TNF-induced lethality does not occur in mice with a PC-specific deletion in the TNF receptor, P55. In PCs, TNF stimulates the IFN pathway and ablates the steady-state unfolded protein response (UPR), effects not observed in mice lacking P55 or IFNAR1. TNF triggers the transcriptional downregulation of IRE1 key genes <em>Ern1</em> and <em>Ern2</em>, which are key mediators of the UPR. This UPR deficiency causes a significant reduction in antimicrobial peptide production and PC antimicrobial activity, causing bacterial translocation to organs and subsequent polymicrobial sepsis, organ failure, and death. This study highlights the roles of PCs in bacterial control and therapeutic targets for sepsis.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"48 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qisheng Gu, Marion Draheim, Cyril Planchais, Zihan He, Fan Mu, Shijie Gong, Chun Shen, Haitao Zhu, Dania Zhivaki, Khashayar Shahin, Jean-Marc Collard, Min Su, Xiaoming Zhang, Hugo Mouquet, Richard Lo-Man
{"title":"Intestinal newborn regulatory B cell antibodies modulate microbiota communities","authors":"Qisheng Gu, Marion Draheim, Cyril Planchais, Zihan He, Fan Mu, Shijie Gong, Chun Shen, Haitao Zhu, Dania Zhivaki, Khashayar Shahin, Jean-Marc Collard, Min Su, Xiaoming Zhang, Hugo Mouquet, Richard Lo-Man","doi":"10.1016/j.chom.2024.08.010","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.010","url":null,"abstract":"<p>The role of immunoglobulins produced by IL-10-producing regulatory B cells remains unknown. We found that a particular newborn regulatory B cell population (nBreg) negatively regulates the production of immunoglobulin M (IgM) via IL-10 in an autocrine manner, limiting the intensity of the polyreactive antibody response following innate activation. Based on nBreg scRNA-seq signature, we identify these cells and their repertoire in fetal and neonatal intestinal tissues. By characterizing 205 monoclonal antibodies cloned from intestinal nBreg, we show that newborn germline-encoded antibodies display reactivity against bacteria representing six different phyla of the early microbiota. nBreg-derived antibodies can influence the diversity and the cooperation between members of early microbial communities, at least in part by modulating energy metabolism. These results collectively suggest that nBreg populations help facilitate early-life microbiome establishment and shed light on the paradoxical activities of regulatory B cells in early life.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"2015 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antiviral RNA interference inhibits virus vertical transmission in plants","authors":"Si Liu, Shou-Wei Ding","doi":"10.1016/j.chom.2024.08.009","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.009","url":null,"abstract":"<p>Known for over a century, seed transmission of plant viruses promotes trans-continental virus dissemination and provides the source of infection to trigger devastating disease epidemics in crops. However, it remains unknown whether there is a genetically defined immune pathway to suppress virus vertical transmission in plants. Here, we demonstrate potent immunosuppression of cucumber mosaic virus (CMV) seed transmission in its natural host <em>Arabidopsis thaliana</em> by antiviral RNA interference (RNAi) pathway. Immunofluorescence microscopy reveals predominant embryo infection at four stages of embryo development. We show that antiviral RNAi confers resistance to seed infection with different genetic requirements and drastically enhanced potency compared with the inhibition of systemic infection of whole plants. Moreover, we detect efficient seed transmission of a mutant CMV lacking its RNAi suppressor gene in mutant plants defective in antiviral RNAi, providing further support for the immunosuppression of seed transmission by antiviral RNAi.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"18 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eiko Hayase, Tomo Hayase, Akash Mukherjee, Stuart C. Stinson, Mohamed A. Jamal, Miriam R. Ortega, Christopher A. Sanchez, Saira S. Ahmed, Jennifer L. Karmouch, Chia-Chi Chang, Ivonne I. Flores, Lauren K. McDaniel, Alexandria N. Brown, Rawan K. El-Himri, Valerie A. Chapa, Lin Tan, Bao Q. Tran, Yao Xiao, Christopher Fan, Dung Pham, Robert R. Jenq
{"title":"Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease","authors":"Eiko Hayase, Tomo Hayase, Akash Mukherjee, Stuart C. Stinson, Mohamed A. Jamal, Miriam R. Ortega, Christopher A. Sanchez, Saira S. Ahmed, Jennifer L. Karmouch, Chia-Chi Chang, Ivonne I. Flores, Lauren K. McDaniel, Alexandria N. Brown, Rawan K. El-Himri, Valerie A. Chapa, Lin Tan, Bao Q. Tran, Yao Xiao, Christopher Fan, Dung Pham, Robert R. Jenq","doi":"10.1016/j.chom.2024.08.004","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.004","url":null,"abstract":"<p>Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (<em>n</em> = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of <em>Bacteroides ovatus</em>. In a murine GVHD model aggravated by carbapenem antibiotics, introducing <em>B. ovatus</em> reduced GVHD severity and improved survival. These beneficial effects of <em>Bacteroides ovatus</em> were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as <em>Bacteroides thetaiotaomicron</em> and <em>Akkermansia muciniphila</em>, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of <em>B. ovatus</em>.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"8 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amy M. Peiper, Joyce Morales Aparicio, Zhengzheng Hu, Lufuno Phophi, Emily W. Helm, Rebecca J. Rubinstein, Matthew Phillips, Caroline G. Williams, Saravanan Subramanian, Michael Cross, Neha Iyer, Quyen Nguyen, Rachel Newsome, Christian Jobin, Stephanie N. Langel, Filemon Bucardo, Sylvia Becker-Dreps, Xiao-Di Tan, Paul A. Dawson, Stephanie M. Karst
{"title":"Metabolic immaturity and breastmilk bile acid metabolites are central determinants of heightened newborn vulnerability to norovirus diarrhea","authors":"Amy M. Peiper, Joyce Morales Aparicio, Zhengzheng Hu, Lufuno Phophi, Emily W. Helm, Rebecca J. Rubinstein, Matthew Phillips, Caroline G. Williams, Saravanan Subramanian, Michael Cross, Neha Iyer, Quyen Nguyen, Rachel Newsome, Christian Jobin, Stephanie N. Langel, Filemon Bucardo, Sylvia Becker-Dreps, Xiao-Di Tan, Paul A. Dawson, Stephanie M. Karst","doi":"10.1016/j.chom.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.003","url":null,"abstract":"<p>The pathogenic outcome of enteric virus infections is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors, with metabolites serving as a key mediator. Noroviruses bind bile acid metabolites, which are produced by the host and then modified by commensal bacteria. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Working in an infant mouse model of norovirus infection, we demonstrate that microbiota and their bile acid metabolites protect from norovirus diarrhea, whereas host bile acids promote disease. We also find that maternal bile acid metabolism determines the susceptibility of newborn mice to norovirus diarrhea during breastfeeding. Finally, targeting maternal and neonatal bile acid metabolism can protect newborn mice from norovirus disease. In summary, neonatal metabolic immaturity and breastmilk bile acids are central determinants of heightened newborn vulnerability to norovirus disease.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"57 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jean Cury, Matthieu Haudiquet, Veronica Hernandez Trejo, Ernest Mordret, Anael Hanouna, Maxime Rotival, Florian Tesson, Delphine Bonhomme, Gal Ofir, Lluis Quintana-Murci, Philippe Benaroch, Enzo Z. Poirier, Aude Bernheim
{"title":"Conservation of antiviral systems across domains of life reveals immune genes in humans","authors":"Jean Cury, Matthieu Haudiquet, Veronica Hernandez Trejo, Ernest Mordret, Anael Hanouna, Maxime Rotival, Florian Tesson, Delphine Bonhomme, Gal Ofir, Lluis Quintana-Murci, Philippe Benaroch, Enzo Z. Poirier, Aude Bernheim","doi":"10.1016/j.chom.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.002","url":null,"abstract":"<p>Deciphering the immune organization of eukaryotes is important for human health and for understanding ecosystems. The recent discovery of antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. However, whether bacterial antiphage proteins can illuminate immune organization in eukaryotes remains unexplored. Here, we use a phylogeny-driven approach to uncover eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes and maintain a role in human immunity. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionarily linked to the antiphage system Mokosh. Additionally, human GTPases of immunity-associated proteins (GIMAPs) as well as two genes encoded in microsynteny, FHAD1 and CTRC, are respectively related to the Eleos and Lamassu prokaryotic systems and exhibit antiviral activity. Our work illustrates how comparative genomics of immune mechanisms can uncover defense genes in eukaryotes.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"5 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher J. Anderson, Laura Boeckaerts, Pricilla Chin, Javier Burgoa Cardas, Wei Xie, Amanda Gonçalves, Gillian Blancke, Sam Benson, Sebastian Rogatti, Mariska S. Simpson, Anna Davey, Sze Men Choi, Sandrien Desmet, Summer D. Bushman, Geert Goeminne, Peter Vandenabeele, Mahesh S. Desai, Lars Vereecke, Kodi S. Ravichandran
{"title":"Metabolite-based inter-kingdom communication controls intestinal tissue recovery following chemotherapeutic injury","authors":"Christopher J. Anderson, Laura Boeckaerts, Pricilla Chin, Javier Burgoa Cardas, Wei Xie, Amanda Gonçalves, Gillian Blancke, Sam Benson, Sebastian Rogatti, Mariska S. Simpson, Anna Davey, Sze Men Choi, Sandrien Desmet, Summer D. Bushman, Geert Goeminne, Peter Vandenabeele, Mahesh S. Desai, Lars Vereecke, Kodi S. Ravichandran","doi":"10.1016/j.chom.2024.07.026","DOIUrl":"https://doi.org/10.1016/j.chom.2024.07.026","url":null,"abstract":"<p>Cytotoxic chemotherapies have devastating side effects, particularly within the gastrointestinal tract. Gastrointestinal toxicity includes the death and damage of the epithelium and an imbalance in the intestinal microbiota, otherwise known as dysbiosis. Whether dysbiosis is a direct contributor to tissue toxicity is a key area of focus. Here, from both mammalian and bacterial perspectives, we uncover an intestinal epithelial cell death-Enterobacteriaceae signaling axis that fuels dysbiosis. Specifically, our data demonstrate that chemotherapy-induced epithelial cell apoptosis and the purine-containing metabolites released from dying cells drive the inter-kingdom transcriptional re-wiring of the Enterobacteriaceae, including fundamental shifts in bacterial respiration and promotion of purine utilization-dependent expansion, which in turn delays the recovery of the intestinal tract. Inhibition of epithelial cell death or restriction of the Enterobacteriaceae to homeostatic levels reverses dysbiosis and improves intestinal recovery. These findings suggest that supportive therapies that maintain homeostatic levels of Enterobacteriaceae may be useful in resolving intestinal disease.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"99 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142084854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robert Thänert, Drew J. Schwartz, Eric C. Keen, Carla Hall-Moore, Bin Wang, Nurmohammad Shaikh, Jie Ning, L. Colleen Rouggly-Nickless, Anna Thänert, Aura Ferreiro, Skye R.S. Fishbein, Janice E. Sullivan, Paula Radmacher, Marilyn Escobedo, Barbara B. Warner, Phillip I. Tarr, Gautam Dantas
{"title":"Clinical sequelae of gut microbiome development and disruption in hospitalized preterm infants","authors":"Robert Thänert, Drew J. Schwartz, Eric C. Keen, Carla Hall-Moore, Bin Wang, Nurmohammad Shaikh, Jie Ning, L. Colleen Rouggly-Nickless, Anna Thänert, Aura Ferreiro, Skye R.S. Fishbein, Janice E. Sullivan, Paula Radmacher, Marilyn Escobedo, Barbara B. Warner, Phillip I. Tarr, Gautam Dantas","doi":"10.1016/j.chom.2024.07.027","DOIUrl":"https://doi.org/10.1016/j.chom.2024.07.027","url":null,"abstract":"<p>Aberrant preterm infant gut microbiota assembly predisposes to early-life disorders and persistent health problems. Here, we characterize gut microbiome dynamics over the first 3 months of life in 236 preterm infants hospitalized in three neonatal intensive care units using shotgun metagenomics of 2,512 stools and metatranscriptomics of 1,381 stools. Strain tracking, taxonomic and functional profiling, and comprehensive clinical metadata identify <em>Enterobacteriaceae</em>, enterococci, and staphylococci as primarily exploiting available niches to populate the gut microbiome. <em>Clostridioides difficile</em> lineages persist between individuals in single centers, and <em>Staphylococcus epidermidis</em> lineages persist within and, unexpectedly, between centers. Collectively, antibiotic and non-antibiotic medications influence gut microbiome composition to greater extents than maternal or baseline variables. Finally, we identify a persistent low-diversity gut microbiome in neonates who develop necrotizing enterocolitis after day of life 40. Overall, we comprehensively describe gut microbiome dynamics in response to medical interventions in preterm, hospitalized neonates.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"4 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142084853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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