PLoS Pathogens最新文献

{"title":"How Klebsiella pneumoniae controls its virulence.","authors":"To Nguyen Thi Nguyen, Gareth Howells, Francesca L Short","doi":"10.1371/journal.ppat.1013499","DOIUrl":"10.1371/journal.ppat.1013499","url":null,"abstract":"<p><p>The bacterial pathogen Klebsiella pneumoniae is a serious public health threat due to its propensity to develop antimicrobial resistance (AMR), the emergence of hypervirulent strains able to cause community-acquired infections, and the more recent development of convergent strains that exhibit both traits. Pathogenesis in K. pneumoniae is attributed to a range of largely horizontally-acquired virulence or fitness factors that collectively mediate immune evasion, attachment, intermicrobial competition and nutrition in different niches within the host. An outstanding research question is how expression of these factors is coordinated during infection, and how this regulatory control varies in genomically distinct lineages. Here we review recent progress in understanding the regulators and networks that control K. pneumoniae virulence or host fitness factor expression, discuss the role of plasmid-chromosome regulatory crosstalk in pathogenesis, and explore the potential of new global approaches to enhance our understanding. This knowledge will be instrumental in accurately predicting virulence from genome sequence in new emergent K. pneumoniae lineages, in order to track and manage this priority pathogen.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013499"},"PeriodicalIF":4.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The fungal STRIPAK complex: Cellular conductor orchestrating growth and pathogenicity.","authors":"Patricia P Peterson, Joseph Heitman","doi":"10.1371/journal.ppat.1013500","DOIUrl":"10.1371/journal.ppat.1013500","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013500"},"PeriodicalIF":4.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connecting basal body and mitochondrial DNA: TAC53 and the tubular organization of the tripartite attachment complex.","authors":"Clirim Jetishi, Salome Aeschlimann, Bernd Schimanski, Sandro Käser, Rachel Mullner, Silke Oeljeklaus, Bungo Akiyoshi, Bettina Warscheid, Falk Butter, André Schneider, Torsten Ochsenreiter","doi":"10.1371/journal.ppat.1013521","DOIUrl":"10.1371/journal.ppat.1013521","url":null,"abstract":"<p><p>The Tripartite Attachment Complex (TAC) is essential for mitochondrial DNA (kDNA) segregation in Trypanosoma brucei, providing a physical link between the flagellar basal body and the mitochondrial genome. Although the TAC's hierarchical assembly and linear organization have been extensively studied, much remains to be discovered regarding its complete architecture and composition - for instance, our identification of a new TAC component underscores these knowledge gaps. Here, we use a combination of proteomics, RNA interference (RNAi), and Ultrastructure Expansion Microscopy (U-ExM) to characterize the TAC at high resolution and identify a novel component, TAC53 (Tb927.2.6100). Depletion of TAC53 in both procyclic and bloodstream forms results in kDNA missegregation and loss, a characteristic feature of TAC dysfunction. TAC53 localizes to the kDNA in a cell cycle-dependent manner and represents the most kDNA-proximal TAC component identified to date. U-ExM reveals a previously unrecognized tubular architecture of the TAC, with two distinct TAC structures per kDNA disc, suggesting a mechanism for precise kDNA alignment and segregation. Moreover, immunoprecipitation and imaging analyses indicate that TAC53 interacts with known TAC-associated proteins HMG44, KAP68, and KAP3, forming a network at the TAC-kDNA interface. These findings redefine our understanding of TAC architecture and function and identify TAC53 as a key structural component anchoring the mitochondrial genome in T. brucei.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013521"},"PeriodicalIF":4.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of host immunity by a novel Legionella pneumophila E3 ubiquitin ligase.","authors":"Shuxin Liu, Chunlin He, Yong Zhang, Siyao Liu, Tao-Tao Chen, Chunxiuli Li, Dong Chen, Songying Ouyang, Lei Song, Jiaqi Fu, Zhao-Qing Luo","doi":"10.1371/journal.ppat.1013522","DOIUrl":"10.1371/journal.ppat.1013522","url":null,"abstract":"<p><p>Legionella pneumophila, the causative agent of Legionnaires' disease, exists ubiquitously in natural and artificial water systems. This pathogen poses serious threat to human health. One salient feature of L. pneumophila pathogenesis is the hundreds of effectors delivered into host cells by its Dot/Icm transporter. These virulence factors interfere with multiple hosts signaling pathways to subvert host defense. The ubiquitin network is essential in host signaling involved in immunity and thus is a common target of L. pneumophila effectors. At least thirteen Dot/Icm effectors have been shown to function as E3 ubiquitin ligases that cooperate with the host ubiquitination machinery by distinct mechanisms. In addition, seven deubiquitinases (DUBs) have been characterized. Furthermore, effectors that utilize catalysis mechanisms that are chemically distinct from the canonical one found in eukaryotes have been reported, indicating that hijacking of the host ubiquitin network by L. pneumophila is extensive and complex. Here, we identified ubiquitin interacting proteins with a proximity labeling method and found that the effector Lug14 (Lpg1106) functions as a novel ubiquitin ligase. Lug14 works with the E2 UbcH5c to catalyze ubiquitination with a preference for K11-linked chains by a mechanism that does not require a cysteine residue. Finally, we found that Lug14 targets ARIH2, a member of the host RBR E3 ligase family, leading to increased activation of the NLRP3 inflammasome in macrophages.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013522"},"PeriodicalIF":4.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interaction between GCN2 and eIF2 mediates the resistance of cotton bollworm to the Bacillus thuringiensis Cry1Ac toxin.","authors":"Caihong Zhang, Jizhen Wei, Ningning Li, Zaw Lin Naing, Ei Thinzar Soe, Jinrong Tang, Huan Yu, Fengyun Fang, Gemei Liang","doi":"10.1371/journal.ppat.1013510","DOIUrl":"10.1371/journal.ppat.1013510","url":null,"abstract":"<p><p>Deciphering the molecular mechanisms underlying insect resistance to Cry toxins produced by the soil bacterium Bacillus thuringiensis (Bt) is crucial for the sustainable utilization of Bt-based products. Previously, we identified that the reduced expression of the CAD, ABCC2 and ABCC3 genes through a eukaryotic translation initiation factor 2 (eIF2) is associated with Bt Cry1Ac resistance in the cotton bollworm, Helicoverpa armigera. Here, we found that an eIF2 alpha kinase, GCN2, is highly conserved in Lepidoptera insects. Its inhibitor GCN2iB (ATP-competitive inhibitor of serine/threonine protein kinase, stress-responsive kinase) could decrease the toxicity of Cry1Ac, and the GCN2 enzyme activities decreased after larvae fed Cry1Ac. The expression level of the HaGCN2 gene and the enzymatic activity of its corresponding protein were significantly down-regulated in the BtR resistant strain. Moreover, both BiFC and Y2H assays demonstrated that eIF2 could interact with GCN2. Finally, the silencing of HaGCN2 expression not only decreased the protein and phosphorylation levels of eIF2α but also reduced the expression of HaCAD, HaABCC2, and HaABCC3. This consequently led to a decrease in the toxicity of Cry1Ac toward Helicoverpa armigera. These results indicate that GCN2 conferring Cry1Ac resistance in H. armigera through regulating the expression of eIF2. This finding deepens our understanding of the transcriptional regulation of midgut Cry receptor genes and the molecular basis of insect resistance to Bt Cry toxins.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013510"},"PeriodicalIF":4.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A genome-wide analysis of YY1 and TFAP2 competition on overlapping motifs reveals their roles in HPV-induced carcinogenesis.","authors":"Yi Liu, Shuang Ding, Haibin Liu","doi":"10.1371/journal.ppat.1013524","DOIUrl":"10.1371/journal.ppat.1013524","url":null,"abstract":"<p><p>The long non-coding RNA lnc-FANCI-2 acts as a host defense RNA and is highly expressed in HPV-positive cervical lesions. Its activation relies on the binding of the transcription factor YY1 to two conserved motifs in its promoter. We used DNA oligo pull-down combined with mass spectrometry to identify proteins binding to the lnc-FANCI-2 promoter, discovering new TFAP2 family members that compete with YY1 for binding at overlapping sites. In primary epithelial cells, TFAP2 binding led to lnc-FANCI-2 silencing. However, in HPV-positive cancer cells, increased YY1 levels displaced TFAP2, alleviating repression. Genome-wide predictions using the JASPAR database identified thousands of YY1 and TFAP2 competition binding sites (CBSs), many overlapping with CHIP-seq peaks for YY1, TFAP2A, and TFAP2C, predominantly in promoter regions. We validated competition at two CBSs in the promoter and found it likely regulates cancer-related genes PPP1R15B and LRRC37A. This suggests that YY1 and TFAP2 competition might influence a broader transcriptional regulation network in HPV-induced cancer. This study reveals a novel transcriptional antagonism mechanism affecting lnc-FANCI-2 and other cancer-related genes, highlighting YY1 and TFAP2 as potential therapeutic targets in HPV-driven carcinogenesis.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013524"},"PeriodicalIF":4.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coronavirus M protein impairs cilium during early infection by enhancing the AurA-HDAC6 axis.","authors":"Tenghan Zhuang, Peng Yang, Mengqin Wang, Shiyu Liu, Wei Wang, Boyan Sun, Yue Xu, Li Chen, Xi Bao, Danchen Aaron Yang, Yongqian Zhao, Baochao Fan, Lei Feng, Bin Li","doi":"10.1371/journal.ppat.1013515","DOIUrl":"10.1371/journal.ppat.1013515","url":null,"abstract":"<p><p>Coronaviruses (CoVs) are implicated in human outbreaks and significant economic losses in the porcine and avian industries. Recent investigations have underscored the potential role of cilia within the respiratory tracts of infected hosts, particularly regarding the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanisms by which other CoVs exert their virulence through ciliary interactions remain inadequately elucidated. In this context, our research has demonstrated that porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) induce ciliary disassembly within six hours post-infection during the early infection stage. Utilizing mass spectrometry, we identified histone deacetylases 6 (HDAC6) or Aurora A (AurA) as binding partners of PEDV or PDCoV membrane (M) proteins. Immunofluorescence studies corroborated that the AurA-HDAC6 axis serves as a principal regulator of ciliary disassembly. Additionally, M proteins from all four CoV genera-PEDV, SARS-CoV-2, PDCoV, and infectious bronchitis virus (IBV)-were observed to congregate at the ciliary base. Molecular techniques, including immunoprecipitation and molecular docking combined with molecular mechanics/generalized born surface area (MM/GBSA) free energy decomposition analysis, further revealed that CoV M proteins interact with both AurA and HDAC6. These interactions depend on conserved residues at the transmembrane-cytosolic junction of M proteins, essential for their binding to the AurA-HDAC6 axis. Mutations disrupting these residues significantly impaired the binding affinity, thus inhibiting the associated ciliary disassembly process. Collectively, our findings illuminate a conserved regulatory mechanism involving CoV M proteins across all four genera, contributing to ciliary disassembly during early infection. This work enhances our understanding of the fundamental interactions between CoVs and host cells, positioning AurA and HDAC6 as potential therapeutic targets for a broad spectrum of CoV infections.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013515"},"PeriodicalIF":4.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fish TOLLIP manipulates ATG5 for autophagic degradation of STING to attenuate antiviral interferon responses.","authors":"Meng-Ze Tian, Yang-Yang Wang, Bao-Jie Cui, Xiao Xu, Chu-Jing Zhou, Can Zhang, Zhuo-Cong Li, Meng-Qian Hong, Na Xu, Dan-Dan Chen, Long-Feng Lu, Shun Li","doi":"10.1371/journal.ppat.1013512","DOIUrl":"10.1371/journal.ppat.1013512","url":null,"abstract":"<p><p>While robust interferon (IFN) responses in fish are critical for viral clearance, dysregulated signalling can trigger detrimental hyperinflammation, necessitating precise immunoregulatory mechanisms. This study identified Toll-interacting protein (TOLLIP) as a pivotal negative regulator of IFN production in grass carp (Ctenopharyngodon idella). Upon grass carp reovirus (GCRV) infection, TOLLIP expression increases significantly in tissues and cells. Furthermore, TOLLIP overexpression reduced GCRV- and polyinosinic-polycytidylic acid (poly I:C)-induced IFN expression, whereas tollip knockdown increased the cellular IFN production capacity. TOLLIP subsequently binds and degrades STING. Further mechanistic studies revealed that TOLLIP degrades STING in a dose-dependent manner via an autophagy-lysosome-dependent pathway. Interestingly, autophagy-related protein 5 (ATG5) was found to interact with TOLLIP and reduce TOLLIP-mediated STING degradation after atg5 knockdown. In addition, TOLLIP attenuated STING-driven IFN activation and compromised antiviral efficacy. These findings demonstrate that fish TOLLIP plays a specialized regulatory role in antiviral innate immunity, balancing immune defence with homeostasis maintenance.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013512"},"PeriodicalIF":4.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive allosteric modulation of emodepside sensitive Brugia malayi SLO-1F and Onchocerca volvulus SLO-1A potassium channels by GoSlo-SR-5-69.","authors":"Mark McHugh, Charity N Njeshi, Nathaniel Smith, Sudhanva S Kashyap, Real Datta, Han Sun, Alan P Robertson, Richard J Martin","doi":"10.1371/journal.ppat.1012946","DOIUrl":"10.1371/journal.ppat.1012946","url":null,"abstract":"<p><p>Human lymphatic filariasis and onchocerciasis are Neglected Tropical Diseases (NTDs), of major public health concern. Prophylaxis and treatment rely on anthelmintics that effectively eliminate migrating microfilariae but lack efficacy against adult filarial worms. To expedite the elimination of both diseases, drugs with adulticidal activity are needed. The broad-spectrum anthelmintic emodepside, a nematode selective SLO-1 K channel activator, is a promising candidate for the treatment of onchocerciasis due to its macrofilaricidal activity against Onchocerca volvulus. Nevertheless, it is less effective against adult Brugia malayi, one of the causative agents of human lymphatic filariasis. Characterizing molecular and pharmacological disparities between highly conserved splice variant isoforms of B. malayi and O. volvulus SLO-1 K channels and identifying allosteric modulators that can increase emodepside potency on B. malayi SLO-1 K channels is necessary for therapeutic advance. In this study, we tested the effects of emodepside and the mammalian BK channel activator, GoSlo-SR-5-69 alone and in combination on Xenopus expressed B. malayi SLO-1F and O. volvulus SLO-1A channels. Additionally, binding poses of emodepside, and GoSlo-SR-5-69 were predicted on both channels using molecular docking. We observed that Ovo-SLO-1A was more sensitive to emodepside than Bma-SLO-1F, with EC50 values of 0.40 ± 0.05 µM and 1.4 ± 0.2 µM for Ovo-SLO-1A and Bma-SLO-1F respectively. GoSlo-SR-5-69 lacked agonist activity on both channel isoforms but acted as a positive allosteric modulator, potentiating the effects of emodepside. Molecular docking analysis revealed that emodepside binds at the S6 pocket below the selectivity filter for Bma-SLO-1F and Ovo-SLO-1A. In contrast, GoSlo-SR-5-69 binds at the RCK1 pocket. This study reveals for the first time, allosteric modulation of filarial nematode SLO-1 K channels by a mammalian BK channel activator and highlights its ability to increase emodepside potency on the B. malayi SLO-1 K channel.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1012946"},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unbiased and comprehensive identification of virus-derived circular RNAs in a large range of viral species and families.","authors":"Alexis S Chasseur, Maxime Bellefroid, Mathilde Galais, Meijiao Gong, Pierre Lombard, Sarah Mathieu, Amandine Pecquet, Estelle Plant, Camille Ponsard, Laure Vreux, Carlo Yague-Sanz, Benjamin G Dewals, Nicolas A Gillet, Benoît Muylkens, Carine M Van Lint, Damien Coupeau","doi":"10.1371/journal.ppat.1013448","DOIUrl":"10.1371/journal.ppat.1013448","url":null,"abstract":"<p><p>Non-coding RNAs play a significant role in viral infection cycles, with recent attention focused on circular RNAs (circRNAs) originating from various viral families. Notably, these circRNAs have been associated with oncogenesis and alterations in viral fitness. However, identifying their expression has proven more challenging than initially anticipated due to unique viral characteristics. This challenge has the potential to impede progress in our understanding of viral circRNAs. Key hurdles in working with viral genomes include: (1) the presence of repetitive regions that can lead to misalignment of sequencing reads, and (2) unconventional splicing mechanisms that deviate from conserved eukaryotic patterns. To address these challenges, we developed vCircTrappist, a bioinformatic pipeline tailored to identify backsplicing events and pinpoint loci expressing circRNAs in RNA sequencing data. Applying this pipeline, we obtained novel insights from both new and existing datasets encompassing a range of animal and human pathogens belonging to Herpesviridae, Retroviridae, Adenoviridae, Flaviviridae and Orthomyxoviridae families. Subsequent RT-PCR and Sanger sequencings validated the accuracy of the developed bioinformatic tool for a selection of new candidate virus-derived circRNAs. These findings demonstrate that vCircTrappist is an open and unbiased approach for comprehensive identification of virus-derived circRNAs.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013448"},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}