PLoS Pathogens最新文献

{"title":"Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium.","authors":"David Vizarraga, Akihiro Kawamoto, Marina Marcos-Silva, Jesús Martín, Fumiaki Makino, Tomoko Miyata, Jorge Roel-Touris, Enrique Marcos, Oscar Q Pich, David Aparicio, Ignacio Fita, Makoto Miyata, Jaume Piñol, Keiichi Namba, Tsuyoshi Kenri","doi":"10.1371/journal.ppat.1012973","DOIUrl":"https://doi.org/10.1371/journal.ppat.1012973","url":null,"abstract":"<p><p>Mycoplasma pneumoniae and Mycoplasma genitalium are bacterial wall-less human pathogens and the causative agents of respiratory and reproductive tract infections. Infectivity, gliding motility and adhesion of these mycoplasmas to host cells are mediated by orthologous adhesin proteins forming a transmembrane adhesion complex that binds to sialylated oligosaccharides human cell ligands. Here we report the cryo-EM structure of M. pneumoniae P1 adhesin bound to the Fab fragment of monoclonal antibody P1/MCA4, which stops gliding and induces detachment of motile cells. The epitope of P1/MCA4 involves residues only from the small C-domain of P1. This epitope is accessible to antibodies only in the \"closed conformation\" of the adhesion complex and is not accessible in the \"open\" conformation, when the adhesion complex is ready for attachment to sialylated oligosaccharides. Polyclonal antibodies generated against the large N-domain of P1 or against the whole ectodomain of P40/P90 have little or no effects on adhesion or motility. Moreover, mutations in the highly conserved Engelman motifs found in the transmembrane helix of M. genitalium P110 adhesin also alter adhesion and motility. These results show that antibodies directed to the C-domain of P1 hinder the large conformational rearrangements in this domain required to alternate between the \"open\" and \"closed\" conformations of the adhesion complex. Since transition between both conformations is essential to complete the attachment/detachment cycle of the adhesion complex, interfering with the gliding of mycoplasma cells and providing a new potential target to confront M. pneumoniae and M. genitalium infections.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1012973"},"PeriodicalIF":5.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735686","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":"Ecotin protects Salmonella Typhimurium against the microbicidal activity of host proteases.","authors":"Lucas Saposnik, Lorena M Coria, Laura Bruno, Francisco F Guaimas, Julieta Pandolfi, Melina Pol, Maria Eugenia Urga, Florencia Sabbione, Michael McClelland, Analia Trevani, Karina A Pasquevich, Juliana Cassataro","doi":"10.1371/journal.ppat.1013013","DOIUrl":"10.1371/journal.ppat.1013013","url":null,"abstract":"<p><p>Salmonella enterica serovar Typhimurium causes acute diarrhea upon oral infection in humans. The harsh and proteolytic environment found in the gastrointestinal tract is the first obstacle that these bacteria face after infection. However, the mechanisms that allow Salmonella to survive the hostile conditions of the gut are poorly understood. The ecotin gene is found in an extensive range of known phyla of bacteria and it encodes a protein that has been shown to inhibit serine proteases. Thus, in the present work we studied the role of ecotin of Salmonella Typhimurium in host-pathogen interactions. We found that the Salmonella Typhimurium ∆ecotin strain exhibited lower inflammation in a murine model of Salmonella induced colitis. The ∆ecotin mutant was more susceptible to the action of pancreatin and purified pancreatic elastase. In addition, the lack of ecotin led to impaired adhesion to Caco-2 and HT-29 cell lines, related to the proteolytic activity of brush border enzymes. Besides, ∆ecotin showed higher susceptibility to lysosomal proteolytic content and intracellular replication defects in macrophages. In addition, we found Ecotin to have a crucial role in Salmonella against the microbicidal action of granule contents and neutrophil extracellular traps released from human polymorphonuclear leukocytes. Thus, the work presented here highlights the importance of ecotin in Salmonella as countermeasures against the host proteolytic defense system.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1013013"},"PeriodicalIF":5.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735733","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":"A Krüppel-like factor establishes cellular heterogeneity during schistosome tegumental maintenance.","authors":"Lu Zhao, George R Wendt, James J Collins Iii","doi":"10.1371/journal.ppat.1013002","DOIUrl":"10.1371/journal.ppat.1013002","url":null,"abstract":"<p><p>Schistosomes are blood dwelling parasitic flatworms that can survive in the circulation of their human hosts for decades. These parasites possess a unique syncytial skin-like surface tissue known as the tegument that is thought to be uniquely adapted for survival in the blood by mediating evasion of host defenses. Previous studies have shown that cell bodies within the tegumental syncytium are turned over and perpetually replaced by new tegumental cells derived from a pool of somatic stem cells called neoblasts. Thus, neoblast-driven tegumental homeostasis has been suggested to be a key part of the parasite's strategy for long-term survival in the blood. However, the comprehensive set of molecular programs that control the specification of tegumental cells are not defined. To better understand these programs, we characterized a homolog of a Krüppel-like factor 4 (klf4) transcription factor that was identified in previous single-cell RNA sequencing (scRNAseq) studies to be expressed in a putative tegument related lineage (TRL) of Schistosoma mansoni. Here, using a combination of RNAi, coupled with scRNAseq and bulk RNAseq approaches, we show that klf4 is essential for the maintenance of an entire TRL. Loss of this klf4+ TRL resulted in loss of a subpopulation of molecularly unique tegument cells, without altering the total number of mature tegumental cells. Thus, klf4 is critical for regulating the balance between different cell populations within the tegumental progenitor pool and thereby influences tegumental production dynamics and the fine-tuning of the molecular identity of the mature tegument. Understanding the functions of distinct populations of cells within the tegumental syncytium is expected to provide insights into parasite defense mechanisms and new avenues for combatting the disease these worms cause.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1013002"},"PeriodicalIF":5.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736234","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":"The \"DDVF\" motif used by viral and bacterial proteins to hijack RSK kinases mimics a short linear motif (SLiM) found in proteins related to the RAS-ERK MAP kinase pathway.","authors":"Martin Veinstein, Vincent Stroobant, Fanny Wavreil, Thomas Michiels, Frédéric Sorgeloos","doi":"10.1371/journal.ppat.1013016","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013016","url":null,"abstract":"<p><p>Proteins of pathogens such as cardioviruses, Kaposi sarcoma-associated herpes virus, varicella zoster virus and bacteria of the genus Yersinia were previously shown to use a common \"DDVF\" (D/E-D/E-V-F) short linear motif (SLiM) to hijack cellular kinases of the RSK (p90 ribosomal S6 kinases) family. Notably, the leader (L) protein of Theiler's murine encephalomyelitis virus (TMEV), a cardiovirus, and protein YopM of Yersinia species were shown to act as adapters to retarget RSKs toward unconventional substrates, nucleoporins and pyrin, respectively. Remarkable conservation of the SLiM docking site targeted by pathogens' proteins in RSK sequences suggested a physiological role for this site. Using SLiM prediction tools and AlphaFold docking, we screened the human proteome for proteins that would interact with RSKs through a DDVF-like SLiM. Co-immunoprecipitation experiments show that two candidates previously known as RSK partners, FGFR1 and SPRED2, as well as two candidates identified as novel RSK partners, GAB3 and CNKSR2 do interact with RSKs through a similar interface as the one used by pathogens, as was recently documented for SPRED2. FGFR1 employs a DSVF motif to bind RSKs and phosphorylation of the serine in this motif slightly increased RSK binding. FGFR1, SPRED2, GAB3 and CNKSR2 act upstream of RSK in the RAS-ERK MAP kinase pathway. Analysis of ERK activation in cells expressing a mutated form of RSK lacking the DDVF-docking site suggests that RSK might interact with the DDVF-like SLiM of several partners to provide a negative feed-back to the ERK MAPK pathway. Moreover, after TMEV infection, ERK phosphorylation was altered by the L protein in a DDVF-dependent manner. Taken together, our data suggest that, in addition to retargeting RSKs toward unconventional substrates, pathogen proteins carrying a DDVF-like motif can compete with endogenous DDVF-containing proteins for RSK binding, thereby altering the regulation of the RAS-ERK MAP kinase pathway.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1013016"},"PeriodicalIF":5.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735918","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":"Selection and characterization of a broadly neutralizing class of HCV anti-E2 VH1-69 antibodies.","authors":"Andreas Soerensen, Filip Popovic, Christina Holmboe Olesen, Blanca Lopez Mendez, Brian Lohse, Zhaochun Chen, Patrizia Farci, Robert H Purcell, Harvey J Alter, Lea Klingenberg Barfod, Jens Bukh, Jannick Prentoe","doi":"10.1371/journal.ppat.1012428","DOIUrl":"https://doi.org/10.1371/journal.ppat.1012428","url":null,"abstract":"<p><p>Identification and characterization of antibody epitope targets on the hepatitis C virus (HCV) envelope proteins remain crucial for developing an effective vaccine. Building on prior research defining E1/E2 antibody epitope clustering, we screened a phage display library derived from a chronic HCV patient against detergent-extracted full-length E1/E2 from both the patient's acute-phase isolate (H77, genotype 1a) and a heterologous isolate (S52, genotype 3a). This approach yielded a panel of VH1-69 derived antibody fragments (Fabs) with similar characteristics. Interestingly, all members of the panel exhibited blocking activity against both antigenic region 2 and 3 (AR2 and AR3) in competition ELISAs, which contrasts with the behavior of most previously identified AR3-targeting antibodies. The VH1-69 derived binders had a high affinity for soluble E2 in both Fab and IgG formats, with dissociation constants in the low picomolar range. These Fab binders were broadly neutralizing against a panel of HCV cell culture viruses of genotype 1-6 with higher potency than the well-characterized reference Fab, AR3A. However, in the IgG format the antibodies had similar potency. These findings expand our understanding of potential targets for vaccine development by characterizing a panel of antibodies targeting an AR3 epitope also involving or occluding the back layer of E2. The broad neutralization and high affinity of these antibodies suggest a benefit to targeting both the back layer and the front layer of E2 in HCV vaccine designs to expand the repertoire of broadly neutralizing antibodies, thereby offering promise for the development of more effective preventive measures against this pervasive human pathogen.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1012428"},"PeriodicalIF":5.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735839","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":"RNAi screening of uncharacterized genes identifies promising druggable targets in Schistosoma japonicum.","authors":"Yuxiang Xie, Xiaoling Wang, Shaoyun Cheng, Wanling Liu, Cun Yi, Yanmin You, Wei Zhang, Yuepeng Wang, Enlu Tang, Jipeng Wang, Wei Hu","doi":"10.1371/journal.ppat.1013014","DOIUrl":"10.1371/journal.ppat.1013014","url":null,"abstract":"<p><p>Schistosomiasis affects more than 250 million people worldwide and is one of the neglected tropical diseases. Currently, the treatment of schistosomiasis relies on a single drug-praziquantel-which has led to increasing pressure from drug resistance. Therefore, there is an urgent need to find new treatments. The development of genome sequencing has provided valuable information for understanding the biology of schistosomes. In the genome of Schistosoma japonicum, approximately 11% of the protein-coding sequences are uncharacterized genes (UGs) annotated as \"hypothetical protein\" or \"protein of unknown function.\" These poorly understood genes have been unjustifiably neglected, although some may be essential for the survival of the parasites and serve as potential drug targets. In this study, we systematically mined the highly expressed UGs in both genders of this parasite throughout key developmental stages in their mammalian host, using our previously published S. japonicum genome and RNA-seq data. By employing in vitro RNA interference (RNAi), we screened 126 UGs that lack homologs in Homo sapiens and identified 8 that are essential for the parasite vitality. We further investigated two UGs, Sjc_0002003 and Sjc_0009272, which resulted in the most severe phenotypes. Fluorescence in situ hybridization demonstrated that both genes were expressed throughout the body without sex bias. Silencing either Sjc_0002003 or Sjc_0009272 reduced the cell proliferation in the body. Furthermore, in vivo RNAi indicated both genes are required for the growth and survival of the parasites in the mammalian host. For Sjc_0002003, we further characterize the underlying molecular cause of the observed phenotype. Through RNA-seq analysis and functional studies, we revealed that silencing Sjc_0002003 reduces the expression of a series of intestinal genes, including Sjc_0007312 (hypothetical protein), Sjc_0008276 (vha-17), Sjc_0002942 (PLA2G15), and Sjc_0003646 (SJCHGC09134 protein), leading to gut dilation. Our work highlights the importance of UGs in schistosomes as promising targets for drug development in the treatment of the schistosomiasis.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1013014"},"PeriodicalIF":5.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735809","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":"Correction: Use of the Puccinia sorghi haustorial transcriptome to identify and characterize AvrRp1-D recognized by the maize Rp1-D resistance protein.","authors":"","doi":"10.1371/journal.ppat.1013022","DOIUrl":"10.1371/journal.ppat.1013022","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.ppat.1012662.].</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1013022"},"PeriodicalIF":5.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732710","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":"Systemic infection by Candida albicans requires FASN-α subunit induced cell wall remodeling to perturb immune response.","authors":"Yajing Zhao, Zhishan Zhou, Guiyue Cai, Dandan Zhang, Xiaoting Yu, Dongmei Li, Shuixiu Li, Zhanpeng Zhang, Dongli Zhang, Jiyao Luo, Yunfeng Hu, Aili Gao, Hong Zhang","doi":"10.1371/journal.ppat.1012865","DOIUrl":"10.1371/journal.ppat.1012865","url":null,"abstract":"<p><p>Invasive fungal infections are a leading cause of mortality and morbidity in patients with severely impaired host defenses, while treatment options remain limited. Fatty acid synthase (FASN), the key enzyme regulating de novo biosynthesis of fatty acids, is crucial for the lethal infection of fungi; however, its pathogenic mechanism is still far from clear. Here, we identified the α subunit of FASN as a potential immunotherapeutic target against systemic Candida albicans infection. The avirulence of the encoded gene (FAS2) -deleted mutant in a mouse model of systemic candidiasis is not due to its fitness defects, because sufficient exogenous fatty acids in serum can overcome FASN inhibition. However, the FAS2-deleted mutant displays increased circulating innate immune responses and enhances activated neutrophil fungicidal activity through the unmasking of immunogenic cell wall epitopes via the Rho-1 dependent Mkc1-MAPK signaling pathway, which facilitates fungal clearance, reduces renal tissue damage and inflammatory cell infiltration, ultimately lowers fungal pathogenicity. Priming with the FAS2-deleted mutant provided significant protection against subsequent lethal infection with wild-type C. albicans in mice as early as one week, and it was well-tolerated with limited toxicity. Our findings indicate that the FASN-α subunit plays key roles in the regulation of neutrophil-associated antifungal immunity and could be a potential target for immunotherapeutic intervention.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1012865"},"PeriodicalIF":5.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732711","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":"Dissecting transmission to understand parasite evolution.","authors":"Luís M Silva, Kayla C King, Jacob C Koella","doi":"10.1371/journal.ppat.1012964","DOIUrl":"10.1371/journal.ppat.1012964","url":null,"abstract":"<p><p>Parasite transmission is a complex, multi-stage process that significantly impacts host-parasite dynamics. Transmission plays a key role in epidemiology and virulence evolution, where it is expected to trade off with virulence. However, the extent to which classical models on virulence-transmission relationships apply in the real world is unclear. This insight piece proposes a novel framework that breaks transmission into three distinct stages: within-host infectiousness, an intermediate between-host stage (biotic or abiotic), and new host infection. Each stage is influenced by intrinsic and extrinsic factors to the parasite, which together will determine its transmission success. Analyzing the transmission stages separately and how they affect each other might enhance our understanding of which host-, parasite- or environmental-driven factors might shape parasite evolution and inform us about new effectors to act on when designing disease control strategies.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1012964"},"PeriodicalIF":5.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711827","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":"Gene deletion as a possible strategy adopted by New World Leishmania infantum to maximize geographic dispersion.","authors":"Monique Florêncio, Marne Coimbra Batalha Chagas, Anderson Guimarães-Costa, Jullyanna Oliveira, Ingrid Waclawiak, Thamara K F Oliveira, Elvira Maria Saraiva, Anita Leocadio Freitas-Mesquita, José Roberto Meyer-Fernandes, Laura Aragão-Farias, Camilly Enes Trindade, Patricia Cuervo, Renata Azevedo do Nascimento, Otacilio C Moreira, Flávia Lima Ribeiro-Gomes, Yara M Traub-Csekö, Erich Loza Telleria, Slavica Vaselek, Tereza Leštinová, Petr Volf, Gerald F Späth, Elisa Cupolillo, Mariana Côrtes Boité","doi":"10.1371/journal.ppat.1012938","DOIUrl":"10.1371/journal.ppat.1012938","url":null,"abstract":"<p><strong>Background: </strong>The present study investigates implications of a sub-chromosomal deletion in Leishmania infantum strains, the causative agent of American Visceral Leishmaniasis (AVL). Primarily found in New World strains, the deletion leads to the absence of the ecto-3'-nucleotidase/nuclease enzyme, impacting parasite virulence, pathogenicity, and drug susceptibility. The factors favoring prevalence and the widespread geographic distribution of these deleted mutant parasites (DEL) in the NW (NW) are discussed under the generated data.</p><p><strong>Methods: </strong>We conducted phenotypic assessments of the sub-chromosomal deletion through in vitro assays with axenic parasites and experimental infections in both in vitro and in vivo models of vertebrate and invertebrate hosts using geographically diverse mutant field isolates.</p><p><strong>Results: </strong>Despite reduced pathogenicity, the DEL strains efficiently infect vertebrate hosts and exhibit relevant differences, including enhanced metacyclogenesis and colonization rates in sand flies, potentially facilitating transmission. This combination may represent a more effective way to maintain and disperse the transmission cycle of DEL strains.</p><p><strong>Conclusions: </strong>Phenotypic assessments reveal altered parasite fitness, with potential enhanced transmissibility at the population level. Reduced susceptibility of DEL strains to miltefosine, a key drug in VL treatment, further complicates control efforts. The study underscores the importance of typing parasite genomes for surveillance and control, advocating for the sub-chromosomal deletion as a molecular marker in AVL management.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 3","pages":"e1012938"},"PeriodicalIF":5.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671636","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}