Infection and Immunity最新文献

{"title":"Emergent <i>emm4</i> group A <i>Streptococcus</i> evidences a survival strategy during interaction with immune effector cells.","authors":"Chioma M Odo, Luis A Vega, Piyali Mukherjee, Sruti DebRoy, Anthony R Flores, Samuel A Shelburne","doi":"10.1128/iai.00152-24","DOIUrl":"10.1128/iai.00152-24","url":null,"abstract":"<p><p>The major gram-positive pathogen group A <i>Streptococcus</i> (GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics have been ascribed to the emergence of clones producing increased amounts of key virulence factors such as streptolysin O (SLO). Herein, we sought to identify mechanisms underlying our recently identified temporal clonal emergence among <i>emm4</i> GAS, given that emergent strains did not produce augmented levels of virulence factors relative to historic isolates. By creating and analyzing isoallelic strains, we determined that a conserved mutation in a previously undescribed gene encoding a putative carbonic anhydrase was responsible for the defective <i>in vitro</i> growth observed in the emergent strains. We also identified that the emergent strains survived better inside macrophages and killed macrophages at lower rates than the historic strains. <i>Via</i> the creation of isogenic mutant strains, we linked the emergent strain \"survival\" phenotype to the downregulation of the SLO encoding gene and upregulation of the <i>msrAB</i> operon which encodes proteins involved in defense against extracellular oxidative stress. Our findings are in accord with recent surveillance studies which found a high ratio of mucosal (i.e., pharyngeal) relative to invasive infections among <i>emm4</i> GAS. Since ever-increasing virulence is unlikely to be evolutionarily advantageous for a microbial pathogen, our data further understanding of the well-described oscillating patterns of virulent GAS infections by demonstrating mechanisms by which emergent strains adapt a \"survival\" strategy to outcompete previously circulating isolates.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Articles of Significant Interest in This Issue.","authors":"","doi":"10.1128/iai.00281-24","DOIUrl":"https://doi.org/10.1128/iai.00281-24","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B cells in perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell signatures identify asymptomatic <i>Mycobacterium tuberculosis</i> lung infection in Diversity Outbred mice.","authors":"Deniz Koyuncu, Thomas Tavolara, Daniel M Gatti, Adam C Gower, Melanie L Ginese, Igor Kramnik, Bülent Yener, Usama Sajjad, Muhammad Khalid Khan Niazi, Metin Gurcan, Anas Alsharaydeh, Gillian Beamer","doi":"10.1128/iai.00263-23","DOIUrl":"10.1128/iai.00263-23","url":null,"abstract":"<p><p>Because most humans resist <i>Mycobacterium tuberculosis</i> infection, there is a paucity of lung samples to study. To address this gap, we infected Diversity Outbred mice with <i>M. tuberculosis</i> and studied the lungs of mice in different disease states. After a low-dose aerosol infection, progressors succumbed to acute, inflammatory lung disease within 60 days, while controllers maintained asymptomatic infection for at least 60 days, and then developed chronic pulmonary tuberculosis (TB) lasting months to more than 1 year. Here, we identified features of asymptomatic <i>M. tuberculosis</i> infection by applying computational and statistical approaches to multimodal data sets. Cytokines and anti-<i>M</i>. <i>tuberculosis</i> cell wall antibodies discriminated progressors vs controllers with chronic pulmonary TB but could not classify mice with asymptomatic infection. However, a novel deep-learning neural network trained on lung granuloma images was able to accurately classify asymptomatically infected lungs vs acute pulmonary TB in progressors vs chronic pulmonary TB in controllers, and discrimination was based on perivascular and peribronchiolar lymphocytes. Because the discriminatory lesion was rich in lymphocytes and CD4 T cell-mediated immunity is required for resistance, we expected CD4 T-cell genes would be elevated in asymptomatic infection. However, the significantly different, highly expressed genes were from B-cell pathways (e.g., <i>Bank1</i>, <i>Cd19</i>, <i>Cd79</i>, <i>Fcmr</i>, <i>Ms4a1</i>, <i>Pax5</i>, and <i>H2-Ob</i>), and CD20+ B cells were enriched in the perivascular and peribronchiolar regions of mice with asymptomatic <i>M. tuberculosis</i> infection. Together, these results indicate that genetically controlled B-cell responses are important for establishing asymptomatic <i>M. tuberculosis</i> lung infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of naturally acquired, strain-transcending antibodies against rosetting <i>Plasmodium falciparum</i> strains in humans.","authors":"Florence E McLean, Yvonne Azasi, Cameron Sutherland, Emmanuel Toboh, Daniel Ansong, Tsiri Agbenyega, Gordon Awandare, J Alexandra Rowe","doi":"10.1128/iai.00015-24","DOIUrl":"10.1128/iai.00015-24","url":null,"abstract":"<p><p>Strain-transcending antibodies against virulence-associated subsets of <i>P. falciparum</i>-infected erythrocyte surface antigens could protect children from severe malaria. However, the evidence supporting the existence of such antibodies is incomplete and inconsistent. One subset of surface antigens associated with severe malaria, rosette-mediating <i>Plasmodium falciparum</i> Erythrocyte Membrane Protein one (PfEMP1) variants, cause infected erythrocytes to bind to uninfected erythrocytes to form clusters of cells (rosettes) that contribute to microvascular obstruction and pathology. Here, we tested plasma from 80 individuals living in malaria-endemic regions for IgG recognition of the surface of four <i>P. falciparum</i> rosetting strains using flow cytometry. Broadly reactive plasma samples were then used in antibody elution experiments in which intact IgG was eluted from the surface of infected erythrocytes and transferred to heterologous rosetting strains to look for strain-transcending antibodies. We found that seroprevalence (percentage of positive plasma samples) against allopatric rosetting strains was high in adults (63%-93%) but lower in children (13%-48%). Strain-transcending antibodies were present in nine out of eleven eluted antibody experiments, with six of these recognizing multiple heterologous rosetting parasite strains. One eluate had rosette-disrupting activity against heterologous strains, suggesting PfEMP1 as the likely target of the strain-transcending antibodies. Naturally acquired strain-transcending antibodies to rosetting <i>P. falciparum</i> strains in humans have not been directly demonstrated previously. Their existence suggests that such antibodies could play a role in clinical protection and raises the possibility that conserved epitopes recognized by strain-transcending antibodies could be targeted therapeutically by monoclonal antibodies or vaccines.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the alleviative effect of <i>Lactobacillus plantarum</i> on <i>Eimeria falciformis</i> infection.","authors":"Yufei Sun, Pufang Liu, Wenhui Guo, Jun Guo, Jia Chen, Xinyu Xue, Chao Duan, Zixuan Wang, Xinlei Yan","doi":"10.1128/iai.00130-24","DOIUrl":"10.1128/iai.00130-24","url":null,"abstract":"<p><p>Coccidia of the genus <i>Eimeria</i> are specialized intracellular parasitic protozoa that cause severe coccidiosis when they infect their hosts. Animals infected with <i>Eimeria</i> develop clinical symptoms, such as anorexia, diarrhea, and hematochezia, which can even cause death. Although the current preferred regimen for the treatment of coccidiosis is antibiotics, this treatment strategy is limited by the ban on antibiotics and the growing problem of drug resistance. Therefore, the exploration of alternative methods for controlling coccidiosis has attracted much attention. <i>Lactobacillus plantarum</i> has been shown to have many beneficial effects. In this study, <i>L. plantarum</i> M2 was used as a research object to investigate the effect of <i>L. plantarum</i> on intestinal inflammation induced by infection with <i>Eimeria falciformis</i> in mice by detecting indicators, such as oocyst output, serum cytokines, and the intestinal microbiota. Compared with that in the infection group, the percent weight loss of the mice that were administered with <i>L. plantarum</i> M2 was significantly reduced (<i>P</i> < 0.05). Supplemented <i>L. plantarum</i> M2 and probiotics combined with diclazuril can reduce the total oocyst output significantly (<i>P</i> < 0.05, <i>P</i> < 0.001). <i>L. plantarum</i> M2 had outstanding performance in maintaining intestinal barrier function, and the levels of the mucin MUC1 and the tight junction protein E-cadherin were significantly elevated (<i>P</i> < 0.01, <i>P</i> < 0.05). Studies have shown that probiotic supplementation can alleviate adverse reactions after infection and significantly improve intestinal barrier function. In addition, probiotics combined with diclazuril could optimize the partial efficacy of diclazuril, which not only enhanced the effect of antibiotics but also alleviated their adverse effects. This study expands the application of probiotics, provides new ideas for alternative strategies for coccidia control, and suggests a basis for related research on lactobacilli antagonizing intracellular pathogen infection.IMPORTANCECoccidia of the genus <i>Eimeria</i> are specialized intracellular parasitic protozoa, and the current preferred regimen for the treatment of coccidiosis is antibiotics. However, due to antibiotic bans and drug resistance, the exploration of alternative methods for controlling coccidiosis has attracted much attention. In this work, we focused on <i>Lactobacillus plantarum</i> M2 and found that probiotic supplementation can alleviate adverse reactions after infection and improve intestinal barrier function. This study proposes the possibility of using lactic acid bacteria to control coccidiosis, and its potential mechanism needs further exploration.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of <i>Babesia microti</i> immunoreactive antigens by phage display cDNA screen.","authors":"Toshihiko Hanada, Maulana A Empitu, Gregory I Mines, Qianni Ma, Iziegbe L Omorodion, Ansel Link, Christopher J Schwake, Rachel M Krueger, Nicholas S DaRosa, Andrew E Levin, Edouard Vannier, Athar H Chishti","doi":"10.1128/iai.00215-24","DOIUrl":"10.1128/iai.00215-24","url":null,"abstract":"<p><p>Human babesiosis is a malaria-like illness caused by protozoan parasites of the genus <i>Babesia</i>. <i>Babesia microti</i> is responsible for most cases of human babesiosis in the United States, particularly in the Northeast and the Upper Midwest. <i>Babesia microti</i> is primarily transmitted to humans through the bite of infected deer ticks but also through the transfusion of blood components, particularly red blood cells. There is a high risk of severe and even fatal disease in immunocompromised patients. To date, serology testing relies on an indirect immunofluorescence assay that uses the whole <i>Babesia microti</i> antigen. Here, we report the construction of phage display cDNA libraries from <i>Babesia microti</i>-infected erythrocytes as well as human reticulocytes obtained from donors with hereditary hemochromatosis. Plasma samples were obtained from patients who were or had been infected with <i>Babesia microti</i>. The non-specific antibody reactivity of these plasma samples was minimized by pre-exposure to the human reticulocyte library. Using this novel experimental strategy, immunoreactive segments were identified in three <i>Babesia microti</i> antigens termed BmSA1 (also called BMN1-9; BmGPI12), BMN1-20 (BMN1-17; Bm32), and BM4.12 (N1-15). Moreover, our findings indicate that the major immunoreactive segment of BmSA1 does not overlap with the segment that mediates BmSA1 binding to mature erythrocytes. When used in combination, the three immunoreactive segments form the basis of a sensitive and comprehensive diagnostic immunoassay for human babesiosis, with implications for vaccine development.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manganese uptake by MtsABC contributes to the pathogenesis of human pathogen group A streptococcus by resisting host nutritional immune defenses.","authors":"Nishanth Makthal, Subhasree Saha, Elaine Huang, Juliane John, Himani Meena, Shifu Aggarwal, Martin Högbom, Muthiah Kumaraswami","doi":"10.1128/iai.00077-24","DOIUrl":"10.1128/iai.00077-24","url":null,"abstract":"<p><p>The interplay between host nutritional immune mechanisms and bacterial nutrient uptake systems has a major impact on the disease outcome. The host immune factor calprotectin (CP) limits the availability of essential transition metals, such as manganese (Mn) and zinc (Zn), to control the growth of invading pathogens. We previously demonstrated that the competition between CP and the human pathogen group A streptococcus (GAS) for Zn impacts GAS pathogenesis. However, the contribution of Mn sequestration by CP in GAS infection control and the role of GAS Mn acquisition systems in overcoming host-imposed Mn limitation remain unknown. Using a combination of <i>in vitro</i> and <i>in vivo</i> studies, we show that GAS-encoded <i>mtsABC</i> is a Mn uptake system that aids bacterial evasion of CP-imposed Mn scarcity and promotes GAS virulence. Mn deficiency caused by either the inactivation of <i>mtsC</i> or CP also impaired the protective function of GAS-encoded Mn-dependent superoxide dismutase. Our <i>ex vivo</i> studies using human saliva show that saliva is a Mn-scant body fluid, and Mn acquisition by MtsABC is critical for GAS survival in human saliva. Finally, animal infection studies using wild-type (WT) and <i>CP-/</i>- mice showed that MtsABC is critical for GAS virulence in WT mice but dispensable in mice lacking CP, indicating the direct interplay between MtsABC and CP <i>in vivo</i>. Together, our studies elucidate the role of the Mn import system in GAS evasion of host-imposed metal sequestration and underscore the translational potential of MtsABC as a therapeutic or prophylactic target.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The SapM phosphatase can arrest phagosome maturation in an ESX-1 independent manner in <i>Mycobacterium tuberculosis</i> and BCG.","authors":"Christian Xander, Saranathan Rajagopalan, William R Jacobs, Miriam Braunstein","doi":"10.1128/iai.00217-24","DOIUrl":"10.1128/iai.00217-24","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is an intracellular pathogen that survives and grows in macrophages. A mechanism used by <i>Mtb</i> to achieve intracellular survival is to secrete effector molecules that arrest the normal process of phagosome maturation. Through phagosome maturation arrest (PMA), <i>Mtb</i> remains in an early phagosome and avoids delivery to degradative phagolysosomes. One PMA effector of <i>Mtb</i> is the secreted SapM phosphatase. Because the host target of SapM, phosphatidylinositol-3-phosphate (PI₃P), is located on the cytosolic face of the phagosome, SapM needs to not only be released by the mycobacteria but also travel out of the phagosome to carry out its function. To date, the only mechanism known for <i>Mtb</i> molecules to leave the phagosome is phagosome permeabilization by the ESX-1 secretion system. To understand this step of SapM function in PMA, we generated identical in-frame <i>sapM</i> mutants in both the attenuated <i>Mycobacterium bovis</i> bacille Calmette-Guérin (BCG) vaccine strain, which lacks the ESX-1 system, and <i>Mtb</i>. Characterization of these mutants demonstrated that SapM is required for PMA in BCG and <i>Mtb</i>. Further, by establishing a role for SapM in PMA in BCG, and subsequently in a <i>Mtb</i> mutant lacking the ESX-1 system, we demonstrated that the role of SapM does not require ESX-1. We further determined that ESX-2 or ESX-4 is also not required for SapM to function in PMA. These results indicate that SapM is a secreted effector of PMA in both BCG and <i>Mtb</i>, and that it can function independent of the known mechanism for <i>Mtb</i> molecules to leave the phagosome.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the immune dynamics of <i>Neisseria</i> persistent oral colonization.","authors":"Mario Alles, Manuja Gunasena, Tauqir Zia, Adonis D'Mello, Saroj Bhattarai, Will Mulhern, Luke Terry, Trenton Scherger, Saranga Wijeratne, Sachleen Singh, Asela J Wijeratne, Dhanuja Kasturiratna, Hervé Tettelin, Nathan J Weyand, Namal P M Liyanage","doi":"10.1128/iai.00048-24","DOIUrl":"10.1128/iai.00048-24","url":null,"abstract":"<p><p>Commensal bacteria are crucial in maintaining host physiological homeostasis, immune system development, and protection against pathogens. Despite their significance, the factors influencing persistent bacterial colonization and their impact on the host still need to be fully understood. Animal models have served as valuable tools to investigate these interactions, but most have limitations. The bacterial genus <i>Neisseria</i>, which includes both commensal and pathogenic species, has been studied from a pathogenicity to humans perspective but lacks models that study immune responses in the context of long-term persistence. <i>Neisseria musculi</i>, a recently described natural commensal of mice, offers a unique opportunity to study long-term host-commensal interactions. In this study, for the first time, we have used this model to study the transcriptional, phenotypic, and functional dynamics of immune cell signatures in the mucosal and systemic tissue of mice in response to <i>N. musculi</i> colonization. We found key genes and pathways vital for immune homeostasis in palate tissue, validated by flow cytometry of immune cells from the lung, blood, and spleen. This study offers a novel avenue for advancing our understanding of host-bacteria dynamics and may provide a platform for developing efficacious interventions against mucosal persistence by pathogenic <i>Neisseria</i>.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction for Bourrel et al., \"Specific interaction between Group B <i>Streptococcus</i> CC17 hypervirulent clone and phagocytes\".","authors":"Anne-Sophie Bourrel, Amandine Picart, Jose-Carlos Fernandez, Constantin Hays, Virginie Mignon, Bruno Saubaméa, Claire Poyart, Agnès Fouet, Asmaa Tazi, Julie Guignot","doi":"10.1128/iai.00188-24","DOIUrl":"10.1128/iai.00188-24","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}