Infection and Immunity最新文献

{"title":"<i>Chlamydia</i> plasmid-encoded protein Pgp2 is a replication initiator with a unique β-hairpin necessary for iteron-binding and plasmid replication.","authors":"Danny Wan, Matthew Pan, Guangming Zhong, Huizhou Fan","doi":"10.1128/iai.00602-24","DOIUrl":"https://doi.org/10.1128/iai.00602-24","url":null,"abstract":"<p><p>The virulence plasmid of the obligate intracellular bacterium <i>Chlamydia</i> encodes eight proteins. Among these, Pgp3 is crucial for pathogenicity, and Pgp4 functions as a transcriptional regulator of both plasmid and chromosomal genes. The remaining proteins, Pgp1, Pgp5, Pgp6, Pgp7, and Pgp8, are predicted to play various roles in plasmid replication or maintenance based on their amino acid sequences. However, the function of Pgp2 remains unknown, even though it is required for transformation. In this study, we utilized AlphaFold to predict the three-dimensional (3-D) structure of <i>Chlamydia trachomatis</i> Pgp2. Despite a lack of apparent sequence homology, the AlphaFold structure exhibited high similarity to experimentally determined structures of several plasmid replication initiators. Notably, Pgp2 features a unique β-hairpin motif near the DNA-binding domain, absent in other plasmid replication initiators with overall 3-D structures similar to Pgp2. This β-hairpin motif is also present in AlphaFold models of Pgp2s across all 13 <i>Chlamydia</i> species. To assess its significance, we engineered a plasmid lacking the 11 amino acids constituting the β-hairpin motif in <i>C. trachomatis</i> Pgp2. Although this deletion did not alter the overall structure of Pgp2, the mutated plasmid failed to transform plasmid-free <i>C. trachomatis</i>. These findings reveal that Pgp2 is a plasmid replication initiator, with the β-hairpin motif playing a critical role in binding to its cognate iteron sequences in the replication origin of the chlamydial plasmid.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0060224"},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364617","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":"<i>Candida albicans</i> enhances iron uptake to maintain fluconazole resistance.","authors":"Rishabh Sharma, Anubhav Nahar, Sumant Puri","doi":"10.1128/iai.00002-25","DOIUrl":"https://doi.org/10.1128/iai.00002-25","url":null,"abstract":"<p><p>Widespread use of fluconazole has led to the emergence of fluconazole-resistant (FR) <i>Candid</i>a spp. causing challenges in clinical treatment. Iron, an essential nutrient, affects the levels of ergosterol (a fluconazole target) in fungal membranes. Our lab-generated FR strain (fluconazole minimum inhibitory concentration [MIC] >125 µg/mL) showed a twofold lower MIC (4.66 µg/mL) for the iron chelator deferasirox (DFX), compared to its patent strain CAI4 (DFX MIC 9.34 µg/mL), suggesting a greater sensitivity to iron chelation. A sublethal dose of DFX (2.33 µg/mL) was able to effectively synergize with 125 µg/mL fluconazole to kill the FR strain. Iron estimation revealed significantly enhanced intracellular iron accumulation in the FR strain compared to CAI4. Expression of iron-uptake genes (<i>FRP1</i>, <i>FRE10</i>, and <i>RBT5</i>) was also significantly upregulated in the FR strain, particularly under high iron. FR strain also showed an increase in the levels of cellular ergosterol, along with an increase in the expression of ergosterol biosynthesis genes (<i>ERG11</i> and <i>ERG9</i>), compared to CAI4, under both low and high iron. The strain further showed increased β-glucan levels and exposure. Additionally, FR strain showed significantly higher survival in high-iron mice compared to low-iron mice, during fluconazole treatment. Finally, we observed a synergistic fungicidal response between 2.33 µg/mL DFX and 125 µg/mL fluconazole, for FR clinical strains. Overall, this suggests that FR <i>C. albicans</i> actively uptakes more iron to maintain cellular conditions needed to support its resistance against fluconazole; and that DFX alone or in conjugation with fluconazole has the potential to overcome fluconazole drug resistance.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0000225"},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364616","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":"Zinc-limited <i>Mycobacterium tuberculosis</i> stimulate distinct responses in macrophages compared with standard zinc-replete bacteria.","authors":"Endrei Marcantonio, Allexa D Burger, Kelly H Chang, Fukun W Hoffmann, Yuanyuan Fu, Vedbar S Khadka, Benoit J Smagghe, Youping Deng, Peter R Hoffmann, Sladjana Prisic","doi":"10.1128/iai.00578-24","DOIUrl":"https://doi.org/10.1128/iai.00578-24","url":null,"abstract":"<p><p>Tuberculosis (TB) is notoriously difficult to treat, likely due to the complex host-pathogen interactions driven by pathogen heterogeneity. An understudied area of TB pathogenesis is host responses to <i>Mycobacterium tuberculosis</i> bacteria (Mtb) that are limited in zinc ions. This distinct population resides in necrotic granulomas and sputum and could be the key player in tuberculosis pathogenicity. In this study, we tested the hypothesis that macrophages differentiate between Mtb grown under zinc limitation or in the standard zinc-replete medium. Using several macrophage infection models, such as murine RAW 264.7 and murine bone marrow-derived macrophages (BMDMs), as well as human THP-1-derived macrophages, we show that macrophages infected with zinc-limited Mtb have increased bacterial burden compared with macrophages infected with zinc-replete Mtb. We further demonstrate that macrophage infection with zinc-limited Mtb trigger higher production of reactive oxygen species (ROS) and cause more macrophage death. Furthermore, the increased ROS production is linked to the increased phagocytosis of zinc-limited Mtb, whereas cell death is not. Finally, transcriptional analysis of RAW 264.7 macrophages demonstrates that macrophages have more robust pro-inflammatory responses when infected with zinc-limited Mtb than zinc-replete Mtb. Together, our findings suggest that Mtb's access to zinc affects their interaction with macrophages and that zinc-limited Mtb may be influencing TB progression. Therefore, zinc availability in bacterial growth medium should be considered in TB drug and vaccine developments.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0057824"},"PeriodicalIF":2.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189082","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":"Contribution of the gonococcal <i>NEIS1446-ispD</i> gene conversion to the pathobiology of the <i>Neisseria meningitidis</i> urethritis clade, <i>Nm</i>UC.","authors":"Emilio I Rodriguez, Yih-Ling Tzeng, Soma Sannigrahi, David S Stephens","doi":"10.1128/iai.00350-24","DOIUrl":"10.1128/iai.00350-24","url":null,"abstract":"<p><p>Over the last decade, a <i>Neisseria meningitidis</i> (<i>Nm</i>) urethritis-causing clade (<i>Nm</i>UC) has emerged to cause clusters of meningococcal urethritis in the United States and globally. One genomic signature of <i>Nm</i>UC is the integration of <i>Neisseria gonorrhoeae</i> (<i>Ng</i>) DNA in an operon, <i>NEIS1446-NEIS1438</i>, which partially replaced the <i>Nm ispD</i> gene. IspD is the 2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase of the terpenoid precursor synthesis pathway, required for the production of ubiquinones of the electron transfer chain. IspD is essential in several gram-negative bacteria. The biological importance of the <i>NEIS1446-ispD</i> gene conversion event for <i>Nm</i>UC was investigated. The <i>ispD</i> gene was found to be essential in <i>Nm</i>UC (CNM3) and non-clade <i>Nm</i> (MC58), and a mutation at the native locus can only be made with the insertion of a second <i>ispD</i> copy in the genome. The IspD_MC58 variant was more efficient at promoting aerobic growth at a low level than IspD_CNM3; the two proteins differ by 15 residues. Maximal aerobic growth densities of strains with an <i>Nm</i>UC background resembled <i>Ng</i> (FA19), and both were significantly lower than <i>Nm</i>. In contrast to non-clade <i>Nm</i>, all <i>Nm</i>UC strains survived well anaerobically. Increasing <i>ispD</i> expression by titrating IPTG in non-clade <i>Nm</i> enhanced anaerobic survival. Translational reporters of the <i>Nm</i>UC and <i>Ng</i> promoters demonstrated similar expression levels, and both were significantly higher than non-clade <i>Nm</i>, under aerobic and microaerobic conditions. Our findings suggest that the integration of gonococcal DNA into the <i>NEIS1446-NEIS1438</i> operon of <i>Nm</i>UC has increased <i>ispD</i> expression<i>,</i> contributing to <i>Nm</i>UC's adaptation to the oxygen-limited environment of the human urogenital tract.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0035024"},"PeriodicalIF":2.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189069","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":"Prevalence and features of hypervirulent <i>Klebsiella pneumoniae</i> in respiratory specimens at a US hospital system.","authors":"Christi L McElheny, Alina Iovleva, Nathalie Chen, Dominic Woods, Akansha Pradhan, Jonah L Sonnabend, Aidan R Matunis, Nathan J Raabe, Janet S Lee, Giraldina Trevejo-Nuñez, Daria Van Tyne, Yohei Doi","doi":"10.1128/iai.00486-24","DOIUrl":"10.1128/iai.00486-24","url":null,"abstract":"<p><p>Hypervirulent <i>Klebsiella pneumoniae</i> (hvKp) strains are considered to be relatively rare in the United States, but cases are increasingly reported. We prospectively and serially collected <i>K. pneumoniae</i> clinical isolates identified in respiratory specimens at a health system in Western Pennsylvania between 2020 and 2022. A total of 273 <i>K</i>. <i>pneumoniae</i> isolates from 216 unique patients were analyzed for markers of hypervirulence by both string test for a hypermucoid phenotype and multiplex PCR to detect isolates carrying cardinal virulence genes <i>rmpA</i>, <i>rmpA2</i>, <i>iutA</i>, and <i>iro</i>. Of the 273 isolates, 13 (4.8%) tested positive by string test including 11 nonduplicate <i>K. pneumoniae</i> isolates, and two of these (0.7%) were positive by PCR for virulence genes <i>rmpA</i>, <i>rmpA2</i>, <i>iutA</i>, and <i>iro</i>. The latter two putative hvKp strains, belonging to sequence types ST23-K1 and ST86-SLV-K2, possessed pLVPK-like plasmids, and were collected from community-associated infections in individuals without known travel histories. Both putative hvKp strains and two additional string test-positive strains were resistant to killing by human serum. The hvKp strains caused significant pneumonia in mice infected by oropharyngeal aspiration, with significantly higher weight loss and increased bacterial burden in the lungs of mice infected with the KL1 (ST23) strain compared to the KL2 (ST86-SLV) strain. We also observed decreased survival of mice infected with the KL1 strain compared to the KL2 strain. These findings add to the growing body of evidence suggesting that hvKp strains, once considered endemic to Asia, may now be circulating in North America.IMPORTANCECertain lineages of <i>Klebsiella pneumoniae</i> are increasingly recognized to cause severe community-associated infection, but information on their prevalence in the United States is limited. In a prospective, sequential cohort of 273 <i>K</i>. <i>pneumoniae</i> respiratory isolates, we identified two of them as genetically defined hypervirulent <i>K. pneumoniae</i>. The isolates were from local residents who developed community-onset pneumonia, suggesting that hypervirulent <i>K. pneumoniae</i> may already be present in the community.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0048624"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806986","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":"Expression of Concern for Galdiero et al., \"Porins from <i>Salmonella enterica</i> Serovar Typhimurium Activate the Transcription Factors Activating Protein 1 and NF-κB through the Raf-1-Mitogen-Activated Protein Kinase Cascade\".","authors":"","doi":"10.1128/iai.00491-24","DOIUrl":"10.1128/iai.00491-24","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0049124"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750716","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":"Expression of Concern for Galdiero et al., \"Role of Surface-Exposed Loops of <i>Haemophilus influenzae</i> Protein P2 in the Mitogen-Activated Protein Kinase Cascade\".","authors":"","doi":"10.1128/iai.00492-24","DOIUrl":"10.1128/iai.00492-24","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0049224"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750739","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":"A newly developed oral infection mouse model of shigellosis for immunogenicity and protective efficacy studies of a candidate vaccine.","authors":"Risha Haldar, Prolay Halder, Hemanta Koley, Shin-Ichi Miyoshi, Santasabuj Das","doi":"10.1128/iai.00346-24","DOIUrl":"10.1128/iai.00346-24","url":null,"abstract":"<p><p><i>Shigella</i> infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl₃) plus desferrioxamine intraperitoneally followed by oral infection with virulent <i>Shigella flexneri 2a</i> resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing <i>Shigella</i> invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against <i>Shigella</i>, indicating that the model is suitable for testing of vaccine candidates. To protect both <i>Shigella</i> and <i>Salmonella</i>, a chimeric recombinant vaccine (rIpaB-T2544) was developed by fusing IpaB with <i>Salmonella</i> outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with <i>Shigella</i> (<i>S. flexneri 2a</i>, <i>Shigella dysenteriae</i>, and <i>Shigella sonnei</i>) using our present mouse model and <i>Salmonella</i> (<i>Salmonella</i> Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral S<i>higella</i> infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against <i>Shigella</i>.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0034624"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846619","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 group A <i>Streptococcus</i> pathogenicity island RD2: virulence role and barriers to conjugative transfer.","authors":"Roshika Roshika, Sushila Baral, Ira Jain, Ashna Prabhu, Ameya Singh, Paul Sumby","doi":"10.1128/iai.00273-24","DOIUrl":"10.1128/iai.00273-24","url":null,"abstract":"<p><p>Serotype M28 isolates of the bacterial pathogen the group A <i>Streptococcus</i> (GAS; <i>Streptococcus pyogenes</i>), but not isolates of other serotypes, have a nonrandom association with cases of puerperal sepsis, a life-threatening infection that can occur in women following childbirth. In prior studies, we established that RD2, a pathogenicity island present in all M28 GAS isolates but mostly absent from other serotypes, is a factor in the M28-puerperal sepsis association. Here, we identified a significant reduction in the RD2 conjugation frequency in inter-serotype conjugation assays relative to intra-serotype assays. As isolates of most GAS serotypes produce an antiphagocytic hyaluronic acid capsule, while M28 isolates do not, we tested whether the capsule served as a barrier to RD2 acquisition or maintenance. The data showed that capsule production had no impact on the RD2 conjugation frequency or on the ability of RD2 to enhance vaginal colonization by GAS, but did inhibit the ability of RD2 to enhance GAS adherence to vaginal epithelial cell lines. Further molecular explanations for the inter-serotype barrier to RD2 conjugative transfer were investigated, and a conserved, chromosomally encoded Type I restriction-modification system was identified as being key. We also identified that RD2 modifies the GAS transcriptome, including mRNAs encoding virulence factors with adherence and dissemination roles, following exposure to human plasma. Our data provide insights into factors that contribute to the restriction of the RD2 pathogenicity island to discrete subsets of the GAS population.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0027324"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726809","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":"<i>bb0689</i> contributes to the virulence of <i>Borrelia burgdorferi</i> in a murine model of Lyme disease.","authors":"Connor Waldron, Sierra George, Christina Thompson, Yu Hsien Liao, Zhiming Ouyang","doi":"10.1128/iai.00459-24","DOIUrl":"10.1128/iai.00459-24","url":null,"abstract":"<p><p><i>Borrelia burgdorferi</i>, the Lyme disease pathogen, continuously changes its gene expression profile in order to adapt to ticks and mammalian hosts. The alternative sigma factor RpoS plays a central role in borrelial host adaptation. Global transcriptome analyses suggested that more than 100 genes might be regulated by RpoS, but the main part of the regulon remains unexplored. Here, we showed that the expression of <i>bb0689</i>, a gene encoding an outer surface lipoprotein with unknown function, was activated by RpoS. By analyzing gene expression using luciferase reporter assays and quantitative reverse transcription PCR, we found that expression of <i>bb0689</i> was induced by an elevated temperature, a reduced pH, and increased cell density during <i>in vitro</i> cultivation. The transcriptional start site and a functional promoter for gene expression were identified in the 5' regulatory region of <i>bb0689</i>. The promoter was responsive to environmental stimuli and influenced by RpoS. We also showed that <i>bb0689</i> expression was expressed in <i>B. burgdorferi</i> during animal infection, suggesting the importance of this gene for infection. We further generated a <i>bb0689</i> mutant and found that the infectivity of the mutant was severely attenuated in a murine infection model. Although <i>bb0689</i>-deficient spirochetes exhibited no defect during <i>in vitro</i> growth, they were defective in resistance to osmotic stress. <i>Cis</i>-complementation of the mutant with a wild-type copy of <i>bb0689</i> fully rescued all phenotypes. Collectively, these results demonstrate that the RpoS-regulated gene <i>bb0689</i> is a key contributor to the optimal infection of <i>B. burgdorferi</i> in animals.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0045924"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827790","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}