EMBO Molecular Medicine最新文献

{"title":"Clinically translatable mitochondrial gene therapy in muscle using tandem mtZFN architecture.","authors":"Pavel A Nash,Keira M Turner,Christopher A Powell,Lindsey Van Haute,Pedro Silva-Pinheiro,Felix Bubeck,Ellen Wiedtke,Eloïse Marques,Dylan G Ryan,Dirk Grimm,Payam A Gammage,Michal Minczuk","doi":"10.1038/s44321-025-00231-5","DOIUrl":"https://doi.org/10.1038/s44321-025-00231-5","url":null,"abstract":"Mutations in the mitochondrial genome (mtDNA) often lead to clinical pathologies. Mitochondrially-targeted zinc finger nucleases (mtZFNs) have been successful in reducing the levels of mutation-bearing mtDNA both in vivo and in vitro, resulting in a shift in the genetic makeup of affected mitochondria and subsequently to phenotypic rescue. Given the uneven distribution in the mtDNA mutation load across tissues in patients, and a great diversity in pathogenic mutations, it is of interest to develop mutation-specific, selective gene therapies that could be delivered to particular tissues. This study demonstrates the effectiveness of in vivo mitochondrial gene therapy using a novel mtZFN architecture on skeletal muscle using adeno-associated viral (AAV) platforms in a murine model harboring a pathogenic mtDNA mutation. We observed effective reduction in mutation load of cardiac and skeletal muscle, which was accompanied by molecular phenotypic rescue. The gene therapy treatment was shown to be safe when markers of immunity and inflammation were assessed. These results highlight the potential of curative approaches for mitochondrial diseases, paving the way for targeted and effective treatments.","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":"29 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819289","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":"Immune training enhances anti-viral responses and improves outcomes in Pax5^-/+ mice susceptible to chronic infection.","authors":"Zhe Lu, Olivia Stencel, Wei Liu, Eleni Vasileiou, Haifeng C Xu, Piyush Pandey, Paweł Stachura, Abdelrahman Elwy, Anastassia Tsombal, Ann-Sophie Mai, Franziska Auer, Mina N F Morcos, Maximilian Seidl, Sarah Koziel, Peter-Martin Bruch, Sascha Dietrich, Sarah Elitzur, Gunther Hartmann, Karl S Lang, Stefan Janssen, Ute Fischer, Sanil Bhatia, Philipp A Lang, Arndt Borkhardt, Julia Hauer, Aleksandra A Pandyra","doi":"10.1038/s44321-025-00208-4","DOIUrl":"10.1038/s44321-025-00208-4","url":null,"abstract":"<p><p>Viral infections pose a significant global burden. Host susceptibility to pathogens is determined by many factors including genetic variation that can lead to immunodeficient or dysregulated antiviral immune responses. Pax5 heterozygosity (Pax5^-/+), resulting in reduced PAX5 levels in mice, mimics germline or somatic PAX5 dysregulation contributing to diseases such as childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). In contrast to the well-characterized roles of PAX5 during early B-cell development, little is known about how Pax5 heterozygosity impacts antiviral responses. We infected Pax5^-/+ mice with the noncytopathic Lymphocytic Choriomeningitis Virus (LCMV) and found that infection with the chronic Docile strain resulted in decreased survival of Pax5^-/+ mice. While early adaptive CD8⁺ T-cell (CTL) immunity was robust in Pax5^-/+ mice, LCMV-specific neutralizing antibody production was compromised leading to impaired long-term viral clearance and a pro-inflammatory milieu in the bone marrow (BM). Here we show that survival outcomes were improved upon prophylactic treatment with the β-glucan immune trainer through induction of heterologous protection against chronic infection. β-Glucan enhanced viral clearance, CTL immunity, neutralizing antibody production and reduced monocyte immunosuppression in multiple LCMV-resident host organs. New insight from this study will help design effective prophylactic treatment strategies against chronic viral infections, particularly in genetically predisposed susceptible hosts.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"696-721"},"PeriodicalIF":9.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623997","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":"Proteomics and personalized PDX models identify treatment for a progressive malignancy within an actionable timeframe.","authors":"Georgina D Barnabas,Tariq A Bhat,Verena Goebeler,Pascal Leclair,Nadine Azzam,Nicole Melong,Colleen Anderson,Alexis Gom,Seohee An,Enes K Ergin,Yaoqing Shen,Agustina Conrrero,Andrew J Mungall,Karen L Mungall,Christopher A Maxwell,Gregor S D Reid,Martin Hirst,Steven Jones,Jennifer A Chan,Donna L Senger,Jason N Berman,Seth J Parker,Jonathan W Bush,Caron Strahlendorf,Rebecca J Deyell,C James Lim,Philipp F Lange","doi":"10.1038/s44321-025-00212-8","DOIUrl":"https://doi.org/10.1038/s44321-025-00212-8","url":null,"abstract":"Genomics has transformed the diagnostic landscape of pediatric malignancies by identifying and integrating actionable features that refine diagnosis, classification, and treatment. Yet, translating precision oncology data into effective therapies for hard-to-cure childhood, adolescent, and young adult malignancies remains a significant challenge. We present the case for combining proteomics with patient-derived xenograft models to identify personalized treatment for an adolescent with primary and metastatic spindle epithelial tumor with thymus-like elements (SETTLE). Within two weeks of biopsy, proteomics identified elevated SHMT2 as a target for therapy with the anti-depressant sertraline. Drug response was confirmed within two months using a personalized chicken chorioallantoic membrane model of the patient's SETTLE tumor. Following failure of cytotoxic chemotherapy and second-line therapy, the patient received sertraline treatment and showed decreased tumor growth rates, albeit with clinically progressive disease. We demonstrate that proteomics and fast-track xenograft models provide supportive pre-clinical data in a clinically meaningful timeframe to impact clinical practice. By this, we show that proteome-guided and functional precision oncology are feasible and valuable complements to the current genome-driven precision oncology practices.","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":"108 1","pages":"625-644"},"PeriodicalIF":11.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818999","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":"Deubiquitination of RIPK3 by OTUB2 potentiates neuronal necroptosis after ischemic stroke.","authors":"Fuqi Mei, Deyu Deng, Zijun Cao, Liyan Lou, Kangmin Chen, Minjie Hu, Zhenhu Zhu, Jiangyun Shen, Jianzhao Zhang, Jie Liang, Jingyong Huang, Min Bao, Ari Waisman, Xu Wang","doi":"10.1038/s44321-025-00206-6","DOIUrl":"10.1038/s44321-025-00206-6","url":null,"abstract":"<p><p>As a common and severe cerebrovascular disease, ischemic stroke casts a significant shadow over global health. Unfortunately, the mechanisms regulating neuronal death in the affected areas remain largely unclear. Here, we found that deletion of the deubiquitinating enzyme Otubain-2 (OTUB2) significantly alleviated ischemia-induced cerebral infarction and neurological deficits, accompanied by a reduction in neuronal loss, glial activation, and neuroinflammation. OTUB2 was predominantly expressed in neurons and its deletion decreased receptor-interacting protein kinase 3 (RIPK3)-mediated neuronal necroptosis. Moreover, OTUB2 increased RIPK3 protein abundance by inhibiting the proteasomal degradation of RIPK3. Mechanistically, OTUB2 removed K48-linked polyubiquitin chains from RIPK3 through its active site C51. Importantly, pharmacological inhibition of OTUB2 alleviated ischemic brain injury in mice and reduced oxygen-glucose deprivation-induced neuronal death in human brain organoids. These results demonstrate that OTUB2 critically regulates ischemic stroke injury by potentiating neuronal necroptosis, suggesting that OTUB2 inhibition may become a potential therapeutic approach for treating ischemic stroke.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"679-695"},"PeriodicalIF":9.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531086","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":"Exposomics: a review of methodologies, applications, and future directions in molecular medicine.","authors":"Melissa Wan, Elisabeth M Simonin, Mary Margaret Johnson, Xinyue Zhang, Xiangping Lin, Peng Gao, Chirag J Patel, Aroub Yousuf, Michael P Snyder, Xiumei Hong, Xiaobin Wang, Vanitha Sampath, Kari C Nadeau","doi":"10.1038/s44321-025-00191-w","DOIUrl":"10.1038/s44321-025-00191-w","url":null,"abstract":"<p><p>The exposome is the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Exposomics is the emerging field of research to measure and study the totality of the exposome. Exposomics can assist with molecular medicine by furthering our understanding of how the exposome influences cellular and molecular processes such as gene expression, epigenetic modifications, metabolic pathways, and immune responses. These molecular alterations can aid as biomarkers for the diagnosis, disease prediction, early detection, and treatment and offering new avenues for personalized medicine. Advances in high throughput omics and other technologies as well as increased computational analytics is enabling comprehensive measurement and sophisticated analysis of the exposome to elucidate their cumulative and combined impacts on health, which can enable individuals, communities, and policymakers to create programs, policies, and protections that promote healthier environments and people. This review provides an overview of the potential role of exposomics in molecular medicine, covering its history, methodologies, current research and applications, and future directions.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"599-608"},"PeriodicalIF":9.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052072","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":"Targeting cIAP2 in a novel senolytic strategy prevents glioblastoma recurrence after radiotherapy.","authors":"Nozomi Tomimatsu, Luis Fernando Macedo Di Cristofaro, Suman Kanji, Lorena Samentar, Benjamin Russell Jordan, Ralf Kittler, Amyn A Habib, Jair Machado Espindola-Netto, Tamara Tchkonia, James L Kirkland, Terry C Burns, Jann N Sarkaria, Andrea Gilbert, John R Floyd, Robert Hromas, Weixing Zhao, Daohong Zhou, Patrick Sung, Bipasha Mukherjee, Sandeep Burma","doi":"10.1038/s44321-025-00201-x","DOIUrl":"10.1038/s44321-025-00201-x","url":null,"abstract":"<p><p>Glioblastomas (GBM) are routinely treated with high doses of ionizing radiation (IR), yet these tumors recur quickly, and the recurrent tumors are highly therapy resistant. Here, we report that IR-induced senescence of tumor cells counterintuitively spurs GBM recurrence, driven by the senescence-associated secretory phenotype (SASP). We find that irradiated GBM cell lines and patient derived xenograft (PDX) cultures senesce rapidly in a p21-dependent manner. Senescent glioma cells upregulate SASP genes and secrete a panoply of SASP factors, prominently interleukin IL-6, an activator of the JAK-STAT3 pathway. These SASP factors collectively activate the JAK-STAT3 and NF-κB pathways in non-senescent GBM cells, thereby promoting tumor cell proliferation and SASP spreading. Transcriptomic analyses of irradiated GBM cells and the TCGA database reveal that the cellular inhibitor of apoptosis protein 2 (cIAP2), encoded by the BIRC3 gene, is a potential survival factor for senescent glioma cells. Senescent GBM cells not only upregulate BIRC3 but also induce BIRC3 expression and promote radioresistance in non-senescent tumor cells. We find that second mitochondria-derived activator of caspases (SMAC) mimetics targeting cIAP2 act as novel senolytics that trigger apoptosis of senescent GBM cells with minimal toxicity towards normal brain cells. Finally, using both PDX and immunocompetent mouse models of GBM, we show that the SMAC mimetic birinapant, administered as an adjuvant after radiotherapy, can eliminate senescent GBM cells and prevent the emergence of recurrent tumors. Taken together, our results clearly indicate that significant improvement in GBM patient survival may become possible in the clinic by eliminating senescent cells arising after radiotherapy.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"645-678"},"PeriodicalIF":9.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457271","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":"Precise mycobacterial species and subspecies identification using the PEP-TORCH peptidome algorithm.","authors":"Duran Bao, Sudipa Maity, Lingpeng Zhan, Seungyeon Seo, Qingbo Shu, Christopher J Lyon, Bo Ning, Adrian Zelazny, Tony Y Hu, Jia Fan","doi":"10.1038/s44321-025-00207-5","DOIUrl":"10.1038/s44321-025-00207-5","url":null,"abstract":"<p><p>Mycobacterial infections pose a significant global health concern, requiring precise identification for effective treatment. However, diagnosing them is challenging due to inaccurate identifications and prolonged times. In this study, we aimed to develop a novel peptidome-based method using mycobacterial growth indicator tube (MGIT) cultures for faster and more accurate identification. We created the PEPtide Taxonomy/ORganism CHecking (PEP-TORCH), an algorithm that analyzes tryptic peptides identified by mass spectrometry to diagnose species and subspecies with predominance scores. PEP-TORCH demonstrated 100% accuracy in identifying mycobacterial species, subspecies, and co-infections in 81 individuals suspected of mycobacterial infections, eliminating the need for a sub-solid culture procedure, the gold standard in clinical practice. A notable strength of PEP-TORCH is its ability to provide information on species and subspecies simultaneously, a process conventionally achieved sequentially. This capability significantly expedites pathogen identification. Furthermore, a targeted proteomics method was validated in 63 clinical samples using the taxa-specific peptides selected by PEP-TORCH, making them suitable as biomarkers in more clinically friendly settings. This comprehensive identification approach holds promise for streamlining treatment strategies in clinical practice.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"841-861"},"PeriodicalIF":9.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556090","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":"Improving the odds of survival: transgenerational effects of infections.","authors":"Victoria M Spanou, Theano P Andriopoulou, Evangelos J Giamarellos-Bourboulis, Mihai G Netea","doi":"10.1038/s44321-025-00192-9","DOIUrl":"10.1038/s44321-025-00192-9","url":null,"abstract":"<p><p>Recent studies argue for a novel concept of the role of chromatin as a carrier of epigenetic memory through cellular and organismal generations, defining and coordinating gene activity states and physiological functions. Environmental insults, such as exposures to unhealthy diets, smoking, toxic compounds, and infections, can epigenetically reprogram germ-line cells and influence offspring phenotypes. This review focuses on intergenerational and transgenerational epigenetic inheritance in different plants, animal species and humans, presenting the up-to-date evidence and arguments for such effects in light of Darwinian and Lamarckian evolutionary theories. An overview of the epigenetic changes induced by infection or other immune challenges is presented, and how these changes, known as epimutations, contribute to shaping offspring phenotypes. The mechanisms that mediate the transmission of epigenetic alterations via the germline are also discussed. Understanding the relationship between environmental fluctuations, epigenetic changes, resistance, and susceptibility to diseases is critical for unraveling disease etiology and adaptive evolution.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"609-624"},"PeriodicalIF":9.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022776","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":"X-linked myopathy with excessive autophagy: characterization and therapy testing in a zebrafish model.","authors":"Lily Huang, Rebecca Simonian, Michael A Lopez, Muthukumar Karuppasamy, Veronica M Sanders, Katherine G English, Lacramioara Fabian, Matthew S Alexander, James J Dowling","doi":"10.1038/s44321-025-00204-8","DOIUrl":"10.1038/s44321-025-00204-8","url":null,"abstract":"<p><p>X-linked myopathy with excessive autophagy (XMEA), a rare childhood-onset autophagic vacuolar myopathy caused by mutations in VMA21, is characterized by proximal muscle weakness and progressive vacuolation. VMA21 encodes a protein chaperone of the vacuolar hydrogen ion ATPase, the loss of which leads to lysosomal neutralization and impaired function. At present, there is an incomplete understanding of XMEA, its mechanisms, consequences on other systems, and therapeutic strategies. A significant barrier to advancing knowledge and treatments is the lack of XMEA animal models. Therefore, we used CRISPR-Cas9 editing to engineer a loss-of-function mutation in zebrafish vma21. The vma21 mutant zebrafish phenocopy the human disease with impaired motor function and survival, liver dysfunction, and dysregulated autophagy indicated by lysosomal de-acidification, the presence of characteristic autophagic vacuoles in muscle fibers, altered autophagic flux, and reduced lysosomal marker staining. As proof-of-concept, we found that two drugs, edaravone and LY294002, improve swim behavior and survival. In total, we generated and characterized a novel preclinical zebrafish XMEA model and demonstrated its suitability for studying disease pathomechanisms and identifying potential therapeutic targets.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"823-840"},"PeriodicalIF":9.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491277","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":"Chaperone-mediated autophagy regulates the metastatic state of mesenchymal tumors.","authors":"Xun Zhou, Eva Berenger, Yong Shi, Vera Shirokova, Elena Kochetkova, Tina Becirovic, Boxi Zhang, Vitaliy O Kaminskyy, Yashar Esmaeilian, Kayoko Hosaka, Cecilia Lindskog, Per Hydbring, Simon Ekman, Yihai Cao, Maria Genander, Marcin Iwanicki, Erik Norberg, Helin Vakifahmetoglu-Norberg","doi":"10.1038/s44321-025-00210-w","DOIUrl":"10.1038/s44321-025-00210-w","url":null,"abstract":"<p><p>Tumors often recapitulate programs to acquire invasive and dissemination abilities, during which pro-metastatic proteins are distinctively stabilized in cancer cells to drive further progression. Whether failed protein degradation affects the metastatic programs of cancer remains unknown. Here, we show that the human cancer cell-specific knockout (KO) of LAMP-2A, a limiting protein for chaperone-mediated autophagy (CMA), promotes the aggressiveness of mesenchymal tumors. Deficient CMA resulted in widespread tumor cell dissemination, invasion into the vasculature and cancer metastasis. In clinical samples, metastatic lesions showed suppressed LAMP-2A expression compared to primary tumors from the same cancer patients. Mechanistically, while stimulating TGFβ signaling dampens LAMP-2A levels, genetic suppression of CMA aggravated TGFβ signaling in cancer cells and tumors. Conversely, pharmacological inhibition of TGFβ signaling repressed the growth of LAMP-2A KO-driven tumors. Furthermore, we found that multiple EMT-driving proteins, such as TGFβR2, are degraded by CMA. Our study demonstrates that the tumor suppressive function of CMA involves negative regulation of TGFβ-driven EMT and uncovers a mechanistic link between CMA and a major feature of metastatic invasiveness.</p>","PeriodicalId":11597,"journal":{"name":"EMBO Molecular Medicine","volume":" ","pages":"747-774"},"PeriodicalIF":9.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585195","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}