Biogerontology最新文献

{"title":"DNA methylation-based epigenetic clocks highlight immune-driven aging acceleration in COVID-19 across diverse populations.","authors":"Manoj Kumar Gupta, Ramakrishna Vadde","doi":"10.1007/s10522-025-10360-6","DOIUrl":"10.1007/s10522-025-10360-6","url":null,"abstract":"<p><p>The SARS-CoV-2 pandemic has affected millions worldwide, with aging being a key risk factor for severe disease outcomes. This study examines the rate of epigenetic aging, as measured by DNA methylation-based aging markers, in COVID-19 patients versus healthy individuals. We found that PCGrimAge, a next-generation epigenetic clock associated with immune dysregulation and inflammation, showed the strongest correlation with the chronological age of the European COVID-19 patients. Several other next-generation epigenetic clocks, including PCGrimAge, DunedinPACE, and ZhangY2017, also exhibited accelerated aging in both older and female COVID-19 patients. Interestingly, first-generation clocks, such as Hannum2013, indicated a significant reduction in epigenetic aging, likely reflecting limitations in their sensitivity to infection-related biological changes rather than an actual deceleration of the aging process. Our results also showed that immune dysregulation, rather than intrinsic cellular aging, may be the primary driver of accelerated epigenetic aging in COVID-19. This is supported by stronger associations observed in Age Acceleration (AA) and Extrinsic Epigenetic Age Acceleration (EEAA) compared to Intrinsic Epigenetic Age Acceleration (IEAA). Furthermore, immune dysregulation may be linked to CpG site demethylation, which in turn influences epigenetic clock dynamics. We also identified disparities between European and non-European populations, characterized by significantly higher IEAA for PCPhenoAge and DunedinPACE among non-European patients with COVID-19. In summary, our results underscore the differential sensitivity of epigenetic clocks to COVID-19-related biological changes.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 1","pages":"12"},"PeriodicalIF":4.1,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian rhythm of amyloid-β in the olfactory bulb and cerebellum of wild-type and APPxPS1 knock-in mice indicates a loss of rhythmicity in regions more vulnerable to amyloid pathology.","authors":"Valeria A Buzinova, Carrie E Johnson, Savannah M Turton, Sarah E Barth, Samantha Padgett, M Tyler Maisel, Katharina Kohler, Haleigh R Whitlock, Adam D Bachstetter, Sridhar Sunderam, Bruce F O'Hara, Marilyn J Duncan, M Paul Murphy","doi":"10.1007/s10522-025-10359-z","DOIUrl":"10.1007/s10522-025-10359-z","url":null,"abstract":"<p><p>Amyloid-β (Aβ) plaques are one of the primary biomarkers of Alzheimer's Disease (AD). Other publications have reported various mechanisms regarding the clearance of Aβ, and recent studies have also investigated the relationship between daily rhythms of Aβ and AD. The intent of this study was to determine if the circadian rhythm of Aβ differed between a region that was more vulnerable to AD-related pathology (the olfactory bulbs; OB) compared to a region that is less vulnerable (the cerebellum; CER). We chose to utilize an APPxPS1 knock-in (KI) mouse strain as this strain expresses amyloid precursor protein (APP) and Aβ under control of its normal promoter as opposed to AD transgenic models that overexpress APP and, as a consequence, Aβ. Mice (N = 128, equally divided between male and female, wild type and KI) were acclimated to a 12:12 light cycle for two weeks, and tissue was collected over a 24-h period in constant darkness. Using a unique immunoassay designed to measure human or rodent Aβ side-by-side, we confirmed a robust circadian Aβ rhythm in the mouse brain and that the OB contains more overall Aβ accumulation than the CER. The circadian Aβ rhythm was not present in the OB of the KI as compared to the WT mice. In contrast, the Aβ rhythm in the CER did not differ between genotypes. These results suggest that the loss of Aβ rhythm in disease-affected brain regions may be associated with the development of AD pathology and could have important implications for therapy.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 1","pages":"11"},"PeriodicalIF":4.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13072434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated single-cell multi-omics profiling reveals a senescence-associated hematopoietic landscape and regulatory network in aging bone marrow.","authors":"Guoyang Zhang, Weixuan Lin, Linghuan Guo, Ziyun Li, Yu Xiang, Luo Wang, Xiaoyu Yan","doi":"10.1007/s10522-025-10352-6","DOIUrl":"10.1007/s10522-025-10352-6","url":null,"abstract":"<p><p>Bone marrow exhibits functional decline, yet cellular heterogeneity and molecular mechanisms remain unclear due to limitations of traditional research methods. This study aims to characterize age-related changes and identify key drivers in bone marrow. Integrated multi-omics analysis was performed using scRNA-seq, proteomics, pseudo-bulk transcriptomics, weighted gene co-expression network analysis (WGCNA)-based transcription factor (TF) network modeling, and CellChat analysis. Samples included 6 young and aged bone marrow specimens. Statistical validation involved differential expression analysis, Cox regression modeling, and receiver operating characteristic (ROC) curve analysis. A novel hematopoietic subpopulation (3.19% of aged samples) was identified, activating the cellular senescence pathway (KEGG) and enhancing inflammatory crosstalk with CD8⁺ T cells via NMU signaling (|avg_log2FC|> 0.58, p < 0.001). Pseudo-bulk and proteomic analyses identified CAPN1, MAP2K1, and JUND as potential signal modules. Immunohistochemistry and Western blot confirmed their co-expression, while molecular docking revealed interaction interfaces. In two independent bulk-RNA cohorts (n = 58), a Cox model based on the CAPN1-MAP2K1-JUND module showed robust predictive value for aging, with AUCs of 0.7507 (p = 0.0154) and 0.90 (p = 0.0274). This study identifies a pivotal molecular module linking single-cell dynamics to tissue-level senescence in bone marrow, providing new insights into aging mechanisms and potential therapeutic targets.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 1","pages":"10"},"PeriodicalIF":4.1,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics-based mechanism of HIIT regulation of hepatic metabolism in aging female rats.","authors":"Jiahan He, Zhuangzhi Wang, Yibo Qiao, Chenkai Zhang, Zhi Yu, Pinshi Ni, Zhengyang Zhao, Jianmei Cui, Fanghui Li","doi":"10.1007/s10522-025-10351-7","DOIUrl":"10.1007/s10522-025-10351-7","url":null,"abstract":"<p><p>High-intensity interval training (HIIT) is capable of reversing many aging-related metabolic differences in the proteome, but studies using proteomics to investigate the mechanism of the effects of HIIT on hepatic metabolic function in aged rats have not been reported. In this study, we investigated the effects of 8 months of HIIT on mitochondrial oxidative function, oxidative stress, and inflammation in the liver of aged rats, and further explored the possible mechanisms of the metabolic effects of HIIT in aged rats by proteomics. The results of the study revealed that HIIT improved liver morphology, enhanced mitochondrial oxidative function, decreased inflammation and apoptosis levels, increased intrahepatic antioxidant function and inhibited ferroptosis in aged rats. Proteomics showed that HIIT altered changes in glycine, serine and threonine metabolic pathways in the liver, and further use of targeted amino acid metabolomics revealed that HIIT markedly increased glycine and serine content in aged livers. In vitro cells demonstrated that exogenous glycine supplementation significantly enhanced the intracellular antioxidant capacity of oxidatively stressed hepatocytes, while decreasing the level of inflammatory factor expression and significantly inhibiting the occurrence of ferroptosis. Our findings suggest that the improvement of metabolic function in aged liver tissue by HIIT may be associated with elevated glycine content, and that glycine within aged livers elevated by HIIT may mediate the maintenance of metabolic homeostasis within liver tissue.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 1","pages":"9"},"PeriodicalIF":4.1,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential dietary geroprotectors and their impact on key mechanisms of aging.","authors":"Alexey Moskalev, Oksana Veselova","doi":"10.1007/s10522-025-10355-3","DOIUrl":"10.1007/s10522-025-10355-3","url":null,"abstract":"<p><p>Aging involves progressive accumulation of molecular and cellular damage, leading to functional decline and increased susceptibility to age-related diseases. Natural low-molecular-weight geroprotectors are substances of plant and food origin capable of modulating key mechanisms of aging. Based on current scientific data, sixteen fundamental mechanisms of aging are analyzed, and compounds from food that demonstrate potential in slowing age-related changes are presented. Special attention is paid to the mechanisms of action of these substances at the molecular and cellular levels, as well as their availability in common food products. This review summarizes the current understanding of the interaction between natural nutrients and fundamental aging processes and opens perspectives for developing dietary strategies for healthy longevity.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 1","pages":"8"},"PeriodicalIF":4.1,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging as the wound that fails to heal: a bioenergetic continuum of resolution failure.","authors":"Torsak Tippairote, Pruettithada Hoonkaew, Aunchisa Suksawang, Prayfan Tippairote","doi":"10.1007/s10522-025-10356-2","DOIUrl":"10.1007/s10522-025-10356-2","url":null,"abstract":"<p><p>Aging may be conceptualized as a wound that fails to heal, characterized by persistent, unresolved inflammation. Building on Ogrodnik's \"unhealed wound\" model, this Perspective extends the Exposure-Related Malnutrition (ERM) framework to propose a bioenergetic interpretation of aging. ERM links chronic stress adaptation, nutrient misallocation, and mitochondrial insufficiency to sustained bioenergetic debt that impedes the transition from catabolic containment to anabolic repair. Across tissues, this energetic shortfall manifests as metabolic inflexibility, lipid-droplet accumulation, and a continuum of adaptive mitochondrial dysfunction that remains reversible until the threshold of senescence-the terminal stage of unresolved adaptation. Recognizing bioenergetic availability as the principal determinant of regenerative success reframes mitochondrial dysfunction and senescence not as primary causes of aging but as downstream consequences of chronic energetic exhaustion. Within this continuum, aging reflects a progressive loss of rhythmic catabolic-anabolic cycling that supports metabolic adaptation. Transient metabolic stress normally induces hormetic activation followed by anabolic recovery, but when this oscillation fails, adaptive hormesis gives way to maladaptive exhaustion. Aging thus emerges from the erosion of bioenergetic rhythm-a transition from recovery with renewal to endurance without repair.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 1","pages":"7"},"PeriodicalIF":4.1,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myosin light chain kinase 2 and Myomesin 2 are related to the stiffness of vocal fold lamina propria in aging rats and humans.","authors":"Ji-Min Kim, Hyoung-Sam Heo, Hyoun-Wook Lee, Gi-Cheol Park, Sung-Chan Shin, Yong-Il Cheon, Ha-Nee Kwon, Byung-Joo Lee","doi":"10.1007/s10522-025-10344-6","DOIUrl":"10.1007/s10522-025-10344-6","url":null,"abstract":"<p><p>Vocal fold fibroblasts play an important role in the production of the extracellular matrix in the vocal folds. Myofibroblasts increase in the aging vocal fold lamina propria with increased alpha-smooth muscle actin. In addition to alpha-smooth muscle actin, various sarcomeric genes are expressed in myofibroblasts. However, there have been no studies on sarcomeric genes with myofibroblast differentiation in aging vocal folds. The purpose of this study was to analyze the changes and functions of sarcomeric genes related to myofibroblast differentiation in aging vocal folds using next-generation sequencing (NGS). Young (6-month-old, 22 rats) and old (22-month-old, 22 rats) male Sprague-Dawley rats were used for this study. NGS was performed on the harvested lamina propria of the vocal folds in each group. NGS data were analyzed using functional annotation, gene ontology, network pathways, and network analysis methods. After identifying the increased expression of sarcomeric genes in aging vocal folds, we evaluated the expression of sarcomeric genes in the normal human vocal fold lamina propria removed after surgery for various vocal fold lesions. The functions of sarcomeric genes in fibroblast senescence, proliferation, differentiation, contraction, and stiffness were investigated. Among the four sarcomeric genes identified through network cluster analysis of the NGS results, the expression levels of myosin light chain kinase 2 (Mylk2) and myomesin 2 (Myom2) were significantly higher in the lamina propria of old rats than in young rats. The increase in Mylk2 and Myom2 expression was associated with cellular senescence but not with the proliferative ability of fibroblasts. However, the expression of Mylk2 and Myom2 increased with myofibroblast differentiation. Inhibition of Mylk2 and Myom2 affects cellular contraction, leading to reduced stiffness. Our results suggest that Mylk2 and Myom2 are novel biomarkers of vocal fold myofibroblasts and are involved in the regulation of vocal fold stiffness in aging rats and humans.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 1","pages":"5"},"PeriodicalIF":4.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-target synergistic anti-aging: QG extends Caenorhabditis elegans lifespan through DAF-16/FOXO pathways, mitochondrial homeostasis and metabolic reprogramming.","authors":"Jiahui Wang, Shuqi Li, Zichen Lei, Yantao Xing, Jieshu Li, Jie Guo, Boshi Duan, Yonggang Liu","doi":"10.1007/s10522-025-10347-3","DOIUrl":"10.1007/s10522-025-10347-3","url":null,"abstract":"<p><p>Aging not only significantly reduces the quality of life for the elderly but also poses multifaceted challenges to society. Its progression involves the synergistic interaction of multidimensional, multipathway molecular mechanisms, including mitochondrial dysfunction, oxidative stress accumulation, chronic inflammation, and genomic damage. Quercetagetin (QG), as a natural flavanol monomer, exhibits significant potential in anti-aging due to its simultaneous targeting of key aging pathways such as oxidative stress and chronic inflammation. We first evaluated QG's safety profile, finding that 0.02 mg/ml QG did not adversely affect motility, feeding, growth, and reproductive capacity in Caenorhabditis elegans (C. elegans). At this concentration, in vivo experiments using wild-type C. elegans confirmed QG's ability to extend lifespan and enhance oxidative stress resistance. The antioxidant and anti-aging effects of QG were further validated using the daf-16 mutant C. elegans DR26. Subsequently, observation of QG's impact on C. elegans mitochondrial morphology revealed significant reductions in area/perimeter and mitochondria coverage ratio following treatment. This indicates that QG treatment shifts the mitochondrial network from fusion toward fission and reduces overall mitochondrial content. QG can also improve age-related dopaminergic, 5-hydroxytryptaminergic and cholinergic neuron degeneration. Mass spectrometry metabolome analysis revealed that QG significantly affected citrate cycle and glycerophospholipid metabolism. Collectively, QG extends C. elegans lifespan by regulating redox homeostasis, DAF-16/FOXO pathways, mitochondrial homeostasis and metabolic reprogramming. This multi-target regulatory capacity positions QG as an ideal candidate molecule for anti-aging drug development.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 1","pages":"6"},"PeriodicalIF":4.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related changes and lack of effect of midlife resistance wheel exercise on afferent connectivity of lumbar alpha motor neurons in ageing mouse spinal cord.","authors":"Vidya S Krishnan, Stuart I Hodgetts, Alan R Harvey, Miranda D Grounds","doi":"10.1007/s10522-025-10348-2","DOIUrl":"10.1007/s10522-025-10348-2","url":null,"abstract":"<p><p>This two part study on the afferent connectivity of lumbar spinal motor neurons in normal ageing mice investigates; Study 1: time course analysis of age-related changes in the synaptic coverage of lumbar spinal cords of male C57BL/BJ mice at 4,15,18 and 24 months of age and Study 2: the effect of long term 8-month resistance wheel exercise (RWE) on lumbar spinal cords of male C57BL/6J mice exercised from 15 to 23 months of age. Uniquely, each study used spinal cords obtained from the same mice that had previously been analysed for changes in skeletal muscles and sciatic nerves in a parallel series of time course and exercise studies. Input to presumed alpha motor neurons was investigated by quantifying VGLUT1 immunoreactive synaptic contacts known to be derived from proprioceptive muscle afferents. Here we found no significant changes in the percentage of synaptic VGLUT1 coverage of motor neurons from 4 to 24 months. Importantly, this differs from our previous results (Krishnan et al., Biogerontology 19:385-399, 2018) where there was about 50% decrease in VGLUT1 innervation of motor neurons in older mice aged 27 months, indicating a rapid deterioration in proprioceptive feedback in late ageing. In the exercise study, 8 months of voluntary wheel running (beginning at 15 months), had no impact on VGLUT1 synaptic connectivity in spinal cords, consistent with our previous report of no effect on peripheral nerves obtained from this same ageing and exercised cohort of mice. Nonetheless there was a significant amount of sarcopenia in these animals. Overall, these studies highlight the variable impact of ageing on different motor-related tissues.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 1","pages":"3"},"PeriodicalIF":4.1,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of cGAS-STING signaling in senescent cells promotes the aging process by remodeling the functions of the immune system.","authors":"Antero Salminen, Kai Kaarniranta, Anu Kauppinen","doi":"10.1007/s10522-025-10353-5","DOIUrl":"10.1007/s10522-025-10353-5","url":null,"abstract":"<p><p>An accumulation of senescent cells within tissues is a hallmark of the aging process. Cellular senescence is associated with an increased level of cytosolic dsDNA which primarily originates from a leakage of mitochondrial DNA (mtDNA) and a loss of genomic DNA integrity. Cytosolic dsDNA is an important alarming factor for cytosolic dsDNA sensors which trigger the remodeling of the immune system through diverse signaling pathways. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) (cGAS-STING) signaling is a major defence mechanism induced by an accumulation of cytosolic dsDNA in senescent cells. The cGAS-STING pathway stimulates immune responses via the interferon regulatory factor 3 (IRF3) and nuclear factor-κB (NF-κB)-driven pathways. The activation of cGAS-STING signaling in senescent cells generates pleiotropic immune responses in a context-dependent manner. For instance, cGAS-STING signaling induces proinflammatory responses by enhancing the secretion of cytokines, chemokines, and colony-stimulating factors. The secretion of many chemokines and colony-stimulating factors can remodel hematopoiesis and enhance thymic involution with aging. Moreover, cGAS-STING signaling promotes proinflammatory responses by stimulating the NLRP3 inflammasomes. On the other hand, cGAS-STING signaling aids in the resolution of inflammation by recruiting immunosuppressive cells into tissues and suppressing the pathogenic activity of T helper 17 cells. In addition, an increased cGAS-STING signaling in senescent cells stimulates the expression of inhibitory immune checkpoint ligands, such as PD-L1, and thus prevents their elimination by immune cells. Recent studies have clearly revealed that cGAS-STING signaling not only induces cellular senescence but it can also promote the aging process.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 1","pages":"4"},"PeriodicalIF":4.1,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12620326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}