Mechanisms of Ageing and Development最新文献

{"title":"How to measure, analyze, and interpret age-related changes in Caenorhabditis elegans: Lessons for mechanistic and evolutionary theories of aging","authors":"Zuzana Kocsisova ,&nbsp;Brian M. Egan ,&nbsp;Andrea Scharf ,&nbsp;Xavier Anderson ,&nbsp;Franziska Pohl ,&nbsp;Aaron Anderson ,&nbsp;Kerry Kornfeld","doi":"10.1016/j.mad.2025.112146","DOIUrl":"10.1016/j.mad.2025.112146","url":null,"abstract":"<div><div>Aging is characterized by progressive degenerative changes in tissue organization and function, some of which increase the probability of mortality. Major goals of aging research are to elucidate the series of events that cause degenerative changes, and to identify environmental, pharmacological, and genetic factors that influence these changes; this information might lead to new strategies to extend health span and lifespan. Mechanistic studies of aging depend on accurate and precise descriptions of age-related changes, since these descriptions define the aging phenotype. Here, we review studies that describe age-related changes in <em>C. elegans,</em> including measurements of integrated functions such as behavior and reproduction, microscopic analyses of tissue organization, and biochemical studies of macromolecules. We discuss studies that analyze the relationships between different age-related changes. We consider the results in light of mechanistic and evolutionary theories of aging. Together, these studies provide fundamental insights into aging in <em>C. elegans</em> that may be relevant to aging in other animals.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112146"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878521","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":"Compatibility and comparative analysis of chronological and biological aging between the legacy 450K and the EPIC v2.0 arrays","authors":"Sven De Pourcq ,&nbsp;Pei-Lun Kuo ,&nbsp;Ann Zenobia Moore ,&nbsp;Stefania Bandinelli ,&nbsp;Steve Horvath ,&nbsp;Luigi Ferrucci ,&nbsp;Valeria Santini","doi":"10.1016/j.mad.2025.112142","DOIUrl":"10.1016/j.mad.2025.112142","url":null,"abstract":"<div><div>Several epigenetic clocks based on DNA methylation arrays have been developed to evaluate biological aging. However, there is limited information on how the newer EPIC v2.0 arrays affect clock estimations, which lack probes initially present on legacy arrays such as the 450K array. Therefore, we analyzed how this absence affects epigenetic clock estimates using data from the InCHIANTI study. Although some clocks showed significant over- or underestimation due to probe loss, correlations between estimates from all 450K probes (unreduced) and shared probes between 450K and EPIC v2.0 (reduced) remained significant. AgeAcceleration estimates were least affected by missing probes.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112142"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701398","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":"The TGF-β1-oxidative stress axis underlies accelerated senescence of endothelial cells exposed to serum from hypertensive patients","authors":"Paweł Uruski ,&nbsp;Justyna Mikuła-Pietrasik ,&nbsp;Andrzej Tykarski ,&nbsp;Krzysztof Książek","doi":"10.1016/j.mad.2025.112128","DOIUrl":"10.1016/j.mad.2025.112128","url":null,"abstract":"<div><h3>Background</h3><div>There is a bidirectional link between hypertension (HT) and cellular senescence of endothelial cells (ECs). However, the mechanisms underlying EC senescence in patients with HT are not yet fully understood.</div></div><div><h3>Methods and Results</h3><div>We analyzed serum from 71 patients with primary HT and compared it to serum from 25 healthy donors to assess its effects on EC biology, including biomarkers, signaling pathways, and cellular senescence effectors. Our findings revealed that exposing ECs to serum from HT patients (20 % for 72 h) impaired cell viability while enhancing proliferation, migration, and tubulogenesis. This effect is accompanied by increased expression of HIF-1α. Additionally, HT serum potentiated the expression of the senescence marker SA-β-Gal, shortened telomeres, and up-regulated cell-cycle inhibitors p16, p21, and p53. Regarding the signaling pathways, HT serum activated ERK1/2, p38 MAPK, AP-1/c-jun, and Notch1. Indices of oxidative stress in ECs treated with HT serum also increased, as indicated by elevated production of superoxides, activation of antioxidants (SOD, CAT), and accumulation of oxidized DNA, proteins, and lipids. Furthermore, mitochondria in these cells displayed decreased inner membrane potential and increased biogenesis, likely due to enhanced activity of PGC-1α. The activity of respiratory chain enzymes, including cytochrome c oxidase and NADH dehydrogenase, was also elevated. When HT serum-treated ECs were pre-incubated with the ROS scavenger PBN, the activity of SA-β-Gal decreased. A similar reduction in SA-β-Gal activity was observed when HT serum, which contained elevated levels of TGF-β1, was pre-incubated with a TGF-β1-neutralizing antibody. Importantly, exogenous TGF-β1, administered at a dose corresponding to its concentration in HT serum, induced senescence in ECs.</div></div><div><h3>Conclusions</h3><div>Our results indicate that serum from HT patients promotes senescence in ECs through mechanisms related to TGF-β1 and oxidative stress signaling.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112128"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635481","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":"Association between metabolic profile and cognitive frailty in community-dwelling older adults: An eight-year cohort study","authors":"Te-Hsuan Huang ,&nbsp;Yen-Ching Chen ,&nbsp;Ching-Yu Lin ,&nbsp;Yu-Ting Wang ,&nbsp;Pei-Yu Wang ,&nbsp;Jeng-Min Chiou ,&nbsp;Jen-Hau Chen","doi":"10.1016/j.mad.2025.112130","DOIUrl":"10.1016/j.mad.2025.112130","url":null,"abstract":"<div><div>Limited studies have explored the link between metabolic profiles and cognitive frailty, its temporal relationship is especially lacking. This study aimed to identify metabolic patterns associated with cognitive frailty over time. This eight-year prospective cohort study (2011–2019) recruited 605 nondemented community-dwelling older adults at baseline. Cognitive frailty, assessed biennially, was defined as physical frailty and mild cognitive impairment. Baseline plasma metabolites were evaluated using ¹H nuclear magnetic resonance. Generalized linear mixed models assessed the longitudinal association between metabolites and cognitive frailty, further stratified by important covariates. We found that one unit increment of baseline fatty acyl chain (CH₂CH₂C<img>C) Z-score was associated with worsening cognitive frailty at baseline [adjusted risk ratio (aRR)= 1.97], which attenuated over eight years (aRR=0.94). In contrast, one unit increment of baseline pyruvate Z-score was associated with attenuation in the progression to the next stage of cognitive frailty (aRR=0.94). These associations were more evident in men, individuals with &gt; 12 years of education, and apolipoprotein E (<em>APOE</em>) ε4 non-carriers (aRR=0.34–0.92). Significant interactions were found between <em>APOE</em> ε4 status and both fatty acyl chain (<em>P</em>_{<em>interaction</em>}=0.004) and pyruvate (<em>P</em>_{<em>interaction</em>}=0.03). Our findings suggest plasma metabolites may serve as markers for predicting cognitive frailty and <em>APOE</em> genotypes modifying this pathogenesis.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112130"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623058","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":"Apelin-13 activates TFEB-mediated autophagy via AMPK to attenuate senescence and pyroptosis in nucleus pulposus cells during intervertebral disc degeneration","authors":"Yuhang Gong ,&nbsp;Jie Xiang ,&nbsp;Ben Wang ,&nbsp;Leyi Hu ,&nbsp;Shengzan Shao ,&nbsp;Yangyang Wu ,&nbsp;Ze Li ,&nbsp;Chao Jiang ,&nbsp;Jianxin Qiu ,&nbsp;Liwei Ying ,&nbsp;Zhenghua Hong ,&nbsp;Haixiao Chen ,&nbsp;Zhangfu Wang","doi":"10.1016/j.mad.2025.112147","DOIUrl":"10.1016/j.mad.2025.112147","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IDD) is an aging-associated disorder driven by chronic inflammation. Impaired autophagy is a hallmark of disc aging, but its upstream regulation remains unclear. Here, we identify Apelin-13 (APL13) as an endogenous peptide that restores autophagic competence in degenerative nucleus pulposus (NP) cells. APL13 alleviated IL-1β-induced senescence and pyroptosis. It also restored autophagic flux by promoting TFEB activation and nuclear translocation. Mechanistically, APL13 activated AMPK signaling pathways. It enhanced TFEB-dependent lysosomal and autophagy programs through both the AMPK-mTOR axis and the AMPK-FOXO3a-SKP2-CARM1 axis. In a lumbar spine instability mouse model, APL13 preserved disc structure, maintained ECM integrity, and reduced senescence-pyroptosis signaling in vivo. These findings position APL13 as a regulator of disc inflammaging. And the AMPK-TFEB axis emerges as a key pathway linking autophagy restoration to NP cell during IDD progression.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112147"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878524","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":"Blood aging: From definition and mechanisms to clinical practice","authors":"Qiliang Yin ,&nbsp;Yan Zhang ,&nbsp;Xingcheng Yi ,&nbsp;Jian Li ,&nbsp;Yun Dai ,&nbsp;Fengyan Jin ,&nbsp;On behalf of the Committee of Experts on Hematology,&nbsp;China Society of Geriatrics, China Association of Gerontology and Geriatrics","doi":"10.1016/j.mad.2025.112144","DOIUrl":"10.1016/j.mad.2025.112144","url":null,"abstract":"<div><div>It is generally believed that hematopoietic aging is a major driver or contributor of human aging. The hematopoietic system undergoes physiological or pathological changes with aging, which drive or contribute to the aging of almost all systems and organs in the body, leading to various age-related diseases, particularly malignant and non-malignant hematologic disorders. Although the term <em>blood aging</em> has been mentioned in a number of publications and is widely used in everyday life, its definition and research scope remain unclear to date. With the rapid advances in the aging research field involving overall, systemic/organ, cellular, and molecular aging, various aspects relevant to blood aging have permeated almost all areas of aging research, including hematopoietic stem/progenitor cell (HSC/HPC) aging, immunosenescence, inflammaging, etc. However, sharply contrasting with aging of other systems and organs, blood aging has not yet formed its own research field. This review article discusses the definition, scope, and mechanisms of blood aging and provides a comprehensive overview on this emerging area, encompassing physiological and pathological blood aging. Overall, this review aims to advance understanding of blood aging, clarify its definition and scope, and highlight underlying mechanisms, thereby providing a foundation for future research and strategies to promote healthy aging.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112144"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781082","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":"Ischemic stroke and comorbidities: Impact on recovery and the role of genetics and epigenetics","authors":"Andreea Cercel ,&nbsp;Abuzan Mihaela ,&nbsp;Thorsten R. Doeppner ,&nbsp;Dirk M. Hermann ,&nbsp;Liviu Martin ,&nbsp;Aurel Popa-Wagner","doi":"10.1016/j.mad.2025.112127","DOIUrl":"10.1016/j.mad.2025.112127","url":null,"abstract":"<div><div>Ischemic stroke (IS) remains a leading cause of long-term disability and mortality worldwide, with recovery outcomes shaped by the interplay between acute vascular injury, pre-existing comorbidities, and individual molecular profiles. Common risk factors—such as diabetes mellitus, atrial fibrillation, hypertension, and dyslipidemia—not only increase stroke susceptibility but also impair neurovascular repair by perpetuating systemic inflammation, endothelial dysfunction, and impaired neuroplasticity. Aging remains an underexplored determinant of epigenetic remodeling in stroke. Beyond these clinical determinants, genetic and epigenetic mechanisms contribute substantially to stroke heterogeneity. Genome-wide association studies (GWAS) have identified loci such as HDAC9, PATJ, PTCH1, and ABO that modulate inflammation, oxidative stress, and vascular remodeling. Complementary epigenetic pathways, including DNA methylation, histone acetylation, and circular RNAs (circRNAs), dynamically regulate gene expression in response to ischemia and comorbid influences, encoding a persistent “molecular memory” that shapes both injury and repair. Functional studies reveal that circRNAs orchestrate apoptosis, angiogenesis, and synaptic remodeling, while selective DNMT and HDAC inhibition can restore neurovascular integrity in experimental models. Recent multi-omics and longitudinal approaches demonstrate that these molecular signatures evolve across acute, subacute, and chronic phases of recovery, yet clinical translation remains limited. Aging and chronic comorbidities further modify epigenetic programs, reducing repair capacity. Although genotype-guided antiplatelet therapy illustrates the feasibility of personalized stroke care, broader genomics- and epigenetics-informed interventions require rigorous validation. This review integrates current knowledge on the interplay between vascular comorbidities, genetic predisposition, and epigenetic regulation in shaping stroke recovery. Understanding these interactions is essential for developing precision medicine approaches that enhance functional outcomes and reduce recurrence in stroke survivors.Integrating multi-omics profiling with comorbidity stratification, functional validation, and longitudinal biomarker tracking will be pivotal to achieving actionable precision medicine and improving outcomes in stroke survivors.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112127"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145587994","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":"Causes and consequences of chromosomal cohesin loss: Novel insights for mechanisms of aging-related oocyte aneuploidy","authors":"Lu‑lu Fu ,&nbsp;Jing‑shun Zhang ,&nbsp;Xue‑ying Zhang ,&nbsp;Ying Xu ,&nbsp;Fu-liang Zhang ,&nbsp;Lian‑wen Zheng","doi":"10.1016/j.mad.2025.112129","DOIUrl":"10.1016/j.mad.2025.112129","url":null,"abstract":"<div><div>Female fertility sharply declines from the mid-thirties of their life, mainly due to age-related decreases in oocyte quality and quantity. Among numerous interconnected maternal factors, an increase in the incidence of aneuploidy caused by meiotic errors is a leading cause of oocyte competence decrease. Why advanced maternal age increases the likelihood of chromosome segregation errors in oocytes remains one of the outstanding questions in reproductive and developmental biology, and it is becoming more important as the age at which women have children continues to rise. A better understanding of this question is crucial for developing effective strategies for prophylaxis or therapeutic interventions for infertility. The progressive loss of cohesin, a ring-shaped protein complex with fundamental roles in chromosome cohesion and architecture, has recently been heavily implicated in the increase in oocyte aneuploidy rates during maternal aging. This review discusses the underlying mechanisms of age-related aneuploidy in oocytes. We particularly ask how chromosomal cohesin loss affects the fidelity of oocyte chromosome segregation and examine physiological factors that contribute to this deterioration.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112129"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623057","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":"cGAS-STING signaling is blunted in senescent macrophages and monocytes in obesity","authors":"Carine Raquel Richter Schmitz ,&nbsp;Lucas Kich Grun ,&nbsp;Bruno Kendi Makiyama ,&nbsp;Luma Smidt Piazza ,&nbsp;Alexandre Vontobel Padoin ,&nbsp;Cláudio Cora Mottin ,&nbsp;Moisés Evandro Bauer ,&nbsp;Fátima Theresinha Costa Rodrigues Guma ,&nbsp;Florencia María Barbé-Tuana","doi":"10.1016/j.mad.2025.112140","DOIUrl":"10.1016/j.mad.2025.112140","url":null,"abstract":"<div><h3>Introduction</h3><div>The cGAS-STING pathway is essential for immunity, detecting cytosolic DNA to trigger defense mechanisms and sterile inflammation linked to aging, obesity, and chronic inflammatory diseases. This study examines cGAS-STING signaling in senescent monocyte-derived macrophages (MDMs) and monocytes within the context of obesity.</div></div><div><h3>Materials and Methods</h3><div>Primary human MDMs were differentiated from peripheral blood of young, healthy, lean donors using M-CSF, to guide monocytes toward the macrophage lineage. MDMs were cultured for 7 or 21 days to induce replicative senescence. Peripheral monocytes were also isolated from age- and sex-matched lean and obese participants.</div></div><div><h3>Results</h3><div>MDMs cultured for 21 days exhibited increased cellular and nuclear area, developed a senescent phenotype marked by increased P16 expression and γH2AX phosphorylation, shorter telomeres, loss of LAMIN B1, diminished phagocytosis, with reduced STING expression and impaired response to cGAS agonist 2′3'-cGAMP. Similarly, <em>ex vivo</em> monocytes from individuals with obesity displayed elevated P16 expression and increased γH2AX and β-galactosidase activity, along with increased STING expression, compromised downstream signaling and reduced cytokine secretion.</div></div><div><h3>Discussion</h3><div>Dysfunctional cGAS-STING signaling and senescence markers suggest a shared mechanism underlying immune dysfunction in aging and obesity. Understanding cGAS-STING’s role in immune cells may provide insights into age-related immune decline and chronic inflammation.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112140"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623059","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":"A role for long-lived nuclear envelope proteins in cardiac ageing","authors":"Mathew Shuen ,&nbsp;Regis R. Lamberts ,&nbsp;Sean Coffey ,&nbsp;Philip W. Sheard","doi":"10.1016/j.mad.2025.112145","DOIUrl":"10.1016/j.mad.2025.112145","url":null,"abstract":"<div><div>Ageing populations present substantial healthcare challenges, with cardiovascular disease (CVD) remaining the predominant cause of morbidity and mortality globally. Cardiac ageing is characterised by progressive cellular and molecular changes, contributing to structural and functional decline and predisposition to CVD. Component proteins (nucleoporins) of the Nuclear Pore Complex (NPC) and the nuclear lamina are both crucial for nuclear integrity and chromatin organisation, and have appeared as key players in cellular homeostasis of post-mitotic cells. Age-related changes in NPC composition and turnover, particularly in non-dividing cells, compromise nucleocytoplasmic compartmentalisation and drive genomic instability, cell death, and senescence. Emerging evidence implicates aberrant NPC components in the core hallmarks of cardiac ageing and in distinct heart diseases. Additionally, the nuclear lamina’s susceptibility to damage and its interactions with NPCs might exacerbate these effects. This review presents evidence linking NPC and nuclear lamina dysfunction to features of the ageing heart and suggests that age-related NPC alterations are potential drivers of cardiomyocyte and cardiac decline with age</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"229 ","pages":"Article 112145"},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797291","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}