Aging Cell最新文献

{"title":"Casual associations between brain structure and sarcopenia: A large-scale genetic correlation and mendelian randomization study","authors":"Guang Yang,&nbsp;Wenqing Xie,&nbsp;Bin Li,&nbsp;Guihu Zhao,&nbsp;Jinchen Li,&nbsp;Wenfeng Xiao,&nbsp;Yusheng Li","doi":"10.1111/acel.14252","DOIUrl":"10.1111/acel.14252","url":null,"abstract":"<p>Sarcopenia presenting a critical challenge in population-aging healthcare. The elucidation of the interplay between brain structure and sarcopenia necessitates further research. The aim of this study is to explore the casual association between brain structure and sarcopenia. Linkage disequilibrium score regression (LDSC) was conducted to estimate the genetic correlations; MR was then performed to explore the causal relationship between Brain imaging-derived phenotypes (BIDPs) and three sarcopenia-related traits: handgrip strength, walking pace, and appendicular lean mass (ALM). The main analyses were conducted using the inverse-variance weighted method. Moreover, weighted median and MR–Egger were conducted as sensitivity analyses. Genetic association between 6.41% of BIDPs and ALM was observed, and 4.68% of BIDPs exhibited causal MR association with handgrip strength, 2.11% of BIDPs were causally associated with walking pace, and 2.04% of BIDPs showed causal association with ALM. Volume of ventromedial hypothalamus was associated with increased odds of handgrip strength (OR: 1.18, 95% CI: 1.02 to 1.37) and ALM (OR: 1.05, 95% CI: 1.01 to 1.09). Mean thickness of G-pariet-inf-Angular was associated with decreased odds of handgrip strength (OR: 0.83, 95% CI: 0.70 to 0.97) and walking pace (OR: 0.97, 95% CI: 0.93 to 0.99). As part of the brain structure forward causally influences sarcopenia, which may provide new perspectives for the prevention of sarcopenia and offer valuable insights for further research on the brain-muscle axis.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329809","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":"Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons","authors":"James N. Sleigh,&nbsp;Francesca Mattedi,&nbsp;Sandy Richter,&nbsp;Emily Annuario,&nbsp;Kristal Ng,&nbsp;I. Emilie Steinmark,&nbsp;Iveta Ivanova,&nbsp;István L. Darabán,&nbsp;Parth P. Joshi,&nbsp;Elena R. Rhymes,&nbsp;Shirwa Awale,&nbsp;Gokhan Yahioglu,&nbsp;Jacqueline C. Mitchell,&nbsp;Klaus Suhling,&nbsp;Giampietro Schiavo,&nbsp;Alessio Vagnoni","doi":"10.1111/acel.14250","DOIUrl":"10.1111/acel.14250","url":null,"abstract":"<p>Mitochondria are dynamic bioenergetic hubs that become compromised with age. In neurons, declining mitochondrial axonal transport has been associated with reduced cellular health. However, it is still unclear to what extent the decline of mitochondrial transport and function observed during ageing are coupled, and if somal and axonal mitochondria display compartment-specific features that make them more susceptible to the ageing process. It is also not known whether the biophysical state of the cytoplasm, thought to affect many cellular functions, changes with age to impact mitochondrial trafficking and homeostasis. Focusing on the mouse peripheral nervous system, we show that age-dependent decline in mitochondrial trafficking is accompanied by reduction of mitochondrial membrane potential and intramitochondrial viscosity, but not calcium buffering, in both somal and axonal mitochondria. Intriguingly, we observe a specific increase in cytoplasmic viscosity in the neuronal cell body, where mitochondria are most polarised, which correlates with decreased cytoplasmic diffusiveness. Increasing cytoplasmic crowding in the somatic compartment of DRG neurons grown in microfluidic chambers reduces mitochondrial axonal trafficking, suggesting a mechanistic link between the regulation of cytoplasmic viscosity and mitochondrial dynamics. Our work provides a reference for studying the relationship between neuronal mitochondrial homeostasis and the viscoelasticity of the cytoplasm in a compartment-dependent manner during ageing.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329808","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":"Correction to “Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD-L1)-mediated immunosuppression”","authors":"","doi":"10.1111/acel.14248","DOIUrl":"10.1111/acel.14248","url":null,"abstract":"<p>Xu Q, Long Q, Zhu D, et al. Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD-L1)-mediated immunosuppression. <i>Aging Cell</i>. 2019;18:e13027. https://doi.org/10.1111/acel.13027</p><p>During the data organization and author preparation of this manuscript, there were a couple of errors inadvertently incorporated into the manuscript and not recognized effectively during the proofing stage. We noticed that the following item needs to be appropriately corrected.</p><p>Figure 5h. Representative IHC images of caspase 3 (cleaved) in tumors at the end of therapeutic regimes. The “Placebo-treated AREG mAb” and “MIT-treated Cetuximab” images were mistakenly picked up by authors to organize the original panel. As a necessary effort, the authors have now located the appropriate representative images and corrected this figure. Please refer to the updated Figure 5h.</p><p>All other parts of this article remain intact, valid, and unchanged. The authors sincerely regret the error and would like to apologize for any inconvenience this may have caused. The corrected figure is provided below. We apologize for this error.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316170","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":"TAF15 downregulation contributes to the benefits of physical training on dendritic spines and working memory in aged mice","authors":"Yun He,&nbsp;Benju Liu,&nbsp;Fu-Yuan Yang,&nbsp;Qun Yang,&nbsp;Benke Xu,&nbsp;Lian Liu,&nbsp;Yuncai Chen","doi":"10.1111/acel.14244","DOIUrl":"10.1111/acel.14244","url":null,"abstract":"<p>Moderate physical training has been shown to hinder age-related memory decline. While the benefits of physical training on hippocampal memory function are well-documented, little is known about its impact on working memory, which is linked to the prelimbic cortex (PrL), one major subdivision of the prefrontal cortex. Here, we examined the effects of physical training on spatial working memory in a well-established animal model of physical training, starting at 16 months of age and continuing for 5 months (running wheel 1 h/day and 5 days/week). This training strategy improved spatial working memory in aged mice (22-month-old), which was accompanied by an increased spine density and a lower TAF15 expression in the PrL. Specifically, physical training affected both thin and mushroom-type spines on PrL pyramidal cells, and prevented age-related loss of spines on selective segments of apical dendritic branches. Correlation analysis revealed that increased TAF15-expression was detrimental to the dendritic spines. However, physical training downregulated TAF15 expression in the PrL, preserving the dendritic spines on PrL pyramidal cells and improving working memory in trained aged mice. When TAF15 was overexpressed in the PrL via a viral approach, the benefits of physical training on the dendritic spines and working memory were abolished. These data suggest that physical training at a moderate pace might downregulate TAF15 expression in the PrL, which favors the dendritic spines on PrL pyramidal cells, thereby improving spatial working memory.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316171","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":"Growth hormone-releasing hormone deficiency confers extended lifespan and metabolic resilience during high-fat feeding in mid and late life","authors":"Joseph Adkins-Jablonsky,&nbsp;Alexander Tate Lasher,&nbsp;Amit Patki,&nbsp;Akash Nagarajan,&nbsp;Liou Y. Sun","doi":"10.1111/acel.14238","DOIUrl":"10.1111/acel.14238","url":null,"abstract":"<p>Growth hormone-releasing hormone-deficient (GHRH-KO) mice have previously been characterized by lower body weight, disproportionately high body fat accumulation, preferential metabolism of lipids compared to carbohydrates, improved insulin sensitivity, and an extended lifespan. That these mice are long-lived and insulin-sensitive conflicts with the notion that adipose tissue accumulation drives the health detriments associated with obesity (i.e., diabetes), and indicates that GH signaling may be necessary for the development of adverse effects linked to obesity. This prompts investigation into the ultimate effect of diet-induced obesity on the lifespan of these long-lived mice. To this end, we initiated high-fat feeding in mid and late-life in GHRH-KO and wild-type (WT) mice. We carried out extensive lifespan analysis coupled with glucose/insulin tolerance testing and indirect calorimetry to gauge the metabolic effect of high-fat dietary stress through adulthood on these mice. We show that under high-fat diet (HFD) conditions, GHRH-KO mice display extended lifespans relative to WT controls. We also show that GHRH-KO mice are more insulin-sensitive and display less dramatic changes in their metabolism relative to WT mice, with GHRH-KO mice fed HFD displaying respiratory exchange ratios and glucose oxidation rates comparable to control-diet fed GHRH-KO mice, while WT mice fed HFD showed significant reductions in these parameters. Our results indicate that GH deficiency protects against the adverse effects of diet-induced obesity in later life.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309673","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":"Anatomical Society Research Studentships 2024/25","authors":"","doi":"10.1111/acel.14253","DOIUrl":"https://doi.org/10.1111/acel.14253","url":null,"abstract":"","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308885","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":"Prediagnosis recognition of acute ischemic stroke by artificial intelligence from facial images","authors":"Yiyang Wang,&nbsp;Yunyan Ye,&nbsp;Shengyi Shi,&nbsp;Kehang Mao,&nbsp;Haonan Zheng,&nbsp;Xuguang Chen,&nbsp;Hanting Yan,&nbsp;Yiming Lu,&nbsp;Yong Zhou,&nbsp;Weimin Ye,&nbsp;Jing Ye,&nbsp;Jing-Dong J. Han","doi":"10.1111/acel.14196","DOIUrl":"10.1111/acel.14196","url":null,"abstract":"<p>Stroke is a major threat to life and health in modern society, especially in the aging population. Stroke may cause sudden death or severe sequela-like hemiplegia. Although computed tomography (CT) and magnetic resonance imaging (MRI) are standard diagnosis methods, and artificial intelligence models have been built based on these images, shortage in medical resources and the time and cost of CT/MRI imaging hamper fast detection, thus increasing the severity of stroke. Here, we developed a convolutional neural network model by integrating four networks, Xception, ResNet50, VGG19, and EfficientNetb1, to recognize stroke based on 2D facial images with a cross-validation area under curve (AUC) of 0.91 within the training set of 185 acute ischemic stroke patients and 551 age- and sex-matched controls, and AUC of 0.82 in an independent data set regardless of age and sex. The model computed stroke probability was quantitatively associated with facial features, various clinical parameters of blood clotting indicators and leukocyte counts, and, more importantly, stroke incidence in the near future. Our real-time facial image artificial intelligence model can be used to rapidly screen and prediagnose stroke before CT scanning, thus meeting the urgent need in emergency clinics, potentially translatable to routine monitoring.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282406","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":"Pip5k1γ promotes anabolism of nucleus pulposus cells and intervertebral disc homeostasis by activating CaMKII-Ampk pathway in aged mice","authors":"Mingjue Chen,&nbsp;Feiyun Li,&nbsp;Minghao Qu,&nbsp;Xiaowan Jin,&nbsp;Tailin He,&nbsp;Shuangshuang He,&nbsp;Sheng Chen,&nbsp;Qing Yao,&nbsp;Lin Wang,&nbsp;Di Chen,&nbsp;Xiaohao Wu,&nbsp;Guozhi Xiao","doi":"10.1111/acel.14237","DOIUrl":"10.1111/acel.14237","url":null,"abstract":"<p>Degenerative disc disease (DDD) represents a significant global health challenge, yet its underlying molecular mechanisms remain elusive. This study aimed to investigate the role of type 1 phosphatidylinositol 4-phosphate 5-kinase (Pip5k1) in intervertebral disc (IVD) homeostasis and disease. All three Pip5k1 isoforms, namely Pip5k1α, Pip5k1β, and Pip5k1γ, were detectable in mouse and human IVD tissues, with Pip5k1γ displaying a highest expression in nucleus pulposus (NP) cells. The expression of Pip5k1γ was significantly down-regulated in the NP cells of aged mice and patients with severe DDD. To determine whether Pip5k1γ expression is required for disc homeostasis, we generated a <i>Pip5k1γ</i>^{<i>fl</i>/<i>fl</i>}; <i>Aggrecan</i>^{<i>CreERT2</i>} mouse model for the conditional knockout of the <i>Pip5k1γ</i> gene in aggrecan-expressing IVD cells. Our findings revealed that the conditional deletion of Pip5k1γ did not affect the disc structure or cellular composition in 5-month-old adult mice. However, in aged (15-month-old) mice, this deletion led to several severe degenerative disc defects, including decreased NP cellularity, spontaneous fibrosis and cleft formation, and a loss of the boundary between NP and annulus fibrosus. At the molecular level, the absence of Pip5k1γ reduced the anabolism of NP cells without markedly affecting their catabolic or anti-catabolic activities. Moreover, the loss of Pip5k1γ significantly dampened the activation of the protective Ampk pathway in NP cells, thereby accelerating NP cell senescence. Notably, Pip5k1γ deficiency blunted the effectiveness of metformin, a potent Ampk activator, in activating the Ampk pathway and mitigating lumbar spine instability (LSI)-induced disc lesions in mice. Overall, our study unveils a novel role for Pip5k1γ in promoting anabolism and maintaining disc homeostasis, suggesting it as a potential therapeutic target for DDD.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260087","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":"Identification of nicotinamide N-methyltransferase as a promising therapeutic target for sarcopenia","authors":"Rui Liang,&nbsp;Qiao Xiang,&nbsp;Miao Dai,&nbsp;Taiping Lin,&nbsp;Dongmei Xie,&nbsp;Quhong Song,&nbsp;Yu Liu,&nbsp;Jirong Yue","doi":"10.1111/acel.14236","DOIUrl":"10.1111/acel.14236","url":null,"abstract":"<p>Sarcopenia is a significant geriatric syndrome that involves the loss of skeletal muscle mass and strength. Due to its substantial endocrine role, the metabolic microenvironment of skeletal muscle undergoes changes with age. Examining the pathogenesis of sarcopenia through focusing on metabolic dysregulation could offer insights for developing more effective intervention strategies. In this study, we analyzed the transcriptomics data to identify specific genes involved in the regulation of metabolism in skeletal muscle during the development of sarcopenia. Three machine learning algorithms were employed to screen key target genes exhibiting strong correlations with metabolism, which were further validated using RNA-sequencing data and publicly accessible datasets. Among them, the metabolic enzyme nicotinamide N-methyltransferase (NNMT) was elevated in sarcopenia, and predicted sarcopenia with an area under the curve exceeding 0.7, suggesting it as a potential therapeutic target for sarcopenia. As expected, inhibition of NNMT improved the grip strength in aging mice and alleviated age-related decline in the mass index of the quadriceps femoris muscles and whole-body lean mass index. Additionally, the NNMTi treatment increased the levels of nicotinamide adenine dinucleotide (NAD⁺) content, as well as PGC1α and p-AMPK expression in the muscles of both the D-galactose-treated mouse model and naturally aging mouse model. Overall, this work demonstrates NNMT as a promising target for preventing age-related decline in muscle mass and strength.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260086","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":"Expression of mitochondrial oxidative stress response genes in muscle is associated with mitochondrial respiration, physical performance, and muscle mass in the Study of Muscle, Mobility, and Aging","authors":"Gregory J. Tranah,&nbsp;Haley N. Barnes,&nbsp;Peggy M. Cawthon,&nbsp;Paul M. Coen,&nbsp;Karyn A. Esser,&nbsp;Russell T. Hepple,&nbsp;Zhiguang Huo,&nbsp;Philip A. Kramer,&nbsp;Frederico G. S. Toledo,&nbsp;Xiping Zhang,&nbsp;Kevin Wu,&nbsp;Christopher A. Wolff,&nbsp;Daniel S. Evans,&nbsp;Steven R. Cummings","doi":"10.1111/acel.14114","DOIUrl":"10.1111/acel.14114","url":null,"abstract":"<p>Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals would further our knowledge of mechanisms related to managing molecular damage that may be targeted to preserve physical resilience. To characterize expression patterns of genes responsible for the oxidative stress response, RNA was extracted and sequenced from skeletal muscle biopsies collected from 575 participants (≥70 years old) from the Study of Muscle, Mobility, and Aging. Expression levels of 21 protein-coding RNAs related to the oxidative stress response were analyzed in relation to six phenotypic measures, including maximal mitochondrial respiration from muscle biopsies (Max OXPHOS), physical performance (VO₂ peak, 400-m walking speed, and leg strength), and muscle size (thigh muscle volume and whole-body D3Cr muscle mass). The mRNA level of the oxidative stress response genes most consistently associated across outcomes are preferentially expressed within the mitochondria. Higher expression of mRNAs that encode generally mitochondria located proteins <i>SOD2</i>, <i>TRX2</i>, <i>PRX3</i>, <i>PRX5</i>, and <i>GRX2</i> were associated with higher levels of mitochondrial respiration and VO₂ peak. In addition, greater <i>SOD2, PRX3,</i> and <i>GRX2</i> expression was associated with higher physical performance and muscle size. Identifying specific mechanisms associated with high functioning across multiple performance and physical domains may lead to targeted antioxidant interventions with greater impacts on mobility and independence.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236541","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}