Aging Cell最新文献_第8页

Neuropeptides regulate embryonic salivary gland branching through the FGF/FGFR pathway in aging klotho-deficient mice. 神经肽通过 FGF/FGFR 通路调节老化 klotho-deficient 小鼠的胚胎唾液腺分支。

IF 8 1区医学

Aging Cell Pub Date : 2024-09-06 DOI: 10.1111/acel.14329

Nguyen Khanh Toan, Soo-A Kim, Sang-Gun Ahn

{"title":"Neuropeptides regulate embryonic salivary gland branching through the FGF/FGFR pathway in aging klotho-deficient mice.","authors":"Nguyen Khanh Toan, Soo-A Kim, Sang-Gun Ahn","doi":"10.1111/acel.14329","DOIUrl":"https://doi.org/10.1111/acel.14329","url":null,"abstract":"Salivary gland branching morphogenesis is regulated by the functional integration of neuronal signaling, but the underlying mechanisms are not fully understood in aging accelerated klotho-deficient (Kl-/-) mice. Here, we investigated whether the neuropeptides substance P (SP) and neuropeptide Y (NPY) affect the branching morphogenesis of embryonic salivary glands in aging Kl-/- mice. In the salivary glands of embryonic Kl-/- mice, morphological analysis and immunostaining revealed that epithelial bud formation, neuronal cell proliferation/differentiation, and the expression of the salivary gland functional marker ZO-1 were decreased in embryonic ductal cells. Incubation with SP/NPY at E12-E13d promoted branching morphogenesis, parasympathetic innervation, and epithelial proliferation in salivary glands of embryonic Kl-/- mice. The ERK inhibitor U0126 specifically inhibited neuronal substance-induced epithelial bud formation in the embryonic salivary gland. RNA-seq profiling analysis revealed that the expression of fibroblast growth factors/fibroblast growth factors (FGFs/FGFRs) and their receptors was significantly regulated by SP/NPY treatment in the embryonic salivary gland (E15). The FGFR inhibitor BGJ389 inhibited new branching formation induced by SP and NPY treatment and ERK1/2 expression. These results showed that aging may affect virtually the development of salivary gland by neuronal dysfunction. The neuropeptides SP/NPY induced embryonic salivary gland development through FGF/FGFR/ERK1/2-mediated signaling.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14329"},"PeriodicalIF":8.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138710","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}

引用次数: 0

Targeting TGF-β signaling, oxidative stress, and cellular senescence rescues osteoporosis in gerodermia osteodysplastica. 以 TGF-β 信号、氧化应激和细胞衰老为靶点可拯救老年性骨质疏松症患者的骨质疏松症。

IF 8 1区医学

Aging Cell Pub Date : 2024-09-05 DOI: 10.1111/acel.14322

W L Chan, C H Bucher, J Goldes, A C Ma, M Steiner, B M Willie, S Mundlos, U Kornak

{"title":"Targeting TGF-β signaling, oxidative stress, and cellular senescence rescues osteoporosis in gerodermia osteodysplastica.","authors":"W L Chan, C H Bucher, J Goldes, A C Ma, M Steiner, B M Willie, S Mundlos, U Kornak","doi":"10.1111/acel.14322","DOIUrl":"https://doi.org/10.1111/acel.14322","url":null,"abstract":"GORAB is a key regulator of Golgi vesicle transport and protein glycanation. Loss of GORAB function in gerodermia osteodysplastica (GO) causes shortening of glycosaminoglycan chains, leading to extracellular matrix disorganization that results in wrinkled skin, osteoporosis and elevated TGF-β signaling. In this study, we investigated the role of TGF-β-signaling, oxidative stress, and resulting cellular senescence in the osteoporosis phenotype of GO. Treatment of GorabPrx1 conditional knockouts with the TGF-β neutralizing antibody 1D11 rescued the trabecular bone loss, indicating that TGF-β overactivation causes osteoporosis in GO. Using an inducible knockout system, we demonstrated that TGF-β dysregulation was not a cell-intrinsic effect of GORAB inactivation, but a consequence of a disorganized extracellular matrix. Enhanced TGF-β signaling caused elevated Nox4 expression in GorabPrx1 mutants and in GO patients' fibroblasts, resulting in overproduction of mitochondrial superoxide. The resulting oxidative stress was detected in GORAB null cells and also in wildtype bystander cells. The same effect was observed in zebrafish after TALEN-mediated gorab inactivation, indicating that the pathway is evolutionarily conserved. Treating GorabPrx1 mutants with the antioxidant N-acetylcysteine ameliorated the osteoporosis phenotype. TGF-β induced oxidative stress coincided with accumulation of DNA damage and elevated expression of senescence markers. Inactivation of Cdkn2a in the GorabPrx1 rescued the osteoporosis phenotype. Reduced colony formation and altered subpopulations of bone marrow stromal cells were normalized upon inactivation of Cdkn2a, thus further demonstrating the relevance of cellular senescence in the pathogenesis. Our results shed light on the causative role of a TGF-β-Nox4-senescence axis and therapeutic strategies for GO.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14322"},"PeriodicalIF":8.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131324","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}

引用次数: 0

Age and duration of obesity modulate the inflammatory response and expression of neuroprotective factors in mammalian female brain. 肥胖的年龄和持续时间会调节哺乳动物雌性大脑的炎症反应和神经保护因子的表达。

IF 8 1区医学

Aging Cell Pub Date : 2024-09-04 DOI: 10.1111/acel.14313

Binnur Eroglu, Carlos Isales, Ali Eroglu

{"title":"Age and duration of obesity modulate the inflammatory response and expression of neuroprotective factors in mammalian female brain.","authors":"Binnur Eroglu, Carlos Isales, Ali Eroglu","doi":"10.1111/acel.14313","DOIUrl":"https://doi.org/10.1111/acel.14313","url":null,"abstract":"Obesity has become a global epidemic and is associated with comorbidities, including diabetes, cardiovascular, and neurodegenerative diseases, among others. While appreciable insight has been gained into the mechanisms of obesity-associated comorbidities, effects of age, and duration of obesity on the female brain remain obscure. To address this gap, adolescent and mature adult female mice were subjected to a high-fat diet (HFD) for 13 or 26 weeks, whereas age-matched controls were fed a standard diet. Subsequently, the expression of inflammatory cytokines, neurotrophic/neuroprotective factors, and markers of microgliosis and astrogliosis were analyzed in the hypothalamus, hippocampus, and cerebral cortex, along with inflammation in visceral adipose tissue. HFD led to a typical obese phenotype in all groups independent of age and duration of HFD. However, the intermediate duration of obesity induced a limited inflammatory response in adolescent females' hypothalamus while the hippocampus, cerebral cortex, and visceral adipose tissue remained unaffected. In contrast, the prolonged duration of obesity resulted in inflammation in all three brain regions and visceral adipose tissue along with upregulation of microgliosis/astrogliosis and suppression of neurotrophic/neuroprotective factors in all brain regions, denoting the duration of obesity as a critical risk factor for neurodegenerative diseases. Importantly, when female mice were older (i.e., mature adult), even the intermediate duration of obesity induced similar adverse effects in all brain regions. Taken together, our findings suggest that (1) both age and duration of obesity have a significant impact on obesity-associated comorbidities and (2) early interventions to end obesity are critical to preserving brain health.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14313"},"PeriodicalIF":8.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124263","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}

引用次数: 0

Rapamycin's lifespan effect is modulated by mito-nuclear epistasis in Drosophila. 雷帕霉素对果蝇寿命的影响受有丝分裂-核上位作用的调节

IF 8 1区医学

Aging Cell Pub Date : 2024-09-03 DOI: 10.1111/acel.14328

Rita Ibrahim, Maria Bahilo Martinez, Adam J Dobson

引用次数: 0

Analysis of the senescence-associated cell surfaceome reveals potential senotherapeutic targets. 衰老相关细胞表面组分析揭示了潜在的衰老治疗靶点。

IF 8 1区医学

Aging Cell Pub Date : 2024-09-03 DOI: 10.1111/acel.14312

Yushuang Deng, Ting Liu, Enzo Scifo, Tao Li, Kan Xie, Bernd Taschler, Sarah Morsy, Kristina Schaaf, Armin Ehninger, Daniele Bano, Dan Ehninger

{"title":"Analysis of the senescence-associated cell surfaceome reveals potential senotherapeutic targets.","authors":"Yushuang Deng, Ting Liu, Enzo Scifo, Tao Li, Kan Xie, Bernd Taschler, Sarah Morsy, Kristina Schaaf, Armin Ehninger, Daniele Bano, Dan Ehninger","doi":"10.1111/acel.14312","DOIUrl":"https://doi.org/10.1111/acel.14312","url":null,"abstract":"The accumulation of senescent cells is thought to play a crucial role in aging-associated physiological decline and the pathogenesis of various age-related pathologies. Targeting senescence-associated cell surface molecules through immunotherapy emerges as a promising avenue for the selective removal of these cells. Despite its potential, a thorough characterization of senescence-specific surface proteins remains to be achieved. Our study addresses this gap by conducting an extensive analysis of the cell surface proteome, or \"surfaceome\", in senescent cells, spanning various senescence induction regimes and encompassing both murine and human cell types. Utilizing quantitative mass spectrometry, we investigated enriched cell surface proteins across eight distinct models of senescence. Our results uncover significant changes in surfaceome expression profiles during senescence, highlighting extensive modifications in cell mechanics and extracellular matrix remodeling. Our research also reveals substantive heterogeneity of senescence, predominantly influenced by cell type and senescence inducer. A key discovery of our study is the identification of four unique cell surface proteins with extracellular epitopes. These proteins are expressed in senescent cells, absent or present at low levels in their proliferating counterparts, and notably upregulated in tissues from aged mice and an Alzheimer's disease mouse model. These proteins stand out as promising candidates for senotherapeutic targeting, offering potential pathways for the detection and strategic targeting of senescent cell populations in aging and age-related diseases.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14312"},"PeriodicalIF":8.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124264","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}

引用次数: 0

Fkbp5 gene deletion: Circadian rhythm profile and brain proteomics in aged mice. Fkbp5 基因缺失：老龄小鼠的昼夜节律特征和脑蛋白质组学

IF 8 1区医学

Aging Cell Pub Date : 2024-09-03 DOI: 10.1111/acel.14314

Niat T Gebru, Jennifer Guergues, Laura A Verdina, Jessica Wohlfahrt, Shuai Wang, Debra S Armendariz, Marsilla Gray, David Beaulieu-Abdelahad, Stanley M Stevens, Danielle Gulick, Laura J Blair

{"title":"Fkbp5 gene deletion: Circadian rhythm profile and brain proteomics in aged mice.","authors":"Niat T Gebru, Jennifer Guergues, Laura A Verdina, Jessica Wohlfahrt, Shuai Wang, Debra S Armendariz, Marsilla Gray, David Beaulieu-Abdelahad, Stanley M Stevens, Danielle Gulick, Laura J Blair","doi":"10.1111/acel.14314","DOIUrl":"10.1111/acel.14314","url":null,"abstract":"FKBP51, also known as FK506-binding protein 51, is a molecular chaperone and scaffolding protein with significant roles in regulating hormone signaling and responding to stress. Genetic variants in FKBP5, which encodes FKBP51, have been implicated in a growing number of neuropsychiatric disorders, which has spurred efforts to target FKBP51 therapeutically. However, the molecular mechanisms and sub-anatomical regions influenced by FKBP51 in these disorders are not fully understood. In this study, we aimed to examine the impact of Fkbp5 ablation using circadian phenotyping and molecular analyses. Our findings revealed that the lack of FKBP51 did not significantly alter circadian rhythms, as detected by wheel-running activity, but did offer protection against stress-mediated disruptions in rhythmicity in a sex-dependent manner. Protein changes in Fkbp5 KO mice, as measured by histology and proteomics, revealed alterations in a brain region- and sex-dependent manner. Notably, regardless of sex, aged Fkbp5 KOs showed elevated MYCBP2, FBXO45, and SPRYD3 levels, which are associated with neuronal-cell adhesion and synaptic integrity. Additionally, pathways such as serotonin receptor signaling and S100 family signaling were differentially regulated in Fkbp5 KO mice. Weighted protein correlation network analysis identified protein networks linked with synaptic transmission and neuroinflammation. The information generated by this work can be used to better understand the molecular changes in the brain during aging and in the absence of Fkbp5, which has implications for the continued development of FKBP51-focused therapeutics for stress-related disorders.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14314"},"PeriodicalIF":8.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118474","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}

引用次数: 0

Unacylated Ghrelin Protects Against Age-Related Loss of Muscle Mass and Contractile Dysfunction in Skeletal Muscle. 单酰化胃泌素可防止骨骼肌中与年龄相关的肌肉质量损失和收缩功能障碍。

IF 8 1区医学

Aging Cell Pub Date : 2024-09-02 DOI: 10.1111/acel.14323

Hyunyoung Kim, Rojina Ranjit, Dennis R Claflin, Constantin Georgescu, Jonathan D Wren, Susan V Brooks, Benjamin F Miller, Bumsoo Ahn

{"title":"Unacylated Ghrelin Protects Against Age-Related Loss of Muscle Mass and Contractile Dysfunction in Skeletal Muscle.","authors":"Hyunyoung Kim, Rojina Ranjit, Dennis R Claflin, Constantin Georgescu, Jonathan D Wren, Susan V Brooks, Benjamin F Miller, Bumsoo Ahn","doi":"10.1111/acel.14323","DOIUrl":"10.1111/acel.14323","url":null,"abstract":"Sarcopenia, the progressive loss of muscle mass and function, universally affects older adults and is closely associated with frailty and reduced quality of life. Despite the inevitable consequences of sarcopenia and its relevance to healthspan, no pharmacological therapies are currently available. Ghrelin is a gut-released hormone that increases appetite and body weight through acylation. Acylated ghrelin activates its receptor, growth hormone secretagogue receptor 1a (GHSR1a), in the brain by binding to it. Studies have demonstrated that acyl and unacylated ghrelin (UnAG) both have protective effects against acute pathological conditions independent of receptor activation. Here, we investigated the long-term effects of UnAG in age-associated muscle atrophy and contractile dysfunction in mice. Four-month-old and 18-month-old mice were subjected to either UnAG or control treatment for 10 months. UnAG did not affect food consumption or body weight. Gastrocnemius and quadriceps muscle weights were reduced by 20%-30% with age, which was partially protected against by UnAG. Specific force, force per cross-sectional area, measured in isolated extensor digitorum longus muscle was diminished by 30% in old mice; however, UnAG prevented the loss of specific force. UnAG also protected from decreases in mitochondrial respiration and increases in hydrogen peroxide generation of skeletal muscle of old mice. Results of bulk mRNA-seq analysis and our contractile function data show that UnAG reversed neuromuscular junction impairment that occurs with age. Collectively, our data revealed the direct role of UnAG in mitigating sarcopenia in mice, independent of food consumption or body weight, implicating UnAG treatment as a potential therapy against sarcopenia.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14323"},"PeriodicalIF":8.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118476","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}

引用次数: 0

Periodic protein-restricted diets extend the lifespan of high-fat diet-induced Drosophila melanogaster males. 定期限制蛋白质饮食可延长高脂饮食诱导的黑腹果蝇雄虫的寿命

IF 8 1区医学

Aging Cell Pub Date : 2024-08-29 DOI: 10.1111/acel.14327

Ruohua Wang, Qiushuang Zhu, He Huang, Mengxia Yang, Xinyue Wang, Yuanjie Dong, Yuqiao Li, Yue Guan, Lei Zhong, Yucun Niu

{"title":"Periodic protein-restricted diets extend the lifespan of high-fat diet-induced Drosophila melanogaster males.","authors":"Ruohua Wang, Qiushuang Zhu, He Huang, Mengxia Yang, Xinyue Wang, Yuanjie Dong, Yuqiao Li, Yue Guan, Lei Zhong, Yucun Niu","doi":"10.1111/acel.14327","DOIUrl":"https://doi.org/10.1111/acel.14327","url":null,"abstract":"Research has shown that sustained protein restriction can improve the effects of a high-fat diet on health and extend lifespan. However, long-term adherence to a protein-restricted diet is challenging. Therefore, we used a fly model to investigate whether periodic protein restriction (PPR) could also mitigate the potential adverse effects of a high-fat diet and extend healthy lifespan. Our study results showed that PPR reduced body weight, lipid levels, and oxidative stress induced by a high-fat diet in flies and significantly extended the healthy lifespan of male flies. Lipid metabolism and transcriptome results revealed that the common differences between the PPR group and the control group and high-fat group showed a significant decrease in palmitic acid in the PPR group; the enriched common differential pathways Toll and Imd were significantly inhibited in the PPR group. Further analysis indicated a significant positive correlation between palmitic acid levels and gene expression in the Toll and Imd pathways. This suggests that PPR effectively improves fruit fly lipid metabolism, reduces palmitic acid levels, and thereby suppresses the Toll and Imd pathways to extend the healthy lifespan of flies. Our study provides a theoretical basis for the long-term effects of PPR on health and offers a new dietary adjustment option for maintaining health in the long term.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14327"},"PeriodicalIF":8.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102449","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}

引用次数: 0

Premature cognitive decline in a mouse model of tuberous sclerosis. 结节性硬化症小鼠模型的认知能力早衰。

IF 8 1区医学

Aging Cell Pub Date : 2024-08-27 DOI: 10.1111/acel.14318

J Krummeich, L Nardi, C Caliendo, D Aschauer, V Engelhardt, A Arlt, J Maier, F Bicker, M D Kwiatkowski, K Rolski, K Vincze, R Schneider, S Rumpel, S Gerber, M J Schmeisser, S Schweiger

引用次数: 0

Pathogenic TDP-43 accelerates the generation of toxic exon1 HTT in Huntington's disease knock-in mice. 致病性 TDP-43 可加速亨廷顿氏病基因敲入小鼠中毒性外显子 1 HTT 的生成。

IF 8 1区医学

Aging Cell Pub Date : 2024-08-26 DOI: 10.1111/acel.14325

Dazhang Bai, Fuyu Deng, Qingqing Jia, Kaili Ou, Xiang Wang, Junqi Hou, Longhong Zhu, Mingwei Guo, Su Yang, Guohui Jiang, Shihua Li, Xiao-Jiang Li, Peng Yin

{"title":"Pathogenic TDP-43 accelerates the generation of toxic exon1 HTT in Huntington's disease knock-in mice.","authors":"Dazhang Bai, Fuyu Deng, Qingqing Jia, Kaili Ou, Xiang Wang, Junqi Hou, Longhong Zhu, Mingwei Guo, Su Yang, Guohui Jiang, Shihua Li, Xiao-Jiang Li, Peng Yin","doi":"10.1111/acel.14325","DOIUrl":"https://doi.org/10.1111/acel.14325","url":null,"abstract":"Huntington's disease (HD) is caused by a CAG repeat expansion in exon1 of the HTT gene that encodes a polyglutamine tract in huntingtin protein. The formation of HTT exon1 fragments with an expanded polyglutamine repeat has been implicated as a key step in the pathogenesis of HD. It was reported that the CAG repeat length-dependent aberrant splicing of exon1 HTT results in a short polyadenylated mRNA that is translated into an exon1 HTT protein. Under normal conditions, TDP-43 is predominantly found in the nucleus, where it regulates gene expression. However, in various pathological conditions, TDP-43 is mislocalized in the cytoplasm. By investigating HD knock-in mice, we explore whether the pathogenic TDP-43 in the cytoplasm contributes to HD pathogenesis, through expressing the cytoplasmic TDP-43 without nuclear localization signal. We found that the cytoplasmic TDP-43 is increased in the HD mouse brain and that its mislocalization could deteriorate the motor and gait behavior. Importantly, the cytoplasmic TDP-43, via its binding to the intron1 sequence (GU/UG)n of the mouse Htt pre-mRNA, promotes the transport of exon1-intron1 Htt onto ribosome, resulting in the aberrant generation of exon1 Htt. Our findings suggest that cytoplasmic TDP-43 contributes to HD pathogenesis via its binding to and transport of nuclear un-spliced mRNA to the ribosome for the generation of a toxic protein product.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14325"},"PeriodicalIF":8.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054228","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}

引用次数: 0