BiogerontologyPub Date : 2023-12-01Epub Date: 2023-07-17DOI: 10.1007/s10522-023-10046-x
Filipe Nogueira Franco, Luciana de Cassia Cardoso, Bárbara Néllita Moura Silva, Glaucy Rodrigues de Araújo, Miriam Martins Chaves
{"title":"Aging: silencing the PKA and AkT/PKB signaling pathways alters the antioxidant capacity of resveratrol.","authors":"Filipe Nogueira Franco, Luciana de Cassia Cardoso, Bárbara Néllita Moura Silva, Glaucy Rodrigues de Araújo, Miriam Martins Chaves","doi":"10.1007/s10522-023-10046-x","DOIUrl":"10.1007/s10522-023-10046-x","url":null,"abstract":"<p><p>One of the theories related to aging is the increase in oxidative stress. Given this, the objective of the study is to evaluate the cellular mechanisms responsible for the resveratrol antioxidant effect on leukocytes from donors aged between 20 and 80 years old. For this, leukocytes from donors of three age groups (20-39, 40-59 and 60-80) were isolated. Image-iT™LIVE Green Reactive Oxygen Species (ROS) Kit was used. Reactive Nitrogen Species (RNS) analysis was performed by measuring nitric oxide and peroxynitrite. The PKA, Akt/PKB and p38-MAPK were evaluated by chemiluminescence. The statistical analysis between age and treatments were performed by Pearson correlation (*p < 0.05). It was possible to observe the antioxidant effect of resveratrol in all age groups. The correlation results show loss of resveratrol effect in decreasing ROS in leukocytes from older donors. We observed an active antioxidant effect of p38-MAPK in all ages, with resveratrol acting on it. The PKA and Akt/PKB were active in leukocytes from donors aged 20-59. In cells from donors older than 60, these pathways are silenced, and an effect is also not observed in cells treated with resveratrol. Therefore, resveratrol showed antioxidant effect in all age, although it was more pronounced in leukocytes from younger. One of resveratrol's mechanisms is due to the activation of the PKA and Akt/PKB, which were activated in younger donor cells.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185304","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}
BiogerontologyPub Date : 2023-12-01Epub Date: 2023-07-08DOI: 10.1007/s10522-023-10047-w
Maximilian Poser, Katie E A Sing, Thomas Ebert, Dirk Ziebolz, Gerhard Schmalz
{"title":"The rosetta stone of successful ageing: does oral health have a role?","authors":"Maximilian Poser, Katie E A Sing, Thomas Ebert, Dirk Ziebolz, Gerhard Schmalz","doi":"10.1007/s10522-023-10047-w","DOIUrl":"10.1007/s10522-023-10047-w","url":null,"abstract":"<p><p>Ageing is an inevitable aspect of life and thus successful ageing is an important focus of recent scientific efforts. The biological process of ageing is mediated through the interaction of genes with environmental factors, increasing the body's susceptibility to insults. Elucidating this process will increase our ability to prevent and treat age-related disease and consequently extend life expectancy. Notably, centenarians offer a unique perspective on the phenomenon of ageing. Current research highlights several age-associated alterations on the genetic, epigenetic and proteomic level. Consequently, nutrient sensing and mitochondrial function are altered, resulting in inflammation and exhaustion of regenerative ability.Oral health, an important contributor to overall health, remains underexplored in the context of extreme longevity. Good masticatory function ensures sufficient nutrient uptake, reducing morbidity and mortality in old age. The relationship between periodontal disease and systemic inflammatory pathologies is well established. Diabetes, rheumatoid arthritis and cardiovascular disease are among the most significant disease burdens influenced by inflammatory oral health conditions. Evidence suggests that the interaction is bi-directional, impacting progression, severity and mortality. Current models of ageing and longevity neglect an important factor in overall health and well-being, a gap that this review intends to illustrate and inspire avenues for future research.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9758841","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}
BiogerontologyPub Date : 2023-12-01Epub Date: 2023-07-03DOI: 10.1007/s10522-023-10043-0
Kento Takaya, Toru Asou, Kazuo Kishi
{"title":"Identification of resibufogenin, a component of toad venom, as a novel senolytic compound in vitro and for potential skin rejuvenation in male mice.","authors":"Kento Takaya, Toru Asou, Kazuo Kishi","doi":"10.1007/s10522-023-10043-0","DOIUrl":"10.1007/s10522-023-10043-0","url":null,"abstract":"<p><p>Senescent cells that accumulate with age have been shown to contribute to age-related diseases and organ dysfunction and have attracted attention as a target for anti-aging therapy. In particular, the use of senescent cell-depleting agents, or senolytics, has been shown to improve the aging phenotype in animal models. Since senescence has been implicated in the skin, particularly in fibroblasts, this study used aged human skin fibroblasts to investigate the effects of resibufogenin. A component of the traditional Chinese medicine toad venom, resibufogenin was investigated for senolytic and/or senomorphic activity. We found that the compound selectively caused senescent cell death without affecting proliferating cells, with a marked effect on the suppression of the senescence-associated secretory phenotype. We also found that resibufogenin causes senescent cell death by inducing a caspase-3-mediated apoptotic program. Administration of resibufogenin to aging mice resulted in an increase in dermal collagen density and subcutaneous fat, improving the phenotype of aging skin. In other words, resibufogenin ameliorates skin aging through selective induction of senescent cell apoptosis without affecting non-aged cells. This traditional compound may have potential therapeutic benefits in skin aging characterized by senescent cell accumulation.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9740488","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":"Retinal microvascular complexity as a putative biomarker of biological age: a pilot study.","authors":"Natasa Popovic, Maša Ždralević, Stela Vujosevic, Miroslav Radunović, Antoaneta Adžić Zečević, Isidora Rovčanin Dragović, Batrić Vukčević, Tomo Popovic, Ljiljana Radulović, Tijana Vuković, Jevto Eraković, Ranko Lazović, Miodrag Radunović","doi":"10.1007/s10522-023-10057-8","DOIUrl":"10.1007/s10522-023-10057-8","url":null,"abstract":"<p><p>Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older \"biological age\" compared to their \"chronological age\". Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82 years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer's dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl's, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl's analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9981964","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}
BiogerontologyPub Date : 2023-12-01Epub Date: 2023-07-13DOI: 10.1007/s10522-023-10041-2
Nádia Silva, Ana Teresa Rajado, Filipa Esteves, David Brito, Joana Apolónio, Vânia Palma Roberto, Alexandra Binnie, Inês Araújo, Clévio Nóbrega, José Bragança, Pedro Castelo-Branco
{"title":"Measuring healthy ageing: current and future tools.","authors":"Nádia Silva, Ana Teresa Rajado, Filipa Esteves, David Brito, Joana Apolónio, Vânia Palma Roberto, Alexandra Binnie, Inês Araújo, Clévio Nóbrega, José Bragança, Pedro Castelo-Branco","doi":"10.1007/s10522-023-10041-2","DOIUrl":"10.1007/s10522-023-10041-2","url":null,"abstract":"<p><p>Human ageing is a complex, multifactorial process characterised by physiological damage, increased risk of age-related diseases and inevitable functional deterioration. As the population of the world grows older, placing significant strain on social and healthcare resources, there is a growing need to identify reliable and easy-to-employ markers of healthy ageing for early detection of ageing trajectories and disease risk. Such markers would allow for the targeted implementation of strategies or treatments that can lessen suffering, disability, and dependence in old age. In this review, we summarise the healthy ageing scores reported in the literature, with a focus on the past 5 years, and compare and contrast the variables employed. The use of approaches to determine biological age, molecular biomarkers, ageing trajectories, and multi-omics ageing scores are reviewed. We conclude that the ideal healthy ageing score is multisystemic and able to encompass all of the potential alterations associated with ageing. It should also be longitudinal and able to accurately predict ageing complications at an early stage in order to maximize the chances of successful early intervention.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9829652","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":"Differential effects of aging on hippocampal ultrastructure in male vs. female rats.","authors":"Mzia Zhvania, Nadezhda Japaridze, Yousef Tizabi, Nino Lomidze, Nino Pochkhidze, Fuad Rzayev, Eldar Gasimov","doi":"10.1007/s10522-023-10052-z","DOIUrl":"10.1007/s10522-023-10052-z","url":null,"abstract":"<p><p>Age-related decline in physical and cognitive functions are facts of life that do not affect everyone to the same extent. We had reported earlier that such cognitive decline is both sex- and context-dependent. Moreover, age-associated ultrastructural changes were observed in the hippocampus of male rats. In this study, we sought to determine potential differences in ultrastructural changes between male and female rats at various stages of life. We performed quantitative electron microscopic evaluation of hippocampal CA1 region, an area intimately involved in cognitive behavior, in both male and female adolescent, adult and old Wistar rats. Specifically, we measured the number of docking synaptic vesicles in axo-dendritic synapses, the length of active zone as well as the total number of synaptic vesicles. Distinct age- and sex-dependent effects were observed in several parameters. Thus, adult female rats had the lowest synaptic active zone compared to both adolescent and old female rats. Moreover, the same parameter was significantly lower in adult and old female rats compared to their male counterparts. On the other hand, old male rats had significantly lower number of total synaptic vesicles compared to both adolescent and adult male rats as well as compared to their female counterparts. Taken together, it may be suggested that age- and sex-dependent ultrastructural changes in the hippocampus may underlie at least some of the differences in cognitive functions among these groups.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9889527","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}
BiogerontologyPub Date : 2023-12-01Epub Date: 2023-07-12DOI: 10.1007/s10522-023-10044-z
Khushboo Srivastava, Rajnikant Mishra
{"title":"Pax6 affects Ras-Raf-ERK1/2 in mouse aging brain.","authors":"Khushboo Srivastava, Rajnikant Mishra","doi":"10.1007/s10522-023-10044-z","DOIUrl":"10.1007/s10522-023-10044-z","url":null,"abstract":"<p><p>Pax6, a transcription factor and multifunctional protein, changes during aging. It also interacts with regulator proteins involved in cell metabolism and survival signalling pathways including Ras-GAP. Many forms of Ras, Raf and ERK1/2 are known but information on their region-specific expression patterns are unavailable from brain during aging. Therefore, it has been intended to evaluate expressions of Pax6 and forms of Ras, Raf, ERK1/2 in hippocampus, caudate nucleus, amygdale, cerebral cortex, cerebellum and olfactory lobe. Association of Pax6 with Ras, Raf and ERK1/2 was evaluated in co-culture (PC-12, C6-glia, U-87 MG) of neuroglia cell lines. Impacts of Pax6 were evaluated by siRNA mediated knockdown and expression patterns Ras-Raf-Erk1/2. Analysis of activities of Pax6 and impacts of 5'AMP, wild-type and mutant ERK were done by RT-PCR and luciferase reporter assay. Results indicate age-dependent changes of Pax6, Ras, Raf, ERK1/2 in different regions of brain of young and old mice. Erk1/2 shows synergistic activities to Pax6.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10129512","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}
BiogerontologyPub Date : 2023-12-01Epub Date: 2023-07-31DOI: 10.1007/s10522-023-10054-x
Pavel Borsky, Drahomira Holmannova, Ctirad Andrys, Jan Kremlacek, Zdenek Fiala, Helena Parova, Vit Rehacek, Tereza Svadlakova, Svatopluk Byma, Otto Kucera, Lenka Borska
{"title":"Evaluation of potential aging biomarkers in healthy individuals: telomerase, AGEs, GDF11/15, sirtuin 1, NAD+, NLRP3, DNA/RNA damage, and klotho.","authors":"Pavel Borsky, Drahomira Holmannova, Ctirad Andrys, Jan Kremlacek, Zdenek Fiala, Helena Parova, Vit Rehacek, Tereza Svadlakova, Svatopluk Byma, Otto Kucera, Lenka Borska","doi":"10.1007/s10522-023-10054-x","DOIUrl":"10.1007/s10522-023-10054-x","url":null,"abstract":"<p><p>Aging is a natural process of gradual decrease in physical and mental capacity. Biological age (accumulation of changes and damage) and chronological age (years lived) may differ. Biological age reflects the risk of various types of disease and death from any cause. We selected potential biomarkers of aging - telomerase, AGEs, GDF11 and 15 (growth differentiation factor 11/15), sirtuin 1, NAD<sup>+</sup> (nicotinamide adenine dinucleotide), inflammasome NLRP3, DNA/RNA damage, and klotho to investigate changes in their levels depending on age and sex. We included 169 healthy volunteers and divided them into groups according to age (under 35; 35-50; over 50) and sex (male, female; male and female under 35; 35-50, over 50). Markers were analyzed using commercial ELISA kits. We found differences in values depending on age and gender. GDF15 increased with age (under 30 and 35-50 p < 0.002; 35-50 and over 50; p < 0.001; under 35 and over 50; p < 0.001) as well as GDF11 (35-50 and over 50; p < 0.03; under 35 and over 50; p < 0.02), AGEs (under 30 and 35-50; p < 0.005), NLRP3 (under 35 over 50; p < 0.03), sirtuin 1 (35-50 and over 50; p < 0.0001; under 35 and over 50; p < 0.004). AGEs and GDF11 differed between males and females. Correlations were identified between individual markers, markers and age, and markers and sex. Markers that reflect the progression of biological aging vary with age (GDF15, GDF11, AGEs, NLRP3, sirtuin) and sex (AGEs, GDF11). Their levels could be used in clinical practice, determining biological age, risk of age-related diseases and death of all-causes, and initiating or contraindicating a therapy in the elderly based on the patient's health status.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9952877","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}
BiogerontologyPub Date : 2023-10-01Epub Date: 2023-05-17DOI: 10.1007/s10522-023-10040-3
Prashanth S Javali, Mouliganesh Sekar, Ashish Kumar, Kavitha Thirumurugan
{"title":"Dynamics of redox signaling in aging via autophagy, inflammation, and senescence.","authors":"Prashanth S Javali, Mouliganesh Sekar, Ashish Kumar, Kavitha Thirumurugan","doi":"10.1007/s10522-023-10040-3","DOIUrl":"10.1007/s10522-023-10040-3","url":null,"abstract":"<p><p>Review paper attempts to explain the dynamic aspects of redox signaling in aging through autophagy, inflammation, and senescence. It begins with ROS source in the cell, then states redox signaling in autophagy, and regulation of autophagy in aging. Next, we discuss inflammation and redox signaling with various pathways involved: NOX pathway, ROS production via TNF-α, IL-1β, xanthine oxidase pathway, COX pathway, and myeloperoxidase pathway. Also, we emphasize oxidative damage as an aging marker and the contribution of pathophysiological factors to aging. In senescence-associated secretory phenotypes, we link ROS with senescence, aging disorders. Relevant crosstalk between autophagy, inflammation, and senescence using a balanced ROS level might reduce age-related disorders. Transducing the context-dependent signal communication among these three processes at high spatiotemporal resolution demands other tools like multi-omics aging biomarkers, artificial intelligence, machine learning, and deep learning. The bewildering advancement of technology in the above areas might progress age-related disorders diagnostics with precision and accuracy.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10501944","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}
BiogerontologyPub Date : 2023-10-01Epub Date: 2023-05-25DOI: 10.1007/s10522-023-10038-x
Ronghua Fang, Jie Chen, Jiangchuan Long, Binghan Zhang, Qixuan Huang, Shengbing Li, Ke Li, Qing Chen, Dongfang Liu
{"title":"Empagliflozin improves kidney senescence induced by D-galactose by reducing sirt1-mediated oxidative stress.","authors":"Ronghua Fang, Jie Chen, Jiangchuan Long, Binghan Zhang, Qixuan Huang, Shengbing Li, Ke Li, Qing Chen, Dongfang Liu","doi":"10.1007/s10522-023-10038-x","DOIUrl":"10.1007/s10522-023-10038-x","url":null,"abstract":"<p><p>Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have received widespread attention because of their significant protective effects on the kidney. Previous studies have shown that Sirt1, as which is an antiaging protein, is closely related to the maintenance of redox homeostasis. The goal of this study was to determine whether empagliflozin could ameliorate D-galactose-induced renal senescence in mice, and examine the possible mechanisms of Sirt1. We constructed a rapid ageing model in mice by administering D-galactose. An ageing model was constructed by treating cells with high glucose. Treadmill and Y-maze tests were used to assess exercise tolerance and learning memory ability. Pathologically stained sections were used to assess kidney injury. Tissue and cell senescence were evaluated by senescence-associated β-galactosidase staining. The expression levels of P16, SOD1, SOD2 and Sirt1 were detected by immunoblotting. D-gal-treated mice exhibited significant age-related changes, as measured by behavioural tests and ageing marker protein levels. empagliflozin alleviated these ageing manifestations. In addition, Sirt1, SOD1 and SOD2 levels were downregulated in model mice and upregulated by empagliflozin treatment. Empagliflozin had similar protective effects at the cellular level, and these effects were reduced by the Sirt1 inhibitor. Empagliflozin has an antiaging effect, which may be related to reducing Sirt1-mediated oxidative stress.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10148118","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}