Biogerontology最新文献

{"title":"Aging, vascular dysfunction, and the blood-brain barrier: unveiling the pathophysiology of stroke in older adults.","authors":"Saleh I Alaqel, Mohd Imran, Abida Khan, Naira Nayeem","doi":"10.1007/s10522-025-10209-y","DOIUrl":"https://doi.org/10.1007/s10522-025-10209-y","url":null,"abstract":"<p><p>The progressive decline of vascular integrity and blood-brain barrier (BBB) function is associated with aging, a major risk factor for stroke. This review describes the cellular and molecular changes in the brain microvasculature of the neurovascular unit (NVU) that contribute to the development of BBB dysfunction in aging, such as endothelial cell senescence, oxidative stress, and degradation of tight junction proteins. Stroke severity and recovery are exacerbated by BBB breakdown, leading to neuroinflammation, neurotoxicity, and cerebral oedema while identifying molecular mechanisms such as the NLRP3 inflammasome, matrix metalloproteinases (MMPs), and non-coding RNAs (e.g., miRNAs and circRNAs) that drive BBB disruption in aging and stroke. Real-time assessment of BBB permeability in stroke pathophysiology is made possible using advanced imaging techniques, such as dynamic contrast-enhanced MRI and positron emission tomography. Furthermore, biomarkers, including claudin-5, PDGFRβ, or albumin concentration, serve as markers of BBB integrity and vascular health. Restoration of BBB function and stroke recovery with emerging therapeutic strategies, including sirtuin modulators (SIRT1 and SIRT3 activators to enhance endothelial function and mitochondrial health), stem cell-derived extracellular vesicles (iPSC-sEVs for BBB repair and neuroprotection), NLRP3 inflammasome inhibitors (MCC950 to attenuate endothelial pyroptosis and inflammation), hydrogen-rich water therapy (to counteract oxidative stress-induced BBB damage), and neuropeptides such as cortistatin (to regulate neuroinflammation and BBB stability), is promising. This review explores the pathophysiological mechanisms of BBB dysfunction in aging and stroke, their relation to potential therapeutic targets, and novel approaches to improve vascular health and neuroprotection.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"67"},"PeriodicalIF":4.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565920","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":"Essential amino acids and branched-chain amino acids are associated with skeletal muscle and inflammatory parameters in older age.","authors":"Ching Wah Donna Li, Catrin Herpich, Ulrike Haß, Bastian Kochlik, Daniela Weber, Tilman Grune, Kristina Norman","doi":"10.1007/s10522-025-10206-1","DOIUrl":"https://doi.org/10.1007/s10522-025-10206-1","url":null,"abstract":"<p><p>Aging is associated with a decline in muscle mass and function, increasing the risk of adverse health outcomes. Amino acid profiling has emerged as a potential tool for assessing skeletal muscle health. This study examines the associations between fasting plasma amino acids, muscle function, and inflammation in healthy older and young adults. Data from 131 participants (101 older adults, 71.5±4.9 years; 30 young adults, 25.5±3.9 years) were analyzed. Skeletal muscle mass was assessed using bioimpedance analysis, and hand grip strength was measured with a dynamometer. Plasma amino acids, kynurenine, and inflammatory markers (CRP, IL-6) were quantified using ultraperformance liquid chromatography with tandem mass spectrometry and commercial immunosorbent assays, respectively. Older adults exhibited lower levels of glutamic acid, isoleucine, leucine, phenylalanine, kynurenine, and kynurenine-to-tryptophan (KYN:TRP) ratio compared to younger individuals (all p<0.05). In older adults, branched-chain and essential amino acids correlated positively with skeletal muscle index (SMI) and hand grip strength, whereas in young adults, only glutamic acid, proline, and KYN:TRP showed positive associations with SMI (all p<0.05). CRP and IL-6 were associated with several amino acids in older adults but not in younger individuals. These findings suggest that age-related shifts in amino acid profiles may reflect underlying changes in muscle metabolism and function, highlighting their potential as early indicators of muscle decline.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"66"},"PeriodicalIF":4.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565925","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":"The role of different physical exercises as an anti-aging factor in different stem cells.","authors":"Jia Xu, Zhe Song","doi":"10.1007/s10522-025-10205-2","DOIUrl":"https://doi.org/10.1007/s10522-025-10205-2","url":null,"abstract":"<p><p>The senescence process is connected to the characteristics of cellular aging. Understanding their causal network helps develop a framework for creating new treatments to slow down the senescence process. A growing body of research indicates that aging may adversely affect stem cells (SCs). SCs change their capability to differentiate into different cell types and decrease their potential for renewal as they age. Research has indicated that consistent physical exercise offers several health advantages, including a reduced risk of age-associated ailments like tumors, heart disease, diabetes, and neurological disorders. Exercise is a potent physiological stressor linked to higher red blood cell counts and an enhanced immune system, promoting disease resistance. Sports impact mesenchymal SCs (MSCs), hematopoietic SCs (HSCs), neuronal SCs (NuSCs), and muscular SCs (MuSCs), among other aged SCs types. These changes to the niche will probably affect the amount and capability of adult SCs after exercise. In this work, we looked into how different types of SCs age. The impact of physical activity on the aging process has been studied. Additionally, there has been discussion and study on the impact of different sports and physical activities on SCs as an anti-aging component.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"63"},"PeriodicalIF":4.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498596","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":"Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging.","authors":"Saurabh Gupta, Muhammad Afzal, Neetu Agrawal, Waleed Hassan Almalki, Mohit Rana, Saurabh Gangola, Suresh V Chinni, Benod Kumar K, Haider Ali, Sachin Kumar Singh, Saurabh Kumar Jha, Gaurav Gupta","doi":"10.1007/s10522-025-10207-0","DOIUrl":"https://doi.org/10.1007/s10522-025-10207-0","url":null,"abstract":"<p><p>Aging and metabolic disorders share intricate molecular pathways, with the Forkhead box O (FOXO)- Sirtuin 1 (SIRT1) axis emerging as a pivotal regulator of cellular stress adaptation, metabolic homeostasis, and longevity. This axis integrates nutrient signaling with oxidative stress defence, modulating glucose and lipid metabolism, mitochondrial function, and autophagy to maintain cellular stability. FOXO transcription factors, regulated by SIRT1 deacetylation, enhance antioxidant defence mechanisms, activating genes such as superoxide dismutase (SOD) and catalase, thereby counteracting oxidative stress and metabolic dysregulation. Recent evidence highlights the dynamic role of reactive oxygen species (ROS) as secondary messengers in redox signaling, influencing FOXO-SIRT1 activity in metabolic adaptation. Additionally, key redox-sensitive regulators such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) interact with this pathway, orchestrating mitochondrial biogenesis and adaptive stress responses. Pharmacological interventions, including alpha-lipoic acid (ALA), resveratrol, curcumin and NAD⁺ precursors, exhibit therapeutic potential by enhancing insulin sensitivity, reducing oxidative burden, and restoring metabolic balance. This review synthesizes current advancements in FOXO-SIRT1 regulation, its emerging role in redox homeostasis, and its therapeutic relevance, offering insights into future strategies for combating metabolic dysfunction and aging-related diseases.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"65"},"PeriodicalIF":4.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514523","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":"Hypoxia-inducible factor and cellular senescence in pulmonary aging and disease.","authors":"Riya Thapa, Arockia Babu Marianesan, A Rekha, Subbulakshmi Ganesan, Mukesh Kumari, Asif Ahmad Bhat, Haider Ali, Sachin Kumar Singh, Amlan Chakraborty, Ronan MacLoughlin, Gaurav Gupta, Kamal Dua","doi":"10.1007/s10522-025-10208-z","DOIUrl":"10.1007/s10522-025-10208-z","url":null,"abstract":"<p><p>Cellular senescence and hypoxia-inducible factor (HIF) signaling are crucial in pulmonary aging and age-related lung diseases such as chronic obstructive pulmonary disease idiopathic pulmonary fibrosis and lung cancer. HIF plays a pivotal role in cellular adaptation to hypoxia, regulating processes like angiogenesis, metabolism, and inflammation. Meanwhile, cellular senescence leads to irreversible cell cycle arrest, triggering the senescence-associated secretory phenotype which contributes to chronic inflammation, tissue remodeling, and fibrosis. Dysregulation of these pathways accelerates lung aging and disease progression by promoting oxidative stress, mitochondrial dysfunction, and epigenetic alterations. Recent studies indicate that HIF and senescence interact at multiple levels, where HIF can both induce and suppress senescence, depending on cellular conditions. While transient HIF activation supports tissue repair and stress resistance, chronic dysregulation exacerbates pulmonary pathologies. Furthermore, emerging evidence suggests that targeting HIF and senescence pathways could offer new therapeutic strategies to mitigate age-related lung diseases. This review explores the intricate crosstalk between these mechanisms, shedding light on how their interplay influences pulmonary aging and disease progression. Additionally, we discuss potential interventions, including senolytic therapies and HIF modulators, that could enhance lung health and longevity.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"64"},"PeriodicalIF":4.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514549","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":"Rejuvenating the gut: young plasma therapy improves cell proliferation, IGF-I and IGF-IR expression, and immune defense in aged male rats jejunum.","authors":"Ender Deniz Asmaz, Murat Tan, Aysun Inan Genç, Hikmet Taner Teker, Taha Ceylani","doi":"10.1007/s10522-025-10204-3","DOIUrl":"10.1007/s10522-025-10204-3","url":null,"abstract":"<p><p>It is well known that aging affects many systems in the body. The digestive system is one of the systems most affected by aging. In our study, we examined the effects of young plasma treatment on cell proliferation, growth factors, immune defense and histological parameters in the jejunum of aged male rats. For this purpose, aged male Sprague Dawley rats (24 months, n = 7) were treated with pooled plasma (0.5 ml/day, intravenously for 30 days) collected from young (5 weeks, n = 51) rats. Aged rats that received young plasma treatment were grouped as the experimental group, while aged rats formed the control group. At the end of the experiment, the jejunums of the groups were collected and histological parameters such as villus height, crypt depth, total mucosal thickness and surface absorption areas were measured and compared. In addition, cell proliferation index and proliferation intensity in the crypt glands of the jejunum were evaluated with proliferating cell nuclear antigen and expressions of growth factors such as insulin-like growth factor I (IGF-I) and its receptor (IGF-IR) expression and effects of immunoglobulin A (IgA), which plays a role in the defense of the digestive system against microorganisms, were examined. In the experimental group, an increase in histological parameters, IGF-R and IGF-IR expression, proliferation density, proliferation index and IgA expression density and IgA cell count were observed compared to the control group. These results suggest that young plasma treatment has a positive effect on the digestive system and may be a potential therapeutic for tissue regeneration.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"62"},"PeriodicalIF":4.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447669","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":"Regulatory Roles of Exosomes in Aging and Aging-Related Diseases.","authors":"Nanyin Xiao, Qiao Li, Guangyu Liang, Zonghao Qian, Yan Lin, Heng Zhang, Yangguang Fu, Xiao Yang, Cun-Tai Zhang, Jiankun Yang, Anding Liu","doi":"10.1007/s10522-025-10200-7","DOIUrl":"https://doi.org/10.1007/s10522-025-10200-7","url":null,"abstract":"<p><p>Exosomes are small vesicles with diameters ranging from 30 to 150 nm. They originate from cellular endocytic systems. These vesicles contain a rich payload of biomolecules, including proteins, nucleic acids, lipids, and metabolic products. Exosomes mediate intercellular communication and are key regulators of a diverse array of biological processes, such as oxidative stress and chronic inflammation. Furthermore, exosomes have been implicated in the pathogenesis of infectious diseases, autoimmune disorders, and cancer. Aging is closely associated with the onset and progression of numerous diseases and is significantly influenced by exosomes. Recent studies have consistently highlighted the important functions of exosomes in the regulation of cellular senescence. Additionally, research has explored their potential to delay aging, such as the alleviatory effects of stem cell-derived exosomes on the aging process, which offers broad potential for the development and application of exosomes as anti-aging therapeutic strategies. This review aims to comprehensively investigate the multifaceted impact of exosomes while concurrently evaluating their potential applications and underscoring their strategic significance in advancing anti-aging strategies.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"61"},"PeriodicalIF":4.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447729","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":"Immune genes involved in synaptic plasticity during early postnatal brain development contribute to post-stroke damage in the aging male rat brain.","authors":"Denisa F V Pirscoveanu, Denissa Greta Olaru, Dirk M Hermann, Thorsten R Doeppner, Flavia Semida Ghinea, Aurel Popa-Wagner","doi":"10.1007/s10522-025-10203-4","DOIUrl":"https://doi.org/10.1007/s10522-025-10203-4","url":null,"abstract":"<p><p>Stroke remains a leading cause of mortality and long-term disability worldwide, underscoring the urgent need to identify novel therapeutic targets to enhance brain circuitry repair and functional recovery. This study explores the concept of longevity assurance genes, which primarily function within genetic pathways responsible for repair and maintenance. These pathways encompass molecular and metabolic processes as well as organ- and system-level functions. To investigate this, we employed comparative transcriptomics to analyze gene expression patterns across three age groups with progressively decreasing brain plasticity: native postnatal day seven brains, and young and old naïve and lesioned rat male brains. Analysis revealed a highly symmetrical distribution of upregulated and downregulated genes in postnatal day 7 brains. In contrast, the gene expression profiles of post-stroke brains exhibited significant asymmetry, with a disproportionate increase in upregulated genes compared to downregulated ones in both young and old post-ischemic brains. Gene variance in juvenile brains predominantly reflected processes associated with brain plasticity (e.g., Dcx, Tubb2b, Dok4, Dpysl5) and cell proliferation (e.g., Bex4). Conversely, gene expression variance in young and aged post-stroke brains was largely linked to inflammatory pathways, driven by cytokine and chemokine signaling. Notably, several genes specifically upregulated in aged brains were identified, including Ehd4, Fut7, Lilrb4, Plek, Slfn13, Slc14a1, and Smpdl3a. Immune genes that facilitate synaptic plasticity during early postnatal brain development-through processes such as pruning and sprouting to establish new connections in response to external stimuli-also contribute to post-stroke damage, confirming the concept of antagonistic pleiotropy. Our results suggest that targeting age-related immune responses could be an effective therapeutic strategy for stroke recovery.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"60"},"PeriodicalIF":4.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447759","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":"Transcriptional activation of genes associated with the matrisome is a common feature of senescent endothelial cells.","authors":"Ignacia González, Sebastián B Arredondo, Rodrigo Maldonado-Agurto","doi":"10.1007/s10522-025-10191-5","DOIUrl":"10.1007/s10522-025-10191-5","url":null,"abstract":"<p><p>Cellular senescence is a stable cell cycle arrest that occurs in response to various stress stimuli and affects multiple cell types, including endothelial cells (ECs). Senescent cells accumulate with age, and their removal has been linked to reduced age-related diseases. However, some senescent cells are important for tissue homeostasis. Therefore, understanding the diversity of senescent cells in a cell-type-specific manner and their underlying molecular mechanisms is essential. Senescence impairs key ECs functions which are necessary for vascular homeostasis, leading to endothelial dysfunction and age-related vascular diseases. In order to gain insights into these mechanisms, we analyzed publicly available RNA-seq datasets to identify gene expression changes in senescent ECs induced by doxorubicin, irradiation, and replication exhaustion. While only a few genes were consistently differentially expressed across all conditions, some gene ontologies (GO) were shared. Among these, our analysis focused on validating the expression of genes associated with the matrisome, which includes genes encoding for extracellular matrix (ECM) structural components and ECM-associated proteins, in a doxorubicin-induced senescence model. Our results show that the matrisome transcriptome undergoes significant remodeling in senescent endothelial cells, regardless of the specific inducers of senescence, highlighting the importance of understanding how ECM alterations affect senescence.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"59"},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413305","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":"Plasma therapy: a novel intervention to improve age-induced decline in deudenal cell proliferation in female rat model.","authors":"Ender Deniz Asmaz, Taha Ceylani, Aysun İnan Genc, Zeynep Tuğçe Sertkaya, Hikmet Taner Teker","doi":"10.1007/s10522-025-10197-z","DOIUrl":"10.1007/s10522-025-10197-z","url":null,"abstract":"<p><p>Aging is associated with a disruptive decline in gastrointestinal health leading to decreased duodenal cell proliferation ultimately affecting the digestive and absorptive capacity of intestines in all species. This study investigates the novel application of blood plasma therapy to enhance duodenal cell proliferation associated with aging. In the presented study, the effects of middle aged plasma therapy on the aged rat duodenum were investigated. For this purpose, using a randomized controlled design, Female Wistar rats (aged 12-15 months) (n:7) were treated with heterologus pooled plasma (0.5 mL per day for 30 days, infused intravenously into the tail vein) collected from middle aged (6 months old, n:28) rats during all stages of the estrous cycle. The groups were divided into three as the Experimental group (aged 12-15 months) receiving middle aged plasma, the control group (aged 12-15 months) not receiving treatment, and the middle aged rat (6 months) as the positive control group. At the end of the experiment, each group's duodenum were collected, fixed, and analyzed using histological techniques for morphometric parameters. Additionally cell proliferation density and proliferation index were determined by proliferating cell nuclear antigen (PCNA). The finding of the study suggests that plasma therapy significantly improves cell proliferation, villus height (µm), crypt depth (µm), total mucosal thickness (µm), the ratio of villus height to crypt depth (µm), and surface absorption area (mm²) in the experimental group compared to control. Likewise, we determined that middle aged plasma application supports cell proliferation. However, further research is warranted to explore the underlying mechanisms and potential clinical applications of this innovative approach.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"57"},"PeriodicalIF":4.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370364","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}