Aging Cell最新文献

{"title":"Intersection clock reveals a rejuvenation event during human embryogenesis","authors":"Csaba Kerepesi,&nbsp;Vadim N. Gladyshev","doi":"10.1111/acel.13922","DOIUrl":"10.1111/acel.13922","url":null,"abstract":"<p>Recent research revealed a rejuvenation event during early development of mice. Here, by examining epigenetic age dynamics of human embryogenesis, we tested whether a similar event exists in humans. For this purpose, we developed an epigenetic clock method, the intersection clock, that utilizes bisulfite sequencing in a way that maximizes the use of informative CpG sites with no missing clock CpG sites in test samples and applied it to human embryo development data. We observed no changes in the predicted epigenetic age between cleavage stage and blastocyst stage embryos; however, a significant decrease was observed between blastocysts and cells representing the epiblast. Additionally, by applying the intersection clock to datasets spanning pre and postimplantation, we found no significant change in the epigenetic age during preimplantation stages; however, the epigenetic age of postimplantation samples was lower compared to the preimplantation stages. We further investigated the epigenetic age of primed (representing early postimplantation) and naïve (representing preimplantation) pluripotent stem cells and observed that in all cases the epigenetic age of primed cells was significantly lower than that of naïve cells. Together, our data suggest that human embryos are rejuvenated during early embryogenesis. Hence, the rejuvenation event is conserved between the mouse and human, and it occurs around the gastrulation stage in both species. Beyond this advance, the intersection clock opens the way for other epigenetic age studies based on human bisulfite sequencing datasets as opposed to methylation arrays.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13922","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093534","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":"Transcriptional changes of the aging lung","authors":"Minxue Jia,&nbsp;Paula A. Agudelo Garcia,&nbsp;Jose A. Ovando-Ricardez,&nbsp;Tracy Tabib,&nbsp;Humberto T. Bittar,&nbsp;Robert A. Lafyatis,&nbsp;Ana L. Mora,&nbsp;Panayiotis V. Benos,&nbsp;Mauricio Rojas","doi":"10.1111/acel.13969","DOIUrl":"10.1111/acel.13969","url":null,"abstract":"<p>Aging is a natural process associated with declined organ function and higher susceptibility to developing chronic diseases. A systemic single-cell type-based study provides a unique opportunity to understand the mechanisms behind age-related pathologies. Here, we use single-cell gene expression analysis comparing healthy young and aged human lungs from nonsmoker donors to investigate age-related transcriptional changes. Our data suggest that aging has a heterogenous effect on lung cells, as some populations are more transcriptionally dynamic while others remain stable in aged individuals. We found that monocytes and alveolar macrophages were the most transcriptionally affected populations. These changes were related to inflammation and regulation of the immune response. Additionally, we calculated the LungAge score, which reveals the diversity of lung cell types during aging. Changes in DNA damage repair, fatty acid metabolism, and inflammation are essential for age prediction. Finally, we quantified the senescence score in aged lungs and found that the more biased cells toward senescence are immune and progenitor cells. Our study provides a comprehensive and systemic analysis of the molecular signatures of lung aging. Our LungAge signature can be used to predict molecular signatures of physiological aging and to detect common signatures of age-related lung diseases.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13969","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10598259","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":"Erratum to: The variant senescence-associated secretory phenotype induced by centrosome amplification constitutes a pathway that activates hypoxia-inducible factor-1α","authors":"","doi":"10.1111/acel.13991","DOIUrl":"10.1111/acel.13991","url":null,"abstract":"<p>Wu, S. K., Ariffin, J., Chian, T. S., &amp; Picone, R. (2023). The variant senescence-associated secretory phenotype induced by centrosome amplification constitutes a pathway that activates hypoxia-inducible factor-1α. <i>Aging Cell</i>, 22, e13766. https://doi.org/10.1111/acel.13766.</p><p>In the published version of Wu et al (2023), the current affiliation, Mechanobiology Institute &amp; Department of Biological Sciences, National University of Singapore, Singapore is incorrectly linked to the authors' Juliana Arrifin and Remigio Picone instead of Selwin K. Wu.</p><p>The present address should be displayed as follows:</p><p>\u0000 <b>Present address.</b>\u0000 </p><p>Selwin K. Wu, Mechanobiology Institute &amp; Department of Biological Sciences, National University of Singapore, Singapore.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10200796","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":"Epigenomic signature of accelerated ageing in progeroid Cockayne syndrome","authors":"Clément Crochemore,&nbsp;Claudia Chica,&nbsp;Paolo Garagnani,&nbsp;Giovanna Lattanzi,&nbsp;Steve Horvath,&nbsp;Alain Sarasin,&nbsp;Claudio Franceschi,&nbsp;Maria Giulia Bacalini,&nbsp;Miria Ricchetti","doi":"10.1111/acel.13959","DOIUrl":"10.1111/acel.13959","url":null,"abstract":"<p>Cockayne syndrome (CS) and UV-sensitive syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and multifunctional CSA or CSB protein, but only CS patients display a progeroid and neurodegenerative phenotype, providing a unique conceptual and experimental paradigm. As DNA methylation (DNAm) remodelling is a major ageing marker, we performed genome-wide analysis of DNAm of fibroblasts from healthy, UVSS and CS individuals. Differential analysis highlighted a CS-specific epigenomic signature (progeroid-related; not present in UVSS) enriched in three categories: developmental transcription factors, ion/neurotransmitter membrane transporters and synaptic neuro-developmental genes. A large fraction of CS-specific DNAm changes were associated with expression changes in CS samples, including in previously reported <i>post-mortem</i> cerebella. The progeroid phenotype of CS was further supported by epigenomic hallmarks of ageing: the prediction of DNAm of repetitive elements suggested an hypomethylation of <i>Alu</i> sequences in CS, and the epigenetic clock returned a marked increase in CS biological age respect to healthy and UVSS cells. The epigenomic remodelling of accelerated ageing in CS displayed both commonalities and differences with other progeroid diseases and regular ageing. CS shared DNAm changes with normal ageing more than other progeroid diseases do, and included genes functionally validated for regular ageing. Collectively, our results support the existence of an epigenomic basis of accelerated ageing in CS and unveil new genes and pathways that are potentially associated with the progeroid/degenerative phenotype.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13959","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178842","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":"Intact mitochondrial function in the setting of telomere-induced senescence","authors":"Daniel I. Sullivan,&nbsp;Fiona M. Bello,&nbsp;Agustin Gil Silva,&nbsp;Kevin M. Redding,&nbsp;Luca Giordano,&nbsp;Angela M. Hinchie,&nbsp;Kelly E. Loughridge,&nbsp;Ana L. Mora,&nbsp;Melanie Königshoff,&nbsp;Brett A. Kaufman,&nbsp;Michael J. Jurczak,&nbsp;Jonathan K. Alder","doi":"10.1111/acel.13941","DOIUrl":"10.1111/acel.13941","url":null,"abstract":"<p>Mitochondria play essential roles in metabolic support and signaling within all cells. Congenital and acquired defects in mitochondria are responsible for several pathologies, including premature entrance to cellar senescence. Conversely, we examined the consequences of dysfunctional telomere-driven cellular senescence on mitochondrial biogenesis and function. We drove senescence in vitro and in vivo by deleting the telomere-binding protein TRF2 in fibroblasts and hepatocytes, respectively. Deletion of TRF2 led to a robust DNA damage response, global changes in transcription, and induction of cellular senescence. In vitro, senescent cells had significant increases in mitochondrial respiratory capacity driven by increased cellular and mitochondrial volume. Hepatocytes with dysfunctional telomeres maintained their mitochondrial respiratory capacity in vivo, whether measured in intact cells or purified mitochondria. Induction of senescence led to the upregulation of overlapping and distinct genes in fibroblasts and hepatocytes, but transcripts related to mitochondria were preserved. Our results support that mitochondrial function and activity are preserved in telomere dysfunction-induced senescence, which may facilitate continued cellular functions.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10187590","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":"Deciphering RNA m6A regulation in aging: Perspectives on current advances and future directions","authors":"Zeming Wu,&nbsp;Jie Ren,&nbsp;Guang-Hui Liu","doi":"10.1111/acel.13972","DOIUrl":"https://doi.org/10.1111/acel.13972","url":null,"abstract":"<p>N⁶-methyladenosine (m⁶A) is a dynamic and reversible RNA modification that has emerged as a crucial player in the life cycle of RNA, thus playing a pivotal role in various biological processes. In recent years, the potential involvement of RNA m⁶A modification in aging and age-related diseases has gained increasing attention, making it a promising target for understanding the molecular mechanisms underlying aging and developing new therapeutic strategies. This Perspective article will summarize the current advances in aging-related m⁶A regulation, highlighting the most significant findings and their implications for our understanding of cellular senescence and aging, and the potential for targeting RNA m⁶A regulation as a therapeutic strategy. We will also discuss the limitations and challenges in this field and provide insights into future research directions. By providing a comprehensive overview of the current state of the field, this Perspective article aims to facilitate further advances in our understanding of the molecular mechanisms underlying aging and to identify new therapeutic targets for aging-related diseases.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13972","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41230096","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":"Fingerstick blood assay maps real-world NAD+ disparity across gender and age","authors":"Pei Wang,&nbsp;Meiting Chen,&nbsp;Yaying Hou,&nbsp;Jun Luan,&nbsp;Ruili Liu,&nbsp;Liuqing Chen,&nbsp;Min Hu,&nbsp;Qiuliyang Yu","doi":"10.1111/acel.13965","DOIUrl":"https://doi.org/10.1111/acel.13965","url":null,"abstract":"<p>Nicotinamide adenine dinucleotide (NAD⁺) level has been associated with various age-related diseases and its pharmacological modulation emerges as a potential approach for aging intervention. But human NAD⁺ landscape exhibits large heterogeneity. The lack of rapid, low-cost assays limits the establishment of whole-blood NAD⁺ baseline and the development of personalized therapies, especially for those with poor responses towards conventional NAD⁺ supplementations. Here, we developed an automated NAD⁺ analyzer for the rapid measurement of NAD⁺ with 5 μL of capillary blood using recombinant bioluminescent sensor protein and automated optical reader. The minimal invasiveness of the assay allowed a frequent and decentralized mapping of real-world NAD⁺ dynamics. We showed that aerobic sport and NMN supplementation increased whole-blood NAD⁺ and that male on average has higher NAD⁺ than female before the age of 50. We further revealed the long-term stability of human NAD⁺ baseline over 100 days and identified major real-world NAD⁺-modulating behaviors.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41229815","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":"Sex- and APOE-specific genetic risk factors for late-onset Alzheimer's disease: Evidence from gene–gene interaction of longevity-related loci","authors":"Serena Dato,&nbsp;Francesco De?Rango,&nbsp;Paolina Crocco,&nbsp;Stefano Pallotti,&nbsp;Michael E. Belloy,&nbsp;Yann Le?Guen,&nbsp;Michael D. Greicius,&nbsp;Giuseppe Passarino,&nbsp;Giuseppina Rose,&nbsp;Valerio Napolioni","doi":"10.1111/acel.13938","DOIUrl":"https://doi.org/10.1111/acel.13938","url":null,"abstract":"<p>Advanced age is the largest risk factor for late-onset Alzheimer's disease (LOAD), a disease in which susceptibility correlates to almost all hallmarks of aging. Shared genetic signatures between LOAD and longevity were frequently hypothesized, likely characterized by distinctive epistatic and pleiotropic interactions. Here, we applied a multidimensional reduction approach to detect gene–gene interactions affecting LOAD in a large dataset of genomic variants harbored by genes in the insulin/IGF1 signaling, DNA repair, and oxidative stress pathways, previously investigated in human longevity. The dataset was generated from a collection of publicly available Genome Wide Association Studies, comprising a total of 2,469 gene variants genotyped in 20,766 subjects of Northwestern European ancestry (11,038 LOAD cases and 9,728 controls). The stratified analysis according to <i>APOE</i>*4 status and sex corroborated evidence that pathways leading to longevity also contribute to LOAD. Among the significantly interacting genes, <i>PTPN1</i>, <i>TXNRD1</i>, and <i>IGF1R</i> were already found enriched in gene–gene interactions affecting survival to old age. Furthermore, interacting variants associated with LOAD in a sex- and <i>APOE</i>-specific way. Indeed, while in <i>APOE</i>*4 female carriers we found several inter-pathway interactions, no significant epistasis was found in <i>APOE</i>*4 negative females; conversely, in males, significant intra- and inter-pathways epistasis emerged according to <i>APOE</i>*4 status. These findings suggest that interactions of risk factors may drive different trajectories of cognitive aging. Beyond helping to disentangle the genetic architecture of LOAD, such knowledge may improve precision in predicting the risk of dementia and enable effective sex- and <i>APOE</i>-stratified preventive and therapeutic interventions for LOAD.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13938","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"7004182","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":"Alterations of lipid-mediated mitophagy result in aging-dependent sensorimotor defects","authors":"Natalia Oleinik,&nbsp;Onder Albayram,&nbsp;Mohamed Faisal Kassir,&nbsp;F. Cansu Atilgan,&nbsp;Chase Walton,&nbsp;Eda Karakaya,&nbsp;John Kurtz,&nbsp;Alexander Alekseyenko,&nbsp;Habeeb Alsudani,&nbsp;Megan Sheridan,&nbsp;Zdzislaw M. Szulc,&nbsp;Besim Ogretmen","doi":"10.1111/acel.13954","DOIUrl":"10.1111/acel.13954","url":null,"abstract":"<p>The metabolic consequences of mitophagy alterations due to age-related stress in healthy aging brains versus neurodegeneration remain unknown. Here, we demonstrate that ceramide synthase 1 (CerS1) is transported to the outer mitochondrial membrane by the p17/PERMIT transporter that recognizes mislocalized mitochondrial ribosomes (mitoribosomes) via 39-FLRN-42 residues, inducing ceramide-mediated mitophagy. P17/PERMIT-CerS1-mediated mitophagy attenuated the argininosuccinate/fumarate/malate axis and induced <span>d</span>-glucose and fructose accumulation in neurons in culture and brain tissues (primarily in the cerebellum) of wild-type mice in vivo. These metabolic changes in response to sodium-selenite were nullified in the cerebellum of CerS1to/to (catalytically inactive for C18-ceramide production CerS1 mutant), PARKIN−/− or p17/PERMIT−/− mice that have dysfunctional mitophagy. Whereas sodium selenite induced mitophagy in the cerebellum and improved motor-neuron deficits in aged wild-type mice, exogenous fumarate or malate prevented mitophagy. Attenuating ceramide-mediated mitophagy enhanced damaged mitochondria accumulation and age-dependent sensorimotor abnormalities in p17/PERMIT−/− mice. Reinstituting mitophagy using a ceramide analog drug with selenium conjugate, LCL768, restored mitophagy and reduced malate/fumarate metabolism, improving sensorimotor deficits in old p17/PERMIT−/− mice. Thus, these data describe the metabolic consequences of alterations to p17/PERMIT/ceramide-mediated mitophagy associated with the loss of mitochondrial quality control in neurons and provide therapeutic options to overcome age-dependent sensorimotor deficits and related disorders like amyotrophic lateral sclerosis (ALS).</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13954","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060942","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":"Inhibition of abnormal C/EBPβ/α-Syn signaling pathway through activation of Nrf2 ameliorates Parkinson's disease-like pathology","authors":"Zefang Lin,&nbsp;Lixuan Huang,&nbsp;Qianqian Cao,&nbsp;Hanyue Luo,&nbsp;Wei Yao,&nbsp;Ji-chun Zhang","doi":"10.1111/acel.13958","DOIUrl":"10.1111/acel.13958","url":null,"abstract":"<p>Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs) in the brain. These LBs are primarily composed of α-Synuclein (α-Syn), which has aggregated. A recent report proposes that CCAAT/enhancer-binding proteins β (C/EBPβ) may act as an age-dependent transcription factor for α-Syn, thereby initiating PD pathologies by regulating its transcription. Potential therapeutic approaches to address PD could involve targeting the regulation of α-Syn by C/EBPβ. This study has revealed that Nrf2, also known as nuclear factor (erythroid-derived 2)-like 2 (NFE2L2), suppresses the transcription of C/EBPβ in SH-SY5Y cells when treated with MPP⁺. To activate Nrf2, sulforaphane, an Nrf2 activator, was administered. Additionally, C/EBPβ was silenced using C/EBPβ-DNA/RNA heteroduplex oligonucleotide (HDO). Both approaches successfully reduced abnormal α-Syn expression in primary neurons treated with MPP⁺. Furthermore, sustained activation of Nrf2 via its activator or inhibition of C/EBPβ using C/EBPβ-HDO resulted in a reduction of aberrant α-Syn expression, thus leading to an improvement in the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) in mouse models induced by 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and those treated with preformed fibrils (PFFs). The data presented in this study illustrate that the activation of Nrf2 may provide a potential therapeutic strategy for PD by inhibiting the abnormal C/EBPβ/α-Syn signaling pathway.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13958","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10435090","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}