Aging Cell最新文献

{"title":"The Redox Activity of Protein Disulphide Isomerase Functions in Non-Homologous End-Joining Repair to Prevent DNA Damage.","authors":"Sina Shadfar, Fabiha Farzana, Sayanthooran Saravanabavan, Ashley M Rozario, Marta Vidal, Cyril Jones Jagaraj, Sonam Parakh, Esmeralda Paric, Kristy C Yuan, Mariana Brocardo, Donna R Whelan, Angela S Laird, Julie D Atkin","doi":"10.1111/acel.70079","DOIUrl":"https://doi.org/10.1111/acel.70079","url":null,"abstract":"<p><p>DNA damage is a serious threat to cellular viability, and it is implicated as the major cause of normal ageing. Hence, targeting DNA damage therapeutically may counteract age-related cellular dysfunction and disease, such as neurodegenerative conditions and cancer. Identifying novel DNA repair mechanisms therefore reveals new therapeutic interventions for multiple human diseases. In neurons, non-homologous end-joining (NHEJ) is the only mechanism available to repair double-stranded DNA breaks (DSB), which is much more error prone than other DNA repair processes. However, there are no therapeutic interventions to enhance DNA repair in diseases affecting neurons. NHEJ is also a useful target for DNA repair-based cancer therapies to selectively kill tumour cells. Protein disulphide isomerase (PDI) participates in many diseases, but its roles in these conditions remain poorly defined. PDI exhibits both chaperone and redox-dependent oxidoreductase activity, and while primarily localised in the endoplasmic reticulum it has also been detected in other cellular locations. We describe here a novel role for PDI in DSB repair following at least two types of DNA damage. PDI functions in NHEJ, and following DNA damage, it relocates to the nucleus, where it co-localises with critical DSB repair proteins at DNA damage foci. A redox-inactive mutant of PDI lacking its two active site cysteine residues was not protective, however. Hence, the redox activity of PDI mediates DNA repair, highlighting these cysteines as targets for therapeutic intervention. The therapeutic potential of PDI was also confirmed by its protective activity in a whole organism against DNA damage induced in vivo in zebrafish. Hence, harnessing the redox function of PDI has potential as a novel therapeutic target against DSB DNA damage relevant to several human diseases.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70079"},"PeriodicalIF":8.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074880","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}

{"title":"Ythdf2 Ablation Protects Aged Retina From RGC Dendrite Shrinking and Visual Decline.","authors":"Fugui Niu, Gaoxin Long, Jian Zhang, Jun Yu, Sheng-Jian Ji","doi":"10.1111/acel.70107","DOIUrl":"https://doi.org/10.1111/acel.70107","url":null,"abstract":"<p><p>Aging-related retinal degeneration and vision loss have been severely affecting the elderly worldwide. Previously, we showed that the m⁶A reader YTHDF2 is a negative regulator for dendrite development and protection of retinal ganglion cells (RGC) in mice. Here, we further show that conditional ablation of Ythdf2 protects the retina from RGC dendrite shrinking and vision loss in aged mice. Additionally, we identify Hspa12a and Islr2 as the potential YTHDF2 target mRNAs mediating these effects. Together, our results indicate that the m⁶A reader YTHDF2 regulates retinal degeneration caused by aging, which might provide important therapeutic potential for developing new treatment approaches against aging-related vision loss.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70107"},"PeriodicalIF":8.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074883","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}

{"title":"Single-Cell RNA-Seq Reveals Aging-Related Impairment of Microglial Efferocytosis Contributing to Apoptotic Cells Accumulation After Retinal Injury.","authors":"Pan Liu, Qi Wang, Shuimiao Wang, Ying Liu, Qiqi Chen, Wanyun Qin, Xinna Liu, Xinqi Ye, Yexuan Jiao, Huiping Yuan, Zhengbo Shao","doi":"10.1111/acel.70097","DOIUrl":"https://doi.org/10.1111/acel.70097","url":null,"abstract":"<p><p>Aging is associated with increased retinal cell apoptosis, which contributes to decreases in retinal function. Apoptotic retinal cell clearance relies on microglial efferocytosis, but the impact of aging on this process has not been fully elucidated. In this study, we aimed to shed light on this by using single-cell RNA sequencing (sc-RNA-seq) to compare young and aged mouse retinal transcriptional profiles, in which 74,412 retinal cells from young and aged mice were classified into 10 transcriptionally distinct retinal cell types, and differentially expressed genes between young versus aged retinas were mainly associated with cellular senescence and apoptosis. Furthermore, ligand-receptor interactions (e.g., AXL-GAS6, MERTK-GAS6) between microglia and other retinal cells were strengthened in aged, compared to young retinas. Additionally, among microglia, Subcluster 4 was found under partial clustering to be associated with efferocytosis, of which aged microglia had downregulated efferocytosis-associated genes. The impact of aging on microglial efferocytosis was further verified in vitro by doxorubicin (DOX)-induced senescent BV2 microglia, and in vivo by a retinal ischemia/reperfusion (I/R) injury mouse model. In vitro, DOX-treated BV2 microglia had significantly lowered efferocytosis, as well as efferocytosis-related MerTK and Axl protein expression; this was also present in vivo in aged retinas post-I/R injury, with increased co-localization of ionized calcium-binding adapter molecule 1⁺ microglia with apoptotic retinal cells, along with reduced efferocytosis-related protein expression. Overall, microglial efferocytosis of apoptotic cells decreased with aging, suggesting that modulating this process could serve as a possible therapeutic target for age-related retinal diseases.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70097"},"PeriodicalIF":8.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074876","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}

{"title":"Quercetin Reduces Vascular Senescence and Inflammation in Symptomatic Male but Not Female Coronary Artery Disease Patients.","authors":"Pauline Mury, Olina Dagher, Annik Fortier, Ariel Diaz, Yoan Lamarche, Pierre-Emmanuel Noly, Marina Ibrahim, Pierre Pagé, Philippe Demers, Denis Bouchard, Pierre-Luc Bernier, Nancy Poirier, Emmanuel Moss, Nicolas Durrleman, Hughes Jeanmart, Michel Pellerin, Guillaume Lettre, Nathalie Thorin-Trescases, Michel Carrier, Eric Thorin","doi":"10.1111/acel.70108","DOIUrl":"https://doi.org/10.1111/acel.70108","url":null,"abstract":"<p><p>Recent studies suggest that vascular senescence and its associated inflammation fuel the inflammaging to favor atherogenesis; whether these pathways can be therapeutically targeted in coronary artery disease (CAD) patients remains unknown. In a randomized, double-blind trial, 97 patients (78 men) undergoing coronary artery bypass graft surgery were treated with either quercetin (500 mg twice daily, 47 patients) or placebo (50 patients) for two days pre-surgery through hospital discharge. Primary outcomes were reduced inflammation and improved endothelial function ex vivo. Exploratory analyses included plasma proteomics and single-nuclei RNA sequencing of internal thoracic artery (ITA) samples. Quercetin treatment showed a trend toward reduced C-reactive protein at discharge (p = 0.073) and differentially modulated circulating inflammatory protein expression between men and women, with a pro-inflammatory effect of quercetin in females. Endothelial acetylcholine-induced relaxation improved significantly with quercetin (p = 0.049), with effects in men (p = 0.043) but not in women (p = 0.852). ITA transcriptomics revealed the overexpression of senescence and inflammaging pathways in male vascular cells, which quercetin reversed. In female cells, quercetin had minimal endothelial benefit and increased inflammaging in fibroblasts. In male cells, a candidate target of quercetin involves interactions between the receptor PLAUR and its ligands PLAU and SERPINE1. Post-operative atrial fibrillation incidence was significantly lower with quercetin, representing 4% of the patients compared to 18% in the placebo group (p = 0.033). In conclusion, short-term quercetin treatment effectively targeted vascular senescence in male CAD patients, improving inflammatory and functional outcomes. However, these benefits were not observed in female patients. Trial Registration: https://clinicaltrials.gov, NCT04907253.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70108"},"PeriodicalIF":8.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075218","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}

{"title":"Human and Mouse Alzheimer's Seeds Differentially Affect Amyloid Deposition and Microglia-Dependent Plaque Response in Aged Mice.","authors":"Juana Andreo-Lopez, Cristina Nuñez-Diaz, Kelly Do Huynh, Marie Minh Thu Nguyen, Celia Da Cunha, Francisco J Cantero-Molina, Cynthia Campos-Moreno, Stefania Zimbone, Francesco Bellia, Maria Laura Giuffrida, Laura Trujillo-Estrada, Juan Antonio Garcia-Leon, Miriam Bettinetti-Luque, Nazaret Gamez, Catalina Valdes, Rodrigo Morales, Stefania Forner, Alessandra C Martini, Antonia Gutierrez, Frank M LaFerla, David Baglietto-Vargas","doi":"10.1111/acel.70094","DOIUrl":"https://doi.org/10.1111/acel.70094","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex neurodegenerative proteinopathy in which Aβ and tau misfold and aggregate into entities that structurally unsettle native proteins, mimicking a prion-like or \"seeding\" process. These Aβ and tau \"seeds\" can arrange in different conformations or strains that might display distinct pathogenic properties. Furthermore, recent evidence suggests that microglia play a key role in the amyloidogenic event and can modulate the propagation and aggregation processes. Here, we employed histological and molecular approaches to determine whether seeds from human AD brains compared to those from transgenic mice (3xTg-AD) are more prone to induce Aβ and tau aggregates in vivo, as well as potential differences in the microglial response to the plaque pathology. Brain homogenates were injected into the hippocampus of 3xTg-AD mice and hAβ-KI mice and examined at 18-20 months of age. The seeds from the human AD brain induced more aggressive amyloid pathology compared to seeds from aged 3xTg-AD mice. However, the AD seeds from aged transgenic mice triggered more tau pathology. Interestingly, such mice seeds impaired microglial clustering around plaques, leading to more severe neuritic pathology. Furthermore, the human AD seeds injected into the hippocampus of hAβ-KI mice were not able to induce plaque formation. These results suggest that multiple variables such as the AD seed, recipient model, and time are critical factors that can modulate the amyloid pathology onset and progression. Thus, more profound understanding of these factors will provide key insight into how amyloid and tau pathology progresses in AD.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70094"},"PeriodicalIF":8.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951607","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}

{"title":"DLK/JNK3 Upregulation Aggravates Hair Cell Senescence in Mice Cochleae via Excessive Autophagy.","authors":"Rui Ding, Weiyi Huang, Chenling Shen, Yi Pan, Yiming Zhong, Bing Kong, Yilin Shen, Mingliang Xiang, Bin Ye","doi":"10.1111/acel.70099","DOIUrl":"https://doi.org/10.1111/acel.70099","url":null,"abstract":"<p><p>Cell death mediated by the abnormal activation of autophagy has been observed in many neurodegenerative diseases. Dual leucine zipper kinase (DLK), a member of the mitogen-activated protein kinase cascade, plays a key role in regulating cellular autophagy and the progression of neurodegenerative diseases. However, its role in age-related hearing loss has not been reported. In this study, we found that DLK, phosphorylated c-Jun N-terminal kinase (p-JNK), and JNK3 expression increased in the cochleae of C57BL/6J mice during aging. The DLK/JNK pathway and autophagy are excessively activated in the House Ear Institute-Organ of Corti 1 (HEI-OC1) senescent hair cell line. After DLK was upregulated in HEI-OC1 cells, autophagy was activated, and cell aging was initiated. Inhibiting the DLK/JNK pathway in senescent HEI-OC1 cells can reduce autophagy activation and senescence, and inhibiting autophagy activation can also alleviate senescence. The inhibition of DLK or JNK3 in vivo significantly reduced age-related cochlear structural damage and hearing loss in C57BL/6J mice. The results of the present study showed that DLK/JNK3 may play a key role in cochlear hair cell senescence and age-related hearing loss through the abnormal activation of autophagy within cochlear hair cells, suggesting that DLK or JNK3 may be potential targets for alleviating age-related hearing loss.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70099"},"PeriodicalIF":8.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953927","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}

{"title":"dVGLUT Is a Mediator of Sex Differences in Dopamine Neuron Mitochondrial Function Across Aging and in a Parkinson's Disease Model.","authors":"Silas A Buck, Samuel J Mabry, Tenzin Kunkhyen, Zilu Yang, Sophie A Rubin, Jinting Yang, Claire E J Cheetham, Zachary Freyberg","doi":"10.1111/acel.70096","DOIUrl":"https://doi.org/10.1111/acel.70096","url":null,"abstract":"<p><p>Sex differences in Parkinson's disease (PD) offer insights into mechanisms of dopaminergic cell resilience. Female dopamine (DA) neurons are more resilient via mechanisms that remain unclear. Here, we discovered key sex and regional differences in mitochondrial generation of cytotoxic reactive oxygen species (ROS) and their implications for DA neuron resilience using the Drosophila model. While aging raised mitochondrial ROS in DA neurons of both sexes, we observed a sexually dimorphic response in the paraquat (PQ) PD model. DA neuron knockdown of the Drosophila vesicular glutamate transporter (dVGLUT) increased mitochondrial ROS only in males, leaving females protected. Cell depolarization, a physiological stressor, similarly raised mitochondrial ROS in DA neurons selectively in males following dVGLUT knockdown. We also identified dVGLUT-dependent changes in intracellular ATP in both sexes. Overall, we discovered sexually dimorphic relationships between dVGLUT, ATP synthesis, and ROS generation in DA neurons, providing a mechanistic basis for DA neuron resilience.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70096"},"PeriodicalIF":8.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954158","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}

{"title":"SGLT2 Inhibition by Enavogliflozin Significantly Reduces Aβ Pathology and Restores Cognitive Function via Upregulation of Microglial AMPK Signaling in 5XFAD Mouse Model of Alzheimer's Disease.","authors":"Jihui Han, Jaehoon Song, Eun Sun Jung, Ji Won Choi, Hye Young Ji, Inhee Mook-Jung","doi":"10.1111/acel.70101","DOIUrl":"https://doi.org/10.1111/acel.70101","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. Metabolic dysfunctions, particularly type 2 diabetes mellitus (T2DM), have been implicated in AD pathogenesis, highlighting the potential for novel therapeutic approaches targeting shared underlying mechanisms. Here, we investigate sodium-glucose cotransporter 2 (SGLT2) inhibition as a therapeutic strategy for AD using Enavogliflozin, a potent SGLT2 inhibitor, in the 5XFAD mouse model. Five-month-old 5XFAD mice were treated with Enavogliflozin (0.1 or 1 mg/kg) or vehicle for 8 weeks. The higher dose significantly improved cognitive performance in Y-maze and Morris Water Maze tests, which correlated with enhanced synaptic plasticity and increased acetylcholine levels. Moreover, Enavogliflozin treatment reduced Aβ pathology and plaque burden, particularly affecting larger plaques. Mechanistically, SGLT2 inhibition attenuated neuroinflammation by suppressing NF-κB signaling and proinflammatory cytokine production while promoting microglial recruitment to plaques. In vitro and ex vivo analyses further revealed that Enavogliflozin enhances microglial phagocytic capacity via AMPK-mediated mitochondrial biogenesis and function. These findings highlight the multifaceted neuroprotective effects of SGLT2 inhibition in AD, demonstrating its potential to mitigate pathology and improve cognitive function. By uncovering its impact on neuroinflammation and microglial function, this study establishes SGLT2 inhibition as a promising therapeutic avenue for AD and other neurodegenerative disorders.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70101"},"PeriodicalIF":8.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957685","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}

{"title":"SQSTM1/p62 Orchestrates Skin Aging via USP7 Degradation.","authors":"Liu Chen, Xiaoping Wang, Yuchen Wang, Qingxin Yao, Yunyao Liu, Yongcheng Zhu, He Huang, Hedan Yang, Yin Yang, Yuan He, Lei Qiang","doi":"10.1111/acel.70078","DOIUrl":"https://doi.org/10.1111/acel.70078","url":null,"abstract":"<p><p>Skin aging is a complex process driven by intrinsic genetic factors and extrinsic environmental influences. In this study, sequestosome1 (SQSTM1/p62) was identified as a key regulator of senescence, the senescence-associated secretory phenotype (SASP), and skin aging. Notably, p62 expression is reduced in senescent cells and aging skin of both humans and mice. The depletion of p62 in the epidermis was found to be positively associated with accelerated aging and the initiation of SASP. Mechanistically, p62 inhibits the accumulation of ubiquitin-specific protease 7 (USP7) during senescence induction by orchestrating its degradation through specific binding interactions. In particular, the Tyr-67 residue within the PB1 domain or Gln-418 within the UBA domain of p62 forms a hydrogen bond with Ala-993 in the Ubl5 domain of USP7. Mutations in either Tyr-67 or Gln-418 of p62, or Ala-993 of USP7, resulted in the induction of cellular senescence, highlighting the critical role of these molecular interactions in the regulation of aging processes.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70078"},"PeriodicalIF":8.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956977","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}

{"title":"Multi-Omic Associations of Epigenetic Age Acceleration Are Heterogeneously Shaped by Genetic and Environmental Influences.","authors":"Gabin Drouard, Sannimari Suhonen, Aino Heikkinen, Zhiyang Wang, Jaakko Kaprio, Miina Ollikainen","doi":"10.1111/acel.70088","DOIUrl":"https://doi.org/10.1111/acel.70088","url":null,"abstract":"<p><p>Connections between the multi-ome and epigenetic age acceleration (EAA), and especially whether these are influenced by genetic or environmental factors, remain underexplored. We therefore quantified associations between the multi-ome comprising four layers-the proteome, metabolome, external exposome (here, sociodemographic factors), and specific exposome (here, lifestyle)-with six different EAA estimates. Two twin cohorts were used in a discovery-replication scheme, comprising, respectively, young (N = 642; mean age = 22.3) and older (N = 354; mean age = 62.3) twins. Within-pair twin designs were used to assess genetic and environmental effects on associations. We identified 40 multi-omic factors, of which 28 were proteins, associated with EAA in the young twins while adjusting for sex, smoking, and body mass index. Within-pair analyses revealed that genetic confounding influenced these associations heterogeneously, with six multi-omic factors -matrix metalloproteinase 9, complement component C6, histidine, glycoprotein acetyls, lactate, and neighborhood percentage of nonagenarians- remaining significantly associated with EAA, independent of genetic effects. Replication analyses showed that some associations assessed in young twins were consistent in older twins. Our study highlights the differential influence of genetic effects on the associations between the multi-ome and EAA and shows that some, but not all, of the associations persist into adulthood.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70088"},"PeriodicalIF":8.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953873","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}