Neuron最新文献

{"title":"TDP-43 seeding induces cytoplasmic aggregation heterogeneity and nuclear loss of function of TDP-43.","authors":"Jens Rummens, Bilal Khalil, Günseli Yıldırım, Pedro Silva, Valentina Zorzini, Nicolas Peredo, Marta Wojno, Meine Ramakers, Ludo Van Den Bosch, Philip Van Damme, Kristofer Davie, Jelle Hendrix, Frederic Rousseau, Joost Schymkowitz, Sandrine Da Cruz","doi":"10.1016/j.neuron.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.03.004","url":null,"abstract":"<p><p>Cytoplasmic aggregation and nuclear depletion of TAR DNA-binding protein 43 (TDP-43) are hallmarks of several neurodegenerative disorders. Yet, recapitulating both features in cellular systems has been challenging. Here, we produced amyloid-like fibrils from recombinant TDP-43 low-complexity domain and demonstrate that sonicated fibrils trigger TDP-43 pathology in human cells, including induced pluripotent stem cell (iPSC)-derived neurons. Fibril-induced cytoplasmic TDP-43 inclusions acquire distinct biophysical properties, recapitulate pathological hallmarks such as phosphorylation, ubiquitin, and p62 accumulation, and recruit nuclear endogenous TDP-43, leading to its loss of function. A transcriptomic signature linked to both aggregation and nuclear loss of TDP-43, including disease-specific cryptic splicing, is identified. Cytoplasmic TDP-43 aggregates exhibit time-dependent heterogeneous morphologies as observed in patients-including compacted, filamentous, or fragmented-which involve upregulation/recruitment of protein clearance pathways. Ultimately, cell-specific progressive toxicity is provoked by seeded TDP-43 pathology in human neurons. These findings identify TDP-43-templated aggregation as a key mechanism driving both cytoplasmic gain of function and nuclear loss of function, offering a valuable approach to identify modifiers of sporadic TDP-43 proteinopathies.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743168","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":"Seeded aggregation of TDP-43 induces its loss of function and reveals early pathological signatures.","authors":"Carlo Scialò, Weijia Zhong, Somanath Jagannath, Oscar Wilkins, Davide Caredio, Marian Hruska-Plochan, Flavio Lurati, Martina Peter, Elena De Cecco, Luigi Celauro, Adriano Aguzzi, Giuseppe Legname, Pietro Fratta, Magdalini Polymenidou","doi":"10.1016/j.neuron.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.03.008","url":null,"abstract":"<p><p>Neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) results from both gain of toxicity and loss of normal function of the RNA-binding protein TDP-43, but their mechanistic connection remains unclear. Increasing evidence suggests that TDP-43 aggregates act as self-templating seeds, propagating pathology through the central nervous system via a prion-like cascade. We developed a robust TDP-43-seeding platform for quantitative assessment of TDP-43 aggregate uptake, cell-to-cell spreading, and loss of function within living cells, while they progress toward pathology. We show that both patient-derived and recombinant TDP-43 pathological aggregates were abundantly internalized by human neuron-like cells, efficiently recruited endogenous TDP-43, and formed cytoplasmic inclusions reminiscent of ALS/FTD pathology. Combining a fluorescent reporter of TDP-43 function with RNA sequencing and proteomics, we demonstrated aberrant cryptic splicing and a loss-of-function profile resulting from TDP-43-templated aggregation. Our data highlight known and novel pathological signatures in the context of seed-induced TDP-43 loss of function.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743060","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":"Molecular pathways and diagnosis in spatially resolved Alzheimer's hippocampal atlas.","authors":"Pan Wang, Lei Han, Lifang Wang, Quyuan Tao, Zhen Guo, Ting Luo, Youzhe He, Zhi Xu, Jiayi Yu, Yuyang Liu, Zihan Wu, Bin Xu, Bufan Jin, Yanrong Wei, Ying Yang, Mengnan Cheng, Yujia Jiang, Chen Tian, Huiwen Zheng, Zhongqin Fan, Peiran Jiang, Yue Gao, Juanli Wu, Shengpeng Wang, Bing Sun, Zheng Fang, Junjie Lei, Benyan Luo, Huiying Wen, Guoping Peng, Yuanchun Tang, Tao Yang, Jing Chen, Zhenkun Zhuang, Xinhui Su, Catherine Pan, Keqing Zhu, Yi Shen, Shiping Liu, Aimin Bao, Jianhua Yao, Jian Wang, Xun Xu, Xiao-Ming Li, Longqi Liu, Shumin Duan, Jing Zhang","doi":"10.1016/j.neuron.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.03.002","url":null,"abstract":"<p><p>We employed Stereo-seq combined with single-nucleus RNA sequencing (snRNA-seq) to investigate the gene expression and cell composition changes in human hippocampus with or without Alzheimer's disease (AD). The transcriptomic map, with single-cell precision, unveiled AD-associated alterations with spatial specificity, which include the following: (1) elevated synapse pruning gene expression in the fimbria of AD, with disrupted microglia-astrocyte communication likely leading to disorganized synaptic structure; (2) a globally increased energy generation in the cornu ammonis (CA) region, with varying degrees across its subregions; (3) a significant reduction in the number of CA1 neurons in AD, while CA4 neurons remained largely unaffected, potentially due to gene alterations in CA4 conferring resilience to AD; and (4) aggravated amyloid-beta (Aβ) plaques in CA1 and stratum lucidum, radiatum, and moleculare (SLRM), and integration of Stereo-seq map with Aβ staining revealed a sequential enrichment of microglia and astrocytes around Aβ plaques. Finally, reduced brain-derived extracellular vesicles carrying cholecystokinin (CCK) and peripheral myelin protein 2 (PMP2) in AD plasma highlighted their diagnostic potential for clinical applications.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764427","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":"Comprehensive characterization of metabolic consumption and production by the human brain.","authors":"Yilong Wang, Lebo Zhou, Nan Wang, Baoshan Qiu, Di Yao, Jie Yu, Miaoqing He, Tong Li, Yufeng Xie, Xiaoqian Yu, Zhanying Bi, Xiangli Sun, Xunming Ji, Zhen Li, Dapeng Mo, Woo-Ping Ge","doi":"10.1016/j.neuron.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.03.003","url":null,"abstract":"<p><p>Metabolism is vital for brain function. However, a systematic investigation to understand the metabolic exchange between the human brain and circulatory system has been lacking. Here, we compared metabolomes and lipidomes of blood samples from the cerebral venous sinus and femoral artery to profile the brain's uptake and release of metabolites and lipids (1,365 metabolites and 140 lipids). We observed a high net uptake of glucose, taurine, and hypoxanthine and identified glutamine and pyruvate as significantly released metabolites by the brain. Triacylglycerols are the most prominent class of lipid consumed by the brain. The brain with cerebral venous sinus stenosis (CVSS) consumed more glucose and lactate and released more glucose metabolism byproducts than the brain with cerebral venous sinus thrombosis (CVST). Our data also showed age-related alterations in the uptake and release of metabolites. These results provide a comprehensive view of metabolic consumption and production processes within the human brain.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730945","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":"Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development.","authors":"Adam P Caccavano, Anna Vlachos, Nadiya McLean, Sarah Kimmel, June Hoan Kim, Geoffrey Vargish, Vivek Mahadevan, Lauren Hewitt, Anthony M Rossi, Ilona Spineux, Sherry Jingjing Wu, Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Yating Wang, Ramesh Chittajallu, Edra London, Xiaoqing Yuan, Steven Hunt, Daniel Abebe, Mark A G Eldridge, Alex C Cummins, Brendan E Hines, Anya Plotnikova, Arya Mohanty, Bruno B Averbeck, Kareem A Zaghloul, Jordane Dimidschstein, Gord Fishell, Kenneth A Pelkey, Chris J McBain","doi":"10.1016/j.neuron.2025.03.005","DOIUrl":"10.1016/j.neuron.2025.03.005","url":null,"abstract":"<p><p>Within adult rodent hippocampus (HPC), opioids suppress inhibitory parvalbumin-expressing interneurons (PV-INs), disinhibiting local microcircuits. However, it is unknown whether this disinhibitory motif is conserved across cortical regions, species, or development. We observed that PV-IN-mediated inhibition is robustly suppressed by opioids in HPC proper but not primary neocortex in mice and non-human primates, with spontaneous inhibitory tone in resected human tissue also following a consistent dichotomy. This hippocampal disinhibitory motif is established in early development when PV-INs and opioids regulate early population activity. Morphine pretreatment partially occludes this acute opioid-mediated suppression, with implications for the effects of opioids on hippocampal network activity important for learning and memory. Our findings demonstrate that PV-INs exhibit divergent opioid sensitivity across brain regions, which is remarkably conserved over evolution, and highlight the underappreciated role of opioids acting through immature PV-INs in shaping hippocampal development.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730946","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":"Key-value memory in the brain.","authors":"Samuel J Gershman, Ila Fiete, Kazuki Irie","doi":"10.1016/j.neuron.2025.02.029","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.02.029","url":null,"abstract":"<p><p>Classical models of memory in psychology and neuroscience rely on similarity-based retrieval of stored patterns, where similarity is a function of retrieval cues and the stored patterns. Although parsimonious, these models do not allow distinct representations for storage and retrieval, despite their distinct computational demands. Key-value memory systems, in contrast, distinguish representations used for storage (values) and those used for retrieval (keys). This allows key-value memory systems to optimize simultaneously for fidelity in storage and discriminability in retrieval. We review the computational foundations of key-value memory, its role in modern machine-learning systems, related ideas from psychology and neuroscience, applications to a number of empirical puzzles, and possible biological implementations.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730949","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":"Vascular motion in the dorsal root ganglion sensed by Piezo2 in sensory neurons triggers episodic neuropathic pain.","authors":"Wenrui Xie, Debora Denardin Lückemeyer, Katherine A Qualls, Arthur Silveira Prudente, Temugin Berta, Mingxia Gu, Judith A Strong, Xinzhong Dong, Jun-Ming Zhang","doi":"10.1016/j.neuron.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.03.006","url":null,"abstract":"<p><p>Spontaneous pain, characterized by episodic shooting or stabbing sensations, is a major complaint among neuropathic pain patients, yet its mechanisms remain poorly understood. Recent research indicates a connection between this pain condition and \"clustered firing,\" wherein adjacent sensory neurons fire simultaneously. This study presents evidence that the triggers of spontaneous pain and clustered firing are the dynamic movements of small blood vessels within the nerve-injured sensory ganglion, along with increased blood vessel density/angiogenesis and increased number of pericytes around blood vessels. Pharmacologically or mechanically evoked myogenic vascular responses increase both spontaneous pain and clustered firing in a mouse model of neuropathic pain. The mechanoreceptor Piezo2 in sensory neurons plays a critical role in detecting blood vessel movements. An anti-VEGF monoclonal antibody that inhibits angiogenesis effectively blocks spontaneous pain and clustered firing. These findings suggest targeting Piezo2, angiogenesis, or abnormal vascular dynamics as potential therapeutic strategies for neuropathic spontaneous pain.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743202","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 spatial transcriptomic atlas of the whole mouse brain.","authors":"Lei Han, Zhen Liu, Zehua Jing, Yuxuan Liu, Yujie Peng, Huizhong Chang, Junjie Lei, Kexin Wang, Yuanfang Xu, Wei Liu, Zihan Wu, Qian Li, Xiaoxue Shi, Mingyuan Zheng, He Wang, Juan Deng, Yanqing Zhong, Hailin Pan, Junkai Lin, Ruiyi Zhang, Yu Chen, Jinhua Wu, Mingrui Xu, Biyu Ren, Mengnan Cheng, Qian Yu, Xinxiang Song, Yanbing Lu, Yuanchun Tang, Nini Yuan, Suhong Sun, Yingjie An, Wenqun Ding, Xing Sun, Yanrong Wei, Shuzhen Zhang, Yannong Dou, Yun Zhao, Luyao Han, Qianhua Zhu, Junfeng Xu, Shiwen Wang, Dan Wang, Yinqi Bai, Yikai Liang, Yuan Liu, Mengni Chen, Chun Xie, Binshi Bo, Mei Li, Xinyan Zhang, Wang Ting, Zhenhua Chen, Jiao Fang, Shuting Li, Yujia Jiang, Xing Tan, Guolong Zuo, Yue Xie, Huanhuan Li, Quyuan Tao, Yan Li, Jianfeng Liu, Yuyang Liu, Mingkun Hao, Jingjing Wang, Huiying Wen, Jiabing Liu, Yizhen Yan, Hui Zhang, Yifan Sheng, Shui Yu, Xiaoyan Liao, Xuyin Jiang, Guangling Wang, Huanlin Liu, Congcong Wang, Ning Feng, Xin Liu, Kailong Ma, Xiangjie Xu, Tianyue Han, Huateng Cao, Huiwen Zheng, Yadong Chen, Haorong Lu, Zixian Yu, Jinsong Zhang, Bo Wang, Zhifeng Wang, Qing Xie, Shanshan Pan, Chuanyu Liu, Chan Xu, Luman Cui, Yuxiang Li, Shiping Liu, Sha Liao, Ao Chen, Qing-Feng Wu, Jian Wang, Zhiyong Liu, Yidi Sun, Jan Mulder, Huanming Yang, Xiaofei Wang, Chao Li, Jianhua Yao, Xun Xu, Longqi Liu, Zhiming Shen, Wu Wei, Yan-Gang Sun","doi":"10.1016/j.neuron.2025.02.015","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.02.015","url":null,"abstract":"<p><p>A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding the function of the brain. Here, using single-nucleus RNA sequencing (snRNA-seq) and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters at single-cell resolution, involving over 4 million cells, as well as for 29,655 genes. We have identified cell clusters exhibiting preference for cortical subregions and explored their associations with brain-related diseases. Additionally, we pinpointed 155 genes with distinct regional expression patterns within the brainstem and unveiled 513 long non-coding RNAs showing region-enriched expression in the adult brain. Parcellation of brain regions based on spatial transcriptomic information revealed fine structure for several brain areas. Furthermore, we have uncovered 411 transcription factor regulons showing distinct spatiotemporal dynamics during neurodevelopment. Thus, we have constructed a single-cell-resolution spatial transcriptomic atlas of the mouse brain with genome-wide coverage.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710904","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":"A pontine center in descending pain control.","authors":"Tianming Li, Wenjie Zhou, Jin Ke, Matthew Chen, Zhen Wang, Lauren Hayashi, Xiaojing Su, Wenbin Jia, Wenxi Huang, Chien-Sheng Wang, Kapsa Bengyella, Yang Yang, Rafael Hernandez, Yan Zhang, Xinglei Song, Tianle Xu, Tianwen Huang, Yuanyuan Liu","doi":"10.1016/j.neuron.2025.02.028","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.02.028","url":null,"abstract":"<p><p>Pain sensation changes according to expectation, context, and mood, illustrating how top-down circuits affect somatosensory processing. Here, we used an intersectional strategy to identify anatomical and molecular-spatial features of supraspinal descending neurons activated by distinct noxious stimulation. This approach captured known descending pain pathways as well as spinal projecting neurons that are anatomically mapped to Barrington's nucleus in the dorsal pontine tegmentum. We determined that this population of neurons expresses corticotropin-releasing hormone in Barrington's nucleus (Bar^Crh) and exhibits time-locked firing in response to noxious stimulation. Chemogenetic activation of Bar^Crh neurons attenuated nocifensive responses as well as tactile neuropathic pain, while silencing these neurons resulted in thermal hyperalgesia and mechanical allodynia. Mechanistically, we demonstrated that pain-related input from the ventrolateral periaqueductal gray recruits Bar^Crh neurons, reduces ascending nociceptive transmission, and preferentially activates spinal dynorphin neurons to mediate analgesia. Our data expose a pontine inhibitory descending pathway that powerfully controls nocifensive sensory input to the brain.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710900","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":"Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer's disease.","authors":"Andrew Octavian Sasmita, Erinne Cherisse Ong, Taisiia Nazarenko, Shuying Mao, Lina Komarek, Maik Thalmann, Veronika Hantakova, Lena Spieth, Stefan A Berghoff, Helena J Barr, Maximilian Hingerl, Friederike Börensen, Johannes Hirrlinger, Mikael Simons, Beth Stevens, Constanze Depp, Klaus-Armin Nave","doi":"10.1016/j.neuron.2024.12.025","DOIUrl":"10.1016/j.neuron.2024.12.025","url":null,"abstract":"<p><p>In Alzheimer's disease (AD) research, the 5xFAD mouse model is commonly used as a heterozygote crossed with other genetic models to study AD pathology. We investigated whether the parental origin of the 5xFAD transgene affects plaque deposition. Using quantitative light-sheet microscopy, we found that paternal inheritance of the transgene led to a 2-fold higher plaque burden compared with maternal inheritance, a finding consistent across multiple 5xFAD colonies. This effect was not due to gestation in or rearing by 5xFAD females. Immunoblotting suggested that transgenic inheritance modulates transgenic protein expression, potentially due to genomic imprinting of the Thy1.2 promoter. Surprisingly, fewer than 20% of 5xFAD studies report breeding schemes, suggesting that this factor might confound previous findings. Our data highlight a significant determinant of plaque burden in 5xFAD mice and underscore the importance of reporting the parental origin of the transgene to improve scientific rigor and reproducibility in AD research.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"838-846.e4"},"PeriodicalIF":14.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009079","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}