Cell stem cell最新文献

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Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy in Parkinson’s disease 人类诱导多能干细胞衍生产品用于帕金森病自体细胞治疗的临床前安全性和有效性
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-02-13 DOI: 10.1016/j.stem.2025.01.006
Jeha Jeon, Young Cha, Yean Ju Hong, In-Hee Lee, Heejin Jang, Sanghyeok Ko, Serhiy Naumenko, Minseon Kim, Hannah L. Ryu, Zenith Shrestha, Nayeon Lee, Tae-Yoon Park, HoeWon Park, Seo-Hyun Kim, Ki-Jun Yoon, Bin Song, Jeffrey Schweitzer, Todd M. Herrington, Sek Won Kong, Bob Carter, Kwang-Soo Kim
{"title":"Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy in Parkinson’s disease","authors":"Jeha Jeon, Young Cha, Yean Ju Hong, In-Hee Lee, Heejin Jang, Sanghyeok Ko, Serhiy Naumenko, Minseon Kim, Hannah L. Ryu, Zenith Shrestha, Nayeon Lee, Tae-Yoon Park, HoeWon Park, Seo-Hyun Kim, Ki-Jun Yoon, Bin Song, Jeffrey Schweitzer, Todd M. Herrington, Sek Won Kong, Bob Carter, Kwang-Soo Kim","doi":"10.1016/j.stem.2025.01.006","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.006","url":null,"abstract":"Human induced pluripotent stem cell (hiPSC)-derived midbrain dopaminergic cells (mDACs) represent a promising source for autologous cell therapy in Parkinson’s disease (PD), but standardized regulatory criteria are essential for clinical translation. In this pre-clinical study, we generated multiple clinical-grade hiPSC lines from freshly biopsied fibroblasts of four sporadic PD patients using episomal reprogramming and differentiated them into mDACs using a refined 21-day protocol. Rigorous evaluations included whole-genome/exome sequencing, RNA sequencing, and <em>in vivo</em> studies, including a 39-week Good Laboratory Practice-compliant mouse safety study. While mDACs from all lines met safety criteria, mDACs from one patient failed to improve rodent behavioral outcomes, underscoring inter-individual variability. Importantly, <em>in vitro</em> assessments did not reliably predict <em>in vivo</em> efficacy, identifying dopaminergic fiber density as a key efficacy criterion. These findings support comprehensive quality control guidelines for autologous cell therapy and pave the way for a clinical trial with eight sporadic PD patients, scheduled to commence in 2025.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"78 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401335","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}
引用次数: 0
Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy 个体化患者肿瘤类器官忠实地保存人类脑肿瘤生态系统并预测患者对治疗的反应
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-02-11 DOI: 10.1016/j.stem.2025.01.002
Tianping Peng, Xiujian Ma, Wei Hua, Changwen Wang, Youjun Chu, Meng Sun, Valentina Fermi, Stefan Hamelmann, Katharina Lindner, Chunxuan Shao, Julia Zaman, Weili Tian, Yue Zhuo, Yassin Harim, Nadja Stöffler, Linda Hammann, Qungen Xiao, Xiaoliang Jin, Rolf Warta, Catharina Lotsch, Ying Mao
{"title":"Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy","authors":"Tianping Peng, Xiujian Ma, Wei Hua, Changwen Wang, Youjun Chu, Meng Sun, Valentina Fermi, Stefan Hamelmann, Katharina Lindner, Chunxuan Shao, Julia Zaman, Weili Tian, Yue Zhuo, Yassin Harim, Nadja Stöffler, Linda Hammann, Qungen Xiao, Xiaoliang Jin, Rolf Warta, Catharina Lotsch, Ying Mao","doi":"10.1016/j.stem.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.002","url":null,"abstract":"Tumor organoids are important tools for cancer research, but current models have drawbacks that limit their applications for predicting response to therapy. Here, we developed a fast, efficient, and complex culture system (IPTO, individualized patient tumor organoid) that accurately recapitulates the cellular and molecular pathology of human brain tumors. Patient-derived tumor explants were cultured in induced pluripotent stem cell (iPSC)-derived cerebral organoids, thus enabling culture of a wide range of human tumors in the central nervous system (CNS), including adult, pediatric, and metastatic brain cancers. Histopathological, genomic, epigenomic, and single-cell RNA sequencing (scRNA-seq) analyses demonstrated that the IPTO model recapitulates cellular heterogeneity and molecular features of original tumors. Crucially, we showed that the IPTO model predicts patient-specific drug responses, including resistance mechanisms, in a prospective patient cohort. Collectively, the IPTO model represents a major breakthrough in preclinical modeling of human cancers, which provides a path toward personalized cancer therapy.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"86 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385072","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}
引用次数: 0
Cognitive impairment in epilepsy progression: Adult neurogenesis loss at critical window 癫痫进展中的认知障碍:关键窗口期成人神经发生丧失
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-02-06 DOI: 10.1016/j.stem.2025.01.004
Yi Wang, Zhong Chen
{"title":"Cognitive impairment in epilepsy progression: Adult neurogenesis loss at critical window","authors":"Yi Wang, Zhong Chen","doi":"10.1016/j.stem.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.004","url":null,"abstract":"The mechanisms underlying cognitive impairment in epilepsy remain poorly understood. Ammothumkandy et al.<span><span><sup>1</sup></span></span> reveal that the loss of adult immature neurons correlates with auditory verbal learning deficits in human mesial temporal lobe epilepsy during a critical disease period, underscoring the pivotal role of adult neurogenesis in specific cognitive domain.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"66 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192641","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}
引用次数: 0
Human iPSCs offer an alternative for modeling vascular malformation 人类多能干细胞为血管畸形建模提供了另一种选择
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-02-06 DOI: 10.1016/j.stem.2025.01.008
Stefanie DeFronzo, Guohao Dai
{"title":"Human iPSCs offer an alternative for modeling vascular malformation","authors":"Stefanie DeFronzo, Guohao Dai","doi":"10.1016/j.stem.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.008","url":null,"abstract":"In this issue of <em>Cell Stem Cell</em>, Pan et al. generated human induced pluripotent stem cell (iPSC)-derived venous endothelial cells (iVECs) by manipulating cell-cycle dynamics and Notch signaling and demonstrated that TIE2-mutant iVECs recapitulate the pathogenesis of venous malformations.<span><span><sup>1</sup></span></span> Their study provides a model for further mechanistic studies and drug discovery.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"62 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192643","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}
引用次数: 0
Neural stem cell quiescence and activation dynamics are regulated by feedback input from their progeny under homeostatic and regenerative conditions 在稳态和再生条件下,神经干细胞的静止和激活动力学是由其后代的反馈输入调节的
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-02-06 DOI: 10.1016/j.stem.2025.01.001
Alina Marymonchyk, Raquel Rodriguez-Aller, Ashleigh Willis, Frédéric Beaupré, Sareen Warsi, Marina Snapyan, Valérie Clavet-Fournier, Flavie Lavoie-Cardinal, David R. Kaplan, Freda D. Miller, Armen Saghatelyan
{"title":"Neural stem cell quiescence and activation dynamics are regulated by feedback input from their progeny under homeostatic and regenerative conditions","authors":"Alina Marymonchyk, Raquel Rodriguez-Aller, Ashleigh Willis, Frédéric Beaupré, Sareen Warsi, Marina Snapyan, Valérie Clavet-Fournier, Flavie Lavoie-Cardinal, David R. Kaplan, Freda D. Miller, Armen Saghatelyan","doi":"10.1016/j.stem.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.001","url":null,"abstract":"Life-long maintenance of stem cells implies that feedback mechanisms from the niche regulate their quiescence/activation dynamics. Here, in the mouse adult subventricular neural stem cell (NSC) niche, we charted a precise spatiotemporal map of functional responses in NSCs induced by multiple niche cells and used machine learning to predict NSC interactions with specific niche cell types. We revealed a feedback mechanism whereby the NSC proliferative state is directly repressed by transient amplifying cells (TAPs), their rapidly dividing progeny. NSC processes wrap around TAPs and display hotspots of Ca<sup>2+</sup> activity at their points of contact, mediated by ephrin (Efn) signaling. The modulation of Efn signaling or TAP ablation altered the Ca<sup>2+</sup> signature of NSCs, leading to their activation. <em>In vivo</em> optogenetic modulation of Ca<sup>2+</sup> dynamics abrogated NSC activation and prevented niche replenishment. Thus, TAP-to-NSC feedback signaling controls stem cell quiescence and activation, providing a mechanism to maintain stem cell pools throughout life.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"42 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192640","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}
引用次数: 0
Pre-birth stem cell education: A gift from mother’s bugs 出生前干细胞教育:来自母亲细菌的礼物
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-02-06 DOI: 10.1016/j.stem.2025.01.009
Chenyan Huang, Ai Ing Lim
{"title":"Pre-birth stem cell education: A gift from mother’s bugs","authors":"Chenyan Huang, Ai Ing Lim","doi":"10.1016/j.stem.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.009","url":null,"abstract":"The maternal gut microbiota undergoes significant changes during pregnancy and plays a pivotal role in offspring development. In this issue, Dang et al. demonstrate that modifying the maternal gut microbiome during pregnancy shapes offspring neural and intestinal stem cells via the mTOR pathway, with long-lasting effects on their functions.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"9 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192642","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}
引用次数: 0
Two is better than one: Advancing gene therapy protocols for enhanced safety and efficacy 二比一好:推进基因治疗方案,提高安全性和有效性
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-02-06 DOI: 10.1016/j.stem.2024.12.009
Giulia Hardouin, Annarita Miccio
{"title":"Two is better than one: Advancing gene therapy protocols for enhanced safety and efficacy","authors":"Giulia Hardouin, Annarita Miccio","doi":"10.1016/j.stem.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.stem.2024.12.009","url":null,"abstract":"In this issue of <em>Cell Stem Cell</em>, two complementary studies from Zeng et al.<span><span><sup>1</sup></span></span> and Demirci et al.<span><span><sup>2</sup></span></span> improve the efficacy of gene therapy for β-hemoglobinopathies using multiplex CRISPR-Cas9 editing. The authors also optimize editing and conditioning protocols to reduce risks associated with current gene therapy procedures.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"15 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192644","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}
引用次数: 0
Molecular signature of primate astrocytes reveals pathways and regulatory changes contributing to human brain evolution 灵长类星形胶质细胞的分子特征揭示了促进人类大脑进化的途径和调节变化
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-02-04 DOI: 10.1016/j.stem.2024.12.011
Katarzyna Ciuba, Aleksandra Piotrowska, Debadeep Chaudhury, Bondita Dehingia, Eryk Duński, Rüdiger Behr, Karolina Soroczyńska, Małgorzata Czystowska-Kuźmicz, Misbah Abbas, Edyta Bulanda, Sylwia Gawlik-Zawiślak, Sylwia Pietrzak, Izabela Figiel, Jakub Włodarczyk, Alexei Verkhratsky, Marcin Niedbała, Wojciech Kaspera, Tomasz Wypych, Bartosz Wilczyński, Aleksandra Pękowska
{"title":"Molecular signature of primate astrocytes reveals pathways and regulatory changes contributing to human brain evolution","authors":"Katarzyna Ciuba, Aleksandra Piotrowska, Debadeep Chaudhury, Bondita Dehingia, Eryk Duński, Rüdiger Behr, Karolina Soroczyńska, Małgorzata Czystowska-Kuźmicz, Misbah Abbas, Edyta Bulanda, Sylwia Gawlik-Zawiślak, Sylwia Pietrzak, Izabela Figiel, Jakub Włodarczyk, Alexei Verkhratsky, Marcin Niedbała, Wojciech Kaspera, Tomasz Wypych, Bartosz Wilczyński, Aleksandra Pękowska","doi":"10.1016/j.stem.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.stem.2024.12.011","url":null,"abstract":"Astrocytes contribute to the development and regulation of the higher-level functions of the brain, the critical targets of evolution. However, how astrocytes evolve in primates is unsettled. Here, we obtain human, chimpanzee, and macaque induced pluripotent stem-cell-derived astrocytes (iAstrocytes). Human iAstrocytes are bigger and more complex than the non-human primate iAstrocytes. We identify new loci contributing to the increased human astrocyte. We show that genes and pathways implicated in long-range intercellular signaling are activated in the human iAstrocytes and partake in controlling iAstrocyte complexity. Genes downregulated in human iAstrocytes frequently relate to neurological disorders and were decreased in adult brain samples. Through regulome analysis and machine learning, we uncover that functional activation of enhancers coincides with a previously unappreciated, pervasive gain of “stripe” transcription factor binding sites. Altogether, we reveal the transcriptomic signature of primate astrocyte evolution and a mechanism driving the acquisition of the regulatory potential of enhancers.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"84 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083533","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}
引用次数: 0
Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals 在哺乳动物中通过直接修饰印迹基因而产生的成年双父系后代
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-01-28 DOI: 10.1016/j.stem.2025.01.005
Zhi-kun Li, Li-bin Wang, Le-yun Wang, Xue-han Sun, Ze-hui Ren, Si-nan Ma, Yu-long Zhao, Chao Liu, Gui-hai Feng, Tao Liu, Tian-shi Pan, Qing-tong Shan, Kai Xu, Guan-zheng Luo, Qi Zhou, Wei Li
{"title":"Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals","authors":"Zhi-kun Li, Li-bin Wang, Le-yun Wang, Xue-han Sun, Ze-hui Ren, Si-nan Ma, Yu-long Zhao, Chao Liu, Gui-hai Feng, Tao Liu, Tian-shi Pan, Qing-tong Shan, Kai Xu, Guan-zheng Luo, Qi Zhou, Wei Li","doi":"10.1016/j.stem.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.005","url":null,"abstract":"Imprinting abnormalities pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning, with no universal correction method owing to their complexity and stochastic nature. In this study, we targeted these defects at their source—embryos from same-sex parents—aiming to establish a stable, maintainable imprinting pattern <em>de novo</em> in mammalian cells. Using bi-paternal mouse embryos, which exhibit severe imprinting defects and are typically non-viable, we introduced frameshift mutations, gene deletions, and regulatory edits at 20 key imprinted loci, ultimately achieving the development of fully adult animals, albeit with a relatively low survival rate. The findings provide strong evidence that imprinting abnormalities are a primary barrier to unisexual reproduction in mammals. Moreover, this approach can significantly improve developmental outcomes for embryonic stem cells and cloned animals, opening promising avenues for advancements in regenerative medicine.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"39 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049994","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}
引用次数: 0
Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation 衰老细胞的全基因组CRISPR激活筛选揭示了SOX5作为年轻化的驱动因素和治疗靶点
IF 23.9 1区 医学
Cell stem cell Pub Date : 2025-01-28 DOI: 10.1016/j.stem.2025.01.007
Yaobin Jing, Xiaoyu Jiang, Qianzhao Ji, Zeming Wu, Wei Wang, Zunpeng Liu, Pedro Guillen-Garcia, Concepcion Rodriguez Esteban, Pradeep Reddy, Steve Horvath, Jingyi Li, Lingling Geng, Qinchao Hu, Si Wang, Juan Carlos Izpisua Belmonte, Jie Ren, Weiqi Zhang, Jing Qu, Guang-Hui Liu
{"title":"Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation","authors":"Yaobin Jing, Xiaoyu Jiang, Qianzhao Ji, Zeming Wu, Wei Wang, Zunpeng Liu, Pedro Guillen-Garcia, Concepcion Rodriguez Esteban, Pradeep Reddy, Steve Horvath, Jingyi Li, Lingling Geng, Qinchao Hu, Si Wang, Juan Carlos Izpisua Belmonte, Jie Ren, Weiqi Zhang, Jing Qu, Guang-Hui Liu","doi":"10.1016/j.stem.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.007","url":null,"abstract":"(Cell Stem Cell <em>30</em>, 1452–1471.e1–e10; November 2, 2023)","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"52 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055386","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}
引用次数: 0
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