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张永清

作者:  发布时间:2023-07-14  阅读次数:

一、基本信息

张永清,博士,教授,博士生导师

研究领域:发育神经生物学和重大神经疾病的动物模型

研究方向:以果蝇、非人灵长类猕猴和家犬为实验体系,通过多学科的研究手段包括基因编辑,脑影像和电生理分析以及行为学和认知功能分析等致力于研究神经突触的发育和功能调控,发现了多个调控突触发育的新通路和新机制,以及相关重大神经疾病特别是自闭症的分子细胞和神经环路机制。

1. 以非人灵长类、家犬和果蝇为模式动物研究人类重要神经疾病包括自闭症的分子遗传和神经环路机制,从而为这类疾病的预防和治疗提供理论依据。传统的模式动物果蝇便于分子遗传和信号通路的解析,而基因编辑大动物模型研究结果更便于临床转化应用。

2. 以果蝇为材料,用分子、细胞、遗传、发育和神经生物学为主要实验检测手段研究神经系统特别是神经突触的结构和功能调控机制。

二、教育背景

19881991  中国农业大学,获博士学位

19851988  中国农业大学,获硕士学位

19811985  华中农业大学,获学士学位

三、工作经历

2023至今       3344体育会员,教授

20042023  中国科学院遗传与发育生物学研究所,研究员

19982003  美国尤他大学和范德比尔特大学,博士后

19951997  英国剑桥大学,博士后

19941995  中国科学院微生物学研究所,副研究员

1994              荷兰瓦赫宁根大学,访问学者

19921993  中国科学院微生物学研究所,博士后

四、科研项目

1. 科技部脑专项社交障碍动物模型的创建2021-2026,参加

2. 科技部重点研发计划项目以家犬为模型解析社交与情感的生物学基础2019-2024277万元,主持

3. 国家自然基金委创新研究群体项目大脑发育创新群体2020.1-2024.12,参加。

4. 国家自然基金委重点项目利用基因编辑技术创建Shank3突变自闭症家犬模型2019.1-2023.12295万元,主持。

5. 中科院先导项目重大精神疾病发病机制2018-2022,参加

6. 国家自然基金委国际合作与交流项目胶质细胞调控神经发育和重构的分子细胞机制2019-2021,主持。

7. 北京市科委脑计划自闭症和抑郁症行为障碍的神经环路机制2018-2021,主持。

8. 国家自然基金重大项目神经突触的发育与功能2015.1 -2019.12,主持。

9. 科技部生殖与发育专项神经元迁移、形态发生和微环路形成的调控机制2014.1-2018.12,首席。

10. 国家自然基金(重大国际合作项目) :解析BMP信号通路在果蝇神经肌肉突触中的调节机制及其在ACSL4相关的智力发育障碍中的作用,2012.1-2016.12,主持。

11. 国家自然基金(重点项目) :脑肿瘤基因brat与脆性智力低下基因dfmr1的互作及其在神经突触的功能,2010.1-2013.12,主持。

12. 农业部转基因专项,2010-2011,参加。

13. 国家科技部973项目脑发育的分子调控机制 2007.1-2011.12,参与。

14. 国家自然基金(国际合作项目) :解析FMRP的功能域和互作蛋白,2007-2009,主持。

15. 四次获得国家自然基金支持国际合作会议,2006-2009年,主持。

16. 国家自然基金(杰出青年基金) :神经突触的去组装及其相关疾病的分子遗传机制,2006.1-2009.12,主持。

17. 国家自然基金(重点项目) :脆性X智力低下的遗传分子基础,2005.1-2008.12,主持。

18. 863项目:智力障碍的临床与基础研究,2006.1-2008.12,主持。

19. 美国FRAXA研究基金会博士后基金,2005-2006,主持。

五、代表性论著

1. Wei Ren, Kang Huang, Yumo Li, Qin Yang, Liping Wang, Kun Guo, Pengfei Wei*, Yong Q. Zhang*. Altered pupil responses to social and non-social stimuli in Shank3 mutant dogs. Mol Psychiatry, accepted

2. Tingting Li, Wenwen Shi, Margaret S. Ho*, Yong Q. Zhang*. A Pvr–AP-1–Mmp1 signaling pathway is activated in astrocytes upon traumatic brain injury. eLife, https://elifesciences.org/reviewed-preprints/87258

3. Md Shafayat Hossain, Aiyu Yao, Xinhua Qiao, Wenwen Shi, Ting Xie, Chang Chen, Yong Q. Zhang. Gbb glutathionylation promotes its proteasome-mediated degradation to inhibit synapse growth. J Cell Biol, 2023, in press. DOI: 10.1083/jcb.202202068

4. Huilin Hong, Chao Guo, Xueru Liu, Liguang Yang, Wei Ren, Hui Zhao, Yuan Li, Zhongyin Zhou, Sin Man Lam, Jidong Mi, Zhentao Zuo, Cirong Liu, Guo-Dong Wang, Yan Zhuo, Ya-ping Zhang, Yixue Li, Guanghou Shui, Yong Q. Zhang*, Ying Xiong*. Differential effects of social isolation on oligodendrocyte development in different brain regions: insights from a canine model. Front Cell Neurosci, 2023. DOI: 10.3389/fncel.2023.1201295

5. Li, B., Zhao, H., Tu, Z., Yang, W., Han, R., Wang, L., Luo, X., Pan, M., Chen, X., Zhang, J., Xu, H., Guo, X., Yan, S., Yin, P., Zhao, Z., Liu, J., Luo, Y., Li, Y., Yang, Z., Zhang, B., Tan, Z., Xu, H., Jiang, T., Jiang, Y.H., Li, S., Yong Q. Zhang, Li, X.J.. CHD8 mutations increase gliogenesis to enlarge brain size in the nonhuman primate. Cell Discov, 2023, 9: 27. DOI: 10.1038/s41421-023-00525-3

6. Xiong, Y., Hong, H., Liu, C., Yong Q. Zhang. Social isolation and the brain: effects and mechanisms. Molecular Psychiatry, 2023, 28:191-201. https://doi.org/10.1038/s41380-022-01835-w

7. Xu, H., Hao, H., Wang, S., Liu, X., Lyu, W., Zuo, Z., Zhuo, Y., Mi, J., Yong Q. Zhang, Tian, R., Zhu, H. A dog carrying mutations in AVP-NPII exhibits key features of central diabetes insipidus. J Genet Genomics, 2022. https://doi.org/10.1016/j.jgg.2022.11.003

8. Hui Zhao, Enqi Liu, Yong Q. Zhang, Dog models of human atherosclerotic vascular diseases. Mammalian Genome, 2022 (invited review). DOI: 10.1007/s00335-022-09965-w

9. Wei Ren, Pengfei Wei, Shan Yu, Yong Q. Zhang, Left-right asymmetry and attractor-like dynamics of dog’s tail wagging during dog-human interactions. iScience, 2022. https://doi.org/10.1016/j.isci.2022.104747

10. Huilin Hong, Zhiguang Zhao, Xiahe Huang, Chao Guo, Hui Zhao, Guo-Dong Wang, Ya-Ping Zhang, Jian-ping Zhao, Jianhui Shi, Qing-Feng Wu, Yong-hui Jiang, Yingchun Wang, Lei M. Li, Zhuo Du, Yong Q. Zhang and Ying Xiong, Brain proteome comparison reveals specific molecular pathways conserved in dog and human. Mol Cell Proteomics, 2022, DOI: 10.1016/j.mcpro.2022.100261

11. Elsayed Metwally, Guoli Zhao, and Yong Q. Zhang, The calcium-dependent protease calpain in neuronal remodeling and neurodegeneration, Trends Neurosci, 2021, 44(9): 741-752. https://doi.org/10.1016/j.tins.2021.07.003

12. Jianbo Li, Ligang Wang, Dawei Yu, Junfeng Hao, Longchao Zhang, Adeniyi C. Adeola, Bingyu Mao, Yun Gao, Shifang Wu, Chunling Zhu, Yong Q. Zhang, Jilong Ren, Changgai Mu, David M. Irwin, Lixian Wang, Tang Hai, Haibing Xie, Yaping Zhang, Single-cell RNA Sequencing Reveals Thoracolumbar Vertebra Heterogeneity and Rib-genesis in Pigs. Genomics, Proteomics & Bioinformatics, 2021, 19(3):423-436

13. 任炜, 余山和张永清, 计算行为学研究进展, 科学通报,2021

14. Kai Zhao, Huilin Hong, Lu Zhao, Sheng Huang, Ying Gao, Elsayed Metwally, Yuqiang Jiang, Stephan J. Sigrist, Yong Q. Zhang, Postsynaptic cAMP Signalling Regulates the Antagonistic Balance of Glutamate Receptor Subtypes. Development, 2020, 147, dev191874.

15. Elsayed Metwally#, Guoli Zhao#, Qifu Wang and Yong Q. Zhang*, Ttm50 facilitates calpain activation by anchoring it to calcium stores and increasing its sensitivity to calcium. Cell Research, 2020, 0:1–17

16. Huilin Hong, Kai Zhao, Shiyan Huang, Sheng Huang, Aiyu Yao, Yuqiang Jiang, Stephan Sigrist, Lu Zhao and Yong Q. Zhang, Structural Remodeling of Active Zones Is Associated with Synaptic Homeostasis. Journal of Neuroscience2020, 40 (14), 2817-2827 (cover story)

17. Hui Zhao#, Qiqi Wang#, Ting Yan, Yu Zhang, Hui-juan Xu, Hao-peng Yu, Zhuchi Tu, Xiangyu Guo, Yong-hui Jiang, Xiao-jiang Li*, Huihui Zhou*, Yong Q. Zhang *. Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates, Translational Psychiatry, (2019) 9:267.

18. Mingyue Jia, Danqing Meng, Mo Chen, Tingting Li, Yong Q. Zhang * and Aiyu Yao*, Drosophila homolog of the intellectual disability-related long-chain acyl-CoA synthetase 4 is required for neuroblast proliferation. Journal of Genetics and Genomics ,20;46(1):5-17, 2019

19. Yan Huang, Sheng Huang, Coralie Di Scala, Qifu Wang, Hans H Wandall, Jacques   Fantini, Yong Q. Zhang *, The glycosphingolipid MacCer promotes synaptic bouton formation in Drosophila by interacting with Wnt, eLife ,2018;7:e38183

20. Elsayed Metwally, Guoli Zhao, Wenhua Li, Qifu Wang and Yong Q. Zhang*, Calcium Activated Calpain Specifically Cleaves Glutamate Receptor IIA but not IIB at the Drosophila Neuromuscular Junction, Journal of Neuroscience, 2019, 2213-17

21. Zhuchi Tu, Hui Zhao, Bang Li, Sen Yan, Lu Wang, Yongjin Tang, Zhujun Li, Dazhang Bai, Caijuan Li, Yingqi Lin, Yuefeng Li, Jianrong Liu, Hao Xu, Xiangyu Guo, Yong-hui Jiang*, Yong Q. Zhang* and Xiao-Jiang Li*, CRISPR/Cas9-mediated disruption of SHANK3 in monkey leads to drug-treatable autism-like symptoms, Human Molecular Genetics, 2019, 28(4),561–571

22. Hui Zhao, Yong-hui Jiang, and Yong Q. Zhang. Modeling Autism in Non-human Primates: Opportunities and Challenges. Autism Research 11, 686-694, 2018 (invited review)

23. Song Wu, Guangming Gan, Zhiping Zhang, Jie Sun, Qifu Wang, Zhongbao Gao, Meixiang Li, Shan Jin, Juan Huang, Ulrich Thomas, Yong-hui Jiang, Yan Li, Rui Tian, Yong Q. Zhang. A pre-synaptic function of Shank protein in Drosophila. Journal of Neuroscience, 2017, 37, 11592-11604, 2017

24. Hui Zhao, Zhuchi Tu, Huijuan Xu, Sen Yan, Huanhuan Yan, Yinghui Zheng, Weili Yang, Jiezhao Zheng, Zhujun Li, Rui Tian, Youming Lu, Xiangyu Guo, Yong-hui Jiang, Xiao-Jiang Li, Yong Q. Zhang. Altered neurogenesis and disrupted expression of synaptic proteins in SHANK3 deficient non-human primate prefrontal cortex. Cell Research, doi:10.1038/cr.2017.95, 2017

25. Chuan-Xi Mao, Xue Wen, Shan Jin, and Yong Q. Zhang. Increased acetylation of microtubules rescues human tau-induced microtubule defects and neuromuscular junction abnormalities in Drosophila. Disease Models and Mechanisms 10, 1245-1252, 2017

26. Yan Huang, Sheng Huang, Sin Man Lam, Zhihua Liu, Guanghou Shui, and Yong Q. Zhang. Acsl, the Drosophila ortholog of intellectual disability-related ACSL4, inhibits synaptic growth by altered lipids. Journal of Cell Science 129, 4034-4045, 2016

27. Fangfang Jiang, Falong Lu, Peixue Li, Wei Liu, Lu Zhao, Qifu Wang, Xiaofeng Cao, Lei Zhang, and Yong Q. Zhang. Drosophila homolog of FMRP maintains genome integrity by interacting with Piwi. Journal of Genetics and Genomics, 43: 11-24, 2016 (cover story)

28. Wenhua Li, Aiyu Yao, Hui Zhi, Kuldeep Kaur, Yong-chuan Zhu, Mingyue Jia, Hui Zhao, Qifu Wang, Shan Jin, Guoli Zhao, Zhi-Qi Xiong, and Yong Q. Zhang. Angelman syndrome protein Ube3a regulates synaptic growth and endocytosis by inhibiting bone morphogenetic protein signaling in Drosophila. PLoS Genetics, doi:10.1371/journal.pgen.1006062

29. Guoli Zhao, Yingga Wu, Li Du, Wenhua Li, Ying Xiong, Aiyu Yao, Qifu Wang and Yong Q. Zhang. Drosophila S6 kinase like inhibits neuromuscular junction growth by downregulating the BMP receptor Thickveins. PLoS Genet doi:10.1371/journal.pgen.1004984

30. Podufall, J., Tian, R., Knoche, E., Puchkov, D., Walter, A.M., Rosa, S., Quentin, C., Vukoja, A., Jung, N., Lampe, A., Wichmann, C. Bohme, M. Depner, H. Yong Q. Zhang. Schmoranzer, J. Sigrist, S. J. Haucke, V. A presynaptic role for the cytomatrix protein GIT in synaptic vesicle recycling. Cell Reports 7, 1417-1425, 2014.

31. Zhihua Liu#, Yan Huang#, Wen Hu, Sheng Huang, Qifu Wang, Junhai Han, and Yong Q. Zhang. Drosophila Acyl-CoA synthetase long-chain family member 4 inhibits synapse growth by attenuating bone morphogenetic protein signaling via endocytic recycling. Journal of Neuroscience, 34:2785-2796, 2014.

32. Chuan-Xi Mao, Ying Xiong, Zhaohuan Xiong, Qifu Wang, Yong Q. Zhang* and Shan Jin*. Microtubule-severing protein katanin regulates neuromuscular junction development and dendritic elaboration in Drosophila. Development, 141:1064-1074, 2014.

33. Wenwen Shi, Yan Chen, Guangming Gan, Dan Wang, Jinqi Ren, Qifu Wang, Zhiheng Xu, Wei Xie, and Yong Q. Zhang. brain tumor regulates neuromuscular synapse growth and endocytosis in Drosophila by suppressing Mad expression.  Journal of Neuroscience, 33:12352-12363, 2013

34. Lu Zhao, Dan Wang, Qifu Wang, Avital A. Rodal, and Yong Q. Zhang. Drosophila cyfip regulates synaptic development and endocytosis by suppressing filamentous actin assembly. PLoS Genet (http://www.plosgenetics.org/doi/pgen.1003450)

35. Ying Xiong, Kai Zhao, Jiaxi Wu, Shan Jin and Yong Q. Zhang. HDAC6 mutations rescue human tau-induced microtubule defects in Drosophila. Proc Natl Acad Sci USA, 110(12): 4604-9, 2013

36. Ethan R. Graf, Vera Valakh, Christina M. Wright, Chunlai Wu, Zhihua Liu, Yong Q. Zhang and Aaron DiAntonio. RIM Promotes Calcium Channel Accumulation at Active Zones of the Drosophila Neuromuscular Junction. Journal of Neuroscience, 32:16586-16596, 2012

37. Wei Liu, Fangfang Jiang, Xiaolin Bi, and Yong Q. Zhang. Drosophila FMRP participates in the DNA damage response by regulating G2/M cell cycle checkpoint and apoptosis. Human Molecular Genetics. 21: 4655-4668, 2012

38. Zhihua Liu, Yan Huang, Yi Zhang, Di Chen, and Yong Q. Zhang *. Drosophila acyl-CoA synthetase long-chain family member 4 regulates axonal transport of synaptic vesicles and is required for synaptic development and transmission.  Journal of Neuroscience,31(6):2052-2063,2011

39. Aiyu Yao, Shan Jin, Xinhai Li, Zhihua Liu, Xuehua Ma, Jing Tang, and Yong Q. Zhang *. Drosophila FMRP regulates microtubule network formation and axonal transport of mitochondria. Human Molecular Genetics, 20(1):51-63,2011

40. Haiying Zhang, Ling Tian, Stephen Tobe, Ying Xiong, Songyan Wang, Xinda Lin, Yanan Liu, William Bendena, Sheng Li, and Yong Q. Zhang *. Drosophila CG10527 mutants are resistant to juvenile hormone and its analog methoprene.  Biochemical and Biophysical Research Communications, 401: 182-187, 2010

41. M Zhang, Yong Q. Zhang and Z Xu* (2010) POSH is Involved in Egr-Bsk (TNF-JNK) Signaling and Embryogenesis in Drosophila. J Genetics and Genomics 37(9):605-19.

42. Zhiwei Liu, Yan Chen, Dan Wang, Songyan Wang, Yong Q. Zhang *. Distinct pre- and postsynaptic dismantling processes of Drosophila neuromuscular junctions during metamorphosis. Journal of Neuroscience, 30: 11624-11634, 2010. Commented on in Faculty of 1000 at http://f1000.com/5488963

43. Dan Wang, Lijun Zhang, Guoli Zhao, Gudrun Wahlstrm, Tapio I. Heino, Jiong Chen*, and Yong Q. Zhang *. Drosophila twinfilin is required for cell migration and synaptic endocytosis. Journal of Cell Science, 123: 1546-1556, 2010

44. Shan Jin, Luyuan Pan, Zhihua Liu, Qifu Wang, Zhiheng Xu, and Yong Q. Zhang. Drosophila tubulin chaperone E functions at neuromuscular synapses and is required for microtubule network formation. Development, 136: 1571-1581, 2009

45. Simon P. Reeve #, Xinda Lin# (co-first author), Bahar H. Sahin, Fangfang Jiang, Aiyu Yao, Zhihua Liu, Hui Zhi, Kendal Broadie, Wei Li, Angela Giangrande, Bassem A. Hassan, Yong Q. Zhang. Mutational analysis establishes a critical role for the N terminus of Fragile X mental retardation protein FMRP.  Journal of Neuroscience, 28(12):3221-3226, 2008

46. Cui J, Zhang M, Yong Q. Zhang, Xu Z* (2007) JNK pathway: diseases and therapeutic potential. Acta Pharmacol Sin. 28(5):601-8.

47. Feng Gu, Hai-Yin Zhang, Shao-Yi Hu, Shang-Zhi Huang, Xu Ma, Yong Q. Zhang. Erectile dysfunction in Fragile X patients. Asian J Androl, 8: 483-487, 2006

48. Yong Q. Zhang and Kendal Broadie. Fathoming fragile X in fruit flies. Trends in Genetics, 21(1): 37-45, 2005

49. Yong Q. Zhang, David Friedman, Zhe Wang, Elvin Woodruff III, Luyuan Pan, Janis O’Donnell and Kendal Broadie, Protein Expression Profiling of the Drosophila Fragile X Mutant Brain Reveals Upregulation of Monoamine Synthesis.  Molecular and Cellular Proteomics, 4(3): 278-290, 2005

50. Luyuan Pan, Yong Q. Zhang, Elvin Woodruff and Kendal Broadie. The Drosophila fragile X gene negatively regulates neuronal elaboration and synaptic differentiation. Current Biology 14: 1863-1870, 2004

51. Yong Q. Zhang, Heinrich J. G. Matthies, Joel Mancuso, Hillary K. Andrews, Elvin Woodruff, III, David Friedman and Kendal Broadie. The Drosophila fragile X-related gene regulates axoneme differentiation during spermatogenesis. Developmental Biology 270(2): 290-307, 2004

52. Hillary Andrews, Yong Zhang, Nick Trotta and Kendal Broadie. Drosophila Sec10 is required for hormone secretion but not general exocytosis or neurotransmission. Traffic 3(12): 906-921, 2002

53. Yong Zhang, Christopher Rodesch and Kendal Broadie. A living synaptic vesicle marker: synaptotagmin-GFP. Genesis: the journal of genetics and development 34: 142-145, 2002

54. Yong Zhang, Adina M. Bailey, Heinrich J. G. Matthies, Robert B. Renden, Mark A. Smith, Sean D. Speese, Gerald M. Rubin and Kendal Broadie. Drosophila fragile X related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 107: 591-603, 2001

55. Yong Zhang, David Featherstone, Warren Davis, Emma Rushton and Kendal Broadie. Drosophila D-Titin is required for myoblast fusion and skeletal muscle striation. Journal of Cell Science 113: 3101-3115, 2000

56. Yong Zhang, John Roote, Saverio Brogna, Andrew W. Davis, Daniel A. Barbash, David Nash and Michael Ashburner. stress sensitive B encodes an adenine nucleotide translocase in Drosophila melanogaster. Genetics 153 (2): 891-903, 1999

57. Christos Louis, Encarna Madueño, Mahmoud Omard, George Papagiannaki, Robert D. C. Saunders, Charalambos Savakis, Inga Sidén-Kiamos, Lefteris Spanos, Pantelis Topalis, Yong Zhang, Michael Ashburner, Panayotis Benos, Viatcheslav N. Bolshakov, Peter Deak, David M. Glover, Siegrun Herrmann and Fotis C. Kafatos. One hundred and five new potential Drosophila melanogaster genes revealed through STS analysis. Gene 195: 187-193, 1997

58. Yong Zhang and Kendal Broadie. Cloning, mapping and tissue specific expression of Drosophila clathrin-associated protein AP50 gene. Gene 233: 171-179, 1999

59. Edwin Chan, Yong Zhang, J. D. Hoheisel and Cahir J. O’kane. Identification and characterization of the gene for Drosophila L3 ribosomal protein. Gene 212: 119-125, 1998

60. Edwin Chan, Yong Zhang and Cahir J. O'Kane. Identification and characterization of the gene for Drosophila S20 ribosomal protein. Gene 200: 85-8, 1997

61. G Bonnema, J Hontelez, R Verkerk, Y Zhang, R van Daelen, A van Kammen and P Zabel. An improved method of partial digestion of plant megabase DNA, suitable for YAC cloning. The Plant Journal 9(1): 125-133, 1996

五、专利

1. 吴梁, 袁思琦, 张永清; 生物信号检测设备, 中国, CN202220361594.9

2. 洪慧琳, 吴梁, 张永清; 一种动物组织切片装置, 中国, CN202220238374

3. 石文文, 张永清; Rosa26基因及其应用, 中国, CN202210391221.0

4. 石文文, 张永清, 吕雯; 特异性靶向犬Rosa26基因的sgRNA及其应用, 中国, CN202210391246.0

5. 米继东, 赵建平, 张永清, 田瑞; 一种用于评价犬认知能力的测试装置及方法,中国, CN202010955803.8

6. 米继东, 赵建平, 张永清, 田瑞; 一种利用多单元装置评价犬与犬社交能力的方法, 中国, CN202010955786.8

7. 石文文, 张永清; 一种用于固定昆虫进行头部损伤实验的装置和方法, 中国, CN201811560013.9

8. 石文文, 张永清; 一种力度可控的造成昆虫创伤性脑损伤的装置和方法, 中国, CN201811561124.1

9. 米继东, 赵建平, 张永清; 自闭症模型犬的建立方法, 中国, CN201811577970.2

10. 石文文, 张永清, 汪奇馥; Brat蛋白的单克隆抗体及应用, 中国, CN201310166971.9

六、招贤纳士

本实验室招讲师,副教授和动物中心主任。神经生物学,生物信息学和兽医专业,以及具有电生理、光遗传学、化学遗传学、磁共振成像、脑电图等研究背景的优先考虑。申请人可将简历发送至recruit@hubu.edu.cn,待遇面议。

欢迎热爱科研、勤于思考的硕士和博士生加入本实验室!

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