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1Upper crustal velocity and seismogenic environment of the M7.0 Jiuzhaigou earthquake region in Sichuan, China显示文摘On August 8,2017,a magnitude 7.0 earthquake occurred in Jiuzhaigou County,Sichuan Province,China.The deep seismogenic environment and potential seismic risk in the eastern margin of Tibetan Plateau have once again attracted the close attention of seismologists and scholars at home and abroad.The post-earthquake scientific investigation could not identify noticeable surface rupture zones in the affected area;the complex tectonic background and the reason(s)for the frequent seismicity in the Jiuzhaigou earthquake region are unclear.In order to reveal the characteristics of the deep medium and the seismogenic environment of the M7.0 Jiuzhaigou earthquake region,and to interpret the tectonic background and genesis of the seismicity comprehensively,in this paper,we have reviewed all available observation data recorded by the regional digital seismic networks and large-scale,dense mobile seismic array(China Array)for the northern section of the North-South Seismic Belt around Jiuzhaigou earthquake region.Using double-difference seismic tomography method to invert the three-dimensional P-wave velocity structure characteristics of the upper crust around the Jiuzhaigou earthquake region,we have analyzed and discussed such scientific questions as the relationship between the velocity structure characteristics and seismicity in the Jiuzhaigou earthquake region,its deep tectonic environment,and the ongoing seismic risk in this region.We report that:the P-wave velocity structure of the upper crust around the Jiuzhaigoug earthquake region exhibits obvious lateral inhomogeneity;the distribution characteristics of the shallow P-wave velocity structure are closely related to surface geological structure and formation lithology;the M7.0 Jiuzhaigou earthquake sequence is closely related to the velocity structure of the upper crust;the mainshock of the M7.0 earthquake occurred in the upper crust;the inhomogeneous variation of the velocity structure of the Jiuzhaigou earthquake area and its surrounding medium appears to be the deep structural factor controlling the spatial distribution of the mainshock and its sequence.The 3D P-wave velocity structure also suggests that the crustal low-velocity layer of northeastern SGB(Songpan-GarzêBlock)stretches into MSM(Minshan Mountain),and migrates to the northeast,but the tendency to emerge as a shallow layer is impeded by the high-velocity zone of Nanping Nappe tectonics and the Bikou Block.Our results reveal an uneven distribution of high-and low-velocity structures around the Tazang segment of the East Kunlun fault zone.Given that the rupture caused by the Jiuzhaigou earthquake has enhanced the stress fields at both ends of the seismogenic fault,it is very important to stay vigilant to possible seismic hazards in the large seismic gap at the Maqu-Maqên segment of the East Kunlun fault zone.DaHu Li ZhiFeng Ding Yan Zhan PingPing Wu LiJun Chang XiangYu Sun 2021Earth and Planetary Physics2021,5,4:4
2TRIB3-GSK-3β interaction promotes lung fibrosis and serves as a potential therapeutic target显示文摘Pulmonary fibrosis(PF)is a chronic,progressive,fatal interstitial lung disease with limited available therapeutic strategies.We recently reported that the protein kinase glycogen synthase kinase-3β(GSK-3β)interacts with and inactivates the ubiquitin-editing enzyme A20 to suppress the degradation of the transcription factor CCAAT/enhancer-binding protein beta(C/EBPβ)in alveolar macrophages(AMs),resulting in a profibrotic phenotype of AMs and promoting the development of PF.Here,we showed that chronic lung injury upregulated the stress response protein tribbles homolog 3(TRIB3),which interacted with GSK-3βand stabilized GSK-3βfrom ubiquitination and degradation.Elevated GSK-3βexpression phosphorylated A20 to inhibit its ubiquitin-editing activity,causing the accumulation of C/EBPβand the production of several profibrotic factors in AMs and promoting PF development.Activated C/EBPβ,in turn,increased the transcription of TRIB3 and GSK-3β,thereby establishing a positive feedback loop in AMs.The knockdown of TRIB3 expression or the pharmacologic disruption of the TRIB3-GSK-3βinteraction was an effective PF treatment.Our study reveals an intact profibrotic axis of TRIB3-GSK-3β-A20-C/EBPβin AMs,which represents a target that may provide a promising treatment strategy for PF.Shanshan Liu Xiaoxi Lv Xupeng Wei Chang Liu Qiao Li Jiali Min Fang Hua Xiaowei Zhang Ke Li Pingping Li Yang Xiao Zhuowei Hu Bing Cui 2021Acta Pharmaceutica Sinica B2021,11,10:2
3Increasing stability of antibody via antibody engineering: Stability engineering on an anti‐hVEGF显示文摘Shuang Wang Ming Liu Dadi Zeng Weiyi Qiu Pingping Ma Yunzhou Yu Hongyan Chang Zhiwei Sun 2014Proteins2014,,:1
4Dy- namic Analytic Model of Mechanism with Links Fabricated from Symmetric Laminates显示文摘Cai Ganwei Chang Pingping Ma Cunzhi 2006Journal of Central South University Technology2006,13,6:1
5Feasibility and physics potential of detecting ^(8)B solar neutrinos at JUNO显示文摘The Jiangmen Underground Neutrino Observatory(JUNO)features a 20 kt multi-purpose underground liquid scintillator sphere as its main detector.Some of JUNO's features make it an excellent location for^8B solar neutrino measurements,such as its low-energy threshold,high energy resolution compared with water Cherenkov detectors,and much larger target mass compared with previous liquid scintillator detectors.In this paper,we present a comprehensive assessment of JUNO's potential for detecting^8B solar neutrinos via the neutrino-electron elastic scattering process.A reduced 2 MeV threshold for the recoil electron energy is found to be achievable,assuming that the intrinsic radioactive background^(238)U and^(232)Th in the liquid scintillator can be controlled to 10^(-17)g/g.With ten years of data acquisition,approximately 60,000 signal and 30,000 background events are expected.This large sample will enable an examination of the distortion of the recoil electron spectrum that is dominated by the neutrino flavor transformation in the dense solar matter,which will shed new light on the inconsistency between the measured electron spectra and the predictions of the standard three-flavor neutrino oscillation framework.IfDelta m^(2)_(21)=4.8times10^(-5);(7.5times10^(-5))eV^(2),JUNO can provide evidence of neutrino oscillation in the Earth at approximately the 3sigma(2sigma)level by measuring the non-zero signal rate variation with respect to the solar zenith angle.Moreover,JUNO can simultaneously measureDelta m^2_(21)using^8B solar neutrinos to a precision of 20% or better,depending on the central value,and to sub-percent precision using reactor antineutrinos.A comparison of these two measurements from the same detector will help understand the current mild inconsistency between the value of Delta m^2_(21)reported by solar neutrino experiments and the KamLAND experiment.Angel Abusleme Thomas Adam Shakeel Ahmad Sebastiano Aiello Muhammad Akram Nawab Ali Fengpeng An Guangpeng An Qi An Giuseppe Andronico Nikolay Anfimov Vito Antonelli Tatiana Antoshkina Burin Asavapibhop João Pedro Athayde Marcondes de André Didier Auguste Andrej Babic Wander Baldini Andrea Barresi Eric Baussan Marco Bellato Antonio Bergnoli Enrico Bernieri David Biare Thilo Birkenfeld Sylvie Blin David Blum Simon Blyth Anastasia Bolshakova Mathieu Bongrand Clément Bordereau Dominique Breton Augusto Brigatti Riccardo Brugnera Riccardo Bruno Antonio Budano Max Buesken Mario Buscemi Jose Busto Ilya Butorov Anatael Cabrera Hao Cai Xiao Cai Yanke Cai Zhiyan Cai Antonio Cammi Agustin Campeny Chuanya Cao Guofu Cao Jun Cao Rossella Caruso Cédric Cerna Jinfan Chang Yun Chang Pingping Chen Po-An Chen Shaomin Chen Shenjian Chen Xurong Chen Yi-Wen Chen Yixue Chen Yu Chen Zhang Chen Jie Cheng Yaping Cheng Alexander Chepurnov Davide Chiesa Pietro Chimenti Artem Chukanov Anna Chuvashova Gérard Claverie Catia Clementi Barbara Clerbaux Selma Conforti Di Lorenzo Daniele Corti Salvatore Costa Flavio Dal Corso Christophe De La Taille Jiawei Deng Zhi Deng Ziyan Deng Wilfried Depnering Marco Diaz Xuefeng Ding Yayun Ding Bayu Dirgantara Sergey Dmitrievsky Tadeas Dohnal Georgy Donchenko Jianmeng Dong Damien Dornic Evgeny Doroshkevich Marcos Dracos Frédéric Druillole Shuxian Du Stefano Dusini Martin Dvorak Timo Enqvist Heike Enzmann Andrea Fabbri Lukas Fajt Donghua Fan Lei Fan Can Fang Jian Fang Marco Fargetta Anna Fatkina Dmitry Fedoseev Vladko Fekete Li-Cheng Feng Qichun Feng Richard Ford Andrey Formozov Amélie Fournier Haonan Gan Feng Gao Alberto Garfagnini Alexandre Göttel Christoph Genster Marco Giammarchi Agnese Giaz Nunzio Giudice Franco Giuliani Maxim Gonchar Guanghua Gong Hui Gong Oleg Gorchakov Yuri Gornushkin Marco Grassi Christian Grewing Maxim Gromov Vasily Gromov Minghao Gu Xiaofei Gu Yu Gu Mengyun Guan Nunzio Guardone Maria Gul Cong Guo Jingyuan Guo Wanlei Guo Xinheng Guo Yuhang Guo Paul Hackspacher Caren Hagner Ran Han Yang Han Miao He Wei He Tobias Heinz Patrick Hellmuth Yuekun Heng Rafael Herrera Daojin Hong YuenKeung Hor Shaojing Hou Yee Hsiung Bei-Zhen Hu Hang Hu Jianrun Hu Jun Hu Shouyang Hu Tao Hu Zhuojun Hu Chunhao Huang Guihong Huang Hanxiong Huang Qinhua Huang Wenhao Huang Xingtao Huang Yongbo Huang Jiaqi Hui Wenju Huo Cédric Huss Safeer Hussain Antonio Insolia Ara Ioannisian Daniel Ioannisyan Roberto Isocrate Kuo-Lun Jen Xiaolu Ji Xingzhao Ji Huihui Jia Junji Jia Siyu Jian Di Jiang Xiaoshan Jiang Ruyi Jin Xiaoping Jing Cécile Jollet Jari Joutsenvaara Sirichok Jungthawan Leonidas Kalousis Philipp Kampmann Li Kang Michael Karagounis Narine Kazarian Amir Khan Waseem Khan Khanchai Khosonthongkee Patrick Kinz Denis Korablev Konstantin Kouzakov Alexey Krasnoperov Svetlana Krokhaleva Zinovy Krumshteyn Andre Kruth Nikolay Kutovskiy Pasi Kuusiniemi Tobias Lachenmaier Cecilia Landini Sébastien Leblanc Frederic Lefevre Liping Lei Ruiting Lei Rupert Leitner Jason Leung Demin Li Fei Li Fule Li Haitao Li Huiling Li Jiaqi Li Jin Li Kaijie Li Mengzhao Li Nan Li Nan Li Qingjiang Li Ruhui Li Shanfeng Li Shuaijie Li Tao Li Weidong Li Weiguo Li Xiaomei Li Xiaonan Li Xinglong Li Yi Li Yufeng Li Zhibing Li Ziyuan Li Hao Liang Hao Liang Jingjing Liang Jiajun Liao Daniel Liebau Ayut Limphirat Sukit Limpijumnong Guey-Lin Lin Shengxin Lin Tao Lin Jiajie Ling Ivano Lippi Fang Liu Haidong Liu Hongbang Liu Hongjuan Liu Hongtao Liu Hu Liu Hui Liu Jianglai Liu Jinchang Liu Min Liu Qian Liu Qin Liu Runxuan Liu Shuangyu Liu Shubin Liu Shulin Liu Xiaowei Liu Yan Liu Alexey Lokhov Paolo Lombardi Claudio Lombardo Kai Loo Chuan Lu Haoqi Lu Jingbin Lu Junguang Lu Shuxiang Lu Xiaoxu Lu Bayarto Lubsandorzhiev Sultim Lubsandorzhiev Livia Ludhova Fengjiao Luo Guang Luo Pengwei Luo Shu Luo Wuming Luo Vladimir Lyashuk Qiumei Ma Si Ma Xiaoyan Ma Xubo Ma Jihane Maalmi Yury Malyshkin Fabio Mantovani Francesco Manzali Xin Mao Yajun Mao Stefano MMari Filippo Marini Sadia Marium Cristina Martellini Gisele Martin-Chassard Agnese Martini Davit Mayilyan Axel Müller Ints Mednieks Yue Meng Anselmo Meregaglia Emanuela Meroni David Meyhöfer Mauro Mezzetto Jonathan Miller Lino Miramonti Salvatore Monforte Paolo Montini Michele Montuschi Nikolay Morozov Pavithra Muralidharan Massimiliano Nastasi Dmitry VNaumov Elena Naumova Igor Nemchenok Alexey Nikolaev Feipeng Ning Zhe Ning Hiroshi Nunokawa Lothar Oberauer Juan Pedro Ochoa-Ricoux Alexander Olshevskiy Domizia Orestano Fausto Ortica Hsiao-Ru Pan Alessandro Paoloni Nina Parkalian Sergio Parmeggiano Teerapat Payupol Yatian Pei Nicomede Pelliccia Anguo Peng Haiping Peng Frédéric Perrot Pierre-Alexandre Petitjean Fabrizio Petrucci Luis Felipe Piñeres Rico Oliver Pilarczyk Artyom Popov Pascal Poussot Wathan Pratumwan Ezio Previtali Fazhi Qi Ming Qi Sen Qian Xiaohui Qian Hao Qiao Zhonghua Qin Shoukang Qiu Muhammad Rajput Gioacchino Ranucci Neill Raper Alessandra Re Henning Rebber Abdel Rebii Bin Ren Jie Ren Taras Rezinko Barbara Ricci Markus Robens Mathieu Roche Narongkiat Rodphai Aldo Romani Bedřich Roskovec Christian Roth Xiangdong Ruan Xichao Ruan Saroj Rujirawat Arseniy Rybnikov Andrey Sadovsky Paolo Saggese Giuseppe Salamanna Simone Sanfilippo Anut Sangka Nuanwan Sanguansak Utane Sawangwit Julia Sawatzki Fatma Sawy Michaela Schever Jacky Schuler Cédric Schwab Konstantin Schweizer Dmitry Selivanov Alexandr Selyunin Andrea Serafini Giulio Settanta Mariangela Settimo Muhammad Shahzad Vladislav Sharov Gang Shi Jingyan Shi Yongjiu Shi Vitaly Shutov Andrey Sidorenkov FedorŠimkovic Chiara Sirignano Jaruchit Siripak Monica Sisti Maciej Slupecki Mikhail Smirnov Oleg Smirnov Thiago Sogo-Bezerra Julanan Songwadhana Boonrucksar Soonthornthum Albert Sotnikov Ondrej Sramek Warintorn Sreethawong Achim Stahl Luca Stanco Konstantin Stankevich DušanŠtefánik Hans Steiger Jochen Steinmann Tobias Sterr Matthias Raphael Stock Virginia Strati Alexander Studenikin Gongxing Sun Shifeng Sun Xilei Sun Yongjie Sun Yongzhao Sun Narumon Suwonjandee Michal Szelezniak Jian Tang Qiang Tang Quan Tang Xiao Tang Alexander Tietzsch Igor Tkachev Tomas Tmej Konstantin Treskov Andrea Triossi Giancarlo Troni Wladyslaw Trzaska Cristina Tuve Stefan van Waasen Johannes van den Boom Guillaume Vanroyen Nikolaos Vassilopoulos Vadim Vedin Giuseppe Verde Maxim Vialkov Benoit Viaud Cristina Volpe Vit Vorobel Lucia Votano Pablo Walker Caishen Wang Chung-Hsiang Wang En Wang Guoli Wang Jian Wang Jun Wang Kunyu Wang Lu Wang Meifen Wang Meng Wang Ruiguang Wang Siguang Wang Wei Wang Wenshuai Wang Xi Wang Xiangyue Wang Yangfu Wang Yaoguang Wang Yi Wang Yifang Wang Yuanqing Wang Yuman Wang Zhe Wang Zheng Wang Zhimin Wang Zongyi Wang Apimook Watcharangkool Lianghong Wei Wei Wei Yadong Wei Liangjian Wen Christopher Wiebusch Steven Chan-Fai Wong Bjoern Wonsak Diru Wu Fangliang Wu Qun Wu Wenjie Wu Zhi Wu Michael Wurm Jacques Wurtz Christian Wysotzki Yufei Xi Dongmei Xia Yuguang Xie Zhangquan Xie Zhizhong Xing Benda Xu Donglian Xu Fanrong Xu Jilei Xu Jing Xu Meihang Xu Yin Xu Yu Xu Baojun Yan Xiongbo Yan Yupeng Yan Anbo Yang Changgen Yang Huan Yang Jie Yang Lei Yang Xiaoyu Yang Yifan Yang Haifeng Yao Zafar Yasin Jiaxuan Ye Mei Ye Ugur Yegin Frédéric Yermia Peihuai Yi Xiangwei Yin Zhengyun You Boxiang Yu Chiye Yu Chunxu Yu Hongzhao Yu Miao Yu Xianghui Yu Zeyuan Yu Chengzhuo Yuan Ying Yuan Zhenxiong Yuan Ziyi Yuan Baobiao Yue Noman Zafar Andre Zambanini Pan Zeng Shan Zeng Tingxuan Zeng Yuda Zeng Liang Zhan Feiyang Zhang Guoqing Zhang Haiqiong Zhang Honghao Zhang Jiawen Zhang Jie Zhang Jingbo Zhang Peng Zhang Qingmin Zhang Shiqi Zhang Tao Zhang Xiaomei Zhang Xuantong Zhang Yan Zhang Yinhong Zhang Yiyu Zhang Yongpeng Zhang Yuanyuan Zhang Yumei Zhang Zhenyu Zhang Zhijian Zhang Fengyi Zhao Jie Zhao Rong Zhao Shujun Zhao Tianchi Zhao Dongqin Zheng Hua Zheng Minshan Zheng Yangheng Zheng Weirong Zhong Jing Zhou Li Zhou Nan Zhou Shun Zhou Xiang Zhou Jiang Zhu Kejun Zhu Honglin Zhuang Liang Zong Jiaheng Zou 2021Chinese Physics C2021,45,2:0
6Status of an MWth integrated gasification fuel cell powergeneration system in China显示文摘Abstract Here,we provide a status update of an integrated gasification fuel cell(IGFC)power-generation system being developed at the National Institute of Clean-and-Low-Carbon in China at the megawatt thermal(MWth)scale.This system is designed to use coal as fuel to produce syngas as a first step,similar to that employed for the integrated gasification combined cycle.Subsequently,the solid-oxide fuel-cell(SOFC)system is used to convert chemical energy to electricity directly through an electrochemical reaction without combustion.This system leads to higher efficiency as compared with that from a traditional coal-fired power plant.The unreacted fuel in the SOFC system is transported to an oxygencombustor to be converted to steam and carbon dioxide(CO_(2)).Through a heat-recovery system,the steam is condensed and removed,and CO_(2) is enriched and captured for sequestration or utilization.Comprehensive economic analyses for a typical IGFC system was performed and the results were compared with those for a supercritical pulverized coal-fired power plant.The SOFC stacks selected for IGFC development were tested and qualified under hydrogen and simulated coal syngas fuel.Experimental results using SOFC stacks and thermodynamic analyses indicated that the control of hydrogen/CO ratio of syngas and steam/CO ratio is important to avoid carbon deposition with the fuel pipe.A 20-kW SOFC unit is under development with design power output of 20 kW and DC efficiency of 50.41%.A 100 kW-level subsystem will consist of 6920-kW power-generation units,and the MWth IGFC system will consist of 59100 kWlevel subsystems.Chang Wei Zhien Liu Chufu Li Surinder Singh Haoren Lu Yudong Gong Pingping Li Hanlin Wang Xia Yang Ming Xu Shujun Mu 2021International Journal of Coal Science & Technology2021,8,3:0
7Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis显示文摘The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis(NASH)remain largely unknown.We aimed to elucidate the roles of hepatic cyclooxygenase 1(COX1)in autophagy and the pathogenesis of diet-induced steatohepatitis in mice.Human nonalcoholic fatty liver disease(NAFLD)liver samples were used to examine the protein expression of COX1 and the level of autophagy.Cox1^(Δhepa)mice and their wildtype littermates were generated and fed with 3 different NASH models.We found that hepatic COX1 expression was increased in patients with NASH and diet induced NASH mice models accompanied by impaired autophagy.COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy.Mechanistically,COX1 directly interacted with WD repeat domain,phosphoinositide interacting 2(WIPI2),which was crucial for autophagosome maturation.Adeno-associated virus(AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1^(Δhepa)mice,indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy.In conclusion,we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2.Targeting the COX1 WIPI2 axis may be a novel therapeutic strategy for NASH.Qian Yu Chang Li Qinghui Niu Jigang Wang Zhaodi Che Ke Lei He Ren Boyi Ma Yixing Ren Pingping Luo Zhuming Fan Huan Zhang Zhaohui Liu George L.Tipoe Jia Xiao 2023Acta Pharmaceutica Sinica B2023,13,6:0
8Molecular Cloning, Expression and Characterization of Peroxisome Proliferators-Activated Receptors Gamma in the Sea Urchin(Strongylocentrotus intermedius)显示文摘Peroxisome proliferators-activated receptor gamma(PPARγ) plays important regulatory roles in adipocyte differentiation. In this study, we cloned the full-length sequence of the PPARγ gene and analyzed its expression profile in different developmental stages and tissues of Strongylocentrotus intermedius. The full-length cDNA of PPARγ contains 2286 base pairs(bp) with a putative open reading frame of 1755 bp, and the gene encodes encoding a polypeptide of 584 amino acid residues. The predicted molecular mass of the protein is 67.27 kDa, and its theoretical isoelectric point(pI) is 10.07. The protein contains conserved motifs, including an RRM(RNA recognition motif) domain. PPARγ expression with the highest level was observed in the gonad, and the lowest was observed in the tube feet of S. intermedius. Time-course expression measurements at different developmental stages showed that the highest expression level of PPARγ is in the eggs and its weakest expression level is in the 32-cells stage. Knock-down of PPARγ by specific siRNA revealed that UCP2 expression is significantly decreased in the gonads and intestines 48 h post-transfection, indicating that the UCP2 is a downstream target gene of PPARγ.This finding suggests that PPARγ and UCP2 have positive regulatory effects in regulating adipocyte differentiation. Changes in fatty acid levels in the gonads before and after PPARγ interference were assessed, and decreased C18:2(trans, n-6) and C20:3(n-6) levels were observed 48 h after siRNA transfection. The results showed the function of PPARγ in fatty acid anabolism, The data are helpful to improve the current understanding of the fatty acid synthesis pathways and regulatory mechanisms in S. intermedius. They also provide an experimental basis for improving fatty acid synthesis in sea urchins, which is important for cultivating sea urchins with high nutritional value.QUAN Zijiao HAN Lingshu CAO Yue GAO Pingping LIU Xiaoyu CHANG Yaqing DING Jun 2021Journal of Ocean University of China2021,20,2:0
9Single cell RNA and immune repertoire prowling of COVID-19 patients reveal novel neutralizing antibody显示文摘There is no doubt that COVID-19 outbreak is currently the biggest public health threat,which has caused catastrophic con sequences in many countries and regions.As host immunity is key to fighting against virus infection,it is important to characterize the immunologic changes in the COVID-19 patients,and to explore potential therapeutic candidates.The most efficient ways to end this pandemic are to vaccinate the susceptible population,and to use specific drugs,such as monoclonal antibodies against the viral spike protein(S protein),to treat the affected individuals.Several promising neutralizing antibodies have recently been reported(Cao et al.,2020;Lv et al.,2020).Fang Li Meng Luo Wenyang Zhou Jinliang Li Xiyun Jin Zhaochun Xu Liran Juan Zheng Zhang Yuou Li Renqiang Liu Yiqun Li Chang Xu Kexin Ma Huimin Cao Jingwei Wang Pingping Wang Zhigao Bu Qinghua Jiang 2021Protein & Cell2021,12,10:0
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