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| 1 | Cryo-EM structure of human mTOR complex 2显示文摘 | Xizi Chen Mengjie Liu Yuan Tian Jiabei Li Yilun Qi Dan Zhao Zihan Wu Min Huang Catherine C. L. Wong Hong-Wei Wang Jiawei Wang Huirong Yang Yanhui Xu | 2018 | Cell Research2018，28，5： | 8 |
| 2 | SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation显示文摘Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is the ongoing global pandemic that poses substantial challenges to public health worldwide.A subset of COVID-19 patients experience systemic inflammatory response,known as cytokine storm,which may lead to death.Receptor-interacting serine/threonine-protein kinase 1(RIPK1)is an important mediator of inflammation and cell death.Here,we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection.We found evidence of RIPK1 activation in human COVID-19 lung pathological samples,and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2.Inhibition of RIPK1 using multiple smallmolecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids.Furthermore,therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load,and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice.Mechanistically,we found that the RNA-dependent RNA polymerase of SARS-CoV-2,NSP12,a highly conserved central component of coronaviral replication and transcription machinery,promoted the activation of RIPK1.Furthermore,NSP12323L variant,encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy,Italy,that carries a Pro323Leu amino acid substitution in NSP12,showed increased ability to activate RIPK1.Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells.Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19. | Gang Xu Ying Li Shengyuan Zhang Haoran Peng Yunyun Wang Dekang Li Taijie Jin Zhuohao He Yilun Tong Chunting Qi Guowei Wu Kangyun Dong Jizhou Gou Yang Liu Tongyang Xiao Jing Qu Liang Li Liang Liu Ping Zhao Zheng Zhang Junying Yuan | 2021 | Cell Research2021，31，12： | 6 |
| 3 | Structural insights into the activation of ATM kinase显示文摘Dear Editor, ATM (ataxia telangiectasia-mutated) is a master regulator in response to DNA damage and activates downstream pathways involved in cell cycle checkpoints, DNA damage repair, transcription regulation, immune response, central nervous system development and metabolism.1,2 Loss of ATM activity in human results in the pleiotropic neurodegeneration disorder ataxia-telangiectasia (A-T) that is characterized by immunodeficiency, cancer predisposition, premature aging and insulin-resistant diabetes.3,4,5 Despite extensive studies over the past two decades,6,7 it remains controversial how ATM is activated. Particularly, whether ATM exists in a monomeric form, whether the monomer is more active than dimer, and how dimer-to-monomer transition affects the ATM kinase activity, remain controversial. | Jianxiong Xiao Mengjie Liu Yilun Qi Yuriy Chaban Chao Gao Beiqing Pan Yuan Tian Zishuo Yu Jie Li Peijun Zhang Yanhui Xu | 2019 | Cell Research2019，29，8： | 1 |
| 4 | Fundamental Characteristics of Tropical Rain Cell Structures as Measured by TRMM PR显示文摘Rain cells are the most elementary unit of precipitation system in nature.In this study,fundamental geometric and physical characteristics of rain cells over tropical land and ocean areas are investigated by using 15-yr measurements of the Tropical Rainfall Measuring Mission(TRMM)Precipitation Radar(PR).The rain cells are identified with a minimum bounding rectangle(MBR)method.The results indicate that about 50%of rain cells occur at length of about 20 km and width of 15 km.The proportion of rain cells with length>200 km and width>100 km is less than1%.There is a a log-linear relationship between the mean length and width of rain cells.Usually,for the same horizontal geometric parameters,rain cells tend to be square horizontally and lanky vertically over land,while vertically squatty over ocean.The rainfall intensity of rain cells varies from 0.4 to 10 mm h-1 over land to 0.4–8 mm h-1 over ocean.Statistical results indicate that the occurrence frequency of rain cells decreases as the areal fraction of convective precipitation in rain cells increases,while such frequency remains almost invariant when the areal fraction of stratiform precipitation varies from 10%to 80%.The relationship between physical and geometric parameters of rain cells shows that the mean rain rate of rain cells is more frequently associated with the increase of their area,with the increasing rate over land greater than that over ocean.The results also illustrate that heavy convective rain rate prefers to occur in larger rain cells over land while heavy stratiform rain rate tends to appear in larger rain cells over ocean.For the same size of rain cells,the areal fraction and the contribution of convective precipitation are about10%–15%higher over land than over ocean. | Yunfei FU Yilun CHEN Xiangdong ZHANG Yu WANG Rui LI Qi LIU Lei ZHONG Qiong ZHANG Aoqi ZHANG | 2020 | Journal of Meteorological Research2020，34，6： | 1 |
| 5 | Cryo-EM structure of SMG1–SMG8–SMG9 complex显示文摘Nonsense-mediated mRNA decay(NMD)targets premature stop codon(PTC)-containing mRNAs for rapid degradation,and is essential for mammalian embryonic development,brain development and modulation of the stress response.The key event in NMD is the SMG1-mediated phosphorylation of an RNA helicase UPF1 and SMG1 kinase activity is inhibited by SMG8 and SMG9 in an unknown mechanism.Here,we determined the cryo-EM structures of human SMG1 at 3.6Åresolution and the SMG1–SMG8–SMG9 complex at 3.4Åresolution,respectively.SMG8 has a C-terminal kinase inhibitory domain(KID),which covers the catalytic pocket and inhibits the kinase activity of SMG1.Structural analyses suggest that GTP hydrolysis of SMG9 would lead to a dramatic conformational change of SMG8–SMG9 and the KID would move away from the inhibitory position to restore SMG1 kinase activity.Thus,our structural and biochemical analyses provide a mechanistic understanding of SMG1–SMG8–SMG9 complex assembly and the regulatory mechanism of SMG1 kinase activity. | Li Zhu Liang Li Yilun Qi Zishuo Yu Yanhui Xu | 2019 | Cell Research2019，29，12： | 0 |
| 6 | Detecting subtle yet fast skeletal muscle contractions with ultrasoft and durable graphene-based cellular materials显示文摘Human bodily movements are primarily controlled by the contractions of skeletal muscles. Unlike joint or skeletal movements that are generally performed in the large displacement range, the contractions of the skeletal muscles that underpin these movements are subtle in intensity yet high in frequency. This subtlety of movement makes it a formidable challenge to develop wearable and durable so?t materials to electrically monitor such motions with high fidelity for the purpose of, for example, muscle/neuromuscular disease diagnosis. Here we report that an intrinsically fragile ultralow-density graphene-based cellular monolith sandwiched between silicone rubbers can exhibit a highly effective stress and strain transfer mechanism at its interface with the rubber, with a remarkable improvement in stretchability(>100%). In particular, this hybrid also exhibits a highly sensitive, broadband-frequency electrical response(up to 180 Hz) for a wide range of strains. By correlating the mechanical signal of muscle movements obtained from this hybrid material with electromyography, we demonstrate that the strain sensor based on this hybrid material may provide a new, so?t and wearable mechanomyography approach for real-time monitoring of complex neuromuscular-skeletal interactions in a broad range of healthcare and human-machine interface applications. This work also provides a new architecture-enabled functional so?t material platform for wearable electronics. | Zijun He Zheng Qi Huichao Liu Kangyan Wang Leslie Roberts Jefferson ZLiu Yilun Liu Stephen JWang Mark JCook George PSimon Ling Qiu Dan Li | 2022 | National Science Review2022，9，4： | 0 |
| 7 | Structural basis of INTAC-regulated transcription显示文摘DearEditor,Eukaryotic transcription by RNA polymerase I(Pol I)is a strictly regulated process that involves the interplay of numerous factors.Promoter-proximal pausing is a regulatory mechanism that connects transcription initiation and productive elongation in metazoans(Core and Adelman,2019).Pol II forms a paused elongation complex(PEC)through binding of two transcriptional regulation factors DSIF and NELF(Vos et al.,2018).Following the duration of pausing,Pol II either proceeds into productive elongation or undergoes promoter-proximal premature transcription termination(PTT)(Kamieniarz-Gdula and Proudfoot,2019),which plays a decisive role in determining transcriptional outputs. | Hai Zheng Qianwei Jin Xinxin Wang Yilun Qi Weida Liu Yulei Ren Dan Zhao Fei Xavier Chen Jingdong Cheng Xizi Chen Yanhui Xu | 2023 | Protein & Cell2023，14，9： | 0 |
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