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| 1 | The PI3K/AKT Pathway and Renal Cell Carcinoma显示文摘The phosphatidylinositol 3 kinase(PI3K)/AKT pathway is genetically targeted in more pathway components and in more tumor types than any other growth factor signaling pathway,and thus is frequently activated as a cancer driver.More importantly,the PI3K/AKT pathway is composed of multiple bifurcating and converging kinase cascades,providing many potential targets for cancer therapy.Renal cell carcinoma(RCC) is a high-risk and high-mortality cancer that is notoriously resistant to traditional chemotherapies or radiotherapies.The PI3K/AKT pathway is modestly mutated but highly activated in RCC,representing a promising drug target.Indeed,PI3 K pathway inhibitors of the rapalog family are approved for use in RCC.Recent large-scale integrated analyses of a large number of patients have provided a molecular basis for RCC,reiterating the critical role of the PI3K/AKT pathway in this cancer.In this review,we summarize the genetic alterations of the PI3K/AKT pathway in RCC as indicated in the latest large-scale genome sequencing data,as well as treatments for RCC that target the aberrant activated PI3K/AKT pathway. | Huifang Guo Peter German Shanshan Bai Sean Barnes Wei Guo Xiangjie Qi Hongxiang Lou Jiyong Liang Eric Jonasch Gordon B.Mills Zhiyong Ding | 2015 | Journal of Genetics and Genomics2015，42，7： | 39 |
| 2 | Structures of EV71 RNA-dependent RNA polymerase in complex with substrate and analogue provide a drug target against the hand-foot-and-mouth disease pandemic in China显示文摘Enterovirus 71(EV71),one of the major causative agents for hand-foot-and-mouth disease(HFMD),has caused more than 100 deaths among Chinese children since March 2008.The EV71 genome encodes an RNAdependent RNA polymerase(RdRp),denoted 3D^(pol),which is central for viral genome replication and is a key target for the discovery of specific antiviral therapeutics.Here we report the crystal structures of EV71 RdRp(3D^(pol))and in complex with substrate guanosine-5'-triphosphate and analog 5-bromouridine-5'-triphosphate best to 2.4Åresolution.The structure of EV71 RdRp(3D^(pol))has a wider open thumb domain compared with the most closely related crystal structure of poliovirus RdRp.And the EV71 RdRp(3D^(pol))complex with GTP or Br-UTP bounded shows two distinct movements of the polymerase by substrate or analogue binding.The model of the complex with the template:primer derived by superimposition with foot-and-mouth disease virus(FMDV)3D/RNA complex reveals the likely recognition and binding of template:primer RNA by the polymerase.These results together provide a molecular basis for EV71 RNA replication and reveal a potential target for anti-EV71 drug discovery. | Yang Wu Zhiyong Lou Yi Miao Yue Yu Hui Dong Wei Peng Mark Bartlam Xuemei Li Zihe Rao | 2010 | Protein & Cell2010，1，5： | 30 |
| 3 | A structural view of the conserved domain of rice stress-responsive NAC1显示文摘The importance of NAC(named as NAM,ATAF1,2,and CUC2)proteins in plant development,transcription regulation and regulatory pathways involving proteinprotein interactions has been increasingly recognized.We report here the high resolution crystal structure of SNAC1(stress-responsive NAC)NAC domain at 2.5Å.Although the structure of the SNAC1 NAC domain shares a structural similarity with the reported structure of the ANAC NAC1 domain,some key features,especially relating to two loop regions which potentially take the responsibility for DNA-binding,distinguish the SNAC1 NAC domain from other reported NAC structures.Moreover,the dimerization of the SNAC1 NAC domain is demonstrated by both soluble and crystalline conditions,suggesting this dimeric state should be conserved in this type of NAC family.Additionally,we discuss the possible NAC-DNA binding model according to the structure and reported biological evidences. | Qingfeng Chen Quan Wang Lizhong Xiong Zhiyong Lou | 2011 | Protein & Cell2011，2，1： | 18 |
| 4 | A structural view of the antibiotic degradation enzyme NDM-1 from a superbug显示文摘Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1(NDM-1)are a type of newly discovered antibioticresistant bacteria.The rapid pandemic spread of NDM-1 bacteria worldwide(spreading to India,Pakistan,Europe,America,and Chinese Taiwan)in less than 2 months characterizes these microbes as a potentially major global health problem.The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations.The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics,allowing the bacteria to escape the action of antibiotics.Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues,the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified.Here,we report the threedimensional structure of NDM-1 with two catalytic zinc ions in its active site.Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity.The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases(MBLs)and implicate its role in wide spectrum drug resistance.We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria.Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases. | Yu Guo Jing Wang Guojun Niu Wenqing Shui Yuna Sun Honggang Zhou Yaozhou Zhang Cheng Yang Zhiyong Lou Zihe Rao | 2011 | Protein & Cell2011，2，5： | 16 |
| 5 | Molecular mechanism of SCARB2-mediatec attachment and uncoating of EV71显示文摘 | Minghao Dang Xiangxi Wang Quan Wang Yaxin Wang Jianping Lin Yuna Sun Xuemei Li Liguo Zhang Zhiyong Lou Junzhi Wang Zihe Rao | 2014 | Protein & Cell2014，5，9： | 13 |
| 6 | Structural basis for the impact of phosphorylation on the activation of plant receptor-like kinase BAK1显示文摘 | Liming Yan Yuanyuan Ma Dan Liu Xiaochao Wei Yuna Sun Xiaoyue Chen Huadong Zhao Jingwen Zhou Zhiyong Wang Wenqing Shui Zhiyong Lou | 2012 | Cell Research2012，22，8： | 10 |
| 7 | The newly emerged SARS-Like coronavirus HCoV-EMC also has an “Achilles’ heel”: current effective inhibitor targeting a 3C-like protease显示文摘From the global outbreak of SARS-CoV caused infection disease in 2003,coronaviruses(CoVs)are known to be a great threat to the human health.Recently,a new SARS-like coronavirus,human betacoronavirus 2c EMC/2012(HCoV-EMC),has been identified and the appearance of this new CoV raises concerns that a new spread of CoV may occurs in the future.By solving the crystal structure of HCoV-EMC main protease with a wide-spectrum anti-CoV inhibitor N3,we confi rmed that that N3 blocks the function of HCoV-EMC main protease through a similar mechanism to other CoVs.Together with the good pharmaceutical features,N3 is conceivable to be effective to HCoV-EMC and other CoVs appearing in the future.These fi ndings make it convincing that CoVs will not be a threat to human health. | Zhilin Ren Liming Yan Ning Zhang Yu Guo Cheng Yang Zhiyong Lou Zihe Rao | 2013 | Protein & Cell2013，4，4： | 10 |
| 8 | Insight into the Ebola virus nucleocapsid assembly mechanism: crystal structure of Ebola virus nucleoprotein core domain at 1.8 A resolution显示文摘 | Shishang Dong Peng Yang Guobang Li Baocheng Liu Wenming Wang Xiang Liu Boran Xia Cheng Yang Zhiyong Lou Yu Guo Zihe Rao | 2015 | Protein & Cell2015，6，5： | 6 |
| 9 | The nucleoprotein of severe fever with thrombocytopenia syndrome virus processes a stable hexameric ring to facilitate RNA encapsidation显示文摘Severe fever with thrombocytopenia syndrome virus(SFTSV),a member of the Phlebovirus genus from the Bunyaviridae family endemic to China,is the causative agent of life-threatening severe fever with thrombocyto-penia syndrome(SFTS),which features high fever and hemorrhage.Similar to other negative-sense RNA viruses,SFTSV encodes a nucleocapsid protein(NP)that is essen-tial for viral replication.NP facilitates viral RNA encapsida-tion and is responsible for the formation of ribonucleopro-tein complex.However,recent studies have indicated that NP from Phlebovirus members behaves in inhomogene-ous oligomerization states.In the present study,we report the crystal structure of SFTSV NP at 2.8Åresolution and demonstrate the mechanism by which it processes a ring-shaped hexameric form to accomplish RNA encapsida-tion.Key residues essential for oligomerization are identi-fi ed through mutational analysis and identifi ed to have a signifi cant impact on RNA binding,which suggests that correct formation of highly ordered oligomers is a criti-cal step in RNA encapsidation.The fi ndings of this work provide new insights into the discovery of new antiviral reagents for Phlebovirus infection. | Honggang Zhou Yuna Sun Ying Wang Min Liu Chao Liu Wenming Wang Xiang Liu Le Li Fei Deng Hualin Wang Yu Guo Zhiyong Lou | 2013 | Protein & Cell2013，4，6： | 4 |
| 10 | A versatile building block:the structures and functions of negative-sense single-stranded RNA virus nucleocapsid proteins显示文摘Nucleocapsid protein(NPs)of negative-sense single-stranded RNA(-ssRNA)viruses function in different stages of viral replication,transcription,and maturation.Structural investigations show that-ssRNA viruses that encode NPs preliminarily serve as structural building blocks that encapsidate and protect the viral genomic RNA and mediate the interaction between genomic RNA and RNA-dependent RNA polymerase.However,recent structural results have revealed other bio-logical functions of-ssRNA viruses that extend our understanding of the versatile roles of virally encoded NPs. | Yuna Sun Yu Guo Zhiyong Lou | 2012 | Protein & Cell2012，3，12： | 3 |
| 11 | Effect of Traditional Chinese Medicine plus narrow-band medium-wave ultraviolet B radiation on moderate-to-severe psoriasis vulgaris in a case series显示文摘OBJECTIVE: To investigate the efficacy and safety of Traditional Chinese Medicine (TCM) therapy combined with ultraviolet B light therapy in the treatment of moderate-to-severe psoriasis. METHODS: Patients with moderate-to-severe psoriasis (skin lesion area > 10% of the body surface area) for 2 consecutive years were treated with TCM (oral and external use of herbal medicines, acupuncture, and herbal bathing) and narrow-band medium-wave ultraviolet B light treatment for 12 weeks. The treatment effect was evaluated based on the Psoriasis Area Severity Index (PASI), the achievement of a 50% reduction in the PASI (PASI50), the achievement of a 75% reduction in the PASI (PASI75), pruritus score, Dermatology Life Quality Index, and safety. RESULTS: A total of 95 outpatients were enrolled, and 92 subjects (96.8%) completed the 12-week treatment course. At baseline, the average proportion of the body surface area covered by skin lesions was 12.4%, and the average PASI was 17.7. All patients had previously been treated with conventional medicine (89.1% of patients received ultraviolet light treatment, 50.0% received glucocorticoids, and 21.7% received acitretin). After the 12-week treatment course, 22 patients (23.9%) achieved PASI75, and 43 (46.7%) achieved PASI50. The post-treatment pruritus score and Dermatology Life Quality Index of all treated patients were significantly lower than the respective baseline values (P < 0.0001). No adverse effects were detected by the monitoring of blood, urine, stools, liver and kidney function, and echocardiography.CONCLUSION: Comprehensive therapy comprising TCM therapy combined with ultraviolet B light therapy achieved good outcomes for patients with moderate-to-severe psoriasis. | Li Tiantian Zhou Dongmei Xu Xuying Qu Jianhua Jiang Chunyan Lan Haibing Lou Weihai Chen Weiwen Jin Li Liu Rongqi Liu Zhiyong Zhang Cang Duan Lanhua Bohua Li Xu Jingna Zhou Tao Jiang Xi Cao Wei Zhang Guangzhong Liu Jianping Sun Liyun Wang Ping | 2019 | Journal of Traditional Chinese Medicine2019，39，5： | 2 |
| 12 | Identification of serotonin 2A receptor as a novel HCV entry factor by a chemical biology strategy显示文摘Hepatitis C virus(HCV)is a leading cause of liver disease worldwide.Although several HCV protease/polymerase inhibitors were recently approved by U.S.FDA,the combination of antivirals targeting multiple processes of HCV lifecycle would optimize anti-HCV therapy and against potential drug-resistanee.Viral entry is an essential target step for antiviral development,but FDA-approved HCV entry inhibitor remains exclusive.Here we identify serotonin 2A receptor(5-HT2aR)is a HCV entry factor amendable to therapeutic intervention by a chemical biology strategy.The silencing of 5-HT2aR and clinically available 5-HT2aR antagonist suppress cell culture-derived HCV(HCVcc)in different liver cells and primary human hepatocytes at late endocytosis process.The mechanism is related to regulate the correct plasma membrane localization of claudin 1(CLDN1).Moreover,phenoxybenzamine(PBZ),an FDAapproved 5-HT2aR antagonist,inhibits all major HCV genotypes in vitro and displays synergy in combination with clinical used anti-HCV drugs.The impact of PBZ on HCV genotype 2a is documented in immune-competent humanized transgenic mice.Our results not only expand the understanding of HCV entry,but also present a promising target for the invention of HCV entry inhibitor. | Lin Cao Jizheng Chen Yaxin Wang Yuting Yang Jie Qing Zihe Rao Xinwen Chen Zhiyong Lou | 2019 | Protein & Cell2019，10，3： | 2 |
| 13 | Crystal structure of a secreted lipase from Gibberella zeae reveals a novel “double-lock” mechanism显示文摘Fusarium graminearum(sexual stage:Gibberella zeae)is the causative agent of Fusarium Head Blight(FHB),which is one of the most destructive plant disease of cereals,accounting for high grain yield losses,especially for wheat and maize.Like other fungal pathogens,several extracellular enzymes secreted by G.zeae are known to be involved in host infection.Among these secreted lipases,G.zeae lipase(GZEL),which is encoded by the FGL1 gene,was demonstrated to be crucial to G.zeae pathogenicity.However,the precise mechanism of GZEL remains unclear due to a lack of detailed structural information.In this study,we report the crystal structure of GZEL at the atomic level.The structure of GZEL displays distinct structural differences compared to reported homologues and indicates a unique“double lock”enzymatic mechanism.To gain insight into substrate/inhibitor recognition,we proposed a model of GZEL in complex with substrate and the lipase inhibitor ebelactone B(based on the reported structures of GZEL homologues),which defines possible substrate binding sites within the catalytic cleft and suggests an“anti sn-l”binding mode.These results pave the way to elucidating the mechanism of GZEL and thus provide clues for the design of anti-FHB inhibitors. | Zhiyong Lou Ming Li Yuna Sun Ye Liu Zheng Liu Wenping Wu Zihe Rao | 2010 | Protein & Cell2010，1，8： | 2 |
| 14 | Three-dimensional domain swapping as a mechanism to lock the active conformation in a super-active octamer of SARS-CoV main protease显示文摘Proteolytic processing of viral polyproteins is indispensible for the lifecycle of coronaviruses.The main protease(M^(pro))of SARS-CoV is an attractive target for anti-SARS drug development as it is essential for the polyprotein processing.M^(pro) is initially produced as part of viral polyproteins and it is matured by autocleavage.Here,we report that,with the addition of an N-terminal extension peptide,M^(pro) can form a domain-swapped dimer.After complete removal of the extension peptide from the dimer,the mature M^(pro) self-assembles into a novel super-active octamer(AO-M^(pro)).The crystal structure of AO-M^(pro) adopts a novel fold with four domainswapped dimers packing into four active units with nearly identical conformation to that of the previously reported M^(pro) active dimer,and 3D domain swapping serves as a mechanism to lock the active conformation due to entanglement of polypeptide chains.Compared with the previously well characterized form of M^(pro),in equilibrium between inactive monomer and active dimer,the stable AO-M^(pro) exhibits much higher proteolytic activity at low concentration.As all eight active sites are bound with inhibitors,the polyvalent nature of the interaction between AO-M^(pro) and its polyprotein substrates with multiple cleavage sites,would make AO-M^(pro) functionally much more superior than the M^(pro) active dimer for polyprotein processing.Thus,during the initial period of SARS-CoV infection,this novel active form AOM^(pro) should play a major role in cleaving polyproteins as the protein level is extremely low.The discovery of AOM^(pro) provides new insights about the functional mechanism of M^(pro) and its maturation process. | Shengnan Zhang Nan Zhong Fei Xue Xue Kang Xiaobai Ren Jiaxuan Chen Changwen Jin Zhiyong Lou Bin Xia | 2010 | Protein & Cell2010，1，4： | 2 |
| 15 | Structures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus显示文摘Coronaviruses are the causative agent of respiratory and enteric diseases in animals and humans.One example is SARS,which caused a worldwide health threat in 2003.In coronaviruses,the structural protein N(nucleocapsid protein)associates with the viral RNA to form the filamentous nucleocapsid and plays a crucial role in genome replication and transcription.The structure of Nterminal domain of MHV N protein also implicated its specific affinity with transcriptional regulatory sequence(TRS)RNA.Here we report the crystal structures of the two proteolytically resistant N-(NTD)and C-terminal(CTD)domains of the N protein from murine hepatitis virus(MHV).The structure of NTD in two different crystal forms was solved to 1.5Å.The higher resolution provides more detailed structural information than previous reports,showing that the NTD structure from MHV shares a similar overall and topology structure with that of SARS-CoV and IBV,but varies in its potential surface,which indicates a possible difference in RNA-binding module.The structure of CTD was solved to 2.0-Åresolution and revealed a tightly intertwined dimer.This is consistent with analytical ultracentrifugation experiments,suggesting a dimeric assembly of the N protein.The similarity between the structures of these two domains from SARS-CoV,IBV and MHV corroborates a conserved mechanism of nucleocapsid formation for coronaviruses. | Yanlin Ma Xiaohang Tong Xiaoling Xu Xuemei Li Zhiyong Lou Zihe Rao | 2010 | Protein & Cell2010，1，7： | 2 |
| 16 | Neuromorphic-computing-based adaptive learning using ion dynamics in flexible energy storage devices显示文摘High-accuracy neuromorphic devices with adaptive weight adjustment are crucial for high-performance computing.However,limited studies have been conducted on achieving selective and linear synaptic weight updates without changing electrical pulses.Herein,we propose high-accuracy and self-adaptive artificial synapses based on tunable and flexible MXene energy storage devices.These synapses can be adjusted adaptively depending on the stored weight value to mitigate time and energy loss resulting from recalculation.The resistance can be used to effectively regulate the accumulation and dissipation of ions in single devices,without changing the external pulse stimulation or preprogramming,to ensure selective and linear synaptic weight updates.The feasibility of the proposed neural network based on the synapses of flexible energy devices was investigated through training and machine learning.The results indicated that the device achieved a recognition accuracy of~95%for various neural network calculation tasks such as numeric classification. | Shufang Zhao Wenhao Ran Zheng Lou Linlin Li Swapnadeep Poddar Lili Wang Zhiyong Fan Guozhen Shen | 2022 | National Science Review2022，9，11： | 1 |
| 17 | Dingxin recipe alleviates atherosclerosis injury in Apo E-knockout mice via downregulation of visfatin expression and inhibition of the visfatin-induced inflammatory response显示文摘OBJECTIVE:To further elucidate the mechanism underlying the anti-atherosclerotic effect of Dingxin recipe(DXR).METHODS:Fifty 6-week-old male Apo E^-/-mice were randomly divided into the following groups:model,simvastatin(5 mg·kg^-1·d^-1),DXR low-dose(9.30 g·kg^-1·d^-1),DXR middle-dose(18.59 g·kg^-1·d^-1)and DXR high-dose(37.18 g·kg^-1·d^-1)(n=10).Ten male C57BL/6J mice were used as the control group.All Apo E^-/-mice were fed a high-fat diet(HFD)and the control mice received a common diet.After HFD for 12 weeks,the mice were treated with DXR or simvastatin for another 12 weeks.The expression of inflammatory cytokines and visfatin was determined in serum and atherosclerotic lesions by enzyme-linked immunosorbent assay.Visfatin expression was also assessed in aortic atherosclerotic plaques.Cultured vessel endothelial cells(VECs)were pretreated with DXR sera prior to visfatin.The effects of DXR were analyzed to elucidate its protective mechanism against visfatin-induced inflammation in VECs.RESULTS:DXR regulated blood lipids and reduced tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),intercellular adhesion molecules-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1)and visfatin expression in Apo E^-/-mice,particularly at the higher doses.The areas of atherosclerotic lesions in the DXR groups were significantly smaller than those in the model group.DXR alleviated visfatin-induced VEC injury via downregulation of TNF-α,IL-6,ICAM-1 and VCAM-1 through mitogen-activated protein kinase pathways.CONCLUSION:DXR alleviated atherosclerosis injury via downregulation of visfatin expression and inhibition of the visfatin-induced inflammatory response in VECs. | Cui Xiaobing Huang Zhiyong Lou Linjie Cheng Saibo Zhang Yu Zhang Yaxin Jia Yuhua Zhou Fenghua | 2020 | Journal of Traditional Chinese Medicine2020，40，6： | 1 |
| 18 | Expression and antigenicity characterization for truncated capsid pro- tein of porcine circovirus type 2 显示文摘 | LOU Zhongzi LI Xuerui LI Zhiyong | 2011 | Can J Vet Res2011，75，1： | 1 |
| 19 | Bipartite double cover and perfect 2-matching covered graph with its algorithm显示文摘让 B (G) 与 v 表示非由两部组成的图 G 的由两部组成的双盖子 2 个顶点和边。我们证明 G 是完美的 2 火柴如果并且仅当 B (G) 是一张 1-extendable 图,盖住图。而且,我们证明 B (G) 是一最低限度地 1-extendable 图如果并且仅当 G 是最低限度地完美的 2 火柴盖住的图并且为每 e = xy E (G) ,在 G 有独立集合 S 以便 |< 潜水艇 class= “ a-plus-plus ” > G (S)|=|S |+ 1, x S 和 |< 潜水艇 class= “ a-plus-plus ” > Gxy (S)|=|S| 。那么,如果 2 火柴盖住图并且仅当 G 是完成式,我们从 B (G) 或 D 是强烈连接的两个字母并成的一个单音的 G 和表演构造两个字母并成的一个单音 D。我们因此在 \ 设计一个算法(O (\sqrt v \varepsilon )\) 决定 G 是否是完美的 2 火柴的时间盖住图。 | Zhiyong GAN Dingjun LOU Zanbo ZHANG Xuelian WEN | 2015 | Frontiers of Mathematics in China2015，10，3： | 0 |
| 20 | Crystal structure of the novel di-nucleotide cyclase from Vibrio cholerae (DncV) responsible for synthesizing a hybrid cyclic GMP-AMP显示文摘 | Zhenhua Ming Wei Wang Yuchen Xie Pengfei Ding Yuchao Chen Dazhi Jin Yuna Sun Bin Xia Liming Yan Zhiyong Lou | 2014 | Cell Research2014，24，10： | 0 |
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