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| 1 | Artificial Intelligence Applications in the Development of Autonomous Vehicles:A Survey显示文摘The advancement of artificial intelligence(AI)has truly stimulated the development and deployment of autonomous vehicles(AVs)in the transportation industry.Fueled by big data from various sensing devices and advanced computing resources,AI has become an essential component of AVs for perceiving the surrounding environment and making appropriate decision in motion.To achieve goal of full automation(i.e.,self-driving),it is important to know how AI works in AV systems.Existing research have made great efforts in investigating different aspects of applying AI in AV development.However,few studies have offered the research community a thorough examination of current practices in implementing AI in AVs.Thus,this paper aims to shorten the gap by providing a comprehensive survey of key studies in this research avenue.Specifically,it intends to analyze their use of AIs in supporting the primary applications in AVs:1)perception;2)localization and mapping;and 3)decision making.It investigates the current practices to understand how AI can be used and what are the challenges and issues associated with their implementation.Based on the exploration of current practices and technology advances,this paper further provides insights into potential opportunities regarding the use of AI in conjunction with other emerging technologies:1)high definition maps,big data,and high performance computing;2)augmented reality(AR)/virtual reality(VR)enhanced simulation platform;and 3)5G communication for connected AVs.This paper is expected to offer a quick reference for researchers interested in understanding the use of AI in AV research. | Yifang Ma Zhenyu Wang Hong Yang Lin Yang | 2020 | IEEE/CAA Journal of Automatica Sinica2020，7，2： | 16 |
| 2 | Gene mutations and clinical phenotypes in Chinese children with Blau syndrome显示文摘The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified10 missense mutations, out of which five were new: R334 L, E383 D, R471 C, C495 R and D512 F. The rest of them, R334 W,R334Q, G481 D, M513 T and R587 C, have been reported previously. Among all the mutations, R334 W, R334 Q and C495 R had the highest frequency. Blau syndrome was found at early age after birth. It began with lepidic rash and symmetric polyarthritis and was phenotypically characterized by typical rash, arthritis, iridocyclitis and arteritis. Cardiac involvement was also found in Blau syndrome. In addition to nerve deafness, renal involvement, osteochondroma and central nervous system involvement were also found in our patients. Therefore, Chinese children with Blau syndrome have unique gene mutations and complicated clinical phenotypes. Pathologic examination and CARD15 mutation testing should be considered for diagnosis as early as possible for suspected patients. | Caifeng Li Junmei Zhang Shipeng Li Tongxin Han Weiying Kuang Yifang Zhou Jianghong Deng Xiaohua Tan | 2017 | Science China(Life Sciences)2017，60，7： | 13 |
| 3 | Theoretical and experimental investigation on a liquid-gas ejector power cycle using ammonia-water显示文摘The purpose of this paper is to investigate a novel power cycle using low-temperature heat sources such as oceanic-thermal, biomass as well as industrial waste heat. Both a reheater and a liquid-gas ejector are used in this ammonia-water based cycle. Energy analysis and parametric analysis are performed to guide the theoretical performance and experimental investigation is done to verify the theoretical results. The results show that the generator pressure, heating source temperature and turbine outlet depressurization made by the ejector can affect the cycle performances. Besides, the experimental thermal efficiency is much lower than the theoretical one on account of the heat losses and irreversibility. Moreover, the performance of liquid-gas ejector is affected by primary flow pressure and temperature. | YUAN Han MEI Ning LI Yan YANG Shuai HU SiYuan HAN YiFang | 2013 | Science China(Technological Sciences)2013，56，9： | 10 |
| 4 | Gene mutations and clinical phenotypes in 15 Chinese children with cryopyrin-associated periodic syndrome(CAPS)显示文摘The aim of our study is to explore the features of clinical manifestations and genetic mutations in Chinese CAPS patients. Fifteen confirmed patients with CAPS were enrolled. The onset time ranges from 2 days after birth to 6 years and 1 month. Recurrent urticaria rash(93.3%) with fever(100%) were two dominant characteristics of these patients that were presented as either acute or chronic process. Systemic involvements were found in all patients except for one with only rash and fever. The top three symptoms were fever(100%), rash(93.3%) and myalgia(76%). Other clinical manifestations include arthritis(11 cases), lung involvement(seven cases), optical dysfunction(seven cases), nerve deafness(six cases), nervous system involvement(five cases), hepatomegaly, splenomegaly and lymphadenectasis(five cases). Also, four patients had heart involvement and one patient suffered kidney involvement. The laboratory inflammation index such as leukocyte counts, platelet counts, erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), serum amyloid A(SAA) and fibrinogen(FIB) increased significantly at initial stage, but decreased after therapy. As for gene mutation detection, Twelve out of 15 patients were confirmed with mutation in NLRP3, including 11 mutant site: c1789 A>G, c.1703 T>A, c.913 G>A, c.1710 G>C, c.1057 G >T, c.2335 C>T, c.932 T>C,c.296 G>C, c.663 C>T, t.1702 T>A, 299 G>A. Mutation sites c.1703 T>A, c.2335 C>T, c.296 G>C, c.663 C>T, and 299 G>A were newly identified. The association between gene mutation and clinical manifestation shows that D305 N was highly associated with severe organs involvements, and therefore, the time of therapy and regimen were critical for the prognosis of disease. As the largest cohort study of Chinese CAPS patients, we confirmed that all patients presented typical clinical manifestations, identified five new mutation sites on NLRP3 and analyzed the correlation between the genotypes and phenotypes. We also raise concerns for one case with serious conditions that only had two nonsense mutations(c.663 C>T and t.1702 T>A) detected. | Caifeng Li Xiaohua Tan Junmei Zhang Shipeng Li Wenxiu Mo Tongxin Han Weiying Kuang Yifang Zhou Jianghong Deng | 2017 | Science China(Life Sciences)2017，60，12： | 9 |
| 5 | A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts显示文摘Terminally differentiated cells can be generated by lineage reprogramming,which is,however,hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming. | Bingqing Xie Da Sun Yuanyuan Du Jun Jia Shicheng Sun Jun Xu Yifang Liu Chengang Xiang Sitong Chen Huangfan Xie Qiming Wang Guangya Li Xuehui LYU Hui Shen Shiyu Li Min Wu Xiaonan Zhang Yue Pu Kuanhui Xiang Weifeng Lai Peng Du Zhenghong Yuan Cheng Li Yan Shi Shichun Lu Hongkui Deng | 2019 | Cell Research2019，29，9： | 9 |
| 6 | Variation in cis-regulation of a NAC transcription factor contributes to drought tolerance in wheat显示文摘Drought is a major environmental factor limiting wheat production worldwide,and developing drought-tolerant cultivars is a central challenge for wheat breeders globally.Therefore,it is important to identify genetic components determining drought tolerance in wheat.In this study,we identified a wheat NAC gene(TaNAC071-A)that is tightly associated with drought tolerance by a genome-wide association study.Knockdown of TaNAC071-A in wheat attenuated plant drought tolerance,whereas its overexpression significantly enhanced drought tolerance through improved water-use efficiency and increased expression of stress-responsive genes.This heightened water-saving mechanism mitigated the yield loss caused by water deficit.Further candidate gene association analysis showed that a 108-bp insertion in the promoter of TaNAC071-A alters its expression level and contributes to variation in drought tolerance among wheat accessions.This insertion contains two MYB cis-regulatory elements(CREs)that can be directly bound by the MYB transcription activator,TaMYBL1,thereby leading to increased TaNAC071-A expression and plant drought tolerance.Importantly,introgression of this 108-bp insertion allele,TaNAC071-AIn-693,into drought-sensitive cultivars could improve their drought tolerance,demonstrating that it is a valuable genetic resource for wheat breeding.Taken together,our findings highlight a major breakthrough in determining the genetic basis underlying phenotypic variation in wheat drought tolerance and showcase the potential of exploiting CRE-containing indels for improving important agronomical traits. | Hude Mao Shumin Li Bin Chen Chao Jian Fangming Mei Yifang Zhang Fangfang Li Nan Chen Tian Li Linying Du Li Ding Zhongxue Wang Xinxiu Cheng Xiaojing Wang Zhensheng Kang | 2022 | Molecular Plant2022，15，2： | 9 |
| 7 | Characteristic of Torsional Vibration of Mill Main Drive Excited by Electromechanical Coupling显示文摘In the study of electromechanical coupling vibration of mill main drive system, the influence of electrical system on the mechanical transmission is considered generally, however the research for the mechanism of electromechanical interaction is lacked. In order to research the electromechanical coupling resonance of main drive system on the F3 mill in a plant, the cycloconverter and synchronous motor are modeled and simulated by the MTLAB/SIMULINK firstly, simulation result show that the current harmonic of the cycloconverter can lead to the pulsating torque of motor output. Then the natural characteristics of the mechanical drive system are calculated by ANSYS, the result show that the modal frequency contains the component which is close to the coupling vibration frequency of 42 Hz. According to the simulation result of the mechanical and electrical system, the closed loop feedback model including the two systems are built, and the mechanism analysis of electromechanical coupling presents that there is the interaction between the current harmonic of electrical system and the speed of the mechanical drive system. At last, by building and computing the equivalent nonlinear dynamics model of the mechanical drive system, the dynamic characteristics of system changing with the stiffness, damping coefficient and the electromagnetic torque are obtained. Such electromechanical interaction process is suggested to consider in research of mill vibration, which can induce strong coupling vibration behavior in the rolling mill drive system. | ZHANG Yifang YAN Xiaoqiang LIN Qihui | 2016 | Chinese Journal of Mechanical Engineering2016，29，1： | 8 |
| 8 | INTEGRATED APPROACH TO ASSEMBLY SEQUENCE PLANNING OF C0MPLEX PRODUCTS显示文摘Assembly sequence planning will be more difficult due to the in-creasing complexity of products.An integrated approach to assembly sequence planning of complex products applying de-composition-planning-combination strategy is presented.First,an assembly is decomposed into a hierarchical structure using an assembly structure representation based on connectors.Then,an assembly planning system is used to generate the sequences that are locally optimal for each leaf partition in the structure hierarchy.By combining the local sequences systematically in a bottom-up manner and choosing suitable ones from the merged sequences,the assembly sequence of each parent structure including the whole assembly is generated.An integrated system has been completed.A complex product is given to illustrate the feasibility and the practicality of the approach. | Wang Junfeng Liu Jihong Zhong Yifang CAD Center,Huazhong University of Science and Technology,Wuhan 430074, China | 2004 | Chinese Journal of Mechanical Engineering2004，17，2： | 8 |
| 9 | A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer显示文摘The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer(CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment(TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death(ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3(Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin(QTN) that elicited reactive oxygen species(ROS). To amelioratein vivo delivery barriers associated with chemotherapeutic drugs, a folate(FA)-targeted polyethylene glycol(PEG)-modified amphiphilic cyclodextrin nanoparticle(NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation(CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC. | Dandan Sun Yifang Zou Liu Song Shulan Han Hao Yang Di Chu Yun Dai Jie Ma Caitriona M.O’Driscoll Zhuo Yu Jianfeng Guo | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 8 |
| 10 | Reputation-based secure spectrum situation fusion in distributed cognitive radio networks显示文摘In distributed cognitive radio(CR) network, the cooperative spectrum situation sensing based on consensus scheme may be disrupted by spectrum sensing data falsification(SSDF) attacks. In this paper, a secure spectrum situation fusion scheme based on reputation is proposed to counter attacks. The neighboring nodes of secondary users(SUs) get the corresponding dynamic trust value according to their behavior, which restrict the impact of the malicious behavior on the premise to ensure information interaction of normal nodes. Theoretical analysis and simulation results show that the consensus fusion scheme based on reputation has better performance than the existing algorithm which eliminates the neighboring node with the biggest deviation value from mean value. It demonstrates that the proposed scheme not only achieves better convergence properties but also has higher detection probability than the existing scheme in the process of spectrum situation fusion. | Li Fangwei Liu Fan Zhu Jiang Nie Yifang | 2015 | The Journal of China Universities of Posts and Telecommunications2015，22，3： | 6 |
| 11 | Pathological changes in the lungs and lymphatic organs of 12 COVID-19 autopsy cases显示文摘Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics.In this study,we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents—findings that evaluated histopathological changes;immune cell signature and inflammatory factor expression in the lungs,spleen and lymph nodes.Here we show that the major pulmonary alterations included diffuse alveolar damage,interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates,macrophage infiltration and abundant production of inflammatory factors(IL-6,IP-10,TNFo?and IL-I f).The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation,including lymphopenia and macrophage accumulation.These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients. | Qian Liu Yu Shi Jun Cai Yaqi Duan Rongshuai Wang Hongyan Zhang Qiurong Ruan Jiansha Li Lei Zhao Yifang Ping Rong Chen Liang Ren Xiaochun Fei Heng Zhang Rui Tang Xi Wang Tao Luo Xindong Liu Xuequan Huang Zhenhua Liu Qilin Ao Yong Ren Jing Xiong Zhicheng He Haibo Wu Wenjuan Fu Pengnan Zhao Xinwei Chen Guoqiang Qu Yunyun Wang Xi Wang Jia Liu Dongfang Xiang Sanpeng Xu Xiaowei Zhou Qingrui Li Jinghong Ma Heng Li Jie Zhang Sizhe Huang Xiaohong Yao Yiwu Zhou Chaofu Wang Dingyu Zhang Guoping Wang Liang Liu Xiu-Wu Bian | 2020 | National Science Review2020，7，12： | 6 |
| 12 | Real-time visualization of 3D city models at street-level based on visual saliency显示文摘Street-level visualization is an important application of 3D city models.Challenges to street-level visualization include the cluttering of buildings due to fine detail and visualization performance.In this paper,a novel method is proposed for streetlevel visualization based on visual saliency evaluation.The basic idea of the method is to preserve these salient buildings in a scene while removing those that are non-salient.The method can be divided into pre-processing procedures and real-time visualization.The first step in pre-processing is to convert 3D building models at higher Levels of Detail(Lo Ds) into LoD 1 models with simplified ground plans.Then,a number of index viewpoints are created along the streets; these indices refer to both the position and the direction of each street site.A visual saliency value is computed for each building,with respect to the index site,based on a visual difference between the original model and the generalized model.We calculate and evaluate three methods for visual saliency:local difference,global difference and minimum projection area.The real-time visualization process begins by mapping the observer to its closest indices.The street view is then generated based on the building information stored in those indexes.A user study shows that the local visual saliency method performs better than do the global visual saliency,area and image-based methods and that the framework proposed in this paper may improve the performance of 3D visualization. | MAO Bo BAN YiFang Lars HARRIE | 2015 | Science China Earth Sciences2015，58，3： | 5 |
| 13 | Development of a coupled supersonic inlet-fan Navier–Stokes simulation method显示文摘A coupled supersonic inlet-fan Navier–Stokes simulation method was developed by using COMSOL-CFD code. The flow turning, pressure rise and loss effects across blade rows of the fan and the inlet-fan interactions were taken into account as source terms of the governing equations without a blade geometry by a body force model. In this model, viscous effects in blade passages can also be calculated directly, which include the exchange of momentum between fluids and detailed viscous flow close to walls. NASA Rotor 37 compressor test rig was used to validate the ability of the body force model to estimate the real performance of blade rows. Calculated pressure ratio characteristics and the distribution of the total pressure, total temperature, and swirl angle in the span direction agreed well with experimental and numerical data. It is shown that the body force model is a promising approach for predicting the flow field of the turbomachinery. Then, coupled axisymmetric mixed compression supersonic inlet-fan simulations were conducted at Mach number 2.8 operating conditions. The analysis includes coupled steady-state performance, and effects of the fan on the inlet. The results indicate that the coupled simulation method is capable of simulating behavior of the supersonic inlet-fan system. | Qiushi LI Yongzhao LYU Tianyu PAN Da LI Ha'nan LU Yifang GONG | 2018 | Chinese Journal of Aeronautics2018，31，2： | 5 |
| 14 | Collaborative validation of GlobeLand30:Methodology and practices显示文摘30-m Global Land Cover(GLC)data products permit the detection of land cover changes at the scale of most human land activities,and are therefore used as fundamental information for sustainable development,environmental change studies,and many other societal benefit areas.In the past few years,increasing efforts have been devoted to the accuracy assessment of GlobeLand30 and other finer-resolution GLC data products.However,most of them were conducted either within a limited percentage of map sheets selected from a global scale or in some individual countries(areas),and there are still many areas where the uncertainty of 30-m resolution GLC data products remains to be validated and documented.In order to promote a comprehensive and collaborative validation of 30-m GLC data products,the GEO Global Land Cover Community Activity had organized a project from 2015 to 2017,to examine and explore its major problems,including the lack of international agreed validation guidelines and on-line tools for facilitating collaborative validation activities.With the joint effort of experts and users from 30 GEO member countries or participating organizations,a technical specification for 30-m GLC validation was developed based on the findings and experiences.An on-line validation tool,GLCVal,was developed by integrating land cover validation procedures with the service computing technologies.About 20 countries(regions)have completed the accuracy assessment of GlobeLand30 for their territories with the guidance of the technical specification and the support of GLCVal. | Jun Chen Lijun Chen Fei Chen Yifang Ban Songnian Li Gang Han Xiaohua Tong Chuang Liu Vanya Stamenova Stefan Stamenov | 2021 | Geo-Spatial Information Science2021，24，1： | 5 |
| 15 | DELAUNAY TRIANGULATION METHOD OF CURVED SURFACES BASED ON RIEMANNIAN METRIC显示文摘A method for quality mesh generation of parametric curved surfaces is proposed. It is shown that the main difference between the proposed method and previous ones is that our meshing process is done completely in the parametric domains with the guarantee of mesh quality. To obtain this aim, the Delaunay method is extended to anisotropic context of 2D domains, and a Riemannian metric map is introduced to remedy the mapping distortion from object space to parametric domain. Compared with previous algorithms, the approach is much simpler, more robust and speedy. The algorithm is implemented and examples for several geometries are presented to demonstrate the efficiency and validity of the method. | Zhao Jianjun Wang QifuZhong Yifang Zhou Ji ZhaoYiCAD Center,Huazhong University of Scienceand Technology,Wuhan 430074, China | 2003 | Chinese Journal of Mechanical Engineering2003，16，1： | 4 |
| 16 | Thermo-optic all-optical devices based on two-dimensional materials显示文摘In this paper, we review our recent work on thermo-optic all-optical devices based on two-dimensional(2 D)materials. The unique properties of 2 D materials enable fast and highly efficient thermo-optic control of light.A few all-optical devices are demonstrated based on various thermo-optic mechanisms. Both fiber and integrated devices will be shown. | KAN WU YIFANG WANG CIYUAN QIU JIANPING CHEN | 2018 | Photonics Research2018，6，10： | 4 |
| 17 | DESIGN OF DIGITAL IMPACTING FILTER IN CP-EBPSK WITH RANDOM-POLAR COMMUNICATION SYSTEM显示文摘To solve the difficulty of designing digital impacting filter in the receiver of random-polar modulated Extended Binary Phase Shift Keying with Continuous Phase (CP-EBPSK), a design method based on Quantum-behaved Particle Swarm Optimization (QPSO) algorithm is proposed. Firstly, QPSO is introduced elaborately, and the basic flow of QPSO is also given. Then, the demodulation principle of digital impacting filter in the communication system of CP-EBPSK with random-polar is demonstrated, and QPSO is utilized to design the digital impacting filter, which also takes the effect of finite word length into consideration when implemented by hardware. Finally, the proposed method is simulated. Simulation results show that the digital impacting filter designed by new method can derive satisfied demodulation performance. | Jin Yi Wu Lenan Chen Yifang Yu Jing | 2012 | Journal of Electronics(China)2012，29，3： | 4 |
| 18 | CAD/CAE OF THE WORKING CHARACTERISTICS OF A NEW TYPE OF FLUID COUPLING SHOCK ABSORBER显示文摘For purpose of simulation of the working characteristics of a new type of fluid coupling shock absorber for vibration protection of sensitive equipment, a physical model is presented by analyzing the internal fluid dynamic phenomenon with respect to the coupling shock absorber and implemented in MATLAB software package. Using the model it is possible to evaluate the importance of different factors for design of the shock absorber. In the meantime, the key-model machine is designed for coupling dynamic test. Comparisons with experimental results confirm the validity of the model. So the CAD/CAE software has been developed in MATLAB for design and experimental test of the new coupling shock absorber. | Yang Ping Zhong Yifang Zhou JiSchool of Mechanical Science and Engineering, Huazhong University of Science and Technology,Wuhan 430074, ChinaLiu Yong Guilin Institute of Electronic Technology | 2002 | Chinese Journal of Mechanical Engineering2002，15，3： | 4 |
| 19 | Precision integration of grating-based polarizers onto focal plane arrays of near-infrared photovoltaic detectors for enhanced contrast polarimetric imaging显示文摘Polarimetric imaging enhances the ability to distinguish objects from a bright background by detecting their particular polarization status,which offers another degree of freedom in infrared remote sensing.However,to scale up by monolithically integrating grating-based polarizers onto a focal plane array(FPA)of infrared detectors,fundamental technical obstacles must be overcome,including reductions of the extinction ratio by the misalignment between the polarizer and the detector,grating line width fluctuations,the line edge roughness,etc.This paper reports the authors’latest achievements in overcoming those problems by solving key technical issues regarding the integration of large-scale polarizers onto the chips of FPAs with individual indium gallium arsenide/indium phosphide(In Ga As/In P)sensors as the basic building blocks.Polarimetric and photovoltaic chips with divisions of the focal plane of 540×4 pixels and 320×256 superpixels have been successfully manufactured.Polarimetric imaging with enhanced contrast has been demonstrated.The progress made in this work has opened up a broad avenue toward industrialization of high quality polarimetric imaging in infrared wavelengths. | Bo Feng Yifang Chen Duo Sun Zongyao Yang Bo Yang Xue Li Tao Li | 2021 | International Journal of Extreme Manufacturing2021，3，3： | 4 |
| 20 | High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors显示文摘A new coronavirus(SARS-CoV-2)has been identified as the etiologic agent for the COVID-19 outbreak.Currently,effective treatment options remain very limited for this disease;therefore,there is an urgent need to identify new anti-COVID-19 agents.In this study,we screened over 6,000 compounds that included approved drugs,drug candidates in clinical trials,and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease(PLpro).Together with main protease(Mpro),PLpro is responsible for processing the viral replicase polyprotein into functional units.There-fore,it is an attractive target for antiviral drug develop-ment.Here we discovered four compounds,YM155,cryptotanshinone,tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 pmol/L.These compounds also exhibit strong antiviral activities in cell-based assays.YM155,an anti-cancer drug candidate in clinical trials,has the most potent antiviral activity with an EC50 value of 170 nmol/L.In addition,we have determined the crystal structures of this enzyme and its complex with YM155,revealing a unique binding mode.YM155 simultaneously targets three'hot'spots on PLpro,including the substrate-binding pocket,the interferon stimulating gene product 15(ISG15)binding site and zinc finger motif.Our results demonstrate the efficacy of this screening and repur-posing strategy,which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments. | Yao Zhao Xiaoyu Du Yinkai Duan Xiaoyan Pan Yifang Sun Tian You Lin Han Zhenming Jin Weijuan Shang Jing Yu Hangtian Guo Qianying Liu Yan Wu Chao Peng Jun Wang Chenghao Zhu Xiuna Yang Kailin Yang Ying Lei Luke W.Guddat Wenqing Xu Gengfu Xiao Lei Sun Leike Zhang Zihe Rao Haitao Yang | 2021 | Protein & Cell2021，12，11： | 4 |
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