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| 1 | Medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors显示文摘Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection.Herein,we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective. | Shenghua Gao Tianguang Huang Letian Song Shujing Xu Yusen Cheng Srinivasulu Cherukupalli Dongwei Kang Tong Zhao Lin Sun Jian Zhang Peng Zhan Xinyong Liu | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 5 |
| 2 | Hd1,Ghd7,and DTH8 synergistically determine the rice heading date and yield-related agronomic traits显示文摘Heading date determines the seasonal and regional adaptation of rice(Oryza sativa L.)varieties and is mainly controlled by photoperiod sensitivity(PS).The core heading date genes Hd1,Ghd7,DTH8,and PRR37 act synergistically in regulating the PS.In this study,we systematically analyze the heading date,PS,and agronomic traits of eight homozygous lines with various combinations of Hd1,Ghd7,and DTH8 alleles in the prr37 background under long-day(LD)and short-day(SD)conditions,respectively.We find that Hd1 alone promotes heading,regardless of the day length.However,under LDs,Hd1 suppresses flowering,in coordination with functional Ghd7 or with Ghd7 and DTH8.These loci cooperate to negatively regulate the Ehd1-Hd3 a/RFT1 pathway and delay heading.Under SDs,Hd1 competes with various heading suppressors to promote heading.Therefore,the dual function of Hd1 is vital for PS.The lines carrying Hd1 alone show reduced plant height with fewer primary and secondary branches in panicles.Lines carrying Ghd7 and DTH8(with hd1)show delayed heading and improve agronomic traits.Overall,our results reveal the regulation of rice PS flowering by the core heading date genes and their effects on agronomic traits,providing valuable information for the selection of rice varieties for adaptation to different light and temperature conditions. | Kangli Sun Minghui Huang Wubei Zong Dongdong Xiao Chen Lei Yanqiu Luo Yingang Song Shengting Li Yu Hao Wanni Luo Bingqun Xu Xiaotong Guo Guangliang Wei Letian Chen Yao-Guang Liu Jingxin Guo | 2022 | Journal of Genetics and Genomics2022，49，5： | 4 |
| 3 | Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors显示文摘The main protease(M^(pro))of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle.The covalent M^(pro)inhibitor nirmatrelvir(in combination with ritonavir,a pharmacokinetic enhancer)and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use.Effective antiviral drugs are needed to fight the pandemic,while non-covalent M^(pro)inhibitors could be promising alternatives due to their high selectivity and favorable druggability.Numerous non-covalent M^(pro)inhibitors with desirable properties have been developed based on available crystal structures of M^(pro).In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^(pro)inhibitors,followed by a general overview and critical analysis of the available information.Prospective viewpoints and insights into current strategies for the development of non-covalent M^(pro)inhibitors are also discussed. | Letian Song Shenghua Gao Bing Ye Mianling Yang Yusen Cheng Dongwei Kang Fan Yi Jin-Peng Sun Luis Menéndez-Arias Johan Neyts Xinyong Liu Peng Zhan | 2024 | Acta Pharmaceutica Sinica B2024，14，1： | 0 |
| 4 | Discovery of novel sulfonamide substituted indolylarylsulfones as potent HIV-1 inhibitors with better safety profiles显示文摘Indolylarylsulfones(IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors(NNRTIs) with a unique scaffold and possess potent antiviral activity.To address the high cytotoxicity and improve safety profiles of IASs,we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket.48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities.Especially,compound R_(10)L_(4) was endowed with significant inhibitory activity towards wild-type HIV-1(EC_(50(WT))=0.007μmol/L,SI=30,930) as well as a panel of single-mutant strains exemplified by L100I(EC_(50)=0.017μmol/L,SI=13,055),E138K(EC_(50)=0.017μmol/L,SI=13,123) and Y181C(EC_(50)=0.045μmol/L,SI=4753) which were superior to Nevirapine and Etravirine.Notably,R_(10)L_(4) was characterized with significantly reduced cytotoxicity(CC_(50)=216.51μmol/L) and showed no remarkable in vivo toxic effects(acute and subacute toxicity).Moreover,the computer-based docking study was also employed to characterize the binding mode between R_(10)L_(4) and HIV-1 RT.Additionally,R_(10)L_(4) presented an acceptable pharmacokinetic profile.Collectively,these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development. | Shenghua Gao Letian Song Yusen Cheng Fabao Zhao Dongwei Kang Shu Song Mianling Yang Bing Ye Wei Zhao Yajie Tang Erik De Clercq Christophe Pannecouque Peng Zhan Xinyong Liu | 2023 | Acta Pharmaceutica Sinica B2023，13，6： | 0 |
| 5 | Smart Design and Manufacturing the Welded Q350 Steel Frames via Lifecycle Management Strategy of Digital Twin显示文摘Artificial intelligent aided design and manufacturing have been recognized as one kind of robust data-driven and data-intensive technologies in the integrated computational material engi-neering(ICME)era.Motivated by the dramatical developments of the services of China Railway High-speed series for more than a decade,it is essential to reveal the foundations of lifecycle man-agement of those trains under environmental conditions.Here,the smart design and manufacturing of welded Q350 steel frames of CR200J series are introduced,presenting the capability and opportu-nity of ICME in weight reduction and lifecycle management at a cost-effective approach.In order to address the required fatigue life time enduring more than 9×10^(6)km,the response of optimized frames to the static and the dynamic loads are comprehensively investigated.It is highlighted that the maximum residual stress of the optimized welded frame is reduced to 69 MPa from 477 MPa of previous existing one.Based on the measured stress and acceleration from the railways,the fatigue life of modified frame under various loading modes could fulfil the requirements of the lifecycle man-agement.Moreover,our recent developed intelligent quality control strategy of welding process mediated by machine learning is also introduced,envisioning its application in the intelligent weld-ing. | Letian Fan Xinchao Wang Yongsheng Chen Li Wang Shumi Liu Yuanfei Wang Xinwei Li Kun Du Jia Zhang Xingyu Gao Feng Sun Haifeng Song William Yi Wang Jinshan Li | 2023 | Journal of Beijing Institute of Technology2023，32，4： | 0 |
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