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| 1 | Boceprevir,GC-376,and calpain inhibitors Ⅱ,Ⅻ inhibit SARS-CoV-2 viral replication by targeting the viral main protease显示文摘A new coronavirus SARS-CoV-2,also called novel coronavirus 2019(2019-nCoV),started to circulate among humans around December 2019,and it is now widespread as a global pandemic.The disease caused by SARS-CoV-2 virus is called COVID-19,which is highly contagious and has an overall mortality rate of 6.35%as of May 26,2020.There is no vaccine or antiviral available for SARS-CoV-2.In this study,we report our discovery of inhibitors targeting the SARS-CoV-2 main protease(Mpro).Using the FRET-based enzymatic assay,several inhibitors including boceprevir,GC-376,and calpain inhibitorsⅡ,andⅫwere identified to have potent activity with single-digit to submicromolar ICs0 values in the enzymatic assay.The mechanism of action of the hits was further characterized using enzyme kinetic studies,thermal shift binding assays,and native mass spectrometry.Significantly,four compounds(boceprevir,GC-376,calpain inhibitorsⅡandⅫ)inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37μM.Notably,boceprevir,calpain inhibitorsⅡandⅫrepresent novel chemotypes that are distinct from known substrate-based peptidomimetic Mpro inhibitors.A complex crystal structure of SARS-CoV-2 Mpro with GC-376,determined at 2.15(A)resolution with three protomers per asymmetric unit,revealed two unique binding configurations,shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro.Overall,the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics. | Chunlong Ma Michael Dominic Sacco Brett Hurst Julia Alma Townsend Yanmei Hu Tommy Szeto Xiujun Zhang Bart Tarbet Michael Thomas Marty Yu Chen Jun Wang | 2020 | Cell Research2020，30，8： | 13 |
| 2 | A natural model of behavioral depression in postpartum adult female cynomolgus monkeys (Macaca fascicularis)显示文摘Within the postpartum period, both mothers and infants are susceptible; but because PPD typically occurs for short durations and has moderate symptoms, there exists challenges in exploring and addressing the underlying cause of the depression. This fact highlights the need for relevant animal models. In the present study, postpartum adult female cynomolgus monkeys(Macaca fascicularis) living in breeding groups were observed for typical depressive behavior. The huddle posture behavior was utilized as an indicator of behavioral depression postpartum(BDP) as it has been established as the core depressive-like behavior in primates. Monkeys were divided into two groups: A BDP group(n=6), which were found to spend more time huddling over the first two weeks postpartum than other individuals that formed a non-depression control group(n=4). The two groups were then further analyzed for locomotive activity, stressful events, hair cortisol levels and for maternal interactive behaviors. No differences were found between the BDP and control groups in locomotive activity, in the frequencies of stressful events experienced and in hair cortisol levels. These findings suggested that the postpartum depression witnessed in the monkeys was not related to external factors other than puerperium period. Interestingly, the BDP monkeys displayed an abnormal maternal relationship consisting of increased infant grooming. Taken together, these findings suggest that the adult female cynomolgus monkeys provide a natural model of behavioral postpartum depression that holds a number of advantages over commonly used rodent systems in PPD modeling. The cynomolgus monkeys have a highly-organized social hierarchy and reproductive characteristics without seasonal restriction—similar to humans—as well as much greater homology to humans than rodents. As such, this model may provide a greater translational efficiency and research platform for systematically investigating the etiology, treatment, prevention of PPD. | Xun-Xun CHU Joshua Dominic Rizak Shang-Chuan YANG Jian-Hong WANG Yuan-Ye MA Xin-Tian HU | 2014 | Zoological Research2014，35，3： | 4 |
| 3 | The effect of solvent and matrix combinations on the analysis of bacteria by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry显示文摘 | Domin MA Welham KJ Ashton DS | | 0，，04： | 1 |
| 4 | The characterization of micro-organisms by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry 显示文摘 | Welham KJ Domin MA Scannell DE | 1998 | Rapid Commun Mass Spectrom1998，12，4： | 1 |
| 5 | OSHA's final rule on occupational exposure to bloodbome pathogens 显示文摘 | Domin MA Smith CE | 1992 | J Healthc Mater Manage1992，10，36： | 1 |
| 6 | Activation of caspase-3 in the skeletal muscle during haemodialysis 显示文摘 | Boivin MA Battah SI Dominic EA | 2010 | Eur J Clin Invest2010，40，： | 1 |
| 7 | Activation of caspase- 3 in the skeletal muscle during haemodialysis显示文摘 | Boivin MA Battah SI Dominic EA | 2010 | Eur J Clin Invest2010，40，： | 1 |
| 8 | Activation of caspase-3 in the skeletal muscle during haemodialysis显示文摘 | Boivin MA Battah SI Dominic EA | | 0，，10： | 1 |
| 9 | Haemodialysis induces mitochondrial dysfunction and apoptosis显示文摘 | Raj DSC Boivin MA Dominic EA | 2007 | Eur J Clin Invest2007，37，12： | 1 |
| 10 | Characterization of fungal spores by laser desorption ionization time-of-flight massspectrometry 显示文摘 | Welham KJ Domin MA Johnson K | 2000 | Rapid Communications in Mass Spectrometry2000，14，5： | 1 |
| 11 | The characterization of micro-organism by matrix-assisted laser desorption/ionization time of flight mass spectrometry显示文摘 | Welham KJ Domin MA Scannell DE | 1998 | Rapid Commun Mass Spectrom1998，12，： | 1 |
| 12 | The effect of solvent and matrix combinations on the analysis of bacteria by matrix assisted laser desorption/ionization time-of-flight mass spectrometry显示文摘 | Domin MA Welham KJ Ashton DS | 1999 | Rapid Commun Mass Spectrom1999，13，： | 1 |
| 13 | Activation of caspase-3 in the skeletal muscle during haemodialysis显示文摘 | Boivin MA Battah SI Dominic EA | | 0，，10： | 1 |
| 14 | Activation of caspase-3 in the skeletal muscle during haemodialysis显示文摘 | Boivin MA Battah SI Dominic EA | 2010 | Eur J Clin Invest2010，40，： | 1 |
| 15 | Characterization of fungal spores by laser desorption/ionization time-of-flight mass spectrometry显示文摘 | Welham KJ Domin MA Johnson K | 2000 | Rapid Communications in Mass Spectrometry2000，14，5： | 1 |
| 16 | High-performance mid-wavelength InAs avalanche photodiode using AlAs0.13Sb0.87as the multiplication layer显示文摘We report on a high-performance mid-wavelength infrared avalanche photodetector(APD)with separate absorption and multiplication regions.InAs is used as the absorber material and high-bandgap AlAs0.13Sb0.87 is used as the multiplication material.At room temperature,the APD’s peak response wavelength is 3.27μm,and the 50%cutoff wavelength is 3.5μm.The avalanche gain reaches 13.1 and the responsivity is 8.09 A/W at 3.27μm when the applied reverse bias voltage is 14.6 V.The measured peak detectivity D*of the device is 2.05×10^9 cm·Hz^0.5/W at 3.27μm. | JIANLIANG HUANG CHENGCHENG ZHAO BIYING NIE SHIYU XIE DOMINIC C.M.KWAN XIAO MENG YANHUA ZHANG DIANA L.HUFFAKER WENQUAN MA | 2020 | Photonics Research2020，8，5： | 0 |
| 17 | Social rank and cortisol among female rhesus macaques(Macaca mulatta)显示文摘In animal societies,some stressful events can lead to higher levels of physiological stress.Such stressors,like social rank,also predict an increased vulnerability to an array of diseases.However,the physiological relationship between social rank and stress varies between different species,as well as within groups of a single species.For example,dominant individuals are more socially stressed at times,while at other times it is the subordinate ones who experience this stress.Together,these variations make it difficult to assess disease vulnerability as connected to social interactions.In order to learn more about how physiological rank relationships vary between groups of a single species,cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups.In despotic groups,cortisol levels were found not to be correlated with social rank,but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies.Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals.These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology.The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status. | Dong-Dong QIN Joshua Dominic Rizak Xiao-Li FENG Xun-Xun CHU Shang-Chuan YANG Chun-Lu LI Long-Bao LV Yuan-Ye MA Xin-Tian HU | 2013 | Zoological Research2013，34，S02： | 0 |
| 18 | Social rank and cortisol among female rhesus macaques (Macaca mulatta)显示文摘In animal societies, some stressful events can lead to higher levels of physiological stress. Such stressors, like social rank, also predict an increased vulnerability to an array of diseases. However, the physiological relationship between social rank and stress varies between different species, as well as within groups of a single species. For example, dominant individuals are more socially stressed at times, while at other times it is the subordinate ones who experience this stress. Together, these variations make it difficult to assess disease vulnerability as connected to social interactions. In order to learn more about how physiological rank relationships vary between groups of a single species, cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups. In despotic groups, cortisol levels were found not to be correlated with social rank, but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies. Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals. These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology. The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status. | Dong-Dong QIN Joshua Dominic Rizak Xiao-Li FENG Xun-Xun CHU Shang-Chuan YANG Chun-Lu LI Long-Bao LV Yuan-Ye MA Xin-Tian HU | 2013 | Zoological Research2013，34，2： | 0 |
| 19 | 奥米纽姆摩天大楼显示文摘法兰克福是一座集欧洲古典街区与当代大都市高楼于一体的城市,在城市中心形成了一个充满生机的建筑群落。这种建筑上的结合提供了紧密与动态变化的天际线,与连接法兰克福北部的陶纳斯山脉遥相呼应。奥米纽姆大厦位于城市中建筑高低混合区域的中心,通过周围的环境和建筑来提供一个合理的、具有雕塑感的剪影。BIG建议设计一座塔楼. | Dominic James Black David Verbeek Gunther Weber Helen Chen Joanna Gajda Joseph James Haberl Lukas Kerner Maria Teresa Fernandez Rojo Natalie Isabel Stachnik Nicolas Millot Sabine Kokina Thomas Sebastian Krall Viktoria Millentrup Yan Ma Emily King Enea Michelesio Gabriel■ Ubarevi■iūt■ Giedrius Mamavicius Jesper Boye Andersen Jakob Lange Joanna Jakubowska Katarzyna Joanna Piekarczyk Julieta Muzillo Lorenzo Boddi Lucas Carriere Lucian Tofan Max Aldunate Reitour Raphael Cirani Sabine Kokina Tore Banke Frank Dinger Nils Koenning 陈思瑾(译) | 2019 | 城市环境设计2019，0，2： | 0 |
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