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Acta Pharmaceutica Sinica B 2022年第10期12卷 3924-3933页

作者： Bo Qin Gregory B.Craven Pengjiao Hou julian Chesti Xinran Lu Emma S.Child Rhodri M.L.Morgan Wenchao Niu Lina Zhao Alan Armstrong david J.Mann Sheng Cui NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100076China Department of Life Sciences Imperial College LondonSouth Kensington CampusLondon SW72AZUK Department of Chemistry Imperial College LondonMolecular Sciences Research HubWhite City CampusWood LaneLondon W120BZUK CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy PhysicsUniversity of Chinese Academy of SciencesBeijing 100049China

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional *** of these proteases exhibit a similar fold and contain an essential catalytic cysteine,offering the opportunity to inhibit these enzymes with electrophilic small *** we describe the successful application of quantitative irreversible tethering(qIT)to identify acrylamide fragments that target the active site cysteine of the 3C protease(3Cpro)of Enterovirus 71,the causative agent of hand,foot and mouth disease in humans,altering the substrate binding ***,we re-purpose these hits towards the main protease(Mpro)of SARS-CoV-2 which shares the 3C-like fold and a similar active *** hit fragments covalently link to the catalytic cysteine of Mpro to inhibit its *** demonstrate that targeting the active site cysteine of Mpro can have profound allosteric effects,distorting secondary structures to disrupt the active dimeric unit.

关键词： SARS-CoV-2 Protease inhibitors Covalent fragments Allosteric inhibition EV71

dentification of AtOPT4 as a Plant Glutathione ;ransporter

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Molecular Plant 2016年第3期9卷 481-484页

作者： Zhongchun Zhang Qingqing Xie Timothy O. Jobe Andrew R. Kau Cun Wang Yunxia Li Baosheng Qiu Qiuquan Wang david G. Mendoza-Cdzatl julian I. Schroeder Division of Biological Sciences Cell and Developmental Biology Section University of California San Diego La Jolla CA 92093-0116 USA School of Life Sciences Central China Normal University Wuhan 430079 Hubei P.R. China Hubei Key Laboratory of Genetic Regulation and Integrative Biology Central China Normal University Wuhan 430079 Hubei P.R. China Department of Chemistry & the MOE Key Lab of Spectrochemical Analysis and Instrumentation College of Chemistry and Chemical Engineering Xiamen University Xiamen Fujian 361005 China Division of Plant Sciences C.S. Bond Life Sciences Center University of Missouri Columbia MO 65211 USA

Glutathione （GSH） is an essential tri-peptide important for several plant processes, including the control of cellular redox status, detoxification of xenobiotics, root development, heavy metal transport and resista... 详细信息

关键词： detoxification Cadmium phytochelatins

Platelet count as a screening tool for compensated cirrhosis in chronic viral hepatitis

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World Journal of Gastrointestinal Pathophysiology 2021年第3期12卷 40-50页

作者： Pallavi Surana julian Hercun Varun Takyar david E Kleiner Theo Heller Christopher Koh Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney DiseasesBethesdaMD 20892United States Laboratory of Pathology National Cancer InstituteBethesdaMD 20892United States

BACKGROUND Simple tools for clinicians to identify cirrhosis in patients with chronic viral hepatitis are medically necessary for treatment initiation,hepatocellular cancer screening and additional medical *** To determine whether platelets or other laboratory markers can be used as a simple method to identify the development of *** Clinical,biochemical and histologic laboratory data from treatment naive chronic viral hepatitis B(HBV),C(HCV),and D(HDV)patients at the NIH Clinical Center from 1985-2019 were collected and subjects were randomly divided into training and validation *** markers were tested for their ability to identify cirrhosis(Ishak≥5)using receiver operating characteristic curves and an optimal cut-off was calculated within the training *** final cut-off was tested within the validation *** Overall,1027 subjects(HCV=701,HBV=240 and HDV=86),66%male,with mean(standard deviation)age of 45(11)years were *** the training cohort(n=715),platelets performed the best at identifying cirrhosis compared to other laboratory markers[Area Under the Receiver Operating Characteristics curve(AUROC)=0.86(0.82-0.90)]and sensitivity 77%,specificity 83%,positive predictive value 44%,and negative predictive value 95%.All other tested markers had AUROCs≤*** optimal platelet cut-off for detecting cirrhosis in the training cohort was 143×109/L and it performed equally well in the validation cohort(n=312)[AUROC=0.85(0.76-0.94)].CONCLUSION The use of platelet counts should be considered to identify cirrhosis and ensure optimal care and management of patients with chronic viral hepatitis.

关键词： Chronic hepatitis B Chronic hepatitis C Chronic hepatitis D Platelets Cirrhosis Non-invasive assessment

Periodic interstellar scintillation variations of PSRs J0613-0200 and J0636+5128 associated with the Local Bubble shell

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中国科学:物理学、力学、天文学英文版 2023年第11期66卷 221-232页

作者： Yulan Liu Robert A.Main Joris P.W.Verbiest Ziwei Wu Krishnakumar M.Ambalappat Jiguang Lu david J.Champion Ismael Cognard Lucas Guillemot Kuo Liu James W.mc Kee Nataliya Porayko Golam.M.Shaifullah Gilles Theureau National Astronomical Observatories Chinese Academy of SciencesBeijing100101China Fakultät für Physik Universität BielefeldBielefeld33501Germany Max-Planck-Institut für Radioastronomie Bonn53121Germany Florida Space Institute University of Central FloridaOrlandoFL32826USA Station de radioastronomie de Nançay Observatoire de ParisNançay18330France Laboratoire de Physique et Chimie de l’Environnement et de l’Espace Universitéd’OrléansOrléans45071France E.A.Milne Centre for Astrophysics University of HullHullHU67RXUK Centre of Excellence for Data Science Artificial Intelligence and ModellingUniversity of HullHullHU67RXUK Dipartimento di Fisica“G.Occhialini” Universitàdi Milano-BicoccaMilano20126Italy INAF-Osservatorio Astronomico di Cagliari Selargius(CA)09047Italy INFN Sezione di Milano-BicoccaMilano20126Italy

Annual variations of interstellar scintillation can be modelled to constrain parameters of the ionized interstellar *** a pulsar is in a binary system,then investigating the orbital parameters is possible through analysis of the orbital variation of *** observations carried out from 2011 to 2020 by the European Pulsar Timing Array radio telescopes,PSRs J0613-0200and J0636+5128 show strong annual variations in their scintillation velocity,while the former additionally exhibits an orbital *** theory and Markov-chain-Monte-Carlo methods are used to interpret these periodic *** assume a thin and anisotropic scattering screen model,and discuss the mildly and extremely anisotropic scattering *** J0613-0200is best described by mildly anisotropic scattering,while PSR J0636+5128 exhibits extremely anisotropic *** measure the distance,velocity,and degree of anisotropy of the scattering screen for our two pulsars,finding that scattering screen distances from Earth for PSRs J0613-0200 and J0636+5128 are 316_(-20)^(+28)pc and 262_(-38)^(+96)pc,*** positions of these scattering screens are coincident with the shell of the Local Bubble towards both *** associations add to the growing evidence of the Local Bubble shell as a dominant region of scattering along many sightlines.

关键词： pulsar interstellar scintillation ionized interstellar medium

Risk factors and outcomes of delayed graft function in renal transplant recipients receiving a steroid sparing immunosuppression protocol

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World Journal of Transplantation 2017年第1期7卷 34-42页

作者： Michelle Willicombe Anna Rizzello Dawn Goodall Vassilios Papalois Adam G mc Lean david Taube Imperial College Kidney and Transplant Centre Hammersmith Hospital

AIM To analyse the risk factors and outcomes of delayed graft function(DGF) in patients receiving a steroid sparing protocol. METHODS Four hundred and twenty-seven recipients of deceased donor kidney transplants were studied of which 135(31.6%) experienced DGF. All patients received monoclonal antibody induction with a tacrolimus based, steroid sparing immunosuppression *** Five year patient survival was 87.2% and 94.9% in the DGF and primary graft function(PGF) group respectively, P = 0.047. Allograft survival was 77.9% and 90.2% in the DGF and PGF group respectively, P < 0.001. Overall rejection free survival was no different between the DGF and PGF groups with a 1 and 5 year rejection free survival in the DGF group of 77.7% and 67.8% compared with 81.3% and 75.3% in the PGF group, P = 0.19. Patients with DGF who received IL2 receptor antibody induction were at significantly higher risk of rejection in the early post-transplant period than the group with DGF who received alemtuzumab induction. On multivariate analysis, risk factors for DGF were male recipients, recipients of black ethnicity, circulatory death donation, preformed DSA, increasing cold ischaemic time, older donor age and dialysis *** Alemtuzumab induction may be of benefit in preventing early rejection episodes associated with DGF. Prospective trials are required to determine optimal immunotherapy protocols for patients at high risk of DGF.

关键词： Allograft failure Deceased donors Delayed graft function Cold ischaemic time Rejection Steroid sparing Alemtuzumab

Extraction Characteristics of Selenium as Affected by Coal Fly Ash Type, Water Extractant, and Extraction Time

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Journal of Environmental Protection 2014年第12期5卷 1126-1144页

作者： Mark A. Cantrell Kristofor R. Brye david M. Miller Esten Mason julian Fairey AEP-Swepco Flint Creek Power Plant Gentry AR USA Department of Crop Soil and Environmental Sciences University of Arkansas Fayetteville AR USA Department of Civil Engineering University of Arkansas Fayetteville AR USA

Selenium (Se) contamination can be a potential groundwater concern near un-lined coal ash landfills. Of all the Environmental Protection Agency’s priority and non-priority pollutants, Se has the narrowest concentration range considered beneficial and detrimental for aquatic and terrestrial organisms. The effects of ash type (i.e., fresh and weathered), water-extractant type (i.e., deionized water, rainwater, and groundwater), and extraction time (i.e., 2 and 6 hours) on Se, arsenic (As), and chromium (Cr) concentrations were investigated from Class C, subbituminous coal fly ash produced at the Flint Creek Power Plant (Benton County, AR). Water-extractable Se concentrations differed (p = 0.03) between ash types across water-extractants, but were unaffected (p > 0.05) by extraction times. Unexpectedly, fresh ash water-extractable Se concentrations were below minimum detection limits (i.e., 2.0 μg·L-1) for all treatments. In contrast, averaged over extraction times, the water-extractable Se concentration from weathered ash was greatest (p < 0.05) with groundwater and rainwater, which did not differ and averaged 60.0 μg·L-1, compared to extraction with deionized water (57.6 μg·L-1). Selenite SeO32- was greater (p ·L-1) than in the weathered ash (0.70 mg·kg-1), while selenate SeO42- concentration was greater (p < 0.001) in the weathered (0.67 mg·kg-1) than in fresh ash (0.48 mg·kg-1). Results from this study indicate that environmental weathering of Class C, subbituminous fly ash promotes oxidation of selenite, to the less toxic, but highly mobile selenate. The formation of hydrated ettringite [Ca6Al2(SO4)3(OH)12·26H2O] and calcium selenite (CaSeO3) likely acted as a sink for weathered ash selenite. Implications of this research include a better understanding of the past, present, and future environmental and health risk potential associated with the release of watersoluble Se, As, and Cr to aid in the development of sustainable fly ash management strategies.

关键词： Arsenic Chromium Coal Fly Ash Landfill Selenium

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梅奥精神之精髓

全科医学临床与教育 2010年第1期8卷 1-2,5页

作者：王家铃 david mc Fadden 浙江大学医学院附属邵逸夫医院院办浙江杭州310016 美国梅奥诊所普内科

美国梅奥诊所（Mayo Clinic），云集全美顶尖医学专家，服务精良，环境一流。梅奥对高水准服务质量的追求，对于细节近乎苛刻的要求，以及对招聘员工价值观的重视程度，都表明梅奥是一所具有丰厚组织文化和价值观底蕴的医疗组织。

关键词：梅奥精髓精神服务质量医学专家重视程度医疗组织组织文化

The effects of a supervised Pilates training program on balance in Parkinson’s disease

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Advances in Parkinson's Disease 2013年第2期2卷 58-61页

作者： Liam Johnson david Putrino Ian James julian Rodrigues Rick Stell Gary Thickbroom Frank L. Mastaglia Australian Neuro-Muscular Research Institute Movement Disorders Clinic Queen Elizabeth II Medical Centre Centre for Neuro- muscular & Neurological Disorders University of Western Australia Crawley Australia Australian NeuroMuscular Research Institute Movement Disorders Clinic Queen Elizabeth II Medical Centre Centre for Neuromuscular & Neurological Disorders University of Western Australia Crawley Australia Australian Neuro-Muscular Research Institute Movement Disorders Clinic Queen Elizabeth II Medical Centre Centre for Neuromuscular & Neurological Disorders University of Western Australia Crawley Australia Australian NeuroMuscular Research Institute Movement Disorders Clinic Queen Elizabeth II Medical Centre Centre for Neuromuscular & Neurological Disorders University of Western Australia Crawley Australia School of Psychological and Clinical Sciences Charles Darwin University Darwin Australia Department of Mathematics and Statistics Murdoch University Murdoch Australia

Pilates therapy improves core muscle function and axial stability but its effects on balance in idiopathic Parkinson’s disease (IPD) have not been evaluated. The objective of this study was to evaluate the effects of a Pilates exercise program on postural stability and balance confidence in people with IPD. Ten IPD patients (Hoehn & Yahr Stage 1-3) with a history of falls or nearfalls had the following assessments before and after completion of a 6-week supervised Pilates exercise program: Activities-Specific Balance Confidence Scale (ABC);Berg Balance Scale (BBS);Schwab and England Scale (SES);Unified Parkinson’s Disease Rating Scale (UPDRS);pull-test;timed-up-and-go (TUG);5-metre walk;static and dynamic posturography. There were significant improvements in BBS score, 5-metre walk time and TUG after the training program, as well as improvement trends in some posturographic measures. Participants also reported improved balance confidence with Activities of Daily Living (ADLs). Our findings suggest that Pilates therapy can be beneficial in IPD and warrants further evaluation in a larger study.

关键词： Parkinson’s Disease Pilates Postural Instability Static Dynamic Posturography

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机器学习系统设计

Impact of sesame lignan on physical and oxidative stability of flaxseed oil-in-water emulsion

作者： (美)戴维·朱利安(david julian)

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Oil Crop Science 2019年第4期4卷 254-266页

作者： Xintian Wang Kun Yu Chen Cheng Xiao Yu david julian mc.lements Wenwen Huang Jia Yang Fenghong Huang Qianchun Deng Key Laboratory of Oilseeds Processing Ministry of AgricultureOil Crops Research InstituteChinese Academy of Agricultural ScienceWuhanChina College of Food and Biological Engineering Henan Collaborative Innovation Center for Food Production and SafetyHenan Key Laboratory of Cold Chain Food Quality and Safety ControlZhengzhou University of Light IndustryZhengzhouChina Department of Food Science University of Massachusetts AmherstAmherstMAUSA

Recent studies have shown that the highly susceptibility to oxidation ofα-linolenic acid(ALA)enriched emulsion delivery system was harmful for human health which limited their incorporation into functional *** of natural sesamol(SOH)and sesamin(SES)on stability of flaxseed oil-in-water emulsion were *** showed that SOH indicated higher antioxidant activity and significantly prolonged the time of emulsion oil-off by retarding oil droplet aggregation in a dose dependent manner throughout ***,SOH showed substantial extended lag phase of lipid oxidation products,especially for secondary oxidation products(thiobarbituric acid-reactive substances,TBARS),with a maximum reduction of 70%with 800 M *** antioxidative efficiency of SOH might relate to its strong ability of scavenging free radical and chelate transition ***,SOH significantly enhanced interfacial barrier property and reduced permeation rate of peroxyl radical across emulsion interface by hydrogen bonds between sugar groups of saponin molecules and ***,no obvious change in barrier property of emulsion was observed in *** improved physicochemical property of flaxseed oil-in-water emulsion with higher antioxidant activity and stronger interfacial barrier property,so that it could be serve as plant-based antioxidant in oil-in-water emulsion delivery system.

关键词： lipid oxidation sesamol sesamin quillaja saponin oil-in-water emulsions