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Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

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World Journal of Gastroenterology 2024年第25期30卷 3182-3184页

作者： Jeffrey A Lowell Michael J Farber keith Sultan Department of Medicine Zucker School of Medicine at HofstraNorth Shore University Hospital-Long Island Jewish Medical CenterManhassetNY 11030United States Preclinical Studies New York Institute of Technology College of Osteopathic MedicineGlen HeadNY 11545United States Division of Gastroenterology Northwell HealthNorth Shore University Hospital and Long Island Jewish Medical CenterGreat NeckNY 10021United States

Inflammatory bowel disease(IBD)is entering a potentially new era of combined *** et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this *** importance of controlled trials should be stressed in establishing new treatment *** prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

关键词： Inflammatory bowel disease Biologics Immunomodulators Dual-therapy Combination therapy

Matt Cutts: Try something new for 30 days

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新世纪智能 2024年第40期 17-19页

作者： keith

当你开始感叹生活枯燥，每天的生活除上学放学、吃饭看书、洗漱睡觉之外再无乐趣可言时，不妨试着改变你的生活方式：培养一种新的爱好，每天做一件你喜欢做的事情，或者培养一种新的生活习惯。每天只需努力一点点，你的生活就会因此而...

当你开始感叹生活枯燥，每天的生活除上学放学、吃饭看书、洗漱睡觉之外再无乐趣可言时，不妨试着改变你的生活方式：培养一种新的爱好，每天做一件你喜欢做的事情，或者培养一种新的生活习惯。每天只需努力一点点，你的生活就会因此而大不相同。A few years ago, I felt like I was stuck in a rut,

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Embracing the Year of the Dragon

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China Today 2024年第2期73卷 30-32页

作者： keith BENNETT Friends of Socialist China based in London

The Lunar New Year has increasingly become a common festival of people throughout the *** people,and people throughout the world,are looking forward to welcoming the Year of the Dragon,which falls on February 10,*** Dragon is considered the most auspicious of the 12 signs in the Chinese zodiac and this year is specifically the Year of the Wood Dragon,the first since *** to Lifestyle Asia,“Wood Dragons enjoy fulfilling ***’re likely to materialize all their ambitions into actions,coming up with truly revolutionary ideas.”

关键词： looking has likely

Five Principles as Relevant Today as 70 Years Ago

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China Today 2024年第8期73卷 18-19页

作者： keith BENNETT 不详

The Chinese initiative has become an international consensus with productive actions.A conference marking the 70th anniversary of the Five Principles of Peaceful Coexistence,a cornerstone of Chinese foreign policy,was held in Beijing on June 28,attracting attendees from around the world,including former political leaders from some 20 *** the conference,President Xi Jinping made an important speech in which he said that the Five Principles“marked a groundbreaking and epoch-making achievement in the history of international relations.”

关键词： corners attracting Peace

Symptom presentation and evolution in the first 48 hours after injury are associated with return to play after concussion in elite Rugby Union

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Journal of Sport and Health Science 2024年第3期13卷 387-397页

作者： Ross Tucker Matt Cross keith Stokes Lindsay Starling Rosy Hyman Simon Kemp Stephen West Martin Raftery Eanna Falvey James Brown Institute of Sport and Exercise Medicine(ISEM) Department of ExerciseUniversity of StellenboschTygerberg 7505South Africa World Rugby Ltd. Dublin D02 AE93Ireland Premiership Rugby London SW1V 1PXUK Centre for Health and Injury and Illness Prevention in SportUniversity of BathClaverton Down BA27AYUK UK Collaborating Centre on Injury and Illness Prevention in Sport(UKCCIIS) University of BathClaverton Down BA27AYUK Rugby Football Union London TW27BAUK London School of Tropical Medicine London WC1E 7HTUK Sport Injury Prevention Research Centre Faculty of KinesiologyUniversity of CalgaryCalgary T2N 1N4Canada Department of Medicine School of Medicine and HealthUniversity College CorkCork T12 EC8PIreland Carnegie Applied Rugby Research(CARR)centre Carnegie School of SportLeeds Beckett UniversityLeeds LS63QSUK

Background:Return to play(RTP)in elite rugby is managed using a 6-stage graduated RTP protocol,which can result in clearance to play within 1 week of *** aimed to explore how symptom,cognitive,and balance presentation and evolution during concussion screens 2 h(head injury assessment(HIA2)and 48 h(HIA3)after injury were associated with time to RTP)to identify whether a more conservative graduated RTP may be ***:A retrospective cohort study was conducted in 380 concussed rugby players from elite men’s rugby over 3 consecutive *** were classified as shorter or longer returns,depending on whether RTP occurred within 7 days(allowing them to be considered to play the match 1 week after injury)or longer than 8 days,***,cognitive,and balance performance during screens was assessed relative to baseline(normal or abnormal)and to the preceding screen(improving or worsening).Associations between sub-test abnormalities and RTP time were explored using odds ratios(OR,longer ***).Median day absence was compared between players with abnormal or worsening results and those whose results were normal or ***:Abnormal symptom results during screens 2 h and 48 h after concussion were associated with longer return time(HIA2:OR=2.21,95%confidence interval(95%CI):1.39-3.50;HIA3:OR=3.30,95%CI:1.89-5.75).Worsening symptom number or severity from the time of injury to 2 h and 48 h post-injury was associated with longer return(HIA2:OR=2.49,95%CI:1.36-4.58;HIA3:OR=3.34,95%CI:1.10-10.15).Median days absence was greater in players with abnormal symptom results at both HIA2 and *** and balance performance were not associated with longer return and did not affect median days ***:Symptom presentation and evolution within 48 h of concussion were associated with longer RTP *** may guide a more conservative approach to RTP,while still adhering to individualized concussion management principles.

关键词： Brain injury Concussion management General return to play Medical management

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欧洲MRO正在积极应对欧盟对俄制裁

航空维修与工程 2024年第8期 21-22页

作者： keith Mwanalushi 文峻

俄乌冲突爆发后，欧盟出台的一系列对俄严格制裁措施，给欧洲MRO市场带来了较大影响，如钛等航空原材料的供应、供应链的管控流程、租赁市场的合规运营等。为此，欧洲MRO供应商正在采取多项策略，努力缓解成本增长、交货期延长和合规风...

俄乌冲突爆发后，欧盟出台的一系列对俄严格制裁措施，给欧洲MRO市场带来了较大影响，如钛等航空原材料的供应、供应链的管控流程、租赁市场的合规运营等。为此，欧洲MRO供应商正在采取多项策略，努力缓解成本增长、交货期延长和合规风险等方面的压力。自2022年2月俄乌冲突爆发以来，欧盟对俄罗斯采取了一系列前所未有的制裁措施。在俄罗斯经济遭受严重打击的情形下，航空维修领域中的MRO企业已明显感受到来自欧盟对俄罗斯制裁的负面影响。为了应对挑战，欧洲MRO通过重新评估发展战略，采用多样化选择供应商的策略来分散供应链风险，努力缓解成本增长、交货期延长和合规风险等方面的压力。

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劳埃晶体学时代的到来

生物物理学报 2002年第1期18卷 1-10页

作者：任重 Dominique Bourgeois John R.Helliwell keith moffat Vukica Srajer Barry L.Stoddard 沈月全杨晓静任匡一顾茵 Department of Biochemistry and Molecular Biology and Consortium for Advanced Radiation Sources European Synchrotron Radiation Facility BP22038043 Grenoble CedexFranceand UPR9015/IBS41 Avenuedes Martyrs Department of Chemistry University of Manchester Program in Structural Biology Division of Basic SciencesFred Hutchinson Cancer Research Center 中国科学院生物物理研究所 Renz ResearchInc.任氏研究所

Singer等人（1993）的研究表明通过仔细选择一个特异的底物有可能改变一个多步反应的动力学轨迹；pH跳跃能提供一个有效的，依赖于扩散的方法在整个晶体范围内触发一个慢催化事件。在这个例子中，丝氨酸蛋白酶胰蛋白酶在亲核反应残基Ser... 详细信息

Singer等人（1993）的研究表明通过仔细选择一个特异的底物有可能改变一个多步反应的动力学轨迹；pH跳跃能提供一个有效的，依赖于扩散的方法在整个晶体范围内触发一个慢催化事件。在这个例子中，丝氨酸蛋白酶胰蛋白酶在亲核反应残基Ser195处被p-胍基苯甲酸（GB）酰化。在这个底物很容易形成一个酰基化酶中间物，但进行水解和再生游离酶却很慢。

关键词：蛋白质晶体学劳埃技术实验方法

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劳埃晶体学时代的到来

生物物理学报 2001年第3期17卷 419-434页

作者： REN Zhong Dominique Bourgeois John R.Helliwell keith moffat VukicaSrajer Barry L.Stoddard 沈月全杨晓静任匡一顾茵任重 Department of Biochemistry and Molecular Biology and Consortium for Advanced Radiation Sources The University of Chicago European Synchrotron Radiation Facility Department of Chemistry University of Manchester Programin Structural Biology Division of Basic SciencesFred Hutchinson Cancer Research Center 中国科学院生物物理研究所 Renz ResearchInc.任氏研究所 Ben May Institute The University of Chicago

近年来 ,人们对古老的劳埃衍射技术重新产生了浓厚的兴趣。这主要是因为世界各地新的同步辐射光源的建成;各种先进的插入件,诸如波形器(wiggler)、波荡器(undulator)的飞速发展 ;以及利用这类光源通过时间分辨晶体学来研究分子结构动态... 详细信息

近年来 ,人们对古老的劳埃衍射技术重新产生了浓厚的兴趣。这主要是因为世界各地新的同步辐射光源的建成;各种先进的插入件,诸如波形器(wiggler)、波荡器(undulator)的飞速发展 ;以及利用这类光源通过时间分辨晶体学来研究分子结构动态变化的前景。在过去的十年中 ,理论研究已经阐明了多波长衍射几何学的特征 ,在很大程度上加深了我们对劳埃法的认识。劳埃数据处理方法及其软件开发也因此有所创新。曾在相当长的时间内限制这项技术应用的劳埃数据处理中的大部分问题现在已经得到解决 ;同步辐射光源 ,束线光学器件及X射线探测器等方面也都取得了显著的进步。静态劳埃实验得到的结构因子振幅在质量上已同单波长数据相当。晶体中反应易于启动的时间分辨劳埃实验已经开始在一系列生物分子体系中得到成功的实践。由此得到的关于结构动力学的信息是任何其它传统的衍射方法所无能为力的。这些静态的及时间分辨的实验说明了劳埃法已经开始走向成熟 ,并指明了今后发展的方向 ,即对晶体的镶嵌度和劳埃衍射点的相应能量宽度的正确处理、扩散散射的考虑、时间分辨实验中低浓度瞬态中间物结构的测定等等。

关键词：劳埃衍射时间分辨晶体学生物分子

EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell Jun Okabe Ishant Khurana Thomas Karagiannis Julia J.Liang Lina Mariana Thomas Loudovaris Thomas Kay Assam El-Osta Epigenetics in Human Health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release *** type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-*** of these cells leads to a lifelong dependence on exogenous insulin administration for ***,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell *** and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation *** transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 *** the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell *** transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin *** EZH2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex *** pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors