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Chemistry-led in.estigation. in.o the mode of action.of n.MPT activators,resultin. in.the discovery of n.n.pyridyl class n.MPT activators

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Acta Pharmaceutica Sin.ca B 2023年第2期13卷 709-721页

作者： Siyuan.Tan. Miguel Garzon.San. Oliver smith An.reas Krämer Dan.el Egbase paul W.Caton.Stefan.Kn.pp Sam Butterworth Division.of Pharmacy an. Optometry School of Health SciencesManchester Academic Health Sciences CentreUniversity of ManchesterManchester M139PLUK Structural Gen.mics Con.ortium(SGC) 60438 Frankfurt Am MainGermany Buchman. In.titute for Life Scien.es(BMLS) 60438 Frankfurt Am MainGermany In.titut für Pharmazeutische Chemie Goethe University60438 Frankfurt Am MainGermany Fran.furt Can.er In.titute(FCI) 60596 Frankfurt Am MainGermany Departmen. of Diabetes School of Cardiovascular and Metabolic Medicine&SciencesFaculty of Life Sciences&MedicineKing's College LondonLondon SE11ULUK

The cofactor n.cotin.mide aden.n. din.cleotide(n.D+)plays a key role in.a wide ran.e of physiological processes an. main.ain.n. or en.an.in. n.D+levels is an.established approach to en.an.in. healthy ***,several classes of n.cotin.mide phosphoribosyl tran.ferase(n.MPT)activators have been.shown.to in.rease n.D+levels in.vitro an. in.vivo an. to demon.trate ben.ficial effects in.an.mal *** best validated of these compoun.s are structurally related to kn.wn.urea-type n.MPT in.ibitors,however the basis for the switch from in.ibitory activity to activation.is n.t well *** we report an.evaluation.of the structure activity relation.hips of n.MPT activators by design.n.,syn.hesisin. an. testin. compoun.s from other n.MPT ligan. chemotypes an. mimetics of putative phosphoribosylated adducts of kn.wn.*** results of these studies led us to hypothesise that these activators act via a through-water in.eraction.in.the n.MPT active site,resultin. in.the design.of the first kn.wn.urea-class n.MPT activator that does n.t utilise a pyridin.-like warhead,which shows similar or greater activity as a n.MPT activator in.biochemical an. cellular assays relative to kn.wn.an.logues.

关键词： n.cotin.mide phosphoribosyl tran.ferase activator Healthy agin. Drug discovery Bioisosteres Medicin.l chemistry

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Muscle force an. movemen. variability before an. after total kn.e arthroplasty: A review

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World Journ.l of Orthopedics 2014年第2期5卷 69-79页

作者： Jessica W smith Jesse C Christen.en.Robin.L Marcus paul C LaStayo Departmen. of Bioen.in.erin. University of Utah Salt Lake City UT 84108-1290 United States Departmen. of Physical Therapy University of Utah Salt Lake City UT 84108-1290 United States Departmen. of Orthopedics University of Utah Salt Lake City UT 84108-1290 United States Departmen. of Exercise an. Sport Scien.e University of Utah Salt Lake City UT 84108-1290 United States

Variability in.muscle force output an. movemen. variability are importan. aspects of iden.ifyin. in.ividuals with mobility deficits, cen.ral n.rvous system impairmen.s, an. future risk of fallin.. This has been.in.estigated in.elderly healthy an. impaired adults, as well as in.adults with osteoarthritis(OA), but the question.of whether the same correlation. also apply to those who have un.ergon. a surgical in.erven.ion.such as total kn.e arthroplasty(TKA) is still bein. in.estigated. While there is a growin. body of literature iden.ifyin. poten.ial rehabilitation.targets for in.ividuals who have un.ergon. TKA, it is importan. to first un.erstan. the un.erlyin. post-operative impairmen.s to more efficien.ly target fun.tion.l deficits that may lead to improvedlon.-term outcomes. The purpose of this article is to review the poten.ial role of muscle force output an. movemen. variability in.TKA recipien.s. The n.rrative review relies on.existin. literature in.elderly healthy an. impaired in.ividuals, as well as in.those with OA before an. followin. TKA. The variables that may predict lon.term fun.tion.l abilities an. deficits are discussed in.the con.ext of existin. literature in.healthy older adults an. older adults with OA an. followin. TKA, as well as the role future research in.this field may play in.providin. eviden.e-based data for improved rehabilitation.targets.

关键词： Osteoarthritis Elderly Total kn.e arthroplasty Movemen. variability

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功函促进钼基异质结电催化剂的电子结构重整提升其析氢反应活性（英文）

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Scien.e Chin. Materials 2025年第1期 189-198页

作者：陈想冯帅谢松苗亚萍高标张旭明黄莉李筠 paul K.Chu 彭祥 Hubei Key Laboratory of Plasma Chemistry an. Advan.ed Materials Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education School of Materials Science and Engineering Wuhan Institute of Technology School of Textile Scien.e an. En.in.erin. Xi'an Polytechnic University The State Key Laboratory of Refractories an. Metallurgy Institute of Advanced Materials and Nanotechnology Wuhan University of Science and Technology Guizhou Wujian. Hydropower Developmen. Co. Ltd. Departmen. of Physics Department of Materials Science and Engineering and Department of Biomedical Engineering City University of Hong Kong

Mo基催化剂在电催化析氢反应（HER）中具有巨大应用潜力.然而,其活性位点的暴露不足、极强的氢吸附能力导致其催化性能未能充分体现.本文在碳布上构筑了Mo2n.MoSe2异质结（Mn.）,以增强Mo基催化剂的HER活性.由于Mn.中的Mo2n.有较低的...

Mo基催化剂在电催化析氢反应（HER）中具有巨大应用潜力.然而,其活性位点的暴露不足、极强的氢吸附能力导致其催化性能未能充分体现.本文在碳布上构筑了Mo2n.MoSe2异质结（Mn.）,以增强Mo基催化剂的HER活性.由于Mn.中的Mo2n.有较低的功函数,能够在异质界面产生内建电场,显著提高了其在HER中电荷转移效率.此外,Mn.中原子之间的强电子相互作用优化了Mo位点的电子结构,降低了氢吸附能力,进一步增强了其本征催化活性.因此, Mn.催化剂产生20 m A cm-2和1 A cm-2的析氢电流密度所需的过电位仅为65和210 mV, Tafel斜率仅为96 mV dec-1.此外, Mn.在1 A cm-2电流密度下稳定运行240小时后,形貌、结构和性能均无明显变化.以上研究结果为工业大电流制氢所需的非贵金属基电催化剂的设计和合成提供了新思路.

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Oxidative stress an. male reproductive health

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Asian.Journ.l of An.rology 2014年第1期16卷 31-38页

作者： Robert J Aitken.Tegan.B smith Matthew S Joblin. Mark A Baker Geoffry n.De Iuliis Priority Research Cen.re in.Reproductive Scien.e Discipline of Biological Sciences Faculty of Science and IT University of Newcastle Callaghan NSW 2308 Australia

On. of the major causes of defective sperm fun.tion.is oxidative stress, which n.t on.y disrupts the in.egrity of sperm Dn. but also limits the fertilizin. poten.ial of these cells as a result of collateral damage to protein. an. lipids in.the sperm plasma membran.. The origin. of such oxidative stress appear to in.olve the sperm mitochon.ria, which have a ten.en.y to gen.rate high leve｜s of superoxide an.on.as a prelude to en.erin. the in.rin.ic apoptotic cascade. Un.ortun.tely, these cells have very little capacity to respon. to such an.attack because they on.y possess the first en.yme in.the base excision.repair （BER） pathway, 8-oxoguan.n. glycosylase 1 （OGG1）. The latter successfully creates an.abasic site, but the spermatozoa can.ot process the oxidative lesion.further because they lack the down.tream protein. （APE1, XRCC1） n.eded to complete the repair process. It is the respon.ibility of the oocyte to con.in.e the BER pathway prior to in.tiation.of S-phase of the first mitotic division. If a mistake is made by the oocyte at this stage of developmen., a mutation.will be created that will be represen.ed in.every cell in.the body. Such mechan.sms may explain.the in.rease in.childhood can.ers an. other diseases observed in.the offsprin. of males who have suffered oxidative stress in.their germ lin. as a con.equen.e of age, en.iron.en.al or lifestyle factors. The high prevalen.e of oxidative Dn. damage in.the spermatozoa of male in.ertility patien.s may have implication. for the health of children.con.eived in.vitro an. serves as a driver for curren. research in.o the origin. of free radical gen.ration.in.the germ lin..

关键词： Dn. damage oxidative stress oxoguan.n. glycosylase 1 oocyte spermatozoa

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Would behavioral thermoregulation.en.ble pregn.n. viviparous tropical lizards to cope with a warmer world?

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In.egrative Zoology 2017年第5期12卷 379-395页

作者： Saúl LÓPEZ-ALCAIDE Miguel n.KAMURA Eric n.smith En.ique MARTÍn.Z-MEYER Departamen. of Zoology Institute of BiologyNational Autonomous University of MexicoMexico CityMexico Cen.er for Research in.Mathematics GuanajuatoMexico Amphibian.an. Reptile Diversity Research Cen.er an. Departmen. of Biology University of Texas at ArlingtonArlingtonTexasUSA

Sceloporus lizards depen. on.extern.l heat to achieve their preferred temperature(Tsel)for performin. physiological *** both in.the field an. laboratory in.icates that pregn.n. females of this Gen.s select body temperatures(Tb)lower than.34℃ as higher temperatures may be lethal to ***,thermoregulation.is crucial for successful embryo *** the in.rease in.global air temperature,it is expected that the first compen.atory respon.e of species that in.abit tropical climates will be behavioral *** tested whether viviparous Sceloporus formosus group lizards in.the wild exhibited differen.es in.thermoregulatory behavior to achieve the kn.wn.Tsel for developin. embryos regardless of local thermal *** quan.ified field active body temperature,thermoregulatory behavior mechan.sms(time of sightin.,microhabitat used an. baskin. time)an. available microhabitat thermal con.ition.(*** temperature)for 10 lizard species durin. gestation.distributed alon. an.altitudin.l *** applied both con.en.ion.l an. phylogen.c an.lyses to explore whether Tb or behavioral thermoregulation.could be regulated in.respon.e to differen. thermal *** species showed n. sign.fican. differen.es in.field Tb durin. gestation.regardless of local thermal *** con.rast,they exhibited sign.fican. differen.es in.their behavioral thermoregulation.associated with local en.iron.en.al *** on.these observation.,the differen.es in.thermoregulatory behavior iden.ified are in.erpreted as compen.atory adjustmen.s to local thermal *** con.lude that these species may deal with higher temperatures predicted for the tropics by modulatin. their thermoregulatory behavior.

关键词： altitudin.l gradien. behavior global warmin. Sceloporus formosus thermal stress

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Dyn.mical An.lysis of A Class of Rotation.theta-equation

Dynamical Analysis of A Class of Rotation-theta-equation

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作者： n.gbo paul-Ren. Marie n.GBO 浙江师范大学

学位级别：硕士

In.this dissertation.we an.lyze the rotation.θ equation.which is the theta equation.augmen.ed with the Coriolis effect,in.uced by the earth *** Rotation.θ equation.is a gen.ralization.of a family of models(in.ludin. the Rotation.CamassaHolm equation.an. the Rotation.Degasperis-Procesi).Our study is con.ucted via the bifurcation.method an. qualitative theory of dyn.mical *** existen.e of n.t on.y smooth solitary wave solution.periodic wave solution.but also peakon.an. periodic peakon.solution. are given.

关键词： Rotation.θ-equation solitary wave solution periodic wave solution peakon.solution periodic peakon.solution

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An.In.estigation.on.Thermization.of Milk in.Can.Usin. Computation.l Fluid Dyn.mics

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Journ.l of Food Scien.e an. En.in.erin. 2011年第1期1卷 35-44页

作者： D. An.n. paul n. Chhan.al C. An.n.haramakrishn.n Human.Resource Developmen. Central Food Technological Research Institute Council of Scientific and Industrial Research （CSIR）Mysore 570020 India

Thermal processin. of milk is an.importan. un.t operation.to in.ctivate the spoilage organ.sm an. en.ymes an. thus in.rease the storage life of milk, It was very difficult to fin. out the temperature distribution.in.ide the can. durin. thermal processin.. A Computation.l Fluid Dyn.mics （CFD） model was developed for thermization.of milk in.the can.heatin. at 65℃ for the first time to determin. the temperature distribution.in.the can.ed milk at station.ry position. This developed CFD model was validated with the experimen.al measuremen.s of temperature. The effects of thermization.temperature on.milk flow profile （velocity）, milk temperature an. viscosity profiles in.ide the can.durin. thermal process were in.estigated. Temperature profiles of milk in.can.at three differen. plan.s （i.e. top, middle an. bottom plan.） were studied. Moreover, thermization.un.t was calculated by correlatin. with temperature an. it was foun. that maximum thermization.un.t was achieved at 540 s of thermal processin. of milk in.can.

关键词： CFD (Computation.l Fluid Dyn.mics) thermization can.ed milk thermization.un.t

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Capitalizin. on.multi-elemen. in.eraction. through bal-an.ed n.trition.—A pathway to improve n.trogen.use efficien.y in.Chin.,In.ia an. n.rth America

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Scien.e Chin.(Life Scien.es) 2005年第z2期48卷 780-790页

作者： paul E.Fixen.K.n.Tiwari Mark D.Stauffer Potash & Phosphate In.titute Brookin.s SD 57006USA Potash & Phosphate In.titute of Can.da Midtown.Plaza SK S7K 1J5Canada

A viable option.for in.reasin. n.trogen.(n. use efficien.y an. mitigation.of n.gative impacts of n.on.the en.iron.en. is to capitalize on.multi-elemen. in.eraction. through implemen.ation.of n.trien. man.gemen. programs that provide balan.ed n.trition. n.merous studies have demon.trated the immediate efficacy of this approach in.the developin. region. like Chin. an. In.ia as well as developed coun.ries in.n.rth America. Based on.241 site-years of experimen.s in.these coun.ries, the first-year n.recovery efficien.y (RE) for the con.en.ion.l or check treatmen.s averaged 21% while the balan.ed treatmen.s averaged 54% RE, for an.average in.rease of 33% in.RE due to balan.ed n.trition. Effective policies to promote adoption.are most likely those that en.ble site-specific approaches to n.trien. man.gemen. decision. rather than.sweepin., n.tion.wide in.en.ives supportin. on. n.trien. over an.ther. Local farmers, advisers an. officials n.ed to be empowered with tools an. in.ormation.to help them defin. n.cessary chan.es in.practices to create more balan.ed n.trien. man.gemen..

关键词： capitalizin., balan.ed n.trition. n.trogen use efficien.y.

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En.in.erin. metabolic pathways in.Amycolatopsis japon.cum for the optimization.of the precursor supply for heterologous brasilicardin.con.en.rs production

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Syn.hetic an. Systems Biotechn.logy 2018年第1期3卷 56-63页

作者： paul n.Schwarz Luisa Roller An.reas Kulik Wolfgan. Wohlleben.Evi Stegman. Microbiology/Biotechn.logy Interfaculty Institute of Microbiology and Infection Medicine Tübingen(IMIT)Eberhard Karls University TübingenTübingenGermany German.Cen.re for In.ection.Research(DZIF) Partner Site TübingenTübingenGermany

The isopren.id brasilicardin.A is a promisin. immun.suppressan. compoun. with a un.que mode of action.high poten.y an. reduced toxicity compared to today's stan.ard ***,production.of brasilicardin.has been.hampered sin.e the producer strain.n.cardia terpen.ca IFM0406 syn.hesizes brasilicardin.in.on.y low amoun.s an. is a biosafety level 2 ***,we were able to heterologously express the brasilicardin.gen. cluster in.the n.cardioform actin.mycete Amycolatopsis *** brasilicardin.con.en.rs,in.ermediates of the BraA biosyn.hesis,were *** chemical syn.hesis of the brasilicardin.core structure has remain.d elusive we in.en.ed to produce high amoun.s of the brasilicardin.backbon. for semi syn.hesis an. ***,we used a metabolic en.in.erin. approach to in.rease heterologous production.of brasilicardin.in.*** heterologous expression.of gen.s en.odin. the MVA pathway an. expression.of diterpen.id specific pren.ltran.ferases were used to in.rease the provision.of the isopren.id precursor isopen.en.l diphosphate(IPP)an. to chan.el the precursor in.o the direction.of diterpen.id *** approaches con.ributed to an.elevated heterologous production.of the brasilicardin.backbon.,which can.n.w be used as a startin. poin. for semi syn.hesis of n.w brasilicardin.con.en.rs with better properties.

关键词： n.rcardia terpen.ca IFM0406 Mevalon.te pathway Isopren.ids Pren.ltran.ferases

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Phage-mediated horizon.al gen. tran.fer an. its implication. for the human.gut microbiome

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Gastroen.erology Report 2022年第1期10卷 78-89页

作者： Tatian. Borodovich An.rey n.Shkoporov R.paul Ross Colin.Hill APC Microbiome Irelan. University College CorkCorkIreland School of Microbiology University College CorkCorkIreland

Horizon.al gen. tran.fer(HGT)in.the microbiome has profoun. con.equen.es for human.health an. *** spread of an.ibiotic resistan.e gen.s,virulen.e,an. pathogen.city determin.n.s predomin.n.ly occurs by way of *** exists of exten.ive horizon.al tran.fer in.the human.gut *** tran.duction.is a type of HGT even. in.which a bacteriophage tran.fers n.n.viral Dn. from on. bacterial host cell to *** abun.an.e of tailed bacteriophages in.the human.gut suggests that tran.duction.could act as a sign.fican. mode of HGT in.the gut *** we review in.detail the kn.wn.mechan.sms of phage-mediated HGT,n.mely specialized an. gen.ralized tran.duction.lateral tran.duction.gen.-tran.fer agen.s,an. molecular piracy,as well as methods used to detect phage-mediated HGT,an. discuss its poten.ial implication. for the human.gut microbiome.

关键词： gut phageome horizon.al gen. tran.fer gen. tran.duction phage-mediated gen. tran.fer

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