简介:Objective:MemorystemTcells(Tscm)haveattractedattentionbecauseoftheirenhancedself-renewal,multipotentcapacity,andanti-tumorcapacities.However,littleisknownaboutTscminpatientswithrenalclearcellcarcinoma(RCC)andtheroleofWntsignalinginthesecells.WeevaluatedTscmfromRCCpatientsconcerningtheiractivationofWntsignalinginvitroandexploredthemechanismofpreferentialsurvival.Methods:FlowcytometryidentifiedsurfacemarkersandcytokinesproducedfromaccumulatedTscminthepresenceoftheglycogensynthasekinasebetainhibitorTWS119.Apoptosiswasevaluatedafterinductionusingtumornecrosisfactor-alpha.ImmunofluorescenceandWesternblotanalyseswereusedtoinvestigatetheactivationofthenuclearfactor-kappaB(NF-КB)pathway.Results:RCCpatientshadasimilarpercentageofCD4~+andCD8~+Tscmashealthydonors.ActivationofWntsignalingbyTWS119resultedintheaccumulationofTscminactivatedTcells,butreversalofdifferentiatedTcellstoTscmwasnotachieved.PreferentialsurvivalofTscmwasassociatedwithincreasedanti-apoptoticabilitymediateddownstreamoftheNF-КBactivationpathway.Conclusions:ThefindingthatTscmcanaccumulatebyWntsignalinginvitroinbloodfromRCCpatientswillhelpindevisingnewcancertherapystrategiesofTscm-basedadoptiveimmunotherapy,suchasdendriticcell-stimulatedTscm,andTcellreceptororchimericantigenreceptor-engineeredTscm.
简介:虽然小学已经开始STEM启蒙,但是中学生才对STEM学习具备自主意识,而且由于中高考衔接涉及未来职业发展方向的选择,所以研究中学生STEM学习态度有助于学科教师改善教学和提供针对性的生涯指导。该研究以江苏省四座城市六所STEM项目试点学校参加STEM项目学习的部分学生为研究对象,通过国外成熟量表工具对483位具有STEM学习经历的中学生进行调查,了解其STEM学习态度以及对STEM相关职业的态度取向。结果发现:研究对象对STEM学习态度整体趋向积极,但是对未来可能从事STEM领域职业的正向态度比例不高;初中生的STEM学习态度比高中生更积极;男生STEM学习态度比女生更为积极;对STEM相关学科教师的喜爱影响STEM学习态度。在研究基础上建议中学教学应关注职业生涯教育,重新审视中学理科的考试改革,提升STEM及相关学科课程教师的核心素养,改善STEM相关学科课堂教学以及提供促进女生STEM教育的干预措施。
简介:Theinsectmidgutepitheliumiscomposedofcolumnar,goblet,andregenerativecells.Columnarepithelialcellsarethemostabundantandhavemembraneprotrusionsthatformthebrushbordermembrane(BBM)ontheirapicalside.Theseincreasesurfaceareaavailableforthetransportofnutrients,butalsoprovideopportunitiesforinteractionwithxenobioticssuchaspathogens,toxinsandhostplantallelochemicals.RecentimprovementsinproteomicandbioinfbrmaticstoolsprovidedanopportunitytodeterminetheproteomeoftheT.niBBMinunprecedenteddetail.ThisstudyreportstheidentificationofproteinsfromBBMvesicles(BBMVs)usingsingledimensionpolyacrylamidegelelec?trophoresiscoupledwithmulti-dimensionalproteinidentificationtechnology.Morethan3000proteinswereassociatedwiththeBBMVofwhich697werepredictedtopossesseitherasignalpeptide,atleastonetransmembranedomainoraGPI-anchorsignal.Ofthese,bioinfbrmaticsanalysisandmanualcurationpredictedthat185maybeassociatedwiththeBBMVorepithelialcellplasmamembrane.Thesearediscussedwithrespecttotheirpredictedfunctions,namelydigestion,nutrientuptake,cellsignaling,development,cell-cellinteractions,andotherfunctions.Webelievethistobethemostdetailedproteomicanalysisofthelepidopteranmidgutepitheliummembranetodate,whichwillprovideinformationtobetterunderstandthebiochemical,physiologicalandpathologicalprocessestakingplaceinthelarvalmidgut.
简介:Objective:ToexaminetheeffectofpSer9-GSK-3βonbreastcancerandtodeterminewhethertheunderlyingmetabolicandimmunologicalmechanismisassociatedwithROS/eIF2Bandnaturalkiller(NK)cells.Methods:WeemployedTWS119toinactivateGSK-3βbyphosphorylatingSer9andexploreditseffectonbreastcancerandNKcells.TheexpressionofGSK-3β,naturalkillergroup2memberD(NKG2D)ligands,eIF2BwasquantifiedbyPCRandWesternblot.Wemeasuredintracellularreactiveoxygenspecies(ROS)andmitochondrialROSusingDCFH-DAandMitoSOXTMprobe,respectively,andconductedquantitativeanalysisofcellularrespirationon4T1cellswithmitochondrialrespiratorychaincomplexⅠ/Ⅲkits.Results:OurinvestigationrevealedthatTWS119downregulatedNKG2Dligands(H60aandRae1),suppressedthecytotoxicityofNKcells,andpromotedthemigrationof4T1murinebreastcancercells.Nevertheless,LY290042,whichattenuatesp-GSK-3βformationbyinhibitingthePI3K/Aktpathway,reversedtheseeffects.WealsofoundthathigherexpressionofpSer9-GSK-3βinducedhigherlevelsofROS,andobservedthatabnormalityofmitochondrialrespiratorychaincomplexⅠ/ⅢfunctioninducedthedysfunctionofGSK-3β-inducedelectrontransportchain,naturallydisturbingtheROSlevel.Inaddition,theexpressionofNOX3andNOX4wassignificantlyup-regulated,whichaffectedthegenerationofROSandassociatedwiththemetastasisofbreastcancer.Furthermore,wefoundthattheexpressionofpSer535-eIF2BpromotedtheexpressionofNKG2Dligands(Mult-1andRae1)followingbyexpressionofpSer9-GSK-3βandgenerationofROS.Conclusions:ThePI3K/Akt/GSK-3β/ROS/eIF2BpathwaycouldregulateNKcellactivityandsensitivityoftumorcellstoNKcells,whichresultedinbreastcancergrowthandlungmetastasis.Thus,GSK-3βisapromisingtargetofanti-tumortherapy.
简介:摘要 ; 随着当前教学时代的转变,教学理念也在发生着巨大的变化 为了提高教师的教学能力 , 改善教学环境,新兴的教学理念对于 当今的教师有很大的积极性,而这其中被广泛运用的就是 STEM 教学理念。
简介:摘要STEM教育是一种项目化、综合化的教育形式,随着课程改革的不断推进,STEM教育已经和各科教学进行了融合。STEM教育与小学语文教学融合,一方面能够使得学生对于世间万物运转的本质有着更好的理解,而且不必受到课堂教学内容的局限,另一方面也能够使得课堂质量得以大幅度提升。