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:translaorsshouldusefreetranslation.Freetranslationisatranslationskillwhichisactive.Butfreetranslationcannotaddpersonalemotiontotheoriginalworks.Translationmustbeacceptablewhichusefreetranslation.Andfreetranslationskillneedsextensiveknowledgeandcultureofbothsourcelanguageandtargetlanguage.Ifatranslatorwantstouseliteraltranslationandfreetranslationproficiently,slationshouldavoidtoaddpersonalemotiontotheoriginalworks.3.3Freetranslationskillneedsextensiveknowledgeandcultureofbothsourcelanguageandtargetlanguage.Freetranslationgivestranslatorssomeleeways.Translatorsshouldusethencorrectly.Notonlyshouldtranslatorscomprehenedthemeaningoftheoriginalmessage,也会说你的坏话.Freetranslationdoesnotstrachytheformoftheoriginal.Iftranslatorswanttousefreetranslationproficiently.You'dbettergraspextensiveknowledgeandcultureofbothsourcelanguageandtargetlanguage.CONCLUTION
简介:摘要3D打印教学活动的开展让学生的想象更容易变成现实,也有利于培养学生的创新意识、鼓励学生的创新实践。通过交流分享,培养学生的表达能力和交流分享的意识和习惯。