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简介：CD8+细胞毒素的T淋巴细胞(CTL)疲劳是为在长期的传染疾病的无效病毒消除的一个主要问题。我们产生了新奇ovalbumin(卵)特定的OVA-Texo和导致治疗学的免疫的HIV特定的Gag-Texo疫苗。在长期的感染估计他们的治疗学的效果，我们由与表示卵的侵入人体气管粘膜的病菌AdVova感染C57BL/6老鼠的i.v开发了一个新长期的感染模型。在长期的AdVova感染期间，老鼠CTL被发现房间死亡protein-1(PD-1)和淋巴细胞激活gene-3(LAG-3)到禁止的分子规划了的快车，证明在T房间增长，IFN-生产和cytolytic的重要缺乏完成机能上地精疲力尽并且。天真的CD8+T房间upregulated禁止的PD-ligand1(PD-L1)，B淋巴细胞和T淋巴细胞衰减器和T房间联系变应力缺乏的分子(圣盘和痒)当时下面调整在在有长期的感染的老鼠的刺激之上的proliferative反应。显著地，OVA-Texo疫苗抵抗了T房间变应力缺乏并且变换了CTL疲劳。后者与(i)被联系为CTL功能的一个标记的upregulation，diacetylatedhistone-H3(diAcH3)，(ii)CTL，宿主DC的发生独立人士或CD4+T细胞的四折的增加，并且(iii)CTLIFN-生产和cytotoxicity的恢复。在vivoOVA-Texo-stimulatedCTLupregulatedmTORC1的活动小径相关的分子Akt，S6，eIF4E和T赌注，和有一个mTORC1禁止者的CTL的处理，rapamycin，显著地在CTL减少了OVA-Texo-induced增加。有趣地，发信号的OVA-Texo-mediatedCD40L在观察免疫学的效果起了一个关键作用。重要地，Gag-Texo疫苗在长期的感染导致了作呕特定的治疗学的免疫。因此，这研究应该为人的免疫不全在新治疗学的疫苗的发展有严肃的影响病毒(HIV-1)感染。

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简介：Ginkgolicacids(GAs),primarilyfoundintheleaves,nuts,andtestaofginkgobiloba,havebeenidentifiedwithsuspectedallergenic,genotoxicandcytotoxicproperties.However,littleinformationisavailableaboutGAstoxicityinkidneysandtheunderlyingmechanismhasnotbeenthoroughlyelucidatedsofar.InsteadofGAsextract,therenalcytotoxicityofGA(15:1),whichwasisolatedfromthetestaofGinkgobiloba,wasassessedinvitrobyusingMDCKcells.TheactionofGA(15:1)oncellviabilitywasevaluatedbytheMTTandneutralreduptakeassays.Comparedwiththecontrol,thecytotoxicityofGA(15:1)onMDCKcellsdisplayedatime-anddose-dependentmanner,suggestingthecellsmitochondriaandlysosomesweredamaged.ItwasconfirmedthatGA(15:1)resultedinthelossofcellsmitochondrialtrans-membranepotential(ΔΨm).Inpropidiumiodide(PI)staininganalysis,GA(15:1)inducedcellcyclearrestattheG0/G1andG2/Mphases,influencingontheDNAsynthesisandcellmitosis.CharacteristicsofnecroticcelldeathwereobservedinMDCKcellsattheexperimentalconditions,asaresultofDNAagarosegelelectrophoresisandmorphologicalobservationofMDCKcells.Inconclusion,thesefindingsmightprovideusefulinformationforabetterunderstandingoftheGA(15:1)inducedrenaltoxicity.

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简介：Littoral-cellangioma(LCA),aprimaryangiomawhichclinicallybelongstosplenichemangioma,canbemostlyfoundinnormalspleenredsinusshorecellsofreticuloendothelialcellsystem.ThecellsofLCAstronglyexpressendothelialandtissuecellassociatedantigensthatindicateadualdifferentiationcharacteristic;whereasonlyendothelialcellmarkersarepositiveinnormalspleenredsinusshorecells.DiagnosisofLCAreliesonhistopathology.Regularfollow-upisneededtomonitorrecurrenceandmetastasis.

简介：Axonaldegenerationisapivotalfeatureofmanyneurodegenerativeconditionsandsubstantiallyaccountsforneurologicalmorbidity.AwidelyusedexperimentalmodeltostudythemechanismsofaxonaldegenerationisWalleriandegeneration(WD),whichoccursafteracuteaxonalinjury.Intheperipheralnervoussystem(PNS),WDischaracterizedbyswiftdismantlingandclearanceofinjuredaxonswiththeirmyelinsheaths.Thisisaprerequisiteforsuccessfulaxonalregeneration.Inthecentralnervoussystem(CNS),WDismuchslower,whichsignificantlycontributestofailedaxonalregeneration.Althoughitiswell-documentedthatSchwanncells(SCs)haveacriticalroleintheregenerativepotentialofthePNS,todatewehaveonlyscarceknowledgeastohowSCs‘sense'axonalinjuryandimmediatelyrespondtoit.Inthisregard,itremainsunknownastowhetherSCsplaytheroleofapassivebystanderoranactivedirectorduringtheexecutionofthehighlyorchestrateddisintegrationprogramofaxons.Olderreports,togetherwithmorerecentstudies,suggestthatSCsmountdynamicinjuryresponsesminutesafteraxonalinjury,longbeforeaxonalbreakdownoccurs.TheswiftSCresponsetoaxonalinjurycouldplayeitherapro-degenerativerole,oralternativelyasupportiverole,totheintegrityofdistressedaxonsthathavenotyetcommittedtodegenerate.Indeed,supportingthelatterconcept,recentfindingsinachronicPNSneurodegenerationmodelindicatethatdeactivationofakeymoleculepromotingSCinjuryresponsesexacerbatesaxonalloss.Ifthisholdstrueinabroaderspectrumofconditions,itmayprovidethegroundsforthedevelopmentofnewglia-centrictherapeuticapproachestocounteractaxonalloss.

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简介：Objective:Signetringcellcarcinomaisararesubtypeofcolorectalcarcinoma(CRC)withanassociatedBRAFV600Emutation.WeinvestigatedfrequenciesofBRAFmutationin28CRCscontainingvariablesignetringcellcomponentandtheirrelationwithclinicopathologicparameters.Methods:Accordingtothepresenceofsignetringcellcomponent,tumorswerecategorizedintogroupsasfollows:0%–9%,10%–24%,25%–49%,and>50%.GenomicDNAwasisolatedandanalyzedforBRAFV600Egenemutationbypolymerasechainreaction-restrictionfragmentlengthpolymorphism.Elevenof28cases(39.3%)showedBRAFV600Emutation,whichwasalsoconfirmedbySangersequencing.Toelucidatetheimportanceofexistenceofsignetringcellcomponentatthemolecularlevel,weseparatedcasesintotwogroupswithcut-offlevelsof10%and50%,whichpertaintopercentagesofsignetringcells.Results:Sevenof19cases(36.8%)underthethresholdof50%andfourofninecases(44.4%)overthisthresholdvaluedemonstratedBRAFmutation.Threeof7cases(42.8%)featuring<10%signetringcellcomponentandeightoutof21cases(38.1%)showing>10%wereBRAFmutated.Conclusions:BRAFmutationmustbecloselyassociatedwiththepresenceofmalignantsignetringcellsregardlessoftheirpercentages.

简介：Esophagealcancerisoneofthemostfataldiseasesworldwidemainlybecauseofitsrapidprogressionandpoorprognosis.AlthoughtheincidenceofesophagealadenocarcinomahasmarkedlyriseninNorthAmericaandEuropeinthepastseveraldecades,esophagealsquamouscellcarcinomaisstillthepredominantsubtypeofesophagealcancer,especiallyinChina.Itaccountsformorethan90%ofallesophagealsquamouscellcarcinomacasesinChina.Geographicaldifferentiationisoneofthemostdistinctivecharacteristicsofesophagealcancer.Theprogression,riskfactors,andprognosisofthesetwosubtypesofesophagealcancerdiffer.Thisstudyreviewstheepidemiology,etiology,andpreventionofesophagealsquamouscellcarcinomainChina,therebyprovidingsystematicreferencesforpolicy-makerswhowilldecideonissuesofesophagealcancerpreventionandcontrol.

简介：流行性感冒病毒红血球凝聚素的梗区域很好相对与球状的头领域相比被保存，它对流行性感冒用作一支通用疫苗使它成为一个潜在的目标。然而，在红血球凝聚素的CD4T房间的角色梗特定的有免疫力的反应不是清楚的。这里，我们识别了在流行性感冒的尚不致命的感染以后从红血球凝聚素梗领域包含残余HA2113-131的老鼠CD4T房间epitope。响应有识别epitope的刺激，从感染的老鼠导出的splenocytes显示出象degranulation一样由IL-2，TNF-和IFN-生产出现的重要polyfunctionality。而且，与相应于这CD4T房间epitope的肽使免疫的老鼠展出了CD4T房间受体分享的interindividual序列，和他们有更高的幸存率与流行H1N1流行性感冒的致命的剂量跟随挑战病毒。因此，我们的数据表明了红血球凝聚素的一个关键角色在对流行性感冒病毒感染的主机免疫者反应的梗特定的CD4T房间。

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简介：Ras-associatedprotein-1(Rap1),asmallGTPaseintheRas-relatedproteinfamily,isanimportantregulatorofbasiccellularfunctions(e.g.,formationandcontrolofcelladhesionsandjunctions),cellularmigration,andpolarization.Throughitsinteractionwithotherproteins,Rap1playsmanyrolesduringcellinvasionandmetastasisindifferentcancers.ThebasicfunctionofRap1isstraightforward;itactsasaswitchduringcellularsignalingtransductionandregulatedbyitsbindingtoeitherguanosinetriphosphate(GTP)orguanosinediphosphate(GDP).However,itsremarkablydiversefunctionisrenderedbyitsinterplaywithalargenumberofdistinctRapguaninenucleotideexchangefactorsandRapGTPaseactivatingproteins.ThisreviewsummarizesthemechanismsbywhichRap1signalingcanregulatecellinvasionandmetastasis,focusingonitsrolesinintegrinandcadherinregulation,RhoGTPasecontrol,andmatrixmetalloproteinaseexpression.

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简介：作为结构的材料，靠近房间的铝泡沫与开的房间铝泡沫相比在产品尺寸，力量和过程经济拥有明显的优点。作为一种结构功能集成材料，靠近房间的铝泡沫的申请由于声波穿入的困难在声学的领域里极大地被限制了。有宏观结构的靠近房间的泡沫在声波的繁殖上有重要效果，这被报导。迄今为止，在宏观结构之间的关系和商业地纯的靠近房间的铝泡沫的声学的性质是模糊的。在这个工作，不同穿孔和空气差距类型为改变泡沫的宏观结构被设计。同时，健全吸收系数和健全减小索引上的宏观结构的效果被调查。结果证明有一半洞的泡沫在高频率范围展出了优秀健全吸收和健全屏蔽行为(>2500?Hz)。另外，没有空气差距，有空气差距的标本与泡沫相比在低频率显示出好健全吸收性质。基于实验结果，繁殖在有不同宏观结构的商业地纯的靠近房间的铝泡沫的声波的结构的模型被造，声学的性质上的宏观结构的影响被讨论。

简介：Theresearchgroupwasinterestedinthetherapeuticpotentialoflimbalfibroblasts,whicharepre-sentinthecorneallimbus.Recently,inmuchstemcellresearch,researchersandadvocatesarestress-ingtheimportanceofutilizingcellsfromthenichewhichtheywilltarget.Thismeans,thatadiposetissueandbonemarrowderivedstemcells,arelikelynotappropriateandevendangeroustoapplyu-biquitouslyastherapiestootherpartsofthebodyincertaincases.Severalresearchgroupsandclini-caltrialshaveshownthistobethecase,includingcasesofblindness,braininflammation,anddeathasadverseevents.

简介：Flowerpetalshavenotonlydiversemacroscopicmorphologiesbutarerichinmicroscopicsurfacepatterns,whicharecrucialtotheirbiologicalfunctions.Bothexperimentalmeasurementsandtheoreticalanalysisareconductedtorevealthephysicalmechanismsunderlyingtheformationofminutewrinklesonflowerpetals.Threerepresentativeflowers,daisy,kalanchoeblossfeldiana,andEustomagrandiflorum,areinvestigatedasexamples.Asurfacewrinklingmodel,incorporatingthemeasuredmechanicalpropertiesandgrowthratio,isusedtoelucidatethedifferenceintheirsurfacemorphologies.Themismatchbetweentheanisotropicepidermalcellgrowthandtheisotropicsecretionofsurficialwaxisfoundtodictatethesurfacepatterns.