简介:美国拥有B2B的微软、IBM、甲骨文等科技巨头,中国在此领域却没有一家市值过百亿美元的互联网科技公司,这为中国B2B领域出现巨无霸的巨头提供了无限的遐想。B2C端电商领域在2015年之后市场已经趋向饱和,淘宝、天猫、京东虽然依旧强势,但扩张的步伐已经明显趋缓,对于GMV增长贡献大部分依赖业务板块的横向拓展而非纵向的渗透。至于两大巨头之外的垂直电商平台,唯品会、苏宁云商、一号店、聚美优品等也褪尽黑马本色逐渐进入了瓶颈期。平台电商之外,O2O模式在风起云涌极度喧哗之后集体失语——生鲜领域几乎全军覆没,服务类O2O对于盈利模式也是苦苦探寻;
简介:Objective:Chroniclymphocyticleukemia(CLL)andmantlecelllymphoma(MCL)cellsover-expressaguanineexchangefactor(GEF),Rasgrf-1.ThisGEFincreasesactiveRasasitcatalyzestheremovalofGDPfromRassothatGTPcanbindandactivateRas.ThisstudyaimstostudythemechanismofactionofRasgrf-1inB-cellmalignancies.Methods:N-terminustruncatedRasgrf-1variantshaveahigherGEFactivityascomparedtothefull-lengthtranscriptthereforeaMCLcelllinewithstableover-expressionoftruncatedRasgrf-1wasestablished.TheB-cellreceptor(BCR)andchemokinesignalingpathwayswerecomparedintheRasgrf-1over-expressingandacontroltransfectedcellline.Results:Cellsover-expressingtruncatedformofRasgrf-1haveahigherproliferativerateascomparedtocontroltransfectedcells.BCRwasactivatedbylowerconcentrationsofanti-IgMantibodyinRasgrf-1over-expressingcellsascomparedtocontrolcellsindicatingthatthesecellsaremoresensitivetoBCRsignaling.BCRsignalingalsophosphorylatesRasgrf-1thatfurtherincreasesitsGEFfunctionandamplifiesBCRsignaling.ThisactivationofRasgrf-1inover-expressingcellsresultedinahigherexpressionofphospho-ERK,AKT,BTKandPKC-alphaascomparedtocontrolcells.BesidesBCR,Rasgrf-1over-expressingcellswerealsomoresensitivetomicroenvironmentstimuliasdeterminedbyresistancetoapoptosis,chemotaxisandERKpathwayactivation.Conclusions:ThisGEFproteinsensitizesB-cellstoBCRandchemokinemediatedsignalingandalsoupregulatesanumberofothersignalingpathwayswhichpromotesgrowthandsurvivalofthesecells.