简介:Objective:ActivatingKRASmutationsarethemostcommondriversinthedevelopmentofnon-smallcelllungcancer(NSCLC).However,unsuccessoftreatmentbydirectinhibitionofKRAShasbeenproven.DeregulationofPI3KsignalingplaysanimportantroleintumorigenesisanddrugresistanceinNSCLC.TheactivityofPI3Kα-selectiveinhibitionagainstKRAS-mutatedNSCLCremainslargelyunknown.Methods:CellproliferationwasdetectedbysulforhodamineBassay.Cellcycledistributionandapoptosisweremeasuredbyflowcytometry.CellsignalingwasassessedbyWesternblotandimmunohistochemistry.RNAinterferencewasusedtodown-regulatetheexpressionofcyclinD1.HumanNSCLCxenograftswereemployedtodetecttherapeuticefficacyinvivo.Results:CYH33possessedvariableactivityagainstapanelofKRAS-mutatedNSCLCcelllines.AlthoughCYH33blockedAKTphosphorylationinalltestedcells,RbphosphorylationdecreasedinCYH33-sensitive,butnotinCYH33-resistantcells,whichwasconsistentwithG1phasearrestinsensitivecells.CombinedtreatmentwiththeCDK4/6inhibitor,PD0332991,andCYH33displayedsynergisticactivityagainsttheproliferationofbothCYH33-sensitiveandCYH33-resistantcells,whichwasaccompaniedbyenhancedG1-phasearrest.Moreover,down-regulationofcyclinD1sensitizedNSCLCcellstoCYH33.Reciprocally,CYH33abrogatedthePD0332991-inducedup-regulationofcyclinD1andphosphorylationofAKTinA549cells.Co-treatmentwiththesetwodrugsdemonstratedsynergisticactivityagainstA549andH23xenografts,withenhancedinhibitionofRbphosphorylation.Conclusions:SimultaneousinhibitionofPI3KαandCDK4/6displayedsynergisticactivityagainstKRAS-mutatedNSCLC.ThesedataprovideamechanisticrationaleforthecombinationofaPI3KαinhibitorandaCDK4/6inhibitorforthetreatmentofKRASmutatedNSCLC.
简介:Inthepresentpaper,novelsidewallmaterialsforaluminumreductioncellwerepreparedinairusingmagnesiaandmagnetiteasstartingmaterials.ThesinteringbehaviorsofthespecimenswereinvestigatedbymeansofX-raydiffraction(XRD)andscanningelectronmicroscope(SEM).AndcorrosiontestsinaNa_3AlF_6-AlF_3-K_3AlF_6bathwereconductedtoevaluatetheelectrolytecorrosionresistance.TheresultsshowthattheFe_3O_4phaseistransformedintoFe_2O_3athightemperatures,whichinturnreactswiththeMgOaddedtoformMgFe_2O_4spinel.AndwithincreasingtheMgOcontentfrom0to30mass%,densificationofthespecimensdecreasesmainlyduetolargervolumeexpansionresultingfromformationofmoreMgFe_2O_4.ThecorrosiontestsshowthatcorrosionlayersareproducedinalltheMgOaddedspecimens.However,forspecimenscontainingMgFe_2O_4phaseonly,Mg(Al,Fe)_2O_4compositespinellayersarealsogenerated,whichremarkablyimprovethecorrosionresistanceofthespecimens.
简介:摘要:本文以三聚氰胺、氢氧化钾为原材料,成功制备了不同掺杂量的K-g-C3N4,再以最佳掺杂量的K-g-C3N4、六氯化钨为原料成功制备了不同复合比的WO3@K-g-C3N4复合材料。经SEM、EDS、XRD等表征手段,证实K成功掺杂进g-C3N4以及WO3纳米粒子成功附着于g-C3N4表面。通过氮氧催化测试以及RhB降解测试确定了K-g-C3N4的最佳掺杂量以WO3@K-g-C3N4的最佳复合比,综合评价了复合材料的光催化性能。实验证明,以质量比为0.1:3制备得到的K-g-C3N4具有最佳的光催化性能,其对RhB的降解率高达89.2%,对NO的降解率为69.87%。以复合比为35%制备得到的具有最优的光催化性能,其对RhB的降解率高达95.8%,对NO的降解率为75.23%。
简介:摘要目的探讨输出蛋白(XPO)4、丝裂原活化蛋白激酶(MAP2K)4及小脑锌指结构蛋白(ZIC)1在子宫内膜癌(EC)组织中的表达及其对EC患者的预后评估价值。方法选择2017年6月至2018年6月,无锡市妇幼保健院、复旦大学附属中山医院青浦分院收治的147例EC患者为研究对象。采用免疫组化染色法检测患者EC组织及癌旁正常组织XPO4、MAP2K4、ZIC1表达水平。采用χ2检验,对患者EC组织及癌旁正常组织XPO4、MAP2K4、ZIC1阳性率,以及不同临床病理特征患者EC组织XPO4、MAP2K4、ZIC1阳性率进行比较。采用Two-stage检验,对EC组织XPO4、MAP2K4、ZIC1呈阳性与呈阴性患者的3年总体生存(OS)率进行比较。本研究遵循的程序经过无锡市妇幼保健院、复旦大学附属中山医院青浦分院伦理委员会批准(审批文号:20160803、20160502)。结果①本组患者EC组织XPO4、MAP2K4阳性率分别为34.7%(51/147)、38.1%(56/147),显著低于癌旁正常组织的66.7%(98/147)与72.8%(107/147),并且差异均有统计学意义(χ2=30.060、35.812,P<0.001)。本组患者EC组织ZIC1阳性率为72.1%(106/147),显著高于癌旁正常组织的40.1%(59/147),并且差异亦有统计学意义(χ2=30.512、P<0.001)。②不同年龄、EC直径及绝经与否患者的EC组织XPO4、MAP2K4、ZIC1阳性率比较,差异均无统计学意义(P>0.05)。不同国际妇产科联盟(FIGO)临床分期、组织病理学分级、子宫肌层侵犯程度及淋巴结转移与否患者EC组织XPO4、MAP2K4、ZIC1阳性率分别比较,差异均有统计学意义(P<0.05)。③本组EC组织XPO4、MAP2K4呈阴性患者的3年OS率分别为42.7%、38.5%,均显著低于XPO4、MAP2K4呈阳性者的68.6%、71.4%,并且差异均有统计学意义(χ2=8.960、P=0.003,χ2=15.077、P<0.001)。EC组织ZIC1呈阳性患者3年OS率为35.8%,显著低于ZIC1呈阴性者的68.3%,并且差异亦有统计学意义(χ2=12.579、P<0.001)。结论在EC组织中,XPO4、MAP2K4呈低表达,而ZIC1则呈高表达。XPO4、MAP2K4、ZIC1表达水平与患者组织病理学分级、淋巴结转移、FIGO临床分期、子宫肌层侵犯及3年OS率显著相关,其在评估EC患者发病、进展及预后中具有一定价值。
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简介:ThecomplexK3H4GeW9V3O40·8H2OcrystallizedinamonocliiniesystemwithspacegroupP2,Mr=2784.67,a=11.099(3),b=16.452(4),c=13.534(4),β=108.14°,Z=2,V=2348.493,F(000):2456,μ=239.7cm-1,De=3.932g/cm3.ThefinalR=0.083for4528non-zeroreflexions.ThestructureofanionsGeW9V3O40andGeW9O34belongstoA--type.
简介:设图G是一个简单图,图G的补图记为^-G,如果G的谱完全由整数组成,就称G是整谱图.本文确定了图^--αKα∪βKb,b中的所有整谱图.