In the last couple of years,there Has been an increased interest among the statisticians to dene new families of distributions by adding one or more additional parameter(s)to the baseline distribution.In this regard,a...In the last couple of years,there Has been an increased interest among the statisticians to dene new families of distributions by adding one or more additional parameter(s)to the baseline distribution.In this regard,a number of families have been introduced and studied.One such example is the Marshall-Olkin family of distributions that is one of the most prominent approaches used to generalize the existing distributions.Whenever,we see a new method,the natural questions come in to mind are(i)what are the genesis of the newly proposed method and(ii)how did the proposed method is obtained.No doubt,the Marshall-Olkin family is a very useful method and has attracted the researchers.But,unfortunately,the authors failed to provide the explanation about the genesis of the method that how this family of distributions is obtained.To address this issue,in this article,an attempt Has been made to provide a straight forward computation about the genesis of the Marshall-Olkin family that somehow completes its derivation.The genesis of the Marshall-Olkin family is based on the T-X family approach.Furthermore,we have showed that other extensions of the Marshall-Olkin family can also be obtained via the T-X family method.Finally,a real-life application form insurance science is presented to illustrate the newly proposed extension of the Marshall-Olkin family.展开更多
目的探讨肺腺癌细胞恶性T细胞扩增序列1(MCTS1)介导骨髓源性抑制细胞(MDSCs)趋化的作用机制。方法利用生物信息学(http://timer.cistrome.org/#tab-8258-2)分析癌症基因组图谱(TCGA)中肺腺癌组织(n=515)MCTS1的表达水平与MDSCs浸润之间...目的探讨肺腺癌细胞恶性T细胞扩增序列1(MCTS1)介导骨髓源性抑制细胞(MDSCs)趋化的作用机制。方法利用生物信息学(http://timer.cistrome.org/#tab-8258-2)分析癌症基因组图谱(TCGA)中肺腺癌组织(n=515)MCTS1的表达水平与MDSCs浸润之间的相关性;利用IL-6+粒细胞-巨噬细胞集落刺激因子(GM-CSF)共同诱导人外周血单个核细胞(PBMCs)中MDSCs的生成,流式细胞术检测MDSCs生成比例,CD33磁珠分选MDSCs;收集肺腺癌SPC-A1细胞野生型以及MCTS1敲减和过表达SPC-A1细胞的无血清细胞上清液,利用Transwell小室进行MDSCs的趋化试验并计算趋化指数;羧基荧光素二醋酸盐琥珀酰亚胺酯(CFSE)标记CD8^(+)T细胞与发生趋化的MDSCs细胞共培养,流式细胞术检测CD8^(+)T细胞的增殖水平;实时荧光定量PCR(qRT-PCR)测定MDSCs相关趋化因子的mRNA水平;流式多因子芯片技术检测细胞上清液中C-X-C基序趋化因子配体1(CXCL1)的含量;Western blot检测janus激酶2(JAK2)的表达水平以及信号转导子和转录激活子1(STAT1)的活化水平。结果肺腺癌组织MCTS1与MDSCs浸润程度呈正相关(Spearmanρ=0.226,P<0.001);与空白对照组比较,IL-6和GM-CSF共同诱导PBMCs后可显著增加MDSCs的比例(4.95±1.03 vs 0.97±0.24,t=6.54,P<0.01);MCTS1过表达的SPC-A1细胞上清液对MDSCs的趋化指数较对照组显著升高(4.88±0.99 vs 2.94±0.27,q=6.29,P<0.01),而经MCTS1敲减的细胞上清液可使MDSCs的趋化指数显著降低(1.50±0.17 vs 2.94±0.27,q=4.69,P<0.05);MCTS1过表达的SPC-A1细胞中CXCL1 mRNA(2.79±0.16 vs 1.00±0.08,q=28.94,P<0.001)和上清液中蛋白质水平(78.20±6.16 vs 37.50±3.31,q=16.83,P<0.001)均显著升高,而敲减MCTS1则可抑制CXCL1 mRNA(0.53±0.03 vs 1.00±0.08,q=7.64,P<0.01)和蛋白质水平(17.33±1.96 vs 37.50±3.31,q=8.34,P<0.01);此外,与对照组比较,MCTS1过表达组JAK2蛋白的表达水平(2.11±0.15 vs 1.00±0.05,q=19.48,P<0.001)和STAT1的活化水平(2.10±0.19 vs 1.00±0.10,q=15.02,P<0.001)显著升高,而MCTS1敲减组JAK2蛋白水平(0.56±0.06 vs 1.00±0.05,q=7.61,P<0.01)和STAT1的活化水平均显著降低(0.46±0.07 vs 1.00±0.05,q=7.45,P<0.01)。结论肺腺癌细胞MCTS1通过JAK2-STAT1信号通路调控CXCL1的表达,并介导MDSCs的趋化。展开更多
基金supported by the Department of Statistics,Yazd University,Yazd,Iran。
文摘In the last couple of years,there Has been an increased interest among the statisticians to dene new families of distributions by adding one or more additional parameter(s)to the baseline distribution.In this regard,a number of families have been introduced and studied.One such example is the Marshall-Olkin family of distributions that is one of the most prominent approaches used to generalize the existing distributions.Whenever,we see a new method,the natural questions come in to mind are(i)what are the genesis of the newly proposed method and(ii)how did the proposed method is obtained.No doubt,the Marshall-Olkin family is a very useful method and has attracted the researchers.But,unfortunately,the authors failed to provide the explanation about the genesis of the method that how this family of distributions is obtained.To address this issue,in this article,an attempt Has been made to provide a straight forward computation about the genesis of the Marshall-Olkin family that somehow completes its derivation.The genesis of the Marshall-Olkin family is based on the T-X family approach.Furthermore,we have showed that other extensions of the Marshall-Olkin family can also be obtained via the T-X family method.Finally,a real-life application form insurance science is presented to illustrate the newly proposed extension of the Marshall-Olkin family.
文摘目的探讨肺腺癌细胞恶性T细胞扩增序列1(MCTS1)介导骨髓源性抑制细胞(MDSCs)趋化的作用机制。方法利用生物信息学(http://timer.cistrome.org/#tab-8258-2)分析癌症基因组图谱(TCGA)中肺腺癌组织(n=515)MCTS1的表达水平与MDSCs浸润之间的相关性;利用IL-6+粒细胞-巨噬细胞集落刺激因子(GM-CSF)共同诱导人外周血单个核细胞(PBMCs)中MDSCs的生成,流式细胞术检测MDSCs生成比例,CD33磁珠分选MDSCs;收集肺腺癌SPC-A1细胞野生型以及MCTS1敲减和过表达SPC-A1细胞的无血清细胞上清液,利用Transwell小室进行MDSCs的趋化试验并计算趋化指数;羧基荧光素二醋酸盐琥珀酰亚胺酯(CFSE)标记CD8^(+)T细胞与发生趋化的MDSCs细胞共培养,流式细胞术检测CD8^(+)T细胞的增殖水平;实时荧光定量PCR(qRT-PCR)测定MDSCs相关趋化因子的mRNA水平;流式多因子芯片技术检测细胞上清液中C-X-C基序趋化因子配体1(CXCL1)的含量;Western blot检测janus激酶2(JAK2)的表达水平以及信号转导子和转录激活子1(STAT1)的活化水平。结果肺腺癌组织MCTS1与MDSCs浸润程度呈正相关(Spearmanρ=0.226,P<0.001);与空白对照组比较,IL-6和GM-CSF共同诱导PBMCs后可显著增加MDSCs的比例(4.95±1.03 vs 0.97±0.24,t=6.54,P<0.01);MCTS1过表达的SPC-A1细胞上清液对MDSCs的趋化指数较对照组显著升高(4.88±0.99 vs 2.94±0.27,q=6.29,P<0.01),而经MCTS1敲减的细胞上清液可使MDSCs的趋化指数显著降低(1.50±0.17 vs 2.94±0.27,q=4.69,P<0.05);MCTS1过表达的SPC-A1细胞中CXCL1 mRNA(2.79±0.16 vs 1.00±0.08,q=28.94,P<0.001)和上清液中蛋白质水平(78.20±6.16 vs 37.50±3.31,q=16.83,P<0.001)均显著升高,而敲减MCTS1则可抑制CXCL1 mRNA(0.53±0.03 vs 1.00±0.08,q=7.64,P<0.01)和蛋白质水平(17.33±1.96 vs 37.50±3.31,q=8.34,P<0.01);此外,与对照组比较,MCTS1过表达组JAK2蛋白的表达水平(2.11±0.15 vs 1.00±0.05,q=19.48,P<0.001)和STAT1的活化水平(2.10±0.19 vs 1.00±0.10,q=15.02,P<0.001)显著升高,而MCTS1敲减组JAK2蛋白水平(0.56±0.06 vs 1.00±0.05,q=7.61,P<0.01)和STAT1的活化水平均显著降低(0.46±0.07 vs 1.00±0.05,q=7.45,P<0.01)。结论肺腺癌细胞MCTS1通过JAK2-STAT1信号通路调控CXCL1的表达,并介导MDSCs的趋化。
