目的筛选直肠癌新辅助放化疗(CRT)疗效预测长链非编码RNA(lncRNA)分子标志物,分析参与CRT疗效调控相关信号通路,建立CRT疗效预测模型。方法利用lncRNA芯片进行lncRNA差异表达检测,使用R软件Limma包在CRT反应组和CRT无反应组间对比筛选差...目的筛选直肠癌新辅助放化疗(CRT)疗效预测长链非编码RNA(lncRNA)分子标志物,分析参与CRT疗效调控相关信号通路,建立CRT疗效预测模型。方法利用lncRNA芯片进行lncRNA差异表达检测,使用R软件Limma包在CRT反应组和CRT无反应组间对比筛选差异lncRNA(P<0.05和|Log2FC|>1),进行分子标志物筛选。采用基因本体(GO)分析对差异表达基因进行功能分析,采用京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)对筛选的差异基因进行信号通路富集分析。进一步采用实时定量反转录聚合酶链式反应(qRT-PCR)检测98例样本。采用logistic回归构建CRT治疗预测模型。绘制受试者操作特征曲线(ROC)计算曲线下面积(AUC)以评价模型的判别区分能力。结果CRT反应组中,823个lncRNA表达上调,216个lncRNA表达下调,449个基因表达上调,81个基因表达下调。新辅助放化疗相关上调排名前10的差异表达lncRNA分别为LUCAT1、LINC02356、HIF1A-AS2、Lnc-ZNF644-1、Lnc-ADAMTS12-3、LINC02356、Lnc-CLIC4-1、Lnc-PTX3-4、DARS-AS1、MIR210HG。下调排名前10的分别为Lnc-COL6A3-2、Lnc-FBN1-2、Lnc-FOXA1-3、Lnc-KRTAP9-7-1、LINC00562、Lnc-NCS1-1、LINC00456、Lnc-FBLL1-2、USP2-AS1、Lnc-INPPL1-2。GO分析结果提示,差异基因主要富集在上皮细胞分化、中间丝、中间丝细胞骨架、突触后膜、颗粒分泌、细胞因子受体活性等分子生物学功能方面。KEGG富集分析提示,差异表达基因主要富集在HIF-1信号通路、Th17细胞分化、戊糖磷酸途径、精氨酸和脯氨酸代谢、果糖和甘露糖代谢、磷脂酶D信号通路、溶酶体等信号通路方面。logistic回归模型显示,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型具有较好的预测能力,AUC为0.887(95%CI 0.820~0.954)。模型回归方程logit(p)=1.582×LINC00562-1.969×LINC02356-0.798×LUCAT1+4.357。模型的灵敏度为81.3%,特异度为84.0%。结论直肠癌CRT反应良好和CRT无反应者间lncRNA分子存在明显的差异表达,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型对CRT疗效具有较好的预测能力。展开更多
The zirconium(Zr)alloy fuel cladding is one of the key structural components of a nuclear reactor and the first and most important line of defense for accommodating fission products.During the operation of nuclear rea...The zirconium(Zr)alloy fuel cladding is one of the key structural components of a nuclear reactor and the first and most important line of defense for accommodating fission products.During the operation of nuclear reactors,Zr alloy fuel cladding is subjected to extreme harsh environments,such as high temperature,high pressure and high flow rate for a long period of time.The wear and corrosion resistance of Zr alloys is important for the safe operation of nuclear reactors.Surface modification can effectively improve the corrosion and wear resistance of fuel cladding.Compared with coating technology,nitriding technology does not have problems for bonding between the coating and the substrate.Current research on surface nitriding of Zr alloys mainly focuses on plasma nitriding and ion implantation techniques.Research on laser nitriding of Zr alloy surfaces and their fretting wear characteristics is scarce.In this study,the surface of Zr alloy was treated with laser nitriding at different laser energies.The microstructure of Zr alloy treated with different laser energies and its fretting wear performance were studied.The results showed that after nitriding with different laser energies,the surface of the Zr alloy showed a typical molten state after melting,vaporizing and cooling under the thermal effect of the laser,and this state was more obvious with the increase of the laser energy.At the same time,doping of N atoms and formation of the ZrN phase led to different cooling rates in the molten zone that produced large tensile stresses after cooling.This led to cracks on the surface of Zr alloys after laser nitriding at different energies,and the crack density increased with increasing laser energy.This also led to an increase in the surface roughness of the Zr alloy with increasing laser energy after laser nitriding treatment.Due to the presence of water in the industrial nitrogen,nitrides were generated on the surface of the sample along with some oxides.When the laser energy was 100 mJ,there was no ZrN generation,and N existed mainly as a diffusion layer within the Zr alloy substrate.ZrN generated when the laser energy reached 200 mJ and above,which increased with the increase of laser energy.Due to the generation of ZrN phase and the presence of some oxides,the surface Vickers hardness of Zr alloys after laser nitriding treatment at different energies increased by 37.5%compared to Zr alloys.After laser nitriding treatment,the wear mechanism of Zr alloys changed.For the untreated Zr alloys,the wear mechanism was dominated by delamination and spalling wear,accompanied by oxidative and abrasive wear.The phenomenon of delamination and peeling decreased with the increase of laser energy.Wear mechanisms changed to predominantly abrasive wear with oxidative wear and delamination spalling.The wear volume of sample nitriding with laser energy 400 mJ was reduced by 46.5%compared with that of untreated Zr alloy.展开更多
文摘目的筛选直肠癌新辅助放化疗(CRT)疗效预测长链非编码RNA(lncRNA)分子标志物,分析参与CRT疗效调控相关信号通路,建立CRT疗效预测模型。方法利用lncRNA芯片进行lncRNA差异表达检测,使用R软件Limma包在CRT反应组和CRT无反应组间对比筛选差异lncRNA(P<0.05和|Log2FC|>1),进行分子标志物筛选。采用基因本体(GO)分析对差异表达基因进行功能分析,采用京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)对筛选的差异基因进行信号通路富集分析。进一步采用实时定量反转录聚合酶链式反应(qRT-PCR)检测98例样本。采用logistic回归构建CRT治疗预测模型。绘制受试者操作特征曲线(ROC)计算曲线下面积(AUC)以评价模型的判别区分能力。结果CRT反应组中,823个lncRNA表达上调,216个lncRNA表达下调,449个基因表达上调,81个基因表达下调。新辅助放化疗相关上调排名前10的差异表达lncRNA分别为LUCAT1、LINC02356、HIF1A-AS2、Lnc-ZNF644-1、Lnc-ADAMTS12-3、LINC02356、Lnc-CLIC4-1、Lnc-PTX3-4、DARS-AS1、MIR210HG。下调排名前10的分别为Lnc-COL6A3-2、Lnc-FBN1-2、Lnc-FOXA1-3、Lnc-KRTAP9-7-1、LINC00562、Lnc-NCS1-1、LINC00456、Lnc-FBLL1-2、USP2-AS1、Lnc-INPPL1-2。GO分析结果提示,差异基因主要富集在上皮细胞分化、中间丝、中间丝细胞骨架、突触后膜、颗粒分泌、细胞因子受体活性等分子生物学功能方面。KEGG富集分析提示,差异表达基因主要富集在HIF-1信号通路、Th17细胞分化、戊糖磷酸途径、精氨酸和脯氨酸代谢、果糖和甘露糖代谢、磷脂酶D信号通路、溶酶体等信号通路方面。logistic回归模型显示,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型具有较好的预测能力,AUC为0.887(95%CI 0.820~0.954)。模型回归方程logit(p)=1.582×LINC00562-1.969×LINC02356-0.798×LUCAT1+4.357。模型的灵敏度为81.3%,特异度为84.0%。结论直肠癌CRT反应良好和CRT无反应者间lncRNA分子存在明显的差异表达,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型对CRT疗效具有较好的预测能力。
文摘The zirconium(Zr)alloy fuel cladding is one of the key structural components of a nuclear reactor and the first and most important line of defense for accommodating fission products.During the operation of nuclear reactors,Zr alloy fuel cladding is subjected to extreme harsh environments,such as high temperature,high pressure and high flow rate for a long period of time.The wear and corrosion resistance of Zr alloys is important for the safe operation of nuclear reactors.Surface modification can effectively improve the corrosion and wear resistance of fuel cladding.Compared with coating technology,nitriding technology does not have problems for bonding between the coating and the substrate.Current research on surface nitriding of Zr alloys mainly focuses on plasma nitriding and ion implantation techniques.Research on laser nitriding of Zr alloy surfaces and their fretting wear characteristics is scarce.In this study,the surface of Zr alloy was treated with laser nitriding at different laser energies.The microstructure of Zr alloy treated with different laser energies and its fretting wear performance were studied.The results showed that after nitriding with different laser energies,the surface of the Zr alloy showed a typical molten state after melting,vaporizing and cooling under the thermal effect of the laser,and this state was more obvious with the increase of the laser energy.At the same time,doping of N atoms and formation of the ZrN phase led to different cooling rates in the molten zone that produced large tensile stresses after cooling.This led to cracks on the surface of Zr alloys after laser nitriding at different energies,and the crack density increased with increasing laser energy.This also led to an increase in the surface roughness of the Zr alloy with increasing laser energy after laser nitriding treatment.Due to the presence of water in the industrial nitrogen,nitrides were generated on the surface of the sample along with some oxides.When the laser energy was 100 mJ,there was no ZrN generation,and N existed mainly as a diffusion layer within the Zr alloy substrate.ZrN generated when the laser energy reached 200 mJ and above,which increased with the increase of laser energy.Due to the generation of ZrN phase and the presence of some oxides,the surface Vickers hardness of Zr alloys after laser nitriding treatment at different energies increased by 37.5%compared to Zr alloys.After laser nitriding treatment,the wear mechanism of Zr alloys changed.For the untreated Zr alloys,the wear mechanism was dominated by delamination and spalling wear,accompanied by oxidative and abrasive wear.The phenomenon of delamination and peeling decreased with the increase of laser energy.Wear mechanisms changed to predominantly abrasive wear with oxidative wear and delamination spalling.The wear volume of sample nitriding with laser energy 400 mJ was reduced by 46.5%compared with that of untreated Zr alloy.
