Objective To observe the effect of meisoindigo onapoptosis and proliferation of JAK2 /V617F heterozygousmutation cell line-SET2 cell line to further explore therole of JAK-STAT pathway in this effect. Methods Cellapop...Objective To observe the effect of meisoindigo onapoptosis and proliferation of JAK2 /V617F heterozygousmutation cell line-SET2 cell line to further explore therole of JAK-STAT pathway in this effect. Methods Cellapoptosis after treated with different concentration of meisoindigo(0,5,and 10 μmol /L) was evaluated by flowcytometry at different time points (24,48,72 h). Cellproliferation with CCK8 test was evaluated at differenttime points (24,48,72,96 h) after administered withdifferent concentration of meisoindigo (0,5,10,and20 μmol /L). After treatment with different concentrationof meisoindigo (0,5,10,and 20 μmol /L),SET2 cellswere collected after 12 h,and then cultured in incom-plete methylcellulose-based medium for clone formation.JAK-STAT signaling pathway and apoptosis related proteinby Western blot test were evaluated 12 h after administeredwith different concentration of meisoindigo(0,5,10,and 20 μmol /L).展开更多
Background:Nuclear receptor-binding SET domain 2(NSD2)is a histone methyltrans-ferase,that catalyzes dimethylation of lysine 36 of histone 3(H3K36me2)and is asso-ciated with active transcription of a series of genes.N...Background:Nuclear receptor-binding SET domain 2(NSD2)is a histone methyltrans-ferase,that catalyzes dimethylation of lysine 36 of histone 3(H3K36me2)and is asso-ciated with active transcription of a series of genes.NSD2 is overexpressed in multiple types of solid human tumors and has been proven to be related to unfavorable prog-nosis in several types of tumors.Methods:We established a mouse model in which the NSD2 gene was conditionally knocked out in intestinal epithelial cells.We used azoxymethane and dextran sodium sulfate to chemically induce murine colorectal cancer.The development of colorectal tumors were investigated using post-necropsy quantification,immunohistochemistry,and enzyme-linked immunosorbent assay(ELISA).Results:Compared with wild-type(WT)control mice,NSD2^(fl/fl)-Vil1-Cre mice exhib-ited significantly decreased tumor numbers,histopathological changes,and cytokine expression in colorectal tumors.Conclusions:Conditional knockout of NSD2 in intestinal epithelial cells significantly inhibits colorectal cancer progression.展开更多
目的探究核受体结合SET结构域蛋白2(Nuclear receptor-binding SET domain-containing protein 2,NSD2)在胃癌(gastric cancer,GC)中的表达模式及其对胃癌细胞生物学行为、顺铂耐药及肿瘤免疫的影响。方法生物信息学分析胃癌中NSD2表达...目的探究核受体结合SET结构域蛋白2(Nuclear receptor-binding SET domain-containing protein 2,NSD2)在胃癌(gastric cancer,GC)中的表达模式及其对胃癌细胞生物学行为、顺铂耐药及肿瘤免疫的影响。方法生物信息学分析胃癌中NSD2表达量及对预后、胃癌免疫细胞及免疫因子的影响;RT-qPCR检测胃及胃癌细胞系中NSD2表达量;使用NSD2抑制剂(LEM-14、UNC6934)建立NSD2低表达胃癌细胞模型,Western Blot检测细胞系NSD2抑制效率;CCK-8、克隆形成实验和划痕愈合实验测NSD2表达对胃癌细胞的增殖及迁移能力的影响;CCK-8实验检测NSD2对顺铂耐药的影响。结果GEPIA2数据库/UALCNA网站分析结果显示,NSD2在胃癌组织中表达高于癌旁组织(P<0.05);Kaplan-Meier Plotter结果提示NSD2低表达的胃癌患者有较好的预后(P<0.05);抑制NSD2表达后胃癌细胞的增殖及迁移能力受到显著抑制(P<0.05);NSD2的表达促进胃癌细胞系顺铂(HGC-27)耐药(P<0.05),提高顺铂IC50(P<0.001);TISDIB分析提示NSD2抑制CD4及CD8免疫细胞浸润,与PD-L1、CTLA4表达呈正相关。结论NSD2在胃癌组织和细胞系中高表达,高表达的胃癌患者预后较差;NSD2促进胃癌细胞增殖及迁移能力、顺铂耐药及增加顺铂IC50、促进胃癌细胞免疫逃逸。展开更多
目的:探讨组蛋白赖氨酸甲基转移酶SET和MYND结构域蛋白2(SET and MYND domain-containing protein 2,SMYD2)在宫颈癌细胞糖代谢中的作用,进一步研究其是否与宫颈癌增殖有关。方法:通过基因表达谱交互分析(gene expression profiling int...目的:探讨组蛋白赖氨酸甲基转移酶SET和MYND结构域蛋白2(SET and MYND domain-containing protein 2,SMYD2)在宫颈癌细胞糖代谢中的作用,进一步研究其是否与宫颈癌增殖有关。方法:通过基因表达谱交互分析(gene expression profiling interactive analysis,GEPIA)数据库分析SMYD家族成员在宫颈癌中的表达和预后价值,通过log-rank检验进行生存差异比较。通过SMYD2的shRNA敲低或过表达技术来研究SMYD2在宫颈癌中的糖代谢作用。结果:宫颈癌组织中SMYD2的表达与患者年龄、性别、肿瘤组织分化程度无关,SMYD2的过表达预示总体生存期较差与临床分期相关(F=4.520,P=0.004)。生物信息分析揭示了SMYD2在调控宫颈癌中Warburg效应中发挥调节作用。通过功能缺失实验,证明SMYD2的敲低抑制了宫颈癌细胞的有氧糖酵解,表现为葡萄糖摄取减少,乳酸生成降低和细胞外酸化减弱,而SMYD2过表达则促进子宫颈癌细胞的糖酵解代谢。此外,SMYD2是宫颈癌细胞生长所必需的,并且这种致癌作用主要依赖糖酵解。结论:SMYD2在宫颈癌细胞中过表达并在肿瘤代谢中发挥重要作用,能够通过调节有氧酵解促进宫颈癌细胞增殖。展开更多
In view of the environment competencies,selecting the optimal green supplier is one of the crucial issues for enterprises,and multi-criteria decision-making(MCDM)methodologies can more easily solve this green supplier...In view of the environment competencies,selecting the optimal green supplier is one of the crucial issues for enterprises,and multi-criteria decision-making(MCDM)methodologies can more easily solve this green supplier selection(GSS)problem.In addition,prioritized aggregation(PA)operator can focus on the prioritization relationship over the criteria,Choquet integral(CI)operator can fully take account of the importance of criteria and the interactions among them,and Bonferroni mean(BM)operator can capture the interrelationships of criteria.However,most existing researches cannot simultaneously consider the interactions,interrelationships and prioritizations over the criteria,which are involved in the GSS process.Moreover,the interval type-2 fuzzy set(IT2FS)is a more effective tool to represent the fuzziness.Therefore,based on the advantages of PA,CI,BM and IT2FS,in this paper,the interval type-2 fuzzy prioritized Choquet normalized weighted BM operators with fuzzy measure and generalized prioritized measure are proposed,and some properties are discussed.Then,a novel MCDM approach for GSS based upon the presented operators is developed,and detailed decision steps are given.Finally,the applicability and practicability of the proposed methodology are demonstrated by its application in the shared-bike GSS and by comparisons with other methods.The advantages of the proposed method are that it can consider interactions,interrelationships and prioritizations over the criteria simultaneously.展开更多
For dealing with large static error due to poor immunity of the traditional fuzzy control, a novel interval type-2 fuzzy control system is proposed. By extending the typical membership functions to interval type-2 mem...For dealing with large static error due to poor immunity of the traditional fuzzy control, a novel interval type-2 fuzzy control system is proposed. By extending the typical membership functions to interval type-2 membership functions, the proposed control system can efficiently reduce the uncertain disturbance from real environment without increasing the design complexity. The simulation results on the water tank level control system showed that the proposed method succeeded in better static and dynamic control with stronger robust performance than the traditional fuzzy control method.展开更多
In this paper, interval type-2 fuzzy sets, fuzzy comprehensive evaluation and the fuzzy control rules are synthesized to realize the control of unmanned vehicle in driving state and behavioral decisions. Compared to t...In this paper, interval type-2 fuzzy sets, fuzzy comprehensive evaluation and the fuzzy control rules are synthesized to realize the control of unmanned vehicle in driving state and behavioral decisions. Compared to the type-1 fuzzy set, type-2 fuzzy sets have more advantages in handling the model based on uncertainties, linguistic information because the membership functions are fuzzy sets. Different membership functions are established for each factor when the unmanned vehicle is driving at different speed intervals. In addition, a new evaluation method is developed to analyze unmanned vehicle’s driving state. Finally, a set of dynamic fuzzy rules are sorted out, which can be applied to the unmanned vehicle’s behavioral decision-making and provide a new idea to related research.展开更多
文摘Objective To observe the effect of meisoindigo onapoptosis and proliferation of JAK2 /V617F heterozygousmutation cell line-SET2 cell line to further explore therole of JAK-STAT pathway in this effect. Methods Cellapoptosis after treated with different concentration of meisoindigo(0,5,and 10 μmol /L) was evaluated by flowcytometry at different time points (24,48,72 h). Cellproliferation with CCK8 test was evaluated at differenttime points (24,48,72,96 h) after administered withdifferent concentration of meisoindigo (0,5,10,and20 μmol /L). After treatment with different concentrationof meisoindigo (0,5,10,and 20 μmol /L),SET2 cellswere collected after 12 h,and then cultured in incom-plete methylcellulose-based medium for clone formation.JAK-STAT signaling pathway and apoptosis related proteinby Western blot test were evaluated 12 h after administeredwith different concentration of meisoindigo(0,5,10,and 20 μmol /L).
基金supported by the National Key Research and Development Program of China (2022YFF0710705)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-0 13)+2 种基金funding support from the Special Research Fund for Central UniversitiesPeking Union Medical College (3332022182)the 111 Project (B20095)
文摘Background:Nuclear receptor-binding SET domain 2(NSD2)is a histone methyltrans-ferase,that catalyzes dimethylation of lysine 36 of histone 3(H3K36me2)and is asso-ciated with active transcription of a series of genes.NSD2 is overexpressed in multiple types of solid human tumors and has been proven to be related to unfavorable prog-nosis in several types of tumors.Methods:We established a mouse model in which the NSD2 gene was conditionally knocked out in intestinal epithelial cells.We used azoxymethane and dextran sodium sulfate to chemically induce murine colorectal cancer.The development of colorectal tumors were investigated using post-necropsy quantification,immunohistochemistry,and enzyme-linked immunosorbent assay(ELISA).Results:Compared with wild-type(WT)control mice,NSD2^(fl/fl)-Vil1-Cre mice exhib-ited significantly decreased tumor numbers,histopathological changes,and cytokine expression in colorectal tumors.Conclusions:Conditional knockout of NSD2 in intestinal epithelial cells significantly inhibits colorectal cancer progression.
文摘目的探究核受体结合SET结构域蛋白2(Nuclear receptor-binding SET domain-containing protein 2,NSD2)在胃癌(gastric cancer,GC)中的表达模式及其对胃癌细胞生物学行为、顺铂耐药及肿瘤免疫的影响。方法生物信息学分析胃癌中NSD2表达量及对预后、胃癌免疫细胞及免疫因子的影响;RT-qPCR检测胃及胃癌细胞系中NSD2表达量;使用NSD2抑制剂(LEM-14、UNC6934)建立NSD2低表达胃癌细胞模型,Western Blot检测细胞系NSD2抑制效率;CCK-8、克隆形成实验和划痕愈合实验测NSD2表达对胃癌细胞的增殖及迁移能力的影响;CCK-8实验检测NSD2对顺铂耐药的影响。结果GEPIA2数据库/UALCNA网站分析结果显示,NSD2在胃癌组织中表达高于癌旁组织(P<0.05);Kaplan-Meier Plotter结果提示NSD2低表达的胃癌患者有较好的预后(P<0.05);抑制NSD2表达后胃癌细胞的增殖及迁移能力受到显著抑制(P<0.05);NSD2的表达促进胃癌细胞系顺铂(HGC-27)耐药(P<0.05),提高顺铂IC50(P<0.001);TISDIB分析提示NSD2抑制CD4及CD8免疫细胞浸润,与PD-L1、CTLA4表达呈正相关。结论NSD2在胃癌组织和细胞系中高表达,高表达的胃癌患者预后较差;NSD2促进胃癌细胞增殖及迁移能力、顺铂耐药及增加顺铂IC50、促进胃癌细胞免疫逃逸。
文摘目的:探讨组蛋白赖氨酸甲基转移酶SET和MYND结构域蛋白2(SET and MYND domain-containing protein 2,SMYD2)在宫颈癌细胞糖代谢中的作用,进一步研究其是否与宫颈癌增殖有关。方法:通过基因表达谱交互分析(gene expression profiling interactive analysis,GEPIA)数据库分析SMYD家族成员在宫颈癌中的表达和预后价值,通过log-rank检验进行生存差异比较。通过SMYD2的shRNA敲低或过表达技术来研究SMYD2在宫颈癌中的糖代谢作用。结果:宫颈癌组织中SMYD2的表达与患者年龄、性别、肿瘤组织分化程度无关,SMYD2的过表达预示总体生存期较差与临床分期相关(F=4.520,P=0.004)。生物信息分析揭示了SMYD2在调控宫颈癌中Warburg效应中发挥调节作用。通过功能缺失实验,证明SMYD2的敲低抑制了宫颈癌细胞的有氧糖酵解,表现为葡萄糖摄取减少,乳酸生成降低和细胞外酸化减弱,而SMYD2过表达则促进子宫颈癌细胞的糖酵解代谢。此外,SMYD2是宫颈癌细胞生长所必需的,并且这种致癌作用主要依赖糖酵解。结论:SMYD2在宫颈癌细胞中过表达并在肿瘤代谢中发挥重要作用,能够通过调节有氧酵解促进宫颈癌细胞增殖。
基金supported by the National Natural Science Foundation of China(71771140)Project of Cultural Masters and“the Four Kinds of a Batch”Talents,the Special Funds of Taishan Scholars Project of Shandong Province(ts201511045)the Major Bidding Projects of National Social Science Fund of China(19ZDA080)。
文摘In view of the environment competencies,selecting the optimal green supplier is one of the crucial issues for enterprises,and multi-criteria decision-making(MCDM)methodologies can more easily solve this green supplier selection(GSS)problem.In addition,prioritized aggregation(PA)operator can focus on the prioritization relationship over the criteria,Choquet integral(CI)operator can fully take account of the importance of criteria and the interactions among them,and Bonferroni mean(BM)operator can capture the interrelationships of criteria.However,most existing researches cannot simultaneously consider the interactions,interrelationships and prioritizations over the criteria,which are involved in the GSS process.Moreover,the interval type-2 fuzzy set(IT2FS)is a more effective tool to represent the fuzziness.Therefore,based on the advantages of PA,CI,BM and IT2FS,in this paper,the interval type-2 fuzzy prioritized Choquet normalized weighted BM operators with fuzzy measure and generalized prioritized measure are proposed,and some properties are discussed.Then,a novel MCDM approach for GSS based upon the presented operators is developed,and detailed decision steps are given.Finally,the applicability and practicability of the proposed methodology are demonstrated by its application in the shared-bike GSS and by comparisons with other methods.The advantages of the proposed method are that it can consider interactions,interrelationships and prioritizations over the criteria simultaneously.
基金Supported by Program for Liaoning Excellent Talents in University (LJQ2011032)the National Natural Science Foundation of China (61203021)the National Science and Technology Support Program (2012BAF05B00)
文摘For dealing with large static error due to poor immunity of the traditional fuzzy control, a novel interval type-2 fuzzy control system is proposed. By extending the typical membership functions to interval type-2 membership functions, the proposed control system can efficiently reduce the uncertain disturbance from real environment without increasing the design complexity. The simulation results on the water tank level control system showed that the proposed method succeeded in better static and dynamic control with stronger robust performance than the traditional fuzzy control method.
基金supported by the National Natural Science Foundation of China(61473048,61074093)
文摘In this paper, interval type-2 fuzzy sets, fuzzy comprehensive evaluation and the fuzzy control rules are synthesized to realize the control of unmanned vehicle in driving state and behavioral decisions. Compared to the type-1 fuzzy set, type-2 fuzzy sets have more advantages in handling the model based on uncertainties, linguistic information because the membership functions are fuzzy sets. Different membership functions are established for each factor when the unmanned vehicle is driving at different speed intervals. In addition, a new evaluation method is developed to analyze unmanned vehicle’s driving state. Finally, a set of dynamic fuzzy rules are sorted out, which can be applied to the unmanned vehicle’s behavioral decision-making and provide a new idea to related research.