胃癌是全球发病率和死亡率均较高的恶性肿瘤之一,开发新的胃癌治疗药物具有重要意义。β,β-二甲基丙烯酰阿卡宁(β,β-dimethylacrylalkannin,β,β-DAL)作为中药紫草中的一种天然产物,其抗胃癌作用研究尚未报道。本研究旨在探究β,β-...胃癌是全球发病率和死亡率均较高的恶性肿瘤之一,开发新的胃癌治疗药物具有重要意义。β,β-二甲基丙烯酰阿卡宁(β,β-dimethylacrylalkannin,β,β-DAL)作为中药紫草中的一种天然产物,其抗胃癌作用研究尚未报道。本研究旨在探究β,β-DAL体外抗胃癌活性及其作用机制。借助CCK-8法、集落形成实验以及EdU染色法发现,β,β-DAL能够抑制人胃癌AGS和HGC-27细胞的体外增殖能力,48 h的IC50值分别约为0.28和0.15μmol·L^(-1)。转录组测序数据分析结果提示β,β-DAL抗胃癌作用与铁死亡调控相关。流式细胞术实验结果显示,β,β-DAL能够上调人胃癌AGS和HGC-27细胞中ROS水平。此外,β,β-DAL还能够增加人胃癌AGS和HGC-27细胞中脂质过氧化的水平,并且铁死亡抑制剂ferrostatin-1能够削弱人胃癌AGS和HGC-27细胞对β,β-DAL的敏感性。免疫印迹实验结果显示,β,β-DAL能够下调人胃癌AGS和HGC-27细胞中硬脂酰辅酶A去饱和酶1(stearoyl-CoA desaturase 1,SCD1)、核因子E2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)的蛋白表达水平,以及能够抑制SCD1/长链脂酰辅酶A合成酶4(acyl-CoA synthetase long chain family member 4,ACSL4)的蛋白比例。综上所述,β,β-DAL可能通过上调ROS水平、增加胞内脂质过氧化,以及抑制SCD1/Nrf2抗氧化通路诱导人胃癌细胞铁死亡,发挥抗胃癌作用。本研究工作为胃癌治疗提供了一个候选研究药物,为β,β-DAL后续抗胃癌深入研究提供了一定的基础。展开更多
Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly inter...Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years.Porphyromonas gingivalis(P.gingivalis)is increasingly considered to be closely related to the development of oral squamous cell carcinoma(OSCC).Nevertheless,the role of P.gingivalis in the stemness of OSCC cells remains uncertain.Herein,we showed that P.gingivalis was positively correlated with CSC markers expression in human OSCC specimens,promoted the stemness and tumorigenicity of OSCC cells,and enhanced tumor formation in nude mice.Mechanistically,P.gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1(SCD1)expression,a key enzyme involved in lipid metabolism,which ultimately resulted in enhanced acquisition of stemness.Moreover,SCD1 suppression attenuated P.gingivalis-induced stemness of OSCC cells,including CSCs markers expression,sphere formation ability,chemoresistance,and tumor growth,in OSCC cells both in vitro and in vivo.Additionally,upregulation of SCD1 in P.gingivalis-infected OSCC cells was associated with the expression of KLF5,and that was modulated by P.gingivalis-activated NOD1 signaling.Taken together,these findings highlight the importance of SCD1-dependent lipid synthesis in P.gingivalis-induced stemness acquisition in OSCC cells,suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.展开更多
针对电力领域文本数据分词准确性较低的问题,提出一种基于改进ADAM(adaptive moment estimation)算法的中文分词技术。选用Skip-Gram模型作为字嵌入模型,将字词转为分布式向量,搭建卷积神经网络-门控循环单元-条件随机场(CNN-Bi-GRU-CRF...针对电力领域文本数据分词准确性较低的问题,提出一种基于改进ADAM(adaptive moment estimation)算法的中文分词技术。选用Skip-Gram模型作为字嵌入模型,将字词转为分布式向量,搭建卷积神经网络-门控循环单元-条件随机场(CNN-Bi-GRU-CRF)模型实现电力领域文本语句的分割,提出一种改进的ADAM算法,通过控制不同时间窗口的学习率优化神经网络模型,提高模型训练速度。将所提算法运用于变电站SCD(system configuration description)文本数据分词的算例分析,通过与其他主流分词算法进行比较,验证所提分词技术的先进性与准确性。展开更多
文摘胃癌是全球发病率和死亡率均较高的恶性肿瘤之一,开发新的胃癌治疗药物具有重要意义。β,β-二甲基丙烯酰阿卡宁(β,β-dimethylacrylalkannin,β,β-DAL)作为中药紫草中的一种天然产物,其抗胃癌作用研究尚未报道。本研究旨在探究β,β-DAL体外抗胃癌活性及其作用机制。借助CCK-8法、集落形成实验以及EdU染色法发现,β,β-DAL能够抑制人胃癌AGS和HGC-27细胞的体外增殖能力,48 h的IC50值分别约为0.28和0.15μmol·L^(-1)。转录组测序数据分析结果提示β,β-DAL抗胃癌作用与铁死亡调控相关。流式细胞术实验结果显示,β,β-DAL能够上调人胃癌AGS和HGC-27细胞中ROS水平。此外,β,β-DAL还能够增加人胃癌AGS和HGC-27细胞中脂质过氧化的水平,并且铁死亡抑制剂ferrostatin-1能够削弱人胃癌AGS和HGC-27细胞对β,β-DAL的敏感性。免疫印迹实验结果显示,β,β-DAL能够下调人胃癌AGS和HGC-27细胞中硬脂酰辅酶A去饱和酶1(stearoyl-CoA desaturase 1,SCD1)、核因子E2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)的蛋白表达水平,以及能够抑制SCD1/长链脂酰辅酶A合成酶4(acyl-CoA synthetase long chain family member 4,ACSL4)的蛋白比例。综上所述,β,β-DAL可能通过上调ROS水平、增加胞内脂质过氧化,以及抑制SCD1/Nrf2抗氧化通路诱导人胃癌细胞铁死亡,发挥抗胃癌作用。本研究工作为胃癌治疗提供了一个候选研究药物,为β,β-DAL后续抗胃癌深入研究提供了一定的基础。
基金supported by the National Natural Science Foundation of China(grant#82370975 and 82170969)。
文摘Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years.Porphyromonas gingivalis(P.gingivalis)is increasingly considered to be closely related to the development of oral squamous cell carcinoma(OSCC).Nevertheless,the role of P.gingivalis in the stemness of OSCC cells remains uncertain.Herein,we showed that P.gingivalis was positively correlated with CSC markers expression in human OSCC specimens,promoted the stemness and tumorigenicity of OSCC cells,and enhanced tumor formation in nude mice.Mechanistically,P.gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1(SCD1)expression,a key enzyme involved in lipid metabolism,which ultimately resulted in enhanced acquisition of stemness.Moreover,SCD1 suppression attenuated P.gingivalis-induced stemness of OSCC cells,including CSCs markers expression,sphere formation ability,chemoresistance,and tumor growth,in OSCC cells both in vitro and in vivo.Additionally,upregulation of SCD1 in P.gingivalis-infected OSCC cells was associated with the expression of KLF5,and that was modulated by P.gingivalis-activated NOD1 signaling.Taken together,these findings highlight the importance of SCD1-dependent lipid synthesis in P.gingivalis-induced stemness acquisition in OSCC cells,suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
文摘针对电力领域文本数据分词准确性较低的问题,提出一种基于改进ADAM(adaptive moment estimation)算法的中文分词技术。选用Skip-Gram模型作为字嵌入模型,将字词转为分布式向量,搭建卷积神经网络-门控循环单元-条件随机场(CNN-Bi-GRU-CRF)模型实现电力领域文本语句的分割,提出一种改进的ADAM算法,通过控制不同时间窗口的学习率优化神经网络模型,提高模型训练速度。将所提算法运用于变电站SCD(system configuration description)文本数据分词的算例分析,通过与其他主流分词算法进行比较,验证所提分词技术的先进性与准确性。
