Isocitrate dehydrogenase 2(IDH2)and glutamate dehydrogenase 1(GLUD1)are key enzymes involved in the production ofα-ketoglutarate(α-KG),a metabolite central to the tricarboxylic acid cycle and glutamine metabolism.In...Isocitrate dehydrogenase 2(IDH2)and glutamate dehydrogenase 1(GLUD1)are key enzymes involved in the production ofα-ketoglutarate(α-KG),a metabolite central to the tricarboxylic acid cycle and glutamine metabolism.In this study,we investigated the impact of IDH2 and GLUD1 on early porcine embryonic development following IDH2 and GLUD1 knockdown(KD)via doublestranded RNA(dsRNA)microinjection.Results showed that KD reducedα-KG levels,leading to delayed embryonic development,decreased blastocyst formation,increased apoptosis,reduced blastomere proliferation,and pluripotency.Additionally,IDH2 and GLUD1 KD induced abnormally high levels of trimethylation of lysine 20 of histone H4(H4K20me3)at the 4-cell stage,likely resulting in transcriptional repression of embryonic genome activation(EGA)-related genes.Notably,KD of lysine methyltransferase 5C(KMT5C)and supplementation with exogenousα-KG reduced H4K20me3 expression and partially rescued these defects,suggesting a critical role of IDH2 and GLUD1 in the epigenetic regulation and proper development of porcine embryos.Overall,this study highlights the significance of IDH2 and GLUD1 in maintaining normal embryonic development through their influence onα-KG production and subsequent epigenetic modifications.展开更多
阐述一个能实现大型企业办公自动化的工作流系统的设计思想。该系统采用了基于.NET框架的多层体系结构,较好地体现了C#面向对象和面向组件的特性,整个系统具有良好的健壮性和可扩展性。同时介绍了在.NET平台下如何结合K2.NET进行工作流...阐述一个能实现大型企业办公自动化的工作流系统的设计思想。该系统采用了基于.NET框架的多层体系结构,较好地体现了C#面向对象和面向组件的特性,整个系统具有良好的健壮性和可扩展性。同时介绍了在.NET平台下如何结合K2.NET进行工作流应用的开发,最终实现了一个具有通用性的功能较为完善的加班费用报销审批子系统TEMA(Transport Expense and MealAllowance)。展开更多
Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly...Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.展开更多
合环电流评估技术对于配电网馈线合环转供电操作具有重要意义,为了提高主动配电网馈线合环电流计算的准确性,文中从融入源荷数据分布特性及预测的角度,提出基于双重K2算法和概率潮流(double K2 algorithm and probability load flow,DK2...合环电流评估技术对于配电网馈线合环转供电操作具有重要意义,为了提高主动配电网馈线合环电流计算的准确性,文中从融入源荷数据分布特性及预测的角度,提出基于双重K2算法和概率潮流(double K2 algorithm and probability load flow,DK2-PLF)的主动配电网馈线合环电流评估方法。首先,采用基于DK2算法的贝叶斯网络描述源荷相关性样本;其次,利用Cholesky分解方法处理获得的源荷相关性样本,以半不变量法计算主动配电网馈线合环电流的累积概率分布;然后,对主动配电网馈线合环电流从合环成功率和越限程度两方面进行安全性评估;最后,以贵州某城市为算例,对10 kV配电网系统开展馈线合环电流评估研究。得出以下结论:一是从概率密度、累积分布、最大误差三方面比较,相比于K2算法,DK2算法源荷预测值的概率密度、累积分布误差较小,验证了DK2算法的优越性;二是从累积分布、最大误差两方面比较,采用Cholesky分解的半不变量法对比未采用Cholesky分解的半不变量法、蒙特卡洛法,其累积分布误差较小,采用Cholesky分解的半不变量法满足主动配电网馈线合环电流评估要求;三是从合环成功率、合环越限程度两方面比较,采用半不变量法计算的合环电流安全性指标结果与仿真结果偏差在电网经验误差5%范围内,说明基于DK2-PLF的主动配电网馈线合环电流评估方法可为合环辅助决策提供参考。展开更多
基金supported by the National Research Foundation(NRF)of Korea grant funded by the Korean government(MSIT)(2022R1A2C300769),Republic of Korea。
文摘Isocitrate dehydrogenase 2(IDH2)and glutamate dehydrogenase 1(GLUD1)are key enzymes involved in the production ofα-ketoglutarate(α-KG),a metabolite central to the tricarboxylic acid cycle and glutamine metabolism.In this study,we investigated the impact of IDH2 and GLUD1 on early porcine embryonic development following IDH2 and GLUD1 knockdown(KD)via doublestranded RNA(dsRNA)microinjection.Results showed that KD reducedα-KG levels,leading to delayed embryonic development,decreased blastocyst formation,increased apoptosis,reduced blastomere proliferation,and pluripotency.Additionally,IDH2 and GLUD1 KD induced abnormally high levels of trimethylation of lysine 20 of histone H4(H4K20me3)at the 4-cell stage,likely resulting in transcriptional repression of embryonic genome activation(EGA)-related genes.Notably,KD of lysine methyltransferase 5C(KMT5C)and supplementation with exogenousα-KG reduced H4K20me3 expression and partially rescued these defects,suggesting a critical role of IDH2 and GLUD1 in the epigenetic regulation and proper development of porcine embryos.Overall,this study highlights the significance of IDH2 and GLUD1 in maintaining normal embryonic development through their influence onα-KG production and subsequent epigenetic modifications.
文摘阐述一个能实现大型企业办公自动化的工作流系统的设计思想。该系统采用了基于.NET框架的多层体系结构,较好地体现了C#面向对象和面向组件的特性,整个系统具有良好的健壮性和可扩展性。同时介绍了在.NET平台下如何结合K2.NET进行工作流应用的开发,最终实现了一个具有通用性的功能较为完善的加班费用报销审批子系统TEMA(Transport Expense and MealAllowance)。
基金supported by the Xiamen High-Level Health Talents Introduction and Training Project(Xiaweidang 2021-124)the National Natural Science Foundation of China(No.81774319).
文摘Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.
文摘合环电流评估技术对于配电网馈线合环转供电操作具有重要意义,为了提高主动配电网馈线合环电流计算的准确性,文中从融入源荷数据分布特性及预测的角度,提出基于双重K2算法和概率潮流(double K2 algorithm and probability load flow,DK2-PLF)的主动配电网馈线合环电流评估方法。首先,采用基于DK2算法的贝叶斯网络描述源荷相关性样本;其次,利用Cholesky分解方法处理获得的源荷相关性样本,以半不变量法计算主动配电网馈线合环电流的累积概率分布;然后,对主动配电网馈线合环电流从合环成功率和越限程度两方面进行安全性评估;最后,以贵州某城市为算例,对10 kV配电网系统开展馈线合环电流评估研究。得出以下结论:一是从概率密度、累积分布、最大误差三方面比较,相比于K2算法,DK2算法源荷预测值的概率密度、累积分布误差较小,验证了DK2算法的优越性;二是从累积分布、最大误差两方面比较,采用Cholesky分解的半不变量法对比未采用Cholesky分解的半不变量法、蒙特卡洛法,其累积分布误差较小,采用Cholesky分解的半不变量法满足主动配电网馈线合环电流评估要求;三是从合环成功率、合环越限程度两方面比较,采用半不变量法计算的合环电流安全性指标结果与仿真结果偏差在电网经验误差5%范围内,说明基于DK2-PLF的主动配电网馈线合环电流评估方法可为合环辅助决策提供参考。
