Objective:Baicalein has been reported to have wide therapeutic effects that act through its antiinflammatory activity.This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy(SIC).Met...Objective:Baicalein has been reported to have wide therapeutic effects that act through its antiinflammatory activity.This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy(SIC).Methods:A thorough screening of a small library of natural products,comprising 100 diverse compounds,was conducted to identify the most effective drug against lipopolysaccharide(LPS)-treated H9C2 cardiomyocytes.The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology.Results:Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes.It exhibited a dose-dependent inhibitory effect on cell injury and inflammation.In the LPSinduced septic mouse model,baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits,inflammatory responses,and ferroptosis.Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit a(HIF1-a)is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury.By combining microRNA(miRNA)screening in LPS-treated myocardium with miRNA prediction targeting HIF1-a,we found that miR-299b-5p may serve as a regulator of HIF1-a.The reduction in miR-299b-5p levels in LPS-treated myocardium,compared to the control group,was reversed by baicalein treatment.The reverse transcription quantitative polymerase chain reaction,Western blotting,and dual-luciferase reporter gene analyses together identified HIF1-a as the target of miR-299b-5p in cardiomyocytes.Conclusion:Baicalein mitigates SIC at the miRNA level,suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-a/ferroptosis pathway.展开更多
本文针对舰载电子装备可靠性预计方法选择难题,开展基于GJB/Z 299C-2006《电子设备可靠性预计手册》的双模型预计方法对比研究。通过建立包含“7/12”表决系统的混合可靠性模型,分别采用元器件应力法和计数法对某型舰载计算保障中心进...本文针对舰载电子装备可靠性预计方法选择难题,开展基于GJB/Z 299C-2006《电子设备可靠性预计手册》的双模型预计方法对比研究。通过建立包含“7/12”表决系统的混合可靠性模型,分别采用元器件应力法和计数法对某型舰载计算保障中心进行平均无故障时间(MTBF:Mean Time Between Failures)预计。依据GJB 899A-2009《可靠性鉴定和验收试验》,结合舰船Nu类环境特性,设计多应力耦合可靠性试验方案,构建包含冷循环和热循环的验证试验剖面。试验数据分析表明:应力法预计值6313 h与验证值6027 h偏差4.75%,显著优于计数法15.7%的偏差率;两种方法在集成电路模块的预测偏差呈现显著差异。研究表明,采用精细化应力分析法可在设计阶段实现误差较小的可靠性预计,为复杂环境下的装备可靠性设计提供有效解决方案。展开更多
基金supported by Natural Science Foundation Project of Ningxia Hui Autonomous Region(No.2021AAC03327)Hunan Provincial Natural Science Foundation(No.2021JJ31058)+2 种基金Shanghai Pujiang Program(No.23PJ1403300)Shanghai Science and Technology Commission(No.23ZR1440700)National Natural Science Foundation of China(No.82000797,82102244,31971077,and 82070255)。
文摘Objective:Baicalein has been reported to have wide therapeutic effects that act through its antiinflammatory activity.This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy(SIC).Methods:A thorough screening of a small library of natural products,comprising 100 diverse compounds,was conducted to identify the most effective drug against lipopolysaccharide(LPS)-treated H9C2 cardiomyocytes.The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology.Results:Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes.It exhibited a dose-dependent inhibitory effect on cell injury and inflammation.In the LPSinduced septic mouse model,baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits,inflammatory responses,and ferroptosis.Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit a(HIF1-a)is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury.By combining microRNA(miRNA)screening in LPS-treated myocardium with miRNA prediction targeting HIF1-a,we found that miR-299b-5p may serve as a regulator of HIF1-a.The reduction in miR-299b-5p levels in LPS-treated myocardium,compared to the control group,was reversed by baicalein treatment.The reverse transcription quantitative polymerase chain reaction,Western blotting,and dual-luciferase reporter gene analyses together identified HIF1-a as the target of miR-299b-5p in cardiomyocytes.Conclusion:Baicalein mitigates SIC at the miRNA level,suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-a/ferroptosis pathway.
文摘本文针对舰载电子装备可靠性预计方法选择难题,开展基于GJB/Z 299C-2006《电子设备可靠性预计手册》的双模型预计方法对比研究。通过建立包含“7/12”表决系统的混合可靠性模型,分别采用元器件应力法和计数法对某型舰载计算保障中心进行平均无故障时间(MTBF:Mean Time Between Failures)预计。依据GJB 899A-2009《可靠性鉴定和验收试验》,结合舰船Nu类环境特性,设计多应力耦合可靠性试验方案,构建包含冷循环和热循环的验证试验剖面。试验数据分析表明:应力法预计值6313 h与验证值6027 h偏差4.75%,显著优于计数法15.7%的偏差率;两种方法在集成电路模块的预测偏差呈现显著差异。研究表明,采用精细化应力分析法可在设计阶段实现误差较小的可靠性预计,为复杂环境下的装备可靠性设计提供有效解决方案。
