Background:Chronic endometritis(CE)is an important pathological factor contributing to female infertility and recurrent pregnancy loss.Although antibiotics are the primary clinical treatment for CE,they do not effecti...Background:Chronic endometritis(CE)is an important pathological factor contributing to female infertility and recurrent pregnancy loss.Although antibiotics are the primary clinical treatment for CE,they do not effectively improve pregnancy outcomes.Wen Yang Hua Zhuo(WYHZ)is a clinically employed classical formula known for its effects in warming yang,tonifying the spleen and kidneys,and resolving dampness.However,its underlying mechanisms remain unclear.This study aimed to elucidate how WYHZ modulates the immunometabolic microenvironment at the maternal-fetal interface in CE by targeting the MCT/HIF-1α/LDHA pathway to promote embryo implantation.Methods:In vivo,the model of CE was established by intrauterine injection of lipopolysaccharide(LPS)(1 mg/mL)into female C57/BL mice,followed by WYHZ treatment for 3 weeks to evaluate its effects on embryo implantation.Mechanistic studies were further conducted using the MCT-1 inhibitor AZD3965 and adeno-associated virus-mediated HIF-1αknockdown.In vitro,an in vitro CE model consisting of M1 macrophages and Ishikawa,as well as an in vitro embryo implantation model mediated by JAR cells,were constructed using Transwell,and the therapeutic mechanisms of WYHZ was validated using AZD3965 and lentiviral sh HIF-1αintervention.Metabolic enzyme activity assays,protein antibody microarrays,immunofluorescence,Western blotting,Seahorse analysis,and ELISA were employed.Results:WYHZ improved the immune-inflammatory microenvironment at the maternal-fetal interface by reducing pro-inflammatory cytokines and increasing anti-inflammatory factors.In parallel,WYHZ reprogrammed endometrial metabolism by enhancing glycolysis and suppressing mitochondrial oxidative phosphorylation,thereby improving endometrial receptivity and embryo implantation.Mechanistically,WYHZ activated the MCT/HIF-1α/LDHA pathway in endometrial epithelial cells,alleviating inflammatory stress and restoring receptivity.Both AZD3965 intervention and HIF-1αknockdown impaired endometrial receptivity and implantation,effects that were reversed by WYHZ.Conclusion:WYHZ modulates the immunometabolic microenvironment of the endometrium in the context of CE by targeting the activation of the MCT/HIF-1α/LDHA pathway,which improves endometrial receptivity and promotes embryo implantation.展开更多
在多无人机协同突防过程中,针对无人机需完成目标分配与探干侦动作选择的任务决策存在模型构建难,对模型求解方法复杂度高的问题,提出一种蒙特卡罗树搜索(Monte Carlo tree search,MCTS)的改进方法实现多无人机多任务联合决策。首先,考...在多无人机协同突防过程中,针对无人机需完成目标分配与探干侦动作选择的任务决策存在模型构建难,对模型求解方法复杂度高的问题,提出一种蒙特卡罗树搜索(Monte Carlo tree search,MCTS)的改进方法实现多无人机多任务联合决策。首先,考虑无人机与雷达对抗中的角度、距离等态势要素,以及当前无人机动作执行成功概率和雷达状态有效概率,构建多无人机目标分配与探干侦动作统一决策数学模型。其次,提出搜索次数自适应调整的改进MCTS算法对模型求解,实现大规模解空间在线快速寻优。仿真结果表明,改进算法使多雷达系统对无人机的威胁程度下降约16.8%,相比多臂赌博机算法效果提升约5.08%,决策时间约0.23 s,比传统MCTS缩短约45.7%,有助于提升无人机战场生存率。展开更多
基金supported by the National Natural Science Foundation of China(grant number:82205172,82274570).
文摘Background:Chronic endometritis(CE)is an important pathological factor contributing to female infertility and recurrent pregnancy loss.Although antibiotics are the primary clinical treatment for CE,they do not effectively improve pregnancy outcomes.Wen Yang Hua Zhuo(WYHZ)is a clinically employed classical formula known for its effects in warming yang,tonifying the spleen and kidneys,and resolving dampness.However,its underlying mechanisms remain unclear.This study aimed to elucidate how WYHZ modulates the immunometabolic microenvironment at the maternal-fetal interface in CE by targeting the MCT/HIF-1α/LDHA pathway to promote embryo implantation.Methods:In vivo,the model of CE was established by intrauterine injection of lipopolysaccharide(LPS)(1 mg/mL)into female C57/BL mice,followed by WYHZ treatment for 3 weeks to evaluate its effects on embryo implantation.Mechanistic studies were further conducted using the MCT-1 inhibitor AZD3965 and adeno-associated virus-mediated HIF-1αknockdown.In vitro,an in vitro CE model consisting of M1 macrophages and Ishikawa,as well as an in vitro embryo implantation model mediated by JAR cells,were constructed using Transwell,and the therapeutic mechanisms of WYHZ was validated using AZD3965 and lentiviral sh HIF-1αintervention.Metabolic enzyme activity assays,protein antibody microarrays,immunofluorescence,Western blotting,Seahorse analysis,and ELISA were employed.Results:WYHZ improved the immune-inflammatory microenvironment at the maternal-fetal interface by reducing pro-inflammatory cytokines and increasing anti-inflammatory factors.In parallel,WYHZ reprogrammed endometrial metabolism by enhancing glycolysis and suppressing mitochondrial oxidative phosphorylation,thereby improving endometrial receptivity and embryo implantation.Mechanistically,WYHZ activated the MCT/HIF-1α/LDHA pathway in endometrial epithelial cells,alleviating inflammatory stress and restoring receptivity.Both AZD3965 intervention and HIF-1αknockdown impaired endometrial receptivity and implantation,effects that were reversed by WYHZ.Conclusion:WYHZ modulates the immunometabolic microenvironment of the endometrium in the context of CE by targeting the activation of the MCT/HIF-1α/LDHA pathway,which improves endometrial receptivity and promotes embryo implantation.
文摘在多无人机协同突防过程中,针对无人机需完成目标分配与探干侦动作选择的任务决策存在模型构建难,对模型求解方法复杂度高的问题,提出一种蒙特卡罗树搜索(Monte Carlo tree search,MCTS)的改进方法实现多无人机多任务联合决策。首先,考虑无人机与雷达对抗中的角度、距离等态势要素,以及当前无人机动作执行成功概率和雷达状态有效概率,构建多无人机目标分配与探干侦动作统一决策数学模型。其次,提出搜索次数自适应调整的改进MCTS算法对模型求解,实现大规模解空间在线快速寻优。仿真结果表明,改进算法使多雷达系统对无人机的威胁程度下降约16.8%,相比多臂赌博机算法效果提升约5.08%,决策时间约0.23 s,比传统MCTS缩短约45.7%,有助于提升无人机战场生存率。
