Aim Alpha7 nicotinic acetylcholine receptor （α7nAChR）, a subtype of nAChR regulating neurotrans- mission in central nervous system, is an essential regulator of cholinergic antiinflammatory pathway in periphery. Th...Aim Alpha7 nicotinic acetylcholine receptor （α7nAChR）, a subtype of nAChR regulating neurotrans- mission in central nervous system, is an essential regulator of cholinergic antiinflammatory pathway in periphery. The present study was to determine the effects of activation of α7nAChR on oxidant stress-induced injury in endo- thelial cells. Methods Cultured human umbilical vein endothelial cells were treated with H202 （400 μmol · L^-1） or H202plus PNU-282987 （ 10 μmol · L^-1 ）. Cell viability and membrane integrity were measured. AnnexinV ＋ PI assay, immunoblotting of bcl-2, bax and cleaved caspase-3, and immunofluorescence of apoptosis inducing factor （AIF） were performed to evaluate apoptosis. Protein expression of vascular peroxidase-1 （ VPO-1 ） and phosphor- JNK were measured by immunoblotting. Results Activation of α7nAChR by a selective agonist PNU-282987 pre-vented H202-indced decrease of cell viability and increase of lactate dehydrogenase release. Activation of α7nAChR markedly reduced cell apoptosis and intracellular oxidative stress level. Moreover, activation of α7nAChR reduced H2 02 -induced VPO-1 protein upregulation and JNK1/2 phosphorylation. The inhibitory effect of α7nAChR activa- tion on VPO-1 was blocked by JNK inhibitor SP600125. In addition, pretreatment of α7nAChR antagonist methyl- lycaconitine blocked the cytoprotective effect of PNU-282987. Conclusion These results provide the first evidence that activation of α7nAChR protects against oxidant stress-induced damage by suppressing VPO-1 in a JNK signa- ling pathway-dependent manner in endothelial cells.展开更多
城市电网在发生N-1故障后,极可能新增运行风险,导致N-1-1时出现大面积停电事故。为管控城市电网N-1后运行风险,该文提出一种改进双智能体竞争双深度Q网络(dueling double deep Q network,D3QN)的城市电网N-1风险管控转供策略。根据风险...城市电网在发生N-1故障后,极可能新增运行风险,导致N-1-1时出现大面积停电事故。为管控城市电网N-1后运行风险,该文提出一种改进双智能体竞争双深度Q网络(dueling double deep Q network,D3QN)的城市电网N-1风险管控转供策略。根据风险管控原则,提出一种无需额外历史数据、考虑备自投装置、单供变电站风险和单供负荷母线风险的N-1场景指标;建立计及动作次序、指标间关系的负荷转供三阶段求解模型。以含预动作-变化探索值选择策略的改进双智能体D3QN方法,将负荷转供分为多个子转供环节学习,使转供思路清晰化,对动作空间进行降维,提高训练寻优效果,得到管控N-1风险的负荷转供策略。通过城市电网多场景算例分析,验证该文模型和方法的有效性。展开更多
文摘Aim Alpha7 nicotinic acetylcholine receptor （α7nAChR）, a subtype of nAChR regulating neurotrans- mission in central nervous system, is an essential regulator of cholinergic antiinflammatory pathway in periphery. The present study was to determine the effects of activation of α7nAChR on oxidant stress-induced injury in endo- thelial cells. Methods Cultured human umbilical vein endothelial cells were treated with H202 （400 μmol · L^-1） or H202plus PNU-282987 （ 10 μmol · L^-1 ）. Cell viability and membrane integrity were measured. AnnexinV ＋ PI assay, immunoblotting of bcl-2, bax and cleaved caspase-3, and immunofluorescence of apoptosis inducing factor （AIF） were performed to evaluate apoptosis. Protein expression of vascular peroxidase-1 （ VPO-1 ） and phosphor- JNK were measured by immunoblotting. Results Activation of α7nAChR by a selective agonist PNU-282987 pre-vented H202-indced decrease of cell viability and increase of lactate dehydrogenase release. Activation of α7nAChR markedly reduced cell apoptosis and intracellular oxidative stress level. Moreover, activation of α7nAChR reduced H2 02 -induced VPO-1 protein upregulation and JNK1/2 phosphorylation. The inhibitory effect of α7nAChR activa- tion on VPO-1 was blocked by JNK inhibitor SP600125. In addition, pretreatment of α7nAChR antagonist methyl- lycaconitine blocked the cytoprotective effect of PNU-282987. Conclusion These results provide the first evidence that activation of α7nAChR protects against oxidant stress-induced damage by suppressing VPO-1 in a JNK signa- ling pathway-dependent manner in endothelial cells.
文摘城市电网在发生N-1故障后,极可能新增运行风险,导致N-1-1时出现大面积停电事故。为管控城市电网N-1后运行风险,该文提出一种改进双智能体竞争双深度Q网络(dueling double deep Q network,D3QN)的城市电网N-1风险管控转供策略。根据风险管控原则,提出一种无需额外历史数据、考虑备自投装置、单供变电站风险和单供负荷母线风险的N-1场景指标;建立计及动作次序、指标间关系的负荷转供三阶段求解模型。以含预动作-变化探索值选择策略的改进双智能体D3QN方法,将负荷转供分为多个子转供环节学习,使转供思路清晰化,对动作空间进行降维,提高训练寻优效果,得到管控N-1风险的负荷转供策略。通过城市电网多场景算例分析,验证该文模型和方法的有效性。
