Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidati...Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.展开更多
NOx sensors, as a core component of diesel engine exhaust treatment system, play an important role in exhaust emission control, which can accurately and quickly detect the NOx and O2 concentration. It has become a nec...NOx sensors, as a core component of diesel engine exhaust treatment system, play an important role in exhaust emission control, which can accurately and quickly detect the NOx and O2 concentration. It has become a necessary option for the detection of existing exhaust emission standards. At present, there is limited and scattered information on knowledge and test methods of NOx sensors, the research of NOx sensors has become a challenging research topic at home and abroad. Based on these requirements, the article systematically integrates the knowledge of principle and testing methods. First of all, through introducing functional description of NOx sensors and the basic principle of NOx sensors, the relevant scholars can have an overall understanding of the product and master the operation mode of products. Secondly, the current status of performance test bench and methods of NOx sensors were described, which can contribute to having a clear understanding of the development process. After that, a new structure of NOx sensors test bench was purposed, which contains six major units including standard gas source, gas mixing unit, analyzer measurement unit, sensor measurement unit, data processing and display unit, exhaust gas treatment unit. And the test bench was validated. The experimental results show that the test bench has the advantages of high-repeatability, high reliability and low cost. And it can realize automatic detection of multiple target values, which is worthy further promotion. Thereby, the article can contribute to the development of its technology indirectly.展开更多
火电厂在稳定运行的同时,不可避免地会排放大量污染气体,尤其是NOx。针对传统测量方法的不足,该文提出一种基于灰狼优化反向传播神经网络(grey wolf optimized-back propagation,GWO-BP)的NOx排放量软测量模型。首先使用典型相关性分析(...火电厂在稳定运行的同时,不可避免地会排放大量污染气体,尤其是NOx。针对传统测量方法的不足,该文提出一种基于灰狼优化反向传播神经网络(grey wolf optimized-back propagation,GWO-BP)的NOx排放量软测量模型。首先使用典型相关性分析(canonical correlation analysis,CCA)将任意两个相关度较高的变量归为一组,并去掉其中一个,从而选择了对NOx排放量影响最大的4个变量作为软测量模型的输入;然后,建立了反向传播(back propagation,BP)神经网络模型以对输入变量和NOx排放量做映射;最后,采用灰狼优化(grey wolf optimizer,GWO)算法优化了所提软测量模型的权重和偏置值,提升了模型的精度。实验结果表明,所提软测量模型可以准确测量NOx的排放量,在传感器故障或伴有噪声的时候很好地替代了传感器的角色,为优化算法及深度学习方法在工业现场的应用提供了参考。展开更多
Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxi...Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein(ox-LDL)particles,a process that induces atherothrombosis.Sulforaphane(SFN)is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities.The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo.Using a series of platelet functional assays in human platelets in vitro,we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation(surface CD62P expression).Mechanistically,studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases,leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling,and resultant inhibition of NADPH oxidase 2(NOX2)-dependent generation of reactive oxygen species(ROS).Moreover,12-week supplementation of SFN-enriched broccoli sprout extract(BSE,0.06%diet)in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity.Studies using pharmacological inhibitors of CD36,protein kinase A(PKA)and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling.Thus,through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity,SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271444(to JP),82271268(to BZ),and 82001346(to YL)the National Key Research and Development Program of China,No.2022YFE0210100(to BZ)。
文摘Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.
文摘NOx sensors, as a core component of diesel engine exhaust treatment system, play an important role in exhaust emission control, which can accurately and quickly detect the NOx and O2 concentration. It has become a necessary option for the detection of existing exhaust emission standards. At present, there is limited and scattered information on knowledge and test methods of NOx sensors, the research of NOx sensors has become a challenging research topic at home and abroad. Based on these requirements, the article systematically integrates the knowledge of principle and testing methods. First of all, through introducing functional description of NOx sensors and the basic principle of NOx sensors, the relevant scholars can have an overall understanding of the product and master the operation mode of products. Secondly, the current status of performance test bench and methods of NOx sensors were described, which can contribute to having a clear understanding of the development process. After that, a new structure of NOx sensors test bench was purposed, which contains six major units including standard gas source, gas mixing unit, analyzer measurement unit, sensor measurement unit, data processing and display unit, exhaust gas treatment unit. And the test bench was validated. The experimental results show that the test bench has the advantages of high-repeatability, high reliability and low cost. And it can realize automatic detection of multiple target values, which is worthy further promotion. Thereby, the article can contribute to the development of its technology indirectly.
文摘火电厂在稳定运行的同时,不可避免地会排放大量污染气体,尤其是NOx。针对传统测量方法的不足,该文提出一种基于灰狼优化反向传播神经网络(grey wolf optimized-back propagation,GWO-BP)的NOx排放量软测量模型。首先使用典型相关性分析(canonical correlation analysis,CCA)将任意两个相关度较高的变量归为一组,并去掉其中一个,从而选择了对NOx排放量影响最大的4个变量作为软测量模型的输入;然后,建立了反向传播(back propagation,BP)神经网络模型以对输入变量和NOx排放量做映射;最后,采用灰狼优化(grey wolf optimizer,GWO)算法优化了所提软测量模型的权重和偏置值,提升了模型的精度。实验结果表明,所提软测量模型可以准确测量NOx的排放量,在传感器故障或伴有噪声的时候很好地替代了传感器的角色,为优化算法及深度学习方法在工业现场的应用提供了参考。
基金supported by the National Natural Science Foundation of China(82003451 and 82003455)Yunnan Fundamental Research Projects(202101AT070033)the Start-Up Fund for Introduction of High-level Talents to Dali University(YBS2021015).
文摘Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein(ox-LDL)particles,a process that induces atherothrombosis.Sulforaphane(SFN)is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities.The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo.Using a series of platelet functional assays in human platelets in vitro,we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation(surface CD62P expression).Mechanistically,studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases,leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling,and resultant inhibition of NADPH oxidase 2(NOX2)-dependent generation of reactive oxygen species(ROS).Moreover,12-week supplementation of SFN-enriched broccoli sprout extract(BSE,0.06%diet)in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity.Studies using pharmacological inhibitors of CD36,protein kinase A(PKA)and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling.Thus,through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity,SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.