BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple b...BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.展开更多
针对油浸式电力变压器瞬态温升计算效率过低的问题,该文提出本征正交分解-αATS(proper orthogonal decomposition-adaptive time stepping based onαfactor,POD-αATS)降阶自适应变步长瞬态计算方法。首先,推导变压器绕组瞬态温升计...针对油浸式电力变压器瞬态温升计算效率过低的问题,该文提出本征正交分解-αATS(proper orthogonal decomposition-adaptive time stepping based onαfactor,POD-αATS)降阶自适应变步长瞬态计算方法。首先,推导变压器绕组瞬态温升计算的有限元离散方程;其次,采用POD降阶算法改善传统瞬态计算中存在的条件数过大及方程阶数过高的问题;同时对于瞬态计算中的时间步长选择问题,提出适用于非线性问题的αATS变步长策略;然后,为验证方法的有效性,基于110 kV油浸式电力变压器绕组的基本结构建立二维八分区数值计算模型,同时将计算结果与基于110 kV绕组的温升实验结果进行对比。数值计算及实验结果表明,所提算法与全阶定步长算法在流场和温度场中的精度几乎相同,且流场计算效率提升约45倍,温度场计算效率提升约38倍,计算速度得到显著提高。这一点在温升实验中同样得到验证,说明该文所提算法的准确性、高效性及一定的工程实用性。展开更多
Glutathione peroxidase (GPx) is an antioxidant that plays an important role in the maintenance of male fertility. The aim of this study was to compare the profile of enzymatic activity of glutathione peroxidase in the...Glutathione peroxidase (GPx) is an antioxidant that plays an important role in the maintenance of male fertility. The aim of this study was to compare the profile of enzymatic activity of glutathione peroxidase in the seminal plasma of normozoosperm and those of pathological sperm. Thus, the activity of glutathione peroxidase was determined in the seminal plasma of 20 normozoosperms, 9 azoosperms and 31 oligoasthenoteratozoosperms. It was 37.58 ± 3.14 U/L in normozoosperms, 39.39 ± 2.27 U/L in oligoasthenoteratozoosperms, and 29.77 ± 2.62 U/L in azoosperms. The mean GPx enzyme activity of normozoosperms did not differ significantly from that of oligoasthenoteratozoosperms and azoosperms. In contrast, comparison of enzyme activity between abnormal sperms gave a significant difference. This study showed that glutathione peroxidase enzymatic activity is not related to sperm quality.展开更多
This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2(NRF2)and glutathione peroxidase 4(GPX4)in primary hepatic carcinoma(PHC).Methods:The expression of NRF2...This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2(NRF2)and glutathione peroxidase 4(GPX4)in primary hepatic carcinoma(PHC).Methods:The expression of NRF2 and GPX4 in peripheral blood of patients with PHC was determined to analyze the diagnostic value of the two combined for PHC.The prognostic significance of NRF2 and GPX4 was evaluated by 3-year followup.Human liver epithelial cells THLE-2 and human hepatocellular carcinoma cells HepG2 were purchased,and the expression of NRF2 and GPX4 in the cells was determined.NRF2 and GPX4 aberrant expression vectors were constructed and transfected into HepG2,and changes in cell proliferation and invasion capabilities were observed.Results:The expression of NRF2 and GPX4 in patients with PHC was higher than that in patients with LC or VH(p<0.05),and the two indicators combined was excellent in diagnosing PHC.Moreover,patients with high expression of NRF2 and GPX4 had a higher risk of death(p<0.05).In in vitro experiments,both NRF2 and GPX4 expression was elevated in HepG2(p<0.05).HepG2 activity was enhanced by increasing the expression of the two,vice versa(p<0.05).Conclusion:NRF2 and GPX4 combined is excellent in diagnosing PHC,and promotes the malignant development of PHC.展开更多
Organoseleniums are a class of compounds attracting attention across the globe owing to their Glutathione peroxidase(GPx)mimicry,which confers on them a strong antioxidant activity.Diphenyl diselenide(DPDS)is an Organ...Organoseleniums are a class of compounds attracting attention across the globe owing to their Glutathione peroxidase(GPx)mimicry,which confers on them a strong antioxidant activity.Diphenyl diselenide(DPDS)is an Organoselenium whose GPx mimetic property has been suggested to rely on the oxidation of non-protein or protein thiols critical to the activities of some sulfhydryl enzymes.This study,therefore investigated the GPx mimic/antioxidant property of DPDS as well as the role of thiols of two key sulfhydryl enzymes,cerebral Na^(+)/K^(+)-ATPase(sodium pump)and hepatic delta-aminolevulinic acid dehydratase(δ-ALAD)in the GPx mimicry of DPDS.Albino Wistar rats were euthanized,and the liver and brain were removed and used to assay for the effect of DPDS on lipid peroxidation induced by two prooxidants[Fe2^(+)(10μM)and H2O2,(1 mM)]as well as the activities of the sulfhydryl enzymes.The results revealed that DPDS profoundly(P<0.05)counteracted Fe2^(+)and H2O2-induced lipid peroxidation in the rats’hepatic and cerebral tissues.Furthermore,the results of assay systems for lipid peroxidation and sodium pump revealed that DPDS inhibited Na^(+)/K^(+)-ATPase and lipid peroxidation in the brain tissue homogenates in the same reaction system.A similar result was obtained in the assay system for lipid peroxidation and hepaticδ-ALAD as DPDS simultaneously inhibited the enzyme’s activity and lipid peroxidation.This suggests that the GPx mimetic property of DPDS may be linked to the enzymes’loss of activity,which further validates the suggestions that the enzymes’inhibition,as well as the antioxidant action of DPDS,rely on the oxidation of critical thiols of the enzymes.However,the GPx mimicry of DPDS should be investigated in the presence of thiol-blocking or oxidizing agents in biological systems in order to further ascertain the role of protein thiols.展开更多
The use of plant extracts as antifungal agents is gaining increasing attention, particularly for the control of black pod disease in cocoa. Despite extensive research, current strategies haven’t been entirely effecti...The use of plant extracts as antifungal agents is gaining increasing attention, particularly for the control of black pod disease in cocoa. Despite extensive research, current strategies haven’t been entirely effective. This study evaluated the effectiveness of Cymbopogon citratus and Blumea balsamifora leaf extracts, both individually and in combination, against Phytophthora megakarya. We assessed the efficacy of the most promising combination (75% B. balsamifera, 25% C. citratus) after storage at room temperature for up to 9 days. Agar microdilution and in vivo bioassays were conducted to determine antifungal susceptibility and effectiveness. Blumea extract exhibited the highest overall inhibitory activity, with the lowest minimum inhibitory concentration (117 µl mL−1) while C. citratus had a narrower range of MIC (146 to 233 µl mL−1). The combination of C. citratus and B. balsamifera demonstrated a synergistic effect against P. megakarya, achieving growth inhibition on V8 media (92.72 ± 4.20% to 100%) and on artificially infected detached pod cortex (92.24 ± 4.53% to 98.75 ± 1.25%), which was not significantly different from the positive control (Ridomil). Furthermore, this combination maintained its effectiveness for up to 9 days at room temperature. These findings suggest that combining plant extracts can enhance their antifungal properties.展开更多
针对风火打捆(wind-thermal-bundled,WTB)系统在受到干扰时可能由于阻尼不足而出现的低频振荡现象以及较高的网损会导致运行成本的增加和阻碍“双碳”目标实现的问题,提出了一种电力系统稳定器(power system stabilizer,PSS)与统一潮流...针对风火打捆(wind-thermal-bundled,WTB)系统在受到干扰时可能由于阻尼不足而出现的低频振荡现象以及较高的网损会导致运行成本的增加和阻碍“双碳”目标实现的问题,提出了一种电力系统稳定器(power system stabilizer,PSS)与统一潮流控制器(unified power flow controller,UPFC)附加功率振荡阻尼控制器(power oscillation damping,POD)参数和UPFC安装位置协调优化策略方法。首先,基于Matlab构建了风火打捆外送系统和控制器模型。然后,利用多目标樽海鞘优化算法(multi-objective salp swarm algorithm,MSSA),将协调优化问题转化为多目标优化问题。目标函数设计中考虑了UPFC装置的调节特性。最后,采用IEEE 4机2区系统和16机5区系统进行多种工况下的仿真。仿真结果显示,协调优化后的控制器可以提高系统阻尼,维持发电机转速的稳定,抑制低频振荡引起的系统有功、电压等的波动,同时降低了系统的有功网损,提高了系统稳定性和运行经济性。MSSA在工程问题上的应用得到了补充。展开更多
基金Supported by National Natural Science Foundation of China,No.82060123Doctoral Start-up Fund of Affiliated Hospital of Guizhou Medical University,No.gysybsky-2021-28+1 种基金Fund Project of Guizhou Provincial Science and Technology Department,No.[2020]1Y299Guizhou Provincial Health Commission,No.gzwjk2019-1-082。
文摘BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.
文摘针对油浸式电力变压器瞬态温升计算效率过低的问题,该文提出本征正交分解-αATS(proper orthogonal decomposition-adaptive time stepping based onαfactor,POD-αATS)降阶自适应变步长瞬态计算方法。首先,推导变压器绕组瞬态温升计算的有限元离散方程;其次,采用POD降阶算法改善传统瞬态计算中存在的条件数过大及方程阶数过高的问题;同时对于瞬态计算中的时间步长选择问题,提出适用于非线性问题的αATS变步长策略;然后,为验证方法的有效性,基于110 kV油浸式电力变压器绕组的基本结构建立二维八分区数值计算模型,同时将计算结果与基于110 kV绕组的温升实验结果进行对比。数值计算及实验结果表明,所提算法与全阶定步长算法在流场和温度场中的精度几乎相同,且流场计算效率提升约45倍,温度场计算效率提升约38倍,计算速度得到显著提高。这一点在温升实验中同样得到验证,说明该文所提算法的准确性、高效性及一定的工程实用性。
文摘Glutathione peroxidase (GPx) is an antioxidant that plays an important role in the maintenance of male fertility. The aim of this study was to compare the profile of enzymatic activity of glutathione peroxidase in the seminal plasma of normozoosperm and those of pathological sperm. Thus, the activity of glutathione peroxidase was determined in the seminal plasma of 20 normozoosperms, 9 azoosperms and 31 oligoasthenoteratozoosperms. It was 37.58 ± 3.14 U/L in normozoosperms, 39.39 ± 2.27 U/L in oligoasthenoteratozoosperms, and 29.77 ± 2.62 U/L in azoosperms. The mean GPx enzyme activity of normozoosperms did not differ significantly from that of oligoasthenoteratozoosperms and azoosperms. In contrast, comparison of enzyme activity between abnormal sperms gave a significant difference. This study showed that glutathione peroxidase enzymatic activity is not related to sperm quality.
文摘This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2(NRF2)and glutathione peroxidase 4(GPX4)in primary hepatic carcinoma(PHC).Methods:The expression of NRF2 and GPX4 in peripheral blood of patients with PHC was determined to analyze the diagnostic value of the two combined for PHC.The prognostic significance of NRF2 and GPX4 was evaluated by 3-year followup.Human liver epithelial cells THLE-2 and human hepatocellular carcinoma cells HepG2 were purchased,and the expression of NRF2 and GPX4 in the cells was determined.NRF2 and GPX4 aberrant expression vectors were constructed and transfected into HepG2,and changes in cell proliferation and invasion capabilities were observed.Results:The expression of NRF2 and GPX4 in patients with PHC was higher than that in patients with LC or VH(p<0.05),and the two indicators combined was excellent in diagnosing PHC.Moreover,patients with high expression of NRF2 and GPX4 had a higher risk of death(p<0.05).In in vitro experiments,both NRF2 and GPX4 expression was elevated in HepG2(p<0.05).HepG2 activity was enhanced by increasing the expression of the two,vice versa(p<0.05).Conclusion:NRF2 and GPX4 combined is excellent in diagnosing PHC,and promotes the malignant development of PHC.
文摘Organoseleniums are a class of compounds attracting attention across the globe owing to their Glutathione peroxidase(GPx)mimicry,which confers on them a strong antioxidant activity.Diphenyl diselenide(DPDS)is an Organoselenium whose GPx mimetic property has been suggested to rely on the oxidation of non-protein or protein thiols critical to the activities of some sulfhydryl enzymes.This study,therefore investigated the GPx mimic/antioxidant property of DPDS as well as the role of thiols of two key sulfhydryl enzymes,cerebral Na^(+)/K^(+)-ATPase(sodium pump)and hepatic delta-aminolevulinic acid dehydratase(δ-ALAD)in the GPx mimicry of DPDS.Albino Wistar rats were euthanized,and the liver and brain were removed and used to assay for the effect of DPDS on lipid peroxidation induced by two prooxidants[Fe2^(+)(10μM)and H2O2,(1 mM)]as well as the activities of the sulfhydryl enzymes.The results revealed that DPDS profoundly(P<0.05)counteracted Fe2^(+)and H2O2-induced lipid peroxidation in the rats’hepatic and cerebral tissues.Furthermore,the results of assay systems for lipid peroxidation and sodium pump revealed that DPDS inhibited Na^(+)/K^(+)-ATPase and lipid peroxidation in the brain tissue homogenates in the same reaction system.A similar result was obtained in the assay system for lipid peroxidation and hepaticδ-ALAD as DPDS simultaneously inhibited the enzyme’s activity and lipid peroxidation.This suggests that the GPx mimetic property of DPDS may be linked to the enzymes’loss of activity,which further validates the suggestions that the enzymes’inhibition,as well as the antioxidant action of DPDS,rely on the oxidation of critical thiols of the enzymes.However,the GPx mimicry of DPDS should be investigated in the presence of thiol-blocking or oxidizing agents in biological systems in order to further ascertain the role of protein thiols.
文摘The use of plant extracts as antifungal agents is gaining increasing attention, particularly for the control of black pod disease in cocoa. Despite extensive research, current strategies haven’t been entirely effective. This study evaluated the effectiveness of Cymbopogon citratus and Blumea balsamifora leaf extracts, both individually and in combination, against Phytophthora megakarya. We assessed the efficacy of the most promising combination (75% B. balsamifera, 25% C. citratus) after storage at room temperature for up to 9 days. Agar microdilution and in vivo bioassays were conducted to determine antifungal susceptibility and effectiveness. Blumea extract exhibited the highest overall inhibitory activity, with the lowest minimum inhibitory concentration (117 µl mL−1) while C. citratus had a narrower range of MIC (146 to 233 µl mL−1). The combination of C. citratus and B. balsamifera demonstrated a synergistic effect against P. megakarya, achieving growth inhibition on V8 media (92.72 ± 4.20% to 100%) and on artificially infected detached pod cortex (92.24 ± 4.53% to 98.75 ± 1.25%), which was not significantly different from the positive control (Ridomil). Furthermore, this combination maintained its effectiveness for up to 9 days at room temperature. These findings suggest that combining plant extracts can enhance their antifungal properties.