Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

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.

HOI延迟对LEO卫星简化动力学POD的影响

通常使用无电离层(IF)线性组合(LC)消除低地球轨道(LEO)卫星简化动力学精密定轨(POD)一阶电离层延迟误差,忽略了高阶电离层(HOI)延迟误差。随着LEO卫星POD技术的发展,计算不同轨道高度的HOI延迟并探索其变化已成为进一步提高POD精度的重要手段。首先,使用国际参考电离层-2016(IRI-2016)和国际地磁参考场第13代(IGRF-13)模型,计算电离层穿刺点(IPP)位置和地磁场强度。其次,使用平滑星载GNSS数据计算电离层斜路径总电子含量(STEC)。然后,分别计算GOCE、GRACE-A和SWARM-A/B卫星的二阶和三阶电离层延迟。最后,评估了HOI延迟对LEO卫星重叠轨道分析、卫星激光测距(SLR)检核和精密科学轨道(PSO)比较结果的影响。实验结果表明:HOI延迟对LEO卫星简化动力学POD的影响大约在毫米至厘米的数量级上;HOI延迟对LEO卫星简化动力学POD外符合精度的影响分别达到0.92,0.22,0.21和0.18 mm;随着LEO卫星轨道高度的增加,HOI延迟对LEO卫星简化动力学POD的影响减小。

基于POD和Kriging的水滴收集量快速预测方法

数值模拟手段预测翼面处水滴撞击特性通常较为耗时,为快速准确计算结冰条件下的翼面处水滴收集量,提出了基于本征正交分解和代理模型的水滴收集量快速预测方法。首先对FAR 25部附录C中连续最大结冰条件进行优化拉丁超立方采样,通过数值模拟手段获得各采样点在翼面处水滴收集量分布,从而构造样本空间。在此基础上,利用本征正交分解(Proper orthogonal decompostion,POD)方法找到表达和重构水滴收集量的本征模态以及相应的拟合系数。最后,利用Kriging模型建立样本空间中各采样点与拟合系数间的代理模型,实现翼面处水滴收集量分布的快速预测。经多组工况验证表明:该方法可较为准确地预测翼面处水滴收集量分布,其计算成本较数值模拟方法大幅降低,能够为无人机防除冰设计提供有益参考。

干旱胁迫对玉米幼苗ROS和POD的影响

山西省内市场上销售的玉米品种多为抗旱品种,为了更好地区分不同品种之间的差异,本研究选取8个玉米品种为试验材料,采用土培的方式,人工控制水量模拟干旱,研究干旱胁迫下不同品种玉米幼苗的活性氧(ROS)和过氧化物酶(POD)的变化。采用双抗体夹心法测定ROS的含量,采用愈创木酚法测定POD活性。结果表明,干旱胁迫下各品种玉米幼苗ROS含量全部上升,其中大丰26、大丰30和并单16的ROS含量增加不显著,其余品种增加显著;干旱胁迫诱导大丰26和大丰30的POD活性显著上升,其余品种的POD活性变化不显著。分析ROS和POD活性指标变化可以看出,与其余7个品种相比,大丰30的抗旱能力更强。

基于POD方法的EPR燃料棒流致振动特性分析

EPR(European pressurized reactor)燃料棒相比M310燃料棒的棒长更长,导致其频率降低、幅值增大,在冷却剂的作用下,会加剧格架与棒束之间微动磨损(grid-to-rod fretting,GTRF),进而造成放射性物质的泄漏.将EPR燃料棒简化为3D梁模型,将刚凸和弹簧对燃料棒的约束等效为弹性约束,将带格架的燃料棒简化为多跨连续简支梁模型,然后基于ANSYS-APDL建立了EPR燃料棒的有限元模型.阐述了湿模态分析和湍流激振响应分析的基本原理,整理了12个格架失效工况,系统地研究了格架失效对湿模态和湍流激振响应的影响.针对EPR燃料棒流致振动问题,提出了采用本征正交分解(proper orthogonal decomposition,POD)原理分析EPR燃料棒流致振动特性的方法,通过对快照矩阵进行POD分解生成投影子空间,将湍流激振响应投影到子空间进行模型降阶,最后在物理空间快速地重构湍流激振响应.结果表明:格架失效会导致频率降低,且湍流激振响应的幅值会在格架失效处增大;当格架失效使得EPR燃料棒模型成为悬臂梁结构时,湍流激振响应最大;前2阶POD降阶模型基本能快速重构燃料棒的湍流激振响应,且误差非常小.文章的研究将有助于核反应堆工程的优化和设计.

Gappy POD算法重构储能电池组核心温度及与BP神经网络预测能力对比

储能电池组中电池核心温度的实时监控对于防控电池热失控有着重要的意义.为克服工业实际中电池组内部无法布置多温度测点导致的温度数据获取不全面等问题,本文将Gappy POD重构算法引入储能电池核心温度实时监控问题中,通过监测电池组表面温度预测内部核心温度.通过搭建简化的拟储能电池实验台模拟电池温升,测试了Gappy POD算法在工况平稳变化和工况剧烈变化条件下的稳定性和对核心温度的实时重构能力;对比了Gappy POD算法的重构能力和BP神经网络(Back propagation neural network)的预测能力,并探究了Gappy POD算法和BP神经网络在不同大小的数据库训练条件下的重构预测能力.研究表明,Gappy POD重构算法具有高预测精度、稳定性强并且对数据库数据量依赖性低等优势,为算法在储能电池热管理中的实际应用提供了基础.

Evaluation of Glutathione Peroxidase Enzymatic Activity in Seminal Plasma of Patients Treated at the Institute Pasteur in Cote d’Ivoire

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.

Evaluation of combined detection of nuclear factor erythroid 2-related factor 2 and glutathione peroxidase 4 in primary hepatic carcinoma and preliminary exploration of pathogenesis

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.

Glutathione peroxidase mimicry of diphenyl diselenide: Plausible contribution of proteins’ thiols

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.

风力机翼型S809绕流流动特性的POD和DMD对比分析

失速时的流动分离现象对风力机叶片的气动性能有重要影响,S809作为典型水平轴风力机翼型,在临界失速攻角下气动性能会大幅降低。基于流动特征提取的非定常流场降阶模型(reduced-order model,ROM)是进一步深入了解非定常流动的重要手段。本文通过计算流体力学方法得到轻、深失速攻角下翼型的流动特征,对时变速度场进行本征正交分解(proper orthogonal decomposition,POD)和动态模态分解(dynamic mode decomposition,DMD)分析,得到轻、深失速下翼型的非定常流场信息(能量占比、模态频率等)。通过两种方法的对比,结果表明,POD和DMD方法能够准确捕捉流动过程中的非定常结构和升力主频相同的典型模态,但是POD方法由于基于能量特征,在捕捉模态时会忽略与升力主频相近但能量较小的流动结构,而基于频率特征的DMD方法能够准确获得场的演化信息(增长率、频率等)。本文研究有利于针对主频结构发展相应的流动控制方法,从而改善翼型流场情况,提高气动性能。

氧化铈纳米酶的结构调控及POD酶活性研究

为探究CeO_(2)纳米粒子表面Ce^(3+)/Ce^(4+)比例变化对过氧化物酶(POD)活性的影响,以实现对POD催化反应的可控调节,本研究使用简易水热法合成CeO_(2)纳米粒子,并通过不同的气氛热处理来调控CeO_(2)纳米粒子表面Ce^(3+)/Ce^(4+)的比例来展开相关探索。

基于MSSA的PSS与UPFC-POD参数和UPFC位置协调优化

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。

基于POD-ATS-HTS混合变步长方法的油浸式电力变压器绕组瞬态温升计算方法研究

针对当前油浸式电力变压器绕组瞬态温升仿真中,采用固定时间步长效率低的问题,提出一种混合变步长方法。首先,采用初始解优化算法,有效减少计算过程中方程的迭代次数;其次,结合本征正交分解算法(properorthogonal decomposition,POD),改善大规模有限元方程组存在的阶数过高、条件数过大的问题,提高了方程的求解效率和数值稳定性;第三,提出自适应(adaptivetimestepping,ATS)-启发式(heuristic time stepping,HTS)混合变步长算法,通过对时间步长的自适应与启发式调整,有效解决瞬态计算中计算效率与计算精度的对立问题;最后,建立油浸式电力变压器绕组二维单分区分匝的流热耦合仿真模型,以验证所提算法的正确性与高效性。数值计算结果表明:在流场中,与固定步长的计算结果相比,混合变步长算法的误差小于0.46%,计算效率提升了18.45倍;在温度场中,与固定步长的计算结果相比,所提算法的误差小于0.04%,计算效率提升了6倍。同时,通过与传统变步长算法的计算结果对比,说明所提混合变步长算法在计算精度、计算效率及变步长效果方面均具有一定优势。此外,还探讨混合变步长计算中,不同的参数设置对瞬态计算结果及状态变化过程的影响,为其工程应用奠定了一定基础。

Polyphenol Oxidase, Peroxidase and PhenylalanineAmmonium Lyase Induced in Postharvest Peach Fruitsby Inoculation with Pichia membranefaciensor Rhizopus stolonifer

Rhizopus rot of peach fruits could be significantly suppressed by Pichia membranefaciens. Polyphenol oxidase (PPO), peroxidase (POD) and phenylalanine ammonium-lyase (PAL) activities induced by inoculation with P. membrane faciens or R. stolonifer were studied in postharvest peach fruits. The activities of PPO and PAL in peaches increased significantly after being inoculated with P. membrane faciens + R. stolonifer by 24 h, the activities maintained at a high level throughout the experiment. Under the condition of infected with R. stolonifer alone, activity of PPO and PAL could also increased, but the levels were lower than those treated with P. membrane faciens+ R. stolonifer. However, fruits inoculaed with P. membrane-faciens + R. stolonifer or R. stolonifer alone did not stimulated POD activity. The results suggest that the activation of these defense enzymes is involved in the action of P. membrane faciens against R. stolonifer.

Imaging of Activity of Horseradish Peroxidase at β-Cyclodextrin Polymer by Scanning Electrochemical Microscopy

The activity of horseradish peroxidase at b-cyclodextrin polymer was imaged by scanning electrochemical microscopy using 3, 3', 5, 5'-tetramethylbenzide and H2O2 as the substrates.

Studies on Manganese Peroxidase Immobilized in Gelatin-containing Microemulsion-based Gels

The immobilized technique of manganese peroxidase(MnP) in gelatin-containing microemulsion-based gels and the effects of storage time and reuse times on its catalytic activity were studied. The results show that the MnP immobilized together with Mn 2+ and H_2O_2 could effectively oxidize syringaldazine in n-heptane. The immobilized MnP still had a high catalytic activity after one-month storage under a freezing condition. The reuse times have a relation to the amount of the immobilized H_2O_2. When the amount of the immobilized H_2O_2 is sufficient, the microemulsion-based gels containing MnP could be used many times.

Enhancement of Phenylalanine Ammonia Lyase,Polyphenoloxidase,and Peroxidase in Cucumber Seedlings by Bemisia tabaci (Gennadius) (Hemiptera:Aleyrodidae) Infestation

In this study, the activities of phenylalanine ammonia lyase （PAL）, polyphenoloxidase （PPO）, and peroxidase （POD） were assayed in cucumber seedlings （Cucumis sativus L.） at 0, 6, 12, 24, 48, 72, and 96 h after they were infested by Bemisia tabaci （Gennadius） using spectrophotometric analysis. The results indicated that herbivore infestation increased the activities of PAL, PPO, and POD. The enzymes showed different activity levels at different times after the infestation. The PAL activity reached the first high peak by 23.1% at 6 h and the highest peak by 29.1% at 48 h compared to the control. The PPO activity reached the first high peak by 22.7% at 6 h and the highest peak by 52.6% at 24 h, and the POD activity reached the highest peak by 213.2% at 6 h and another higher peak value by 135.2% at 96 h. The results suggest that the enhanced activities of the enzymes may contribute to bioprotection of cucumber plants against B. tabaci infestation.

Cloning of catalase and expression patterns of catalase and selenium-dependent glutathione peroxidase from Exopalaemon carinicauda in response to low salinity stress

Catalase （CAT） and selenium-dependent glutathione peroxidase （Se-GPx） play a vital role in protecting organisms against various oxidative stresses by eliminating H202, The objective of this paper is to evaluate the roles of these antioxidant molecules in the ridgetail white prawn Exopalaemon carinicauda in response to low salinity stress. A complementary DNA （cDNA） containing the complete coding sequence of CAT was cloned from the hepatopancreas using reverse-transcription polymerase chain reaction （RT-PCR） and rapid amplification of cDNA ends. The full-length cDNA of CAT （2 649 bp） contains a 5＇-untranslated region （UTR） of 78 bp, a 3＇- UTR of 1 017 bp, with a poly （A） tail, and an open reading frame of 1 554 bp encoding a 517-amino-acid polypeptide with predicted molecular mass of 58.46 kDa and estimated isoelectric point of 6.64. This CAT sequence contained the proximal active site signature （60FDRERIPERWHAKGAG76）, proximal heme-ligand signature sequence （350RLFSYPDTH358） and three catalytic amino acid residues （His71, Asn144 and Tyr354）. Sequence comparison showed that the CAT deduced amino acid sequence of E. carinicauda shared 68%-92% of identities with those of other species. Quantitative real-time PCR analysis revealed that CAT mRNA was widely expressed in the hepatopancreas （highest）, hemocyte, eyestalk, heart, gill, muscle, ovary and stomach. Under low salinity stress, CAT and GPx mRNA expression levels both in the gill and hepatopancreas increased significantly at the first 48 h and 6 h respectively, indicating a tissue- and time-dependent antioxidant response in E. carinicauda. All these results indicate that E. carinicauda CAT is a member of the CAT family and might be involved in the acute response against low salinity stress.

Expression of lignin peroxidase H2 from Phanerochaete chrysosporium by multi-copy recombinant Pichia strain

The lipH2 gene, encoding the expression of lignin peroxidase, was cloned from Phanerochaete chrysosporium BKM-F-1767 and expressed in Pichia pastoris X-33, a yeast. The cDNA of LiPH2 was generated from total RNA extracted from P chrysosporium by PCR with primers that do not contain a P. chrysosporium lignin peroxidase secretion signal. The gene was then successfully inserted into the expression vector pPICZα, and resulted in the recombinant vector pPICZα-lipH2. The transformation was conducted in two ways. One was using the wild Pichia pastoris as the recipients, which results in the recombinant P. pastoris with single or low lipH2 gene copy. The second was using P. pastoris and single or low lipH2 gene copy as the recipients, which results in the recombinant P. pastoris with multi-copies of lipH2 genes. This study firstly expressed the gene lipH2 in P. pastoris and achieved the successful expression of the lipH2 depending upon the generation of a recombinant strain that contained multiple copies. The lignin peroxidase activity reached a maximum of 15 U/L after 12 h induction.

Effects of different valences of cerium ion on conformation of Horseradish Peroxidase

Our previous studies demonstrated that Ce^4＋could induce reactive oxygen species （ROS） burst as a signal to promote pacilitaxel biosynthesis in suspension cultured Taxus cuspidate cells. To further understand the mechanism of cerium ions inducing ROS burst, circular dichroism （CD）, synchronous fluorescence, and electron paramagnetic resonance （EPR） were used to detect them inducing conformational change of horseradish peroxidase （HRP）. Horseradish peroxidase activity was reduced by 78% by 0.1 mmol/L Ce^4＋, whereas it was only reduced by 28% by 0.1 mmol/L Ce^3＋. Circular dichroism spectra showed that the percentage of transition from helical content and other structure to β strands and flturns was 23.1 when induced by Ce^4＋, whereas it was only 13.2 when induced by Ce^3＋. In synchronous fluorescence spectra, Ce^4＋ led to red shift and intensity-elevation of tryptophan fluorescence emission maximum, whereas in the case of Ce^3＋, the results were a contrast to the above. Furthermore, g factor （gx and gy） in electron paramagnetic resonance （EPR） induced by Ce^4＋ and Ce^3＋ was significantly different. These results indicated that the different valence of cerium ion induced various conformations of HRP, and Ce^4＋ was more effective than Ce^3＋. This suggested that Ce^4＋ affected the burst of ROS through changing the conformation of oxidoreductase.