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.

An NMOS output-capacitorless low-dropout regulator with dynamic-strength event-driven charge pump

In this paper,an NMOS output-capacitorless low-dropout regulator(OCL-LDO)featuring dual-loop regulation has been proposed,achieving fast transient response with low power consumption.An event-driven charge pump(CP)loop with the dynamic strength control(DSC),is proposed in this paper,which overcomes trade-offs inherent in conventional structures.The presented design addresses and resolves the large signal stability issue,which has been previously overlooked in the event-driven charge pump structure.This breakthrough allows for the full exploitation of the charge-pump structure's poten-tial,particularly in enhancing transient recovery.Moreover,a dynamic error amplifier is utilized to attain precise regulation of the steady-state output voltage,leading to favorable static characteristics.A prototype chip has been fabricated in 65 nm CMOS technology.The measurement results show that the proposed OCL-LDO achieves a 410 nA low quiescent current(IQ)and can recover within 30 ns under 200 mA/10 ns loading change.

Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer

Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

Unraveling the regulatory network of flower coloration in soybean:Insights into roles of GmMYBA3 and GmMYBR1

Anthocyanins play crucial roles in pollen protection and pollinator attraction in flowering plants.However,the mechanisms underlying flower color determination and whether floral anthocyanin regulators participate in other processes remain largely unresolved in soybeans(Glycine max).In this study,we investigated the genetic components and mechanisms governing anthocyanin biosynthesis in soybean flowers.Molecular and genetic studies have characterized two antagonistic regulators,the positive activator GmMYBA3 and the negative repressor GmMYBR1,that modulate the gene expression of anthocyanin biosynthesis in soybean flowers.Further findings revealed a regulatory interplay between GmMYBA3 and GmMYBR1 bridged by GmTT8a,highlighting the complexity of anthocyanin regulation in different soybean organs.Exploration of additional soybean cultivars demonstrated the universality of GmMYBA3 and GmMYBR1 in regulating floral anthocyanin biosynthesis-related genes,with GmF3’5’H identified as a crucial determinant of white flower color.This study provides a molecular mechanism underlying soybean flower color determination,paving the way for the molecular modification of soybean flowers to probably enhance their resistance to abiotic stresses and attractiveness to pollinators.

An overview of pigment gland morphogenesis and its regulatory mechanism

Cotton has enormous economic potential,providing high-quality protein,oil,and fibre.But the comprehensive utilization of cottonseed is limited by the presence of pigment gland and its inclusion.Pigment gland is a common characteristic of Gossypium genus and its relatives,appearing as visible dark opaque dots in most tissues and organs of cotton plants.Secondary metabolites,such as gossypol,synthesized and stored in the cavities of pigment glands act as natural phytoalexins,but are toxic to humans and other monogastric animals.However,only a few cotton genes have been identified as being associated with pigment gland morphogenesis to date,and the developmental processes and regulatory mechanism involved in pigment gland formation remain largely unclear.Here,the research progress on the process of pigment gland morphogenesis and the genetic basis of cotton pigment glands is reviewed,for providing a theoretical basis for cultivating cotton with the ideal pigment gland trait.

Regarding the Regulatory Sandbox Route and Mechanism for Governance of Artificial Intelligence

The main challenge in AI governance today is striking a balance between controlling AI dangers and fostering AI innovation.Regulators in a number of nations have progressively extended the regulatory sandbox,which was first implemented in the banking sector,to AI governance in an effort to reduce the conflict between regulation and innovation.The AI regulatory sandbox is a new and feasible route for AI governance in China that not only helps to manage the risks of technology application but also prevents inhibiting AI innovation.It keeps inventors'trial-and-error tolerance space inside the regulatory purview while offering a controlled setting for the development and testing of novel AI that hasn't yet been put on the market.By providing full-cycle governance of AI with the principles of agility and inclusive prudence,the regulatory sandbox offers an alternative to the conventional top-down hard regulation,expost regulation,and tight regulation.However,the current system also has inherent limitations and practical obstacles that need to be overcome by a more rational and effective approach.To achieve its positive impact on AI governance,the AI regulatory sandbox system should build and improve the access and exit mechanism,the coordination mechanism between the sandbox and personal information protection,and the mechanisms of exemption,disclosure,and communication.

Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis

Age-related macular degeneration(AMD)is a complicated disease that causes irreversible visual impairment.Increasing evidences pointed retinal pigment epithelia(RPE)cells as the decisive cell involved in the progress of AMD,and the function of anti-oxidant capacity of PRE plays a fundamental physiological role.Nuclear factor erythroid 2 related factor 2(Nrf2)is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative genes.Its functions of protecting RPE cells against oxidative stress(OS)and ensuing physiological changes,including inflammation,mitochondrial damage and autophagy dysregulation,have already been elucidated.Understanding the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD pathogenesis.For the first time,this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis,including proteins and miRNAs,and their underlying molecular mechanisms,which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.

The virulence regulator AbsR in avian pathogenic Escherichia coli has pleiotropic effects on bacterial physiology

Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for antimicrobials.However,a deep understanding of the AbsR regulatory mechanism as well as its regulon is lacking.In this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)methods.We found that AbsR directly regulates 99 genes and indirectly regulates 667 genes.Furthermore,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC virulence.Finally,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC strains.Altogether,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule production.Interestingly,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.

Contribution to Computer Waste Management:Knowledge of the Regulatory Framework by Industry Stakeholders in Guinea

In African countries,regulations on the management of WTE(Waste from Information Technology Equipment)are non-existent or sometimes insufficient,if they exist.This study shows how to mention waste from information technology equipment in a country that does not have a regulatory legislative framework or organized management channels.A methodological approach based on documentary research and semi-directed interviews was adopted in this work.The results showed that 54.55%of institutional managers are unaware of the existence of regulations for the management of WTE,both at the national and international levels;72.72%of these managers do not have a specific implementing text for this management;72.73%of institutions have adopted an acquisition policy based on the needs of workers and 81.82%of institutions store WTE in warehouses.Relations with waste collection SMEs(Small and Midsize Enterprises),especially for IT equipment,are limited for 72.73%of institutions.In terms of improving the capacity to manage WEEE(Waste Electrical and Electronic Equipment),90.91%of institutions do not offer training or awareness raising.Overall,no significant indicators are in place to assess WEEE management in institutions,which reflects a lack of commitment and awareness among institutional managers.In addition,there are no financial means for ecological and sustainable management.Although 27.27%of managers are aware of the dangers to human health and the environment related to IT equipment,they are often unaware of the harmful consequences of abandoning it in nature.

The Effect of Plant Growth Regulators on Physico-Chemical Properties of Safflower (Carthamus tinctorius L.) Derived Biodiesel

Global concerns about the environmental impact of combustion emissions from petroleum fuels influence new research to seek for alternative energy sources. The current study investigates the possibility of using safflower (Carthamus tinctorius L.) as an alternative biodiesel raw material. Four plant growth regulators (PGR) were used to boost the production of safflower. Thirteen treatments were constituted from the four plant regulators and applied to the safflower crop arranged in completely randomised design, repeated three times. The results show that the effect of plant growth regulators was not more than that of the control. More studies have to be channelled towards the relationship between safflower and plant growth regulators.

Low Level of Cystic Fibrosis Transmembrane Conductance Regulator Is Associated with Human Sperm Autophagy and Vitality

Low sperm motility is one of the main causes of male infertility. Cystic fibrosis transmembrane conductance regulator (CFTR, an anion channel protein) is related to the progressive motility of sperm. CFTR disruptor CFTRinh-172 or forskolin (FSK) in this study were used to treat human sperm separately, and the rates of sperm autophagy and progressive motility, mitochondrial membrane potential (MMP) and ATP concentration, and the expression levels of related factors were detected to explore their relationship. It was showed that sperms treated with CFTRinh-172 or FSK reduced the levels of cAMP, CFTR and PKA, but increased sperm autophagy rate, expression levels of AMPK and LC3B. However, reactive oxygen species content had no significant difference. It was indicated that low level of CFTR performed with cAMP and its downstream effectors such as PKA and AMPK to regulate mitochondrial structure and function, leading to increased autophagy rate and reduced vitality of sperm.

基于移相控制统一模型的双有源桥DC-DC变换器基波环流优化控制策略

为充分利用双有源桥DC-DC变换器的容量,减小无功功率,提升工作效率,提出一种基于变换器移相控制统一模型的基波环流优化控制策略。通过引入基波移相比对变换器的所有移相控制方式进行统一描述,并采用傅里叶分解法建立全桥交流电压及电感电流的统一模型。该统一模型降低了多控制变量下变换器多模态分析的复杂性,适用于不同移相控制的所有工作模式,具有普适性。基于频域分析法和功率因数角,构建变换器传输功率及无功功率的统一数学模型。在此基础上,提出考虑无功基波分量的环流优化控制策略,并对传导损耗进行建模与分析。该策略简单有效,能够很好地减小变换器无功功率和改善系统效率,更有利于工程实际的应用。搭建了实验平台,对比了所提基波环流优化控制策略与传统移相控制方式下变换器的功率因数及变换效率,仿真和实验结果验证了理论分析的正确性和所提控制策略的可行性。

基于时变权重模型预测的双向DC-DC优化控制方法

双向DC-DC变换器是电动汽车的关键电压变换部件,提高其动态负载下的响应速度与鲁棒性对电动汽车低压供电系统有重要意义。提出一种基于模糊时变权重的MPC(model predictive control)控制方法。基于状态空间平均法建立变换器动态模型。基于MPC原理搭建变换器MPC模型,实现对电压的跟踪控制;在分析权重对动态负载下电压跟踪性能的影响的基础上,设计权重模糊调节器,实现权重的在线调节。基于HM-cSPACE搭建实验平台验证所提方法的准确性。在Matlab/Simulink环境下与PI控制和传统MPC控制进行对比,结果表明:在负载变化时采用时变权重MPC控制的变换器有更好的动态性能和鲁棒性,超调量降低26.1%。该方法对提高双向DC-DC变换器动态负载下的优化控制具有重要意义。

三有源桥DC-DC变换器广义状态空间平均模型及控制策略研究

基于移相加占空比控制策略的三有源桥TAB(triple active bridge)DC-DC变换器具有效率高和软开关范围可扩展等优点,但其小信号建模过程复杂、闭环控制环路参数整定困难。针对该问题,提出1种TAB工作在移相加占空比控制下的全阶连续广义状态平均建模和PI控制器设计方法。首先,分析TAB的运行原理和Y型等效结构;然后,结合移相加占空比控制的特点和交流方波源等效方法,推导出TAB的广义状态空间平均模型;接着,在推得模型的基础上求得输入到输出的传递函数,设计出PI控制器参数。最后,结合数字仿真及样机实验验证了所提方法的正确性及有效性。

基于改进LSTM-SVM的双向DC-DC电力变换器故障诊断

目的为了解决双向DC-DC电力变换器的软故障诊断精度不高的问题,方法提出基于改进LSTM-SVM的双向DC-DC电力变换器故障诊断模型。首先,分析双向DC-DC电力变换器中电容、电感和MOSFET管的故障机理,通过仿真实验模拟各元件失效后变换器的输出电气参数变化,从而确定变换器不同元件故障时对应的故障特征参数;其次,构建改进的LSTM-SVM双向DC-DC电力变换器故障诊断组合模型,在LSTM中添加Mogrifier门机制,提高LSTM提取时间序列原始数据中微弱特征的能力;最后,由于传统LSTM的末端分类器为Softmax,其主要解决单一元件诊断问题,变换器故障类型较多,维数较高,所以采用麻雀搜索算法优化的SVM代替原有的Softmax函数,对LSTM输出的数据进行故障分类,提高故障诊断的准确率。设置双向DC-DC电力变换器充放电两种状态下,包含电解电容、电感和MOSFET单双管故障在内的24组故障,分别采用本文构建的改进的LSTM-SVM和原始的LSTM-SVM双向DC-DC变换器故障诊断模型进行诊断。结果结果表明,改进的LSTM-SVM故障诊断模型诊断准确率平均值为99.71%,原始的LSTM-SVM故障诊断模型诊断准确率平均值为88.48%,改进的LSTM-SVM故障诊断模型对各元件的故障诊断正确率均高于原始的LSTM-SVM故障诊断模型的。结论基于改进LSTM-SVM的双向DC-DC电力变换器故障诊断模型实现了对双向DC-DC电力变换器中的电解电容、电感和MOSFET单双管故障的准确诊断。

一种新型准Z源高增益DC-DC升压变换器

针对传统准Z源阻抗网络DC-DC升压变换器存在电压增益低和元件电压应力高的问题,提出一种新型准Z源高增益DC-DC升压变换器(HSQZSC)。首先,分析HSQZSC变换器两种模态工作原理,并对其进行稳态分析和参数设计。其次,与现已提出的Z源变换器进行性能对比,表明HSQZSC变换器具有高电压增益和元件电压应力低的优势。然后,对其建立状态空间模型进行小信号分析、稳定性分析和控制器的设计。最后,搭建100 W实物样机,实验结果验证了HSQZSC变换器的可行性与有效性。

基于SEPIC的新型高增益DC-DC变换器及衍生拓扑分析

针对光伏并网系统中单开关升压变换器(如SEPIC、Boost、准Z源、二次型)电压增益低和半导体器件电压应力大的问题,提出1种基于SEPIC的外部升压型高增益DC-DC变换器。首先对所提变换器在电感电流连续导通模式和断续导通模式下的工作原理和稳态特性进行详细分析,并与其他新型拓扑进行性能对比。在此基础上,给出了基于外部升压网络的衍生拓扑。最后,通过搭建1台400 V/200 W的实验样机证明了理论分析的准确性。所提变换器利用阻抗网络和开关电容单元构成的外部升压网络提升了SEPIC变换器的电压增益,并改善了半导体器件电压应力大的缺点。

集成有源开关电感和Y源倍压单元的高增益DC-DC变换器

针对光伏发电系统中光伏组件电压等级的提升,提出一种集成有源开关电感和Y源倍压单元的高增益DC-DC变换器。所提变换器能够实现低开关管电压应力,具有高自由度电压调节能力,在满足一定升压条件下仍能保证电路的效率,在光伏发电中具有较大的应用潜力。对变换器的工作模态、器件电压电流应力、参数设计和损耗效率进行详细阐述。最后通过实验验证所提拓扑结构的可行性。

基于LLC谐振变换器的双向DC-DC光伏储能回路设计

针对光储逆变器的储能回路效率较低,控制较为复杂等问题,该文设计了一款基于双向全桥LLC谐振变换器的双向储能电路。对双向全桥LLC谐振变换器的正向导通特性和反向导通特性进行介绍和分析,基于采用基波分析法得到的LLC谐振变换器等效电路,推导出变换器实现软开关的条件。通过推导得到的条件对LLC谐振变换器进行硬件参数设计,并成功搭建一台样机进行实验验证,实验结果表明,变换器可以在全负载领域实验软开关,并具有较高的效率,验证了理论分析的正确性。

新能源船用双向DC-DC控制系统设计

为适应太阳能电池板昼夜输出电压变化较大的情况,保证母线上用电设备的电压稳定,设计一种新能源船用双向DC-DC控制系统。系统利用STM32作为主控芯片,主电路采用Buck-Boost拓扑结构,用隔离放大器采集电路中的电流和电压信号,电流电压信号经过预处理再经STM32内部A/D转换后作为被控参数,控制程序分为软启动和正常运行两部分,测试结果证明,所设计系统满足应用要求。