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LQR对直线倒立摆的稳摆控制研究及实现

针对倒立摆的稳摆控制问题,研究设计了一个LQR控制器。首先,考虑摆杆摆动的阻力矩,采用牛顿力学分析方法推导出直线倒立摆的数学模型,建立了其线性状态空间模型,并分析了系统的稳定性、能控性与能观性。通过采用仿真试凑确定加权矩阵Q、R,得到状态反馈增益矩阵K,完成LQR控制器的设计。之后,搭建了以开放式运动控制器为核心的倒立摆实验平台,在计算机上开发了实时人机交互程序,在运动控制器里编写了倒立摆控制算法。最后,进行了仿真与实测实验,验证了所设计的LQR控制器的有效性和可行性。

基于前馈补偿LQR与PID的矿井无轨胶轮车横纵向控制研究

无人驾驶技术是实现无轨胶轮车井下安全、智能、高效运输的重要方案之一,为了提高无人驾驶过程中的轨迹跟踪精度,提出了基于前馈补偿的横向线性二次型调节器(Linear Quadratic Regulator,LQR)与纵向比例积分微分(Proportion Integration Derivative,PID)位移速度调节器相结合的控制策略,实现车辆的横纵向协调控制。通过建立考虑轮胎侧偏特性的2自由度无轨胶轮车动力学模型和跟踪误差模型,并采用井下无轨胶轮车实车参数建立其电机模型,得到车辆的驱动制动输出。利用Carsim和Matlab/Simulink搭建联合仿真环境,分别在井下双车道工况、单车道工况与颠簸路面工况下进行了轨迹跟踪仿真验证。结果表明:在3种工况下车辆轨迹跟踪过程中的最大横向误差仅为5 cm,最大纵向误差仅为10 cm,速度误差控制在1 m/s以内,航向误差范围为±0.1 rad,前轮偏转角变化平稳未出现抖动现象。为验证控制器在井下实际环境下的跟踪性能,使用实验室小车于陕西某井下巷道进行了现场试验验证,结果表明:井下实际巷道下试验结果误差仍在合理范围内,解决了车辆运行过程中的速度和路径的时变问题,反映出该控制器具有较高的精度和较好的稳定性。

Theoretical Study of Double Cost Function Linear Quadratic Regulator(LQR)

Double cost function linear quadratic regulator (DLQR) is developed from LQR theory to solve an optimal control problem with a general nonlinear cost function. In addition to the traditional LQ cost function, another free form cost function was introduced to express the physical need plainly and optimize weights of LQ cost function using the search algorithms. As an instance, DLQR was applied in determining the control input in the front steering angle compensation control (FSAC) model for heavy duty vehicles. The brief simulations show that DLQR is powerful enough to specify the engineering requirements correctly and balance many factors effectively. The concept and applicable field of LQR are expanded by DLQR to optimize the system with a free form cost function.

基于模糊LQR的Spar型海上浮式风力机载荷抑制

针对复杂环境变化易引起海上浮式风力机不稳定的问题,提出一种基于模糊LQR、模糊PI相结合且易于工程应用的桨距控制新方案,实现维持浮式风力发电机组输出功率稳定、抑制浮台运动、减少叶根及塔基疲劳载荷的目的。模糊PI根据发电机转子转速误差变化动态选择期望的PI增益,模糊LQR基于模糊规则自适应调整闭环反馈增益,在保证风力机输出功率和浮台稳定的基础上,进一步减小叶根和塔基疲劳载荷。基于FAST与Matlab/Simulink在不同环境条件下进行联合仿真,验证所提方案的有效性和优越性;通过时域、频域分析表明,与PI控制相比,所提方案在减少叶根处平面外载荷和塔基横向载荷方面有明显改善效果。

采用转角补偿LQR的自动驾驶集卡路径跟踪控制

为了解决自动驾驶集卡中半挂车在行驶过程中的路径偏移问题,提出了一种引入铰接角偏差和转角补偿的线性二次调节器(LQR)控制方法。基于集卡三自由度动力学模型建立了考虑铰接角偏差的路径跟踪误差模型;通过采用比例-积分-微分(PID)算法进行转角补偿设计了LQR路径跟踪控制器;通过MATLAB/Simulink和TruckSim搭建联合仿真平台,在不同工况下进行仿真分析验证。结果表明:通过采用提出的路径跟踪算法,引入PID转角补偿,牵引车平均距离偏差降低62%以上,半挂车平均距离偏差降低31%以上,航向偏差和铰接角偏差也均有所改善。因此,该文提出的控制算法具有较好的路径跟踪性能,提高了对期望路径跟踪的精度和稳定性。

基于改进人工蜂群算法的受电弓LQR控制器设计

针对受电弓LQR控制策略中性能指标的权重系数依靠人工经验选取不足的问题,建立SS400型受电弓三元质量模型,设计受电弓LQR控制器,以接触力标准差和弓头位移标准差之比为评价指标建立目标函数,由于标准人工蜂群算法存在的收敛速度慢、易陷入局部最优的缺点,通过改进蜂群算法的选择策略和搜索方式对LQR控制器的权重系数进行优化。在MATLAB/Simulink环境中建立弓网耦合模型分别在250 km/h、300 km/h的速度下进行仿真,通过与被动控制和标准蜂群算法寻优的结果对比,改进后弓网接触力标准差与弓头位移标准差分别优化了52.8%、37.5%、27.8%、31.8%、40.5%、43.1%、9.3%、7%,显著改善受电弓受流质量。

基于LQR控制的两轮自平衡小车设计

采用LQR控制算法,实现一种两轮自平衡小车的系统设计.搭建了以STM32F103RCT6为主控制器、MPU6050模块为姿态数据采集、N10激光雷达模块为测距的硬件系统.根据两轮自平衡小车的数学模型,利用LQR控制算法实现小车系统的平衡控制,使用Matlab/Simulink进行系统仿真及分析,并在硬件平台上进行实际测试.实验结果表明:小车功能多样、系统运行平稳、抗干扰能力强、调节速度快,具有应用推广价值.

主动悬架的遗传算法优化LQR控制策略研究

为了提高车辆的行驶平顺性和操纵稳定性,本文提出了一种基于遗传算法的线性二次型调节器(linear quadratic regulator,LQR)控制,求解最佳权重矩阵参数的方法。此控制算法克服了传统的LQR控制方法中,由经验主观性确定的权重矩阵Q和R的缺点,使其达到最优的控制效果。本文首先建立了1/4车辆主动悬架模型和道路输入模型,并将遗传算法优化的LQR控制器应用于主动悬架系统中。以主动悬架作为被控对象,车身垂向加速度、悬架弹簧动挠度以及轮胎动位移作为评价指标,通过仿真分析,相比被动控制和LQR控制的主动悬架系统,此优化算法可以显著减小车身垂向加速度与悬架弹簧动挠度,而轮胎动位移的影响不大,从而验证了控制策略的有效性。

基于LQR的自矫正路径跟踪控制器设计方法

针对农业机械自动驾驶提出了一种基于线性二次调节器(LQR)的自矫正路径跟踪控制器设计方法。该方法通过将车辆系统建模为多输入单输出(MISO)状态空间系统,使用LQR设计控制器,以实现对车辆在给定路径上的稳定跟踪和抗干扰能力。针对LQR控制器中存在的系统误差引入了基于反馈误差的自矫正机制,以实现快速准确的路径跟踪,同步降低农业机械自动驾驶中的轨迹误差值。在仿真与实验中进行了验证,并与传统LQR控制器进行比较。结果表明,该控制器设计方法可以有效实现自动驾驶农业机械在复杂路径上的精确跟踪和强鲁棒性性能,曲线路径跟踪平均最大横向误差小于等于0.0530m,平均最大绝对平均误差小于等于0.0331,平均标准差小于等于0.0273m。