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.

Nonholonomic Theory of Principal-direction Orthonormal Basis for a Layer of Surfaces

In order to carry out tensor analysis in a neighborhood of a reference surface,the principal-direction orthogonal basis accompanying with Lame s coefficients or general curvilinear coordinate systems are widely used.A novel kind of field theory termed as the nonholonomic theory of the Principal-Direction Orthonormal Basis(PDOB)is presented systematically in the present paper,in which the formal Christoffel symbols are related directly to the principal and geodesic curvatures with respect to the principal directions of the surface.Furthermore,a systematic and simple way to determine the curvatures of the surface are presented with some examples.It provides a way to recognize qualitatively the bending property of a surface.

Principal Equatorial Null Geodesic Congruences in the Kerr Metric, and Their Quantum Propagators

Using the Raychaudhuri equation, we associate quantum probability amplitudes (propagators) to equatorial principal ingoing and outgoing null geodesic congruences in the Kerr metric. The expansion scalars diverge at the ring singularity;however, the propagators remain finite, which is an indication that at the quantum level singularities might disappear or, at least, become softened.

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.

Using deep neural networks coupled with principal component analysis for ore production forecasting at open-pit mines

Ore production is usually affected by multiple influencing inputs at open-pit mines.Nevertheless,the complex nonlinear relationships between these inputs and ore production remain unclear.This becomes even more challenging when training data(e.g.truck haulage information and weather conditions)are massive.In machine learning(ML)algorithms,deep neural network(DNN)is a superior method for processing nonlinear and massive data by adjusting the amount of neurons and hidden layers.This study adopted DNN to forecast ore production using truck haulage information and weather conditions at open-pit mines as training data.Before the prediction models were built,principal component analysis(PCA)was employed to reduce the data dimensionality and eliminate the multicollinearity among highly correlated input variables.To verify the superiority of DNN,three ANNs containing only one hidden layer and six traditional ML models were established as benchmark models.The DNN model with multiple hidden layers performed better than the ANN models with a single hidden layer.The DNN model outperformed the extensively applied benchmark models in predicting ore production.This can provide engineers and researchers with an accurate method to forecast ore production,which helps make sound budgetary decisions and mine planning at open-pit mines.

A Hybrid Optimization Approach of Single Point Incremental Sheet Forming of AISI 316L Stainless Steel Using Grey Relation Analysis Coupled with Principal Component Analysiss

We investigated the parametric optimization on incremental sheet forming of stainless steel using Grey Relational Analysis(GRA) coupled with Principal Component Analysis(PCA). AISI 316L stainless steel sheets were used to develop double wall angle pyramid with aid of tungsten carbide tool. GRA coupled with PCA was used to plan the experiment conditions. Control factors such as Tool Diameter(TD), Step Depth(SD), Bottom Wall Angle(BWA), Feed Rate(FR) and Spindle Speed(SS) on Top Wall Angle(TWA) and Top Wall Angle Surface Roughness(TWASR) have been studied. Wall angle increases with increasing tool diameter due to large contact area between tool and workpiece. As the step depth, feed rate and spindle speed increase,TWASR decreases with increasing tool diameter. As the step depth increasing, the hydrostatic stress is raised causing severe cracks in the deformed surface. Hence it was concluded that the proposed hybrid method was suitable for optimizing the factors and response.

Rock strength weakening subject to principal stress rotation:Experimental and numerical investigations

During the construction and operation of gas storage reservoirs,changes in the principal stress direction can induce fracture propagation under conditions of lower differential stress,potentially leading to failure in the surrounding rock.However,the weakening of strength due to pure stress rotation has not yet been investigated.Based on fracture mechanics,an enhanced Mohr-Coulomb strength criterion considering stress rotation is proposed and verified with experimental and numerical simulations.The micro-damage state and the evolution of the rock under the pure stress-rotation condition are analyzed.The findings indicate that differential stress exceeding the crack initiation stress is a prerequisite for stress rotation to promote the development of rock damage.As the differential stress increases,stress rotation is more likely to induce rock damage,leading to a transition from brittle to plastic failure,characterized by wider fractures and a more complex fracture network.Overall,a negative exponential relationship exists between the stress rotation angle required for rock failure and the differential stress.The feasibility of applying the enhanced criterion to practical engineering is discussed using monitoring data obtained from a mine-by tunnel.This study introduces new concepts for understanding the damage evolution of the surrounding rock under complex stress paths and offers a new theoretical basis for predicting the damage of gas storage reservoirs.

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.

Robust Principal Component Analysis Integrating Sparse and Low-Rank Priors

Principal Component Analysis (PCA) is a widely used technique for data analysis and dimensionality reduction, but its sensitivity to feature scale and outliers limits its applicability. Robust Principal Component Analysis (RPCA) addresses these limitations by decomposing data into a low-rank matrix capturing the underlying structure and a sparse matrix identifying outliers, enhancing robustness against noise and outliers. This paper introduces a novel RPCA variant, Robust PCA Integrating Sparse and Low-rank Priors (RPCA-SL). Each prior targets a specific aspect of the data’s underlying structure and their combination allows for a more nuanced and accurate separation of the main data components from outliers and noise. Then RPCA-SL is solved by employing a proximal gradient algorithm for improved anomaly detection and data decomposition. Experimental results on simulation and real data demonstrate significant advancements.

A Modified Principal Component Analysis Method for Honeycomb Sandwich Panel Debonding Recognition Based on Distributed Optical Fiber Sensing Signals

The safety and integrity requirements of aerospace composite structures necessitate real-time health monitoring throughout their service life.To this end,distributed optical fiber sensors utilizing back Rayleigh scattering have been extensively deployed in structural health monitoring due to their advantages,such as lightweight and ease of embedding.However,identifying the precise location of damage from the optical fiber signals remains a critical challenge.In this paper,a novel approach which namely Modified Sliding Window Principal Component Analysis(MSWPCA)was proposed to facilitate automatic damage identification and localization via distributed optical fiber sensors.The proposed method is able to extract signal characteristics interfered by measurement noise to improve the accuracy of damage detection.Specifically,we applied the MSWPCA method to monitor and analyze the debonding propagation process in honeycomb sandwich panel structures.Our findings demonstrate that the training model exhibits high precision in detecting the location and size of honeycomb debonding,thereby facilitating reliable and efficient online assessment of the structural health state.

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.

Principals’and Teachers’Awareness,Knowledge,and Differentiation of Privatization-A Secondary Publication

Based on the keynote report by Professor Martin Thrupp,this paper discusses the hollowing out of education provision by the state and the permeation of managerialism.It was pointed out that principals and boards of trustees in socioeconomically advantaged areas may not be willing to share their benefits with schools in less advantaged areas.The new liberal policies have hollowed out state provision of education,so the education system has come to rely heavily on private actors.This paper also presents the current stage of privatization in Japan and the principals’and teachers’perceptions of privatization.

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.

Comparative Analysis of Differences among Northern,Jiangnan,and Lingnan Classical Private Gardens Using Principal Component Cluster Method

This paper investigates the design essence of Chinese classical private gardens,integrating their design elements and fundamental principles.It systematically analyzes the unique characteristics and differences among classical private gardens in the Northern,Jiangnan,and Lingnan regions.The study examines nine classical private gardens from Northern China,Jiangnan,and Lingnan by utilizing the advanced tool of principal component cluster analysis.Based on literature analysis and field research,273 variables were selected for principal component analysis,from which four components with higher contribution rates were chosen for further study.Subsequently,we employed clustering analysis techniques to compare the differences among the three types of gardens.The results reveal that the first principal component effectively highlights the differences between Jiangnan and Lingnan private gardens.The second principal component serves as the key to defining the types of Northern private gardens and distinguishing them from the other two types,and the third principal component indicates that Lingnan private gardens can be categorized into two distinct types as well.