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.

Protective Effect of Silent Mating Type Information Regulation 2 Homolog 1 on TGF-β1 Pathway via mTOR in Diabetic Nephropathy

Objective: To demonstrate whether the expression of silent mating type information regulation 2 homolog 1 (SIRT1) affects the level of TGF-β1 and Smad3 in HEK293 cells through regulating mTOR. Methods: First, recombinant plasmids DNA (rSIRT1) and siRNA targeting SIRT1 were constructed which were transfected into Human Embryonic Kidney 293 cell (HEK293) cells, respectively. Then, the generation of intracellular ROS in cells was examined by flow cytometry using the oxidation-sensitive probe. Last, the expressions of TGF-β1, smad3, P53, mTOR, p-mTOR, LC3-I and LC3-II in cells were detected to observe the effect of SIRT1 on TGF-β1 Pathway by western blot analysis. Results: We demonstrated that overexpressing of SIRT1 may decrease TGF-β1 and Smad3 expression in HEK293 cells through regulating mTOR. In addition, the result is the opposite when SIRT1 was silent in HEK293 cells. Conclusions: SIRT1 is closely related to TGF-β1/Smad3 pathway that correlates with the regulation of mTOR and ROS generation and causes diabetic nephropathy. The available evidence implies that SIRT1 has great potential as a clinical target for the prevention and treatment of renal fibrosis in the development of DN.

Regulation role of miR-204 on SIRT1/VEGF in metabolic memory induced by high glucose in human retinal pigment epithelial cells

AIM:To examine the regulatory role of microRNA-204(miR-204)on silent information regulator 1(SIRT1)and vascular endothelial growth factor(VEGF)under highglucose-induced metabolic memory in human retinal pigment epithelial(hRPE)cells.METHODS:Cells were cultured with either normal(5 mmol/L)or high D-glucose(25 mmol/L)concentrations for 8d to establish control and high-glucose groups,respectively.To induce metabolic memory,cells were cultured with 25 mmol/L D-glucose for 4d followed by culture with 5 mmol/L D-glucose for 4d.In addition,exposed in 25 mmol/L D-glucose for 4d and then transfected with 100 nmol/L miR-204 control,miR-204 inhibitor or miR-204 mimic in 5 mmol/L D-glucose for 4d.Quantitative reverse transcription-polymerase chain reaction(RT-qPCR)was used to detect miR-204 mRNA levels.SIRT1 and VEGF protein levels were assessed by immunohistochemical and Western blot.Flow cytometry was used to investigate apoptosis rate.RESULTS:It was found that high glucose promoted miR-204 and VEGF expression,and inhibited SIRT1 activity,even after the return to normal glucose culture conditions.Upregulation of miR-204 promoted apoptosis inhibiting SIRT1 and increasing VEGF expression.However,downregulation of miR-204 produced the opposite effects.CONCLUSION:The study identifies that miR-204 is the upstream target of SIRT1and VEGF,and that miR-204 can protect hRPE cells from the damage caused by metabolic memory through increasing SIRT1 and inhibiting VEGF expression.

Cyber Resilience through Real-Time Threat Analysis in Information Security

This paper examines how cybersecurity is developing and how it relates to more conventional information security. Although information security and cyber security are sometimes used synonymously, this study contends that they are not the same. The concept of cyber security is explored, which goes beyond protecting information resources to include a wider variety of assets, including people [1]. Protecting information assets is the main goal of traditional information security, with consideration to the human element and how people fit into the security process. On the other hand, cyber security adds a new level of complexity, as people might unintentionally contribute to or become targets of cyberattacks. This aspect presents moral questions since it is becoming more widely accepted that society has a duty to protect weaker members of society, including children [1]. The study emphasizes how important cyber security is on a larger scale, with many countries creating plans and laws to counteract cyberattacks. Nevertheless, a lot of these sources frequently neglect to define the differences or the relationship between information security and cyber security [1]. The paper focus on differentiating between cybersecurity and information security on a larger scale. The study also highlights other areas of cybersecurity which includes defending people, social norms, and vital infrastructure from threats that arise from online in addition to information and technology protection. It contends that ethical issues and the human factor are becoming more and more important in protecting assets in the digital age, and that cyber security is a paradigm shift in this regard [1].

Research on Residents’Willingness to Protect Privacy in the Context of the Personal Information Protection Law:A Survey Based on Foshan Residents’Data

The Personal Information Protection Law,as the first law on personal information protection in China,hits the people’s most concerned,realistic and direct privacy and information security issues,and plays an extremely important role in promoting the development of the digital economy,the legalization of socialism with Chinese characteristics and social public security,and marks a new historical development stage in the protection of personal information in China.However,the awareness of privacy protection and privacy protection behavior of the public in personal information privacy protection is weak.Based on the literature review and in-depth understanding of current legal regulations,this study integrates the relevant literature and theoretical knowledge of the Personal Protection Law to construct a conceptual model of“privacy information protection willingness-privacy information protection behavior”.Taking the residents of Foshan City as an example,this paper conducts a questionnaire survey on their attitudes toward the Personal Protection Law,analyzes the factors influencing their willingness to protect their privacy and their behaviors,and explores the mechanisms of their influencing variables,to provide advice and suggestions for promoting the protection of privacy information and building a security barrier for the high-quality development of public information security.

miR-211 promotes lens epithelial cells apoptosis by targeting silent mating-type information regulation 2 homolog 1 in age-related cataracts

AIM： To detect the expression of miR-211 in age-related cataract tissue, explore the effects of miR-211 on lens epithelial cell proliferation and apoptosis, and identify its target gene.METHODS： This study used real-time quantitative polymerase chain reaction（RT-q PCR） to measure the expression of miR-211 and its predicted target gene [silent matingtype information regulation 2 homolog 1（SIRT1）] in 46 anterior lens capsules collected from age-related cataract patients. Human lens epithelial cell line（SRA01/04） cells were transfected with either miR-211 mimics, mimic controls, miR-211 inhibitors or inhibitor controls, 72 h after transfection, miR NA and protein expression of SIRT1 were measured using RT-qP CR and Western blotting; then cells were exposed to 200 μmol/L H2O2 for 1h, whereupon cell viability was measured by MTS assay, caspase-3 assay was performed. Dual luciferase reporter assay was performed to verify the relationship between miR-211 of SIRT1.RESULTS： Compared to the control group, expression of miR-211 was significantly increased（P〈0.001）, the miR NA and protein expression of SIRT1 were significantly decreased（P〈0.001） in the anterior lens capsules of patients with age-related cataracts. Relative to the control group, SIRT1 miR NA and protein levels in the miR-211 mimic group were significantly reduced, cell proliferation activity significantly decreased, and caspase-3 activity was significantly increased（P〈0.001）. In the miR-211 inhibitor group, SIRT1 miRNA and protein expression were significantly increased, cell proliferation activity significantly increased, and caspase-3 activity was significantly decreased（P〈0.001）. A dual luciferase reporter assay confirmed that SIRT1 is a direct target of miR-211.CONCLUSION： miR-211 is highly expressed in the anterior lens capsules of patients with age-related cataracts. By negatively regulating the expression of SIRT1, miR-211 promotes lens epithelial cell apoptosis and inhibits lens epithelial cell proliferation.

Interpretation of Information Processing Regulations

Laws and policies impose many information handling requirements on business practices. Compliance with such regu-lations requires identification of conflicting interpretations of regulatory conditions. Current software engineering methods extract software requirements by converting legal text into semiformal constraints and rules. In this paper we complement these methods with a state-based model that includes all possibilities of information flow. We show that such a model provides a foundation for the interpretation process.

The Legal Regulation of the Information Exchange for Trade Association in China

In the modem society where information is efficient, information exchange is an important affair and function of trade association. However, information exchange behaviors of industry association will have double and legal effect on market and competition, which can not only promote the communication among members of the industry to find a solution to the industry benefit maximization, but also can produce inhibition and barriers to competition in the market. So in this paper, the industry association analysis will be made on the pros and cons of the information exchange, and the legislative defects and the insufficiency of information exchange industry association in our country. According to the practice in our country, the author puts forward the system design of our country industry association information exchange behavior.

Ministry of Information Industry Regulation:Mobile Charger Interfaces must be Unified

Recently, the Ministry of Information Industry (MII) printed and distributed the Notification on the Implementation of the Technical Requirements and Testing Method for Mobile Charger and Interface by Mobile Network Connection and Detection.……

Regulations for the Protection of the Right of Communication through Information Network

Article 1 These Regulations have been formulated under the Copyright Law of the People's Republic of China (hereinafter referred to as the Copyright Law) with a view to protecting the right of communication through information network enjoyed by copyright owners, performers and producers of sound recordings and video recordings (hereinafter collectively referred to as the right owners) and to encouraging creation and communication of works conducive to the building of a socialist society that is advanced ethically and materially.

Regulations on Open Government Information

On April 24, 2007 the State Council promulgated Regulations of the People＇s Republic of China on Open Governrnent Information （referred to as Regulations below）, which will become effective on May 1, 2008. As the first administrative role of the central government of China that aims to safeguard the public＇s right to know, the Regulations are of great significance in China＇s democratization and its establishment of the role of law.

Enforcement of Regulations of the People's Republic of China on Disclosure of Government Information and Continual Development of a Group of Basic Human Rights

Introduction 2013 saw the sixth anniversary of the formulation of Regulations of the People＇s Republic of China on Disclosure of Government Information （hereinafter referred to as the Regulations） and the fifth anniversary of their being put into effect. As the Regulations were stipulated and put into force,

Tracking and Monitoring Leaf Development, Coupling Law and Regulation Techniques during Flowering Period of Hybrid Foxtail Millet (<i>Setaria italica</i>(L.) P. Beauv.) Parental Lines

The determining factor of Setaria italica (L.) P. Beauv. is the coupling of its flowering stage and outcrossing rate which leads to low and unstable seed yields in self-pollinated foxtail millet hybrids and thereby limits their large-scale application. In this study, Datong 27, Datong 29 and gu 83 were screened and identified through meticulous observations of their pollination habitats. High exposure rate, degree of exposure and plump of stigma are good factors to accept foreign pollen. Datong 27 and Datong 29 have some additional characteristics, such as long filaments and exposed and full anthers that contain a large amount of pollen. We transformed into a series of stigma-exposed and plump sterile lines that easily accepted exotic pollen. New restorer lines with anthers that were full of powder and exhibited quick recovery, which improved the parental lines’ heterosexual characteristics. By tracking and monitoring the leaf development of the new sterile and restorer lines, a coupling law of leaf development was determined and a series of flowering control measures were formulated. These factors ensured that the parental lines encounter one another during the flowering stage. By utilizing fertilizer and water, the vitality of the female stigma, amount of powder scattered and powder loosening time were prolonged, which increased hybrid seed yields from 1500 to 3000 kg/hm2. These findings were helpful in resolving the technical problems of seed production that restricted the propagation of foxtail millet hybrids and supporting future large-scale applications.

The Quantitative Law of Network Information Growth

Based on the assumptions of ＂information transfer＂ and ＂information creation＂, this paper educes the multiplied growth mechanism of network information： that the gross quantity of network information （Im） is about n times as much as the quantity of real network information （Ir）. According to this theoretical model, we give a uniform explanation to all kinds of information growth models in existence, and put forward some proposals, such as ＂forbidding information transfer＂ and ＂building up the central information base＂, to control the repeated information flooding on the network and facilitate the full use of network information.

Sirtuin 1 in regulating the p53/glutathione peroxidase 4/gasdermin D axis in acute liver failure

In this editorial,we comment on the article by Zhou et al.The study reveals the connection between ferroptosis and pyroptosis and the effect of silent information regulator sirtuin 1(SIRT1)activation in acute liver failure(ALF).ALF is characterized by a sudden and severe liver injury resulting in significant hepatocyte damage,often posing a high risk of mortality.The predominant form of hepatic cell death in ALF involves apoptosis,ferroptosis,autophagy,pyroptosis,and necroptosis.Glutathione peroxidase 4(GPX4)inhibition sensitizes the cell to ferroptosis and triggers cell death,while Gasdermin D(GSDMD)is a mediator of pyroptosis.The study showed that ferroptosis and pyroptosis in ALF are regulated by blocking the p53/GPX4/GSDMD pathway,bridging the gap between the two processes.The inhibition of p53 elevates the levels of GPX4,reducing the levels of inflammatory and liver injury markers,ferroptotic events,and GSDMDN protein levels.Reduced p53 expression and increased GPX4 on deletion of GSDMD indicated ferroptosis and pyroptosis interaction.SIRT1 is a NAD-dependent deacetylase,and its activation attenuates liver injury and inflammation,accompanied by reduced ferroptosis and pyroptosis-related proteins in ALF.SIRT1 activation also inhibits the p53/GPX4/GSDMD axis by inducing p53 acetylation,attenuating LPS/D-GalN-induced ALF.

Iterated Logarithm Laws on GLM Randomly Censored with Random Regressors and Incomplete Information

In this paper, we define the generalized linear models (GLM) based on the observed data with incomplete information and random censorship under the case that the regressors are stochastic. Under the given conditions, we obtain a law of iterated logarithm and a Chung type law of iterated logarithm for the maximum likelihood estimator (MLE) in the present model.

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.

Stakeholders’ Compliance with Existing Construction Health and Safety Related Laws and Regulations in Ghana

This paper explored stakeholders’ compliance with existing laws and regulations related to construction health and safety (CHS) in the Ghanaian construction industry (GCI). Qualitative research approach was adopted for the data collection, using semi-structured interview guide. An in-depth face-to-face interview based on the grounded theory approach was conducted with actors who play important roles in ensuring health and safety at the construction site as well as key officers and professionals who are the major stakeholders in the GCI. Content analysis was adopted for the analysis of the qualitative data. The findings of the study show customary laws, bye laws, Labour Act, 2003 (Act 651), Local Governance Act, 2016 (Act 936) and the contract document as the key existing CHS related laws and regulations that the stakeholders comply with. The stakeholders also identified the following construction health and safety related regulations in the GCI which have low compliance rate: Factories, Shops and Offices Act, 1974 (Act 323), Environmental Protection Act, 1994 (Act 490), among others. The findings of the research contribute to knowledge of stakeholders’ compliance with existing laws and regulations related to CHS, and underscore the need to ensure monitoring and enforce compliance in the GCI. The findings further identify areas for stakeholders to focus attention on ensuring good health and safety practices, and also expose critical training and education needs for stakeholders in the GCI. The findings provide valuable insights on stakeholders’ compliance with laws and regulations related to CHS in Ghana, which may be applicable to other developing countries with similar construction industry.

Study on the Development of the Chip Information Industry Based on Moore’s Law

Chips are the carriers of ICs (integrated circuits). As a result of design, manufacturing, and packaging and testing processes, chips are typically wholly independent entities intended for immediate use. According to known data, one unit of chip output can drive up to ten units of output in the electronic information industry and 100 units of GDP (Gross Domestic Product). The Chip Information Industry is a strategic industry in most developed countries in Europe and North America. The development of the Chip Information Industry is related to national economies and personal livelihoods. Moore discovered a certain trend after analyzing data: in general, every newly produced chip has twice the capacity of the previous generation, and it takes 18 to 24 months for the next generation to be subsequently invented. This trend has come to be known as Moore’s Law. It applies not only to the development of memory chips but also to the evolutionary paths of processor capability and disk drive storage capacity. Moore’s Law has become the basis of performance prediction in several industries. However, since 2011, the size of silicon transistors has been approaching its physical limit at the atomic level. Due to the nature of silicon, additional breakthroughs in the running speed and performance of silicon transistors are severely limited. Elevated temperature and leakage are the two main sources that invalidate Moore’s Law. To counter these issues, This paper analyzes specific problems challenges in the Chip Information Industry, including the development of carbon nanotube chips and fierce competition in the international Chip Information Industry. In addition, this paper undertakes a critical analysis of the Chinese Chip Information Industry and countermeasures to Chinese Chip Information Industry development.

Regulation Law of Turbine and Generator in Organic Rankine Cycle Power Generation Experimental System

In the performance experiment of organic Rankine cycle power generation experimental system, the loadresistance-regulation method is one of the most important regulation methods. However, the regulation law has not been clear enough to guide the experiment, which is unfavorable to the experimental research on organic Rankine cycle. In this paper the regulation law of turbine and generator by the load-resistance-regulation method is studied theoretically and experimentally. The results show that when the thermal cycle parameters keep constant, the turbine speed increases with the increase of load resistance and there is a maximum value of transmission-generator efficiency with the variation of the turbine speed; when the turbine speed and generator speed keep constant, the transmissiongenerator efficiency decreases and gradually tends to zero with the increase of load resistance.