Information Regulator Research Articles

Analysis of Local Governance and Legal Protection of Students' Information Security in the Context of Sustainable Development of Digital Education

Local governments are dealing with student information more and more frequently, resulting in the risk of student information being leaked, so it is necessary to introduce relevant policies, laws and regulations to standardize information collection activities and improve the level of social information governance. Therefore, this study proposes three hypotheses: on the one hand, whether the information policy issued by the local government can guide students' information collection activities, and on the other hand, whether the introduction of local laws and regulations can provide protection for students' information security; Finally, whether public participation can provide supervision for student information collection and governance, and create a good public management environment. The results show that local information laws and regulations can regulate the behavior of students' information collection and clarify the purpose and direction of students' information collection. At the same time, laws and regulations such as privacy protection and local codes of conduct can improve the security of student information and ensure the legal collection of information. The active participation of the public is conducive to the public information collection environment and ensures the overall security of student information. Therefore, local government policies, laws, and regulations can provide assurance and support for students' information security and promote the sustainable development of digital education.

Abstract 4138344: High fat diet induced the premature senescence of white adipose tissue through downregulating SIRT1 expression and promoting its S-nitroslyation modification

Background and Objectives: The dysfunction of subcutaneous white adipose tissue is one of the early manifestations of obesity, which was associated with accelerated cellular process in aging induced by high fat-diet. The premature senescence of adipose-derived mesenchymal stem cells (AMSCs) is the key factor contributing to the aging of subcutaneous white adipose tissue. However, the underlying mechanism was not clear. Here, we explored the role and mechanism of obesity on the aging of white adipose tissue and AMSCs, and evaluated the anti-aging effect of resveratrol on this process. Methods: Subcutaneous white adipose tissue in non-elderly obese individuals and mice fed with high fat-diet was obtained to detect the TG metabolism and premature senescence. Then the postprandial triglyceride-rich lipoproteins (TRL) after high-fat diet was extracted, and the role and mechanism of TRL on the senescence of AMSCs were explored. Finally, the anti-aging effect of resveratrol on the white adipose tissue and AMSCs was evaluated. Results: Postprandial TG metabolism was abnormal in non-elderly obese humans and mice, and high-fat diet remarkably aggravated white adipose tissue senescence in mice (Fig. 1). TRL induced the premature senescence of AMSCs, with the downregulation of of silent mating-type information regulation 2 homolog 1 (SIRT1) via protein kinase B/forkhead box protein O1 pathway. Besides, the S-nitrosylation of SIRT1 was increased which was regulated by ten-eleven translocation 1/S-nitrosoglutathione reductase pathway. Resveratrol, a SIRT1 agonist, inhibited the TRL-induced AMSCs senescence, resulting in the amelioration of white adipose tissue senescence in obese mice (Fig. 2). Conclusions: These findings established a new mechanism for high-fat diet-induced white adipose tissue senescence and provided a potential therapeutic strategy for high-fat diet induced white adipose tissue senescence and metabolic disorders.

ScImmOmics: a manually curated resource of single-cell multi-omics immune data.

Single-cell sequencing technology has enabled the discovery and characterization of subpopulations of immune cells with unique functions, which is critical for revealing immune responses under healthy or disease conditions. Efforts have been made to collect and curate single-cell RNA sequencing (scRNA-seq) data, yet an immune-specific single-cell multi-omics atlas with harmonized metadata is still lacking. Here, we present scImmOmics (https://bio.liclab.net/scImmOmics/home), a manually curated single-cell multi-omics immune database constructed based on high-quality immune cells with known immune cell labels. Currently, scImmOmics documents >2.9 million cell-type labeled immune cells derived from seven single-cell sequencing technologies, involving 131 immune cell types, 47 tissues and 4 species. To ensure data consistency, we standardized the nomenclature of immune cell types and presented them in a hierarchical tree structure to clearly describe the lineage relationships within the immune system. scImmOmics also provides comprehensive immune regulatory information, including T-cell/B-cell receptor sequencing clonotype information, cell-specific regulatory information (e.g. gene/chromatin accessibility/protein/transcription factor states within known cell types, cell-to-cell communication and co-expression networks) and immune cell responses to cytokines. Collectively, scImmOmics is a comprehensive and valuable platform for unraveling the heterogeneity and diversity of immune cells and elucidating the specific regulatory mechanisms at the single-cell level.

Shifting Under Pressure: Timing Practices within Regulatory Information Disclosure Programs

Research examines the process through which regulatory agencies and other powerful third parties publicly disseminate information about organizations in order to reduce the information asymmetry between those organizations and their dispersed or less powerful stakeholders. These disclosure programs are presumed to work by mobilizing stakeholders to pressure organizations for change. Prior studies focus on organizations’ resistance to that external pressure, often drawing from theories of institutional forces and organizational legitimacy. Instead, the present study examines the public disclosure process itself, and adapts research on organizational learning and collective attention focus to develop new theory regarding how organizations may selectively time their practices to influence these disclosures in their favor. Results suggest that organizations may respond to disclosure programs and other governance structures when actively monitored, but may drift out of compliance during intervening periods. Findings also suggest that strong governance outside of the regulatory disclosure process can help to reduce these problems. The study contributes to corporate governance, organizational learning, and other literatures by developing new theory regarding the timing of organizational responses to regulatory interventions, and by providing evidence that overlapping forms of oversight may mitigate the limitations within any one particular governance mechanism.

Aerobic exercise alleviates statin-induced PCSK9 upregulation by increasing epoxyeicosatrienoic acid levels through the FoxO3a-Sirt6 axis

BackgroundStatins are the cornerstone of low-density lipoprotein cholesterol (LDL-C)-lowering therapy; however, the therapeutic efficacy of statins in countering atherosclerotic cardiovascular disease (ASCVD) is compromised by the concurrent elevation of proprotein convertase subtilisin/kexin type 9 (PCSK9), a pivotal molecule that increases LDL-C levels. Aerobic exercise lowers PCSK9 levels, but the underlying mechanism remains unclear. Therefore, we investigated how aerobic exercise can ameliorate statin-induced increases in PCSK9 levels. MethodsThree-week-old male American Institute of Cancer Research (ICR) mice were fed a high-fat-cholesterol diet (HFD) for 12 weeks and then administered atorvastatin alone or atorvastatin combined with aerobic exercise (Statin+Ex). Moreover, a total of 165 participants with stable coronary heart disease (CHD) enrolled at the inpatient and outpatient departments of the Second Xiangya Hospital of Central South University from January 2018 to July 2020 were randomized into the Statin group (male/female = 51/33) and Statin+Ex group (male/female = 52/29). Patients in the Statin+Ex group underwent treadmill exercise of 45–60 min/day for 7 days. ResultsAerobic exercise effectively alleviated statin-induced PCSK9 upregulation in human patients with CHD and hypercholesterolemic ICR mice (all p< 0.05). Mechanistically, our findings revealed that aerobic exercise induced elevated epoxyeicosatrienoic acids (EETs) plasma levels while concurrently reducing the activity of soluble epoxide hydrolase (sEH) (all p < 0.05), an enzyme responsible for EETs degradation. Further, EETs significantly suppressed PCSK9 expression, subsequently reducing the LDL-C levels (all p < 0.05); this effect was mediated via the activation of the Forkhead box O3a-Silent mating type information regulation 2 homolog 6 (FoxO3a-Sirt6) axis, with no impact on the Sterol Regulatory Element Binding Protein 2 and 3-hydroxy-3-methylglutaryl-CoA reductase(SREBP2-HMGCR) pathway. ConclusionOur study sheds light on the paradigm of "Exercise is Medicine", providing evidence to support the use of statins combined with exercise in reducing LDL-C levels, and unveils potential avenues for clinical applications of sEH inhibitors, presenting novel prospects for therapeutic interventions in ASCVD.

Acetylation of FOXO1 is involved in cadmium-induced rat kidney injury via mediating autophagosome-lysosome fusion blockade and autophagy inhibition

Cadmium (Cd), a potentially toxic elements, has the potential to cause harm to the kidneys. Studies has demonstrated that autophagosome-lysosome fusion blockade and consequent autophagy inhibition is related to Cd-induced kidney injury. Studies indicate that acetylation of forkhead box protein O1 (FOXO1) as a transcriptional factor of lysosomal and autophagy genes, but its roles in Cd-exposed kidney tissues remains unclear till now. Therefore, the present study was conducted to elucidate this issue. Data found that Cd enhances the acetylation level of FOXO1 and inhibits the expression level of silent information regulator 1 (Sirt1, deacetylase of FOXO1). Pharmacological activation of Sirt1 (SRT2104 treatment) decreases Cd-increased acetylation level of FOXO1, enhances Cd-inhibited transcription level of Ras-related protein 7 (Rab7), restores Cd-blocked fusion of autophagosome and lysosome, and alleviates Cd-induced autophagy inhibition. Moreover, data corroborated that inhibiting the acetylation level of FOXO1 is conductive to mitigating Cd-induced kidney injury. Collectively, these results demonstrate that acetylation of FOXO1 mediates the autophagosome-lysosome fusion blockade and autophagy inhibition during Cd-induced kidney injury, while regulating the acetylation level of FOXO1 may be a potential mechanism of treating nephrotoxicity after Cd exposure.

Comparative Genomics Reveal Distinct Environment Preference and Functional Adaptation Among Lineages of Gemmatimonadota

Bacteria in the phylum Gemmatimonadota are globally distributed and abundant in microbial communities of various environments, playing an important role in driving biogeochemical cycling on Earth. Although high diversities in taxonomic composition and metabolic capabilities have been reported, little is known about the environmental preferences and associated functional features that facilitate adaptation among different Gemmatimonadota lineages. This study systematically analyzed the relationships between the environments, taxonomy, and functions of Gemmatimonadota lineages, by using a comparative genomics approach based on 1356 Gemmatimonadota genomes (213 high-quality and non-redundant genomes) available in a public database (NCBI). The taxonomic analysis showed that the 99.5% of the genomes belong to the class Gemmatimonadetes, and the rest of the genomes belong to the class Glassbacteria. Functional profiling revealed clear environmental preference among different lineages of Gemmatimonadota, and a marine group and two non-marine groups were identified and tested to be significantly different in functional composition. Further annotation and statistical comparison revealed a large number of functional genes (e.g., amiE, coxS, yfbK) that were significantly enriched in genomes from the marine group, supporting enhanced capabilities in energy acquisition, genetic information regulation (e.g., DNA repair), electrolyte homeostasis, and growth rate control. These genomic features are important for their survival in the marine environment, which is oligotrophic, variable, and with high salinity. The findings enhanced our understanding of the metabolic processes and environmental adaptation of Gemmatimonadota, and further advanced the understanding of the interactions of microorganisms and their habitats.

Development of a PCR assay for rapid and accurate detection of an emerging vanB Enterococcus faecium clone in the Capital Region of Denmark.

To develop and validate a real-time PCR assay detecting the sequence bridging Tn1549 and the Enterococcus faecium chromosome in the emerging vanB vancomycin-resistant E. faecium (VREfm) clone (ST80/CT2406). The Tn1549 insertion site was determined on routinely sequenced VREfm isolates. The outer boundaries of Tn1549 and adjoining host bacterial sequences were determined using a BLAST search in the silent information regulator gene sir2. Next, the primers and probe were developed, targeting the sequence bridging Tn1549 and the E. faecium chromosome. Finally, the PCR assay was validated on well-characterized strains and prospectively performed on rectal screening samples submitted to our laboratory. The PCR assay proved to be accurate and provide rapid diagnosis of the emerging vanB VREfm in rectal screening samples.

Ferulic Acid Interferes with Radioactive Intestinal Injury Through the DJ-1-Nrf2 and Sirt1-NF-κB-NLRP3 Pathways.

Radiation-induced intestinal injury is a common complication of radiotherapy for abdominal and pelvic malignancies. Due to its rapid proliferation, the small intestine is particularly sensitive to radiation, making it a critical factor limiting treatment. Ferulic acid (FA), a derivative of cinnamic acid, exhibits antioxidant, anti-inflammatory, and anti-radiation properties. In this study, we established a mouse model of radiation-induced intestinal injury using a dose of 11 Gy at a rate of 96.62 cGy/min. Our findings indicate that FA's protective effects against radiation-induced intestinal injury may be mediated through the parkinsonism-associated deglycase (DJ-1) nuclear factor erythroid 2-related factor 2 (Nrf2) and silent mating type information regulation 2 homolog 1 (Sirt1) nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) NOD-like receptor family, pyrin domain containing 3 (NLRP3). FA was found to mitigate changes in oxidative stress indices and inflammatory factors induced by radiation, as well as to attenuate radiation-induced pathological alterations in the small intestine. Furthermore, FA enhanced the expression of DJ-1 and Nrf2 at both the transcriptional and protein levels, inhibited NLRP3 protein fluorescence intensity, and reduced the expression of NLRP3, interleukin-18 (IL-18), and interleukin-1 beta (IL-1β). Additionally, FA suppressed the transcription and translation of NF-κB, NLRP3, cysteine-aspartic acid protease-1 (Caspase-1), IL-18, and IL-1β by upregulating Sirt1, thereby alleviating radiation-induced inflammatory injury in the small intestine. Thus, FA holds promise as an effective therapeutic agent for ameliorating radiation-induced intestinal injury.

Global Supply Chain Information Sharing Platforms: Challenges, Opportunities, and Trends

With the deepening process of globalization, the rapid development of information technology and the diversification of logistics methods, supply chain management faces increasingly complex challenges. This study explores the future development trends, challenges and opportunities of information sharing platforms in global supply chains. In global supply chains, information sharing platforms are of great significance. It facilitates real-time data exchange and collaboration among supply chain segments and help improve supply chain transparency, flexibility and efficiency. However, global supply chain information sharing faces many challenges, including problems in information security, technical standards, cultural differences, and laws and regulations. In response to these challenges, this paper proposes future directions for developing a global supply chain information sharing platform, including digitization, automation, cross-platform cross-border collaboration, data security and privacy protection, application of new technologies, and flexibility and adaptability. This study provides useful insights and guidance for future global supply chain management by exploring the global supply chain information sharing platform.

Onion Peel Extract Prevents Intestinal Inflammation via AMK-Activated Protein Kinase Activation in Caco-2/HT-29 Cells.

Obesogenic diets cause intestinal inflammation and dysfunction. Polyphenols have shown a positive impact on reducing inflammation in in vitro studies. However, their bioactivity may not be the same in the in vivo system due to structural alteration by the gastrointestinal digestive process. The purpose of this study was to investigate the anti-inflammatory effect of onion peel and its major bioactive compound, quercetin, in the intestine and further examine the impact of intestinal digestion on this effect. Onion peel extract (OPE) and quercetin (Q) were digested using gastrointestinal digestive enzymes in vitro and then treated into lipopolysaccharide (LPS)-stimulated Caco-2/HT-29 cells. Genes and proteins related to tight junction, inflammation, and epithelial integrity were measured. OPE and digested OPE (DOPE) had a higher protective effect on LPS-induced tight junction and inflammatory genes and paracellular permeability than Q and digested Q (DQ). DOPE was more effective than OPE, while digestion did not change the activity of Q. The anti-inflammatory effect of OPE and Q with or without digestion was achieved by inhibiting nuclear factor kappa B through AMP-activated protein kinase-activated silent mating-type information regulation 2 homolog 1. It was the first to find that a crude extract, after undergoing gastrointestinal digestion, demonstrated a notably superior anti-inflammatory effect in the cell study, suggesting the consumption of onion peels could potentially yield similar benefits in the human intestine. This discovery underscores the potential of onion peel polyphenols in combating intestinal inflammation, making them a compelling area of research for future therapeutic applications using food byproducts.

Effect of Nicotinamide Riboside Against the Exhaustion of CD8+ T Cells via Alleviating Mitochondrial Dysfunction.

Background: Targeting mitochondria and protecting the mitochondrial function of CD8+ T cells are crucial for enhancing the clinical efficacy of cancer immunotherapy. Objectives: In this study, our objective was to investigate the potential of nicotinamide riboside (NR) in preserving the mitochondrial function of CD8+ T cells and mitigating their exhaustion. Methods: We established two in vitro models to induce CD8+ T cell exhaustion either by tumor cell-conditioned medium (TCM) or by continuous stimulation with OVA(257-264) peptide. CD8+ T cells were treated in the absence/presence of NR. Results: Our findings demonstrated that NR supplementation effectively inhibited CD8+ T cell exhaustion and preserved mitochondrial function in both models. Moreover, apoptosis of CD8+ T cells was reduced after NR treatment. Western blot data indicated that NR treatment upregulated Silent information regulator 1 (SirT1) expression. Further inhibition of Sirt1 activity using EX527 uncovered that the inhibitory effect of NR on CD8+ T cell exhaustion and its protective effect on mitochondria were attenuated. Conclusions: In conclusion, our results indicate that NR supplementation attenuates CD8+ T cell exhaustion, and its underlying mechanism is associated with increased mitochondrial function regulated by the SirT1 pathway. Our research provides evidence that NR may assist in enhancing the clinical efficacy of immunotherapy.

Implications of Personal Data Protection Law in Consumer Health Data Management to Improve Secure and Confidential Handling in Indonesia

The purpose of this study is to understand the impact of the implementation of the Personal Data Protection Law (PDP Law) on the management of consumer health data in Indonesia, with a focus on enhancing secure and confidential handling. In the midst of the rapidly evolving digitalisation era, the management of personal data, especially those related to health information, requires strict and effective legal regulation. This is becoming increasingly urgent given the increasing incidents of data leaks and privacy violations, one of which occurred in the leak of the Indonesian Ministry of Health's server which collected 6 million patient medical record data. The research method used is normative juridical with a conceptual approach and a statutory approach, where secondary data is broken down into three different types of legal materials, namely primary, secondary, and tertiary legal materials. The PDP Law and Consumer Protection Law are the primary legal sources, accompanied by the use of relevant literature as secondary legal sources as well as dictionaries and encyclopedias as tertiary legal materials to further explain. The novelty of this research lies in the comprehensive analysis of the existing regulations and their applicability in the health context, as well as considering the increasing public awareness of their rights to personal data. The results show that although challenges such as uneven technological infrastructure and lack of awareness among health staff still exist, the measures taken through the PDP Law have created a strong foundation for better health data protection in the future, improving security and confidentiality in health data management.

Supplemental oxygen alters the pentose phosphate pathway in the developing mouse brain through SIRT signaling

Oxygen support plays a critical role in the management of preterm infants in neonatal intensive care units. On the other hand, the possible effects of oxygen supplementation on cellular functions, specifically glucose metabolism, have been less understood. Purposeof the study is to investigate whether supplemental oxygen alters glucose metabolism and pentose phosphate pathway (PPP) activity in the brain tissue and its relevance with silent information regulator proteins (SIRT) pathway. For this purpose, newborn C57BL/6 pups were exposed to 90% oxygen from birth until postnatal day 7 (PN7) and metabolites of glysolysis and PPP were investigated through metabolomics analysis. SIRT1, glucose-6-phosphate dehydrogenase (G6PD) and transaldolase (TALDO) proteins were examined immunohistochemically and molecularly in the prefrontal and hippocampus regions of the brain. Later on, SIRT1 inhibition was carried out.Our results indicate that supplemental oxygen causes an increase in PPP metabolites as well as activation of G6PD enzyme in the brain tissue, which is reversed by SIRT1 inhibition. Our study underlines a connection between supplemental oxygen, glucose metabolism, PPP pathway and the SIRT signaling. Understanding these intricate relationships not only deepens our knowledge of cellular physiology but also holds promise for therapeutic interventions for creating neuroprotective strategies in preterm brain.

GRASSIUS 2.0: A gene regulatory information knowledgebase for maize and other grasses

Grass species, which include the major cereal crops maize, wheat, rice, and sugarcane, are an integral part of our global agriculture and source of food and energy for a growing world population. GRASSIUS was established as a knowledgebase for transcription factors (TFs) and coregulators (CoRegs) in maize and several other species in the grass family. TFs are a primary component of the gene regulatory networks (GRNs) and the underlying gene regulatory grids (GRGs) that govern all aspects of plant growth and metabolism. GRASSIUS is the source for all information pertaining to the maize TFome collection, which serves as a powerful resource for the discovery of GRNs in maize and other cereals [1,2]. Here we describe the release of the GRASSIUS 2.0 knowledgebase (www.grassius.org) with updated data, query, and tool features, as well as the ability to expand to accommodate future datasets. The membership and annotation of all TF and CoReg families has been updated and revised to include gene models from v3, v4, and v5, of the maize B73 genome and recent genome versions of rice, sorghum, Brachypodium, and sugarcane. A translation tool enables cross referencing of Gene IDs between versions of the maize genome. Protein-DNA interactions (PDIs) have been added incorporating results derived from various gene- and TF-centered PDI discovery tools and visualized through a new web-based interface. A filtering tools permits the selection and visualization of PDIs within a ± 2 kb distance from the transcriptional start site (TSS) of a gene of interest. A new BLAST (Basic Local Alignment Search Tool) tool facilitates searching of the maize TFome as well as v3, v4, and v5 TF gene model sets. Lastly, we describe the methodology used to implement GRASSIUS 2.0 which can guide others in developing and updating similar plant gene regulatory knowledgebases.

VERMEER FCM: A tool integrating exposure and hazard modelling for chemicals migrating from food contact materials

A new tool, VERMEER FCM, was developed to support the risk assessment of single organic chemicals migrating from plastic food contact materials (FCM). The freely available tool is integrated into MERLIN-Expo and has been designed in line with Regulation (EU) No 10/2011 for plastic FCM. Overall, the tool consists of three modules that allow (i) to model the migration of chemicals into food, (ii) to predict toxicological endpoints relevant to risk assessment of FCM chemicals, and (iii) to automatically check whether the chemical of interest is included in Regulation (EU) No 10/2011. To apply the VERMEER FCM tool, users need to provide information regarding the chemical(s) of interest, the FCM, the food and other parameters (e.g. contact time and temperature). The three modules can be run either separately or in combination. Migration is predicted by a recently developed migration model, whereas hazard predictions for genotoxicity, subchronic toxicity, reproductive and developmental toxicity and carcinogenicity are provided by QSAR models selected from the publicly available VEGA HUB. The major novelty of the tool is that it combines information on hazard and exposure (i.e. migration) with regulatory information. Several case studies were performed to demonstrate the application of the tool.

Tauroursodeoxycholic acid combined with selenium accelerates bone regeneration in ovariectomized rats.

More recently, increased studies have revealed that antioxidants can cure osteoporosis by inhibiting oxidative stress. Tauroursodeoxycholic acid (TUDCA) and Selenium (Se) have been confirmed to possess potent anti-oxidative effects and accelerate bone regeneration. In addition, very little is currently known about the effects of a combination with Se and TUDCA on bone defects in osteoporotic states. We, therefore, aimed to assess the protective effect of combination with Se and TUDCA on bone regeneration and investigate the effect and underlying mechanisms. When MC3T3-E1 was cultured in the presence of H2H2, Se, TUDCA and Se/TUDCA therapy could increase the matrix mineralization and promote expression of anti-oxidative stress markers in MC3T3-E1, while reducing intracellular reactive oxygen species (ROS) and mitochondrial ROS levels. Meanwhile, silent information regulator type 1 (SIRT1) was upregulated in response to Se, TUDCA and Se/TUDCA exposures in H2H2 treated-MC3T3-E1. In the OVX rat model, Se, TUDCA and Se/TUDCA showed a clear positive effect against impaired bone repair in osteoporosis. The results above demonstrate that Se/TUDCA exhibits superior efficacy in both cellular and animal experiments, as compared to Se and TUDCA. In conclusion, combination with Se and TUDCA stimulates bone regeneration and is a promising candidate for promoting bone repair in osteoporosis.

Protective Effect of Aloe-emodin on Cognitive Function in Copper-loaded Rats Based on The Inhibition of Hippocampal Neuron Ferroptosis.

Aloe-emodin (AE), a monomer derived from traditional Chinese medicine, has demonstrated remarkable efficacy in the clinical management of cognitive disorders. Ferroptosis (FPT), a specialized form of programmed cell death, plays a critical role in the pathological progression of various cognitive diseases. This study explored the therapeutic potential of AE in a rat model of Wilson's disease cognitive impairments (WDCI) and examined whether these effects are mediated through the silencing information regulator 1 (SIRT1)-regulated FPT signaling pathway. Employing techniques, such as the Morris water maze (MWM), Hematoxylin & eosin (H&E) staining, Transmission electron microscopy (TEM), Immunofluorescence (IF), assessments of oxidative stress markers, and measurements of FPT-related protein levels, we evaluated the extent of SIRT1-mediated FPT and the therapeutic efficacy of AE. The findings from the WD copper-loaded rat model experiments revealed that MWM, H&E, TEM, and IF outcomes indicated AE's potential to promote the restoration of learning and memory functions, ameliorate hippocampal neuronal morphological damage, and preserve cell membrane integrity. Results from western blot (WB) and ELISA analyses demonstrated that AE markedly upregulated the expression of SIRT1, nuclear factor erythroid-2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SCL7A11), and glutathione peroxidase 4 (GPX4) proteins while simultaneously reversing the expression of oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), and reactive oxygen species (ROS). Consequently, we posit that AE may attenuate WD copper-loaded rat model hippocampal neuronal FPT by activating the SIRT1-mediated signaling pathway. These findings suggested that AE mitigates WD copper-loaded rat model hippocampal neuronal damage through the activation of SIRT1-mediated FPT, thereby presenting a valuable candidate Chinese herbal monomer for the clinical treatment of WDCI.

Medicaid managed care restrictions on medications for the treatment of opioid use disorder.

To examine whether Medicaid managed care plan (MCP) utilization management policies for buprenorphine-naloxone and injectable naltrexone are related to key state Medicaid program policy decisions. We abstracted data on state Medicaid regulatory and policy information from publicly available sources and publicly available insurance benefit documentation from all 241 Medicaid MCPs operating in 2021. In this cross-sectional study, we used bivariate and multivariate analyses to examine whether Medicaid MCP prior authorization and quantity limits on receipt of buprenorphine and injectable naltrexone were associated with key state Medicaid choices to leverage federal funds to expand coverage and eligibility (Medicaid expansion, 1115 waivers) and to regulate Medicaid MCPs (uniform preferred drug lists, medical loss ratio remittance). Models were adjusted for MCP characteristics, including profit status, behavioral health contracting arrangement, National Committee for Quality Assurance accreditation, size, market share, and state opioid overdose death rates. Average marginal effects (AME) were reported. Utilization management was common among MCPs, and restrictions were more commonly applied to buprenorphine than injectable naltrexone, despite its higher cost. States that required MCPs to comply with utilization management policies stipulated in a uniform preferred drug list were more likely to require prior authorization for buprenorphine (AME: 0.29, 95% CI: 0.15-0.42) and injectable naltrexone (AME: 0.25, 95% CI: 0.12-0.38). MCPs in states that required plans to pay back earnings above a certain threshold were less likely to require prior authorization for buprenorphine (AME: -0.30, 95% CI: -0.43 to -0.18). Restrictions on medications for opioid use disorder are widespread among MCPs and vary by medication. State Medicaid regulatory and policy characteristics were strongly linked to MCPs' utilization management approaches. State Medicaid policy and contracting approaches may be levers to eliminate utilization management restrictions on medications for opioid use disorder.

Understanding the fundamental mechanisms and conditions of the tumor-suppressive and oncogenic roles of sirtuins in cancer: A review

Silent information regulators (SIRTs) or sirtuins represent a group of class III nicotinamide adenine dinucleotide&amp;ndash;dependent histone deacetylases. In mammals, seven types of sirtuins are distinguished, differing in their target structures, enzymatic activities, and subcellular localization. Histone deacetylation is a form of epigenetic regulation of gene expression that can cause activation or deactivation of selected genetic targets. Activation of sirtuins is part of the response to nutritional and environmental stimuli (starvation, DNA damage, and oxidative stress). Activated sirtuins subsequently stimulate specific transcriptional programs to make mitochondrial oxidative metabolism more efficient in the fight against oxidative stress or regulate proteins responsible for DNA repair after damage. As a result of their multifunctional involvement in cellular metabolism, dysregulation and aberrant expression of sirtuins have been observed in various cancers. Sirtuins play a dual role in carcinogenesis, acting as either oncogenes or tumor suppressors and affecting the proliferation, apoptosis, and survival of cancerous cells.