Impact Of Regulation Research Articles

Health benefits of phasing out coal-fired power plants in Ontario, Alberta, and Canada

Coal-fired power plants (CFPPs) in Ontario were decommissioned in a phased approach from 2003 to 2014. After Ontario's commitment to eliminate coal-based electricity generation, Alberta and Canada have planned on phasing out coal in the electricity sector. The coal regulation in Canada targets coal-free electricity generation by 2030, accelerating the criteria air pollutant emission reductions in the CFPPs nationwide. The Regulatory Impact Analysis Statement (RIAS) under the coal regulation estimated substantial health benefits based on scenario analysis. Here we use adjoint sensitivity analysis as an alternative approach to estimate the health impacts of CFPPs and non-coal electric generating units (EGUs). The adjoint of the U.S. EPA's Community Multiscale Air Quality (CMAQ) model is used to attribute PM2.5-related health impacts for primary and precursor PM2.5 emissions emitted from the CFPPs and non-coal EGUs in Canada using various epidemiological studies. Our findings suggest that the reduction of CFPP emissions yields more total benefits rather than other fuel types in EGUs. A significant amount of total health burden is estimated to occur within the province that hosts the facility, and with a larger portion of this benefit coming in warmer seasons. Our retrospective analysis of Ontario coal phase-out estimates $1B CAD total annual health benefits in 2003, or projected 2014 benefits of $1.8 B CAD. The transboundary impact of emission reductions from coal-fired power plants in the U.S. entails significant health benefits to Ontario and Canada, more than twice that of Ontario's own coal phase-out. Nationwide, total health burden estimate for CFPPs and non-coal EGUs is $418M CAD in 2014. The choice of epidemiological model has a sizeable impact on estimated burdens or benefits.

Circular RNA RRM2 alleviates metabolic dysfunction-associated steatotic liver disease by targeting miR-142-5p to increase NRG1 expression.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition worldwide, demanding further investigation into its pathogenesis. Circular RNAs (circRNAs) are emerging as pivotal regulators in MASLD processes, yet their pathological implications in MASLD remain poorly understood. This study focused on elucidating the role of circular RNA ribonucleotide reductase subunit M2 (circRRM2) in MASLD progression. In this study, we used both in vitro and in vivo MASLD models using long-chain-free fatty acid (FFA)-treated hepatocytes and high-fat diet (HFD)-induced MASLD in mice, respectively. We determined the expression patterns of circRRM2, microRNA-142-5p (miR-142-5p), and neuregulin 1 (NRG1) in livers of MASLD-afflicted mice and MASLD hepatocytes by RT-qPCR. Dual-luciferase reporter assays verified the binding relationships among circRRM2, miR-142-5p, and NRG1. We conducted further analyses of their roles in MASLD hepatocytes and modulated circRRM2, miR-142-5p, and NRG1 expression in vitro by transfection. Our findings were validated in vivo. The results demonstrated reduced levels of circRRM2 and NRG1, along with elevated miR-142-5p expression in MASLD livers and hepatocytes. Overexpression of circRRM2 downregulated lipogenesis-related genes and decreased triglycerides accumulation in livers of MASLD mice. MiR-142-5p, which interacts with circRRM2, effectively counteracted the effects of circRRM2 in MASLD hepatocytes. Furthermore, NRG1 was identified as a miR-142-5p target, and its overexpression mitigated the regulatory impact of miR-142-5p on MASLD hepatocytes. In conclusion, circRRM2, via its role as a miR-142-5p sponge, upregulating NRG1, possibly influenced triglycerides accumulation in both in vitro and in vivo MASLD models.NEW & NOTEWORTHY CircRRM2 expression was downregulated in free fatty acid (FFA)-challenged hepatocytes and high-fat diet (HFD) fed mice. Overexpressed circular RNA ribonucleotide reductase subunit M2 (circRRM2) attenuated metabolic dysfunction-associated steatotic liver disease (MASLD) development by suppressing FFA-induced triglycerides accumulation. CircRRM2 targeted microRNA-142-5p (miR-142-5p), which served as an upstream inhibitor of neuregulin 1 (NRG1) and collaboratively regulated MASLD progression.

METTL14-mediated N6-methyladenosine modification of TCP1 mRNA promotes acute myeloid leukemia progression

BackgroundAcute myeloid leukemia (AML) is a prevalent hematologic malignancy characterized by a steady rise in morbidity and mortality rates over time. The upregulation of methyltransferase-like 14 (METTL14) expression in AML has been identified; however, its specific contributions to AML progression and underlying molecular mechanisms have yet to be elucidated. MethodMETTL14-bound mRNAs were predicted using bioinformatics methods, analyzed, and screened to identify T-complex protein 1 (TCP1). The regulatory impact of METTL14 on TCP1 was observed. TCP1 expression in AML clinical samples was assessed using quantitative real-time PCR and western blot analysis. The involvement of TCP1 in AML malignant progression was assessed through in vitro and in vivo functional assays. The String database was utilized for predicting proteins that interact with TCP1, while western blot assays and immunoprecipitation were employed to validate the associated signaling pathways. ResultsMETTL14 overexpression upregulates TCP1 expression in AML cells. AML patients exhibit high levels of TCP1 expression. Elevated TCP1 levels in HL60 and U937 cells in vitro lead to increased proliferation, migration, invasion, and inhibition of apoptosis, while in vivo, it accelerates AML proliferation and tumorigenesis. Mechanistically, METTL14 modulates AML progression by influencing TCP1 transcript stability via m6A methylation, thereby regulating TCP1 expression. Additionally, PPP2R2C potentially serves as a crucial functional target of TCP1 implicated in the malignant progression of AML. ConclusionUpregulation of TCP1 expression in AML through METTL14-mediated m6A modification accelerates the malignant progression of the disease. Therefore, targeting the m6A modification of TCP1 could be a potential therapeutic strategy to enhance the treatment of AML.

The Regulatory Impact of CFLAR Methylation Modification on Liver Lipid Metabolism.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease worldwide. Caspase 8 and FADD-like apoptosis regulator (CFLAR) has been identified as a potent factor in mitigating non-alcoholic steatohepatitis (NASH) by inhibiting the N-terminal dimerization of apoptosis signal-regulating kinase 1 (ASK1). While arginine methyltransferase 1 (PRMT1) was previously reported to be associated with increased hepatic glucose production, its involvement in hepatic lipid metabolism remains largely unexplored. The interaction between PRMT1 and CFLAR and the methylation of CFLAR were verified by Co-IP and immunoblotting assays. Recombinant adenoviruses were generated for overexpression or knockdown of PRMT1 in hepatocytes. The role of PRMT1 in NAFLD was investigated in normal and high-fat diet-induced obese mice. In this study, we found a significant upregulation of PRMT1 and downregulation of CFLAR after 48h of fasting, while the latter significantly rebounded after 12h of refeeding. The expression of PRMT1 increased in the livers of mice fed a methionine choline-deficient (MCD) diet and in hepatocytes challenged with oleic acid (OA)/palmitic acid (PA). Overexpression of PRMT1 not only inhibited the expression of genes involved in fatty acid oxidation (FAO) and promoted the expression of genes involved in fatty acid synthesis (FAS), resulting in increased triglyceride accumulation in primary hepatocytes, but also enhanced the gluconeogenesis of primary hepatocytes. Conversely, knockdown of hepatic PRMT1 significantly alleviated MCD diet-induced hepatic lipid metabolism abnormalities and liver injury in vivo, possibly through the upregulation of CFLAR protein levels. Knockdown of PRMT1 suppressed the expression of genes related to FAS and enhanced the expression of genes involved in FAO, causing decreased triglyceride accumulation in OA/PA-treated primary hepatocytes in vitro. Although short-term overexpression of PRMT1 had no significant effect on hepatic triglyceride levels under physiological conditions, it resulted in increased serum triglyceride and fasting blood glucose levels in normal C57BL/6J mice. More importantly, PRMT1 was observed to interact with and methylate CFLAR, ultimately leading to its ubiquitination-mediated protein degradation. This process subsequently triggered the activation of c-Jun N-terminal kinase 1 (JNK1) and lipid deposition in primary hepatocytes. Together, these results suggested that PRMT1-mediated methylation of CFLAR plays a critical role in hepatic lipid metabolism. Targeting PRMT1 for drug design may represent a promising strategy for the treatment of NAFLD.

Evaluating Audit Oversight Board’s Regulatory Impact: Analysis of Sanctions Imposed on Malaysian Audit Firms

This study analyzes the 12-year trend of cases involving auditor wrongdoing as disclosed on the Audit Oversight Board (AOB) Malaysia's website from 2012 to 2023. Utilizing content analysis, the research examines the nature, frequency, and severity of penalties or sanctions imposed on audit firms for various offenses. Findings indicate a dynamic pattern of regulatory actions, reflecting Malaysia's evolving landscape of audit quality and regulatory oversight. It was revealed that a total of 56 breaches of the Securities Commission Act 1993 involving 30 audit firms were reported and disclosed by the Audit Oversight Board over the period from 2012 to 2023. The findings revealed that most misconduct cases relate to the failure of audit firms to comply with the requirements of International Auditing Standards, International Standard on Quality Control and Malaysian Institute of Accountant By-Laws. There has been a notable decrease in cases involving auditors over the past six years. This could also indicate the dedication of the AOB to monitoring auditors' conduct to prevent their involvement in malpractice. This study contributes to the understanding of audit regulation effectiveness and the behavioral patterns of auditors in response to regulatory scrutiny.

El análisis psicológico del Derecho en la regulación jurídica. El sandbox español de inteligencia artificial”.

The close collaboration between Psychology and Law has contributed to the enrichment of the legislative technique. The application of psychological behavioural analysis to law breaks the current paradigm and offers a unique perspective for lawmaking through the study of people's behaviour in the face of laws. Legal experimentation, an innovative practice, emerges as a crucial tool for law-making and regulatory impact assessment in novel areas whose subject matter may be potentially burdensome to individual rights and freedoms. In the context of the Spanish artificial intelligence sandbox, the application of psychology to law is of particular importance, as it contributes to the emerging and much-needed legal regulation. This cooperation between doctrines promises not only to boost normative evolution, but also to ensure a more effective and protective regulation in a world increasingly influenced by technology.

It's time for artificial intelligence governance

Advances in Internet of Things and Artificial Intelligence have transformed society with the potential to foster the prosperity of human beings and improving societal welfare. However, at the same time, there are concerns about their potential negative impact. In this regard, it is of utmost importance to establish a regulatory framework for the Artificial Intelligence and the Internet of Things that will ensure that human rights and fundamental freedoms are respected, promoted, and protected.In this sense, the goal of this article is to propose the Artificial Intelligence and the Internet of Things Governance model. To achieve a better regulation concept, for the Regulatory Impact Assessment we used the Analytical Hierarchy Process method.

Chitosan boosts ginger disease resistance: Insights from transcriptomic and metabolomic analyses

Chitosan exhibits efficacy in controlling ginger diseases, yet its systemic regulatory mechanisms remain unknown. This study explored the potential mechanisms underlying chitosan-regulated resistance by conducting physiological, comparative transcriptome, and metabolome analyses in Fusarium solani-inoculated ginger rhizomes with and without chitosan treatment. Chitosan treatment decreased decay severity and water loss, and reduced reactive oxygen species accumulation by enhancing antioxidant enzyme activities. Chitosan increased PAL, C4H, and CHI activities, along with elevated levels of lignin, total phenolic, total flavonoid, and the accumulation of suberin polyphenolic. RNA-seq analysis identified 1158 differentially expressed genes, predominantly involved in active oxygen and phenylpropanoid metabolism. Metabolomics identified 226 differential metabolites, including numerous phenylpropanoids and flavonoids. Integrated RNA-seq and metabolome analyses revealed chitosan's regulatory impact on gene expression and metabolite accumulation in the phenylpropanoid metabolism. These findings provide novel insights into chitosan's mechanisms against Fusarium solani.

The target of rapamycin signaling pathway regulates vegetative development, aflatoxin biosynthesis, and pathogenicity in Aspergillus flavus.

The target of rapamycin (TOR) signaling pathway is highly conserved and plays a crucial role in diverse biological processes in eukaryotes. Despite its significance, the underlying mechanism of the TOR pathway in Aspergillus flavus remains elusive. In this study, we comprehensively analyzed the TOR signaling pathway in A. flavus by identifying and characterizing nine genes that encode distinct components of this pathway. The FK506-binding protein Fkbp3 and its lysine succinylation are important for aflatoxin production and rapamycin resistance. The TorA kinase plays a pivotal role in the regulation of growth, spore production, aflatoxin biosynthesis, and responses to rapamycin and cell membrane stress. As a significant downstream effector molecule of the TorA kinase, the Sch9 kinase regulates aflatoxin B1 (AFB1) synthesis, osmotic and calcium stress response in A. flavus, and this regulation is mediated through its S_TKc, S_TK_X domains, and the ATP-binding site at K340. We also showed that the Sch9 kinase may have a regulatory impact on the high osmolarity glycerol (HOG) signaling pathway. TapA and TipA, the other downstream components of the TorA kinase, play a significant role in regulating cell wall stress response in A. flavus. Moreover, the members of the TapA-phosphatase complexes, SitA and Ppg1, are important for various biological processes in A. flavus, including vegetative growth, sclerotia formation, AFB1 biosynthesis, and pathogenicity. We also demonstrated that SitA and Ppg1 are involved in regulating lipid droplets (LDs) biogenesis and cell wall integrity (CWI) signaling pathways. In addition, another phosphatase complex, Nem1/Spo7, plays critical roles in hyphal development, conidiation, aflatoxin production, and LDs biogenesis. Collectively, our study has provided important insight into the regulatory network of the TOR signaling pathway and has elucidated the underlying molecular mechanisms of aflatoxin biosynthesis in A. flavus.

Salidroside Alleviates Furan-Induced Impaired Gut Barrier and Inflammation via Gut Microbiota-SCFA-TLR4 Signaling.

As a food contaminant that can be quickly absorbed through the gastrointestinal system, furan has been shown to disrupt the intestinal flora and barrier. Investigation of the intestinal toxicity mechanism of furan is of great significance to health. We previously identified the regulatory impact of salidroside (SAL) against furan-provoked intestinal damage, and the present work further explored whether the alleviating effect of SAL against furan-caused intestinal injury was based on the intestinal flora; three models, normal, pseudo-germ-free, and fecal microbiota transplantation (FMT), were established, and the changes in intestinal morphology, barrier, and inflammation were observed. Moreover, 16S rDNA sequencing observed the variation of the fecal flora associated with inflammation and short-chain fatty acids (SCFAs). Results obtained from the LC-MS/MS suggested that SAL increased furan-inhibited SCFA levels, activated the mRNA expressions of SCFA receptors (GPR41, GPR43, and GPR109A), and inhibited the furan-activated TLR4/MyD88/NF-κB signaling. Analysis of protein-protein interaction further confirmed the aforementioned effects of SAL, which inhibited furan-induced barrier damage and intestinal inflammation.

Understanding Regulatory Changes: Deep Learning in Sustainable Finance and Banking

This paper examines the regulatory impact on the European Banking Sector using advanced deep learning techniques to analyze the relationship between Sustainable Finance guidelines and the SX7P Index from January 2012 to December 2023. Utilizing Long Short-Term Memory Auto-encoder (LSTM-AE), Variational Autoencoder (VAE), and Convolutional Neural Network (CNN) for anomaly detection, the study compares anomalies and investigates their correlation with European Banking Authority (EBA) events and Sustainable Finance guidelines from January 2020 to December 2023. Through the analysis of 43 pertinent EBA documents, the research identifies patterns and variations in anomalies, assessing their association with regulatory changes. The results reveal significant anomalies aligning with regulatory events, indicating a potential causal relationship. Notably, the VAE methodology shows the strongest correlation between EBA Sustainable Finance events and anomalies. This research advances the understanding of deep learning applications in financial markets and offers valuable insights for policymakers and financial institutions regarding regulatory shifts in Sustainable Finance.

A foundational large language model for edible plant genomes

Significant progress has been made in the field of plant genomics, as demonstrated by the increased use of high-throughput methodologies that enable the characterization of multiple genome-wide molecular phenotypes. These findings have provided valuable insights into plant traits and their underlying genetic mechanisms, particularly in model plant species. Nonetheless, effectively leveraging them to make accurate predictions represents a critical step in crop genomic improvement. We present AgroNT, a foundational large language model trained on genomes from 48 plant species with a predominant focus on crop species. We show that AgroNT can obtain state-of-the-art predictions for regulatory annotations, promoter/terminator strength, tissue-specific gene expression, and prioritize functional variants. We conduct a large-scale in silico saturation mutagenesis analysis on cassava to evaluate the regulatory impact of over 10 million mutations and provide their predicted effects as a resource for variant characterization. Finally, we propose the use of the diverse datasets compiled here as the Plants Genomic Benchmark (PGB), providing a comprehensive benchmark for deep learning-based methods in plant genomic research. The pre-trained AgroNT model is publicly available on HuggingFace at https://huggingface.co/InstaDeepAI/agro-nucleotide-transformer-1b for future research purposes.

The primary carbon metabolism in cyanobacteria and its regulation.

Cyanobacteria are the only prokaryotes capable of performing oxygenic photosynthesis. Many cyanobacterial strains can live in different trophic modes, ranging from photoautotrophic and heterotrophic to mixotrophic growth. However, the regulatory mechanisms allowing a flexible switch between these lifestyles are poorly understood. As anabolic fixation of CO2 in the Calvin-Benson-Bassham (CBB) cycle and catabolic sugar-degradation pathways share intermediates and enzymatic capacity, a tight regulatory network is required to enable simultaneous opposed metabolic fluxes. The Entner-Doudoroff (ED) pathway was recently predicted as one glycolytic route, which cooperates with other pathways in glycogen breakdown. Despite low carbon flux through the ED pathway, metabolite analyses of mutants deficient in the ED pathway revealed a distinct phenotype pointing at a strong regulatory impact of this route. The small Cp12 protein downregulates the CBB cycle in darkness by inhibiting phosphoribulokinase and glyceraldehyde 3-phosphate dehydrogenase. New results of metabolomic and redox level analyses on strains with Cp12 variants extend the known role of Cp12 regulation towards the acclimation to external glucose supply under diurnal conditions as well as to fluctuations in CO2 levels in the light. Moreover, carbon and nitrogen metabolism are closely linked to maintain an essential C/N homeostasis. The small protein PirC was shown to be an important regulator of phosphoglycerate mutase, which identified this enzyme as central branching point for carbon allocation from CBB cycle towards lower glycolysis. Altered metabolite levels in the mutant ΔpirC during nitrogen starvation experiments confirm this regulatory mechanism. The elucidation of novel mechanisms regulating carbon allocation at crucial metabolic branching points could identify ways for targeted redirection of carbon flow towards desired compounds, and thus help to further establish cyanobacteria as green cell factories for biotechnological applications with concurrent utilization of sunlight and CO2.

Exploration of the miR-187-3p/CNR2 pathway in modulating osteoblast differentiation and treating postmenopausal osteoporosis through mechanical stress.

This study aimed to explore how mechanical stress affects osteogenic differentiation via the miR-187-3p/CNR2 pathway. To conduct this study, 24 female C57BL/6 mice, aged 8 weeks, were used and divided into four groups. The Sham and OVX groups did not undergo treadmill exercise, while the Sham + EX and OVX + EX groups received a 8-week treadmill exercise. Post-training, bone marrow and fresh femur samples were collected for further analysis. Molecular biology analysis, histomorphology analysis, and micro-CT analysis were conducted on these samples. Moreover, primary osteoblasts were cultured under osteogenic conditions and divided into GM group and CTS group. The cells in the CTS group underwent a sinusoidal stretching regimen for either 3 or 7 days. The expression of early osteoblast markers (Runx2, OPN, and ALP) was measured to assess differentiation. The study findings revealed that mechanical stress has a regulatory impact on osteoblast differentiation. The expression of miR-187-3p was observed to decrease, facilitating osteogenic differentiation, while the expression of CNR2 increased significantly. These observations suggest that mechanical stress, miR-187-3p, and CNR2 play crucial roles in regulating osteogenic differentiation. Both invivo and invitro experiments have confirmed that mechanical stress downregulates miR-187-3p and upregulates CNR2, which leads to the restoration of distal femoral bone mass and enhancement of osteoblast differentiation. Therefore, mechanical stress promotes osteoblasts, resulting in improved osteoporosis through the miR-187-3p/CNR2 signaling pathway. These findings have broad prospect and provide molecular biology guidance for the basic research and clinical application of exercise in the prevention and treatment of PMOP.

The possibilities of using foreign experience in tax regulation of socio-economic processes in Kazakhstan

The article analyzes the foreign experience of tax regulation of socio-economic processes in the EU countries and the possibility of its adaptation to the Kazakh economy. A significant analogy has been revealed in the main taxes in European countries with common political and economic interests, historically interacting in solving problems of global development. The mechanisms of the regulatory impact of taxes on the social and economic development of foreign countries are studied: VAT, excise taxes, corporate income tax, personal income tax. The advantages and disadvantages of applying various tax benefits and preferences, principles of taxation organization in the world taxation practice are revealed. Tax systems differ significantly in the number of taxes and their structure, organization and management methodology. Along with this, it is impossible not to recognize the significant similarity of the main taxes in countries geographically close to each other, having common political and economic interests, historically interacting in solving global development issues. The study of historical experience also allows us to assert the social significance of such a tax as VAT, given its application to the consumption of luxury goods. Taxation of these goods made it possible to partially make additional withdrawals of income from the well-to-do segments of the population and redistribute them, to a certain extent serving social equalization. The results of the study confirm the significant similarity of the instruments of tax regulation of socio-economic processes in different countries, caused by historical, geographical and economic-globalization factors. In turn, this allows us to use the advantages of foreign experience in Kazakhstan, adapting its individual elements to domestic conditions and taking into account the peculiarities of the development of the national economy and the specifics of the circumstances of the formation of the tax system of our state.

Does digital tax enforcement drive corporate digitalization? Evidence from the Golden tax project III in China: A pre-registered study

This pre-registered study executes the empirical design approved in the associated pre-registered report (Chen and He, 2024) to analyze the interaction between the tax enforcement and corporate behavior based on a digital perspective, with the Golden Tax Project III in China as the quasi-natural experiment. The study finds following conclusions: 1) the implementation of the Golden Tax Project III significantly promotes the firm digitalization. 2) the Golden Tax Project III has formed a regulatory impact on firm tax risk management, driving firms to promote digitalization for better tax risk management. 3) the promotion effect of the Golden Tax Project III on the firm digitalization helps to improve firms' total factor productivity. This article extends the economic consequences of tax digitalization and provides a new perspective for promoting high-quality economic development through the coordinated advancement of digital government and digital economy.

Organizational and economic mechanism of financing agricultural production in conditions of market transformation

The article is devoted to the problems of financial support for agricultural sector of economy of Kazakhstan. The goal is to study organizational and economic mechanism of financing agricultural industry in conditions of market transformation in order to develop recommendations for optimizing this system to improve access to financial sources for agricultural enterprises, develop financial instruments, and promote the expansion of market relations. Methods – abstract-logical, graphic, comparative analysis, generalization. Results - available financial resources for agro-industrial complex are analyzed: budgetary funds, investments, loans based on the use of various state financial assistance programs. The relevance of the study lies in the possibility of implementing individual proposals when developing rules for financing, lending, changing the criteria for subsidizing AIC, as well as the effective use of investment funds, loans and other financial resources. The need for additional attraction of internal and external investors has been identified. Conclusions - the state has a regulatory impact on the investment process by ensuring rational pricing, increasing flexibility of lending, tax and depreciation policies, stimulating business activity by providing investors with benefits, and highlighting priority areas of investment. It is necessary to monitor current and future factors of external and internal environment at the state, regional levels and enterprises. There is a need in the near and medium term for effective measures to financially support production and processing of competitive products, increase the variety of produced goods and maintain high quality at all stages of their production. Financial decisions are the basis for effective investment projects.

Exploring the Therapeutic Potential of Benzoxazolone Derivatives on the Circadian Clock: An In Silico and Hypothetical Approach

Objective: Pain conditions exhibit variations linked to circadian rhythms. Circadian rhythms, regulated by clock proteins, impact melatonin levels and immune functions. Melatonin, structurally similar to indomethacin, a non-steroidal anti-inflammatory drug, serves as an alternative in pain-related conditions. Literature suggests a correlation between melatonin-dependent regulation of circadian rhythm and reductions in pain complaints. 2(3<i>H</i>)-Benzoxazolone, known for its anti-inflammatory and analgesic properties, is a promising scaffold for drug design. In this study, pharmacophore analysis focused on benzoxazolone derivatives, evaluating their impact on clock proteins, and providing insights into potential chronotherapeutic implications. Methods: Molecular docking and dynamics simulations were conducted on CLOCK:BMAL1, PER1, PER2, CRY1, and CRY2 clock proteins using benzoxazolone and its 5-substituted derivatives. Molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) calculations were employed to analyze binding free energies. Benzoxazolone derivatives, especially 5-nitro-2-benzoxazolone and 5-fluoro-2-benzoxazolone, exhibited elevated binding affinities on clock proteins compared to melatonin and indomethacin, the reference molecules. The interaction profiles and stability of complexes were maintained throughout the simulations. Results: The results suggest a regulatory impact on CRY proteins, emphasizing their role in circadian rhythm and pain modulation. In addition, the benzoxazolone ring and its derivatives, structurally resembling the core structure of melatonin and indomethacin, demonstrate promising affinities on clock proteins. Conclusion: These findings provide preliminary data and hypothetically propose benzoxazolone derivatives as potential candidates for dual functionality in analgesic activity and circadian rhythm regulation, warranting further in vitro and clinical investigations.

Identification and differentiation of rice ferritin gene in two different chromosomes in several local Indonesian rice varieties

Abstract. Permatasari SE, Salamah A. 2024. Identification and differentiation of rice ferritin gene in two different chromosomes in several local Indonesian rice varieties. Biodiversitas 25: 2547-2555. The presence of ferritin protein in rice plants indicates a regulatory response to environmental iron stress. It prevents the destructive effects of the chain reaction resulting from Fe2+ accumulation in the cell. This study aimed to detect and identify the location of the ferritin gene (OsFER) in eight local rice varieties in Indonesia. OsFER2, as the target gene was amplified using PCR, visualized by electrophoresis, and then sequenced. The sequencing results were analyzed using DNA Baser, BioEdit, and ClustalX2. The predicted proteins were visualized using the SWISS-MODEL server, Rice Genome Annotation Project Database, and chromosome map tools. The results show that all rice varieties studied have 100% alignment similarity and OsFER characteristics on chromosome 11 at LOC_Os11g01530 and chromosome 12 at LOC_Os12g01530, which have striking differences. The complete protein structure of the complex is found on chromosome 12, while only a portion of alpha-helix ferritin is found on chromosome 11. Differences in the position of the ferritin gene at different chromosomes impact the functional changes in the ferritin protein as an iron homeostasis key role. The two genes show different characteristics and are located at different genomic positions, suggesting a potential regulatory impact on the level of iron stress resistance in Indonesian rice varieties.

Neuro-cardiac-guided transcranial magnetic stimulation: Unveiling the modulatory effects of low-frequency and high-frequency stimulation on heart rate.

Transcranial magnetic stimulation (TMS) is pivotal in the field of major depressive disorder treatment. Due to its unsatisfied response rate, an increasing number of researchers have turned their attention towards optimizing TMS site localization. Since the influence of TMS in reducing heart rate (HR) offers insights into its regulatory impact on the autonomic nervous system, a novel approach, called neurocardiac-guided TMS (NCG-TMS), has been proposed to pinpoint the brain region eliciting the maximal individual reduction in HR as a personalized optimal stimulation target. The present study intends to systematically explore the effects of stimulation frequency, left and right hemispheres, stimulation positions, and individual differences on HR modulation using the NCG-TMS method. In experiment 1, low-frequency TMS was administered to 30 subjects, and it was found that low-frequency NCG-TMS significantly downregulated HR, with more significant effects in the right hemisphere than in the left hemisphere and the prefrontal cortex than in other brain areas. In experiment 2, high-frequency NCG-TMS stimulation was administered to 30 subjects, showing that high-frequency NCG-TMS also downregulated HR and had the greatest modulatory effect in the right prefrontal region. Simultaneously, both experiments revealed sizeable individual variability in the optimal stimulation site, which in turn validated the feasibility of the NCG-TMS method. In conclusion, the present experiments independently replicated the effect of NCG-TMS, provided an effect of high-/low-frequency TMS stimulation to downregulate HR, and identified a right lateralization of the HR modulation effect.