Regulatory Systems Research Articles

Transactivation of the novel 5' cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax.

The mouse mammary tumor virus (MMTV) encodes a 5' element crucial for transcription of its genome along with the Rem/Rem-responsive element (RmRE) responsible for nuclear export of this unspliced RNA. Whether the 5' element is Rem-responsive or has any functional interaction with host/viral factors to facilitate MMTV gene expression was tested in this study. Our results reveal that the 5' element is non-responsive to Rem, but can be transactivated by both HIV Tat and HTLV-1 Tax activators. Reciprocally, MMTV could transactivate not only HIV TAR (similar to HTLV Tax), but also its 5' element. Furthermore, we reveal involvement of pTEFb, a general elongation factor associated with transactivation by Tat/Tax. This makes MMTV the first betaretrovirus to encode both Rem/RRE and Tat/TAR-Tax/TRE-like transcription regulatory systems. This study should enhance not only our understanding of retrovirus replication and virally-induced cancers/immunodeficiency syndromes, but also development of improved retroviral vectors for human gene therapy.

Environmental Antimicrobial Resistance: Implications for Food Safety and Public Health

Antimicrobial resistance (AMR) is a serious global health issue, aggravated by antibiotic overuse and misuse in human medicine, animal care, and agriculture. This study looks at the different mechanisms that drive AMR, such as environmental contamination, horizontal gene transfer, and selective pressure, as well as the severe implications of AMR for human and animal health. This study demonstrates the need for concerted efforts across the scientific, healthcare, agricultural, and policy sectors to control the emergence of AMR. Some crucial strategies discussed include developing antimicrobial stewardship (AMS) programs, encouraging targeted narrow-spectrum antibiotic use, and emphasizing the significance of strict regulatory frameworks and surveillance systems, like the Global Antimicrobial Resistance and Use Surveillance System (GLASS) and the Access, Watch, and Reserve (AWaRe) classification. This study also emphasizes the need for national and international action plans in combating AMR and promotes the One Health strategy, which unifies environmental, animal, and human health. This study concludes that preventing the spread of AMR and maintaining the effectiveness of antibiotics for future generations requires a comprehensive, multidisciplinary, and internationally coordinated strategy.

Association between immune cells and urticaria: a bidirectional Mendelian randomization study

Urticaria is characterized by transient itchy symptoms on the skin, usually accompanied by swelling, which is caused by mast cell activation leading to increased vascular permeability and dilation of the dermis. Urticaria involves recurrent activation of mast cells, T cells, eosinophils, and other immune cells around lesioned venules, with complex regulatory systems affecting mast cell functions, potentially contributing to urticaria pathogenesis. The direct causal relationship between immune cells and urticaria is currently unclear. To address this, our study utilized a bidirectional Mendelian randomization analysis, employing instrumental variables (IVs) associated with immune cells and urticaria, to investigate this causal relationship. First, by utilizing Genome-wide Association Study (GWAS) data, we identified 31 immunophenotypes associated with urticaria risk, with 18 increasing and 13 decreasing the risk. Through rigorous criteria, we identified 4 immunophenotypes that have a strong causal relationship with urticaria. Notably, HLA DR+ CD4+AC, CD45 on CD8br, and HLA DR on plasmacytoid dendritic cells were associated with an increased risk, while CD8dim NKT %lymphocyte was identified as a protective factor. Sensitivity analyses, including the MR-Egger intercept test, scatter plots, funnel plots, and leave-one-out analysis, supported the robustness of the findings. Reverse MR analysis suggested an inverse causal effect of urticaria on CD8dim NKT %lymphocyte, reinforcing the potential bidirectional nature of the relationship between urticaria and immune cell phenotypes. Our research substantiates the bidirectional causal relationship between immune cells and urticaria, thus benefiting for urticaria-targeted therapy development.

Research on the effect of multiple credit ratings from the perspective of financial regulatory systems in Chinese bond market.

This paper, starting from the effects of financial regulatory policies, considers the interaction between Chengxin_Moody and Lianhe_Fitch with the dual rating system and the multi-rating system, constructs a new ordered Logit model, and attempts to explore the impact of the Notice, the dual rating system and the multiple rating system on the probability of Chinese corporate bond defaults, rating upgrades, rating downgrades, and the magnitude of credit rating migrations. This study compares the effectiveness of different rating regulatory systems. Using nine thousand two hundred and sixty-two data of Chinese corporate bonds as the research samples. Empirical analysis and robustness test reveal the following findings: (1) The issuance of the Notice has a significant positive effect on the implementation of both the dual rating system and the multiple rating system, with a greater impact on the implementation of the multiple rating system; (2) The issuance of the Notice, along with the dual rating system and the multiple rating system, can all reduce the probability of corporate bond defaults, with the multiple rating system showing the best preventive effect against corporate bond defaults; (3) The dual rating system is more effective in promoting rating agencies to adjust rating behaviors, accurately correcting corporate bond ratings and effectively alleviating the issue of rating inflation. Competition among rating agencies intensifies rating shopping; (4) Under the dual rating system, rating agencies are more likely to expand the magnitude of credit rating upgrades and downgrades, enhancing the differentiation between high-quality corporate bonds and junk corporate bonds; (5) The selection of rating information from Chengxin_Moody and Lianhe_Fitch can appropriately adjust the degree of flexibility or tightening in response to rating regulatory systems. Chengxin_Moody demonstrates a more sensitive reaction compared to Lianhe_Fitch regarding the rating regulatory systems. This study provides valuable references for the formulation and evaluation of the effectiveness of Chinese corporate bond rating regulatory policies.

МЕДИКО-БІОЛОГІЧНІ ОСНОВИ ВПЛИВУ ФІЗИЧНИХ ВПРАВ НА ЗБЕРЕЖЕННЯ ЗДОРОВ’Я СТУДЕНТСЬКОЇ МОЛОДІ

The article examines the medical and biological basis of the influence of physical exercises on the health of student youth. Literary sources related to the topic of the study were analyzed. The problem is described in its general form, which concerns the way of life of modern student youth. It is noted that only in-depth knowledge of the medical and biological influence will help to form students' desire and motivation to engage in physical exercises, as well as to observe the basics of a healthy lifestyle. The morpho-functional changes occurring in the human body during physical exercises are revealed. The division of the organism's reserves into biological and social is presented. The functional effects of exercises on life expectancy is described. A comparative analysis of the influence of motor activity and hypokinesia on the human body was carried out. The basics of adaptation of individual body systems to physical exertion are revealed, namely: changes in the composition and physicochemical properties of blood and the circulatory system, functional effects of adaptation of the respiratory system, features of adaptation of the digestive and metabolic systems, as well as functional effects of adaptation of neurohumoral regulation systems. In the process of research, it was concluded that it is difficult to overestimate the medical and biological impact of physical exercises on the process of preserving the health of student youth, since physical activity affects the human body in a complex way, on all its systems, processes of exchange and accumulation of functional reserves. It was concluded that with the help of physical exercises you can achieve many positive effects and affect the overall life expectancy of a person. Prospects for further research in this direction are seen in determining the level of awareness of student youth in the issues of medical and biological bases of the influence of physical exercises on preserving their own health, as well as finding new approaches for working with students in this direction in order to achieve the formation of sustainable motivation for physical activities exercises and adherence to the basics of a healthy lifestyle.

Building permits-control of type IV pilus assembly by PilB and its cofactors.

Many bacteria produce type IV pili (T4P), surfaced-exposed protein filaments that enable cells to interact with their environment and transition from planktonic to surface-adapted states. T4P are dynamic, undergoing rapid cycles of filament extension and retraction facilitated by a complex protein nanomachine powered by cytoplasmic motor ATPases. Dedicated assembly motors drive the extension of the pilus fiber into the extracellular space, but like any machine, this process is tightly organized. These motors are coordinated by various ligands and binding partners, which control or optimize their functional associations with T4P machinery before cells commit to the crucial first step of building a pilus. This review focuses on the molecular mechanisms that regulate T4P extension motor function. We discuss secondary messenger-dependent transcriptional or post-translational regulation acting both directly on the motor and through protein effectors. We also discuss the recent discoveries of naturally occurring extension inhibitors as well as alternative mechanisms of pilus assembly and motor-dependent signaling pathways. Given that T4P are important virulence factors for many bacterial pathogens, studying these motor regulatory systems will provide new insights into T4P-dependent physiology and efficient strategies to disable them.

Installation and Management of Regulation Systems of a Hydroelectric Power Plant with Doubly Fed Induction Generator and Results of a Case Study

Installation and Management of Regulation Systems of a Hydroelectric Power Plant with Doubly Fed Induction Generator and Results of a Case Study

Implementation of thermoelectric wall systems for sustainable indoor environment regulation in buildings through numerical and experimental performance analysis

With buildings representing a substantial portion of global energy consumption, exploring alternatives to traditional fossil fuel-based heating and cooling systems is critical. Thermoelectricity offers a promising solution by converting temperature differentials into electrical voltage or vice versa, enabling efficient indoor thermal regulation. This paper presents a comprehensive investigation into the integration of thermoelectric wall systems for sustainable building climate control through numerical simulations and experimental analyses. Numerical simulations using computational fluid dynamics (CFD) techniques were conducted to model fluid flow and heat transfer within the thermoelectric wall systems under various operating conditions. These simulations provided insights into the system’s thermal behavior, which were validated through experimental setups designed to measure temperature differentials, airflow rates, and power consumption. The results showed that power consumption is directly correlated with electrical current, ranging from 0.19 W to 77.4 W as the current increased from 0.1 A to 2 A. Additionally, the heat absorbed by the system increased significantly with electrical current, by 706–1044%, depending on the air velocity. The thermal energy released from the hot side of the thermoelectric modules also rose substantially, ranging from 9850 to 5285% with increasing electrical current, and from 275 to 51% with higher air velocities. Moreover, increasing air velocity led to a 6.78–9.37% reduction in power consumption for currents between 0.1 A and 2 A. The coefficient of performance (COP) analysis revealed that optimizing both electrical current and air velocity is essential for maximizing system efficiency. While fan power consumption reduces COP at higher air velocities, neglecting fan power consumption results in COP improvements ranging from 6.5 × 10⁻⁴ to 49.0%. These findings highlight the potential of thermoelectric wall systems to enhance indoor comfort and energy efficiency in buildings.

World Health Organization Guidance on Health Practitioner Regulation: An Overview

ABSTRACT: The World Health Organization has released its first comprehensive Guidance document on health practitioner regulation, addressing a critical gap in global health policy. This Commentary provides an overview of the Guidance, which aims to support countries in strengthening their regulatory systems for health practitioners. The Guidance, developed through a rigorous process involving a literature review and expert consultation, covers a broad range of health practitioners and focuses on optimizing their utilization to meet population health needs. Key highlights include the description of the global regulatory landscape, identification of regulatory challenges in all societies, and policy considerations to realize dynamic, effective, and agile regulation. The COVID-19 pandemic is cited as an important example of a catalyst for regulatory reforms that enhanced workforce availability and access. This paper, co-authored by members of the World Health Organization Technical Expert Group, emphasizes the importance of aligning regulatory systems with broader health workforce and system priorities, adopting a risk-based approach, and addressing implementation gaps. It encourages policymakers, regulators, and researchers to use the Guidance to assess and update their regulatory systems and to generate more robust evidence on the impact of health practitioner regulation on health outcomes.

When thinking about pain contributes to suffering: the example of pain catastrophizing

Abstract The extensive literature on the potent role negative thoughts about pain have on the experience of pain and pain-related suffering has documented associations with important neurobiological processes involved in amplifying nociceptive signals. We focus this review on pain catastrophizing (pCAT)— appraisals of pain as threatening, overwhelming, and unmanageable— and review the evidence that these thoughts are learned in childhood through experience and observation of others, particularly caretakers and parents. For children who have learned pCAT, repeated exposures to pain over time activate pCAT and likely contribute to further amplification of pain through changes in the neurobiological pain regulatory systems, which overlap with those regulating the stress response. We propose that repeated pain and stress exposures throughout childhood, adolescence, and into adulthood alter the neurobiology of pain via a repetitive positive feedback loop that increases risk for heightened pain sensitivity over time with repeated exposures. At some point, often precipitated by an acute episode of pain and possibly influenced by allostatic load, pCAT contributes to persistence of episodic or acute pain and exacerbates pain-related suffering. This developmental trajectory is not inevitable, as the impact of pCAT on pain and pain-related suffering can be influenced by various factors. We also present future directions for work in this area.

A narrative review of veterinary pharmacovigilance situations and prospects in East African countries

BackgroundVeterinary pharmaceuticals must be safe and effective for treating and preventing diseases in animal sectors. Strict adherence to regulations at every stage of production, storage, and administration is necessary as the global sector grows in order to lower the possibility of adverse veterinary drug events. Strong pharmacovigilance regulatory systems are critical in monitoring and managing safety concerns related with veterinary pharmaceuticals.ObjectiveThis review aimed to investigate the implementation of veterinary pharmacovigilance, collaborative initiatives, and reporting practices within the veterinary sector across East African countries.MethodsA thorough search was performed using online platforms such as Google Scholar, PubMed, the Web of Sciences, and regulatory Web sites. The search strategies relied heavily on selecting relevant published findings related to veterinary pharmacovigilance status, veterinary adverse drug event reporting practice, and collaborative efforts in veterinary pharmaceutical sectors within the East African landscape. This article search approach confirmed the inclusion state of veterinary pharmacovigilance and associated collaborative initiatives in the region.ResultsIn comparison to more developed regions, the review indicated that the veterinary pharmacovigilance system in East African countries was still in its early state. A strong legislative foundation and a large commitment from the veterinary profession are needed to establish a nationwide veterinary pharmacovigilance system. The review reveals a significant lack of consistency in the infrastructure of veterinary pharmacovigilance among the countries of East Africa. Tanzania, Kenya, and Ethiopia have some institutional processes for veterinary pharmaceutical safety, but they lack thorough documentation, which suggests that this systems still require improvement. The analysis emphasizes how inadequate the reporting systems are for adverse veterinary medication events in the majority of East African nations. Given the challenges East Africa faces, customized strategies are required to guarantee the safety and oversight of veterinary medications and improve veterinary pharmacovigilance. For systems to be more effective, veterinary pharmaceutical legal frameworks must be strengthened and stakeholder collaboration must be improved. Stakeholders include legislators, law enforcement, customs officials, regulatory organizations, scientists, pharmaceutical businesses, veterinarians, farmers, and the general public.ConclusionA multidisciplinary strategy is needed to solve current gaps in veterinary pharmacovigilance and improve overall veterinary drug safety in East Africa. It is feasible to create more reliable methods for tracking and guaranteeing the safety of veterinary medications by combining the efforts of numerous stakeholders, including as legislators, regulatory agencies, veterinary practitioners, and the general public.

The Role of Carbon Trading in Climate Change Mitigation: A Juridical Analysis of Policies and Regulations in Environmental Law in Indonesia

This paper examines the role of carbon trading in climate change mitigation through a juridical analysis of Indonesia's environmental law and regulatory frameworks. Carbon trading has emerged as a critical tool for reducing greenhouse gas emissions, but its success depends on the strength of the legal and regulatory systems supporting it. By analyzing Indonesia’s Carbon Economic Value policy, environmental laws, and international commitments such as the Paris Agreement, this study identifies key regulatory gaps, overlapping jurisdictional issues, and enforcement challenges. The findings highlight the need for stronger monitoring, reporting, and verification mechanisms, as well as clearer regulatory frameworks to ensure the effectiveness of carbon trading in Indonesia. Recommendations are made to enhance institutional capacity, align national policies with international standards, and promote private sector participation. These improvements are crucial for achieving Indonesia’s emissions reduction targets and contributing to global climate change efforts.

Discrepancies in Australian jurisdiction-based regulation of invasive plants

Abstract Effective regulation is essential for preventing the establishment of new invasive plants and managing the environmental, social, and economic impacts of those already established. Invasive plants are regulated by jurisdictions at a variety of local, regional, national, and international levels. Enhanced coordination of policy and regulations has been identified as a key strategy for addressing the impacts of invasive species (IPBES 2023; Pluess et al. 2012); however, coordination between jurisdictions, and even within jurisdictions, is not always considered. To review regulatory coordination in Australia, we compiled a comprehensive dataset of noxious weeds (defined as invasive plants and potentially invasive plants with controls specified in regulation) in each Australian jurisdiction (i.e., State or Territory). We found that jurisdictions on average shared c. 67% (SD = 15%) of noxious weed listings. Neighbouring jurisdictions were not more similar than separated jurisdictions in their noxious weed listings. There were significant differences in the biogeographic native ranges of noxious weeds between jurisdictions, with species native to temperate Asia being most frequently listed overall. The predominant likely entry pathway for noxious weeds in Australia was the ornamental trade. Listings were primarily dedicated to proactive control, prohibiting the cultivation of noxious weeds to avoid their naturalisation. There were 415 noxious weeds regulated in a harmonious manner across jurisdictions. However, there were 327 noxious weeds regulated by jurisdictions in a discordant manner, potentially leaving neighbouring jurisdictions vulnerable to invasion. We suggest jurisdictions reassess the regulation of these 327 discordant noxious weeds in Australia and utilise a national taxonomic standard to avoid problematic synonyms. Improved cohesion of policies could be achieved through wider adoption of existing regulatory systems and co-development of regulations between government and industry.

A Comprehensive Review of Thyroid Eye Disease Pathogenesis: From Immune Dysregulations to Novel Diagnostic and Therapeutic Approaches.

Thyroid eye disease is a complex inflammatory disorder of the orbit that has gained tremendous interest over the past years, and numerous scientific efforts have been deployed to elucidate its pathophysiology for novel drug development. Our manuscript will delve into the molecular dysregulations involved in the pathogenesis of thyroid eye disease that led to its clinical manifestations. Abnormalities within the apoptotic pathway, inflammatory cascade, and autoimmune regulatory systems will be covered. We will further discuss the challenges involved in its diagnosis and management and provide a summary of the current diagnostic tools (i.e., molecular biomarkers, diagnostic scores) from the perspective of clinicians. Finally, our comprehensive literature review will provide a thorough summary of most recent preclinical and clinical studies around the topic of thyroid eye disease, with an emphasis on the manuscripts published within the last five years. We believe our manuscript will bring novelty within the field by bridging the fundamental sciences with the clinical aspect of this disease. This review will be a great tool for clinicians in better understanding the pathogenesis of thyroid eye disease while providing an outlook on future perspectives (i.e., liquid biopsies, artificial intelligence).

Involvement of E3 Ubiquitin Ligases in Viral Infections of the Human Host.

Viral infections are one of the principal causes of global primary health crises, with increased rate of infection and mortality demonstrated by the newer progeny of viruses. Viral invasion of the host involves utilization of various cellular machinery. Ubiquitination is one of a few central regulatory systems used by viruses for establishment of the infections in the host. Members of the ubiquitination system are involved in carrying out proteasomal degradation or functional modification of proteins in numerous cellular processes. E3 ubiquitin ligases play a major role in this system through recognition and recruitment of protein substrates and catalyzing the transfer of ubiquitin to these substrates. The versatility of ubiquitin ligases frequently makes them useful tools for the viruses, for either utilizing or degrading other cellular machineries, for carrying out their multiplication or inactivating the defensive strategies of the host. Therefore, these ligases are important targets for aiming at major pathways causing viral protein degradation or functional modification of the infection process. In this review, we have discussed the role and mechanism of different types of ubiquitin ligases in the context of infections of mainly human viruses, highlighting the viral proteins directly interacting with the ligases. Knowledge about these direct interactions is central in understanding the ubiquitin-dependent processes. This comprehensive account may also be beneficial for pharmaceutical exploration of E3 ligase-based broad-spectrum antiviral treatment.

Traceability for strengthening supply chain systems and enhancing real-time visibility: Focus of NAFDAC on advancing vaccine traceability in Nigeria

This study explores the successful implementation of activities aimed at scaling traceability for COVID-19 and routine immunization (RI) vaccines to the local government area and selected healthcare facilities in Nigeria, funded by the Bill and Melinda Gates Foundation. The study was executed by the National Agency for Food and Drug Administration and Control (NAFDAC) and sought to enhance supply chain systems by deploying advanced traceability mechanisms and ensuring real-time stock visibility. The article discusses the accomplishments, challenges, and regulatory framework of NAFDAC, emphasizing GS1 technology-driven traceability, and presents the results of the field scanning activities conducted in July 2023. The approach involved a phased public sector pilot, showcasing the feasibility and challenges of tracking vaccine movement through the supply chain. The result shows the detection of 43 unique products across 1022 facilities from a total of 110,113 scans, offering valuable insights into vaccine distributions. The strategic goals of the project aligned with developing safety surveillance systems in low- and middle-income countries (LMICs) to facilitate patient access to global health products. Similarly, significant improvement in traceability through automated data capture (barcode scanning) and expanded coverage for COVID-19 and selected RI vaccines in Nigeria was found. Against this background, the information derived from this report will build confidence in patients regarding vaccine authenticity, establish a transparent and robust supply chain, and foster pharmacovigilance capability through integration with the track-and-trace systems. Thus, the study provides invaluable insights and opportunities for global health practitioners, policymakers, and researchers to incorporate track-and-trace into regulatory systems by other national regulatory authorities.

Legal Standards for Selenium Enriched Foods and Agricultural Products: Domestic and International Perspectives.

Background/Objectives: Selenium is indispensable for human health, yet vast regions worldwide grapple with selenium-deficient soils, rendering dietary intake a critical avenue for supplementation. This narrative review aims to systematically examine and compare domestic and international regulations and standards related to selenium enrichment, providing insights to enhance regulatory frameworks and standardization within the selenium-enrichment industry. Methods: From June to September 2024, we conducted a comprehensive search of official websites belonging to international organizations (e.g., Codex Alimentarius Commission, European Union) and governmental agencies of countries such as China and the United States. Keywords, like "selenium enrichment", "selenium standards", and "selenium detection methods", were employed to identify pertinent regulations, standards, and guidelines encompassing intake benchmarks, detection methodologies, product specifications, technical guidelines for production, labeling requirements, and certification management norms. Results: Our analysis reveals several challenges within the current selenium-enriched regulatory and standardization systems, including inconsistent product determination criteria and limit settings, incomplete technical guidelines for selenium-enriched agricultural production, and a lack of unified regulations for labeling selenium-enriched agricultural products. Conclusions: These findings underscore the need for harmonization of standards and enhanced regulatory oversight. To address these issues, we recommend bolstering safety risk assessments for selenium-enriched agricultural products, establishing and refining a comprehensive standard system for selenium-enriched agriculture, and intensifying quality and safety supervision. This study offers a valuable reference for policymakers and stakeholders to promote the sustainable development of the selenium-enrichment industry.

Functional analysis of the extraplastidial TRX system in germination and early stages of development of Arabidopsis thaliana

A series of processes occur during seed formation, including remarkable metabolic changes that extend from early seed development to seedling establishment. The changes associated with processes initiated mainly after seed imbibition are usually characterized by extensive modification in the redox state of seed storage proteins and of pivotal enzymes for reserve mobilization and usage. Such changes in the redox state are often mediated by thioredoxins (TRXs), oxidoreductase capable of catalyzing the reduction of disulfide bonds in target proteins to regulate its structure and function. Here, we analyzed the previously characterized Arabidopsis mutants of NADPH-dependent TRX reductase types A and B (ntra ntrb), two independent mutant lines of mitochondrial thioredoxin o1 (trxo1) and two thioredoxin h2 (trxh2) mutant lines. Our results indicate that plants deficient in the NADPH dependent thioredoxin system are able to mobilize their reserves, but, at least partly, fail to use these reserves during germination. TRX mutants also show decreased activity of regulatory systems required to maintain redox homeostasis. Moreover, we observed reduced respiration in mutant seeds and seedlings, which in parallel with an impaired energy metabolism affects core biological processes responsible for germination and early development of TRX mutants. Together, these findings suggest that the lack of TRX system induces significant change in the respiration of seeds and seedlings, which undergo metabolic reprogramming to adapt to the new redox state.

Strong financial regulation and enterprise digital innovation: promoting or inhibiting?

ABSTRACT Modern financial regulatory systems are vital in bridging the gap between digital and real economies. In this context, enterprises have the opportunity to achieve digital innovation transformation. This study examines the causal relationship between strong financial regulation and enterprise digital innovation using a quasi-natural experiment, focusing on the ‘Guiding Opinions on Regulating the Asset Management Business of Financial Institutions’ (NAMR). We observed a significant improvement in enterprises’ level of digital innovation after the NAMR implementation. Channel analysis confirms the micro-mechanisms of strong financial regulation, eased corporate financing constraints, increased R&D investment, and digital innovation. Furthermore, digital innovation driven by strong financial regulation can significantly improve corporate profitability. We also found that the positive effect of strong financial regulation on enterprise digital innovation is particularly significant in non-state-owned enterprises, highly competitive industries, and regions with high financial development levels. This study expands the understanding of how strong financial regulation affects enterprises’ digital innovation, with practical significance for understanding the relationship between financial regulation, corporate financial investment, and innovation decision-making.

Fpa (YlaN) is an iron(II) binding protein that functions to relieve Fur-mediated repression of gene expression in Staphylococcus aureus.

Iron (Fe) is a trace nutrient required by nearly all organisms. As a result of the demand for Fe and the toxicity of non-chelated cytosolic ionic Fe, regulatory systems have evolved to tightly balance Fe acquisition and usage while limiting overload. In most bacteria, including the mammalian pathogen Staphylococcus aureus, the ferric uptake regulator (Fur) is the primary transcriptional regulator controlling the transcription of genes that code for Fe uptake and utilization proteins. Fpa (formerly YlaN) was demonstrated to be essential in Bacillus subtilis unless excess Fe is added to the growth medium, suggesting a role in Fe homeostasis. Here, we demonstrate that Fpa is essential in S. aureus upon Fe deprivation. Null fur alleles bypassed the essentiality of Fpa. The absence of Fpa abolished the derepression of Fur-regulated genes during Fe limitation. Bioinformatic analyses suggest that fpa was recruited to Gram-positive bacteria and, once acquired, was maintained in the genome as it co-evolved with Fur. Consistent with a role for Fpa in alleviating Fur-dependent repression, Fpa and Fur interacted in vivo, and Fpa decreased the DNA-binding ability of Fur in vitro. Fpa bound Fe(II) in vitro using oxygen or nitrogen ligands with an association constant that is consistent with a physiological role in Fe homeostasis. These findings have led to a model wherein Fpa is an Fe(II) binding protein that influences Fur-dependent regulation through direct interaction.IMPORTANCEIron (Fe) is an essential nutrient for nearly all organisms. If Fe homeostasis is not maintained, Fe may accumulate in the cytosol, which can be toxic. Questions remain about how cells efficiently balance Fe uptake and usage to prevent overload. Iron uptake and proper metalation of proteins are essential processes in the mammalian bacterial pathogen Staphylococcus aureus. Understanding the gene products involved in the genetic regulation of Fe uptake and usage and the physiological adaptations that S. aureus uses to survive in Fe-depleted conditions provides insight into pathogenesis. Herein, we demonstrate that the DNA-binding activity of the ferric uptake regulator transcriptional repressor is alleviated under Fe limitation, but uniquely, in S. aureus, alleviation requires the presence of Fpa.