Nutrition plays a fundamental role in maintaining human health and modulating disease risk across the life course. This narrative review synthesizes contemporary evidence on the clinical significance of macronutrients, including carbohydrates, proteins, and fats, and micronutrients, including vitamins and minerals, establishing nutritional balance as a central determinant of human health, disease susceptibility, and therapeutic efficacy. These nutrient categories function within an integrated metabolic network in which macronutrients provide energy and structural substrates, while micronutrients serve as essential cofactors and regulatory agents in enzymatic, hormonal, and cellular signalling processes. The synthesis demonstrates that nutritional imbalance, arising from either deficiency, such as iron-deficiency anaemia and vitamin D insufficiency, or excess, including high intakes of refined carbohydrates and saturated fats, constitutes a major contributor to global disease burden, particularlythe phenomenon described as the double burden of malnutrition. In response to these challenges, the review highlights the role of evidence-based nutritional therapy, encompassing established dietary patterns such as the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets, as well as the clinical implementation of medical nutrition therapy in chronic disease management. It further emphasizes a paradigmatic shift from population-level dietary recommendations toward precision nutrition, an emerging framework that integrates nutrigenomics, metabolomics, and gut microbiome profiling to inform personalized dietary interventions. By conceptualizing nutrition as a dynamic and interactive system, this review offers a comprehensive perspective that integrates biochemical mechanisms with individualized clinical care, positioning nutritional balance as a foundational component of contemporary preventive and therapeutic medicine.

Cadmium (Cd) contamination poses serious ecological and health risks, and although hyperaccumulator plants offer a sustainable phytoremediation strategy, their field performance is often constrained by low biomass and limited tolerance under metal stress. Recent studies indicate that rare earth elements (REEs), especially lanthanum (La³+) and cerium (Ce³+), can influence multiple plant and soil processes that are relevant to Cd phytoextraction. Low-dose REEs have been reported to stimulate plant growth, modulate phytohormone signaling, enhance root development, and support antioxidant responses, which may collectively improve Cd tolerance and uptake. REEs can also modify soil chemical conditions and shape rhizosphere microbial communities that contribute to Cd mobilization. In some model species, REE exposure has been associated with the induction of systemic endocytosis, a process that may provide an additional pathway for the uptake of external ions, including Cd. Here, we synthesize current evidence on how REEs interact with plant physiological processes, soil Cd speciation, and rhizosphere microbial function, and we summarize emerging insights into REE-induced systemic endocytosis. We further propose a conceptual REE–plant–soil–microbe interaction framework to integrate these regulatory pathways. Finally, we discuss key uncertainties and research needs related to mechanism verification, ecological safety, and field applicability. This review provides a foundation for evaluating the potential of REEs as regulatory agents to enhance Cd phytoremediation using hyperaccumulator plants.

This study aimed to investigate the role and clinical significance of RHNO1 in nonsmall cell lung cancer (NSCLC). By analyzing clinical samples and cell lines, we assessed RHNO1 expression and its correlation with clinicopathological features and patient prognosis, validating its potential as a diagnostic and prognostic biomarker. Furthermore, in vitro and in vivo experiments revealed the functional role of RHNO1 in NSCLC progression and its molecular interaction with the NF-κB signaling pathway, defining the regulatory mechanism of the "RHNO1-NF-κB axis." In parallel, we developed a chitosan-based delivery system (CS-1@RHNO1), which markedly enhanced the loading efficiency and targeting specificity of RHNO1 regulatory agents, enabling precise modulation of the "RHNO1-NF-κB axis." Our findings demonstrate that RHNO1 functions not only as a potential diagnostic and prognostic marker but also as a promising therapeutic target, while the CS-1@RHNO1 system provides a novel strategy for targeted delivery in NSCLC. Collectively, this study offers new theoretical insights and technological advances for understanding NSCLC pathogenesis and developing targeted therapies.

Purpose This paper aims to examine the relationship between domestic enforcement and textual attributes of risk factor disclosures of foreign firms listed in the USA. Using an international sample of American depositary receipts (ADR) firms, it analyzes how the level of domestic enforcement influences the readability and tone of the information disclosed in the risk factors section of Form 20-F. Design/methodology/approach The analysis spans the period from 2000 to 2023 and, following this procedure, includes 1,343 ADR firm-year observations across 30 countries. The authors use multiple regression and conduct robust tests to confirm their analysis. Findings The results suggest that a higher level of enforcement is associated with lower readability and a more biased tone in risk factor disclosures. This suggests that although domestic enforcement aims to enhance information quality, it may lead to more complex and potentially strategic communications. The authors argue that this effect may arise both from the need for strict compliance with detailed regulations and the pressure to meet the expectations of various market participants. Research limitations/implications The measures of readability and tone, although widely used in the accounting and finance literature, have limitations and may not fully reflect the quality of textual attributes. Practical implications This study contributes to investors by providing further evidence of the direct effect of domestic legal enforcement on textual attributes in accounting, which directly affects their judgments about companies’ disclosures. Moreover, the results contribute to regulatory agents with evidence that domestic legal enforcement may affect the quality of companies’ disclosures, providing them with insights for adopting mechanisms of compliance with legislation. Originality/value The results contribute to previous international accounting literature by empirically demonstrating how institutional factors influence corporate communication in international markets. Additionally, they provide valuable insights for investors and regulators, highlighting the potential negative impacts of excessive regulation on the clarity of disclosed information, a topic that has rarely been discussed in the literature from both theoretical and practical perspectives.

This study reports the isolation of two natural compounds, zearalenone and hyrtiosulawesine, from the endophytic fungus Penicillium chrysogenum isolate SR192 which is associated with the invasive plant species Solanum rostratum . In general, both isolated compounds exhibited a dose-dependent stimulatory effect on the growth of four weed species when concentrations ranging from 5 to 100 µg mL-1 were tested. However, suppressive effects were observed when the concentration was increased to 500 µg mL-1, suggesting a biphasic response. Our findings indicate that these compounds have the potential to be further investigated as environment-friendly plant growth regulatory agents.

Exploring LAT-derived miRNAs as regulatory agents of EphrinA3 in glioblastoma multiforme.

Artificial intelligence (AI) and quantum computing will change the course of new drug discovery and approval. By generating computational data, predicting the efficacy of pharmaceuticals, and assessing their safety, AI and quantum computing can accelerate and optimize the process of identifying potential drug candidates. In this viewpoint, we demonstrate how computational models obtained from digital computers, AI, and quantum computing can reduce the number of laboratory and animal experiments; thus, computer-aided drug development can help to provide safe and effective combinations while minimizing the costs and time in drug development. To support this argument, 83 academic publications were reviewed, pharmaceutical manufacturers were interviewed, and AI was used to run computational data for determining the toxicity of collagen as a case example. The research evidence to date has mainly focused on the ability to create computational in silico data for comparison to actual laboratory data and the use of these data to discover or approve newly discovered drugs. In this context, “in silico” describes scientific studies performed using computer algorithms, simulations, or digital models to analyze biological, chemical, or physical processes without the need for laboratory (in vitro) or live (in vivo) experiments. Digital computers, AI, and quantum computing offer unique capabilities to tackle complex problems in drug discovery, which is a critical challenge in pharmaceutical research. Regulatory agents will need to adapt to these new technologies. Regulatory processes may become more streamlined, using adaptive clinical trials, accelerating pathways, and better integrating digital data to reduce the time and cost of bringing new drugs to market. Computational data methods could be used to reduce the cost and time involved in experimental drug discovery, allowing researchers to simulate biological interactions and screen large compound libraries more efficiently. Creating in silico data for drug discovery involves several stages, each using specific methods such as simulations, synthetic data generation, data augmentation, and tools to generate, collect, and affect human interaction to identify and develop new drugs.

IntroductionThis study aimed to identify the role of aquaporin‑4 (AQP4) in uveitis, and screen for a novel therapeutic target of potential.MethodsAQP4 knockout mice were applied in this study. The manifestations of mice oculi and inflammatory factors were monitored and compared between the conditions of wild-type and endotoxin-induced uveitis (EIU).ResultsIn the mouse retina, immunofluorescence showed that AQP4 is mainly expressed by Müller cells. The results showed that EIU caused obvious inflammatory reactions in the oculi of wild-type mice, including the ascendence of vitreous cells and thickened retinal layers, compared with the AQP4 knockout mice. According to the scoring criteria of the anterior segment, the ciliary congestion, hypopyon, posterior adhesion of iris, and anterior chamber cell counts were significantly deteriorated by EIU modeling, between which the AQP4 ablation attenuated the inflammation. Further investigations were performed to explore the information on inflammatory factors: The pro-inflammatory cytokines, IL-1β, IL-6, and TNF-α were increased in the mice oculi under EIU, while they were maintained in lower levels by AQP4 ablation; The inflammation regulatory agents, cd-20 and arg-1, were massively increased in the mice oculi by EIU modeling, while AQP4 ablation further enhanced their expression level.ConclusionAQP4 is a participant in EIU, where it promotes inflammation via reconstructing the balance of the ocular immune condition. The results of the current study highlight the potential of AQP4 to become a therapeutic target in the eyes for uveitis.

The growing interest in blockchain and cryptocurrencies is driving the research and use of attacks that can target different parts of the system. For example, some attacks target the network or the system itself through sharding, DDOS attacks, or wormhole attacks. Some other attacks, such as the 51% attack, aim to acquire a majority share of the production capacity in the system. With these powers, an attacker or group of attackers can rewrite the blockchain at will, perform double-spend attacks, or censor any entity they choose. Other attack types combine multiple attack vectors into one, building a competitive chain using unknown participants that were previously isolated from the network via an obfuscation attack. Other attack methods also exist through exploitation of smart contracts/decentralized applications bugs. Most decentralized applications are susceptible to favouritism attacks, where an attacker unfairly exploits information related to events that have not yet been recorded on the blockchain. Provided list of attack vectors, despite its inexhaustibility, is aimed to emphasize the fact that blockchain systems have vulnerabilities. The presence of the latter indicates the need to promote detailed information about blockchain security mechanisms through their simulation. This article is designed to explore the possibilities of modeling the most common types of attacks on the blockchain by using an organization-oriented modeling method, as well as to show in practice the method of modeling regulatory mechanisms through the reproduction of special meta-agents – regulatory agents – responsible for the coordinated operation of the entire system, and in particular contributing to resistance attacks on the network by checking the proposed transactions for compliance with the rules laid down in them, which results in endorsement or rejection of the former. Further research may involve modeling the motivation of system agents in the event of rejection of transactions by regulatory agents.

Regulatory Compliance Agents powered by artificial intelligence are transforming how enterprises navigate increasingly complex regulatory environments. These intelligent systems autonomously monitor, interpret, and implement regulatory requirements across multiple jurisdictions, offering unprecedented efficiency improvements in compliance management. By leveraging advanced natural language processing and machine learning technologies, these agents demonstrate remarkable capabilities in processing regulatory documents, identifying relevant changes, and translating abstract requirements into concrete operational controls. Implementation across diverse industries including financial services, healthcare, energy, and pharmaceuticals shows consistent benefits in reducing compliance costs, improving accuracy, and accelerating regulatory response times. While offering transformative potential, these solutions face challenges related to interpretive accuracy, regulatory acceptance, and technical integration. Organizations implementing these systems must carefully address governance frameworks and human-agent collaboration models to maximize benefits while maintaining appropriate oversight. As regulatory landscapes continue to evolve, AI-powered compliance agents represent not merely technological innovations but strategic assets that fundamentally reshape how organizations approach compliance management, enabling more proactive, efficient, and comprehensive regulatory navigation in an increasingly regulated global economy.

Abstract This article adopts the lens of ingroup bias to study why regulatory firms tasked with enforcing regulatory compliance may underperform in their duties. We theorize that ingroup bias can lead regulatory agents to grant unwarranted trust to ingroup clients with whom they share salient characteristics, resulting in less stringent inspections for these clients compared to outgroup clients. We further examine how this effect is moderated by inspectors' professionalism, a human capital dimension reflecting an individual's engagement with their profession and internalization of its norms and standards. Using a difference‐in‐differences approach on micro‐data tracking 86 inspectors across 24,650 inspections of 462 vessels at a marine inspection firm, we find compelling evidence of ingroup bias and show that inspectors' professionalism mitigates its impact on regulatory enforcement stringency.

Harnessing the potential of long non-coding RNAs in the pathophysiology of Alzheimer's disease.

This article presents a systematic review of sustainable watershed management at the international level. Based on the risk regulation approach, this review approaches the specific gaps in the literature related to relevant issues outlining the international freshwater resources socio-environmental regulation issue, especially in regards to its sociological dimensions: the organizational capabilities of agents involved in regulatory efforts, issue-implicit challenges, and regulatory effort-generated socio-environmental risks. The study identifies the reflexive components of the involved institutions, outlines the deployment of organizational processes in normative regulatory components, and explores the modalities for addressing change and complexity in the regulatory field. A corpus of 64 articles published in the Web of Science (WoS) and Scopus databases between 2021 and 2024 was analyzed, and the following findings are demonstrated: (1) regulatory requirements emerge across the three dimensions due to sociological factors, with the need for broad-ranging coordination capacities and socio-technical improvements highlighted, (2) while high political–technical capacities are exhibited by regulatory agents in the field of study, significant regulatory challenges persist, complicating the sustainable management of watersheds, and (3) decision-making based on socio-environmental risks is deemed feasible within the field of study, enabling advancements in techno-scientific and socio-political areas, although achieving this is considered challenging. It is concluded that sustainable watershed management can be better understood when the risk-based approach is used as an explanatory framework, particularly in priority areas for addressing—and regulating—the global and local dilemmas involved in governing water resources. As this field has been scarcely examined from this perspective, a series of potential research avenues with substantial scope are faced by the social sciences. Socio-environmental challenges related to water should be rigorously analyzed in future studies through innovative approaches, with the social components of the issue prioritized.

Exploring quinoline-type inhibitors of ergosterol biosynthesis: Binding mechanism investigation via molecular docking, pharmacophore mapping, and dynamics simulation approaches.

Ailanthone induces triple-negative breast cancer cells death involving the inhibition of OTUB1-mediated ERRα deubiquitylation

Objective: Stem cell therapy has emerged as a pioneering front in the biomedical domain, characterized by its rapid strides in innovation and progress. Such advancements hold profound implications for public health. Notably, Europe, the United States, Japan, and China have all crafted comprehensive regulatory frameworks to expedite the fruition of stem cell therapy. This article meticulously scrutinizes and evaluates the progression of clinical trials in cell therapy across major global jurisdictions. It delineates the trajectory of regulatory evolution in Europe, the United States, Japan, and China, and systematically collates the pivotal normative guidelines. This article is crafted with the intent to serve as a reference for regulatory agents, enterprises, and professionals in the field. Methods: Stem cell therapy, a paragon of innovative medical technology, heralds a new era of treatment possibilities for hitherto intractable diseases. It is more than just a benchmark of technological advancement; it represents a revolutionary shift in the pharmaceutical landscape. Since Dr.Thomas was awarded the Nobel Prize for his research on bone marrow transplantation in 1990, he has gradually moved from the laboratory to the clinical application stage, bringing new hope for treatment to patients. Stem cell therapy is a type of cell therapy. There are various types of cell therapy, which can be classified into stem cell therapy and immune cell therapy based on their cell sources. They can also be classified into autologous, allogeneic, and heterologous cells based on their donor sources. As a cutting-edge application technology in life science research, cell therapy has shown great therapeutic potential in various disease fields such as malignant tumors, genetic diseases, and chronic degenerative diseases. Multiple cell therapy products have been successfully launched and demonstrated excellent efficacy, among which stem cell therapy stands out due to its long application history and active research trend. Bone marrow/hematopoietic stem cell therapy is the earliest stem cell therapy, mainly used for bone marrow/hematopoietic stem cell transplantation to treat hematological malignancies such as leukemia. Human derived stem cells and their derived therapeutic products, as important regenerative medicine products, have great potential in cell replacement, tissue repair, disease treatment, and other fields. Nearly 70% of the stem cells used in clinical studies are hematopoietic stem cells and mesenchymal stem cells derived from bone marrow, peripheral blood, and umbilical cord. Technical methods include purification, in vitro culture and amplification, drug treatment, or gene modification. Immune cell therapy is a method of treating diseases using immune cells, which was originally mainly used to treat malignant tumors. According to the specificity of immune cell therapy, it can usually be divided into specific immune cell therapy and non-specific immune cell therapy. Specific immune cell therapy includes chimeric antigen receptor T-cell (CAR-T) therapy, T-cell receptor engineered T cell therapy, chimeric antigen receptor natural killer cell therapy (CAR-NK), and DC-CIK immunotherapy. Nonspecific immune cell therapy mainly includes lymphokine activated killer cell therapy and cytokine induced killer cell therapy. In addition, extracellular vesicles, as cell derivatives, have the advantage of non-living properties that are easier to characterize, store, package, and transport than living cells, and their research has shown explosive growth. Extracellular vesicle is a general term for lipid bilayer membrane-bound vesicles released by cells into the extracellular space, with a diameter range of 50-2,000 nanometers. Exosomes are extracellular vesicles with a diameter of 30-150 nanometers. At present, the Food and Drug Administration (FDA) has approved at least 8 extracellular vesicle products to enter phase II/III clinical trials. In recent years, the development of organoid technology, cell lineage tracing technology, single-cell spatial omics-sequencing technology, single-molecule technology, micro proteomics and proximity labeling technology has greatly promoted the progress of stem cell research and laid a good technical reserve for achieving functional organ reconstruction. Results: In the realm of emerging technologies, industry development often precedes regulatory frameworks. The swift progression of innovative stem cell therapy products not only propels medical innovation but also challenges existing regulatory technologies and institutions. Regulatory agencies must, therefore, continually innovate their strategies and technologies. Conclusion: Countries worldwide have crafted regulatory policies and technical evaluation systems tailored to their specific contexts. The variety of stem cell therapy types and applications defined by national regulations reflects this diversity. This article delves into the clinical research status of stem cell therapy through statistical analysis and dissects the regulatory frameworks governing it across nations, offering a valuable resource for stakeholders in this dynamic field.

Alkylphenols (APs) and Alkylphenols ethoxylates (APEs), are ubiquitous estrogenic chemicals, widely distributed in fish due to their persistence and lipophilicity. This study determined levels of APs and APEs, and the associated human health risk in two fish species, 16 Labeo coubie (African carp) and 16 Hydrocynus vittatus (African Tiger fish) sampled quarterly from River Benue, central Nigeria between September 2019 and June 2020. Compounds were identified and quantified using Gas Chromatography with Mass Spectrometric detection (GC-MS). Levels of twenty APs (∑20APs) in Labeo cubie ranged from ND-16.0 ng g-1 wet wt, with total and maximum values of 94.5 ng g-1 wet wt, and 16.0 ng g-1 wet wt respectively. Residues of four APEs (∑4APEs) ranged from ND-3.1 ng g-1 wet wt, total of 5.0 ng g-1 wet wt, and maximum of 3.1ng g-1 wet wt respectively. In Hydrocynus vitatus, ∑20APs ranged from ND-27.8 ng g-1 wet wt, total and maximum of 205 and 27.8 ng g-1 wet wt, respectively. Estimated risk from ingestion of compounds in Labeo cubie and Hydrocynus vitatus by adult and children indicate no immediate potential harm as the hazard quotient (HQ) value was less than one (HQ < 1). However, children could suffer higher body burdens of these pollutants than adults if they are fed with these fish. This study provides baseline data on levels and estimated human health risk from ingestion of these two species of fish contaminated by APs and APEs to regulatory agents and future researchers.

Background and ObjectivesAnkylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease primarily affecting the axial skeleton. Despite significant advances, its pathogenic mechanisms remain unclear, posing challenges to early diagnosis and effective treatment. This study aims to elucidate the pathogenic pathways of AS and explore potential therapeutic strategies.MethodsBlood routine test results from AS and non-AS patients were collected, and t-tests and logistic regression analyses were performed on blood cell count parameters. Key findings from the blood tests were validated using GEO transcriptomic datasets. Single-cell data from GEO were then used to conduct in-depth analyses of immune cell subsets and their functions. To validate findings, single-cell sequencing was performed on bone marrow samples collected from AS and fracture control patients, followed by pathway analysis through GSEA. Finally, upstream regulatory mechanisms and potential therapeutic agents were investigated.ResultsThis study identified a classical monocyte–macrophage–inflammatory macrophage differentiation trajectory in AS, demonstrating that monocytes/macrophages play a critical role in AS pathogenesis via the NOD-like receptor signaling pathway, primarily mediated by NLRP3. Several regulatory factors, including hsa-miR-3682-3p, AR, IRF4, MYB, RUNX1, and TAL1, were found to modulate NLRP3 expression. Additionally, various chemical compounds, anticancer drugs, and cinnamaldehyde were identified as potential therapeutic agents targeting NLRP3.ConclusionIn AS, the classical monocyte–macrophage–inflammatory macrophage differentiation pathway is enhanced, with monocyte/macrophage-derived NLRP3 driving disease progression via the NOD-like receptor signaling pathway. Regulatory factors and potential therapeutic agents targeting NLRP3 were identified, offering new insights into AS pathogenesis and therapeutic strategies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10875-025-01961-4.

Abstract Owing to Nigeria's poor road maintenance culture, informal road menders (IRMs) have emerged who fill potholes on urban and sub‐urban roads in exchange for money from road users. This article interrogates the micropolitics of this phenomenon as a relatively new means of informal livelihood within the context of the ethnography of road infrastructure, informal agency and the everyday struggle for socioeconomic survival. Conceiving informal road mending as a livelihood offers a promising lens for discussing how IRMs gain and retain access to space, navigate risks, and harness relationships with other road users and state institutions along the road. Drawing on conversations with drivers and commuters during ‘go‐alongs’ in public transport and on interviews with IRMs, private car owners and state regulatory agents, the article shows how IRMs and other road users appropriate the risks and opportunities associated with potholes as socioeconomic resources through which they leverage the precarious road transport experience in the country. This contributes to the literature on the ethnography of road infrastructures and the micropolitics of informal work in urban Africa.

The negative health consequences of cigarette smoking have been well documented. Cigarette smoking prevalence is high in Nigeria. A very high proportion of smokers in Nigeria are aware of the dangerous effects of cigarette smoking and most of them want to quit, but their quitting attempts often prove unsuccessful. Evidence shows that tobacco harm reduction (THR) products such as electronic cigarettes are effective in helping smokers to quit. Patent medicine vendors (PMVs) have been successfully integrated into several public health interventions in Nigeria and could prove useful in the provision of tobacco harm reduction products to smokers. This study sought to assess the knowledge and attitudes of patent medicine vendors towards tobacco harm reduction in Ebonyi State, Nigeria. A convergent mixed methods design was used. Cross-sectional survey and indepth interviews (IDIs) were conducted among from 320 PMVs and 25 PMVs, respectively. Descriptive univariate and Pearson's chi square analysis and thematic data analysis were done for survey and IDI data, respectively. There were low awareness and poor knowledge of tobacco harm reduction among the PMVS. Most of them (95.9%, n = 307) said they will seek out and attend training on THR while 89.1% (n = 285) opined that PMVs have a role in providing THR products to smokers. Most (86.9, n = 298) said they will encourage their colleagues to participate in the provision of THR products. Curiously, only 56.9% (n = 182) expressed the desire to include THR products in their stock at the moment; this is explained by two factors: Lack of knowledge of THR and the fear of harassment and extortion by Police and pharmaceutical regulatory agents. Patent medicine vendors represent a very important platform for the provisioning of THR products to smokers, but low awareness and poor knowledge are key constraints. Therefore, there is a need for awareness creation and improvement of PMV's knowledge of THR.