Search Results (20,939)

Substance Use Disorder (SUD) constitutes a major and persistent global public health burden, accounting for approximately 600,000 deaths annually, largely driven by opioid use. Despite substantial advances in addiction neuroscience, currently approved therapeutic strategies remain limited in efficacy, as they predominantly target isolated neurobiological processes and fail to concurrently address core mechanisms such as glutamatergic hyperactivity, mesolimbic hypodopaminergic, and dysfunction of cortical and executive control networks. This mechanistic fragmentation contributes to persistently high relapse rates and underscores the need for integrative and multitarget therapeutic approaches. Within this context, ibogaine has re-emerged as a clinical candidate due to its distinctive multimodal neuropharmacological profile and its reported capacity to modulate multiple pathways implicated in addictive behaviours. However, the clinical translation of ibogaine remains substantially constrained by fragmented and heterogeneous evidence, the absence of regulatory frameworks in several jurisdictions, limited phytochemical validation and standardization of available formulations, and unresolved concerns regarding cardiac safety. This scoping review critically synthesizes the available preclinical and clinical literature on ibogaine in the treatment of SUD, with particular emphasis on reported effects on withdrawal symptoms and craving, dose–response relationships, and the occurrence of cardiac adverse events. By clarifying the current state of the evidence and delineating key translational constraints, this review defines the conditions under which ibogaine, an indole alkaloid isolated from Tabernanthe iboga Baill. (Apocynaceae), may warrant continued investigation. The hypothesis of a neurobiological “reset”, supported by emerging preclinical and clinical data, positions ibogaine as a compound of relevance in addiction research and highlights the need for rigorous pharmacological, toxicological, and regulatory evaluation to inform safer and more standardized clinical pathways. Full article

Background: Explainable Artificial Intelligence (XAI) is deployed in Internet of Things (IoT) ecosystems for smart cities and precision agriculture, where opaque models can compromise trust, accountability, and regulatory compliance. Objective: This survey investigates how XAI is currently integrated into distributed and federated IoT architectures and identifies systematic gaps in evaluation under real-world resource constraints. Methods: A structured search across IEEE Xplore, ACM Digital Library, ScienceDirect, SpringerLink, and Google Scholar targeted publications related to XAI, IoT, edge/fog computing, smart cities, smart agriculture, and federated learning. Relevant peer-reviewed works were synthesized along three dimensions: deployment tier (device, edge/fog, cloud), explanation scope (local vs. global), and validation methodology. Results: The analysis reveals a persistent resource–interpretability gap: computationally intensive explainers are frequently applied on constrained edge and federated platforms without explicitly accounting for latency, memory footprint, or energy consumption. Only a minority of studies quantify privacy–utility effects or address causal attribution in sensor-rich environments, limiting the reliability of explanations in safety- and mission-critical IoT applications. Contribution: To address these shortcomings, the survey introduces a hardware-centric evaluation framework with the Computational Complexity Score (CCS), Memory Footprint Ratio (MFR), and Privacy–Utility Trade-off (PUT) metrics and proposes a hierarchical IoT–XAI reference architecture, together with the conceptual Internet of Things Interpretability Evaluation Standard (IOTIES) for cross-domain assessment. Conclusions: The findings indicate that IoT–XAI research must shift from accuracy-only reporting to lightweight, model-agnostic, and privacy-aware explanation pipelines that are explicitly budgeted for edge resources and aligned with the needs of heterogeneous stakeholders in smart city and agricultural deployments. Full article

Steatosis extends beyond the liver to the pancreas, heart, and skeletal muscle, yet prevailing definitions remain narrowly organ-focused. This narrative review introduces the Metabolic Steatotic Axis (MSA) as a framework that captures the dynamic, bidirectional interactions among these organs, driving systemic metabolic dysfunction. We synthesize evidence linking lipotoxicity, inflammatory signaling, and endocrine cross-talk into a self-amplifying network accelerating insulin resistance, β-cell failure, and cardiometabolic risk. The MSA concept provides a rationale for axis-based staging systems and composite biomarker panels to quantify cumulative disease burden better and refine risk stratification. We highlight phenotypic heterogeneity within MSA stages, the possible hierarchy of organ vulnerability, and the implications for prognosis and therapy. Viewing pharmacological and lifestyle interventions through the MSA lens reframes them as systemic modulators rather than organ-specific treatments, underscoring the need for multi-organ endpoints in clinical trials. Finally, we outline priorities for longitudinal imaging, multi-omics integration, and global harmonization to translate the MSA from a conceptual construct to a clinically actionable paradigm. By unifying fragmented observations into a systemic model, the MSA has the potential to reshape disease classification, therapeutic strategies, and precision medicine in metabolic disorders. Full article

Forest structural parameters, such as canopy closure, stand density, diameter at breast height, tree height, leaf area index, stand age, and biomass, are fundamental for quantifying forest ecosystem functioning and supporting sustainable forest management. Remote sensing has become an indispensable tool for forest structural parameter estimation. Commonly used data sources include optical imagery, synthetic aperture radar (SAR), light detection and ranging (LiDAR), unmanned aerial vehicles (UAVs), and multisource data fusion. Correspondingly, modeling approaches have evolved from empirical and statistical methods to machine learning, deep learning, and hybrid physical-data-driven models, enabling improved characterization of nonlinear and complex forest structures. Each data source and modeling strategy offers unique strengths and limitations with respect to accuracy, scalability, interpretability, and transferability. This review provides a concise synthesis of recent advances in remote sensing data sources and model algorithms for forest structural parameter estimation, evaluates the strengths and limitations of different sensors and algorithms, and highlights key challenges related to uncertainty, scalability, transferability, and model interpretability. Finally, future research directions are discussed, emphasizing cross-scale integration, multisource data fusion, and physically informed deep learning frameworks as promising pathways toward more accurate, robust, and ecologically interpretable forest structural parameter modeling at regional to global scales. Full article

The simplest definition of light pollution (LP) is the presence of artificial light at night (ALAN) at inappropriate times, intensity, and inappropriate amounts and colors. All these parameters of anthropogenic light clearly indicate that the presence of ALAN can disrupt the proper functioning of not only humans but all organisms on Earth that have evolved in conditions of alternating day and night, closing within a 24 h day. Cities are the primary source of LP, and the ever-increasing global urbanization makes LP one of the fastest-growing threats to our civilization. It is particularly dangerous because public awareness of its existence is exceptionally weak, as the presence of light is usually perceived as a good thing, generating safety and beauty, and it is difficult for people to understand that excess of light may turn against us. However, LP dysregulates the well-known circadian rhythms of humans and animals and disrupts normal plant physiology. Furthermore, in a light-polluted world, plant–pollinator relationships are also endangered, which can lead to disruptions in food chains. In this review, we will present various aspects of excessive lighting and propose solutions to mitigate the increasing LP, considering the threats it poses to all living organisms. Full article

Wetlands occupy a mere 6% of Earth’s land surface, yet they contribute 25–45% of global natural methane (CH₄) emissions. A key contradiction emerges here: it is the soil of these wetlands that serves as the host for methane-trophic microorganisms, which can oxidize the vast majority of the methane they produce under specific conditions (for example, the aerobic interface). A wetland’s role as either a net source or sink for atmospheric CH₄ is therefore a primary driver of hydrological variability. This research synthesis current understandings of how wet–dry cycles regulate methanotrophic communities and their CH₄ consumption capacity. Shifts in the water table directly modulate methanotroph physiology, community structure, and metabolic activity. These hydrological effects are further amplified or attenuated by nitrogen availability, plant-derived exudates, and edaphic properties. Herein, key knowledge gaps concerning the adaptive responses of methanotrophs to hydrological change are identified, and targeted research priorities improving predictions of wetland CH₄ fluxes under contrasting moisture regimes are accordingly outlined. This review synthesizes recent advances to highlight the mechanistic understanding essential for guiding wetland management strategies. Full article

Driven by rapid socioeconomic progress and changing lifestyles, the global burden of cardiovascular diseases (CVDs) continues to escalate, with surging morbidity and mortality rates imposing a severe threat to public health. Clinical treatments are focused on the alleviation of treatments, highlighting the need for a deeper understanding of CVDs pathogenesis and the development of targeted therapies. Recent studies have identified imbalances in intracellular Ca²⁺ homeostasis as a key pathological mechanism in the progression of CVDs. Notably, sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2), a membrane protein encoded by the ATP2A2 gene and ranging from 97 to 115 kDa in molecular weight, plays a pivotal role in regulating intracellular Ca²⁺ levels. Extensive evidence links abnormal SERCA2 function to various CVDs, including heart failure, cardiac hypertrophy, atherosclerosis, and diabetic cardiomyopathy. This review systematically explores the regulatory mechanisms of SERCA2 expression and its functional regulation—including transcriptional regulation, post-translational modifications, and protein–protein interactions—and further investigates its pathological roles in cardiovascular diseases as well as its potential as a therapeutic target. By synthesizing current knowledge, this article aims to provide new insights for future basic research and establish a theoretical foundation for clinical applications. Full article

The global poultry industry continues to face significant challenges due to Salmonella infections, which pose severe public health concerns and economic losses. Recently, the reemergence of antimicrobial resistance has led to the restriction of antibiotic use in poultry, especially as growth promoters, thus accelerating the search for sustainable alternatives. Among these, probiotics have gained attention as potential candidates for improving poultry health and mitigating Salmonella colonization in the gut. This review summarizes the key mechanisms through which probiotics exert anti-Salmonella effects, including competitive exclusion, production of antimicrobial substances, reinforcement of the intestinal barrier, and modulation of host immune responses. Commonly used probiotic strains in poultry such as Lactobacillus and Bacillus are discussed, alongside emerging candidates derived from non-poultry hosts that may offer additional functional benefits. Despite encouraging findings, the use of probiotics in poultry faces several challenges, including strain-specific efficacy, variation in results across studies, environmental influences, and regulatory limitations. Therefore, we further explore future directions that are aimed at improving probiotic application in poultry production, such as microbiome-guided strain selection, advanced delivery systems, and combination therapies. Advancing our understanding of probiotic-pathogen-host interactions will be essential for optimizing probiotic use to enhance poultry health, reduce zoonotic transmission of Salmonella, and contribute to safer and more sustainable food systems. Full article

Childhood overweight and obesity represent a major global public health emergency, with a steadily increasing prevalence over recent decades in both developed and developing countries. Approximately one fifth of children and adolescents are overweight or obese, with marked differences across ethnic groups and geographical areas. Accurate estimation of this condition is complicated by the lack of a unique and universally accepted definition of childhood obesity, which is based on different anthropometric criteria. Although body mass index (BMI) remains the most widely used tool, growing evidence indicates that abdominal obesity, assessed by waist circumference and waist-to-height ratio, is a better predictor of cardiometabolic risk, even in children with a normal BMI. Childhood obesity is associated with several comorbidities, including arterial hypertension, non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea syndrome (OSAS). Early diagnosis and an integrated therapeutic approach are essential to reduce the risk of long-term complications. Although lifestyle modifications remain the cornerstone of treatment, new pharmacological options for pediatric obesity have been approved in recent years. This narrative review explores the impact of childhood obesity on the early development of hypertension, NAFLD, and OSAS, emphasizing the implications that can already be observed during childhood and adolescence. It examines the association between pediatric obesity and these conditions by synthesizing current epidemiological evidence, describing the underlying pathophysiological mechanisms linking excess adiposity to disease onset, and reviewing pediatric-specific diagnostic criteria as well as preventive and therapeutic strategies. Full article

RNA viruses pose a persistent global threat due to their high mutation rates, zoonotic potential, and rapid adaptability. Emergence events have risen steadily, as demonstrated by major outbreaks caused by Influenza A, Ebola, Zika, and Chikungunya viruses, followed by the coronavirus epidemics of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and culminating in the COVID-19 pandemic. These characteristics frequently compromise the durability of existing vaccines and antiviral therapies, highlighting the urgent need for new antiviral agents. Alkaloids, a structurally diverse class of nitrogen-containing natural compounds, have gained attention for their ability to interfere with multiple stages of the viral life cycle, including entry, replication, protein synthesis, and host immune modulation. To our knowledge, this review compiles all currently reported alkaloids with antiviral activity against RNA viruses and summarizes their proposed mechanisms of action, distinguishing evidence from in vitro, in vivo, and in silico studies. Quaternary alkaloids are discussed separately because their permanent ionic charge enables distinctive interactions with membranes and host pathways. Although many findings are promising, clinical translation remains limited by incomplete mechanistic validation, scarce in vivo data, suboptimal bioavailability, narrow therapeutic windows, and inconsistent experimental methodologies. To advance the field, future research should prioritize RT-qPCR–based antiviral evaluation to accurately quantify viral replication, incorporate mechanistic assays to clarify modes of action, apply structure–activity relationship (SAR) approaches for rational optimization, and expand in vivo pharmacokinetic and efficacy studies to assess therapeutic feasibility. Overall, alkaloids represent a promising yet underdeveloped reservoir for next-generation antiviral discovery against rapidly evolving RNA viruses. Full article

Off-pump coronary artery bypass grafting (OPCAB) represents one of the most significant technical innovations in contemporary cardiac surgery. Developed as an alternative to conventional on-pump coronary artery bypass grafting (ONCAB), OPCAB avoids cardiopulmonary bypass and its associated systemic inflammatory response, aiming to reduce perioperative morbidity and improve recovery. Over the past three decades, advances in stabilization devices, intracoronary shunts, anesthetic management, and surgical training have refined the procedure, making it safer and more reproducible. Despite these developments, OPCAB adoption remains inconsistent worldwide, reflecting ongoing debate about its relative benefits and limitations. Evidence from randomized controlled trials, meta-analyses, and large registries suggests that OPCAB achieves comparable early mortality to ONCAB, with potential advantages in reducing renal dysfunction, neurocognitive decline, and perioperative bleeding. These benefits appear most pronounced in high-risk subgroups, including elderly patients and those with significant comorbidities. However, concerns persist regarding long-term graft patency, completeness of revascularization, and variability in outcomes depending on surgeon experience and institutional expertise. Cost-effectiveness analyses have suggested potential resource savings, but these are offset by training requirements and the technical complexity of the procedure. Global practice variation highlights the influence of surgical culture, guideline ambiguity, and institutional resources. Barriers to universal adoption include technical challenges, inconsistent long-term outcomes, and limited exposure in training programs. In the future, robotic and minimally invasive OPCAB, as well as hybrid revascularization strategies, may expand its role. This review synthesizes current evidence, explores barriers to widespread implementation, and outlines future directions for integrating OPCAB into balanced, evidence-based clinical practice. Full article

Reactive oxygen species (ROS) have traditionally been viewed as pathological by-products of metabolism that drive tissue damage through oxidative stress. However, accumulating evidence across chronic diseases, including metabolic, cardiovascular, neurodegenerative disorders, and cancer, indicates that ROS also function as tightly regulated signaling molecules essential for cellular adaptation and survival. This paradigm shift from oxidative stress to redox signaling necessitates a fundamental re-evaluation of how redox imbalance contributes to chronic disease pathogenesis. In this review, we propose that chronic diseases should be understood as disorders of maladaptive redox homeostasis rather than simple consequences of excessive oxidative damage. We delineate the distinction between oxidative stress and redox signaling, emphasizing how chronic redox remodeling stabilizes pathological cellular states through coordinated regulation of key redox-sensitive transcriptional nodes, including KEAP1–NRF2, FOXO, HIFs, and NF-κB. Using cancer as a representative model, we illustrate how elevated but buffered ROS levels support oncogenic signaling, metabolic rewiring, and therapeutic resistance through redox addiction. We further discuss why non-specific antioxidant strategies have largely failed and argue that effective intervention requires context-dependent redox modulation rather than global ROS suppression. Finally, we introduce therapeutic redox reprogramming and outline future directions for precision redox medicine based on biomarker-guided stratification and disease stage-specific targeting strategies. Full article

Background: Pharmacology plays a central role in linking biomedical science concepts with their application in clinical practice across medical and healthcare education. Globally, the pharmacological curriculum has evolved, just like other disciplines, through the integration of case-based, problem-based, and hybrid teaching models that led to firm clinical reasoning and long-term learning. Thus, this study aims to evaluate and compare the learning outcomes of pharmacology curricula across the globe by adopting a systematic review and meta-analysis research approach. Methods: This comprehensive review was conducted with transparency and integrity in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines and was registered with PROSPERO (CRD420251207753). Five electronic databases, including MEDLINE (PubMed), EMBASE, CINAHL, PsycINFO, and the Cochrane Library were searched from January 2000 to October 2025. The Cochrane Library tool was used for the risk of bias assessment of randomised controlled trials, while the Joanna Briggs Institute (JBI) checklist was used for mixed-design, quasi-experimental, and cross-sectional cohorts. Review Manager 5.4 was used for statistical analysis. Results: Out of 3300 identified studies, 11 met the inclusion criteria, spanning 11 countries (published between 2007 and 2025). Integrated and case-based curricula significantly improved pharmacology knowledge compared to traditional lecture-based methods (SMD = 0.35; 95% CI: 0.07–0.64; I² = 75%). Student satisfaction also favours integrated learning (OR = 1.53; 95% CI: 1.16–2.02; I² = 46%). Most included studies were of moderate-to-high methodological quality. Conclusion: Globally, active and integrated pharmacology curricula foster greater cognitive understanding and learner satisfaction than conventional models. However, significant variability persists in resource-limited settings, leading to unequal competency in prescribing and therapeutic reasoning. Australian pharmacology programmes align broadly with international standards but require greater standardisation in assessment and experiential learning. Full article

The agri-food sector is a major contributor to global greenhouse gas emissions while facing increasing demand for food production driven by population growth. Transitioning towards sustainable and low-carbon agricultural systems is therefore critical. Green hydrogen, produced from renewable energy sources, holds significant promise as a clean energy carrier and chemical feedstock to decarbonize multiple stages of the agri-food supply chain. This systematic review is based on a structured analysis of peer-reviewed literature retrieved from Web of Science, Scopus, and Google Scholar, covering over 120 academic publications published between 2010 and 2025. This review provides a comprehensive overview of hydrogen’s current and prospective applications across agriculture and the food industry, highlighting opportunities to reduce fossil fuel dependence and greenhouse gas emissions. In agriculture, hydrogen-powered machinery, hydrogen-rich water treatments for crop enhancement, and the use of green hydrogen for sustainable fertilizer production are explored. Innovative waste-to-hydrogen strategies contribute to circular resource utilization within farming systems. In the food industry, hydrogen supports fat hydrogenation and modified atmosphere packaging to extend product shelf life and serves as a sustainable energy source for processing operations. The analysis indicates that near-term opportunities for green hydrogen deployment are concentrated in fertilizer production, food processing, and controlled-environment agriculture, while broader adoption in agricultural machinery remains constrained by cost, storage, and infrastructure limitations. Challenges such as scalability, economic viability, and infrastructure development are also discussed. Future research should prioritize field-scale demonstrations, technology-specific life-cycle and techno-economic assessments, and policy frameworks adapted to decentralized and rural agri-food contexts. The integration of hydrogen technologies offers a promising pathway to achieve carbon-neutral, resilient, and efficient agri-food systems that align with global sustainability goals and climate commitments. Full article

Microplastics (MPs) enter terrestrial ecosystems through various pathways, including the use of plastic mulching films, treated sewage sludge, and chemical and organic fertilizers. Polypropylene (PP) and polyethylene (PE) are the dominant polymers found in both traditional and facility-based farmland soils. MPs negatively impact soil microbial communities and harm soil invertebrates such as earthworms, nematodes, and springtails. In plants, MPs can induce oxidative stress, damage cells and inhibit growth. Polystyrene (PS) is often identified as the most hazardous polymer, frequently linked to reduced plant growth, which is the most commonly reported effect of soil MP contamination. This review provides novel insights beyond those reported in the previous literature, revealing that greenhouse-based cultivation, vegetable crops, orchards, and vineyards are significant contributors to increased microplastic soil contamination. Furthermore, the findings underscore pronounced global heterogeneity in microplastic concentrations within paddy soils, with recorded levels varying widely from 16 to 10,300 items kg⁻¹. Oxidative stress and additive leaching are the dominant mechanisms driving soil microplastic toxicity across exposed organisms. Quantitative studies of fungal-mediated microplastic biodegradation report mean degradation efficiencies of ~7.5% after 50 days, with mass losses of ~23.8% after 30 days and 35–38% after 90 days. Full article