Search Results (5,309)

Fatty acid-binding proteins (FABPs) are a family of intracellular lipid chaperones that transport fatty acids and other hydrophobic molecules, playing essential roles in cellular lipid metabolism, signaling, and brain function. Within the central nervous system, FABP3, FABP5, and FABP7 facilitate the trafficking of long-chain polyunsaturated fatty acids and endocannabinoids, thereby modulating key regulatory pathways including the endocannabinoid system (ECS), peroxisome proliferator-activated receptor (PPAR) signaling, and dopaminergic neurotransmission. Peripherally, FABP1 and FABP4 contribute to hepatic drug metabolism, kidney excretion, and inflammatory processes in both tissues, with implications for the pharmacokinetics of substances of abuse. This narrative review synthesizes the current literature on FABPs and their involvement in substance use and addiction-related behaviors. Evidence from transgenic knockout models, pharmacological inhibition studies, and adeno-associated virus vector approaches demonstrates that manipulation of FABP subtypes can alter reward-related behaviors across multiple substances, including THC, ethanol, nicotine, and cocaine. Reduction or knockout of FABP7 alters THC metabolite levels in a sex-dependent manner. FABP3 shows involvement with dopamine receptor expression; however, interaction between FABP3 modulation and specific substances has sparsely been investigated. FABP5 has vastly diverging interactions with addictive behavior and appears to be substance dependent, as downregulation reduces cocaine self-administration, but knockout enhances nicotine conditioned place preference (CPP) and increases brain uptake of THC. Combined deletion of FABP5 and 7 additionally reduces cocaine CPP and reinstatement, while showing promising decreases in ethanol consumption paradigms. FABPs may be a potential therapeutic target for treating substance use disorders and underlying reward deficiency mechanisms underlying addiction and further research is required to elucidate specific mechanistic effects and eliminate potential adverse consequences of chronic FABP modulation. Full article

Achieving integrated water resources management at all levels, as called for by Sustainable Development Goal (SDG) target 6.5, requires assessment tools that operate at the local administrative scale. However, watershed sustainability assessments are mostly conducted at the whole-basin or provincial scale, which masks the spatial disparities that matter for local water management. This study develops a sub-district-scale Watershed Sustainability Index (WSI) for the Nong Han Basin, Thailand, by integrating the HELP framework (Hydrology, Environment, Life, and Policy) with the Pressure–State–Response structure, a calibrated QSWAT hydrological model, and spatial analysis in a geographic information system, covering 25 sub-districts. The results show that the basin has a moderate-to-high level of sustainability, with a mean WSI of 0.620: 18 sub-districts are classified as high and 7 as moderate, and none fall into the low category. The Life and Hydrology dimensions are the strongest, whereas the Policy dimension is the limiting factor in most sub-districts. This limitation arises from a low Response component (0.19) rather than from a lack of institutional capacity, as confirmed by the finding that sub-districts with low and high policy scores differ only in the Policy dimension. The apparently uniform aggregate index, combined with the high disparity among dimensional scores, confirms the value of diagnosis at the sub-district scale. The proposed framework translates the assessment results into spatial prioritization, an agency-linked decision matrix, and an intervention typology, thereby supporting evidence-based water management by local administrative organizations. Full article

Degraded tax forms and other legal–administrative documents require restoration methods that impose strict constraints on content fidelity. This paper presents a structure-aware restoration framework for degraded tax documents that combines geometric normalization, canonical template guidance, and supervised image restoration within a common alignment space. Documents are first mapped to a canonical layout through homography estimation based on Scale-Invariant Feature Transform (SIFT) and Random Sample Consensus (RANSAC), using the canonical visual template as the reference. Restoration is then performed using template priors and masked constraints designed to preserve the fixed document structure while recovering variable content. Under a fixed-budget comparative protocol, U-Net with template priors achieved the highest visual and structural quality, whereas the proposed hybrid model obtained the best functional OCR performance on synthetic data, reaching a Character Error Rate (CER) of 0.1091 and a Word Error Rate (WER) of 0.3495. As a complementary evaluation on 37 real-world documents with human-generated textual ground truth, restoration increased full-page word coverage across all three OCR engines evaluated, yielding absolute improvements ranging from 4.15 to 18.05 percentage points. Full article

This article examines the Carbon Border Adjustment Mechanism (CBAM) as a regulatory instrument of the European Union, situated at the intersection of international trade law, customs law and environmental protection. The primary objective of the study is to assess the legal nature of the CBAM, evaluate its compatibility with World Trade Organisation (WTO) law and analyse its implications for sustainable global trade governance and climate policy. Particular attention is paid to Articles I, III and XX of the GATT, as well as relevant WTO case law, including the cases of United States—Gasoline, United States—Shrimp, European Communities—Asbestos and Brazil—Retreaded Tyres. The study further examines the procedural transformation of customs authorities, particularly in relation to the verification of emissions, the burden of proof and administrative enforcement. The article also assesses the environmental effectiveness of the CBAM in preventing carbon leakage and in enforcing higher environmental standards in third countries, addressing the legal and economic issues of discrimination, proportionality, administrative complexity and potential impact on developing economies. The research is based on doctrinal legal analysis, comparative legal methodology and a review of relevant international and European legal sources, including WTO case law and Regulation (EU) 2023/956. The authors demonstrate that the CBAM represents a hybrid regulatory mechanism combining elements of environmental taxation, regulatory charges and trade policy instruments implemented through customs procedures. The originality of the article lies in its integrated and comprehensive analysis of the CBAM from the perspective of customs law, international trade law and environmental regulation with a focus on sustainability. In contrast to existing studies focusing primarily on trade or climate aspects, the article highlights the evolving regulatory role of customs authorities in the framework of European Union climate governance. The findings suggest that the CBAM is generally compatible with WTO law, provided that it is implemented in a transparent, proportionate, flexible and non-discriminatory manner. The authors conclude that the CBAM can become an important model for the future development of sustainable international economic regulation and climate-related trade governance. Full article

Global biodiversity policy increasingly depends on community-led conservation, yet the comparative evidence base contains little from South Asia’s frontier regions. This article asks how a long-running grassroots organisation in a politically and ecologically marginal region combined community mobilisation, vernacular knowledge, scientific evidence, and engagement with public institutions in pursuing conservation outcomes, and which features of that process may be relevant beyond Northeast India. Four campaigns of Nature’s Beckon, founded in Dhubri, Assam, in 1982, are compared as distinct types of intervention: species-led protected-area mobilisation at Chakrashila; landscape-scale conservation against extractive pressure at Dihing Patkai; species research with public ecological education; and community-managed institution-building. The available evidence indicates a documented and substantial, though not exclusive, role in campaigns associated with the notification of two protected areas whose current notified areas total approximately 279.83 km². Advocacy alone does not adequately explain these outcomes: where a formal government decision was required, sustained organisational capacity became consequential only when it coincided with a favourable political and administrative opening. Measured against four design features associated with successful community-based conservation, the model corresponds strongly to capacity-building investment and external linkage, in qualified form to equitable benefit-sharing, and only partly to tenure security. The article develops an ecology of the margins framework and specifies which elements appear transferable and which do not. Full article

This study examines the socio-spatial dynamics of rural overtourism and landscape commodification in a peripheral municipality in Northwestern Italy. Employing a qualitative, longitudinal ethnographic design, data were collected between May 2020 and October 2021 in San Giovanni (Piedmont). The methodology combined extensive participant observation in public, commercial, and agricultural spaces with ethnographic interviews with six stakeholder groups: local promoters, municipal administrators, professional farmers, long-term residents, shopkeepers, and visiting tourists. Qualitative data were processed using inductive thematic analysis. The results indicate that visitor surges were initiated endogenously by local promoters through the installation of an open-access, gamified “Big Bench” attraction designed to counter long-term demographic and economic contraction. The influx of day-trippers generated localized spatial intrusion, traffic congestion, and physical disruptions to agricultural operations during peak harvest periods, as well as to residents’ daily activities. Rather than driving generalized economic revitalization, the intervention produced host–visitor friction and intra-community polarization between local promoters seeking external visibility and residents experiencing spatial disruptions and loss of privacy. The study demonstrates that overtourism can develop endogenously through promoter-led self-commodification and provides a three-tiered governance framework encompassing policy, destination management, and community-level strategies for fragile rural territories. Full article

Chemistry teaching in youth and adult education has faced challenges related to students’ disengagement, interrupted educational trajectories, and difficulty in connecting scientific concepts with learners’ everyday and professional experiences. In Brazil, Professional and Technological Secondary Education Integrated with Youth and Adult Education (PROEJA) aims to address its challenges by combining basic education with vocational training. This study investigated how a contextualized pedagogical intervention based on the production of aromatic candles contributed to students’ engagement, contextualized conceptual learning and vocational reflection in a technical administration course offered at the Brazilian Federal Institute (IFMS-CG), Campo Grande, Mato Grosso do Sul, Brazil. A qualitative participatory action research design was adopted, and qualitative data were generated through participatory observations, classroom interactions, students’ written reflections, photographic records, and reflective discussions. Data were interpreted by Reflexive Thematic Analysis. Throughout the intervention, students explored Organic Chemistry concepts related to hydrocarbons, n-paraffins, physicochemical properties, volatility, combustion, formulation and laboratory safety while simultaneously discussing entrepreneurship, branding, product development and income generation. The qualitative findings demonstrated students’ active participation, collaborative teacher–student interactions, contextualized conceptual learning and a broader perception of Chemistry as a socially and professionally relevant discipline connected to everyday life, vocational education and entrepreneurial practice. Students’ written reflections further revealed that scientific knowledge was increasingly associated with technological innovation, product quality, professional opportunities and income generation. These findings suggest that contextualized, interdisciplinary and humanized pedagogical practices may promote meaningful scientific learning while strengthening vocational reflection and reinforcing the relevance of Chemistry within youth and adult professional and technological education. Full article

Background/Objectives: The health-protective properties of olive oil phenolics, including their potential chemopreventive and anticancer effects, have attracted considerable scientific interest. However, their in vivo efficacy and mechanisms of action remain insufficiently understood. Recent advances in extraction and purification technologies have enabled large-scale production of highly purified olive oil phenols and phenolic-rich extracts, facilitating translational research. Methods: Herein, the antitumor efficacy of isolated olive oil phenols and phenolic-rich formulations was investigated in an MDA-MB-231 triple-negative breast cancer (TNBC) xenograft model. Results: Intraperitoneal administration of oleocanthal (OLC), oleuropein aglycone (OleA) or their combination reduced endpoint tumor burden, with OLC exhibiting the most pronounced effect. Oral administration of total olive oil phenolics (OOPs) achieved comparable efficacy. Pre-treatment initiated before tumor cell implantation conferred the greatest protection, consistent with a prophylactic mode of action. In contrast, delayed intervention displayed diminished or no antitumor benefit. Phenolic-rich extra virgin olive oil likewise showed an inhibition trend in tumor progression. Mechanistically, OOPs attenuated plasma protein oxidation, modulated proteasome mediated proteolysis, and reduced γH2AX levels in vivo. Furthermore, OOPs negatively affected the MDA-MB-231 cell migration in a concentration-dependent manner in vitro. Conclusions: Collectively, these findings are consistent with antitumor activities of olive oil phenolics via multiple mechanisms and support their further investigation as prophylactic agents in TNBC and as nutraceuticals. Full article

Peptide therapeutics occupy a unique position between small organic compounds and large protein biomolecules, combining high specificity, strong pharmacological efficacy, and favourable safety profiles. Consequently, they have emerged as important therapeutic agents for a wide range of diseases, including metabolic and oncological disorders. However, oral administration of peptide drugs remains a major challenge due to extensive enzymatic degradation, low intestinal permeability, mucus entrapment, and presystemic metabolism within the gastrointestinal tract. This review provides a comprehensive overview of contemporary strategies for improving oral peptide delivery, with special emphasis on emerging pharmaceutical formulation technologies, bioinspired delivery systems and ingestible device-assisted approaches. A qualitative literature search was conducted using major scientific databases and included relevant publications available up to May 2026. The analysis identified the main barriers responsible for low oral bioavailability of peptide drugs, as well as promising approaches to overcoming these obstacles, including peptide modification, enzyme inhibition, permeation enhancement, mucolytic strategies, and advanced carrier systems. Special attention is given to multifunctional carrier systems, ingestible medical devices and bile acid-inspired technologies as emerging directions in oral peptide delivery. The convergence of pharmaceutical sciences, bioinspired formulation strategies and biomedical engineering is expected to accelerate the clinical translation of oral peptide formulations and enable their therapeutic potential to be fully exploited. Full article

Macroscopic and microscopic aggregation patterns of reconstituted poly-L-lactic acid (PLLA) products may vary with product formulation, diluent, preparation protocol, and time. This descriptive in vitro pilot study compared two commercial formulations, StiCol Volume (150 mg PLLA reconstituted to 9 mL) and StiCol Soft (50 mg PLLA reconstituted to 6 mL), under 11 diluent conditions and 2 composite preparation protocols: roller mixing for 30 min and manual shaking for 3 min followed by 3 h of hydration. One preparation was evaluated for each formulation–diluent–protocol combination. Gross appearance was documented immediately and at 15, 30, 45, and 60 min and 24 h; microscopy was performed at ×40 and ×100 from 15 min onward. Two evaluators applied an ordinal visual aggregation scale, and the findings were analyzed descriptively. In the observed preparations, the StiCol Soft formulation generally showed lower aggregation grades than StiCol Volume; however, the products differed in nominal PLLA concentration, particle size, and excipient composition, so this pattern cannot be attributed to concentration alone. SWFI-based conditions tended to show fewer microscopic clusters than NSS-based conditions. The roller/30 min protocol also tended to show lower grades than the manual/3 h protocol, although mixing mode and hydration duration were inseparable. Macroscopic upper-layer accumulation was interpreted as vertical phase separation with creaming/flotation-like behavior rather than sedimentation. These exploratory findings generate hypotheses for replicated studies incorporating standardized sampling, redispersibility, particle size, rheological, and injectability testing; they do not establish an administration window or improved clinical safety. Full article

Background/Objectives: Differentiating high-grade glioma recurrence from treatment-related changes remains challenging on conventional MRI. This study evaluated non-contrast arterial spin labeling (ASL) perfusion MRI for this distinction and compared its performance with dynamic susceptibility contrast (DSC) perfusion MRI. Methods: Postoperative follow-up MRI examinations obtained between November 2019 and May 2021 were retrospectively reviewed. The cohort included 63 MRI examinations from 36 adults treated for high-grade glioma. ASL, routine MRI, and DSC images were independently assessed by two neuroradiologists. Final diagnosis was based on histopathology or longitudinal clinical and imaging follow-up. Reader agreement, diagnostic performance, and an exploratory patient-level grouped machine learning analysis using ASL-only, DSC-only, and combined ASL–DSC features were evaluated. Results: ASL- and DSC-derived perfusion parameters were significantly higher in tumor recurrence than in treatment-related changes (all p < 0.001). Both techniques showed high diagnostic performance; DSC achieved the highest accuracy, whereas ASL provided high specificity across readers. Inter-reader agreement ranged from substantial to almost perfect. In grouped cross-validation, ASL-only, DSC-only, and combined models achieved mean AUCs of 0.946, 0.997, and 0.997, respectively. Permutation testing confirmed that combined-model performance exceeded chance expectations (empirical p = 0.002). Conclusions: Non-contrast ASL perfusion showed diagnostic performance comparable to DSC for differentiating high-grade glioma recurrence from treatment effects. ASL may provide a reliable non-invasive alternative for longitudinal surveillance, particularly when gadolinium administration is undesirable or contraindicated. Full article

Higher education institutions operate complex digital environments that combine administrative services, research infrastructures, learning platforms, identity systems, and heterogeneous departmental IT. In the European Union, the NIS2 Directive increases the need for structured cybersecurity governance, while ISO/IEC 27001:2022 provides a mature information security management system standard that can support implementation. This paper proposes a design science artefact for aligning NIS2 obligations with ISO/IEC 27001:2022 clauses and Annex A controls in the context of higher education institutions. The framework organizes cybersecurity governance, asset and service scoping, risk management, incident handling, business continuity, supplier and cloud dependencies, access control, awareness, monitoring, and continual improvement into a staged maturity model. The artefact is instantiated for a Romanian public university context and assessed through internal traceability analysis, including mappings between NIS2 Articles 20, 21, and 23, Romanian NIS2 transposition requirements, and ISO/IEC 27001:2022 control areas. The institutional illustration identifies candidate assessment domains and evidence requirements but does not assign maturity levels because the internal records required by the scoring protocol were unavailable; it therefore does not constitute an audit, verified institutional measurement, or empirical validation. The contribution is therefore a structured and reusable compliance design artefact, together with a transparent mapping method that can support future expert validation, institutional pilots, and audit-oriented refinement. Full article

Most active pharmaceutical ingredients (APIs) reach their target by passive systemic distribution, so the dose required for efficacy at the lesion is set by what healthy tissue can tolerate; conventional dosage forms consequently produce pharmacokinetic profiles that oscillate between toxic peaks and sub-therapeutic troughs. Nanoparticulate carriers (liposomes, lipid nanoparticles, polymeric and inorganic systems, and biomimetic carriers) and hydrogels (natural, synthetic, supramolecular, and microgel-assembled) have emerged as the dominant strategies to address this, increasingly combined as hybrid nanoparticle–hydrogel constructs in which the gel provides locoregional retention and the nanoparticles provide cargo protection, intracellular delivery and stimuli responsiveness. Stimuli-responsive chemistries (pH, redox, enzyme, ROS, hypoxia, temperature, light, magnetic, ultrasound, glucose, and multi-stimuli logic) translate the molecular signatures of a disease into spatiotemporally controlled cargo release. This narrative review consolidates the state of the art (prioritizing 2022–2026) and departs from the conventional carrier-type survey in one respect: the literature is read along an explicit chain—disease cue, sensing chemistry, carrier architecture, release mechanism and kinetics, administration route, and clinical readiness—which exposes a variable that classification by carrier type conceals. Across all three material classes, what governs release behavior is not primarily the carrier chemistry but the identity of the released species (dissolved drug, drug from an embedded nanoparticle, an intact nanoparticle, and a matrix fragment) and the transport step that limits it. This is why power-law exponent analysis developed for dissolved drug fits particulate release poorly, why statistical goodness-of-fit cannot by itself establish a release mechanism, and why carrier class predicts clinical readiness less well than administration route and regulatory product type. Translational hurdles—CMC complexity, regulatory fragmentation, anti-PEG immunogenicity, and the structural mismatch between preclinical promise and clinical efficacy—are critically appraised in light of previously reported <1% delivery efficiency analysis. This review identifies converging strategies that could move stimuli-responsive controlled release from an aspirational outcome to a routine clinical reality. Full article

With the backdrop of the coexistence of sustainable development of marine economy and ecological environment restrictions, how to enhance the efficiency of marine environmental governance (MEGE) has become a significant topic whereby coastal regions should attain green transformation. The research object in this paper is 11 coastal provincial administrative units in mainland China between 2013 and 2021, and marine environmental governance is divided into two stages of production and governance. MEGE and its stage efficiency are measured with the help of the two-stage super-efficiency Network SBM model, and the efficiency growth is characterized with the help of the Network Malmquist index. It is on this basis that, using the technology–organization–environment (TOE) framework, six antecedent conditions of digital economy, technological innovation, marine industrial structure, marine industrial agglomeration, environmental regulation, and degree of openness are chosen and fsQCA is applied to determine the multiple configuration paths of high MEGE growth. The findings indicate the following: (1) The MEGE in the coastal regions of China is improving in general, although the differences in the region remain evident. The efficiency characteristics of the production stage and the governance stage differ, and the inter-provincial differentiation of the governance stage is more pronounced. (2) No single condition is required to achieve high MEGE growth but four equifinal configurations created by the combined action of several conditions can be further reduced to three types, namely technology–environment driven, technology–organization–environment synergistic and technology–organization driven. (3) There exists apparent synergy, compensation, and substitution relationships between technology, organization, and environmental conditions. The most important aspect of high-efficiency growth is not that all positive conditions are on a high level simultaneously, but that a complex of conditions corresponding to the foundation of regional development is created. (4) High and non-high MEGE growth have a strong causal asymmetry and the effective driving routes in various regions are also different. This paper extends the study of the efficiency of marine environmental governance in the two dimensions of internal stage structure and configuration mechanism, and applies accurate, path adaptation, and regional differentiation governance to coastal regions. Full article

Background: Memantine, an uncompetitive and voltage-dependent N-methyl-D-aspartate (NMDA) receptor antagonist, is clinically established for moderate-to-severe Alzheimer’s disease. Its pharmacodynamic profile, low-to-moderate affinity, rapid open-channel block, and strong voltage dependency allows selective inhibition of pathological NMDA overactivation while preserving physiological neurotransmission. Increasing evidence shows that these same mechanistic principles operate in the peripheral nervous system, where NMDA receptors contribute to excitotoxicity, oxidative stress, neuroinflammation, and maladaptive nociceptive signaling. Purpose: To synthesize emerging preclinical and clinical evidence demonstrating memantine’s modulatory and neuroprotective actions in peripheral neurons and glia and to outline implications for drug repurposing across neurology, pain medicine, oncology, supportive care, and ophthalmology. Methodology: A narrative integration of mechanistic studies, in vivo preclinical models, and heterogeneous clinical trials evaluating memantine’s effects on peripheral sensory neurons, autonomic neurons, Schwann cells, retinal ganglion cells, and neuromuscular junction physiology. Evidence was examined across conditions involving excitotoxicity, oxidative injury, mitochondrial dysfunction, apoptotic signaling, neuroinflammation, and neuropathic pain amplification. Results: Memantine consistently attenuates peripheral excitotoxic calcium influx, suppresses NOX-2–mediated ROS generation, stabilizes mitochondrial membrane potential, modulates Bax/Bcl-2 signaling, and reduces neuroinflammatory cytokine activity. It also inhibits dorsal horn wind-up selectively under neuropathic conditions. These convergent mechanisms yield protective effects across chemotherapy-induced peripheral neuropathy (CIPN), diabetic neuropathy, traumatic nerve injury, phantom limb pain, retinal ganglion cell excitotoxicity, and organophosphate-induced neuromuscular toxicity. Clinical evidence includes improved multimodal neuropathy outcomes in diabetic neuropathy when combined with gabapentin, reduced phantom limb pain prevalence and intensity at six months, and a five-fold reduction in post-mastectomy neuropathic pain with pre-emptive administration. Conclusions: Memantine should be conceptually reframed as a system-wide neuroprotective agent with substantial translational potential beyond the CNS. Priorities for future development include NR2B-selective peripheral NMDA antagonists, peripherally restricted formulations, single-cell transcriptomic mapping of peripheral NMDA receptor subtypes, and adequately powered PNS-specific randomized trials. Full article