Search Results (364)

Coastal sediments can store contaminants for decades and become exposure sources when disturbance alters partitioning, transport, or biological contact. We propose the Coastal Sediment Toxicological Activation Protocol (CSTAP), a theoretical and empirically testable protocol for organizing event-conditioned toxicological activation potential in coastal sediments. The associated Coastal Sediment Toxicological Activation Index (CSTAI) is an exploratory, semi-quantitative score intended for hypothesis generation and future calibration, not a validated toxicity endpoint or regulatory threshold. The CSTAP separates chemical burden, effective bioavailability, mixture pressure, event activation, receptor vulnerability, evidence adequacy, uncertainty priority, and procedural integrity. The primary score alone assigns the exploratory class, whereas evidence adequacy, uncertainty priority, and forensic readiness qualify interpretation without changing the class. The protocol includes benchmark selection, information-source safeguards against double counting, route-resolved receptor weighting, event and mass-conservation checks, data-tier declarations, and validation logic. Limiting-case tests, a reproducible worked example, and illustrative Mediterranean case encodings show internal coherence and reporting structure. The CSTAP is intended to guide monitoring design, scenario comparison, and calibration with paired chemistry, exposure, bioassay, and ecological-effect datasets. Full article

V-agents are exceedingly toxic oily substances, among which phosphonothiolates VX and VR have been extensively studied. Nevertheless, V-agents encompass a large family of nerve agents with diverse structures, including the phosphonate esters of alkyl acetoacetates or 2-alkoxycarbonyl-1-methylvinyl cycloalkyl methylphosphonates. These agents exist in two geometric isomers, and their properties remain largely unknown. Due to continuous concerns about chemical terrorism and safety, it is necessary to study their properties in order to develop effective countermeasures. Here, we applied computational tools to predict their ADME profile, chemical properties, and structure-related toxicity. These agents exhibited optimal drug-like properties, and it was predicted that they can penetrate the skin, acting as percutaneous hazards, and further penetrate the gastrointestinal tract and the blood–brain barrier. Certain CYP450 enzymes could differentially recognize the E- and Z-isomers, and this may explain the observation that E-isomers are significantly more toxic than their Z-counterparts. Analyses of the E- and Z-isomer stabilities also offered evidence for the reported lability of the Z-isomers. In conclusion, this study provides the first detailed in silico description of these V-agents, requiring future targeted experimental validation. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative condition marked by a gradual decline in cognitive abilities, a reduction in acetylcholine (ACh) levels, and the accumulation of β-amyloid (Aβ) plaques. In a healthy brain, approximately 80% of ACh is broken down by acetylcholinesterase (AChE). Meanwhile, butyrylcholinesterase (BChE) serves a supportive function, gaining significance as AChE activity diminishes during the progression of Alzheimer’s disease. Modern therapeutic approaches focus on creating dual inhibitors of AChE and BChE that also aim to diminish Aβ-amyloidogenesis through interactions with the peripheral anionic site (PAS). This study combined fragment-based molecular design (CReM), AI-assisted retrosynthetic feasibility assessment, and in silico evaluation (docking, molecular dynamics, and ADMET profiling) to identify novel Donepezil derivatives as potential dual AChE/BChE inhibitors. A series of 10,000 derivatives were developed through computational methods and carefully assessed based on stringent drug-likeness, synthetic accessibility, and medicinal chemistry standards. This was succeeded by comprehensive ADMET profiling. Nine candidates were identified with predicted CNS pharmacokinetics, adequate toxicological profiles and reduced cytochrome P450 liabilities. Molecular docking yielded improved predicted binding affinities relative to Donepezil. Several derivatives, particularly D4 and D5, showed dual-site binding poses spanning both the catalytic gorge and the PAS. MD simulations indicated the stability of these poses over 100 ns. These computational results suggest that the proposed derivatives may preserve or improve upon Donepezil’s pharmacokinetic profile while offering potentially balanced AChE/BChE inhibition and anti-amyloidogenic activity, pending experimental validation. Full article

Single-needle electrospinning and needle-free electrospinning were applied to fabricate cellulose acetate (CA) fibrous mats containing rosemary (RO), clove (CL) and thyme (TH) essential oils (EO) from binary or ternary solvent mixture solutions. When an acetone, dichloromethane, and dimethylformamide mixture was used as the solvent system, cylindrical nanofibers with an average diameter between 255 and 617 nm were obtained. Removing dimethylformamide from the spinning solution resulted in flattened microfibers with significantly larger diameters, varying from 1242 to 2939 nm. Furthermore, CA nanofibers loaded with RO, CL or TH essential oils with diameter distributions ranging from 55 to 176 nm, from 69 to 215 nm and from 44 to 291 nm, respectively, were produced from ternary solvent mixture solutions using needle-free electrospinning equipment. FTIR and TGA studies revealed the incorporation of essential oils into the fiber structure, and GC-MS was used to evaluate the release of bioactive components from fibrous mats. The electrospun nanofibers of CA/RO, CA/CL and CA/TH showed excellent antioxidant activity and antimicrobial properties against Escherichia coli, Pseudomonas aeruginosa and Listeria monocytogenes. In addition, the CA/CL fibrous mat was tested in the storage of fresh beef steaks. Full article

Deep eutectic solvents (DESs) have undergone a remarkable transformation over the past two decades, evolving from a laboratory curiosity into one of the most actively investigated solvent platforms in green chemistry. Yet, despite this rapid expansion, and although the field is well served by numerous topical reviews, it still lacks a corpus-wide, cross-disciplinary synthesis capable of guiding strategic research priorities, identifying critical knowledge gaps, and informing policy and industrial investment decisions. The present work addresses this need through a thorough analysis of global DES research from 2003 to 2025, based on a deduplicated corpus of 17,757 publications retrieved from the Web of Science Core Collection and Scopus following PRISMA-adapted screening guidelines. The analysis maps temporal publication dynamics, geographic and institutional contributions, thematic evolution, journal landscape, component usage patterns, international collaboration networks, market projections, and alignment with the United Nations Sustainable Development Goals. The results document an exponential growth trajectory—from a single publication in 2004 to 3954 in 2025 (CAGR > 30%)—and reveal a clear thematic transition from early electrochemistry-dominated research toward extraction, pharmaceutical, and environmental applications, with machine-learning-assisted design and hydrophobic DES formulations emerging as the most dynamic current frontiers. China leads global output with 6819 publications (38.4%), while the United States and Malaysia achieve the highest citation-per-publication ratios among the leading nations (≈46.7 and ≈38.9, respectively, versus ≈27.6 for China), and Spain pairs a comparatively modest output with a high h-index, indicating that impact is large relative to volume. Type III DESs and NADESs collectively account for approximately 69% of the literature, with choline chloride present in 72% of reported formulations. The global DES market, valued at approximately USD 166 million in 2024, is projected to reach USD 370 million by 2030. Despite this progress, critical translational barriers persist: fewer than 0.3% of publications include techno-economic or life cycle assessment analysis, standardized characterization protocols remain absent, and toxicological datasets are systematically incomplete. This panoramic analysis is intended to serve as an evidence-based reference for researchers prioritizing future directions, for funding agencies assessing the maturity and needs of the field, and for industrial stakeholders evaluating the readiness of DES technologies for scale-up. Full article

Background: Transdermal films are promising dosage forms for controlled delivery of active pharmaceutical ingredients through the skin. Polyvinyl alcohol (PVA)-based matrices are particularly attractive due to their biocompatibility, film-forming ability, and versatility. However, the development of films for volatile compounds such as menthol remains challenging due to high potential losses during processing and application. This study compares PVA-based transdermal films fabricated by 3D printing, solvent casting, and electrospinning, focusing on the effect of fabrication method on film properties, release behaviour, and skin delivery performance. Methods: A comprehensive characterization included morphology, structure, thickness, moisture content, mechanical properties, adhesion, menthol content, in vitro release, ex vivo permeation, and stability. Results: Fabrication method significantly influenced film microstructure, menthol entrapment, and stability. Menthol acted as a plasticiser, increasing thickness and moisture content while reducing mechanical strength via disruption of intermolecular interactions within the PVA matrix. The 3D-printed films exhibited the highest entrapment efficiency (14.40%, corresponding to 4.00% menthol content in the dried matrix) and superior menthol retention after 6 months (75.0%), compared to solvent-cast and electrospun films, due to their dense layered structure limiting volatile losses. All formulations showed biphasic release behaviour, strongly dependent on fabrication method. Electrospun films released menthol fastest (68.94% at 1 h), followed by solvent-cast films (63.48% at 1 h), whereas 3D-printed films exhibited a more sustained profile (46.14% at 2 h), reflecting differences in porosity and diffusion pathways. These structural differences also affected skin delivery, with 3D-printed systems demonstrating higher epidermal flux than the other formulations. Conclusions: Overall, fabrication method governed film microstructure and thereby controlled menthol entrapment, release, and transdermal performance. Extrusion-based 3D printing offers a promising strategy for designing transdermal systems for volatile compounds with improved structural control and delivery efficiency. Full article

This study presents new morphological, mineralogical, and chemical data on fibrous erionite, a carcinogenic zeolite, discovered for the first time in the volcanic rocks of the Vulsini Volcanic District, Italy. The erionite fibers were investigated using OM, TGA, SEM-EDS, XRPD, and EDXRF techniques. They occur as inhalable aggregates composed of extremely thin, tangled crystals with very high aspect ratios, features that may enhance both inhalability and toxicological significance. Mineralogical associations with saponite indicate formation under low-temperature hydrothermal conditions (<150 °C), likely related to late- to post-magmatic fluid circulation through cavities and vesicles in the host volcanic rocks. Chemical analyses identify the zeolite as erionite-K, reflecting the potassic character of associated volcanic lithologies and highlighting the influence of host-rock and fluid chemistry on zeolite formation. Trace-element contents, particularly in As, V, Rb, and Pb, may represent an additional factor influencing fiber toxicity through synergistic effects. The occurrence of carcinogenic fibrous erionite in volcanic lithologies widely exploited for quarrying and industrial applications raises significant environmental and occupational health concerns for zeolitized volcanic terrains in central Italy. These findings highlight the need for detailed fiber characterization and mineralogical investigations to support exposure prevention and environmental risk assessment in future excavation and quarrying activities. Full article

Chemical artificial intelligence increasingly relies on molecular property prediction models trained from proprietary compound libraries, bioassay records, and reaction-screening data. However, these data often contain commercially sensitive structures, confidential activity labels, and privacy-relevant experimental metadata, making direct centralization impractical. This paper proposes PrivMol, a privacy-preserving computational chemistry framework for federated molecular representation learning. PrivMol introduces two novel algorithms: Secure Substructure-Aware Federated Optimization and Differentially Private Molecular Gradient Calibration. The first algorithm decomposes molecular graphs into privacy-sensitive and task-relevant substructure regions, enabling local clients to train graph neural networks while transmitting only securely aggregated model updates. The second algorithm adaptively calibrates clipping and perturbation according to atom- and substructure-level contribution scores, reducing unnecessary utility loss on chemically informative fragments while retaining formal differential privacy guarantees. To improve robustness under heterogeneous chemical spaces, PrivMol incorporates local contrastive molecular alignment without exposing raw molecules, labels, scaffolds, substructure masks, or embeddings. Experimental evaluation on widely used public molecular benchmarks, including ESOL, FreeSolv, Lipophilicity, BBBP, BACE, HIV, and Tox21, demonstrates that PrivMol provides a favorable trade-off among prediction accuracy, communication efficiency, empirical leakage resistance, and privacy protection. The study offers a practical route toward secure collaborative chemical intelligence for computer-aided drug discovery, toxicology prediction, and materials informatics. Full article

Background: Conventional ophthalmic eye drops have low bioavailability (<5%) and poor patient adherence, driving the development of sustained-release ophthalmic drug delivery systems. The lacrimal drainage system represents a unique anatomical site for minimally invasive depot formulations. Objective: To summarize and critically appraise punctal and intracanalicular drug delivery systems, occlusive devices, and in situ-forming hydrogels with respect to composition, release mechanisms, clinical efficacy, safety, and critical quality attributes (CQAs). Methods: A narrative literature review was conducted using PubMed, Scopus, Web of Science, Google Scholar, ClinicalTrials.gov, and patent/regulatory sources, including FDA materials and Google Patents, covering 2001–2026. Anatomical features, materials, active pharmaceutical ingredients, release profiles, and adverse events were analyzed. Results: Seventy-one sources were included. Occlusive plugs without an active pharmaceutical ingredient demonstrate premature expulsion in up to 57.4% of cases and bacterial colonization in 44%. Drug delivery systems provide release from 7 days (PEGDA hydrogels) to 3 months (Eximore, Ocular Therapeutix™). DEXTENZA^® (dexamethasone) is FDA-approved for postoperative inflammation, whereas pivotal trials of travoprost (OTX-TP) and latanoprost systems (L-PPDS, EXP-LP) did not demonstrate superiority over placebo or eye drops. In situ systems eliminate size-fitting requirements but face challenges related to gelation control and biodegradation. Conclusions: We propose the following candidate CQAs: retention (>80% over 4 weeks), swelling degree (30–60%), controlled burst release (<40% within 24 h), and mechanical compatibility. The proposed QTPP matrices for punctal, intracanalicular, and in situ systems may guide the development of ophthalmic drug delivery platforms. Full article

Zinc oxide (ZnO) nanoparticles are semiconductor nanomaterials widely used in biomedical, environmental, and catalytic applications due to their unique physicochemical properties. However, their increasing environmental release has raised concerns regarding potential toxicity in aquatic ecosystems. In this study, pure ZnO, 1% Au-modified ZnO, and 5% Au-modified ZnO nanoparticles were synthesized via a reflux-assisted method to evaluate the effects of Au incorporation on morphology, crystallinity, optical behavior, surface chemistry, and ecotoxicological responses, using Artemia salina as a marine bioindicator. Structural characterization was performed using high-resolution transmission electron microscopy (HRTEM), electron diffraction, high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), and energy-dispersive X ray spectroscopy (EDS) elemental mapping, while optical and surface analyses were conducted using UV–Vis and Fourier-transform infrared (FT-IR) spectroscopy. Although Au-rich domains were identified, the available data do not allow definitive determination of whether Au is incorporated into the ZnO lattice or present as surface-associated metallic Au. Increasing Au content promoted greater nanoparticle agglomeration and broader particle size distributions while preserving the hexagonal wurtzite ZnO crystalline structure. UV-Vis and FT-IR analyses demonstrated that Au modification altered the optical response and surface chemical environment of the nanoparticles. Toxicological evaluations revealed concentration- and time-dependent toxicity. Pure ZnO nanoparticles exhibited LC₅₀ values of 531.25 ppm after 24 h and 65.15 ppm after 48 h exposure. In contrast, 1% Au-modified ZnO nanoparticles showed reduced toxicity, whereas 5% Au-modified ZnO nanoparticles exhibited increased toxicity after prolonged exposure. These findings demonstrate that Au modification significantly influences the physicochemical properties and biological interactions of ZnO nanoparticles. Full article

Polycyclic aromatic hydrocarbons (PAHs) represent a major class of ubiquitous environmental pollutants, posing significant risks to ecosystems and human health due to their persistence, toxicity, and potential for bioaccumulation. This review provides a comprehensive synthesis of current scientific knowledge on PAHs, integrating insights from chemical kinetics, environmental fate, and toxicological mechanisms. The fundamental structural chemistry of PAHs and its direct influence on their physicochemical properties and environmental properties are discussed. The major anthropogenic and natural sources of PAHs are detailed, alongside the chemical kinetics behind their formation during incomplete combustion and their transformation in environmental media. Unlike previous reviews that address PAH sources, remediation, or health effects as separate topics, this review uniquely traces the mechanistic continuum from molecular formation kinetics through physicochemical partitioning and environmental transport to toxicological endpoints, providing a causally linked framework for understanding how structural properties ultimately determine biological outcomes. A central focus is placed on the environmental fate and transport of PAHs across atmospheric, aquatic, and terrestrial compartments, highlighting processes such as gas–particle partitioning, sediment accumulation, and long-range transport. The review further elucidates the complex toxicological pathways of PAHs, including metabolic activation to reactive intermediates, DNA adduct formation, oxidative stress, and their roles in carcinogenesis and other systemic health effects. The analysis reveals strong scientific consensus on the carcinogenic mechanism of parent PAHs via CYP450-mediated metabolic activation to diol-epoxide intermediates while identifying critical areas of uncertainty: the current regulatory framework based on 16 priority PAHs underestimates total carcinogenic risk by a factor of 2–5, mixture toxicology remains poorly characterized, and dose–response relationships for non-cancer endpoints (cardiovascular, neurodevelopmental, immunotoxic) lack the quantitative data needed for robust risk assessment. Finally, human exposure pathways and health risk characterization approaches are discussed, highlighting the need for cumulative, mixture-based assessment frameworks. Full article

The transition toward a circular economy is accelerating the development of high-performance, sustainable polymeric materials derived from renewable resources. Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) represent a versatile class of biodegradable polyesters with inherent flexibility and tunable side-chain chemistry, making them attractive candidates for advanced polymer applications. Here, we report a novel class of bio-based polyurethanes (PUs) incorporating mcl-PHAs as soft segments, marking their first application in polyurethane synthesis and shifting towards greener PU synthesis. Polyurethane networks were prepared using castor oil (CO) and mcl-PHAs as polyols, with hexamethylene diisocyanate (HMDI) as a hard segment. Material properties were systematically tuned by varying the mcl-PHA/CO ratio (100/0 to 0/100), enabling precise control over structure–property relationships. Comprehensive characterization confirmed urethane bond formation and revealed predominantly amorphous materials with tunable thermal and mechanical behavior. Increasing mcl-PHA content enhanced elasticity and influenced phase organization, underscoring its role as a flexible, bio-derived soft segment. The resulting materials exhibited competitive mechanical performance alongside adjustable swelling behavior and morphology. Importantly, in vitro biocompatibility (MRC-5 fibroblasts) and eco-toxicological evaluation (Caenorhabditis elegans) confirmed the absence of toxicity. These findings highlight the potential of mcl-PHAs as sustainable building blocks for advanced polyurethane systems. Full article

Microplastics and nanoplastics (MNPLs) are increasingly recognized as dynamic vectors capable of transporting a wide range of environmental contaminants, as well as acting as physical particulates. Their small size, high surface reactivity and strong sorption capacity allow them to carry metals, pesticides, pharmaceuticals and endocrine-active compounds into biological systems. This narrative review examines how these particle-contaminant complexes influence oxidative stress, inflammatory signaling and endocrine function during early development. Relevant literature was identified through structured searches of PubMed, Scopus, Web of Science and Google Scholar, with a focus on the physicochemical properties of plastics, sorption mechanisms, gut barrier physiology and developmental toxicology. Early developmental stages are particularly sensitive, as immature mucus layers, permeable epithelial junctions and underdeveloped detoxification pathways facilitate the uptake and systemic distribution of MNPLs. Once internalized, these particles and their chemical cargo promote the generation of reactive oxygen species through redox-active contaminants, surface-catalysed reactions and mitochondrial dysfunction. The resulting oxidative imbalance activates stress-responsive pathways, including Nrf2–Keap1 signaling, and promotes lipid peroxidation, DNA damage and cellular dysfunction. MNPLs also stimulate inflammatory cascades by activating pattern-recognition receptors, altering cytokine profiles and disrupting epithelial homeostasis. These responses are intensified in the presence of sorbed pollutants, leading to sustained inflammatory states that can be particularly detrimental during organogenesis and immune maturation. Endocrine function is likewise affected, as MNPLs transport hormonally active chemicals and can interfere with hormone-responsive pathways through oxidative and inflammatory mechanisms. These interactions may disrupt thyroid signaling, metabolic regulation and the development of the reproductive axis, with potential long-term physiological consequences. Integrating evidence from polymer chemistry, contaminant behavior and developmental physiology, this review shows that MNPLs act as biologically active vectors that may increase oxidative, inflammatory and endocrine disturbances during early development. These findings highlight the importance of considering particle–contaminant interactions as a critical component of early-life risk assessment. Full article

Optimizing the extraction of bioactive compounds from Solidago sp. is essential for the development of plant-derived products with therapeutic and nutraceutical potential. Microwave-assisted (MW) and thermal maceration (TM) extraction of S. canadensis aerial parts were comparatively investigated to maximize total flavonoid content (TFC). The obtained extracts were subsequently freeze-dried for storage prior to chemical and biological analyses. Extraction conditions were optimized using a Box–Behnken design. Chemical characterization was performed by FTIR, HPLC-PDA, LC-MS/MS, and GC-MS, enabling detailed profiling of phenolic compounds and terpenoids. Antioxidant capacity was assessed using the DPPH radical scavenging assay, while cytotoxic activity was evaluated against HepG2, HCT-8, and HT-29 tumor cell lines, with HEK-293 cells used as a non-tumorigenic control cell line. Multivariate analysis (PCA) was applied to establish relationships between phytochemical composition and biological responses. Higher TFC values were obtained using MW extraction, whereas TM extracts exhibited greater antioxidant activity. Both extract types induced selective cytotoxic effects against tumor cell lines, while maintaining negligible toxicity toward normal HEK-293 cells. PCA revealed distinct clustering patterns between MW and TM extracts and confirmed a strong association between phenolic composition and bioactivity. The combination of optimized extraction, freeze-drying, and integrated chemical–biological evaluation produced S. canadensis extracts with well-defined phytochemical profiles and biological activity, supporting their potential use in nutraceutical, and pharmaceutical applications. Full article

Background: Interpretation of pesticide residues in fruits requires tight integration of surveillance evidence, analytical capability, regulatory context, and mitigation data. Methods: This critical integrative review synthesises analytical chemistry, cumulative risk assessment (CRA), regulatory divergence, and mitigation evidence, strengthened by quantitative monitoring summaries and auditable regulatory examples. Routine enforcement continues to rely on validated QuEChERS extraction coupled with targeted LC-MS/MS and GC-MS/MS. High-resolution mass spectrometry (HRMS) adds unique value for metabolites, transformation products (TPs), and incident response, but its routine enforcement role remains constrained by confirmation logic and harmonised validation. Results: Monitoring shows that exposure is typically multi-residue rather than single-compound; the key interpretive challenge therefore shifts toward CRA prioritisation, sensitive-subpopulation assumptions, and transparent distinction between compliance signals and toxicological inference. We provide (i) headline compliance metrics from EU and US programmes, (ii) surveillance-derived high-frequency residue patterns and co-occurrence motifs to guide CRA prioritisation, (iii) an illustrative, traceable comparison of EU/US/Codex MRL divergence for emblematic citrus residues with EU evidence extracts and US/Codex traceability records, and (iv) mitigation evidence statements standardised by study type and transformation-product reporting. Conclusions: Pesticide residues in fruits should be interpreted through a risk-based framework that distinguishes compliance findings from toxicological concern, prioritises relevant multi-residue drivers, and evaluates mitigation according to both residue reduction and transformation-product uncertainty. Full article