Search Results (943)

Titanium dioxide nanoparticles (TiO₂ NPs) are incorporated into automotive coatings to enhance durability, corrosion, UV resistance, and, in some formulations, photocatalytic self-cleaning. While the toxicology of pristine TiO₂ is well studied, the behavior of TiO₂ NPs embedded in polymer matrices and subjected to real-world aging, maintenance, and removal remains poorly characterized. This narrative review synthesizes 24 publications spanning the lifecycle of TiO₂ nano-enabled automotive coatings, from synthesis and formulation through application, in-service weathering, repair, refinishing, and end-of-life environmental fate. Upstream properties, such as coating functionality and performance, have been examined as determinants of later-life release, exposure, and fate. Across studies, dispersion state, interfacial compatibility, and surface modification—together with transformations such as agglomeration, photocatalysis, weathering, and eco-corona formation—shape particle stability, release, exposure relevance, and toxicological risk. Evidence indicates that sanding and accelerated weathering predominantly generate matrix-associated, polymer-fragment-dominated aerosols rather than pristine TiO₂ NPs, while NP-specific exposure measurements during spray application remain limited. Hazard data suggest matrix embedding may attenuate, but does not eliminate, biological responses relative to pure particles. Wastewater treatment plants and biosolids have been shown to act as sinks with potential for soil accumulation following sludge application. Regulatory frameworks rarely account for aging, transformation, and release, stressing the need for synchronized testing of aged materials and nano-specific exposure metrics to support safer-by-design coatings and risk governance. Full article

Microplastics (MPs) and nanoplastics (NPs) have emerged as pervasive contaminants across diverse environments—including soil, water, and the atmosphere—posing substantial risks to resident organisms. Concurrently, alien plant invasion represents a significant driver of environmental change, introducing considerable ecological risks to terrestrial ecosystems. Synthesizing evidence from 26 original research articles, this review examines the bidirectional interactions between micro(nano)plastics (MNPs) and terrestrial invasive plants. A growing body of evidence indicates that MNPs alter the growth and performance of both invasive and native plants. In most documented cases, MNPs appear to enhance the competitive ability of invasive plants, thereby elevating invasion potential. However, counterexamples exist wherein MNPs strengthen the competitiveness of native plants, consequently mitigating invasion risk. These divergent outcomes are likely attributable to a suite of influencing factors, notably the characteristics of the MNPs (e.g., type, size, concentration), the specific invasive and native plant species involved, and variations in experimental conditions. Key mechanistic pathways involve MNPs-induced disturbances in soil microecology—particularly nutrient dynamics and rhizosphere microbiomes—and allelopathic interactions. Conversely, invasive plants may adsorb/absorb MNPs and subsequently modify their environmental fate and behaviors (e.g., degradation, transport). Finally, we delineate critical knowledge gaps and propose prioritized directions for future research. This review advances our understanding of the ecological risks associated with plant invasions in an era of pervasive MNP pollution and offers a scientific foundation for developing informed management strategies. Full article

Background: The principal glial cells of the retina, Müller glia, play a central role in retinal regeneration in teleost fish and have recently attracted attention as potential sources of neuronal regeneration in mammals. Objectives: In this study, we examined whether SV40-immortalized rat Müller glia could be directed toward neuronal differentiation using a non-genetic approach with defined culture conditions. Methods: Comprehensive transcriptomic profiling by RNA sequencing indicated that changes in culture medium alone could induce transcriptional reprogramming toward a neuronal lineage. Results: Specifically, expression of Müller glia-related genes decreased, while a subset of photoreceptor-related transcription factors and specific genes showed altered expression, suggesting early-stage induction toward a photoreceptor-like fate. This finding suggests that even immortalized cells may exhibit activation of neuronal genes through non-genetic culture interventions. Gene set enrichment analysis further revealed upregulation of pathways related to the synaptic vesicle cycle, metabolic activation, oxidative stress defense, and lysosomal function, consistent with initiation of neuronal differentiation. Conversely, pathways associated with cell cycle regulation and stemness signaling were downregulated, reflecting a transition from a proliferative to a differentiation-prone state. Collectively, these results provide preliminary molecular markers for early neuronal induction and potential targets for chemical screening. Conclusions: Importantly, this strategy enables neuronal-like differentiation of Müller glia without genetic manipulation, offering a safe and cost-effective platform. Overall, our findings may support the development of in vitro models for retinal neuroregeneration and facilitate research toward regenerative therapies for retinal disorders. Full article

Transcriptional regulation is pivotal for developmental processes and cell fate specification in homeostasis. One particularly relevant group of transcription factors is the sine oculis homeobox (SIX) family, which is involved in a wide range of molecular processes from development to tissue maintenance. Within this family, distinct subfamilies exhibit specific DNA-binding preferences and can function as transcriptional activators or repressors. In this review, we focus on the Optix/SIX3–SIX6 subfamily and discuss their roles as transcriptional regulators, as well as the consequences of their deregulation for neuronal and ocular development and for the maintenance of tissue homeostasis. We further examine how SIX3 can act either as a tumour suppressor or as a marker of poor prognosis in different cancer types. Moreover, we summarize recent findings on the role of SIX3 in pancreatic β cells and highlight emerging evidence that SIX2 also contributes to β-cell identity and regulatory stability. Downregulation of SIX2 and SIX3 alters gene regulatory programs associated with β-cell homeostasis and contributes to type 2 diabetes. As accumulating evidence links members of the SIX family to cancer and metabolic disease, it is crucial to characterize how these transcription factors regulate cell identity, with important implications for disease mechanisms and therapeutic strategies. Full article

Emerging contaminants (ECs) comprise diverse pollutant classes that are increasingly detected in remote environments due to their persistence and long-range transport potential. In cold regions, atmospheric cold-trapping processes favour their accumulation in high-altitude and high-latitude snow and ice, which act as sensitive archives and secondary sources of contamination. While previous studies have addressed individual environmental compartments (e.g., snowpack, glacier ice, meltwater), focusing on specific contaminant classes, a systematic review integrating the occurrence, behaviour and impacts of major EC groups in polar and alpine snow and ice is still lacking. To fill this gap, this work synthesised current knowledge on the environmental fate of three key EC categories in the cryosphere: metals and metalloids (MMs), industrial chemicals and by-products (ICBs), and pharmaceuticals and personal care products (PPCPs). PRISMA guidelines were accurately followed for research, which was based on a Google Scholar search combining keywords on cryospheric matrices (snow, firn, ice cores), geographical regions (Arctic, Antarctic, Alps, high mountains), and contaminant classes. Of 350 records initially identified, 300 met the eligibility criteria (post-industrial snow, firn, or ice cores studies) after excluding studies focused on aerosol or meltwater-only, method-focused papers, pre-industrial datasets, urban-only investigations, and duplicates. Risk of bias was qualitatively assessed through manual screening, evaluating matrix eligibility, temporal consistency, analytical methods, detection limits, and duplicate data, with particular attention to inconsistencies in ECs classification. Strict operational definitions were therefore applied to ensure methodological coherence. Concentration data were harmonised into a standardised database, and findings were synthesised through a structured narrative supported by tabulated datasets organised by matrix and site. Overall, the evidence indicates widespread occurrence of ECs in the global cryosphere, with spatial variability linked to emission sources, long-range transport pathways, and snow physicochemical properties. Climate-change-driven alterations of snow dynamics, glacier retreat and permafrost thaw are expected to modify partitioning equilibria and enhance the secondary release of legacy and contemporary contaminants. However, significant limitations persist, including geographical gaps, variability in analytical sensitivity, lack of long-term monitoring for certain EC classes, and inconsistencies in contaminant classification frameworks. Despite these constraints, the synthesis highlights consistent emerging patterns and underscores the need to strengthen existing environmental protocols to mitigate potential risks to ecosystems and human health. Full article

The aim of this work is to present the Peripatetic doctrine of fate (heimarmene) according to Alexander of Aphrodisias in his treatise Peri heimarmenes or De fato. The central thesis of this Alexandrian work is that everything that occurs kata ten physin (in accordance with nature) occurs kath’ heimarmenen (in accordance with fate). In order to reconstruct the doctrine underlying this claim, I alternate between an exposition of the Aristotelian concepts addressed in Alexander’s writings and his own theoretical elaborations. The paper begins by outlining the terms of the debate on fate as presented by Alexander. It then reconstructs the Alexandrian account of the causality of fate, along with the Aristotelian presuppositions that support it. Finally, it examines specific aspects and limits of Alexander’s notion of fate, particularly in relation to other key concepts in his philosophy, such as what occurs katà symbebekos, human proairesis, and divine pronoia. De fato is the main reference for this paper, but other relevant works, including the Quaestiones and De Providentia, are also considered. Full article

Fluorescent dyes are commonly used as tracers in hydrological investigations to quantify transport pathways, residence times, mixing behavior, and connectivity in surface water, groundwater, and coastal systems. Despite their long history of application, the ecological implications of deliberate dye releases are not well understood. This review synthesizes current knowledge on the physico-chemical characteristics, environmental behavior, and ecotoxicological effects of major dye classes, with emphasis on rhodamines, fluorescein derivatives, and sulfonated xanthene dyes commonly used in water tracing studies. Toxicity data for algae, cyanobacteria, invertebrates, and fish show large inter-specific variability. Some dyes, particularly rhodamine B and eosin Y, show acute or sub-lethal effects at concentrations detected during poorly controlled applications. By contrast, dyes with high polarity and extensive sulfonation (e.g., rhodamine WT, sulforhodamine B, pyranine, and fluorescein) show consistently low toxicity and minimal bioaccumulation potential. Environmental fate processes, including photolysis, sorption, and transformation into potentially more reactive products, influence exposure dynamics, especially in clear, shallow, or slow-moving systems. This review also evaluates regulatory frameworks and operational guidance for safe use, identifies gaps in toxicological and fate data, and proposes recommendations for minimizing environmental impact through dye selection, mass optimization, injection design, and monitoring. The findings support the continued use of fluorescent dyes but highlight the need for more systematic assessment of transformation products, chronic and sub-lethal responses, and cumulative exposure in sensitive environments. Full article

Type I interferons (IFN-I) are pleiotropic cytokines best known for their antiviral impacts. However, they are known to also impact immune responses outside of viral infection through directly signaling many populations of innate and adaptive immune cells. Here, we focus on the complex body of findings from viral, bacterial, and parasitic infection models, cancer and autoimmunity studies, as well as in vitro experiments using human and murine T cells, demonstrating that IFN-I can be directly sensed by CD4 T cells. Such signaling has been shown to influence many central aspects of antigen-specific CD4 T cell responses, including proliferation, apoptosis, effector subset differentiation, and memory formation. These effects are frequently divergent and sometimes opposing, likely reflecting how differences in variables related to the IFN-I signal, overall inflammatory milieu, and the CD4 T cell integrate to shape outcomes. Indeed, we discuss findings supporting a framework in which dynamic engagement of canonical and non-canonical signaling pathways downstream of IFN-I, which are contingent on a cell’s activation state, play a key role in determining whether and how IFN-I promotes, restrains, or otherwise reprograms CD4 T cell fates. Together, these observations highlight the impressive scope of regulation that IFN-I signals to CD4 T cells can exert, parallel to its actions on other immune and non-immune cell types. They also suggest that harnessing such signaling could offer powerful therapeutic strategies to shape CD4 T cell immunity in diverse context-dependent situations. Full article

Background/Objectives: Commiphora gileadensis (Balm of Gilead) is an aromatic medicinal plant with a history of traditional use in ancient and Arabic medicine. It has been used traditionally to treat inflammation, infections, and wounds. Despite its long-standing cultural and economic importance, modern pharmacological validation requires a comprehensive synthesis of current scientific data. This review aims to provide a thorough comparative summary of the phytochemical composition and biological activities of its diverse products. Methods: An updated literature search was conducted using databases such as ScienceDirect, PubMed, Scopus, and Google Scholar, covering publications from approximately 2000 to 2025. The review included English-language peer-reviewed articles, books, and reports providing phytochemical analyses or biological evaluations. Data were manually extracted and categorized by plant parts (resin, leaves, bark, stems), major constituents, and specific pharmacological activities. Results: The review identified ten diverse chemical groups, mainly terpenoids (mono-, sesqui-, di-, and triterpenes) and flavonoids. Other remarkable classes included phenolic acids, phytosterols, lignans, coumarins, and fatty acids. However, the essential oil chemical profile is highly variable, influenced by geographical origin and preparation technique. Pharmacological studies demonstrated a wide spectrum of bioactivities, in particular antioxidant, anti-inflammatory, antimicrobial, anticancer, antidiabetic, and wound-healing properties. Toxicological studies classified the plant as generally non-toxic; however, there is a notable lack of clinical and pharmacokinetic data. Conclusions:C. gileadensis possesses a rich and diverse secondary metabolite profile, validating its traditional ethnobotanical applications. Future research should prioritize pre-clinical and clinical trials to establish its safety, bioavailability, and metabolic fate for its successful integration into modern medicine. Full article

Dysregulation of iron and copper homeostasis is a pivotal driver of regulated cell death through two distinct yet interconnected modalities: ferroptosis and cuproptosis. This comprehensive review evaluates the therapeutic modulation of these metal-driven pathways within a dual paradigm: their deployment as a cytotoxic weapon in oncology and their inhibition for neuroprotection. We synthesize evidence ranging from small-molecule synergy to advanced nanomedicine, examining how the interplay between iron and copper governs cellular fate in resistant malignancies and neurodegenerative diseases such as Parkinson’s disease and Multiple Sclerosis. In oncology, bimetallic nanoplatforms and CRISPR-Cas9 nano-ionophores exploit “iron addiction” and metabolic vulnerabilities to induce fatal lipid peroxidation and FDX1-mediated proteotoxic stress, often by circumventing efflux transporters like ATP7A/B. Conversely, neuroprotective strategies focus on site-specific chelation, utilizing brain-penetrant molecules like SK4 (targeting the LAT1 transporter) and radical trapping antioxidants like Cu^II(atsm). Importantly, we elucidate the “iron trap” mechanism, where copper deficiency inactivates multicopper ferroxidases—including ceruloplasmin and hephaestin—thereby triggering iron-dependent ferroptosis. Our analysis reveals a self-amplifying cycle of oxidative damage driven by metal-induced ATP depletion and glutathione exhaustion. By delineating the molecular machinery of iron and copper metabolism, this article provides a roadmap for leveraging regulated cell death to overcome apoptosis resistance in cancer and preserve neural integrity in chronic degeneration. Full article

Background/Objectives: Bone marrow adipose tissue (BMAT) serves multiple physiological roles but accumulates with age, compromising skeletal health. This expansion is largely driven by an adipogenic drift of bone marrow mesenchymal stromal cells (BMSCs), shifting attention toward stromal cell fate regulation as a target to preserve bone marrow homeostasis. Preventing adipogenic commitment may be as relevant as directly inducing osteogenesis for maintaining a bone-permissive marrow microenvironment. Here, we investigated whether olive leaf extract (OLE) and its purified secoiridoid components, oleacin (OC) and oleuropein aglycone (OA), modulate the adipogenic differentiation and proliferative capacity of human BMSCs. Methods: Human BMSCs were induced to undergo adipogenic differentiation and treated with OLE, OC, or OA. Intracellular lipid accumulation and the expression of key adipogenic regulators were assessed. Proliferative capacity was evaluated under both maintenance and adipogenic conditions. Results: Under adipogenic conditions, OLE markedly reduced intracellular lipid accumulation and induced a coordinated downregulation of PPARγ, PLIN1, FABP4, ADIPOQ, LEP and the adipogenesis-associated miR-422a. In contrast, OC and OA exerted more selective and specific effects on biomarkers, indicating the partial and complementary modulation of adipogenic programs. Notably, OLE also increased BMSC proliferation under both maintenance and adipogenic conditions, suggesting the preservation of a less committed stromal cell pool. Although the relative contribution of enhanced proliferation versus the direct inhibition of adipogenic pathways cannot be fully disentangled, the combined molecular and functional data support a dual action of OLE on stromal cell fate. Conclusions: OLE limits adipogenic commitment while maintaining stromal cell proliferative competence, processes that are critically involved in BMAT expansion and bone marrow dysfunction. OC and OA contribute to OLE bioactivity deserving further investigation, particularly in combination, as potential modulators of BMAT expansion. Full article

Periodontal disease is a chronic inflammatory condition that destroys tooth-supporting tissues, particularly the alveolar bone and the periodontal ligament, and effective regenerative therapies remain limited. While the role of metabolic–epigenomic crosstalk in determining cell fate is well established, the specific mechanism by which a tricarboxylic acid (TCA) cycle metabolite can modulate chromatin regulation to promote periodontal regeneration remains to be elucidated. The impact of one TCA cycle metabolite, alpha-ketoglutarate (α-KG), was examined in human periodontal ligament fibroblasts cultured under osteogenic induction and profiled by ALP assays, RT-qPCR, analyses of multiple histone modifications, ATAC-seq, and RNA-seq. α-KG increased ALP activity and upregulated genes associated with osteogenesis and the extracellular matrix (ECM). ATAC-seq revealed minimal genome-wide accessibility changes, whereas histone analyses showed reduced H3K27me3, consistent with an epigenetic mechanism that does not require extensive chromatin opening. The RNA-seq identified 14 upregulated α-KG-induced genes, including multiple components of the OGN-OMD-PLAP1/ASPN-ECM2 loci, supporting an osteogenic/ECM transcriptional program. In a mouse periodontal regeneration model, oral administration of α-KG enhanced alveolar bone regeneration and reduced H3K27me3 signals and collagen-rich tissue organization within the periodontal ligament space. These findings identify α-KG as a metabolite-driven epigenetic modulator that alleviates H3K27me3-mediated repression and supports periodontal regeneration. Full article

Plastic contamination in agricultural soils constitutes an emerging threat to plant growth, nutrient acquisition, and food safety. Micro- and nanoplastics (NPs) elicit oxidative stress, perturb root morphology, and interfere with key physiological processes. Despite extensive studies in aquatic systems, the mechanistic understanding of NP behavior in soils, particularly the formation of soil-specific eco-coronas, remains limited. This review provides a mechanistic synthesis of current evidence on the role of root exudates, comprising proteins, amino acids, lipids, and low-molecular-weight metabolites, in modulating NP fate and plant responses within the rhizosphere. We delineate key processes, including exudate adsorption onto NP surfaces, eco-corona formation, aggregation, transport, root uptake, and species- and polymer-specific effects. Root exudation dynamically alters NP surface properties, mediates heteroaggregation, modulates mobility, and regulates interactions with plant roots. At the same time, NP exposure induces species-specific metabolic responses, including enhanced secretion of organic acids, stress-related metabolites, and secondary compounds (e.g., flavonoids). Despite extensive research in aquatic and hydroponic systems, mechanistic understanding of NPs behavior in soils, particularly regarding eco-corona formation and the modulatory role of root exudates, remains limited. This review synthesizes these insights to propose a conceptual framework linking eco-corona dynamics with root exudation processes, thereby providing a foundation for future soil-focused investigations. Full article

Breast cancer is the leading cause of cancer-related death in women, and despite advances in preventive screening as well as in molecular classification, many patients still do not benefit from existing therapies, highlighting the importance of identifying new molecular determinants of treatment resistance. The Paired-box (PAX) family of developmental transcription factors are central regulators of tissue morphogenesis and lineage specification, yet their reactivation in tumors and contribution to breast cancer progression remain only partially defined. Here, a multi-level analysis integrating RNA sequencing and protein profiling in twenty-one primary breast carcinomas shows that distinct PAX members are directly correlated to distinct fundamental cancer hallmarks, including proliferation, cell death, epithelial–mesenchymal transition, immune evasion, and genomic instability. Specifically, PAX1 and PAX9 correlates with both cell death and proliferative markers, indicating dual roles in the regulation of cell fate. PAX1 and PAX9 correlate with both proliferative and apoptotic markers, indicating dual roles in cell fate regulation. PAX3, PAX5, and PAX8 are mainly associated with immune checkpoint expression, including PD-L1 and TIGIT, while PAX6 is linked to microsatellite instability and tumor mutational burden, implicating it in genomic dysregulation. Therefore, PAX-based molecular signatures identify that accurately predict lymph node metastasis at transcriptomic (PAX2–PAX7) levels. These findings establish PAX transcription factors as key modulators of breast cancer biology and support their potential as clinically relevant biomarkers for prognostic refinement and therapeutic stratification. Full article

The endoplasmic reticulum (ER) is a central hub of cellular proteostasis, coordinating protein folding, lipid metabolism, calcium signaling, and inter-organelle communication. Disruptions in ER function activate the unfolded protein response (UPR), an evolutionarily conserved signaling network mediated by PERK, IRE1α, and ATF6. Initially viewed primarily as a stress-mitigating mechanism, the UPR is now recognized as a central coordinator of diverse cellular stress-response pathways. This review focuses on mechanistic insights into UPR signaling, with particular emphasis on its crosstalk with oxidative stress regulation, mitochondrial function and mitochondria–ER contact sites, autophagy, inflammatory signaling, and metabolic sensing. The analysis integrates evidence from biochemical and structural studies, genetic and pharmacological perturbation models, and selected in vivo investigations from PubMed and Google Scholar between 2000 and 2025, focusing on mechanistic, experimental and translational studies addressing UPR signaling and ER stress. Together, these studies demonstrate how transient UPR activation promotes cellular adaptation through coordinated transcriptional, translational, and organelle-specific responses. We further discuss how sustained or unresolved ER stress alters UPR outputs, shifting signaling toward maladaptive outcomes such as mitochondrial dysfunction, dysregulated autophagy, oxidative imbalance, and apoptosis. By placing the UPR within a network of interconnected stress pathways, this work provides a framework for understanding how ER proteostasis is linked to cell fate decisions under stress. Full article