Search Results (134,399)

Mitochondrial dysfunctions contribute to the pathogenesis of tauopathies, a group of neurodegenerative diseases with abnormal accumulation of microtubule-associated protein tau. The combination of 5-aminolevulinic acid (5-ALA) and sodium ferrous citrate (SFC) is known to improve mitochondrial functions. Here, we report that 5-ALA combined with SFC (5-ALA/SFC) improves mitochondrial functions and mitigates neurodegeneration in transgenic Drosophila expressing human tau. We found that tau reduces ATP levels, decreases mitochondrial distribution to neurites, and increases mitochondrial reactive oxygen species (ROS). Expression of oxidative phosphorylation (OXPHOS) genes was upregulated, and activities of complexes I and IV were elevated. Feeding 5-ALA/SFC to tau flies lowers oxidative damage without correcting OXPHOS activities or mitochondrial distribution. 5-ALA/SFC treatment suppressed pathological tau phosphorylation and mitigated tau-induced neurodegeneration. These results suggest that 5-ALA/SFC attenuates a neurodegenerative pathway involving tau, mitochondria, and ROS. Full article

Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor, has garnered attention for its cardiovascular benefits beyond glycemic control. Ferroptosis, a novel form of regulated cell death, contributes to the pathogenesis of diabetic cardiomyopathy (DCM). However, whether EMPA mitigates DCM by suppressing ferroptosis remains unclear. Here, Type 2 diabetic db/db mice were used to establish a DCM model and treated with EMPA (10 mg/kg/day) for 12 weeks. EMPA significantly improved cardiac function, reduced myocardial fibrosis, and attenuated ferroptosis, concomitant with upregulated silent information regulator 3 (SIRT3) expression. In the rat cardiomyocytes (H9c2 cells) exposed to high glucose and palmitic acid, EMPA treatment or SIRT3 overexpression alleviated oxidative stress, mitochondrial dysfunction, and ferroptosis. Mechanistically, molecular docking, molecular dynamics simulation, cellular thermal shift assay and drug affinity responsive target stability assay confirmed that SIRT3 is the drug target of EMPA, stabilizing its protein levels and reducing acetylated p53 expression. Notably, SIRT3 silencing abolished EMPA’s beneficial effects on oxidative stress and ferroptosis. Our findings demonstrate that EMPA exerts cardioprotective effects by inhibiting oxidative stress and ferroptosis in cardiomyocytes, which is mediated by SIRT3. This study provides novel insights into the mechanisms underlying EMPA’s therapeutic effects in DCM. Full article

Background: Chronic stress is a major contributing factor to mood disorders, including depression and anxiety; however, the molecular mechanisms underlying individual differences in susceptibility to such disorders remain poorly understood. DNA methyltransferase 3a (Dnmt3a), a key epigenetic regulator, has been increasingly implicated in stress-related neurobiological adaptations. In this study, we employed a well-established mouse model of chronic social defeat stress (CSDS) to investigate the functional role of Dnmt3a in modulating individual susceptibility to social stress. Methods: Male C57BL/6J mice were exposed to chronic/submaximal social defeat stress (CSDS/SSDS). AAV vectors were used to achieve Dnmt3a overexpression or global and oligodendrocyte-specific knockdown in the nucleus accumbens (NAc). Behavioral tests, including social interaction, open field, and elevated zero maze, were conducted alongside Western blotting and immunofluorescence assays. Results: CSDS selectively increased Dnmt3a expression in NAc oligodendrocytes of stress-susceptible mice. Overexpression of Dnmt3a in the NAc enhanced susceptibility to stress, whereas its knockdown conferred resilience, without affecting baseline behaviors. Dnmt3a negatively regulated myelin basic protein (MBP) and dopamine D1 receptor expression. Stress-susceptible mice exhibited shortened myelinated segments and reduced D1 receptor levels, while D2 receptor expression remained unchanged. Conclusions: Dnmt3a in NAc oligodendrocytes modulates susceptibility to social stress through a Dnmt3a-MBP/D1 receptor-NAc pathway, highlighting a critical glia-neuron interaction. This mechanism extends our understanding of the neurobiological basis of stress-related disorders and positions Dnmt3a as a promising therapeutic target for developing precision interventions or biomarkers. Full article

The aim of this study is to conduct a comprehensive assessment of the water quality of the Sidi Mohammed Ben Taiba (SMBT), one of the largest drinking water reservoirs in northwestern Algeria, by integrating chemical and biological indicators. The assessment combines the Drinking Water Quality Index (DWQI), the Irrigation Water Quality Index (IWQI), the Organic Pollution Index (OPI) and zooplankton-based biological indicators (Zoo-IQ). A total of 23 physicochemical parameters were analyzed and interpreted using multivariate statistical approaches. This study fills an important knowledge gap by evaluating long-term temporal variability (January 2018–May 2025) and recent spatial heterogeneity (June 2023–May 2025), aiming to support sustainable water management. The results indicate that the reservoir water quality is generally suitable for drinking purposes (22.3 < DWQI < 54.0), is deemed excellent for agricultural irrigation (65 < IWQI < 69) and that the reservoir surface waters are slightly polluted to unpolluted (0.3 < OPI < 1.1). However, a deterioration in water quality has been detected in recent years, linked to increasing nutrient concentrations, as confirmed by the TSI–SD index. Despite the early signs of nutrient enrichment, the Zoo-IQ index remained within the moderate to good range, suggesting a certain degree of resilience in the zooplankton community. However, pronounced seasonal fluctuations observed in the Zoo-IQ and species diversity (H′) during periods of environmental stress serve as an early warning signal of emerging problems that may negatively affect water quality indices (WQI, IWQI, OPI). Station S4, located at the confluence of Wadi Belhassen and Wadi Farhat, descending from the Dahra mountain range in Algeria, has been identified as the most sensitive area and a potential hotspot for future pollution. The study provides robust data on the quality of reservoir water, offering a valuable decision-making tool for artificial reservoir managers and contributing to sustainable water management by identifying risk areas and supporting the implementation of preventive measures. Full article

Prestressed concrete railway sleepers are key structural components that determine the safety, durability, and serviceability of modern railway infrastructure. This study presents a comprehensive investigation of the design, testing, and acceptance of prestressed concrete sleepers in accordance with EN 13230, with particular reference to the requirements applied on the Polish railway network. The analysis integrates normative provisions, analytical calculations, finite element modeling, and experimental verification, including static, dynamic, and fatigue load tests. Special attention is given to the k_t coefficient, which accounts for prestress losses, fatigue degradation, and the development of concrete strength throughout the service life. This coefficient plays a critical role in the acceptance criteria for sleepers during mandatory product testing. The influence of concrete age on the variability of k_t is examined, showing that the highest variability occurs within the first 180 days of curing. Full-scale laboratory tests performed on PS-94 sleepers confirm compliance with standard requirements regarding cracking loads, crack width limits, and ultimate load capacity under both exceptional and fatigue loading conditions. Numerical simulations provide additional insight into stress and displacement distributions in critical cross-sections, supporting the experimental findings. The results indicate that most of prestressing force losses occur during the early service period. This observation supports the application of age-dependent acceptance criteria, which may improve conformity assessment procedures for prestressed concrete railway sleepers in contemporary railway engineering practice. Full article

Objectives: This study evaluates the research landscape of the cyanobacterium Spirulina (recently reclassified as Limnospira), a strategic resource in the nutraceutical, pharmaceutical, and functional food industries. The central objective is to transition from the traditional “superfood” narrative to a structured analysis of its modern therapeutic potential as reflected in current scientific literature. This study employs bibliometric analysis to highlight research trends and thematic directions in Spirulina-related studies, rather than to experimentally validate therapeutic effects. Methods: The investigation employed an exploratory bibliometric analysis of 996 peer-reviewed articles indexed in the Web of Science (2016–2025). Using VOSviewer software, we mapped keyword co-occurrence networks, international collaborations, and institutional clusters to identify dominant thematic directions and emerging research frontiers in biotechnology and medicine. Results: Bibliometric mapping illustrates research trends and thematic associations reported in the scientific literature centered on pathophysiological mechanisms, particularly oxidative stress, inflammation, and hepatoprotection. While often referred to as “microalgae”, Spirulina is biologically a photosynthetic prokaryote with a unique lipid profile characterized by high gamma-linolenic acid (GLA) content, although clinical evidence remains heterogeneous. The analysis highlights a robust regional research hub in the Middle East and North Africa, led by Egypt and Saudi Arabia, in contrast to fragmented inter-continental collaboration. Conclusions: The steady upward trend in publications confirms expanding academic interest in Spirulina as a functional ingredient. However, this study underscores a persistent gap between in vitro bioactivity and standardized clinical validation. These findings provide a roadmap for future biotechnological developments, emphasizing the need for more rigorous, multi-center clinical trials to bridge the “superfood” perception with evidence-based therapeutic applications. Full article

Background/Objectives: Excess consumption of energy-dense foods (EDF; ultra-processed snacks, sweets, and sugar-sweetened beverages) among preschool-aged children is a public health concern, particularly in low-income families. Caregiver parenting style, psychological stress, and food-parenting practices (FPP) may shape children’s EDF consumption, yet little is known about how these factors operate in real time. This exploratory pilot study examined (1) associations between baseline characteristics and EDF feeding episodes across 1 week and (2) whether caregivers’ momentary stress during EDF episodes related to FPP used. Methods: In total, 22 caregivers of Head Start children (ages 3–5) completed baseline measures and 7 days of ecological momentary assessment (up to seven prompts/day). At each prompt, caregivers reported child EDF consumption in the past hour; if confirmed, they reported FPP used and rated momentary stress. Aim 1 used Poisson regression to model caregiver-level EDF episode counts. Aim 2 tested momentary stress–practice associations during EDF episodes using GEE, with within-person and between-person stress modeled separately. Results: Authoritarian parenting was associated with a higher weekly rate of EDF episodes (RR = 1.43, 95% CI 1.23–1.66, p < 0.001); authoritative parenting trended lower (RR = 0.90, p = 0.065). Higher baseline stress was associated with more EDF episodes (RR = 1.25, p = 0.001). Momentarily, elevated stress above a caregiver’s own average increased odds of using food as a reward (OR = 1.08 per +10 points, p = 0.011), while higher average momentary stress was associated with co-eating (OR = 1.59, p = 0.042). Domain-level FPP composites showed no association with momentary stress. Conclusions: Authoritarian parenting and higher caregiver stress were associated with increased EDF feeding, and momentary stress was linked to reward-based feeding during those episodes. These hypothesis-generating findings suggest potential behavioral targets for just-in-time adaptive intervention, pending replication in adequately powered studies. Full article

Proteomic research in the genus Vitis has progressed from early biochemical studies of soluble proteins to high-resolution, quantitative analyses encompassing all major organs and derived products. This review provides a comprehensive synthesis of advances in grapevine and wine proteomics. In leaves, studies have revealed extensive remodeling of photosynthetic, antioxidant, and defense pathways under biotic (e.g., Plasmopara viticola, Erysiphe necator, Xylella fastidiosa, Candidatus Phytoplasma vitis) and abiotic stresses (drought, salinity, heat, light). Bud proteomics elucidated hormonal regulation and mechanisms of dormancy release, while root studies identified nitrate-dependent metabolic shifts and adaptive protein networks. Cell culture models enabled controlled investigation of elicitor responses, stilbene biosynthesis, and temperature-induced proteome changes. In berries, proteomics clarified developmental transitions from fruit set to ripening, emphasizing proteins related to secondary metabolism, vacuolar transport, and stress tolerance. Comparative analyses across cultivars and environments identified biomarkers linked to aroma, color, and texture. The wine proteome revealed selective persistence of grape-derived proteins (e.g., thaumatin-like proteins, chitinases) and yeast peptides influencing stability and sensory properties, while Botrytis cinerea infection significantly alters this balance by degrading PR proteins and introducing fungal enzymes. Altogether, the Vitis proteome emerges as a dynamic, multifunctional system crucial for understanding plant adaptation, enological quality, and biomarker discovery. Full article

CCAAT/enhancer-binding protein δ (C/EBPδ) is a rapidly responsive transcription factor that occupies an important regulatory position in adipocytes. Induced during the early stage of adipocyte differentiation, C/EBPδ integrates hormonal, inflammatory, metabolic, and stress-related cues and contributes to the coordination of downstream transcriptional and functional programs. Beyond its role in the initiation of differentiation, C/EBPδ is also involved in adipogenic progression, metabolic regulation, and immune-related functions in adipocytes. Current evidence indicates that C/EBPδ participates in early adipogenic regulatory networks, contributes to lipid metabolic programs, and is associated with immune-regulatory processes linked to lipid antigen presentation. Notably, the biological output of C/EBPδ is strongly shaped by tissue type, developmental stage, and microenvironmental context, ranging from promotion of adipogenic differentiation to regulation of inflammatory, metabolic, and adaptive stress responses under distinct physiological and pathological conditions. This review summarizes the upstream regulatory network, downstream functional framework, and context-dependent roles of C/EBPδ in adipocytes, and further discusses its potential relevance to adipose-related diseases as well as the opportunities and challenges for future precision intervention strategies. Full article

The intensive use of agricultural inputs and the increasing incorporation of nano-materials into crop management practices raise concerns about their ecotoxicological interactions in plant systems. This study evaluated phytotoxicity, cytotoxicity, and genotoxicity in Allium cepa L. under experimental nano-agrochemical exposure scenarios combining two conventional nitrogen fertilizers—ammonium sulfate (AS) and urea—with silver nanoparticles (AgNPs). Biological responses were assessed across fertilizer concentrations (0.03–0.5 g/L), applied individually, simultaneously, and sequentially, to identify modulatory effects of AgNPs on plant proliferative activity and genomic stability. Results showed the relative stability of morphophysiological indicators associated with root growth, whereas cytogenetic biomarkers exhibited selective alterations under specific conditions. Significant increases in genetic damage markers were detected at intermediate ammonium sulfate concentrations, suggesting sublethal phytotoxicity windows not reflected by macroscopic growth parameters. In addition, modulation of the mitotic index and absence of generalized genotoxic effects in most combined or sequential treatments indicate that AgNPs primarily acted as modulators of proliferative responses rather than direct cytotoxic agents. Overall, these findings highlight the dynamic and non-linear nature of nano-agrochemical interactions in plant systems and underscore the importance of multibiomarker approaches for the early detection of genomic instability. The results provide experimental evidence relevant to the environmental risk assessment of nano-enabled fertilization strategies under realistic mixed-exposure scenarios. This study contributes to advancing the ecotoxicological understanding of emerging agricultural technologies and supports the need for further mechanistic research and field-based evaluations to guide the safe and sustainable use of nanomaterials in crop production. Full article

Numerical simulation of sequential fracturing in horizontal wells for shale gas and oil extraction requires careful consideration of mechanical interactions between proppant and fracture surfaces—a challenge that remains largely unresolved. This study proposes a novel phase-field model featuring a strain-based formulation and a width-dependent proppant reaction force. Unlike previous studies, we integrate an empirical propped force solution, adapted from established work to account for rock properties and proppant support, to capture nonlinear fracture closure. Results show that reaction stress models significantly dictate propped geometry. The model’s fracture length, width, and closure predictions are validated against theoretical solutions. We conducted a sensitivity analysis to evaluate how fracture deflection angles and widths vary with dimensionless fracture spacing, in situ stress contrast, and proppant strength. Numerical results show that proppants induce pronounced morphological asymmetry and distinct geometric discrepancies. Specifically, the heterogeneous support provided by proppants and the resulting stress redistribution alter fracture propagation paths, leading to an 8% reduction in fracture length and a marked difference in fracture orientation of approximately 80° between supported and unsupported fractures, highlighting the important role of proppants in governing fracture geometry. Both dimensionless fracture spacing and in situ stress contrast strongly influence fracture deflection, with proppant strength also contributing. The propped-force formulation is further extended to nonplanar fractures, enabling application to sequential fracturing with multiple fractures. These results highlight fracture propagation mechanisms and demonstrate the robustness of the proposed phase-field model. Full article

Microbial communities associated with the rhizosphere and phyllosphere are recognized as fundamental components influencing essential plant processes, including nutrient acquisition, growth promotion, and tolerance to stress. Biological control agents (BCAs), such as Trichoderma spp. and Bacillus spp., are widely applied in citrus crops. However, while BCAs effectiveness against plant pathogens is widely established, their resulting impact on indigenous, non-target bacterial and fungal communities remains poorly understood. The aim of this study was to evaluate the non-target effects of two commercial microbial formulations—one containing Trichoderma asperellum ICC 012 and T. gamsii ICC 080, and the other Bacillus amyloliquefaciens QST 713—on the resident microbiomes of Citrus volkameriana seedlings by using the amplicon-based metagenomic analysis, targeting the 16S rRNA and ITS1 regions. The application of the Trichoderma formulation as a soil drench in the rhizosphere resulted in minimal changes to the overall composition and diversity (α- and β-diversity) of the bacterial communities. This stability is considered a desirable trait for overall soil health. However, specific taxonomic changes were observed, such as a notable decrease in the genus Rhodococcus (0.4% vs. 1.5% in controls) among bacteria. In the fungal communities, the treatment led to a significant shift in phylum relative abundance, characterized by an increase in Basidiomycota (38% vs. 28% in controls) and a corresponding decrease in Ascomycota (51% vs. 56% in controls). Successful colonization was confirmed by a substantially higher relative abundance of the inoculated Trichoderma genus compared to control plants (1.4% vs. 0.1% in controls). Conversely, the foliar application of the Bacillus product induced a substantial restructuring of the phyllosphere bacterial community. This treatment caused a statistically significant reduction in bacterial α-diversity and a clear differentiation in community composition (β-diversity) relative to untreated controls. The successful colonization by the BCA resulted in the dominance of the Bacillus genus in the treated samples (27% vs. 2% in controls). Importantly, this ecological shift was accompanied by the enrichment of other beneficial bacterial taxa, including Sphingomonas (15% vs. 4% in controls) and the Burkholderia-Caballeronia-Paraburkholderia group (4% vs. 2% in controls). While fungal phyla abundances remained generally stable in the phyllosphere, specific genera such as Cladosporium (15% vs. 23% in controls) and Symmetrospora (21% vs. 13% in controls) prevailed post-treatment. In conclusion, these findings highlight the importance of considering non-target microbiome shift when implementing microbial biocontrol strategies in citrus production systems, since in this study was demonstrated that commercial BCAs exert a markedly differential influence based on the compartment of application: Trichoderma promoted ecological stability in the rhizosphere, whereas Bacillus induced a directional community shift in the phyllosphere. Full article

Cerebral ischemic stroke is caused by impaired blood flow to the brain parenchyma due to acute vessel occlusion. Although current therapies focusing on rapid restoration of blood flow achieve high rates of recanalization, outcomes remain unfavorable in a significant proportion of patients. Part of this discrepancy is due to intravascular inflammation driven by thrombo-inflammatory mechanisms that add to cerebral tissue loss. Despite being an inevitable consequence of vessel occlusion, altered shear stress remains largely overlooked as a contributor to endothelial dysfunction in stroke. To directly assess the impact of disturbed flow on the endothelial phenotype, human brain endothelial cells were cultured under controlled flow conditions using an ibidi pump system and exposed to flow alternating in both magnitude and direction. Subsequently, the expression of key endothelial proteins, including Claudin-5, PECAM-1, CD62e and endoglin, was analyzed. We show here that the sequence of shear-stress modulation, recapitulating the hemodynamic conditions of large-vessel occlusion and subsequent reperfusion in stroke, is sufficient to cause an inflammatory phenotype in human brain endothelial cells. In addition, we demonstrate that platelet activation induces the mechanosensors Piezo1 and syndecan-1, sensitizing brain endothelial cells to shear-stress alterations characteristic of ischemic stroke. Targeting shear-stress-mediated inflammatory activation of the brain endothelium may therefore offer a complementary strategy in stroke therapy, particularly in large-vessel occlusion with abrupt flow changes. Full article

This study aimed to detect growth stress at the individual-tree level in chestnut (Castanea crenata Sieb. et Zucc.) plantations using UAV-based RGB orthomosaic and multispectral imagery and to determine an optimal NDVI threshold for stress classification. UAV surveys were conducted over a 21 ha chestnut orchard located in Gongju, Chungcheongnam-do, Republic of Korea. NDVI was calculated and analyzed at the individual-tree level using multispectral imagery. Based on field observations, 100 healthy trees and 23 stressed trees were selected for statistical analysis. The mean NDVI value was 0.900 ± 0.012 for healthy trees and 0.816 ± 0.013 for stressed trees, showing a highly significant difference (p < 0.001). ROC analysis showed excellent classification performance with an AUC of 1.00. The optimal NDVI threshold determined using Youden’s index was 0.855. Independent validation in another chestnut plantation approximately 1 km away achieved high classification accuracy using the same threshold. These results indicate that UAV-based multispectral imagery combined with NDVI analysis provides an effective approach for early detection of growth stress and precision monitoring at the individual-tree level in chestnut plantations. This study provides a practical and efficient approach for the early detection of growth stress at the individual-tree level, enabling early intervention against potential declines in tree vitality and proactive management in chestnut orchards. The proposed NDVI threshold-based method offers a simple yet robust tool that can be readily applied in precision forestry and smart agriculture to support large-scale monitoring and informed management decisions for maintaining orchard productivity, enabling cost-effective early intervention at the individual-tree level, which is difficult to achieve using conventional ground-based surveys in complex mountainous orchards. Full article

Internet Gaming Disorder (IGD) has emerged as an increasingly prevalent behavioral health concern among late adolescent university students, a vulnerable population with emotional distress due to the developmental changes and academic pressures. This research explored the direct correlations between IGD and Mental Health Disorder (MHD), such as depression, anxiety, and stress in Saudi Arabia (SA) with study discipline as a moderator. A total of 480 students participated in the developed self-structured questionnaire, and Partial Least Squares Structural Equation Modeling (PLS-SEM) was employed to analyze the obtained data. The results showed that IGD can exert a positive and significant association with all three aspects of MHD. Moreover, the PLS-SEM slope analysis indicated that study discipline can significantly moderate the link from IGD to both anxiety and depression, with university students in health, science, and engineering fields displaying higher symptoms of depression and anxiety as compared to their peers in humanities and social sciences. However, study discipline failed to moderate the link from IGD to stress. These findings can be interpreted through maladaptive coping mechanisms and behavioral addiction, whereby extreme IG can contribute to social withdrawal, reduce sleep quality, and worsen stress regulation, specifically during the late adolescence period. The results extend current research on IGD by emphasizing the disciplinary differences in mental health vulnerability and offering more empirical evidence from a Middle Eastern context. The study highlighted the urgent need for discipline-oriented mental health screening and targeted proactive interventions to deal with unsettled IG attitude within a higher education context. Full article