Search Results (37,438)

Background/Objectives: Amniotic-derived biologics have emerged as powerful modulators of tissue regeneration. This study evaluates the composition and characteristics of a human stem cell-conditioned media (hSCCM) that is a sterile, cell-free, amniotic-derived solution, and the presumed efficacy of hSCCM as an active ingredient in an enriched cosmetic lotion. Methods: Data from preclinical benchtop studies and an exploratory observational assessment were reviewed. First, an investigation of the active ingredient, hSCCM, was completed. Flow cytometry assays were completed for mesenchymal stem cell (MSC) characterization. Cellular proliferation assays were conducted to evaluate concentration response, shelf life, and temperature stability. ELISA and LC-MS/MS were used to specify and detail the proteomics of the hSCCM. Second, the hSCCM-enriched lotion’s cosmetic safety and efficacy were evaluated. Preliminary microbial, stability, and early-stage nonclinical retrospective user evaluation of the hSCCM-enriched lotion was conducted to help characterize the cosmetic and evaluate topical safety and efficacy. Results: Flow cytometry demonstrated alignment with ISCT (International Society for Cell and Gene Therapy) characterization for MSCs. Initial in vitro data demonstrated enhanced proliferative effects at hSCCM concentrations as low as 5% (p-value < 0.0001); no statistically significant trend in proliferative capability in aged samples (p-value = 0.79), and no significant effect on proliferative capability when exposed to acute temperature changes (p-values all above 0.05) were observed. Proteomic characterization showed an enriched amniotic-derived solution. Microbial testing of the enriched lotion demonstrated success with multiple unique preservative formulations. hSCCM-enriched lotion demonstrated stability across acute cold- and heat-stress representative scenarios. An exploratory retrospective observational analysis revealed promising trends. Conclusions: The hSCCM demonstrates topical efficacy across in vitro dermal and follicular assays via proliferative and regenerative mechanisms and protein enrichment. The enriched lotion showed success in early-stage microbial and stability testing and demonstrates positive trends in topical skin outcomes. These findings support their potential translational application in dermatologic and aesthetic usage, and broader integumentary contexts. Full article

Larix olgensis, a keystone timber species in Northeast China, is increasingly threatened by Neofusicoccum laricinum-induced shoot blight, a devastating disease that compromises forest health and necessitates sustainable management strategies. Here, we demonstrate that the endophytic bacterium Bacillus amyloliquefaciens JL54 elicits multifaceted defense responses in L. olgensis, enhancing resistance to pathogen infection. Greenhouse assays revealed that JL54 pretreatment reduced disease incidence by 12.5% and achieved 43.75% control efficacy while maintaining host vigor. Histochemical analyses identified JL54-induced rapid hydrogen peroxide (H₂O₂) accumulation, extensive lignin deposition, and localized programmed cell death (PCD), indicative of a primed immune response. Transcriptomic analyses uncovered distinct temporal defense patterns: early-stage responses (0 h post-inoculation) were characterized by upregulation of cutin, suberin, and wax biosynthesis pathways, reinforcing physical barriers, whereas late-stage responses (12 h post-inoculation) were dominated by ribosome- and proteostasis-related pathways (e.g., heat shock proteins [HSPs], glutathione S-transferases [GSTs]) to mitigate cellular damage. Biochemical assays corroborated these findings, with JL54 colonization reducing membrane lipid peroxidation (27.2% decrease in malondialdehyde content) and significantly elevating the activity of key defense enzymes, including peroxidase (POD), phenylalanine ammonia-lyase (PAL), and GST. Phytohormone profiling implicated jasmonic acid (JA) as the central mediator of induced systemic resistance (ISR), with JL54-potentiated JA signaling preceding pathogen containment. Collectively, these results demonstrate that JL54 contributes to a coordinated defense strategy in L. olgensis, integrating structural reinforcement (cuticle/lignin), oxidative stress management, and JA-mediated immune priming. These insights advance the understanding of endophyte-conferred resistance in conifers and highlight JL54’s potential as a biocontrol agent for sustainable forestry. Full article

Pseudomonas plecoglossicida causes bacterial hemorrhagic ascites in ayu (Plecoglossus altivelis), a lethal disease characterized by abdominal distension with hemorrhagic ascites, multifocal organ hemorrhages, and histopathologically evident hepatocellular necrosis and inflammatory infiltration. The lack of effective treatments exacerbates mass mortalities, posing a significant threat to aquaculture. Given the severe pathogenesis of P. plecoglossicida infection—which involves bacterial colonization, tissue necrosis, and host immune dysregulation—effective therapeutic strategies are urgently needed. Through a screen of traditional Chinese medicine monomers, we identified harmine, an indole alkaloid derived from Peganum harmala seeds, as a potent agent against this pathogen. In vivo, harmine exhibited direct bactericidal activity by disrupting membrane integrity, as evidenced by increasing membrane permeability, and inhibiting biofilm formation. In an ayu infection model, harmine significantly increased host survival, reduced tissue bacterial load, and enhanced innate immunity by augmenting monocyte/macrophage phagocytosis and bactericidal capacity while suppressing pro-inflammatory cytokine release and apoptosis. Mechanistically, the Drug Affinity Responsive Target Stability assay was used to identify the molecular target of harmine, followed by functional validation through PRDX6−knockdown experiments. Harmine exhibited direct bactericidal activity by disrupting membrane integrity and inhibiting biofilm formation. In the ayu infection model, harmine significantly increased host survival, reduced tissue bacteria1 load, and enhanced innate immunity by augmenting monocyte/macrophage system and bactericidal capacity while suppressing pro-inflammatory cytokine release and apoptosis, the latter likely through modulation of PRDX6−mediated oxidative stress and downstream caspase signaling. Mechanistically, DARTS revealed that harmine binds to peroxiredoxin 6 (PRDX6), a multifunctional enzyme possessing peroxidase, phospholipase A₂, and lysophosphatidylcholine acyltransferase activities. This binding liberates TNF receptor-associated factor 6 (TRAF6), facilitating its mitochondrial translocation and association with the ECSIT signaling integrator complex, thereby amplifying mitochondrial reactive oxygen species (mROS) production and potentiating macrophage-mediated bacterial killing. These findings establish harmine as a promising therapeutic candidate for controlling P. plecoglossicida infections and underscore the value of host-directed immunomodulation derived from natural products in aquaculture medicine. Full article

Background: Small-sided games (SSG) and running-based high-intensity interval training (HIIT) are commonly used in soccer conditioning to improve aerobic fitness and performance. Although both modalities induce high cardiovascular stress, their acute neuromuscular, perceptual, and cognitive responses remain incompletely understood when examined within the same cohort. This study compared the acute physical, psychophysiological, and cognitive responses to SSG and Tabata-type HIIT in amateur male soccer players. Methods: Thirty-two male amateur players (n = 32; age: 20.53 ± 1.65 years) completed a counterbalanced within-subject crossover design. Participants performed a 4v4 SSG protocol and a running-based Tabata-HIIT protocol (8 × 20 s, 10 s recovery) on separate days (48 h apart). Countermovement jump (CMJ), squat jump (SJ), 20-m sprint, agility t-test, heart rate, perceived exertion (Borg CR-10), mental effort, and cognitive performance (d2 test) were assessed pre- and post-exercise. Parametric variables were analyzed using 2 × 2 repeated-measures ANOVA (time × protocol; η²p), and non-parametric data were analyzed using Friedman and Wilcoxon tests (r) (p < 0.05). Results: Both protocols elicited similar cardiovascular responses (~90% HR_max). A significant protocol × time interaction was observed for CMJ (p < 0.001), showing a decline after Tabata-HIIT, whereas performance was maintained after SSG. No inter-protocol differences were found for SJ, sprint, or agility. Perceived exertion and mental effort during recovery were higher following Tabata-HIIT (p < 0.05). Cognitive performance improved after both protocols (p < 0.001), with no between-protocol differences. Conclusions: Despite comparable cardiovascular load, Tabata-HIIT was associated with greater acute neuromuscular and perceptual strain, whereas SSG preserved neuromuscular performance. Perceptual and mental responses may therefore differ despite similar physiological intensity, which may inform soccer training prescription. Full article

With the increasing functional and geometric complexity of modern steel buildings, irregular beam-to-column joints are becoming increasingly common in engineering practice, while their seismic performance and force transfer mechanisms remain insufficiently understood. Based on previous full-scale cyclic loading tests on unequal-depth steel beam (UDSB) and staggered steel beam (SSB) joints incorporating inclined internal diaphragms, this study presents numerical simulations and parametric analyses of irregular steel beam to concrete-filled steel tube (CFST) column joints. Three-dimensional nonlinear finite element models were developed using ABAQUS and validated against experimental results. The strengthening effects of internal diaphragms and concrete infill were then comparatively investigated. The results indicate that internal diaphragms increase the initial stiffness and load-carrying capacity of the joints to approximately 2.0–2.3 times and 1.16–1.8 times, respectively, compared with joints without diaphragms, whereas concrete infill provides smaller enhancements of about 1.3 times in stiffness and 1.2–1.3 times in strength. In addition, the hysteretic response of joints without diaphragms shows good agreement with the post-fracture behavior observed in the experiments, validating the diaphragm fracture mechanism. A parametric study further demonstrates that, under cyclic loading, the beam depth ratio, staggered floor ratio, column wall thickness, column width, diaphragm thickness, and diaphragm opening diameter have significant influences on joint strength and stress distribution, while the effect of axial load ratio is relatively minor. Finally, a strength prediction method applicable to inclined-diaphragm UDSB and SSB joints is proposed, and corresponding fitted expressions are derived based on the parametric results. The findings provide useful guidance for the seismic design of irregular steel beam–CFST column joints incorporating internal diaphragms. Full article

Chronic exposure to artificial light at night (ALAN) is increasingly recognized as an environmental risk factor that disrupts circadian regulation of endocrine and metabolic systems. In this study, we investigated the effects of extreme ALAN on oxidative stress and gut microbiota composition in mice using two complementary experiments. In Experiment 1, adult female mice were maintained under either as a standard 12 h light/12 h dark cycle (12 h group) or continuous 24 h light exposure (24 h group) throughout pregnancy and lactation. In Experiment 2, the offspring from the 12 h group were maintained under the same photoperiod, whereas offspring from the 24 h group were divided into a 12 h light/12 h dark group or a continuous 24 h light group, with treatments initiated on postnatal day 19 and continued until 2 months of age. For all 12 h groups, light exposure occurred from 8:00 to 20:00. Compared with dams in the 12 h group, dams exposed to continuous light exhibited significantly increased catalase activity, while their offspring maintained under the 12 h photoperiod showed elevated glutathione levels. No significant changes were detected in immune organ indices. These results suggest that extreme ALAN modulates antioxidant defenses, potentially reflecting adaptive responses to oxidative stress. Moreover, offspring exposed early to extreme ALAN showed significantly reduced gut microbial α-diversity, accompanied by decreased abundances of Firmicutes, Bacteroidota, Campylobacterota, and Desulfobacterota, and an increase in Proteobacteria. Notably, Verrucomicrobiota and Akkermansia failed to recover following photoperiod normalization, indicating persistent microbiota dysbiosis. Overall, these findings demonstrate that extreme ALAN induces oxidative stress and long-lasting alterations in gut microbiota composition, highlighting potential health risks associated with night-time light pollution. Full article

Inflammation is associated with metabolic alterations that can lead to the release of volatile organic compounds (VOCs) reflecting cellular biochemical activity. Profiling these volatile metabolites may provide insight into cellular responses to inflammatory stimuli, although their characterization in skin-derived cells remains limited. In this exploratory proof-of-concept study, we investigated the volatile metabolite profiles of human skin fibroblasts exposed to different inflammatory stimuli. Fibroblast cell lines were stimulated with polyinosinic:polycytidylic acid (Poly I:C), tumor necrosis factor-alpha (TNF-α), and lipopolysaccharide (LPS) to model viral-, cytokine-, and bacterial-associated stress conditions. Headspace solid-phase microextraction coupled with comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS) was applied to analyze volatile metabolites released from the cell cultures, enabling exploratory profiling of the fibroblast volatilome. A data-processing workflow including pairwise comparisons between experimental groups and statistical filtering was implemented to identify volatile features associated with the different conditions. Several VOCs were tentatively identified, mainly belonging to alcohol, ester, and hydrocarbon classes, and showed differential abundance patterns between stimulated and control samples. Multivariate analysis indicated a separation between stimulated and non-stimulated groups, suggesting stimulus-associated differences in the volatile profiles of fibroblast cultures. While these observations may reflect metabolic responses occurring under inflammatory stimulation, the chemical identity and biochemical origins of several detected features remain to be confirmed. All in all, this study demonstrates the feasibility of applying HS-SPME-GC×GC-TOFMS-based volatilome profiling to investigate stimulus-associated changes in fibroblast cultures. The detected VOC patterns should therefore be considered preliminary observations requiring further chemical characterization and independent validation. Future studies including larger sample numbers, complementary biological verification of the inflammatory response, and more physiologically relevant experimental models will be necessary to further assess the robustness and potential relevance of these volatile signatures in the context of inflammatory processes. Full article

Precision Livestock Farming (PLF) tools are increasingly used in dairy production, but their success depends on farmers’ perceptions, needs and investment capacity. This study explores the current use of digital technologies, satisfaction levels and future expectations among Italian dairy farmers. An online questionnaire with 19 questions collected 53 complete responses between May and November 2025. Most of the farms were free-stall Holstein dairy farms located in the Po Valley and managed by relatively young and well-educated farmers, many of whom had a background in animal production. The adoption of PLF tools was widespread: management software (73.6%), automated total mixed ration (TMR) preparation (66.0%), heat stress mitigation systems (62.3%) and collar sensors (52.8%) were the most adopted technologies. Satisfaction with current tools was high, although installation costs and poor system integration were consistently identified as major constraints. Farmers expressed clear priorities for future devices, particularly early diagnosis of health problems, calving, heat, lameness, and feeding and rumination functions. The results suggest that PLF in Italian dairy systems is moving from the adoption phase to that of consolidation. However, improvements in interoperability, affordability and farmer-centred design remain essential to support a wider and more equitable spread of the technology across the sector. Full article

Two-pore channels (TPCs) are evolutionarily conserved intracellular cation channels found in both plants and animals, where they mediate ion fluxes across endomembrane compartments. While historically the plant channel was among the first plant ion channels to be characterized, thanks to the relative ease of applying the patch-clamp technique to isolated plant vacuoles, where it is localized, the functional properties of the two main human isoforms, HsTPC1 and HsTPC2, expressed in endosomal and lysosomal membranes, were elucidated much later. In plants, TPCs are typically represented by a single isoform, exemplified by AtTPC1 in the model plant Arabidopsis thaliana, which functions as a voltage-dependent, Ca²⁺-regulated channel. The physiological role of plant TPCs is not yet fully clarified, although evidence suggests that they may contribute to systemic signaling and stress responses. In humans, two main isoforms, HsTPC1 and HsTPC2, are expressed in endosomal and lysosomal membranes. Human TPCs are primarily regulated by the phosphoinositide PI(3,5)P₂ and display a high selectivity for Na⁺. However, these channels also appear as a non-selective cationic conductance when activated by the potent Ca²⁺-mobilizing messenger NAADP, likely through interaction with an accessory protein. Functionally, human TPCs are involved in endolysosomal trafficking, membrane fusion, and intracellular signaling, with emerging roles in immunity, metabolism, and disease. Overall, TPCs represent key components of intracellular ion homeostasis and cellular physiology; however, their precise regulatory mechanisms and integrated physiological roles remain only partially understood and, in several respects, are still elusive. Full article

This study explores how school leadership styles are perceived to relate to teacher resilience during crises in Arab schools in Israel. Drawing on twenty semi-structured interviews with principals and vice-principals, findings show that transformational and participative leadership, characterized by emotional support, accessibility, active listening, and shared decision-making, are perceived to foster teachers’ sense of security, self-efficacy, and collective resilience. In contrast, authoritarian and rigid approaches are described as contributing to increased stress, reduced motivation, and diminished coping capacity. The study highlights the significance of socio-cultural and political contexts, indicating that effective leadership in crises involves not only professional guidance but also cultural awareness, flexibility, and responsiveness to staff needs. These findings underscore the value of integrative leadership approaches and targeted professional development to support teacher well-being and organizational resilience in crisis-prone settings. By focusing on leaders’ perspectives, the study contributes to understanding how culturally sensitive and adaptive leadership practices may support educational stability under conditions of uncertainty. Full article

Dynamic instability of water-saturated granular coal in tectonic stress zones is a critical safety issue in coal mining. This study adopts raw coal granules from the Daping Coal Mine to investigate the dynamic response and instability mechanisms under coupled confining pressure, median particle size (d₅₀), and water saturation via dynamic impact tests, 2D equivalent modeling, and theoretical analysis. The results indicate that confining pressure and median particle size jointly regulate the dynamic mechanical properties of coal, with liquid bridge volume serving as a key mediating variable. The study reveals a dual-path coupling instability mechanism of “liquid bridge softening and confining pressure strengthening”: a critical confining pressure of 12 MPa divides the dominant force from liquid bridge to friction. Small-particle units show a stronger strengthening effect, and large-particle units have a slightly higher critical confining pressure. Field observation validates the theoretical patterns, identifying areas near faults as high-risk zones for dynamic instability. Accordingly, a three-tier prevention and control strategy of “tectonic stress unloading, flexible support, grouting modification” is proposed. The research findings enhance the theory of water-saturated granular coal instability and provide theoretical and engineering foundations for disaster prevention and control in tectonic stress zones of coal mines. Full article

Diabetic retinopathy (DR), recognized as a progressive neurovascular and microvascular complication of diabetes, remains one of the leading causes of visual disability worldwide, within the context of a sustained increase in ophthalmic diseases and retinal vascular disorders that compromise vision. This study aimed to characterize the progression of diabetic retinopathy in a streptozotocin (STZ)-induced Wistar rat model. A single dose of 65 mg/kg body weight was administered, with follow-up periods at 2, 4, 8, and 10 weeks, compared to healthy controls. STZ-induced rats exhibited reduced weight gain compared to the control group. They also showed markedly variable hyperglycemia, with glucose concentrations ranging from 250 to 530 mg/dL. Histological analysis of retinal tissue at week 4 revealed early signs of vascular compromise, including early indications of a microenvironment conducive to neovascularization and edema. By week 8, retinal damage had progressed to hemorrhage, persistent edema, and layer-specific vascular disruption. At week 10, intensified neovascularization and exacerbated edema indicated advanced microvascular deterioration. Immunofluorescence analysis demonstrated a temporal accumulation of CD8⁺ T cells in the retina, correlating with photoreceptor degeneration. The coordinated dynamics of CD4⁺ and CD8⁺ T cells suggested transient immune activation during STZ-induced retinal degeneration. Gene expression profiling revealed a proinflammatory and pro-oxidative retinal microenvironment, characterized by the overexpression of angiogenic pathways and proliferative signals. Simultaneously, the antioxidant response appeared partially impaired. Collectively, these findings provide mechanistic perspective on the multifactorial nature of diabetic retinopathy. Oxidative stress, inflammation, and angiogenesis converge to disrupt retinal homeostasis. This experimental model may serve as a reliable platform for future studies aimed at elucidating disease pathophysiology, identifying novel therapeutic targets, and evaluating emerging ophthalmic antidiabetic interventions. Full article

Background: Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine associated with inflammation, metabolic dysfunction, and cardiovascular disease. Its role as a biomarker of microvascular complications in type 2 diabetes (T2D) remains incompletely defined. Objective: To evaluate circulating GDF-15 levels and their association with microvascular complications in patients with T2D. Methods: This cross-sectional study included 160 participants divided into three groups: T2D (n = 93), obesity without carbohydrate disorders (n = 36), and healthy controls (n = 31). Microvascular complications (neuropathy, nephropathy, retinopathy) were assessed. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed. Results: GDF-15 levels were significantly higher in T2D compared with non-diabetic individuals (267.5 ± 168.9 vs. 118.3 ± 55.5 pg/mL, p < 0.001). Higher GDF-15 was associated with neuropathy (odds ratio (OR) 1.985; 95% confidence interval (CI) 1.431–2.753) and nephropathy (OR 1.673; 95% CI 1.243–2.254) in unadjusted models. After adjustment, only nephropathy remained independently associated (OR 1.405; 95% CI 1.026–1.923). ROC analysis showed moderate discriminative ability for nephropathy (area under the curve (AUC) = 0.763). Conclusions: Circulating GDF-15 levels are significantly elevated in patients with T2D and are associated with microvascular complications, with the strongest independent association observed for diabetic nephropathy. These findings suggest that GDF-15 may represent a promising biomarker reflecting metabolic stress and risk of diabetic complications. Full article

Ovarian cancer (OC) remains one of the deadliest gynecological malignancies, largely due to late diagnosis and the emergence of resistance to platinum–based chemotherapy. Long non–coding RNAs (lncRNAs) have recently emerged as key regulators of tumor progression and therapeutic adaptation. In this study, we performed integrative transcriptomic profiling of patient–derived TCGA ovarian tumor samples and carboplatin–resistant A2780 (CBDCA–R–A2780) cells to identify lncRNAs whose dysregulation overlaps between a cell–line resistance model and patient tumors. Our analyses revealed extensive transcriptional remodeling across both datasets, with MNX1–AS1 consistently emerging as a strongly deregulated transcript. Differential expression analysis showed robust upregulation of MNX1–AS1 in resistant cells and tumor tissues, accompanied by correlations with epithelial–mesenchymal transition (EMT)–related transcription factors such as FOXA1 and SNAI2 and inverse associations with epithelial markers including CDH1. Computational predictions using RIblast identified specific MNX1–AS1 binding regions with candidate miRNAs and mRNAs, prioritizing EMT–related transcripts (e.g., SNAI2, FOXA1, ZEB1) with favorable hybridization energies for future validation. Additional prioritized interactors included genes linked to stress response (IER2, FOSB) and invasion (MMP11, MMP1). Because A2780 has been discussed as an endometrioid–like/non–serous ovarian cancer model, mechanistic inferences primarily apply to this in vitro context, while TCGA analyses provide associative support rather than mechanistic validation. Collectively, these findings highlight MNX1–AS1 as a candidate regulator associated with transcriptional reprogramming in OC and a promising prognostic biomarker warranting further functional testing. Full article

Music therapy (MT) is increasingly being integrated into intensive care unit (ICU) settings to modulate pain, stress, and emotional dysregulation. Although clinically promising, objective biomarkers for quantifying its neurophysiological effects are still missing. In this context, the electroencephalogram (EEG) represents a valid tool to assess cortical dynamics associated with cognitive–affective engagement elicited by MT. Our study aims to evaluate the role of electroencephalography as an objective tool for monitoring cortical responses to MT in the ICU. EEGs acquired from nine burn patients undergoing MT in the ICU were considered. Signals were preprocessed to improve the signal-to-noise ratio. Then, six frequency bands (delta, theta, alpha, beta, gamma, and sensorimotor rhythm) were extracted to compute band powers and derive 37 involvement indexes, which were statistically compared across three experimental phases: before, during, and after MT. Results demonstrate that involvement indexes effectively capture neurophysiological shifts induced by MT. Significant differences were observed in 22 indexes when comparing During-MT and Post-MT phases, with 2 indexes being statistically different also when comparing During-MT and Pre-MT phases; 5 indexes differed statistically when comparing Pre-MT and Post-MT phases. These results suggest a transient cortical engagement elicited during MT in ICU settings. Our findings align with previous research reporting EEG (and certain EEG-derived involvement indexes) sensitivity to capture music-induced cognitive and emotional modulation. This confirms electroencephalography potential to objectively reflect MT effects and support its integration in multidisciplinary burn care; however, analysis on larger cohorts is necessary to validate EEG as a clinical tool in MT. Full article