Search Results (25,085)

Diabetic cardiomyopathy (DCM) is a distinct myocardial disorder that develops independently of coronary artery disease and hypertension and represents a major contributor to heart failure in patients with diabetes. Beyond hemodynamic alterations, DCM is driven by complex molecular mechanisms involving metabolic dysregulation, mitochondrial dysfunction, inflammation, and fibrotic remodeling. Increasing evidence identifies oxidative stress as a central integrative process linking these pathogenic pathways in the diabetic heart. Chronic hyperglycemia, insulin resistance, and altered substrate utilization promote excessive generation of reactive oxygen species, overwhelming endogenous antioxidant defenses and disrupting myocardial redox homeostasis. Oxidative stress induces direct damage to lipids, proteins, and DNA while simultaneously activating redox-sensitive signaling pathways that amplify inflammation, endothelial dysfunction, cardiomyocyte apoptosis, and fibrosis. In addition, epicardial and visceral adipose tissue have emerged as active contributors to myocardial oxidative stress through paracrine and systemic mechanisms, reinforcing inflammatory and fibrotic crosstalk. This review provides a comprehensive overview of the molecular sources and targets of oxidative damage in DCM, examines the impairment of antioxidant defense systems, and discusses emerging therapeutic strategies aimed at restoring redox balance. Full article

Skin aging is characterized by fibroblast senescence, extracellular matrix (ECM) degradation, and impaired wound healing, driven by oxidative stress and telomere dysfunction. Here, we investigated the anti-aging effects of a standardized microwave-assisted propolis extract (MAPE) in both H₂O₂-induced and replicative senescence models of human dermal fibroblasts (HDFs). MAPE significantly reduced reactive oxygen species (ROS) accumulation and enhanced antioxidant gene expression (NQO1, GCLM), indicating activation of NRF2-dependent defense pathways. It suppressed senescence markers (CDKN2A, CDKN1A, IL6), decreased SA-β-gal activity, and attenuated inflammaging. Moreover, MAPE inhibited MMP1 expression, restored COL1A1, and improved fibroblast wound closure, thereby maintaining ECM homeostasis. Importantly, MAPE modulated Wnt/β-catenin signaling by upregulating WNT3A and LEF1 while suppressing DKK1, and increased TERT expression, suggesting involvement of telomerase-related regulatory pathways. These effects resembled those of CHIR99021, a canonical Wnt activator, while providing additional antioxidant protection. Together, our findings suggest that MAPE is a propolis-derived bioactive ingredient that counteracts fibroblast senescence through coordinated modulation of NRF2 and Wnt/β-catenin–TERT signaling pathways, supporting its potential as a cosmeceutical ingredient for mitigating skin aging. Full article

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, currently represent one of the major challenges in contemporary medicine and geriatrics. Progressive degeneration of the nervous system affects not only patients’ physical functioning but also their psychosocial well-being, often leading to social isolation and disruption of interpersonal relationships. These processes are most strongly associated with individuals over 65 years of age, in whom metabolic syndrome is frequently diagnosed and constitutes a significant factor predisposing them to the exacerbation of neuropathological changes. This review analyzes the role of selected vitamins in modulating the course of neurodegenerative disorders, with particular emphasis on their neuroprotective potential. Specific attention is given to their involvement in antioxidant defense mechanisms, regulation of inflammatory pathways, prevention of abnormal protein aggregation, participation in neurotransmitter synthesis, and support of mitochondrial function and cellular energy metabolism. The review also considers key interactions between vitamins and coenzyme Q10, which synergistically enhance neuroprotective mechanisms. Deficiencies in certain vitamins may exacerbate oxidative stress, impair synaptic transmission, and intensify neuroinflammatory responses, thereby contributing to disease progression. The study analyzes the available data on therapeutic doses of vitamins and compares them with the recommended dietary intake and the upper tolerable intake levels (UL). The available evidence suggests that personalized vitamin supplementation, when integrated with a well-balanced and nutrient-dense diet, may constitute a valuable adjunctive therapeutic strategy. Such an approach may help attenuate disease progression, support neuronal integrity, and improve functional outcomes. Ultimately, targeted nutritional interventions may enhance overall well-being and quality of life in patients affected by neurodegenerative diseases. Full article

Chromatin remodelers play essential roles in modulating nucleosome structure and enabling dynamic transcriptional control. Arabidopsis calmodulin-binding transcription activators CAMTA1/2/3 negatively regulate plant immunity by suppressing the expression of biosynthesis genes of major defence hormones salicylic acid (SA) and N-hydroxy-pipecolic acid (NHP). The autoimmunity of the camta2/3 mutant is partially suppressed by loss of the NHP biosynthesis enzyme SAR deficient 4 (SARD4). During a forward genetic screen with the mildly autoimmune camta2/3 sard4 mutant, we identified chromatin-remodelling factor 5 (chr5) as its partial suppressor. The chr5 single mutants displayed decreased SA biosynthesis and compromised basal immunity. Further RNA-sequencing with chr5 defined immune-related genes that were downregulated in the mutants, including those involved in SA and NHP biosynthesis and signalling, PTI and ETI pathways. Our analysis highlights the roles of CHR5 in immune-specific chromatin remodelling events, contributing to transcriptional reprogramming during plant defence responses. Full article

Drought stress during germination impairs seed germination and seedling development in wheat. Seed germination depends on embryo lipid mobilization for energy supply; however, the molecular mechanisms underlying lipid mobilization in drought stress germination remain unclear. Two wheat cultivars with significant differences in drought resistance, Shannong 28 (SN28) and Xinmai 296 (XM296), were subjected to integrated transcriptomic, metabolomic, and lipidomic analyses to reveal molecular response differences. SN28 exhibited increased root length (RL), while XM296 showed significant decreases in germination energy (GE), vigor index (VI), and single seedling dry weight (SSDW). Multi-omics integration revealed that SN28 maintained efficient lipid mobilization under drought through a distinctive regulatory strategy: suppressing jasmonic acid synthesis to prevent excessive growth inhibition, activating α-DOX1 signaling to maintain defense function, and coordinating these with low expression of ABA signaling factors MYB96 and ABI4 to relieve lipid mobilization suppression. Upregulated lipase and nsLTP genes (TaLTPIe.1, TaLTPIg.1) promoted lipid mobilization, while coordinated activation of arginine–proline metabolism, zeatin biosynthesis, and antioxidant defense pathways provided metabolic support. In contrast, XM296’s extensive inhibition of lipoxygenase enzymes and insufficient lipid mobilization capacity directly underlies its drought susceptibility. These findings indicate that cultivar-specific lipid metabolism patterns are key determinants of germination-stage drought resistance, providing candidate genes for wheat breeding. Full article

Web application firewalls (WAFs) are critical defenses against persistent threats to web applications, yet their security evaluation remains challenging. Traditional manual testing methods are often inefficient and resource-intensive, while existing reinforcement learning (RL)-based automated approaches face two key limitations: (1) attackers cannot perceive opaque WAF rule logic; (2) boolean feedback from WAFs results in sparse/delayed rewards—sparse rewards trap agents in blind exploration, and delayed rewards hinder the association between early actions and final outcomes, adversely affecting learning efficiency. To address those challenges, we propose Ouroboros—a framework integrating genetic algorithm-based symbolic rule reconstruction (translating WAF rules into interpretable RNNs for fine-grained confidence scoring), timing side-channel analysis (evaluating rule-matching depth), and a multi-tiered reward mechanism to enable self-evolving RL testing. Experiments show that the framework reaches 89.2% bypass success rate on signature-based WAFs. This paper presents an efficient solution for automated WAF testing and delivers insights for optimizing rule logic and anomaly detection mechanisms. Full article

Heat stress severely impairs normal plant growth and yield, which significantly limits the horticultural and productive application of most Rhododendron species. In contrast, Rhododendron hainanense exhibits considerable heat tolerance due to its unique growing environment; however, the molecular mechanisms underlying its response to heat stress remain poorly understood. In this study, R. hainanense plants were subjected to heat stress treatment. Combined transcriptomic and metabolomic analyses identified 5454 differentially expressed genes and 152 differential metabolites. The results demonstrated that heat stress significantly induced the accumulation of flavonoids in R. hainanense. Notably, derivatives of myricetin, quercetin, and kaempferol were abundantly accumulated, suggesting their potential role in aiding plant defense against heat stress. The significant up-regulation of specific Rh4CL and RhFLS genes under high-temperature stress, coupled with the substantial accumulation of their flavonoid products (myricetin, quercetin, and kaempferol), indicates a potential role for these metabolites in the thermotolerance of Rhododendron hainanense. These findings provide novel insights into the heat stress response and flavonoid biosynthesis regulation in R. hainanense, highlighting the critical role of flavonoids in plant adaptation to heat stress. This study offers valuable references for the genetic improvement of Rhododendron cultivars with high stress resistance. Full article

Security organizations increasingly rely on cyber threat intelligence (CTI) sharing to enhance their resilience against cyberattacks. Indicators of Compromise (IoCs) play a critical operational role in CTI by providing malicious artifacts that support threat detection, incident response, and facilitate proactive defense. However, the rapid growth of social media as CTI sources, characterized by short-text content, poses significant challenges to automated IoC extraction, contextual interpretation, operational integration, and reliable verification. To address these challenges, this study proposes a comprehensive framework that integrates Large Language Models (LLMs) across multiple stages of the CTI pipeline. The framework leverages LLM-driven data augmentation, a hybrid classification model, and contextual summarization to enhance short-text understanding while supporting expert-in-the-loop validation for operational reliability. Extensive experimental evaluations demonstrate that LLM-driven data augmentation substantially improves model robustness and generalization while reducing false-positive alerts, achieving a precision of $98.87$%. Quantitative diversity analysis and expert-based human evaluation further confirm the linguistic quality and correctness of the generated augmented samples. In addition, IoC reports are validated using both reference-based and reference-free evaluation metrics that show strong alignment and high semantic adequacy. Moreover, a technology acceptance model was integrated with cybersecurity domain constructs to assess the acceptance factors of the proposed framework. Regression analysis showed that perceived usefulness, behavioral intention, trust in automation, and risk were the strongest predictors of actual use. These predictors are commonly interpreted as indicators of technology acceptance. Full article

Cytokines are central regulators of inflammation and immune responses within the tumor microenvironment and have been implicated in cancer progression and prognosis. However, the prognostic value of coordinated cytokine-related transcriptional programs across cancer types has not been systematically explored. Pan-cancer transcriptomic and clinical data were analyzed to construct a cytokine-related prognostic signature using least absolute shrinkage and selection operator (LASSO) Cox regression. Patients were stratified into high-risk and low-risk groups based on the derived risk score. Prognostic performance was evaluated in training and test cohorts, and biological relevance was assessed through survival analyses and pathway-level investigations. A 16-gene cytokine-related signature was established that consistently stratified patients into distinct prognostic groups across multiple cancer types. High cytokine-related risk scores were significantly associated with unfavorable survival outcomes and were linked to enhanced cell cycle activity, epithelial-mesenchymal transition, and extracellular matrix remodeling. Integration of the risk score with clinical variables improved individualized survival prediction. Immunohistochemical analyses further confirmed increased protein expression of representative risk-associated genes, including pannexin 1 (PANX1) and FERM domain containing 8 (FRMD8), in multiple tumor tissues compared with corresponding normal tissues. The cytokine-related prognostic signature captures key inflammatory and immune-related programs underlying tumor aggressiveness and provides a robust tool for pan-cancer risk stratification with potential clinical utility. Full article

Background: As the body’s first line of defense against environmental stressors, the skin is highly susceptible to UVB-induced damage, which triggers inflammation and impairs barrier function. This study investigates the protective effects of safflower seed oil (SSO) and fermented Artemisia annua oil (FAAO) against UVB-induced skin injury. Methods: The protective effects of SSO and FAO against UVB irradiation was first tested in HaCaT keratinocyte. Subsequently, a UVB-irradiated SKH-1 mouse model was established to evaluate these two oils. RNA-seq analysis was employed to investigate the potential molecular mechanisms by which SSO and FAO repair the skin barrier. Results: In vitro experiments demonstrated that SSO (0.25%) and FAAO (0.1%) significantly enhanced HaCaT keratinocyte viability following UVB exposure while selectively modulating pro-inflammatory cytokine production. In a UVB-irradiated SKH-1 mouse model, standalone SSO or FAAO treatment partially ameliorated epidermal hyperplasia and restored UV-reduced collagen content, while the 1:1 SSO/FAAO combination exhibited superior efficacy in restoring skin architecture, reducing erythema and edema, and suppressing immune cell infiltration. Transcriptomic profiling revealed that the combined treatment promoted structural repair by attenuating inflammatory responses and preserving extracellular matrix homeostasis. Conclusions: Together, these findings underscore the potential of SSO/FAAO as a multifunctional botanical intervention for mitigating UVB-induced cutaneous damage. Full article

Respiratory infections remain a significant global health concern, especially as multidrug-resistant (MDR) respiratory pathogens reduce the effectiveness of conventional antibiotics. Patients with chronic lung diseases face persistent biofilm-related infections that are difficult to treat, underscoring the urgency for new solutions. This challenge has renewed focus on bacteriophage therapy as a promising alternative in respiratory antimicrobial management. Bacteriophages are viruses that selectively infect and lyse bacteria, showing strong potential as a precise and effective therapy for resistant pulmonary infections. This review focuses on the mechanisms of phage biology and therapy in lung infections, highlighting their unique interactions with mucus, surfactants, and immune defenses—all of which are central to their clinical promise. The review examines advances in phage engineering, delivery strategies, and inhaled formulations aimed at maximizing phage stability and targeting within the airways. It summarizes recent preclinical and clinical progress targeting MDR respiratory pathogens and discusses regulatory, manufacturing, and safety considerations key to integrating phage therapy into mainstream respiratory care. Full article

Background/Objectives: Osteoarthritis (OA) is a chronic inflammatory disease with limited disease-modifying therapies. This study explored a novel immunomodulatory approach using autologous, antigen-pulsed semi-mature dendritic cells (DCs) to modulate the inflammatory milieu in knee OA patients. Methods: In this open-label, quasi-experimental study, 29 subjects received a single subcutaneous injection of autologous DCs. Outcomes assessed at baseline and 4 weeks included the WOMAC index for symptoms and serum levels of IL-6 and TNF-α. Responses were analyzed in the overall cohort and by BMI subgroups. Results: The overall cohort showed a non-significant trend in WOMAC improvement (p = 0.080) and no change in IL-6 (p = 0.785) or TNF-α (p = 0.330). Subgroup analysis revealed differential patterns of response: WOMAC scores improved significantly only in normal-weight patients (p = 0.030), while serum TNF-α decreased significantly only in overweight patients (p = 0.025). IL-6 levels were unchanged across all groups. Conclusions: Autologous antigen-pulsed DC administration was associated with differential responses across BMI subgroups. Symptomatic benefit was observed in normal-weight individuals, while a reduction in systemic TNF-α occurred in overweight patients. These findings suggest that the host metabolic state may modulate the response to DC-based immunotherapy, and therefore warrant validation in a randomized, placebo-controlled trial. Full article

Background: The exocyst complex, a conserved hetero-octameric complex including the EXO70 subunit, is a pivotal regulator of various cellular and developmental processes in plants. Among the diverse EXO70 isoforms, the specific function of EXO70E2—a primary organizer of exocyst-positive organelles (EXPOs)—remains to be fully elucidated. Methods: Here, we investigated the functional impact of constitutive EXO70E2 overexpression in Arabidopsis thaliana. Results: We observe that EXO70E2 overexpression leads to severe etiolation and dwarfism, accompanied by dose-dependent inhibition of primary root elongation. The YFP-labeled EXO70E2 localizes to distinct punctate structures. Histochemical analysis shows EXO70E2 expression in root tips and leaf vasculature, and its promoter activity is strongly induced by the salicylic acid analog INA and pathogen infection. Further function dissection demonstrates that EXO70E2-overexpressing plants exhibit enhanced susceptibility to the necrotrophic fungus Botrytis cinerea, manifested as larger lesions, accelerated host cell death, and increased fungal biomass. Conclusions: Our findings position EXO70E2 as a key negative regulator of plant development and defense outcomes, which may play a role in the balance between growth and immunity. Full article

The health risks associated with excessive alcohol consumption have emerged as a public health challenge, with alcohol-associated liver disease (ALD) and hyperuricemia (HUA) being particularly prominent health issues. Current treatments often have side effects, driving the need for safe, multi-target natural alternatives. Based on the dual barrier strategy of “metabolic regulation–antioxidant defense”, this study developed bioactive peptides from corn germ meal via enzymatic hydrolysis, which simultaneously activated alcohol dehydrogenase (ADH), inhibited xanthine oxidase (XOD), and exhibited antioxidative properties. The fraction <3 kDa emerged with stronger triple bioactivity while also demonstrating sensitivity to strong acids and enhanced activity under trypsin treatment in in vitro stability tests. A total of 841 unique peptides were obtained from purified peptide fractions. After computer-aided screening and molecular docking, three corn-derived peptides (LMFP, FEGLFR, and QLPSYR) were identified, which acted synergistically. Docking simulations revealed that they bind to ADH and XOD via hydrogen bonds and hydrophobic interactions, suggesting potential interactions with these enzymes that may influence their activity. The corn-derived bioactive peptides developed in this study may serve as potential resources for alleviating alcohol metabolism and hyperuricemia symptoms. Full article

Flooding, as a major abiotic stress, significantly impacts the growth and survival of poplar plantations in the floodplains of the middle and lower reaches of the Yangtze River. Elucidating the molecular mechanisms underlying flooding responses in poplar is crucial for enhancing plantation productivity. In this study, two important eastern cottonwood cultivars, Populus deltoides ‘Jianghan 1’ (HBI) and P. deltoides Bartr. CL (CL), were investigated. By integrating long-term growth surveys and transcriptome sequencing, we analyzed their phenotypic traits and molecular responses to flooding stress. After 7 years of seasonal flooding, HBI exhibited a survival rate of 73.91%, along with superior height (23.1 m) and diameter at breast height (DBH, 26.3 cm), compared with CL, indicating HBI as a flooding-tolerant cultivar. Transcriptome analysis identified 1098 shared differentially expressed genes (DEGs) in the leaves of flooded HBI and CL, which were mainly enriched in stress signal perception, oxidative stress regulation, energy metabolism and circadian rhythm. Cultivar-specific DEG analysis revealed that CL mainly activated pathways related to oxidative stress and damage repair pathways, whereas HBI-specific genes were significantly enriched in hormone signal transduction, growth regulation, flavonoid synthesis and photosynthesis. Based on this distinct enrichment pattern in the tolerant cultivar HBI, we propose that it possesses adaptive advantages under flooding stress. Specifically, HBI likely coordinates multiple physiological processes by activating ethylene and other hormone-related genes, thereby regulating hypoxia adaptation, reoxygenation-induced oxidative stress, photosynthetic recovery, and flavonoid-mediated antioxidant defense. This coordinated regulation collectively sustains growth vigor and enhances survival under seasonal inundation. Our findings demonstrate clear transcriptomic divergence underlying flooding tolerance among poplar cultivars, laying a theoretical foundation for the selection of flooding-tolerant varieties and the sustainable development of forestry in flood-prone regions. Furthermore, these results broaden the current knowledge of flooding stress biology in woody plants. Full article