Search Results (129,712)

Background/Objectives: Emotional dysregulation (ED) is emerging as a major contributor to functional impairment in Autism Spectrum Disorder (ASD). Although effective behavioral interventions exist, pharmacological treatments remain constrained by side effects and variable tolerability. Given their neurobiological roles that include neurotransmission, inflammation, and neuroplasticity, vitamin D and omega-3 polyunsaturated fatty acids (PUFAs) have been identified as promising candidates for modulating emotional and behavioral dysregulation. This systematic review aimed to evaluate the efficacy of combined vitamin D and omega-3 supplementation in improving emotional and behavioral regulation in individuals with ASD. Methods: This review was conducted in accordance with PRISMA guidelines. Included studies were English peer-reviewed studies involving participants with ASD that assessed combined vitamin D and omega-3 suppleupplementation with outcomes related to emotional or behavioral dysregulation. The search was restricted to 2015–2025 to ensure inclusion of recent, methodologically consistent studies and to minimize heterogeneity in diagnostic criteria and supplementation protocols. Results: Of 649 records initially screened, 3 studies met inclusion criteria: one randomized controlled trial, one observational study, and one case report, involving participants ranging from early childhood to young adulthood. Across studies, combined supplementation was associated with improvements in irritability, hyperactivity, agitation, and self-injurious behaviors. These clinical effects were accompanied by specific biochemical changes, including reductions in the AA/EPA ratio, increases in serum 25(OH)D and omega-3 indices, and decreased urinary levels of HVA and VMA. Conclusions: This review indicates that co-supplementation with vitamin D and omega-3 fatty acids may exert preliminary beneficial effects on emotional and behavioral dysregulation in individuals with ASD, potentially through anti-inflammatory and neuroregulatory mechanisms. However, the available evidence remains limited due to a small number of studies, their modest sample size, and methodological heterogeneity. Further, biomarker-driven randomized studies are needed to confirm efficacy and delineate optimal dosing strategies for application in clinics. Full article

Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate the therapeutic potential of two dietary antioxidants—astaxanthin and Garcinia indica (kokum)—in modulating hepatic redox status, lysosomal function, and metabolic gene expression in a murine model of diet-induced NAFLD. A total of 120 male Swiss Webster mice were allocated into control and steatotic groups, followed by a 90-day supplementation period with astaxanthin, kokum, or their combination. Liver tissue was collected post-supplementation for biochemical, antioxidant, and qRT-PCR analyses. Outcomes included lysosomal enzymes activities, superoxide dismutase (SOD), GSH, vitamin C, total polyphenols, DPPH radical-scavenging activity, and total antioxidant capacity (TAC). NAFLD induced marked oxidative stress, lysosomal overactivation, and alteration of antioxidant-related gene expression. Combined supplementation restored GSH, enhanced TAC, reduced lysosomal stress markers, and significantly upregulated nuclear factor erythroid 2-related factor 2 (Nfe2l2) while downregulating fatty acid synthase (FASN) and partially rescuing lipoprotein lipase (LpL). Correlation analyses revealed strong associations between antioxidant capacity, lysosomal function, and transcriptional regulation, supporting the therapeutic relevance of combined antioxidant therapy for concurrent redox and lysosomal dysregulation in NAFLD. These findings underscore the therapeutic potential of targeting redox and cellular degradation pathways with antioxidant-based interventions to re-establish hepatic metabolic balance in NAFLD and related disorders. Full article

Modern lifestyles are increasingly plagued by physical inactivity, social disconnection, digital addiction, and excessive time indoors—factors that negatively impact the health and well-being of both humans and their companion dogs (Canis familiaris). Evidence shows that nature exposure, physical activity, and human–animal bond (HAB) each enhance physical, mental, and social well-being, yet these domains have rarely been examined together as an integrated therapeutic triad. We introduce a new conceptual framework of bonded green exercise, defined as shared physical activity between a bonded human and dog in natural environments. Synthesizing existing evidence across human and canine sciences into a testable conceptual integration, we posit that bonded green exercise may plausibly activate evolutionarily conserved, synergistic mechanisms of physiological, behavioural, and affective co-regulation. Four testable hypotheses are proposed: (H1) triadic synergy: combined domains produce greater benefits than additive effects; (H2) heterospecific benefit: parallel health gains occur in both species; (H3) behavioural amplification: dogs acts as catalysts to drive human participation in nature-based activity; and (H4) scalable health promotion: bonded green exercise represents a low-cost, accessible, One Health approach with population-level potential. This framework highlights how intentional, shared physical activity in nature may potentially offer a novel low-cost and accessible model for enhancing health, lifespan, welfare, and ecological stewardship across species. Full article

Obesity is a major global health concern, being associated with insulin resistance and multiple metabolic disorders. Gremlin 1 (GREM1), a bone morphogenetic protein (BMP) antagonist, is increasingly recognized as a key regulator of adipose tissue dysfunction and impaired thermogenesis in obesity. Orlistat, a lipase inhibitor that reduces dietary fat absorption, is one of the most commonly used pharmacological agents for obesity management. White tea has demonstrated antioxidant and anti-obesity properties in experimental models. The aim of this study was to evaluate the effects of white tea on metabolic parameters (HOMA-IR, BMP4, Gremlin1) and GREM1 expression in rats made obese by a high-fat diet (HFD). A total of 40 male Sprague-Dawley rats were randomized into five groups: a standard diet group (STD); a high-fat diet group (HFD); an HFD + orlistat group (ORL); an HFD + 50 mg/kg white tea group (WT50); and an HFD + 150 mg/kg white tea group (WT150). Obesity was induced by feeding the rats a 45% high-fat diet for 3 weeks. Serum insulin, glucose and HOMA-IR levels were measured. Levels of GREM1 and BMP4 in serum and retroperitoneal adipose tissue were assessed. White tea supplementation significantly reduced weight gain and HOMA-IR compared to the HFD group. GREM1 mRNA expression in visceral adipose tissue decreased markedly in the WT50 and WT150 groups (p = 0.002 and p = 0.017, respectively). Serum GREM1 levels were significantly lower in the white tea-treated groups than in the HFD group (p = 0.011). Tissue BMP4 levels were only significantly reduced in the WT50 group (p = 0.005), indicating a non-linear dose–response pattern. There was a negative correlation between serum BMP4 levels and weight gain (rho = –0.440, p = 0.015). White tea was associated with improvements in metabolic parameters in an HFD-induced obesity model. These observations suggest a potential association between white tea bioactives and adipose tissue-related molecular pathways implicated in obesity. Given the short intervention duration and the exploratory design of this animal study, the findings should be interpreted with caution. Full article

Background: Head and neck squamous cell carcinoma remains a highly aggressive malignancy with limited predictive biomarkers for prognosis and radiotherapy response. Increasing evidence indicates that pseudogenes are functionally active regulators of cancer biology, yet their clinical relevance in HNSCC is poorly defined. Methods: Using transcriptomic and clinical data from The Cancer Genome Atlas, we analyzed the expression and clinical significance of two pseudogenes, ANXA2P2 and PA2G4P4, in HNSCC. Associations with clinicopathological features, HPV status, tumor subtypes, survival, genomic instability, radiotherapy response, and immune landscape were assessed using bioinformatic tools. Results: Both pseudogenes were significantly upregulated in HNSCC compared to normal tissues. Higher expression levels correlated with adverse clinicopathological features, increased tumor proliferation and wound-healing capacity, and unfavorable TCGA molecular subtypes. High ANXA2P2 and PA2G4P4 expression was associated with reduced overall survival, while their combined low-expression signature identified patients with significantly improved overall and disease-free survival. Notably, lower expression of both pseudogenes was observed in patients responding to radiotherapy, whereas higher expression was linked to genomic instability parameters and enrichment of oncogenic pathways, including MYC, PI3K/AKT/mTOR, cell cycle regulation, and DNA repair. ANXA2P2 expression differed significantly by HPV status, showing reduced levels in HPV-positive tumors. Furthermore, pseudogene expression stratified distinct immune profiles, including immune subtypes, stromal and immune scores, and specific immune cell populations. Conclusions:ANXA2P2 and PA2G4P4 are clinically relevant pseudogenes associated with tumor aggressiveness, immune modulation, and radiotherapy response in HNSCC. These findings support their potential utility as prognostic and predictive biomarkers and provide a rationale for further functional validation in experimental models. Full article

Ferulic acid (FA) is a green feed additive. To investigate the molecular mechanisms by which FA attenuates heat stress-induced hepatic and intestinal oxidative stress, as well as cholesterol metabolism disorders in Megalobrama amblycephala (9.75 ± 0.04 g), individuals were fed diets supplemented with 0, 100, or 200 mg/kg FA for eight weeks, followed by exposure to heat stress at 34 °C for 48 h. The results indicated that FA supplementation reduced malondialdehyde levels and downregulation genes involved in inflammatory responses (e.g., interleukin-6), apoptosis (e.g., caspase 8), and endoplasmic reticulum stress (e.g., immunoglobulin binding protein) (p < 0.05), which collectively alleviated heat stress-induced hepatic and intestinal oxidative stress. FA supplementation increased the expression of ATP-binding cassette transporter A1, apolipoprotein A1, and liver X receptor α (p < 0.05), and restored liver and plasma TC levels to pre-stress levels (p < 0.05). Additionally, FA ameliorated the heat stress-induced dysbiosis of the intestinal microbiota and modulated the composition and abundance of metabolites in intestinal contents and plasma, some of which are associated with cholesterol metabolism. In conclusion, dietary FA can alleviate heat stress-induced hepatic and intestinal oxidative stress, maintain the stability of the intestinal microbiota and regulate metabolic profiles, and improve the cholesterol metabolism disorders caused by heat stress. Full article

Predicting neoadjuvant chemotherapy response in breast cancer remains critical for optimizing treatment strategies, yet robust predictive biomarkers are lacking. This study implemented an ensemble machine learning approach to identify a gene expression signature predicting pathological complete response (pCR) versus residual disease (RD) using bulk RNA-sequencing data from GSE163882 (138 RD, 80 pCR). We employed TMM normalization with differential expression analysis (250 genes, FDR < 0.05, |log2FC| ≥ 1), ensemble feature selection across five classifiers (Random Forest, Gradient Boosting, SVM, k-NN, and Neural Network) with 10-fold repeated cross-validation, and stacked ensemble development. Consensus selection identified a 17-gene signature consistently ranked across algorithms. The stacked ensemble achieved 0.97 AUC post-testing on hold-out test data. External validation on the independent GSE240671 cohort (37 pCR, 25 RD) following ComBat batch correction achieved ROC AUC of 0.78 and PR AUC of 0.85 with isotonic calibration, demonstrating balanced accuracy of 0.71 and 0.86 sensitivity for pCR detection. Pathway enrichment revealed associations with cell cycle regulation (E2F3, MKI67), DNA repair (BRCA2), and transcriptional control (MED1), with six priority genes (MED1, BRCA2, E2F3, PITPNB, H1-1, and FARP2) showing established breast cancer relevance. This externally validated 17-gene signature provides a biologically grounded tool for NAC response prediction in precision oncology. Full article

Long bone formation in vertebrates proceeds via endochondral ossification, a sequential process that begins with mesenchymal condensation, advances through cartilage anlage formation, and culminates in its replacement by mineralized bone. Recent advances in inducible lineage tracing and single-cell genomics have revealed that, rather than being a uniform event, mesenchymal condensation rapidly segregates into progenitor pools with distinct fates. Centrally located Sox9⁺/Fgfr3⁺ chondroprogenitors expand into the growth plate and metaphyseal stroma, peripheral Hes1⁺ boundary cells refine condensation via asymmetric division, and outer-layer Dlx5⁺ perichondrial cells generate the bone collar and cortical bone. Concurrently, dorsoventral polarity established by Wnt7a–Lmx1b and En1 ensures that dorsal progenitors retain positional identity throughout development. These lineage divergences integrate with signaling networks, including the Ihh–PTHrP, FGF, BMPs, and WNT/β-catenin networks, which impose temporal control over chondrocyte proliferation, hypertrophy, and vascular invasion. Perturbations in these programs, exemplified by mutations in Fgfr3, Sox9, and Dlx5, underlie region-specific skeletal dysplasias, such as achondroplasia, campomelic dysplasia, and split-hand/foot malformation, demonstrating the lasting impacts of embryonic patterning errors. Based on these insights, regenerative strategies are increasingly drawing upon developmental principles, with organoid cultures recapitulating ossification centers, biomimetic hydrogels engineered for spatiotemporal morphogen delivery, and stem cell- or exosome-based therapies harnessing developmental microRNA networks. By bridging developmental biology with biomaterials science, these approaches provide both a roadmap to unravel skeletal disorders and a blueprint for next-generation therapies to reconstruct functional bones with the precision of the embryonic blueprint. Full article

Accurate perception of dynamic carbon intensity is a prerequisite for low-carbon demand-side response. However, traditional grid-average carbon factors lack the spatio-temporal granularity required for real-time regulation. To address this, this paper proposes a “Prediction-Optimization” closed-loop framework for electric vehicle (EV) fleets. First, a hybrid forecasting model (VMD-BSLO-CTL) is constructed. By integrating Variational Mode Decomposition (VMD) with a CNN-Transformer-LSTM network optimized by the Blood-Sucking Leech Optimizer (BSLO), the model effectively captures multi-scale features. Validation on the UK National Grid dataset demonstrates its superior robustness against prediction horizon extension compared to state-of-the-art baselines. Second, a multi-objective Model Predictive Control (MPC) strategy is developed to guide EV charging. Applied to a real-world station-level scenario, the strategy navigates the trade-offs between user economy and grid stability. Simulation results show that the proposed framework simultaneously reduces economic costs by 4.17% and carbon emissions by 8.82%, while lowering the peak-valley difference by 6.46% and load variance by 11.34%. Finally, a cloud-edge collaborative deployment scheme indicates the engineering potential of the proposed approach for next-generation low-carbon energy management. Full article

Problematic Internet use is a major health issue among adolescents, underscoring the need for further research on the variables related to this dysfunctional usage pattern. This study examined the predictive capacity of four indicators of psychosocial adjustment (depressed mood, perceived stress, loneliness, and life satisfaction) for different dimensions of problematic Internet use (preference for online social interaction, Internet use for mood regulation, deficient self-regulation of Internet use, and negative consequences) in male and female adolescents. A sample of 628 adolescents, aged 12 to 18 years (M age = 14.11; SD = 1.52), participated. The results indicated that all dimensions of problematic Internet use were positively correlated with depressive mood, perceived stress, and loneliness, and negatively correlated with life satisfaction. However, notable differences emerged in how these psychosocial variables related to the four PIU dimensions. Loneliness and life satisfaction showed the strongest and most consistent associations. Loneliness predicted Internet use for mood regulation in both males and females and, additionally, predicted preference for online social interaction and negative consequences among males. Life satisfaction was a significant negative predictor of three PIU dimensions among females. Perceived stress stood out as the only predictor of deficient self-regulation in males and females. Finally, depressive mood predicted only the Internet-use-for-mood-regulation dimension among males. These findings may be useful for developing intervention programs aimed at reducing problematic Internet use among adolescents. Full article

Biofilm formation represents a key survival strategy employed by Vibrio cholerae to adapt to the complex intestinal environment of the host. While most previous studies on V. cholerae biofilms have focused on genetic regulation and monospecies cultures, its ability to form dual-species biofilms with other intestinal pathogens is still poorly understood. In this study, using samples from both cholera patients and healthy individuals, Fusobacterium nucleatum was identified as a bacterium capable of co-aggregating with V. cholerae. Untargeted metabolomic analysis revealed that F. nucleatum-derived metabolites, specifically 6-hypoxanthine, enhance biofilm formation in V. cholerae. Further validation confirmed that these F. nucleatum-derived metabolites upregulate the biofilm-associated regulatory gene vpsT. In an adult mouse model, co-infection with F. nucleatum and V. cholerae significantly enhanced the intestinal adaptability of V. cholerae compared to infection with V. cholerae alone. Together, these findings elucidate the mechanism enabling the co-infection of F. nucleatum and V. cholerae in the host intestine, thereby shedding new light on how other pathogenic bacteria can assist in V. cholerae infection. Full article

Previous studies have shown that miR-5110 regulates pigmentation by cotargeting melanophilin (MLPH) and WNT family member 1 (WNT1). In order to find the possible molecular mechanism for pigmentation, we examined the mRNA expression profiles in melanocytes of alpaca transfected with miR-5110, inhibitor or negative control (NC) plasmids using high-throughput RNA sequencing. The results showed that a total of 91,976 unigenes were assembled from the reads, among which 13,262 had sequence sizes greater than 2000 nucleotides. According to the KEGG pathway analysis, four pathways related to melanogenesis, the MAPK signaling pathway, Wnt signaling pathway, and cAMP signaling pathway were identified. Compared to the NC, 162 gene were upregulated and 41 genes were downregulated in melanocytes over expressed by miR-5110. The differential expressions of mRNAs Dickkopf 3 (DKK3), premelanosome protein (Pmel), insulin-like growth factor 1 receptor (IGF1R), cyclin-dependent kinase 5 (CDK5), endothelin receptor type B (Ednrb), kit ligand (Kitl), Myc, and S100 were verified using qRT-PCR, which agreed with the results of RNA sequencing. We also verified the differential expressions of mRNAs of some genes in the MAPK signaling pathway using qRT-PCR, which agreed with the results of RNA sequencing. Interestingly, several genes were screened as candidates for the melanogenesis regulated by miR-5110, including Kitl and MAPK-activated protein kinase 3 (MAPKAPK3). These findings provide new insights for further molecular studies on the effects of miR-5110 on the melanogenesis and pigmentation. Full article

The capability of wind turbines (WTs) to provide frequency response is crucial for future power systems with high wind power penetration. Existing strategies primarily focus on mitigating initial and secondary frequency drop (SFD), often overlooking the adverse effects of rotor speed recovery on turbine safety and sustained grid support. Moreover, the lack of a dynamic linkage between the frequency support stage (FSS) and speed recovery stage (SRS) impedes multi-objective coordination encompassing initial drop suppression, SFD mitigation, and rapid rotor speed recovery. To address these gaps, this paper proposes a two-stage coordinated control strategy. In the FSS, the frequency regulation coefficients (K_p and K_d) are adaptively adjusted based on available kinetic energy, ensuring its rational release. Subsequently, the switching timing from FSS to SRS is optimized using these coefficients to suppress the SFD and accelerate recovery. Finally, a fuzzy logic-based PI controller dynamically governs the SRS to restore rotor speed efficiently while further alleviating the SFD. Simulation results confirm the effectiveness of the proposed strategy under two wind speeds. It improves the initial frequency nadir by up to 0.197 Hz over no frequency control, reduces the secondary frequency drop by as much as 0.106 Hz compared to the stepwise method, and accelerates rotor speed recovery by over 30%, quantitatively validating its superior coordinated performance. Full article

Tillage and crop rotation alter soil environments, thereby influencing both crop yields and methane-cycling microbiomes, yet their combined effects on microbial diversity, assembly, and interaction networks remain unclear. Using a two-factor field experiment, we assessed the impacts of raised seedbed vs. flat cultivation and rice–oilseed rape vs. rice–faba bean rotations on crop productivity and the ecology of methanogen (mcrA) and methanotroph (pmoA) communities. Raised seedbed cultivation significantly increased yields: rice yields were 7.6–9.6% higher in 2020 and 4.7–5.8% higher in 2021 than under flat cultivation (p < 0.05). Faba bean and oilseed rape yields were also improved. Flat rice–bean plots developed more reduced conditions and higher organic matter, with a higher NCM goodness-of-fit for methanogens (R² = 0.466), indicating patterns more consistent with neutral (stochastic) assembly, whereas the lower fit for methanotrophs (R² = 0.269) suggests weaker neutrality and stronger environmental filtering, accompanied by reduced richness and network complexity. In contrast, raised seedbed rice–oilseed rape plots improved redox potential and nutrient availability, sustaining both mcrA and pmoA diversity and fostering synergistic interactions, thereby enhancing community stability and indicating a potential for methane-cycle regulation. Overall, raised seedbed cultivation combined with legume rotation offers yield benefits and ecological advantages, providing a sustainable pathway for paddy management with potentially lower greenhouse gas risks. Full article

Cannabinoids can bind to several cannabinoid receptors and modulate cellular signaling and gene expression relevant to inflammation and lipid homeostasis. Likewise, several vitamin E analogs can modulate inflammatory signaling and foam cell formation in macrophages by antioxidant and non-antioxidant mechanisms. We analyzed the regulatory effects on the expression of genes involved in cellular lipid homeostasis (e.g., CD36/FAT cluster of differentiation/fatty acid transporter and scavenger receptor SR-B1) and inflammation (e.g., inflammatory cytokines, TNFα, IL1β) by cannabinoids (cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC)) in human THP-1 macrophages with/without co-treatment with natural alpha-tocopherol (RRR-αT), natural RRR-αTA (αTAn), and synthetic racemic all-rac-αTA (αTAr). In general, αTAr inhibited both lipid accumulation and the inflammatory response (TNFα, IL6, IL1β) more efficiently compared to αTAn. Our results suggest that induction of CD36/FAT mRNA expression after treatment with THC can be prevented, albeit incompletely, by αTA (either αTAn or αTAr) or CBD. A similar response pattern was observed with genes involved in lipid efflux (ABCA1, less with SR-B1), suggesting an imbalance between uptake, metabolism, and efflux of lipids/αTA, increasing macrophage foam cell formation. THC increased reactive oxygen species (ROS), and co-treatment with αTAn or αTAr only partially prevented this. To study the mechanisms by which inflammatory and lipid-related genes are modulated, HEK293 cells overexpressing cannabinoid receptors (CB1 or TRPV-1) were transfected with luciferase reporter plasmids containing the human CD36 promoter or response elements for transcription factors involved in its regulation (e.g., LXR and NFκB). In cells overexpressing CB1, we observed activation of NFκB by THC that was inhibited by αTAr. Full article