Search Results (20,779)

Fipronil (FPN), a widely used insecticide, poses health risks through environmental contamination. Although its toxicity is increasingly recognized, the impact of fipronil on glucose metabolism remains poorly understood. In this study, mice on a normal diet (ND) or high-fat diet (HFD) received a daily oral administration of fipronil (0, 0.25, 1, or 4 mg/kg) for 35 days. Blood glucose and insulin were measured, and glucose/insulin/pyruvate tolerance tests were performed. We found that fipronil compromised glucose tolerance in mice fed an ND. Gut microbiota composition was assessed by 16S rRNA sequencing and the expression of inflammatory factors was detected in the tissues. Serum fibroblast growth factor 15 (FGF15) and bile acid were determined. In HFD-fed mice, fipronil exacerbated glucose metabolic disorders and enhanced insulin resistance. These metabolic disturbances were associated with gut microbiota dysbiosis, particularly a marked reduction in Akkermansia muciniphila (A. muciniphila) abundance, and increased systemic inflammation. Fipronil exposure also decreased serum FGF15 and elevated serum bile acids. Our results suggest that fipronil disrupts glucose metabolism in association with gut microbiota alterations, impairment of the FGF15-bile acid axis, and induction of inflammation, highlighting its potential relevance to diabetes risk. Further studies are warranted to validate our findings. Full article

R2R3-MYB and bHLH transcription factors (TFs) are key regulators of floral secondary metabolism and epidermal development in flowering plants. Orchids exhibit remarkable floral diversity, which is critical for pollination success and ornamental value, yet the evolutionary and functional diversification of these TF families within the genus remains largely unexplored. Here, we conducted a comprehensive pan-genome dissection of R2R3-MYB and bHLH TF families across 18 Dendrobium species, integrating orthologs assignment, phylogenetics, duplication profiling, cis-regulatory annotation, and tissue-specific expression analysis. We identified 3074 R2R3-MYB and 2282 bHLH genes, classified into 69 and 61 orthologous gene groups (OGGs), respectively. Core OGGs accounted for two-thirds of both families, indicating strong evolutionary conservation, whereas variable OGGs reflected lineage-specific diversification. Phylogenetic analyses resolved R2R3-MYBs into 24 canonical subfamilies and revealed conserved heterogeneous expansion patterns in bHLH subfamilies. Promoter architectures of R2R3-MYB genes were enriched in hormone-, stress-, and light-responsive elements, whereas bHLH promoters were dominated by development-related motifs. Tissue-specific expression profiling in Dendrobium ‘Chao Praya Smile’ showed that floral bud-enriched genes were associated with flavonoid/anthocyanin biosynthesis, whereas root-enriched genes were linked to stress and hormone responses. Integration of pan-genomics and transcriptomics highlighted evolutionary trajectory and functional divergence between core and variable gene sets within Dendrobium. Our study establishes a comprehensive, genus-wide framework for understanding the evolutionary and functional characteristics of MYB–bHLH regulatory networks in Dendrobium. These findings provide valuable genetic resources and key candidate targets for functional characterization and molecular breeding, with important implications for genetic improvement of reproductive traits, floral quality, stress resistance, and ornamental and agronomic value in orchids. Full article

Background: Ocular candidiasis is a serious metastatic complication of candidemia that may lead to irreversible visual impairment. Although recent meta-analyses suggest an overall prevalence of approximately 10%, real-world data from Southeast Asia remain limited. Regional differences in Candida species distribution, antifungal resistance patterns, and health-care resources may influence both the incidence of ocular candidiasis and the utilization of ophthalmic evaluation in routine practice. Methods: We conducted a retrospective cohort study of patients aged ≥15 years with candidemia at a 900-bed tertiary-care university hospital in southern Thailand between January 2014 and August 2025. Only the first episode of candidemia per patient was included. Ophthalmic evaluation was defined as a dilated funduscopic examination performed by an ophthalmologist within 4 weeks of candidemia onset. Ocular candidiasis was classified as Candida chorioretinitis or Candida endophthalmitis according to established definitions. Multivariable logistic regression was used to identify factors independently associated with receipt of ophthalmic evaluation. Results: Among 337 patients with candidemia, 67 (19.9%) underwent ophthalmic evaluation. Ocular candidiasis was diagnosed in 9 of 67 evaluated patients (13.4%), corresponding to an overall incidence of 2.7% in the entire cohort. Five patients (7.5%) had Candida chorioretinitis and four (6.0%) had Candida endophthalmitis, including two concordant and two discordant cases. Visual symptoms were assessable in 35 patients, among whom only 4 (11.4%) reported visual complaints; most patients with ocular candidiasis were asymptomatic at diagnosis. Candida albicans and Candida tropicalis accounted for 55.6% and 44.4% of ocular candidiasis cases, respectively, and bilateral ocular involvement was observed in 77.8%. Ophthalmic findings led to modification of antifungal therapy in 7 of 9 patients with ocular candidiasis (77.8%), most commonly through addition or switching to an azole-based regimen and/or prolongation of treatment duration. In multivariable analysis, vasopressor use at candidemia onset was independently associated with a lower likelihood of ophthalmic evaluation, whereas early infectious diseases consultation was independently associated with increased odds of receiving ophthalmic evaluation. Conclusions: In this Southeast Asian cohort, ophthalmic evaluation was infrequently performed but yielded clinically actionable findings and frequently altered antifungal management. The observed incidence of ocular candidiasis among examined patients was higher than that reported in Western countries. Underutilization of an ophthalmic evaluation appears to reflect illness severity and care pathway factors rather than low disease burden, suggesting that the true incidence of ocular candidiasis may be underestimated. Integrating ophthalmic evaluation into standardized candidemia care pathways may improve detection of ocular involvement, particularly in resource-limited settings. Full article

Intestinal bacteria play crucial roles in maintaining host health and regulating disease. While much of the current research has focused on how changes in the gut microbiota affect various physiological functions of the host, little is known about how the host’s genetic factors shape gut microbiota diversity or how gut-dominant bacteria influence host innate immunity and lifespan. In this study, we demonstrated that a mutation in the Caenorhabditis elegans ERK-encoding gene, mpk-1, promotes the enrichment of Raoultella planticola in the gut of worms, and the bacterium confers resistance to infection by the pathogenic bacterium Pseudomonas aeruginosa PA14 (PA14) in worms. Mechanistically, a compromised immune response, which is dependent on the let-60–mpk-1 pathway, promotes the colonization of R. planticola in mpk-1 mutants. Importantly, R. planticola induces autophagy, thereby enhancing nematode resistance to PA14 infection and extending its lifespan. Our findings shed light on how immune-compromised mpk-1 mutants increase colonization permissiveness and utilize R. planticola to bolster their antibacterial immunity against pathogenic P. aeruginosa, offering new insights into the regulatory mechanisms of host–microbiota interactions. These results emphasize the complex interplay between host genetics, the microbiota, and immune responses, providing potential therapeutic strategies to modulate the microbiota for improved health outcomes. Full article

The operational reliability of the elastic wheel, essential for specialized vehicle mobility on complex terrain, is critically constrained by fatigue failure under multi-axis ground loads. While high-fidelity physics-based simulation provides an accurate assessment, its “one-simulation-per-test” paradigm is inefficient for exploring multi-condition, multi-parameter designs. Conversely, purely data-driven methods are hindered by the scarcity of high-quality fatigue data. This paper proposes LightGBM-CH, an integrated framework that couples Discrete Element Method–Multi-Body Dynamics (DEM-MBD) simulation with an enhanced LightGBM model to overcome these limitations. The framework first converts high-fidelity simulations into a configurable data generator, producing batches of dynamic load–stress response data. A physics-informed feature engineering scheme then extracts 122 discriminative features characterizing six-dimensional loads, fatigue damage metrics, and load–stress coupling. To address the “small-sample, high-dimensional” challenge, a tailored training strategy incorporating robust scaling, correlation-based feature selection, and stability-constrained hyperparameter optimization is developed. Simulation experiments demonstrate that the LightGBM-CH model achieves a determination coefficient of 0.9251 and a root mean square error of 67.06, significantly outperforming benchmark models in accuracy and generalization. The study validates the framework’s engineering efficacy, identifies key influencing factors such as peak–stress ratio, and provides an intelligent, data-informed pathway for fatigue-resistant elastic wheel design. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. While early-stage HCC can often be treated with surgical resection, ablation, or liver transplantation, advanced disease typically relies on systemic chemotherapy. Sorafenib is the standard first-line therapy for advanced and unresectable HCC; however, both intrinsic and acquired resistance remain major clinical challenges. The Y-box binding protein-1 (YBX1), a transcription factor implicated in drug resistance across multiple cancers, is highly expressed in HCC and represents a potential therapeutic target. This study aimed to identify novel YBX1 inhibitors using a drug repurposing strategy to overcome sorafenib resistance. Methods: A combined in silico and in vitro approach was employed. The cold shock (DNA-binding) domain of YBX1 was modeled, and a comprehensive library of experimental and FDA-approved compounds from the DrugBank database was screened using multi-layered high-throughput virtual screening (HTVS). Candidate compounds with predicted direct interaction with YBX1 were further evaluated through literature review and experimental validation. Results: Virtual screening identified 22 potential compounds predicted to interact with YBX1. Further literature review and feasibility assessment narrowed the list to six candidates: malonaldehyde, mercaptoethanol, glycine, para-chlorophenol, methoxyamine, and ethanolamine. For further evaluation, glycine (a food supplement with no toxicity) was selected for detailed functional studies and was shown to inhibit YBX1 and downregulate its target genes. Conclusions: These findings support YBX1 as a promising therapeutic target in hepatocellular carcinoma and demonstrate the utility of drug repurposing to rapidly identify candidate inhibitors. Targeting YBX1 may provide a viable strategy for enhancing treatment efficacy and overcoming sorafenib resistance in advanced HCC. Full article

Stress corrosion cracking (SCC) is a critical failure mechanism that arises from the synergistic interaction between tensile stress and corrosive environments, leading to sudden and often catastrophic failures in structural components across various industries, including aerospace, nuclear energy, oil and gas, and marine engineering. This review synthesizes current understanding of SCC mechanisms, including film rupture and anodic dissolution, hydrogen embrittlement, and adsorption-induced cleavage, and evaluates material susceptibility across steels, aluminum alloys, nickel-based alloys, titanium, and emerging high-entropy alloys. Environmental factors such as aqueous chemistry, temperature, pressure, pH, and dissolved gases are examined for their roles in SCC initiation and propagation. Advanced testing methodologies, including slow strain rate testing, bent-beam configurations, electrochemical monitoring, and high-resolution microscopy, are discussed for characterizing SCC behavior. Engineering mitigation strategies are presented, encompassing material selection, stress reduction, surface treatments, and environmental control. Case studies illustrate real-world SCC failures and inform best practices. Emerging trends highlight the potential of machine learning for predictive maintenance and the development of SCC-resistant materials through additive manufacturing and microstructural engineering. This comprehensive review provides mechanical engineers with actionable insights for designing, maintaining, and safeguarding components against SCC in demanding service environments. Full article

Epithelial ovarian cancer (EOC) is a highly lethal malignancy characterized by significant heterogeneity and poor prognosis due to late-stage diagnosis and chemotherapy resistance. Traditional two-dimensional (2D) models fail to replicate the complexity of the tumor microenvironment (TME), necessitating the development of advanced in vitro systems. Here, we present a novel microfluidic tumor-on-a-chip (ToC) system that accurately models key features of EOC, including heterogeneity and vascularization. The developed cellular model was evaluated for functionality. It was demonstrated that endothelial cells of blood vessels within a collagen matrix successfully migrated toward the cancerous tissue, while the multicellular and multilayered tumor construct secreted pro-angiogenic factors. Additionally, long-term culture conditions induced inflammatory responses, mimicking in vivo tumor progression. This innovative platform enables precise investigations into EOC biology, angiogenesis, and TME interactions. Furthermore, it holds significant potential for drug screening, assessing therapeutic efficacy, and advancing personalized oncology approaches. Full article

This review highlights recent progress in the sustainable extraction, production and application of plant fiber-reinforced biopolymer composites. The review mainly focuses on properties of these materials—mechanical, thermal, and interfacial—and explores how factors such as fiber type, extraction methods, and surface treatments (e.g., enzymatic retting, deep eutectic solvents, steam explosion) affect fiber morphology and bonding with the polymer matrix. The work also discusses strategies to select and modify biopolymer matrices (e.g., PLA, PHA) for better compatibility, recyclability, and long-term performance, addressing challenges like fire resistance and environmental impact. Special attention is given to cellulose surface modification, which improves wettability and interfacial adhesion, while highlighting alternatives to conventional chemical treatments due to cellulose’s high crystallinity and strong hydrogen bonding. Despite advances in surface treatments and manufacturing, persistent challenges include moisture sensitivity, processing reproducibility, and standardization. Future research should prioritize application-tailored extraction, scalable eco-friendly modifications, and standardized testing to optimize durability and circular economy alignment. These fiber-reinforced biopolymer composites offer a viable path to fossil-free, high-performance materials. Overall, this review provides a comprehensive perspective that bridges sustainability and industrial applicability, offering practical guidance for developing high-performance, eco-friendly composites. Full article

Soil salinization is a global ecological issue that severely constrains forest tree growth and ecological restoration. The salt-alkali stress response mechanisms of Quercus mongolica, a key temperate forest species in China, remain unclear. A two-factor pot experiment was conducted using NaCl (0, 50, 100, 200 mmol·L⁻¹) and NaHCO₃:Na₂CO₃ (1:1; 0, 50, 100, 150 mmol·L⁻¹). Plant traits, soil properties, and enzyme activities were measured. Furthermore, high-throughput sequencing revealed that microbial responses enhanced network cooperation under 100 mmol·L⁻¹ salt stress and improved network stability under 50 mmol·L⁻¹ alkali stress. These responses also upregulated resistance genes and increased soil enzyme activities. This activation of seedling antioxidant and osmotic adjustment systems was directly associated with an increase in growth parameters. Under combined stress, however, soil environment deterioration and microbial network disruption, along with reduced key soil enzyme activities, resulted in an insufficient defense system to counteract reactive oxygen species (ROS) accumulation, thereby reducing growth parameters. The study found that low-concentration individual salt or alkali stress promoted Quercus mongolica seedling growth, while combined stress was associated with significant inhibition. This study refines the theoretical framework for non-salt-tolerant trees and establishes a basis for determining their survival thresholds in saline-alkali soils. Full article

Plant SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) constitute a large superfamily and play pivotal roles in diverse biological processes and responses to various abiotic stresses. Quinoa (Chenopodium quinoa wild.) is a nutritionally superior crop endowed with robust tolerance to environmental stresses. In this study, we identified 88 CqSNARE genes in quinoa, which are unevenly distributed across 18 chromosomes and classified into 23 subfamilies. We systematically analyzed their physicochemical properties, phylogenetic relationships, gene and protein structures, and cis-acting elements. Furthermore, transcriptome analysis of quinoa leaves under saline–alkaline stress revealed that CqSNAP30a was the most significantly upregulated. This gene is predominantly expressed in leaves and localized on the plasma membrane. Constitutive expression of CqSNAP30a enhanced plant stress resistance by regulating ion homeostasis and antioxidant capacity. Our findings provide valuable insights into the SNARE genes of stress-tolerant crops and lays a theoretical foundation for the genetic improvement of stress resilience. Full article

As a key technology for achieving building heating electrification and decarbonization, the air-source heat pump (ASHP) has long been constrained by outdoor heat exchanger frosting in cold and humid regions. Frosting leads to increased thermal resistance, a sharp rise in air-side pressure drop, and the attenuation of heating capacity, while traditional active defrosting methods, such as reverse-cycle defrosting, suffer from high energy consumption and heating interruption. This review aims to systematically present the recent research progress of superhydrophobic surfaces (SHSs) as a highly efficient passive anti-frosting strategy. First, the complex phase-change dynamics of frosting and key influencing factors such as environment and surface characteristics are deeply analyzed. Second, it elucidates how superhydrophobic surfaces achieve delayed frosting and sloughing off defrosting by delaying nucleation, promoting droplet self-removal, and reducing ice adhesion. Furthermore, fabrication processes suitable for complex fin structures are systematically reviewed from the perspectives of subtractive manufacturing, in situ growth, and additive coatings, and their industrialization prospects are compared. Finally, the practical effects of this technology in improving heat transfer coefficients, reducing fan energy consumption, and improving defrosting efficiency are evaluated. Although superhydrophobic technology has significant energy-saving potential, it still faces challenges such as poor long-term durability, wettability failure under extreme conditions, and residual micro-droplets. Future research should focus on the development of highly durable materials, the matching design of micro–nano structures with macro flow channels, and active–passive synergistic anti-frosting strategies. Full article

Background/Objectives: Factors modulating phenotypic variability in Rett syndrome (RTT, OMIM 312750) include X chromosome inactivation (XCI), type of MECP2 variant, and/or disease modifiers. Emerging evidence also points to multi-locus genetic variants. Understanding the phenotypic variability associated with multi-locus genetic diagnoses in individuals with RTT and MECP2-related disorders would be important not only for accurate diagnosis, risk stratification and clinical management but also to explain symptoms that might not be typically associated with RTT. Methods: We present a case series of five individuals with a diagnosis of RTT or an MECP2-related disorder with co-occurring genetic findings, including pathogenic variants, variants of unknown significance and chromosome duplications. Clinical features such as neurodevelopmental history and comorbid medical conditions were assessed alongside the genetic findings. Results: A review of 200 cases with RTT identified five cases (all females aged 7–27 years) with a co-occurring genetic finding. Each case harboured at least one additional genetic variant that included a beta thalassaemia trait, Calmodulin 3 (CALM3) missense variant, maternally inherited 22q12.3 to q13.1 duplication, 7p14.3 and Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) variants of uncertain significance and a pathogenic Set Domain-containing protein 5 (SETD5) variant. A rare triple genetic finding was illustrated in a single case, combining MECP2, CALM3, and DYNC1H1 variants. Conclusions: This case series supports the premise that RTT and MECP2-related disorders exist in a more complex neurogenetic spectrum than previously defined. It also emphasises the complexity within MECP2-related disorders. They are not static, and in the context of severe treatment resistant epilepsy, MECP2 disorders can evolve over time, necessitating diagnostic reclassification. Although the co-occurrence of multiple genetic disorders in RTT and MECP2-related disorders is rare, these cases underscore the importance of considering cumulative genetic burden when evaluating individuals with atypical features or evolving neurodevelopmental phenotypes. Full article

Background/Objectives: Familial Mediterranean Fever (FMF) is a chronic autoinflammatory disease in which some patients develop resistance to colchicine, resulting in persistent attacks and increased disease burden. This study aimed to compare clinical characteristics, disease activity, psychological status, and quality of life between colchicine-tolerant and colchicine-resistant FMF patients, and to identify clinical factors independently associated with colchicine resistance. Methods: This exploratory cross-sectional observational study was conducted in 120 FMF patients followed at a tertiary rheumatology center. Patients were classified as colchicine-tolerant or colchicine-resistant. Disease activity and damage were assessed using the International Severity Scoring System for FMF (ISSF) and the Autoinflammatory Disease Damage Index (ADDI). Quality of life was evaluated using the FMF–Health-Related Quality of Life (FMF-HQL) and WHO Quality of Life–BREF (WHOQoL-BREF) questionnaires. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Results: Colchicine-resistant patients had significantly higher attack frequency and disease activity scores (p < 0.001). Quality of life was impaired, with higher FMF-HQL and lower WHOQoL-BREF scores across all domains (p < 0.001). Anxiety and depression scores were also higher. ISSF and Doctor Global Assessment (DGA) were independently associated with colchicine resistance. Conclusions: Colchicine resistance in FMF was associated with increased disease activity, impaired quality of life, and greater psychological burden. Full article

Salinization stress poses a major environmental factor that adversely affects maize (Zea mays L.) growth and development. Thus, identifying and utilizing alkaline tolerance-related genes in maize is crucial for enhancing resistance to alkaline stress. In this study, a genome-wide association study (GWAS) was conducted to analyze alkali tolerance in seedlings, focusing on biomass-related traits at the seedling stage across a panel of 212 maize inbred lines. The analysis found nine single-nucleotide polymorphism (SNP) loci significantly associated with alkali tolerance during the seedling stage. Within the confidence intervals of these loci, 57 genes with clear functional annotations were identified, among which eight were predicted to be involved in alkali tolerance based on functional annotation and homology analysis. qRT-PCR expression validation of selected candidate genes revealed that the relative expression level of GRMZM2G028089 was similar between in L99 and M-J244-3 lines. In contrast, the expression levels of GRMZM2G071196, GRMZM2G313162 and GRMZM5G883126 were higher in the L99 line compared to M-J244-3, suggesting their potential positive regulatory roles in the response to alkaline stress. These findings provide important theoretical support for the targeted breeding of alkali-resistant maize varieties. Full article