Search Results (14,124)

Marine algal polysaccharides have been widely investigated as antiviral candidates, yet nearly all anti-dengue studies have focused on sulfated species. Whether algal polysaccharides lacking prominent sulfation can inhibit dengue virus (DENV) remains unexplored. Here, we profiled the stage-specific antiviral activity of a heteropolysaccharide (GLHP) from Gracilaria lemaneiformis, whose Fourier-transform infrared (FT-IR) spectrum lacks characteristic sulfate ester absorption bands, against DENV serotype 2 (DENV-2) in Huh7 and BHK-21 cells. GLHP exhibited low cytotoxicity (CC₅₀ exceeding 1000 μg/mL in Huh7 cells and approximately 950 μg/mL in BHK-21 cells). Time-of-addition analysis revealed that co-inoculation GLHP treatment (Co-inoc.) produced the strongest and most consistent inhibition of intracellular viral RNA, whereas pre-inoculation GLHP treatment (Pre-inoc.) was ineffective, indicating that the antiviral activity is predominantly associated with the virus–cell contact and entry stage. GLHP additionally reduced extracellular progeny virus output under post-inoculation GLHP treatment (Post-inoc.) conditions, and this reduction exceeded the corresponding change in intracellular viral RNA levels, suggesting an additional effect that may involve either a late replication step or secondary entry blockade of progeny virions. Attenuation of virus-induced cytopathic effects under Co-inoc. conditions further supported the antiviral activity. To our knowledge, these findings identify GLHP as the first non-sulfated marine polysaccharide shown to exhibit stage-defined antiviral activity against DENV-2 and support further investigation of its antiviral potential and structural determinants. Full article

Coronavirus disease 2019 (COVID-19) has been associated with an increased long-term cardiovascular risk, potentially mediated by magnitude of the acute inflammatory response inflammation. Interleukin-6 (IL-6) and serum amyloid A (SAA) are key components of the inflammatory cascade and may serve as biomarkers of post-COVID cardiovascular vulnerability. This longitudinal observational study investigated the association between post- COVID-19 infection IL-6 and SAA levels and major cardiovascular events over a six-year follow-up period. A total of 97 individuals with documented prior SARS-CoV-2 infection were included. Circulating IL-6 and SAA concentrations were measured in the acute phase. The composite endpoint included incident arrhythmia, myocardial infarction, and all-cause mortality. Biomarker distributions were right-skewed and were therefore analyzed using non-parametric methods and penalized logistic regression models. During follow-up, 14.4% of participants experienced the composite endpoint. Individuals with adverse outcomes had significantly higher IL-6 and SAA levels compared with event-free participants. IL-6 demonstrated the strongest association with mortality, whereas SAA showed particularly robust associations with the composite endpoint, and with myocardial infarction. Both biomarkers independently predicted long-term adverse events. Circulating IL-6 and SAA concentrations measured during the acute phase of SARS-CoV-2 infection were analyzed in relation to long-term cardiovascular outcomes. These findings support the hypothesis that the magnitude of the acute inflammatory response during SARS-CoV-2 infection may be associated with long-term cardiovascular outcomes and suggest that combined assessment of IL-6 and SAA may have potential utility for hypothesis-generating prognostic signal requiring validation, pending validation in larger studies. Full article

Rice (Oryza sativa L.) straw-return can improve soil carbon (C) sequestration, but its adoption in intensive rice systems is limited by short fallow periods (< 30 days), which likely lead to incomplete straw decomposition and increase methane emissions under continuous flooding (CF). Brittle rice straw, characterized by lower recalcitrant fiber content and rapid decomposition, may overcome this constraint; however, its environmental performance under alternate wetting and drying (AWD) remains unclear, such as broader C allocation. This 150-day microcosm study evaluated the interaction of straw type (brittle vs. non-brittle) and water management (CF vs. AWD) on greenhouse gas (GHG) emissions, dissolved C production, soil C storage, and aggregate formation in two contrasting paddy soils (sandy loam vs. silty clay loam). Compared with non-brittle straw, brittle straw returns reduced net GHG emissions by approximately 28.4% under CF and 39.6% under AWD. The combination of brittle straw with AWD produced the lowest net GHG emissions (0.61 kg CO_2-eq m⁻²), indicating that intermittent oxygen input effectively mitigated the early decomposition-related emission risk. Brittle straw also increased the concentrations of dissolved inorganic C by 14.2% and nitrate by 64.3% under AWD, suggesting enhanced mineralization and potential inorganic C stabilization. Regardless of straw type, straw return improved soil C stocks by 27.3% in sandy loam and 29.6% in silty clay loam, while also promoting macroaggregate formation. Overall, this study demonstrated that coupling brittle rice straw with AWD can reduce GHG emissions while maintaining soil C benefits, offering a promising residue management strategy for intensive rice cultivation. Full article

Xinjiang Ziziphus jujuba ‘Huizao’ wine, a characteristic fruit wine in China, is facing industrial bottlenecks such as flavor homogenization and lack of specialized fermentation yeasts, which limits its high-quality development. To solve these problems, four laboratory-preserved indigenous yeast strains (NZ5, NZ6, BH4, BH2) were compared with four commercial strains (FR, RW, RA, SY) in terms of fermentation dynamics, volatile flavor compound synthesis (HS-SPME-GC-MS/GC-FID), and sensory quality to screen the optimal yeast for Ziziphus jujuba ‘Huizao’ wine fermentation. Molecular identification revealed that NZ5 and NZ6 belong to Saccharomyces cerevisiae, while BH4 and BH2 are closely related to Pichia kudriavzevii, respectively, indicating their non-Saccharomyces characteristics with distinct metabolic potentials. The results showed that indigenous strains exhibited significantly superior performance to commercial strains: (1) Saccharomyces strains NZ5 and NZ6 had higher fermentation efficiency, with 12.5–25% shorter fermentation cycles and 14% higher cumulative CO₂ release than commercial strains; (2) Non-Saccharomyces strain BH4 synthesized the most diverse volatile flavors (99 compounds), with ethyl acetate content reaching 314.92 mg/L, which was 13-fold higher than that of commercial yeast FR (24.09 mg/L). Meanwhile, its phenethyl alcohol content reached 3.12 mg/L, 7.2 times that of commercial yeast RW; (3) Sensory evaluation showed that BH4-fermented wine had the highest score (88.59), significantly higher than commercial strains (63.57–67.67). In conclusion, BH4 is the optimal strain for improving the flavor quality of Xinjiang Ziziphus jujuba ‘Huizao’ wine, and NZ5/NZ6 are suitable for efficient industrial fermentation. This study provides valuable microbial resources and technical guidance for the quality improvement and industrial development of Xinjiang characteristic fruit wine. Full article

Lectin receptor-like kinases (LecRLKs) are a large subfamily of receptor-like kinases (RLKs), and their N-terminal lectin domain is predicted to reversibly bind to carbohydrates. Within this family, G-type LecRLKs represent a distinct subclass defined by an extracellular S-locus glycoprotein (SLG) domain, which was originally identified for its role in governing self-incompatibility in Brassica species. Emerging evidence suggests that G-type LecRLKs are involved in plant immunity; however, only a small fraction have been functionally characterized, leaving the roles of most family members largely unknown. In this study, we identified RK3 (Receptor Kinase 3) as the most strongly induced gene within the G-type LecRLK clade VI upon infection with Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). Through both gain- and loss-of-function analyses, we demonstrated that RK3 positively regulates flg22-induced immune signaling events, including oxidative burst and mitogen-activated protein kinase (MAPK) activation, as well as downstream responses such as defense gene expression and ethylene production. Remarkably, the immune-enhancing activity of RK3 does not require its kinase domain. Critically, both full-length RK3 and a kinase-deleted variant (RK3-ΔK) constitutively interact with FLS2 (Flagellin-Sensing 2) and BAK1 (BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1). This provides direct evidence that RK3 functions primarily as a co-regulatory component within the PRR complex, independent of its kinase activity. Moreover, ectopic expression of RK3 in tomato enhanced resistance to Pst DC3000, highlighting its potential utility in engineering disease resistance in crops. Thus, RK3 reveals a non-canonical, kinase-independent mechanism by which a G-type LecRLK potentiates plant immunity, expanding our understanding of RLK signaling complexity. Full article

Urban traffic congestion presents a complex challenge driven by intricate spatial dependencies and non-stationary temporal dynamics. While Multi-Agent Deep Reinforcement Learning has shown promise for Traffic Signal Control, existing approaches often struggle with partial observability and fail to coordinate effectively across large-scale, heterogeneous road networks. In this paper, we propose HydraLight (HYbrid Deep Reinforcement Learning Architecture for Traffic Lights), a novel spatio-temporal framework that integrates Graph Attention Networks and Temporal Transformers. To overcome the localized myopia of standard graph methods, HydraLight introduces a Global Pooling Context module that broadcasts macroscopic, citywide traffic summaries, enabling agents to proactively mitigate systemic gridlock. Furthermore, to facilitate robust multi-scenario training, we introduce a Unified Prioritized Experience Replay (Unified PER) module that normalizes Temporal-Difference errors, preventing task dominance across diverse topologies. Extensive experiments on the RESCO benchmark across five synthetic and real-world networks demonstrate that HydraLight consistently outperforms state-of-the-art baselines (including X-Light and CoSLight).Byreducing traffic congestion, travel delays, and idle waiting times, the proposed framework also contributes to more sustainable urban mobility through improved traffic flow efficiency, lower fuel consumption, and reduced vehicular carbon emissions. Notably, the proposed architecture excels in structurally irregular environments, achieving up to 13.07% reduction in average travel time on complex arterial networks and consistently improving queue stability and waiting-time minimization across both synthetic and real-world RESCO benchmarks compared to state-of-the-art baselines. Full article

Background: Diffuse Large B-cell Lymphoma (DLBCL) is a biologically heterogeneous subtype of non-Hodgkin’s lymphoma (NHL), accounting for 30–40% of cases worldwide. Despite the incorporation of rituximab into standard chemo-immunotherapy regimen, approximately one-third of patients present with relapsed or refractory disease, implicating the need for improved prognostic markers and therapeutic targets. Gene expression profiling successfully classified DLBCL into Germinal Center B-cell-like (GCB) and non-GCB subtypes, which differ in genetic alterations, response to therapy, and clinical outcome. While intrinsic tumor biology has been extensively studied, the contribution of the tumor microenvironment (TME) to disease progression and therapeutic resistance still remains incompletely understood. Methods: In this study, we investigated the mutational landscape of stromal-related genes in DLBCL and evaluated their impact on gene expression, downstream signaling pathways, and tumor progression. Results: A total of 176 DLBCL patients were screened, of which 113 were enrolled based on availability of complete clinical data. The cohort demonstrated male predominance (male:female ratio: 2.1:1), advanced disease stage in 72.6% of patients, and elevated serum lactate dehydrogenase levels in 57.5%. Based on immunohistochemistry, 43.4% cases were classified as GCB-DLBCL and 56.6% as non-GCB DLBCL. Although the International Prognostic Index (IPI) retained prognostic significance for event-free survival (EFS) and overall survival (OS), considerable heterogeneity was observed within similar risk groups. Whole-exome sequencing (WES) uncovered recurrent somatic mutations in key oncogenic and epigenetic regulators, including TNFAIP3, NFIB, NOTCH1, TSC2, EZH2, EP300, KMT2D, and B2M, with subtype-specific distribution. Pathway enrichment analysis implicated role of Notch, Wnt, mTOR, JAK-STAT, TGF-β, and antigen-presentation pathways. Comprehensive WES analysis identified multiple novel mutations in genes associated with the stromal/extracellular matrix with distinct patterns in GCB and non-GCB DLBCL, accompanied by concordant alterations in gene expression profiles, suggesting functional relevance within the TME. Functional validation through primary cell culture demonstrated significantly elevated Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) cytokines in co-cultures containing both neoplastic cells and stromal components, underscoring the role of TME in DLBCL progression. Conclusions: Taken together, this study provides novel insights into stromal mutational signatures and cytokine-mediated tumor–stroma interactions, offering potential prognostic biomarkers and therapeutic targets for the improved management of DLBCL. Full article

Aflatoxins are widespread hepatotoxic food contaminants, yet age-specific cumulative exposure to multiple aflatoxins and associated health risks remain poorly characterized. This study assessed cumulative dietary exposure to aflatoxin B₁ (AFB₁), B₂, G₁, and G₂, and hepatocellular carcinoma (HCC) risk across five age groups, evaluating the influence of packaging and retail sources on contamination. Contamination data of 1179 food samples and consumption data were integrated to calculate the margin of exposure (MoE) and annual HCC incidence. AFB₁ was most frequently detected and often co-occurred with other aflatoxins; bulk vegetable oils showed the highest total aflatoxin detection rate. Roasted peanuts contributed most to aflatoxin exposure, particularly among children aged 3–6 (MoE 900–1206). Rice, rice products, and coarse grains were primary contributors to aflatoxin-attributable HCC risk (0.008 cases per 100,000 person-years). Overall contamination was significantly higher in bulk products than in pre-packaged foods (p < 0.05) and in samples from farmers’ markets and grocery stores than in other sites (p < 0.05). These findings reveal non-negligible aflatoxin-related health risks for Guangzhou residents, especially young children and frequent consumers of staple grains and nuts. Targeted monitoring of high-risk foods and retail environments and age-specific dietary guidance are recommended to reduce population-level aflatoxin exposure and HCC risk. Full article

Developing bifunctional non-noble metal electrocatalysts with high activity, stability, and cost-effectiveness is essential for large-scale sustainable water splitting, yet remains challenging. Herein, 2P-FeCoNi-MOF was synthesized via hydrothermal reaction of FeCoNi-LDH followed by phosphidation. Its layered structure, integrated with 3D nickel foam, creates a hierarchical porous architecture that increases surface area and accelerates electron transport. Synergistic effects among Fe, Co, Ni in the trimetallic phosphides, together with an amorphous carbon layer, boost catalytic performance. Moreover, superhydrophilic and superaerophobic surfaces enhance mass transfer. In 1 M KOH, 2P-FeCoNi-MOF achieves low overpotentials of 70 mV for HER and 225 mV for OER at 10 mA cm⁻², with excellent stability for 100 h at 100 mA cm⁻². For the overall water splitting, it requires only 1.54 V to reach 10 mA cm⁻² and maintains stability for 100 h at 100 mA cm⁻². Therefore, this study provides a new approach for the preparation of high-performance self-supported non-noble metal-based electrocatalysts for water splitting. Full article

Injecting CO₂ into gas reservoirs is a crucial approach for enhancing natural gas recovery and achieving CO₂ geological storage, where the gas–gas diffusion behavior between CO₂ and CH₄ directly influences gas mixing efficiency. Direct observation of the spatiotemporal evolution of concentration fields during diffusion remains insufficient. In this study, a gas–gas diffusion experimental system capable of multi-time and multi-space stratified sampling within a high-temperature high-pressure PVT cell was established based on real reservoir fluid compositions. Non-equilibrium diffusion experiments were conducted under different pressures, different initial CO₂ mole fractions, and different diffusion times. A diffusion model was developed according to Fick’s second law. The results suggest that the gas column can be divided into a natural gas zone, a transition zone, and a CO₂ zone by the dimensionless concentration gradient threshold. At 5 MPa, the transition zone width expands rapidly within the first 4 h (dimensionless width increases from 0 to 0.6902), after which growth slows. Increasing pressure significantly inhibits diffusion, reducing transition zone width and prolonging equilibration time. Rising initial CO₂ concentration also suppresses diffusion mixing, particularly in the later stage. Component profile analysis confirms that, under high pressures and high CO₂ concentrations, the diffusion flux across the interface is weakened. Compared to CH₄, the diffusion equilibration time of CO₂ is shorter and more sensitive to pressure changes. The obtained diffusion coefficients (CH₄: 2.92 × 10⁻⁸ to 4.79 × 10⁻⁸ m²/s; CO₂: 3.91 × 10⁻⁸ to 6.08 × 10⁻⁸ m²/s) are on the order of 10⁻⁸ m²/s, consistent with bulk-phase PVT literature data, validating the reliability of the experimental method and inversion model. This study lays an experimental foundation for predicting multi-component gas mass transfer under conditions of CO₂-enhanced gas recovery and CO₂ geological storage. Full article

Solanum lycopersicum is highly sensitive to water deficits, which negatively affect photosynthesis and increase oxidative stress. Although chitosan nanoparticles (ChNPs) offer a sustainable solution, research on their effects on this species is scarce. This study evaluated whether ChNPs mitigate the physiological and biochemical effects of water deficit on S. lycopersicum seedlings. Thirty-day-old seedlings were grown under greenhouse conditions, and two irrigation levels were established: 80% of substrate water-holding capacity (well-watered, WW), and 50% of water-holding capacity (mild-to-moderate water deficit, WD). Spherical ChNPs with a size of 39.52 ± 10.9 nm were suspended in 1% acetic acid and foliar-applied at 0, 60, or 120 mg L⁻¹. After 10 days, biomass accumulation, chlorophyll fluorescence parameters (F_v′/F_m′, ΦPSII, and ETR), gas exchange, and non-enzymatic antioxidant traits were determined. Even under this early-stage stress regime, water deficit significantly reduced shoot and root biomass, net photosynthesis, and stomatal conductance, while increasing lipid peroxidation. Foliar application of ChNPs, particularly at 60 mg L⁻¹, restored dry matter production and improved photochemical efficiency and electron transport rate by 14%; likewise, net CO₂ assimilation increased by 11.7%. In addition, this dose enhanced antioxidant activity and total phenols by 66% and 1.6-fold, respectively. ChNPs at 60 mg L⁻¹ mitigated the effects of WD in S. lycopersicum by increasing antioxidant and photosynthetic performances. Nevertheless, additional molecular studies, including enzymatic antioxidant characterization and compatible solute profiling, are required to elucidate the mechanisms involved. Full article

This study investigates the effect of mass-based replacement of natural coarse aggregate with electric arc furnace (EAF) slag on the performance of ordinary Portland cement (OPC) concrete. Replacement levels of 0%, 30%, 50%, and 100% were examined, with particular attention to the volumetric changes induced by the higher density of EAF slag, which leads to an increase in paste volume. Fresh, mechanical, durability-related, and microstructural properties were evaluated. Results show a continuous reduction in workability with increasing slag content, despite the increase in paste volume, indicating the dominant influence of aggregate morphology on rheological behavior. Mechanical performance exhibited a non-linear response. Within the tested series, the 50% replacement mixture showed the highest mean compressive and splitting tensile strengths; however, the compressive strength difference relative to the control mixture remained small and within typical experimental scatter. In contrast, water absorption decreased progressively, reflecting improved matrix densification. However, this densification did not translate into enhanced mechanical performance, highlighting a decoupling between durability-related indicators and strength. A screening-level CO₂ assessment further showed that reductions in aggregate-related emissions were offset by increased cement content associated with mass-based replacement. The results emphasize the importance of considering volumetric effects when interpreting the behavior and sustainability of slag-based concrete. Note: all strength comparisons are based on mean values from three-specimen sets without formal statistical testing and should be regarded as exploratory observations. Full article

Background: Increasing evidence suggests that COVID-19 can induce or exacerbate autoimmune disorders, including immune-mediated thyroid dysfunction. The most common autoimmune thyroid diseases are Graves’ disease and Hashimoto’s thyroiditis; the mechanisms by which viral infections like SARS-CoV-2 trigger these diseases are not fully understood. Objectives: This study aims to systematically review published clinical evidence on the presentation, laboratory characteristics, and outcomes of autoimmune thyroid diseases after COVID-19 infection. Methods: The review followed the PRISMA 2020 framework. Scopus, Web of Science, and PubMed were searched for English-language studies between January 2020 and December 2025 using the terms COVID-19, SARS-CoV-2, autoimmune thyroiditis, Graves’ disease, Hashimoto’s thyroiditis, and autoimmune thyroid disease. Results: In total, 46 studies (five cohort studies and 41 case reports/series) involving 3856 patients were analyzed. The findings indicate that a significant increase in TPOAb prevalence occurs post-COVID-19 infection (15.7% vs. 7.7% in controls). New-onset Graves’ disease (GD) post-COVID-19 presented with higher fT3/fT4 ratios and more aggressive thyrotoxicosis compared to non-viral cases. Rare but severe manifestations included thyrotoxic periodic paralysis, Hashimoto’s encephalopathy, and dilated cardiomyopathy. Conclusions: SARS-CoV-2 may act as a trigger for autoimmune thyroid diseases, particularly in moderate-to-severe infections; however, the strength of this association warrants further investigation with controlled prospective data. Standard therapy remains effective, but thyroid function monitoring is advisable during post-COVID-19 recovery. An interdisciplinary approach is essential for early diagnosis and management of systemic complications. Full article

Background: Pneumococcal conjugate vaccines (PCVs) have substantially reduced pneumococcal disease in children; however, serotype distribution varies geographically, and residual disease due to non-PCV13 serotypes persists. Biological E’s PNEUBEVAX 14^® (BE-PCV14), a WHO-prequalified 14-valent PCV, expands coverage by including serotypes 22F and 33F. As PCVs are co-administered with routine Expanded Programme on Immunization (EPI) vaccines, post-licensure data on safety, co-administration, and lot-to-lot consistency are essential. This multicenter phase IV study evaluated BE-PCV14 in healthy PCV-naïve infants aged 6–8 weeks across 31 sites in India. Methods: A total of 2600 infants were enrolled and vaccinated at 6, 10, and 14 weeks of age; 2300 received BE-PCV14 and 300 received PCV13. All participants received concomitant DTwP-HepB-IPV-Hib and oral rotavirus vaccines per routine schedule. Safety was assessed through solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). Immunogenicity subsets evaluated responses to co-administered vaccines and serotype-specific responses across three BE-PCV14 lots. Results: Among 2600 vaccinated infants, at least one AE occurred in 26.35% (95% CI: 24.59, 28.19) of BE-PCV14 and 24.67% (95% CI: 20.13, 29.84) of PCV13 recipients; most were mild. Injection-site pain and pyrexia were the most common events. Immune responses to co-administered vaccines were comparable between groups and met the non-inferiority criteria: lower bound of the two-sided 95% CI > −10 percentage points for seroprotection/seroconversion rate differences using the Farrington–Manning method. Lot-to-lot consistency was demonstrated, with all GMC ratios within the predefined equivalence margin (0.5–2.0). Conclusions: BE-PCV14 was well tolerated. Immune responses to co-administered routine EPI vaccines met predefined non-inferiority criteria, supporting the interpretation that BE-PCV14 did not result in clinically meaningful immune interference. Consistent immune responses across manufacturing lots further support its use in infant immunization programs. Full article

Background/Objectives: Propranolol (PROP) is a non-selective β-blocker widely prescribed for cardiovascular and neurological disorders. Its pharmacokinetics (PK) are highly variable, and co-administration with omeprazole (OME), a CYP2C19 substrate and inhibitor, may alter systemic exposure. Herein, this study aimed to investigate factors influencing PROP PK variability and evaluate the effect of OME coadministration using physiologically based pharmacokinetic (PBPK) modeling and population PK (popPK) analysis. Methods: PBPK models for PROP and OME were developed and validated against published data. DDI simulations were conducted across clinically relevant dosing regimens. A two-period fixed-sequence virtual trial of 125 subjects was simulated with PROP alone and PROP combined with OME. Population PK (popPK) analysis was performed on simulated plasma concentration data to identify covariates affecting PROP disposition and quantify DDI magnitude. Results: PBPK models were successfully developed and validated. PROP disposition was best described by a two-compartment model with linear elimination. Health status was found to influence clearance, and body surface area (BSA) affected the central volume of distribution. Co-administration with OME increased PROP exposure, with larger effects in patients with renal impairment. Simulated plasma concentrations remained below established toxicity thresholds. Conclusions: Virtual clinical trials integrating PBPK and popPK modeling provide a robust approach to identifying key determinants of PK variability and DDI risk. Although these findings were not directly translated to clinical observations, this helps identify sources of PK variability in PROP treatment settings and factors that may intensify its interaction with OME, thereby supporting model-informed precision dosing to enhance safety and efficacy. Full article