Search Results (450)

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and the formation of immune complexes (ICs), which lead to widespread inflammation and tissue damage. Neutrophil extracellular traps (NETs), web-like structures composed of DNA, histones, and antimicrobial proteins released by activated neutrophils, play a crucial role in innate immunity by defending against pathogens. However, excessive NET formation and ineffective clearance of these structures contribute to the development of SLE. This review explores the mechanisms behind NET formation in SLE, their relationship with oxidative stress, and the potential role of antioxidants in treatment. Research indicates that SLE patients exhibit two key abnormalities: excessive NET formation and impaired NET clearance. Excessive NET formation is driven by proinflammatory low-density granulocytes (LDGs) and immune complexes (ICs). Impaired NET clearance stems from reduced DNase1/DNase1L3 activity or anti-nuclease autoantibodies. These two abnormalities lead to elevated circulating NETs. These NETs act as autoantigen reservoirs, forming pathogenic NET–ICs that amplify autoimmune responses. Oxidative stress drives NET formation by activating NADPH oxidase. In contrast, various antioxidants, including enzymatic and non-enzymatic types, can inhibit NET formation via scavenging reactive oxygen species (ROS) and blocking NADPH oxidase activation. Preclinical studies show that antioxidants such as curcumin, resveratrol, and mitochondrial-targeted MitoQ reduce NET formation and ameliorate lupus nephritis; clinical trials confirm that curcumin and N-acetylcysteine (NAC) lower SLE disease activity and reduce proteinuria, supporting their role as safe adjuvant therapies. However, high-dose vitamin E may exacerbate autoimmunity, highlighting the need for dose optimization. Future research should aim to clarify the mechanisms underlying NET formation in SLE and to optimize new antioxidant therapies, including assessments of their long-term efficacy and safety. Full article

Deep Reactive Ion Etching (DRIE), as a key process in silicon micromachining, remains constrained in high-precision applications by sidewall angle deviation and aspect ratio limitations. This study systematically investigates the mapping relationship between process parameters and etching morphology, focusing on the following aspects: the influence mechanism of C₄F₈ passivation time and bottom RF power on sidewall perpendicularity; and the effect patterns of etch cycle count, single-step time, and bottom RF power on aspect ratio and top–bottom line width (CD) difference. The findings reveal that dynamic adjustment of bottom RF power significantly influences sidewall angle: incremental adjustment tends to cause sharp angles (decreased angular precision), while decremental adjustment tends to form obtuse angles. Simply increasing the cycle count leads to a bottleneck in etch depth growth. Combining incremental bottom RF power adjustment can overcome depth limitations but induces axial variation in aperture dimensions. Optimizing the passivation-to-etch time ratio effectively controls etch morphology characteristics. This study achieved an etch depth of 112.2 μm for a 5 μm wide trench with an overall aperture size difference of 0.279 μm, providing a theoretical basis and practical guidance for parameter optimization in DRIE processes for high-precision silicon structure fabrication. Full article

This review examines data-driven road traffic safety modeling, aiming to provide a comprehensive overview of the state-of-the-art and persistent research gaps. The study is structured around data sources, influencing factors, reactive and proactive modeling approaches, and key challenges. Data sources, including crashes, trajectories, traffic, roadway geometry, and environmental data, are first reviewed in the context of reactive and proactive safety analysis. To address the substantial heterogeneity across studies, a vote-counting strategy is adopted to aggregate directional evidence reported in the literature. The synthesis indicates that traffic demand variables exhibit consistently positive associations with crash occurrence, while speed-related effects are strongly context-dependent. Road geometry and surface conditions have largely consistent directional impacts on safety outcomes. From a methodological perspective, reactive approaches remain dominant, while proactive approaches exhibit potential for early risk identification but remain insufficiently validated due to data quality constraints. In addition, empirical evidence on conflict–crash relationships is still limited. Notably, model performance varies substantially across safety tasks, with algorithm effectiveness primarily driven by data structure, outcome definition, and aggregation level, rather than by the intrinsic superiority of any single approach. Overall, this review highlights challenges related to data integration, spatio-temporal modeling, interpretability, and transferability, and provides practical guidance for model selection in operational road safety analysis. Full article

Soil-borne pathogens cause devastating root rot diseases in forest ecosystems, often by inducing dysbiosis in the rhizosphere microbiome. While antagonistic bacteria can suppress disease, their effects frequently extend beyond direct inhibition to include ecological restructuring of resident microbial communities. However, the causal relationships between such microbiome restructuring and disease suppression in tree species remain poorly understood. Here, we show that the antagonistic bacterium B. mojavensis dxk33 effectively suppresses F. solani-induced root rot in C. lanceolata, and that this disease suppression coincides with a partial reversal of pathogen-associated dysbiosis in the rhizosphere. Inoculation with dxk33 significantly promoted plant growth and reduced the disease index by 72.19%, while concurrently enhancing soil nutrient availability and key C-, N- and P-cycling enzyme activities. High-throughput sequencing revealed that dxk33 inoculation substantially reshaped the rhizosphere microbiome, counteracting the pathogen’s negative impact on microbial diversity and coinciding with a shift toward a more stable community structure. Under pathogen stress, dxk33 enriched beneficial bacterial taxa such as Pseudomonas and Sphingomonas and suppressed pathogenic fungi while promoting beneficial fungi such as Mortierella. Linear discriminant analysis and functional prediction further indicated that dxk33 remodeled ecological guilds enriched for mycorrhizal and saprotrophic fungi, and reactivated bacterial metabolic pathways and signaling networks that were suppressed by the pathogen. Taken together, our findings are consistent with a multi-tiered mode of action in which direct antagonism by B. mojavensis dxk33 operates alongside associated changes in the rhizosphere microbiome that resemble a disease-suppressive state, although the present experimental design does not allow a strictly causal role for microbiome reconfiguration in disease suppression to be established. This study provides a mechanistic framework for understanding how microbiome engineering may mitigate soil-borne diseases in perennial trees and highlights the potential of targeted microbial interventions for sustainable forest management. Full article

Conventional synthesis of polycarboxylate superplasticizers (PCEs) typically relies on high-temperature processes, posing challenges for sustainable production. Ethylene glycol monovinyl polyethylene glycol ether (EPEG), characterized by the high reactivity of its vinyloxy double bond, offers a promising sustainable alternative for low-temperature synthesis. This study systematically investigates the aqueous free radical copolymerization of EPEG and acrylic acid, identifying a reaction temperature of 20 °C as the kinetic optimum that achieves a macromonomer conversion rate exceeding 95% under ambient conditions. Through the variation in five key process parameters, a clear “synthesis–structure–property” relationship was established, revealing that the weight-average molecular weight (M_w) acts as the pivotal regulator of performance. High-M_w PCEs exhibited superior initial dispersion driven by strong electrostatic repulsion and high adsorption but suffered from poor slump retention due to the rapid depletion of free polymers. Conversely, low-M_w variants, regulated by chain transfer agent dosage, significantly reduced the pore solution surface tension, thereby enhancing wetting ability and workability retention. The optimal synthesis conditions (20 °C, 4:1 acid-to-ether ratio, 2.5% initiator, 1.5% chain transfer agent) yielded PCEs with an ideal balance between initial dispersion and retention. Furthermore, the synthesis demonstrated excellent process robustness with a broad dosing window (>60 min). These findings provide a vital theoretical basis for the robust and low-temperature industrial production of EPEG-based PCEs for sustainable infrastructure materials. Full article

Yeast-derived biomolecules are redefining the boundaries of green nanotechnology. Biosurfactants, exopolysaccharides, enzymes, pigments, proteins, and organic acids—when sourced from carbohydrate-rich lignocellulosic hydrolysates—offer a molecular toolbox capable of directing, stabilizing, and functionalizing nanoparticles (NPs) with unprecedented precision. Beyond their structural diversity and intrinsic biocompatibility, these biomolecules anchor a paradigm shift: the convergence of biorefineries with nanotechnology to deliver multifunctional materials for the circular bioeconomy. This review explores: (i) the expanding portfolio of metallic and metal oxide NPs synthesized through yeast biomolecules; (ii) molecular-level mechanisms of reduction, capping, and surface tailoring that dictate NP morphology, stability, and reactivity; (iii) synergistic roles in intensifying lignocellulosic processes—from enhanced hydrolysis to catalytic upgrading; and (iv) frontier applications spanning antimicrobial coatings, regenerative packaging, precision agriculture, and environmental remediation. We highlight structure–function relationships, where amphiphilicity, charge distribution, and redox activity govern resilience under saline, acidic, and thermally harsh industrial matrices. Yet, critical bottlenecks remain: inconsistent yields, limited comparative studies, downstream recovery hurdles, and the absence of comprehensive life-cycle and toxicological evaluations. To bridge this gap, we propose a translational roadmap coupling standardized characterization with real hydrolysate testing, molecular libraries linking biomolecule chemistry to NP performance, and integrated techno-economic and environmental assessments. By aligning yeast biotechnology with nanoscience, we argue that yeast-biomolecule-driven nanoplatforms are not merely sustainable alternatives but transformative solutions for next-generation lignocellulosic biorefineries. Full article

Antibodies against low-molecular-weight compounds exhibit cross-reactivities (CRs) with their structural analogs, varying by orders of magnitude for different substances. This variability limits the informativeness of antibody applications as analytical reagents and for other aims when samples contain several members of the same family, their derivatives, or partial degradation products. Therefore, there is a demand to find some criteria for understanding the relationships between the structural characteristics of antigens of a given chemical class and their immunochemical activity. This study presents an experimental and theoretical investigation of the properties of a monoclonal antibody (MAb) against the S-stereoisomer of gatifloxacin, a member of the widely used (fluoro)quinolone (FQ) family of antibiotics, characterized by high structural diversity. The aim was to determine FQs that form complexes with MAb and suggest a methodology to predict their CRs in silico. For this, the interaction of MAb with 26 FQs was studied using the enzyme-linked immunosorbent assay and presented as CR values to the target antigen. The most pronounced CRs were observed for lomefloxacin, sarafloxacin, and ciprofloxacin. Molecular dynamics (MD) simulations were performed to identify differences in analyte interactions at the MAb antigen-binding site, which determines binding affinity. It has been shown that molecular docking fails to discriminate cross-reactive from non-cross-reactive compounds because FQs have similar cores. Therefore, advanced analysis of MD trajectories was carried out. It allowed for clarification of the dynamic features of analyte–antibody interactions responsible for binding. It was shown by the dynamical network analysis that the sum of betweenness centrality between a node corresponding to the quinolone ring and nodes representing MAb amino acids is higher for cross-reactive haptens. The found regularities can be transferred to other analyte–antibody systems as a binary classifier that discriminates cross-reactive and non-cross-reactive compounds. Full article

Background/Objectives: The study aimed to examine the impact of allostatic load on healthy ageing over a decade and whether social participation attenuates this relationship among older American adults. Methods: Data were extracted from three waves (wave 8, wave 10, wave 13) of the Health and Retirement Study, a longitudinal survey of American adults. The analysis included allostatic load, socioeconomic (education) and demographic (gender, age, ethnicity, and marital status) factors at baseline, social participation in wave 10, and healthy ageing in wave 10 and wave 13. A latent variable was created for allostatic load that included waist circumference, C-reactive protein, glycated hemoglobin, and blood pressure. Healthy ageing was defined as an aggregate measure including freedom from disability, freedom from cognitive impairment, and high physical functioning. Social participation was a dichotomous variable that included individuals’ work status, perceived neighbourhood safety, and partaking in volunteer work. Structural equation modelling was used to examine the direct and indirect relationships between these factors and healthy ageing. Results: A total of 14,537 participants with complete data in all waves were included in the analysis. The mean age at baseline was 68.7 years. Results showed a significant association between higher allostatic load and lower healthy ageing (estimate = −0.12, 95% CI: −0.14, −0.11). Allostatic load was negatively associated with social participation (estimate = −0.32, 95% CI: −0.34, −0.30). Social participation showed a positive significant association with healthy ageing, indicating partial buffering that accounted for 12% of the total effect. Higher educational attainment was associated with better healthy-ageing outcomes, whereas non-Black ethnicity was linked to poorer healthy ageing. Conclusions: Elevated allostatic load was associated with poorer ageing outcomes, with social participation partially attenuating the relationship. Higher education predicted more favourable trajectories, while ethnic differences suggested resilience among older Black adults. These results indicate that both physiological and social factors contribute to variations in healthy ageing. Full article

The growing demand for sustainable and high-performance lubricants has accelerated interest in biolubricants derived from renewable feedstocks. Vegetable oils are attractive candidates due to their biodegradability, low toxicity, and favorable viscosity index. However, their application is limited by poor oxidative and thermal stability. The epoxidation of unsaturated fatty acids offers a versatile route to address these drawbacks by enhancing stability and introducing reactive epoxy groups for further functionalization. This review highlights the advances in the use of epoxidized vegetable oils (EVOs), as platforms for lubricant design. Post-epoxidation modifications, such as ring-opening reactions, crosslinking, hybridization with additives, and click-type chemistries, are critically examined with emphasis on their impact on viscosity, polarity, tribofilm formation, and overall tribological behaviour. Structure–property relationships were discussed to establish design principles linking chemical modifications with lubrication regimes, wear resistance, and film-forming ability. In addition, sustainability aspects, including biodegradability, ecotoxicity, and life cycle assessment, are reviewed to evaluate the trade-offs between performance enhancement and environmental compatibility of these modifications. Current challenges and future perspectives are outlined, including the need for standardized testing protocols, the integration of multifunctional modifications, and predictive modelling tools. By bridging molecular engineering, tribological performance, and sustainability, this review provides a roadmap for the rational design of advanced epoxidized oil-based biolubricants. Full article

The power system is constantly changing. New elements are being added. The network structure is being changed. Existing network infrastructure is being modernised. This results in the need to perform various types of computational analyses. These analyses are designed to assess the impact of new and existing power system components on its operation. These analyses can be complicated, complex and difficult. These analyses are influenced by the size of the actual grid, technical conditions, and the specific requirements of grid operators. Therefore, there is a constant search for methods that simplify them without significantly compromising the accuracy of the obtained results. In real networks, computation time is also a crucial parameter, which can be excessive when analysing multiple operating variants. Linearisation of the computational model significantly contributes to reducing computational time but also affects their accuracy. Particular attention should be paid to two frequently used and compared linearization methods: the DC method and the first-order Taylor expansion. The DC (Direct Current) method offers relatively simple formulas. These relationships are based on simplifying assumptions. They are well suited for error analysis, at the expense of neglecting reactive power and voltage changes. Taylor linearization preserves the full AC structure around a selected operating point. It takes reactive power and voltage changes into account. Its accuracy is local and depends on the base point. It may require re-linearization for large changes in the power system operating states. This article presents a detailed literature review. It concerns the linearization of the power flow problem in the context of solving various computational problems in the power system. Selected works are grouped and categorised by topic. Linearisation methods used in the literature are presented, and the most frequently used ones are also indicated. Research gaps that may be addressed in future work are highlighted. Full article

The removal of synthetic dyes from industrial effluents remains challenging due to their chemical stability and poor biodegradability. Here we engineer metal-doped carbon dots (CDs) as heterogeneous Fenton-like catalysts and elucidate how dopant identity governs structure–activity relationships and reactive oxygen species (ROS) pathways. Fe-, Cu-, Zn- and Mg-doped CDs were prepared via a one-pot hydrothermal route and comprehensively characterised by TEM, FTIR, XPS and zeta-potential analysis. The resulting nanoparticles displayed narrow size distributions (10.2–15.2 nm) and dopant-dependent surface chemistries and charges. Catalytic tests with methylene blue (MB) and rhodamine B (RB) show that Fe-doped CDs deliver the highest activity toward MB degradation (k = 0.0218 min⁻¹), attributable to efficient Fe²⁺/Fe³⁺ redox cycling coupled with hydroxyl-rich surfaces that promote H₂O₂ activation. Zn-doped CDs achieve complete RB decolourisation under Fenton-like conditions, which we ascribe to their higher surface charge and abundant oxygenated sites that enhance pollutant adsorption and ROS generation. Cu- and Mg-doped CDs exhibit intermediate and dopant-specific performances consistent with their respective redox and adsorption characteristics. Collectively, these results establish clear correlations between dopant chemistry, surface functionality, and ROS formation routes, providing mechanistic guidance for the rational design of carbon-based Fenton catalysts for sustainable water remediation. Full article

Background: Mapping anti–HLA class I cross-reactivity from single-antigen bead (SAB) mean fluorescence intensity (MFI) data supports donor selection. However, interpretation is complicated by analytical choices and assay variability. Methods: A total of 4327 SAB assays were analyzed (antigen × test matrix) using an interpretable, distance-based workflow. Antigen profiles were z-scored across tests. Multidimensional scaling (MDS) was used for visualization and hierarchical clustering analysis (HCA) for grouping, and complemented these with a common PCA space for model selection (K-Means via Silhouette; Gaussian Mixture Models via BIC), agglomerative (Ward and average-link on 1–correlation), spectral clustering on correlation-derived affinities, and a graph approach (k-NN ∪ minimum-spanning-tree with modularity-based communities). Non-linear embeddings (t-SNE/UMAP) and density-based HDBSCAN were used only for visual analytics, not for primary inference. Results: The pipeline revealed coherent reactivity neighborhoods that partially overlapped known cross-reactive antigen groups (CREGs) and eplet-based expectations while also highlighting less-documented relationships. Robustness was confirmed through bootstrap resampling, graph modularity, and consensus clustering across methods. Conclusions: This unified, auditable workflow converts descriptive maps into method-robust summaries of antibody reactivity and cross-reactivity. While exploratory and performed on a single dataset without linked outcomes, the approach provides a reproducible structure for comparing cohorts and prioritizing hypotheses that could be prospectively validated for clinical decision support in transplantation. Full article

With-No-Lysine (WNK) kinases constitute a subgroup within the serine/threonine protein kinase family, characterized by the absence of a catalytic lysine residue in the kinase subdomain II located in their N-terminal region. These kinases play critical roles in regulating plant growth, development, and responses to abiotic stressors. However, members of the WNK and their responses to heat stress in pepper (Capsicum annuum L.) remain unexplored. In the present study, we identified eleven WNK genes within the genome of pepper cultivar ‘UCD-10X-F1’ and designated them CaWNK1 to CaWNK11 according to their chromosomal positions. Comprehensive analyses were conducted to elucidate their phylogenetic relationships, chromosomal distribution, collinearity, gene structure, protein properties, and cis-acting elements within promoter regions. The findings revealed that the CaWNK gene family segregates into five distinct subgroups. Comparative genomic analysis identified eleven and nine segmental duplication gene pairs between pepper and tomato and between pepper and Arabidopsis, respectively. Within the pepper genome, two pairs of segmentally duplicated genes and two pairs of tandemly repeated genes were also detected. The CaWNK gene sequences in pepper exhibited a high degree of conservation; however, variations were observed in the number of introns and exons. Analysis of the promoter regions revealed an abundance of cis-acting elements associated with growth and development, stress responses, and hormone regulation. Subsequent transcriptomic analyses demonstrated that CaWNK genes displayed tissue-specific expression patterns and differential expression levels following treatments with exogenous plant hormones and abiotic stresses. Notably, the expression of CaWNK6 was significantly up-regulated under heat stress conditions. To elucidate the functional role of CaWNK6, virus-induced gene silencing (VIGS) was employed to suppress its expression in pepper seedlings. Silencing of CaWNK6 resulted in disrupted tissue architecture, stomatal closure, and diminished heat tolerance. These phenotypic changes correlated with excessive accumulation of reactive oxygen species (ROS), reduced activity of antioxidant enzymes, and down-regulation of heat shock factor (HSF) genes in the silenced plants. Collectively, these findings offer valuable insights into the functional roles of CaWNK genes and hold significant implications for the development of novel heat-tolerant pepper cultivars. Full article

The emergence of drug-resistant Candida species has created an urgent need for non-toxic molecules that inhibit fungal growth, biofilm development, and hyphal formation. In this study, fifty multi-halogenated indole derivatives were screened against ten Candida species, including azole-resistant C. albicans, C. auris, C. glabrata, and C. parapsilosis. Among them, 4,6-dibromoindole and 5-bromo-4-chloroindole exhibited the strongest antifungal and antibiofilm effects, with minimum inhibitory concentration (MIC) values of 10–50 µg/mL, outperforming ketoconazole and comparable to miconazole. Both di-halogenated indoles markedly inhibited cell aggregation, yeast-to-hyphae transition, and induced reactive oxygen species (ROS) accumulation, contributing to fungicidal activity. Microscopic analyses revealed the disruption of hyphal networks and reduced biofilm biomass. They showed moderate cytotoxicity in human hepatocellular carcinoma (HepG2) cells (median lethal dose, LD₅₀ = 35.5 µg/mL and 75.3 µg/mL) and low phytotoxicity in plant assays. The quantitative structure–activity relationship (QSAR) model identified halogen substitution at C4, C5, and C6 positions as optimal for antifungal activity due to enhanced hydrophobic and electron-withdrawing effects. Together, these findings demonstrate that di-halogenated indoles serve as potent, low-toxicity inhibitors of Candida growth, biofilms, and morphogenesis, providing a promising scaffold for next-generation antifungal agents targeting drug-resistant Candida species. Full article

Background: Sleep disorders, particularly insomnia, represent a significant health concern in medical education. Neuroticism, characterized by emotional instability and stress reactivity, shows cross-sectional associations with sleep disturbances in healthcare trainees. Limited research examines these relationships among South Asian medical students. This cross-sectional study investigated insomnia symptom prevalence, personality correlates, and environmental factors among Pakistani medical students. Methods: We conducted a cross-sectional study among 364 undergraduate medical and dental students in Peshawar, Pakistan (June–November 2024). Data collection occurred during examination months. Data collection employed validated instruments: the Insomnia Severity Index (ISI) and the NEO Five-Factor Inventory neuroticism subscale (NEO-FFI-12). Statistical analyses included Pearson correlations, chi-square tests, and multivariate regression with interaction terms. Results: Among 364 participants (mean age 21.3 ± 2.3 years, 52.2% female), 47.0% reported severe insomnia symptoms (ISI 22–28), with 89.0% experiencing at least subthreshold symptoms (ISI ≥ 8) during the 2-week assessment period. These prevalence rates reflect symptom severity over a 2-week period during examination months and do not represent clinical diagnoses of chronic insomnia disorder, which requires ≥3 months of symptoms with clinical confirmation. High neuroticism (NEO-FFI ≥ 37) characterized 59.8% of students. Multivariate regression revealed a robust cross-sectional association between neuroticism and insomnia symptom severity (β = 0.239, 95% CI [0.173, 0.305], standardized β = 0.342, p < 0.001) and may reflect measurement during peak examination stress rather than stable trait-outcome relationships. Hostel residents showed non-significantly higher clinical insomnia prevalence than day scholars (75.9% vs. 67.5%, p = 0.081). Clinical-year students demonstrated significantly lower insomnia severity than pre-clinical students (β = −1.271, p < 0.001), a finding that contradicts assumptions about increasing stress through training progression. The neuroticism × living arrangement interaction was non-significant (p = 0.118); however, post hoc power analysis indicated the study was underpowered to detect small moderation effects, making this finding inconclusive. Conclusions: This study documents high insomnia symptom severity during a 2-week assessment period in Pakistani medical students, with a robust cross-sectional association with neuroticism. However, these findings must be interpreted within the constraints of the cross-sectional design, which cannot establish temporal precedence or causality between neuroticism and insomnia symptoms. These symptom prevalence rates likely reflect a combination of chronic sleep disorders and transient examination-related stress. Living arrangements showed small, non-significant associations with insomnia. The observed association between neuroticism and insomnia may be partially mediated or confounded by unmeasured variables, including academic stress, psychiatric comorbidities, substance use, and other sleep disorders. Findings suggest potential benefits from interventions addressing cognitive-emotional factors, though comprehensive diagnostic assessment is needed to distinguish chronic insomnia disorder from transient, stress-related sleep difficulties. Longitudinal research with objective sleep measures, structured psychiatric assessment, and systematic confounder evaluation is essential to establish causal relationships and intervention efficacy in this population. Full article