Search Results (35,400)

The focus in this study was to investigate the proteolytic functions of matrix metalloproteinases (MMPs) and a disintegrin and metalloprotease (ADAM) proteins in the progression of diabetic retinopathy (DR) and to evaluate their potential as therapeutic targets for eye diseases. This study involved three groups: non-proliferative diabetic retinopathy patients (NPDR) (n = 27), proliferative diabetic retinopathy patients (PDR) (n = 32), and a control group of 30 healthy individuals. Serum levels of ADAM9 and MMP9 were measured across these groups for comparative analysis. Serum ADAM9 levels were significantly lower in the NPDR and PDR groups than in the control group (p = 0.031, p < 0.001). Although ADAM9 levels were lower in the PDR group than in the NPDR group, this difference was not significant (p = 0.142). Serum MMP9 levels in the PDR group were significantly lower than those in both the control and NPDR groups (p = 0.039, p = 0.013). The findings of this study indicate that ADAM9, MMP9, and left-eye ocular parameters may have potential value in the assessment of DR. The notable variation in the MMP9 marker in the proliferative stage, as opposed to its stability in the non-proliferative stage, suggests a distinct role in retinopathy staging. This underscores the specific importance of MMP9 in the proliferative stage. Full article

Soil erosion in granite-derived weathering mantles poses serious threats to slope stability and ecological sustainability in subtropical regions. While polyacrylamide (PAM) is widely used to improve soil structure, its concentration-dependent effects on multiple soil functions remain unclear. This study developed a multifunctional Soil Function Index (SFI) framework integrating erosion resistance (SFI₁), water regulation (SFI₂), and ecological function (SFI₃) to evaluate the effects of PAM application (0‰, 1‰, 3‰, 5‰, 7‰) on gully-prone sandy material. Herein, SFI₁ was quantified through shear strength (τ) and soil erodibility (K_r); SFI₂ was assessed using soil hydraulic parameters (saturated hydraulic conductivity and water retention curves) and SFI₃ was derived from the grass root system analysis. The results showed that SFI₁ and SFI₂ increased nonlinearly with PAM concentration, reaching maximum values of 0.983 and 0.980 at 7‰, with K_r reduced by 77.3% and non-capillary porosity (NAP) increased by 8.1%. In contrast, SFI₃ peaked at 0.858 under 3‰ and declined sharply to 0.000 at 7‰, due to micropore over-compaction, reduced aeration, and limited plant-available water. The total SFI exhibited a unimodal trend, with a maximum of 0.755 at 3‰, beyond which ecological suppression offset physical improvements. These findings demonstrate that PAM modifies soil multifunctionality through pore-scale restructuring, inducing function-specific thresholds and trade-offs. A PAM concentration of 3‰ is identified as optimal, achieving a balance between erosion control, hydrological performance, and ecological viability in the management of subtropical granite-derived sandy slopes. Full article

Retinoblastoma is a rare but malignant pediatric retinal tumor, affecting 1 in 15,000–20,000 live births annually. It arises from biallelic mutations in the RB1 tumor suppressor gene (chromosome 13q14.2), leading to uncontrolled cell cycle progression. Clinically, it presents as unilateral (60%) or bilateral (40%) disease, with leukocoria and strabismus as hallmark signs. Untreated, retinoblastoma is fatal due to metastatic spread. The disease follows Knudson’s two-hit model: heritable forms (30–40% of cases) involve a germline RB1 mutation (M1) and a somatic second hit (M2), predisposing to bilateral/multifocal tumors and secondary cancers. Non-heritable cases (60–70%) result from somatic RB1 mutations or, rarely, MYCN amplification (2%). Genetic testing is critical to classify risk (H0, H1, and HX categories), guide surveillance, and inform family counseling. Bilateral cases almost always harbor germline mutations, while 15% of unilateral cases may carry germline/mosaic RB1 defects. Advanced techniques (Sanger/NGS sequencing for mutation detection, NGS for copy number alterations, and methylation assays) detect RB1 mutations, CNVs, and epigenetic silencing. Tumor DNA analysis resolves ambiguous cases. H1 patients require intensive ocular and brain MRI surveillance, while H0 cases need no follow-up. Prenatal/preimplantation genetic diagnosis (PGD) can prevent transmission in high-risk families. Emerging research explores additional genes (BCOR, CREBBP) and MYCN-amplified subtypes. Genetic counseling addresses recurrence risks, reproductive options, and long-term cancer monitoring. Integrating genetic insights into clinical practice enhances precision medicine, reducing morbidity and healthcare costs. Future directions include whole-genome sequencing and functional studies to refine therapeutic strategies. Full article

Background: Dental professionals are particularly susceptible to occupational stress and burnout, which are amplified during armed conflicts. Civilian dentists continuing to provide care under wartime conditions face unique psychological challenges. This study aimed to evaluate their psychological wellbeing and professional quality of life during military conflict. Methods: A cross-sectional study was conducted using an anonymous online questionnaire distributed through the national dental association. The survey included the Professional Quality of Life Scale (ProQOL, version 5) to assess compassion satisfaction, burnout, and secondary traumatic stress; and the Generalized Anxiety Disorder 7-item scale (GAD-7) to measure anxiety severity. Additional items captured demographic information, professional experience, pre-conflict workload, current work status, family circumstances, and subjective financial impact. The final sample included 239 civilian dentists. Statistical analysis included descriptive statistics, Pearson correlations, chi-square tests for categorical variables, Mann-Whitney U and Kruskal-Wallis tests for between-group comparisons, and multiple regression to identify predictors of psychological outcomes. Results: High compassion satisfaction was reported by 38.9% of respondents, while 70.3% exhibited average burnout levels; only 0.4% had high burnout. Secondary traumatic stress was low in 85.4% of participants. Minimal anxiety was found in 54% of respondents. Significant correlations were found between professional satisfaction and lower anxiety (p < 0.001), lower burnout (p < 0.001), and higher compassion satisfaction (p < 0.001). Dentists with more years of experience and older age reported lower anxiety and burnout levels. Higher pre-conflict workloads were associated with increased anxiety during the conflict (p < 0.001). Dentists working in Health Maintenance Organizations (HMOs) reported significantly higher anxiety levels compared to their non-HMO counterparts (p = 0.022), although reported income loss was similar between groups. Conclusions: Civilian dentists demonstrated resilience and overall positive professional functioning during prolonged conflict. However, public sector dentists, especially those in HMOs, showed greater vulnerability to anxiety. These findings underscore the need for systemic strategies to support dental professionals’ mental health during national crises, with emphasis on those in the public health system. Full article

Background: Pelemir (Cephalaria syriaca) is a bitter-tasting ancestral legume with a high polyphenol content and emerging potential as a functional food ingredient. This study investigated the acute metabolic effects of pelemir-enriched bread in adults. Methods: In this two-phase non-randomized trial, 60 participants in three groups (n = 20 per group: healthy controls [HCs], individuals with obesity [OB], and individuals with type 2 diabetes [T2D]) consumed regular or pelemir-enriched bread on two separate test days. Postprandial glucose, insulin, C-peptide, GLP-1, PYY, ghrelin, leptin, triglyceride, and IL-6 were measured over 120 min. Subjective appetite ratings were evaluated using visual analog scales (VASs). The incremental area under the curve (iAUC) values were compared using Wilcoxon tests and linear mixed-effects models. Results: Pelemir-enriched bread significantly increased iAUCs for insulin (p = 0.014), C-peptide (p = 0.046), and GLP-1 (p = 0.039) compared to regular bread. There was no significant change in iAUC for glucose. Group-stratified analyses showed a higher postprandial iAUC of glucose, insulin, and C-peptide in the OB group compared to the HC group. VAS-based appetite ratings did not show significant changes in hunger, fullness, or desire to eat, but a borderline significant reduction was observed in prospective food consumption after pelemir-enriched bread (p = 0.050). Conclusions: Acute consumption of pelemir-enriched bread may modulate postprandial insulin and incretin responses. Its modest impact on subjective appetite regulation supports further investigation of pelemir as a functional food rich in polyphenols, especially in populations with metabolic dysfunction. Full article

Runoff prediction plays a critical role in water resource management and flood mitigation. Traditional runoff prediction methods often rely on single-layer optimization frameworks that process the data without decomposition and employ relatively simple prediction models, leading to suboptimal performance. In this study, a novel two-layer optimization framework is proposed that integrates data decomposition techniques with multi-model combination strategies, establishing a closed-loop feedback mechanism between decomposition and prediction processes. The framework employs the Snow Ablation Optimizer (SAO) to optimize combination weights across both layers. Its adaptive fitness function incorporates three evaluation metrics—Mean Absolute Percentage Error (MAPE), Relative Root Mean Square Error (RRMSE), and Nash–Sutcliffe Efficiency (NSE)—to enable adaptive data processing and intelligent model selection. We validated the framework using observational data from Huangzhuang Hydrological Station in the Hanjiang River Basin. The results demonstrate that, at the decomposition layer, optimal performance was achieved by combining non-decomposition, Singular Spectrum Analysis (SSA), and Complementary Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) (with coefficients 0.4061, 0.6115, and −0.0063), paired with the long short-term memory (LSTM) model. At the prediction layer, the proposed algorithm achieved a 32.84% improvement over the best single decomposition method and a 30.21% improvement over the best single combination optimization approach. These findings confirm the framework’s effectiveness in enhancing runoff data decomposition and optimizing multi-model selection. Full article

Background/Objectives: Heart rate variability (HRV) is a reliable, non-invasive marker of autonomic nervous system function and is often impaired in individuals with metabolic syndrome (MetS). Physical exercise has emerged as an effective strategy to improve autonomic modulation; however, the comparative effects of different training modalities on HRV in individuals with MetS remain unclear. This systematic review and meta-analysis aimed to evaluate the impact of various exercise interventions on HRV and to identify which training types yield the most significant improvements. Methods: A systematic search was conducted in PubMed and Scopus up to April 2025. Eligible studies (n = 16) included adults with obesity and MetS (n = 752) who underwent structured exercise interventions with HRV assessments pre- and post-intervention. Standardized mean differences were calculated using random effects models. Subgroup analyses were performed based on training modality (endurance training [ET], resistance training [RT], high-intensity interval training [HIIT], and concurrent training [CT]). Results: Sixteen studies of moderate to high quality were included, with eleven studies eligible for meta-analysis. ET and HIIT significantly improved time-domain indices (Root mean square of differences of successive R-R intervals —rMSSD—, Standard deviation of the R-R interval series —SDNN—) and frequency-domain parameters (high-frequency —HF—), suggesting enhanced parasympathetic activity. RT showed inconsistent effects, while CT improved long-term HF and total power (TP). Non-linear indices were the least reported due to insufficient data. Conclusions: Physical exercise—particularly ET and HIIT—appears to enhance cardiac autonomic modulation in individuals with obesity and MetS. These findings support incorporating targeted training strategies into clinical practice to optimize cardiovascular health in these populations. Full article

Although mulberry leaf (Morus alba L., ML) and Siraitia grosvenorii (SG) individually demonstrate anti-diabetic properties, their combined efficacy against type 2 diabetes mellitus (T2DM) remains unexplored. This study systematically explored the multi-target mechanisms and synergistic potential of the MLSG combination (MLSG) for T2DM intervention. We evaluated the in vitro inhibitory activities of MLSG, ML, and SG on α-amylase and α-glucosidase, alongside antioxidant capacity assessments through DPPH/ABTS radical scavenging, reducing power, and FRAP assays. Bioactive metabolites were identified using non-targeted metabolomics, while core targets and pathways were predicted using network pharmacology and validated through molecular docking. The results reveal MLSG’s significantly enhanced inhibition of α-amylase (IC₅₀ = 14.06 mg/mL) and α-glucosidase (IC₅₀ = 0.02 mg/mL) compared to individual extracts, exhibiting 1.3–15.5-fold higher potency with synergistic effects (combination index < 1). MLSG also showed improved antioxidant capacity, outperforming SG in DPPH/ABTS⁺ scavenging and reducing power (p < 0.05), and surpassing ML in ABTS⁺ scavenging, reducing power, and FRAP values (p < 0.05). Metabolomics identified 26 MLSG-derived metabolites with anti-T2DM potential, and network analysis pinpointed 26 active components primarily targeting STAT3, AKT1, PIK3CA, EGFR, and MAPK1 to regulate T2DM pathways. Molecular docking confirmed strong binding affinities between these components and core targets. Collectively, MLSG exerts potent synergistic anti-T2DM effects through dual-enzyme inhibition, elevated antioxidant activity, and multi-target pathway regulation, providing a solid foundation for developing MLSG as functional food ingredients. Full article

Background: Colon capsule endoscopy (CCE) has seen increased adoption since the COVID-19 pandemic, offering a non-invasive alternative for lower gastrointestinal investigations. However, inadequate bowel preparation remains a key limitation, often leading to higher conversion rates to colonoscopy. Manual assessment of bowel cleanliness is inherently subjective and marked by high interobserver variability. Recent advances in artificial intelligence (AI) have enabled automated cleansing scores that not only standardise assessment and reduce variability but also align with the emerging semi-automated AI reading workflow, which highlights only clinically significant frames. As full video review becomes less routine, reliable, and consistent, cleansing evaluation is essential, positioning bowel preparation AI as a critical enabler of diagnostic accuracy and scalable CCE deployment. Objective: This CESCAIL sub-study aimed to (1) evaluate interobserver agreement in CCE bowel cleansing assessment using two established scoring systems, and (2) determine the impact of AI-assisted scoring, specifically a TransUNet-based segmentation model with a custom Patch Loss function, on both interobserver and intraobserver agreement compared to manual assessment. Methods: As part of the CESCAIL study, twenty-five CCE videos were randomly selected from 673 participants. Nine readers with varying CCE experience scored bowel cleanliness using the Leighton–Rex and CC-CLEAR scales. After a minimum 8-week washout, the same readers reassessed the videos using AI-assisted CC-CLEAR scores. Interobserver variability was evaluated using bootstrapped intraclass correlation coefficients (ICC) and Fleiss’ Kappa; intraobserver variability was assessed with weighted Cohen’s Kappa, paired t-tests, and Two One-Sided Tests (TOSTs). Results: Leighton–Rex showed poor to fair agreement (Fleiss = 0.14; ICC = 0.55), while CC-CLEAR demonstrated fair to excellent agreement (Fleiss = 0.27; ICC = 0.90). AI-assisted CC-CLEAR achieved only moderate agreement overall (Fleiss = 0.27; ICC = 0.69), with weaker performance among less experienced readers (Fleiss = 0.15; ICC = 0.56). Intraobserver agreement was excellent (ICC > 0.75) for experienced readers but variable in others (ICC 0.03–0.80). AI-assisted scores were significantly lower than manual reads by 1.46 points (p < 0.001), potentially increasing conversion to colonoscopy. Conclusions: AI-assisted scoring did not improve interobserver agreement and may even reduce consistency amongst less experienced readers. The maintained agreement observed in experienced readers highlights its current value in experienced hands only. Further refinement, including spatial analysis integration, is needed for robust overall AI implementation in CCE. Full article

Background/Objectives: Parkinson’s disease (PD) and multiple sclerosis (MS) are neurological conditions that result in debilitating non-motor symptoms, such as anxiety and depression, which significantly reduce quality of life and often persist despite pharmacological treatment. As a result, effective alternative treatment strategies are needed. Exercise therapy—particularly aerobic training—has shown promise in alleviating non-motor symptoms, potentially through neuroplastic adaptations. However, traditional aerobic exercise is often time-consuming and monotonous, limiting long-term adherence. High-intensity interval training (HIIT) offers a time-efficient and potentially more engaging alternative, though its effects on non-motor symptoms in PD and MS remain understudied. Methods: This transdiagnostic randomized controlled trial will enroll 48 participants (24 PD, 24 MS) with clinically significant affective symptoms (hospital anxiety and depression scale [HADS] ≥ 8). The participants will be randomly assigned to one of three 8-week interventions: (1) HIIT, 5–6 intervals of 45 s of high-intensity cycling; (2) continuous aerobic training (CAT), 50 min of low-intensity cycling; (3) movement advice (MA), step goals, and physical education. The primary (affective symptoms) and secondary outcomes (cognition, fatigue, sleep, motor function) will be assessed at four time points: 4 and 1 weeks pre intervention, and 1 and 4 weeks post intervention. Weekly blood samples and pre/post brain imaging will be collected to study biofluid and MRI measures for potential neuroplasticity. Linear mixed models will analyze the time and group effects. Discussion: This trial will assess whether HIIT can more effectively improve non-motor and motor symptoms in PD and MS than CAT or MA. A multimodal approach will explore both the clinical outcomes and underlying mechanisms, informing scalable and engaging rehabilitation strategies. Full article

This article introduces two numerical methods based on the Theory of Functional Connections (TFC) for solving linear ordinary differential equations that involve step discontinuities in the forcing term. The novelty of the first proposed approach lies in the direct incorporation of discontinuities into the free function of the TFC framework, while the second proposed method resolves discontinuities through piecewise constrained expressions comprising particular weighted support functions systematically chosen to enforce continuity conditions. The accuracy of the proposed methods is validated for both a second-order initial value and boundary value problem. As a final demonstration, the methods are applied to a third-order differential equation with non-constant coefficients and multiple discontinuities, for which an analytical solution is known. The methods achieve error levels approaching machine precision, even in the case of equations involving functions whose Laplace transforms are not available. Full article

Ginger, an economically important crop, fulfills multifunctional roles as a spice, vegetable, and raw material for medicinal and chemical products. The family of Auxin Response Factors (ARFs) plays an essential role in facilitating auxin signal transduction and regulating plant growth and development. However, the role of ARF genes in ginger, a crop of considerable economic importance, remains elucidated. In this study, a total of 26 ZoARF genes were identified in the ginger genome, which were further categorized into four subfamilies (I–IV) and displayed a non-uniform distribution across 11 chromosomes. The proteins are predominantly localized to the nucleus. Promoter regions contained numerous cis-elements linked to light signaling, phytohormones, growth, development, and stress responses. Collinearity analysis revealed 9 pairs of fragment duplication events in ZoARFs, all uniformly distributed across their related chromosomes. In addition, the expression profiles of ZoARFs in ginger were analyzed during development and under several stress conditions like ABA, cold, drought, heat, and salt, employing RNA-seq data and qRT-PCR analysis. Notably, expression profiling revealed tissue-specific functions, with ZoARF#04/05/12/22 associated with flower development and ZoARF#06/13/14/23 implicated in root growth. This work provides an in-depth insight into the ARF family and establishes a foundation for future investigations of ZoARF gene functions in ginger growth, development, and abiotic stress tolerance. Full article

Thermoresponsive hydrogels that undergo reversible sol-gel transitions near physiological temperatures are highly attractive for biomedical applications, such as injectable drug delivery and embolization therapies. In this study, a library of polyurethane-based hydrogels was synthesized via step-growth polymerization using polyethylene glycol (PEG) of varying molecular weights, different diisocyanates, and a series of functional diols derived from diethanolamine with increasing hydrophobicity. The resulting polymers exhibited sol–gel transition behaviors without the need for external crosslinkers, relying solely on non-covalent interactions. The thermal responsiveness was systematically investigated using UV–Vis turbidimetry, and the cloud point temperature (T_CP) was found to be tunable within a range of 26–49 °C by modulating the monomer composition. Statistical modeling identified PEG molecular weight and diol structure as the primary determinants of T_CP, while diisocyanate type and diol-to-PEG ratio had negligible effects. Only diethanolamine (DEA)-based polymers formed stable hydrogels above a critical gelation temperature (LCGT), attributed to enhanced intermolecular interactions via free amine groups. In vitro degradation assays confirmed good hydrolytic stability under physiological conditions over four weeks, with degradation profiles strongly influenced by the PEG chain length and hydrophobic content. These findings establish a structure–property framework for the rational design of injectable, thermoresponsive polyurethane hydrogels with tailored sol–gel behavior for biomedical applications. Full article

Alzheimer’s disease (AD) is a significant global health challenge, further exacerbated by the anticipated increase in prevalence in the coming years. The accumulation of β-amyloid peptide plays a critical role in the onset of AD; however, emerging evidence suggests that soluble oligomers of β-amyloid may primarily drive the neuronal impairments associated with this condition. Additionally, neurodegenerative diseases like AD are linked to oxidative stress and reduced antioxidant capacity in the brain. Natural products, particularly polysaccharides extracted from mushrooms, have garnered interest due to their neuroprotective properties and the potential to enhance the value of natural sources in addressing human diseases. This study examines the antioxidant and neuroprotective properties of polysaccharides derived from Cyttaria espinosae Lloyd (CePs), a relatively underexplored fungus native to Chile. Using Fourier Transform Infrared Spectroscopy (FT-IR) and Gas Chromatography-Mass Spectrometry (GC-MS), we characterized CePs. We assessed their antioxidant capacity using DPPH and ABTS assays, yielding maximum inhibition rates of 32.14% and 19.10%, respectively, at a concentration of 10 mg mL⁻¹. CePs showed no toxicity in zebrafish embryos and maintained high cell viability in PC-12 cells exposed to amyloid β peptide (Aβ). Our findings suggest that CePs exhibit significant antioxidant and neuroprotective properties against Aβ peptide toxicity while remaining non-toxic to zebrafish embryos. This underscores the potential of the polysaccharides from this mushroom to serve as functional foods that mitigate oxidative stress and warrant further investigation into their mechanisms in the context of the physiopathology of Alzheimer’s disease. Full article

The aim of the article is to present a comprehensive procedure for processing and evaluating directional data from vehicle license plates, focusing on the specific challenges of areas that are sparsely or not at all equipped with permanently located standard license plate recognition systems. This remains a current issue, especially in smaller towns; it leads to the implementation of short-term directional traffic surveys, often using inexpensive measurement devices, in order to obtain directional traffic data. In this research, a procedure for evaluating license plate recognition data is proposed with a primary focus on its simple adaptability and automation for any subsequent use. The data sources considered are primarily the above-mentioned traffic surveys; however, the proposed evaluation procedure is theoretically transferable to any off-line data obtained from license plate recognition systems. Identifying potential inaccuracies in the data is also an integral part of the evaluation process. The design of the proposed procedure follows the Checkland soft systems methodology and the functionality of the resulting procedure was validated through a case study of a directional survey in Prague. The proposed procedure contributes to greater accuracy of the conclusions drawn from evaluated traffic engineering parameters under non-ideal, but common conditions of smaller cities, not only in the Czech Republic. Full article