Search Results (10,677)

Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article

The aim was to investigate the genetic effects of a SNP located in the precursor region of gga-miR-3528. (1) Single-nucleotide polymorphisms within precursor regions of microRNAs play crucial biological roles. (2) Utilizing a Gushi–Anka F₂ resource population (n = 860), we screened and validated miRNA SNPs. A SNP mutation in the miR-3528 precursor region was identified. Specific primers were designed to amplify the polymorphic fragment. Genotyping was performed for this individual SNP across the population, using the MassArray system. Association analyses were conducted between this SNP and chicken growth and body measurement traits, carcass traits, meat quality traits, and serum enzyme activities. (3) The rs14098602 (+12 bp A > G) was identified within the precursor region of gga-miR-3528. Significant associations (p < 0.05) were observed between this SNP and chicken growth traits (body weight at the age of 0 day, body weight at the age of 2 weeks, and body weight at the age of 4 weeks), carcass traits (evisceration weight), meat quality traits (subcutaneous fat rate and pectoral muscle density), and serum enzyme activities (total protein, albumin, globulin, cholinesterase, and lactate dehydrogenase). (4) These findings suggest that the polymorphism at rs14098602 may influence chicken growth, meat quality, and serum biochemical indices, through specific mechanisms. The gga-miR-3528 gene likely plays an important role in chicken development. Therefore, this SNP can serve as a molecular marker for genetic breeding and auxiliary selection of growth-related traits, facilitating the rapid establishment of elite chicken populations with superior genetic resources. Full article

The regulation of calcium (Ca²⁺) homeostasis is a critical process in both plant and animal systems, involving complex interplay between various organelles and a diverse network of channels, pumps, and transporters. This review provides a concise overview of inter-organellar Ca²⁺ homeostasis, highlighting key regulators and mechanisms in plant and animal cells. We discuss the roles of key Ca²⁺ channels and transporters, including IP₃Rs, RyRs, TPCs, MCUs, TRPMLs, and P2XRs in animals, as well as their plant counterparts. Here, we explore recent innovations in structural biology and advanced microscopic techniques that have enhanced our understanding of these proteins’ structure, functions, and regulations. We examine the importance of membrane contact sites in facilitating Ca²⁺ transfer between organelles and the specific expression patterns of Ca²⁺ channels and transporters. Furthermore, we address the physiological implications of inter-organellar Ca²⁺ homeostasis and its relevance in various pathological conditions. For extended comparability, a brief excursus into bacterial intracellular Ca²⁺ homeostasis is also made. This meta-analysis aims to bridge the gap between plant and animal Ca²⁺ signaling research, identifying common themes and unique adaptations in these diverse biological systems. Full article

Macrophages are undoubtedly one of the most widely studied cells of the immune system, among other reasons, because they are involved in a wide variety of biological processes. Deregulation of their activity is observed in a number of different disorders, including autoimmune diseases. At the same time, mammalian target of rapamycin (mTOR) is attracting increasing research attention because the pathways dependent on this kinase are activated by a variety of signals, including cytokines and proinflammatory mediators, mediate essential processes for cell survival and metabolism, and can be regulated epigenetically via microRNAs. Therefore, our narrative review aimed to summarize and discuss recent advances in the knowledge of the activation of mTOR signaling in macrophages, with a special focus on autoimmune disorders and the possibility of mTOR control by microRNAs. The summarized research observations allowed us to conclude that the effects of activity and/or inhibition of individual mTOR complexes in macrophages are largely context dependent, and therefore, these broad immunological contexts and other specific conditions should always be taken into account when attempting to modulate these pathways for therapeutic purposes. Full article

Persistent reactive azo dyes released from textile finishing are a serious threat to water systems, but effective methods using sunlight to break them down are still limited. Everzol Yellow 3RS (EY-3RS) is particularly recalcitrant: past studies have relied almost exclusively on physical adsorption onto natural or modified clays and zeolites, and no photocatalytic pathway employing engineered nanomaterials has been documented to date. This study reports the synthesis, characterization, and performance of a visible-active ternary nanocomposite, Cu₄O₃/ZrO₂/TiO₂, prepared hydrothermally alongside its binary (Cu₄O₃/ZrO₂) and rutile TiO₂ counterparts. XRD, FT-IR, SEM-EDX, UV-Vis, and PL analyses confirm a heterostructured architecture with a narrowed optical bandgap of 2.91 eV, efficient charge separation, and a mesoporous nanosphere-in-matrix morphology. Photocatalytic tests conducted under midsummer sunlight reveal that the ternary catalyst removes 91.41% of 40 ppm EY-3RS within 100 min, markedly surpassing the binary catalyst (86.65%) and TiO₂ (81.48%). Activity trends persist across a wide range of operational variables, including dye concentrations (20–100 ppm), catalyst dosages (10–40 mg), pH levels (3–11), and irradiation times (up to 100 min). The material retains ≈ 93% of its initial efficiency after four consecutive cycles, evidencing good reusability. This work introduces the first nanophotocatalytic strategy for EY-3RS degradation and underscores the promise of multi-oxide heterojunctions for solar-driven remediation of colored effluents. Full article

The original Modbus specification for RS-485 and RS-232 buses supported broadcast transmission. As the protocol evolved into Modbus-TCP, to use the TCP transport, this useful feature was lost, likely due to the point-to-point nature of TCP connections. Later proposals did not restore the broadcast transmission capability, although they used UDP as transport and UDP, by itself, would have supported it. Moreover, they did not address the inherent lack of reliable delivery of UDP, leaving datagram loss detection and recovery to the application layer. This paper describes a novel redesign of Modbus-UDP that addresses the aforementioned shortcomings. It achieves a mean round-trip time of only 38% with respect to Modbus-TCP and seamlessly supports a previously published protocol based on Modbus broadcast. In addition, the built-in retransmission of Modbus-UDP reacts more efficiently than the equivalent Modbus-TCP mechanism, exhibiting 50% of its round-trip standard deviation when subject to a 1% two-way IP datagram loss probability. Combined with the lower overhead of UDP versus TCP, this makes the redesigned Modbus-UDP protocol better suited for a variety of Industrial Internet of Things systems with limited computing and communication resources. Full article

To determine the association between FGFR4 (rs351855 and rs7708357) gene variants, serum levels, and immunohistochemical markers (Ki-67 and p53) in pituitary adenoma (PA), a case-control study was conducted involving 300 subjects divided into two groups: the control group (n = 200) and a group of PA (n = 100). The genotyping of FGFR4 rs351855 and rs7708357 was carried out using the real-time polymerase chain reaction (RT-PCR) method. The serum FGFR4 levels were measured using the ELISA method. Immunohistochemical analysis (Ki-67 and p53) was conducted. Statistical analysis of the data was performed using IBM SPSS Statistics 30.0 software. There were no statistically significant differences after analyzing the genotypes and alleles of FGFR4 rs351855 and rs7708357 in patients with PA and control groups (all p > 0.05). After evaluating the distribution of genotypes and alleles of FGFR4 rs351855 and rs7708357 in micro/macro, invasiveness, activity, and recurrence of PA and the control groups, the analysis showed no statistically significant differences between the groups (p > 0.05). Similarly, no significant differences in FGFR4 levels were observed between PA patients and control group (median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, p = 0.121). Immunohistochemistry for Ki-67 revealed a labeling index (LI) of <1% in 25.5% of patients with PA, an LI of 1% in 10.9%, and an LI of >1% in 63.6% of patients. Further analyses showed no statistically significant associations with tumor size, invasiveness, activity, or recurrence. Immunohistochemistry for p53 revealed that macroadenomas had a significantly higher p53 H-score compared to microadenomas (median (IQR): 30.33 (28.68) vs. 18.34 (17.65), p = 0.005). Additionally, a moderate, statistically significant positive correlation between the Ki-67 LI and the p53 expression was found (Spearman’s ρ = 0.443, p = 0.003, n = 43). FGFR4 variants and serum protein levels were not significantly associated with PA risk or tumor features. Conversely, immunohistochemical markers Ki-67 and p53 were more informative, with higher p53 expression in macroadenomas and a moderate positive correlation between Ki-67 and p53, highlighting their potential relevance in tumor growth assessment. Full article

Background: Amyotrophic lateral sclerosis is a systemic, complex, multifactorial, and fatal neurodegenerative disease with various factors involved in its etiology. This study aimed to understand the effects of SNPs in the MTHFR, MTR, SLC19A1, and VAPB genes on protein functionality and structure and their influence on ALS susceptibility. Methods: The dbSNP and ClinVar databases were used for SNP data annotation, while UniProt and PDB provided protein sequences. We performed functional and structural predictions of SNPs using PolyPhen-2 and SNAP2. We modeled mutant proteins using AlphaFold 2 and visualized them in PyMOL to compare native and mutant forms. Results: Our results identified SNP rs74315431 as pathogenic, inducing structural and functional changes and exhibiting visible alterations in the three-dimensional structure. Although predicted as non-pathogenic, SNPs rs1801131, rs1805087, and rs1051266 caused protein structural alterations, a finding confirmed by three-dimensional visualization. SNP rs1801133 diverged from the others, being predicted as pathogenic but without causing changes in protein structure or function. Conclusions: Our study found a strong correlation between SNAP2-predicted alterations and those predicted by AlphaFold 2, whereas PolyPhen-2 results did not directly correlate with three-dimensional structure changes. Full article

Rainwater harvesting for sustainable agriculture (RWHSA) offers a viable and eco-friendly strategy to alleviate water scarcity in semi-arid regions, particularly for agricultural use. This study aims to identify optimal sites for implementing RWH systems in northern Iraq to enhance water availability and promote sustainable farming practices. An integrated geospatial approach was adopted, combining Remote Sensing (RS), Geographic Information Systems (GIS), and Multi-Criteria Decision Analysis (MCDA). Key thematic layers, including soil type, land use/land cover, slope, and drainage density were processed in a GIS environment to model runoff potential. The Soil Conservation Service Curve Number (SCS-CN) method was used to estimate surface runoff. Criteria were weighted using the Analytical Hierarchy Process (AHP), enabling a structured and consistent evaluation of site suitability. The resulting suitability map classifies the region into four categories: very high suitability (10.2%), high (26.6%), moderate (40.4%), and low (22.8%). The integration of RS, GIS, AHP, and MCDA proved effective for strategic RWH site selection, supporting cost-efficient, sustainable, and data-driven agricultural planning in water-stressed environments. Full article

Cucumber, a high-yielding crop commonly grown in facility environments, is particularly susceptible to nitrogen (N) deficiency due to its rapid growth and high nutrient demand. This study used cucumber as its experimental subject and established a spectral dataset of leaves under four nutritional conditions, normal supply, nitrogen deficiency, phosphorus deficiency, and potassium deficiency, aiming to develop an efficient and robust method for quantifying N in cucumber leaves using Raman spectroscopy (RS). Spectral data were preprocessed using three baseline correction methods—BaselineWavelet (BW), Iteratively Improve the Moving Average (IIMA), and Iterative Polynomial Fitting (IPF)—and key spectral variables were selected using 4-Dimensional Feature Extraction (4DFE) and Competitive Adaptive Reweighted Sampling (CARS). These selected features were then used to develop a N content prediction model based on Partial Least Squares Regression (PLSR). The results indicated that baseline correction significantly enhanced model performance, with three methods outperforming unprocessed spectra. A further analysis showed that the combination of IPF, 4DFE, and CARS achieved optimal PLSR model performance, achieving determination coefficients (R²) of 0.947 and 0.847 for the calibration and prediction sets, respectively. The corresponding root mean square errors (RMSEC and RMSEP) were 0.250 and 0.368, while the residual predictive deviation (RPDC and RPDP) values reached 4.335 and 2.555. These findings confirm the feasibility of integrating RS with advanced data processing for rapid, non-destructive nitrogen assessment in cucumber leaves, offering a valuable tool for nutrient monitoring in precision agriculture. Full article

Background/Objectives: The increased risk of developing tendinopathies in athlete populations has led to investigations of several genes associated with tendon properties, suggesting that some individuals have a greater genetic predisposition for developing tendinopathies. The main purpose of this study was to investigate how the functional polymorphisms within the COL5A1, COL27A1 and TNC genes impact the risk of developing tendinopathies in high-level Croatian athletes. Methods: For this case–control genetic study, we recruited 63 high-level athletes with a diagnosis of tendinopathies and 92 healthy asymptomatic individuals as controls. All individuals were genotyped for three single-nucleotide polymorphisms (SNPs) within the COL5A1, COL27A1 and TNC genes using the pyrosequencing method. Results: TNC rs2104772 TT (p = 0.0089) and the T-T-T haplotype (p = 0.0234), constructed from rs12722, rs946053 and rs2104772, were significantly overrepresented in cases versus controls, implicating a predisposition for tendinopathies. COL27A1 rs946053 GG (p = 0.0118) and the G-A-C haplotype (p = 0.0424), constructed from rs12722, rs946053 and rs2104772, were significantly overrepresented in controls, implicating a protective role. Conclusions: These results further support associations between functional polymorphisms within the COL27A1 and TNC genes and the risk of tendinopathies in high-level athletes. Further research is needed to replicate these results in various populations and larger cohorts. Full article

Background/Objectives: Schizophrenia exhibits symptoms linked to the hippocampus and parahippocampal gyrus. This includes the entorhinal cortex (ERC) and perirhinal cortex (PRC) as anterior parts, along with the posterior segment known as the parahippocampal cortex (PHC). However, recent research has detailed atlases based on cytoarchitectural characteristics and the hippocampus divided into four subregions: cornu ammonis (CA), dentate gyrus (DG), subiculum (SUB), and hippocampal–amygdaloid transition (HATA). This study aimed to explore the functional connectivity (FC) changes between these hippocampal subregions and the parahippocampal gyrus structures (ERC, PRC, and PHC) as well as between hippocampal subregions and various functional brain networks in schizophrenia. Methods: In total, 50 individuals with schizophrenia and 50 matched healthy subjects were examined using resting state functional magnetic resonance imaging (rs-fMRI). Results: The results showed alterations characterized by increases and decreases in the strength of the positive connectivity between the parahippocampal gyrus structures and the four hippocampal subregions when comparing patients with schizophrenia with healthy subjects. Alterations were observed among the hippocampal subregions and functional brain networks, as well as the formation of new connections and absence of connections. Conclusions: There is strong evidence that the different subregions of the hippocampus have unique functions and their connectivity with the parahippocampal cortices and brain networks are affected by schizophrenia. Full article

Background/Objectives: While intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke (AIS) within 4.5 h of symptom onset, many patients present beyond this time window. Recent trials suggest that IVT may be both effective and safe in selected patients treated after the standard time window. Methods: We searched MEDLINE, Scopus, and ClinicalTrials.gov for randomized-controlled clinical trials (RCTs) and individual patient-data meta-analyses (IPDMs) of RCTs comparing IVT plus best medical treatment (BMT) to BMT alone in AIS patients who were last-known-well more than 4.5 h earlier. The primary efficacy outcome was a 90-day excellent functional outcome [modified Rankin Scale (mRS)-scores of 0–1]. Secondary efficacy outcomes included good functional outcome (mRS-scores 0–2) and reduced disability (≥1-point reduction across all mRS-strata). The primary safety outcome was symptomatic intracranial hemorrhage (sICH); secondary safety outcomes were any ICH and 3-month all-cause mortality. Subgroup analyses were performed stratified by different thrombolytics, time-windows, imaging modalities, and affected circulation. Results: Nine studies were included, comprising 1660 patients in the IVT-group and 1626 patients in the control-group. IVT significantly improved excellent functional outcome (RR = 1.24; 95%CI:1.14–1.34; I² = 0%) and good functional outcome (RR = 1.18; 95%CI:1.05–1.33; I² = 70%). IVT was associated with increased odds of reduced disability (common OR = 1.3; 95%CI:1.15–1.46; I² = 0%) and increased risk of sICH (RR = 2.75; 95%CI:1.49–5.05; I² = 0%). The rates of any ICH and all-cause mortality were similar between the two groups. No significant subgroup differences were documented. Conclusions: IVT in the extended time window improved functional outcomes without increasing mortality, despite a higher rate of sICH. Full article

Background/Objectives: Direct oral anticoagulants (DOACs) are now the guideline-recommended alternative to vitamin K antagonists (VKAs) for long-term anticoagulation in patients with non-valvular atrial fibrillation. However, accurately assessing their impact on ischemic stroke outcomes remains challenging, primarily due to uncertainty regarding anticoagulation status at the time of hospital admission. This preliminary study addresses this gap by using point-of-care testing (POCT) to confirm DOAC activity at bedside, allowing for a more accurate comparison of 90-day functional outcomes between anticoagulated and non-anticoagulated stroke patients. Methods: We conducted a retrospective cohort study of 786 ischemic stroke patients admitted to the University of Pécs between February 2023 and February 2025. Active DOAC therapy was confirmed using the ClotPro^® viscoelastic testing platform, with ecarin Clotting Time (ECT) employed for thrombin inhibitors and Russell’s Viper Venom (RVV) assays for factor Xa inhibitors. Patients were categorized as non-anticoagulated (n = 767) or DOAC-treated with confirmed activity (n = 19). Mahalanobis distance-based matching was applied to account for confounding variables including age, sex, pre-stroke modified Rankin Scale (mRS), and National Institutes of Health Stroke Scale (NIHSS) scores at admission and 72 h post-stroke. The primary outcome was the change in mRS from baseline to 90 days. Statistical analysis included ordinary least squares (OLS) regression and principal component analysis (PCA). Results: After matching, 90-day functional outcomes were comparable between groups (mean mRS-shift: 2.00 in DOAC-treated vs. 1.78 in non-anticoagulated; p = 0.745). OLS regression showed no significant association between DOAC status and recovery (p = 0.599). In contrast, NIHSS score at 72 h (p = 0.004) and age (p = 0.015) were significant predictors of outcome. PCA supported these findings, identifying stroke severity as the primary driver of outcome. Conclusions: This preliminary analysis suggests that ischemic stroke patients with confirmed active DOAC therapy at admission may achieve 90-day functional outcomes comparable to those of non-anticoagulated patients. The integration of bedside POCT enhances the reliability of anticoagulation assessment and underscores its clinical value for real-time management in acute stroke care. Larger prospective studies are needed to validate these findings and to further refine treatment strategies. Full article

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) was a 3-year, multicenter, randomized controlled trial to test the effects of the MIND diet on cognitive decline in 604 individuals at risk for Alzheimer’s dementia. Here, we describe the genotyping, imputation, and quality control (QC) procedures for the genetic data of trial participants. Methods: DNA was extracted from either whole blood or serum, and genotyping was performed using the Infinium Global Diversity Array. Established sample and SNP QC procedures were applied to the genotyping data, followed by imputation using the 1000 Genomes Phase 3 v5 reference panel. Results: Significant study-site, specimen type, and batch effects were observed. A total of 494 individuals of inferred European ancestry and 58 individuals of inferred African ancestry were included in the final imputed dataset. Evaluation of the imputed APOE genotype against gold-standard sequencing data showed high concordance (98.2%). We replicated several known genetic associations identified from previous genome-wide association studies, including SNPs previously linked to adiponectin (rs16861209, p = 1.5 × 10⁻⁵), alpha-linolenic acid (rs174547, p = 1.3 × 10⁻⁷), and alpha-tocopherol (rs964184, p = 0.003). Conclusions: This dataset represents the first genetic resource derived from a dietary intervention trial focused on cognitive outcomes. It enables investigation of genetic contributions to variability in cognitive response to the MIND diet and supports integrative analyses with other omics data types to elucidate the biological mechanisms underlying cognitive decline. These efforts may ultimately inform precision nutrition strategies to promote cognitive health. Full article