Search Results (3,030)

Alzheimer’s disease (AD) is a complex neurodegenerative condition marked by a gradual decline in cognitive abilities, a reduction in acetylcholine (ACh) levels, and the accumulation of β-amyloid (Aβ) plaques. In a healthy brain, approximately 80% of ACh is broken down by acetylcholinesterase (AChE). Meanwhile, butyrylcholinesterase (BChE) serves a supportive function, gaining significance as AChE activity diminishes during the progression of Alzheimer’s disease. Modern therapeutic approaches focus on creating dual inhibitors of AChE and BChE that also aim to diminish Aβ-amyloidogenesis through interactions with the peripheral anionic site (PAS). This study combined fragment-based molecular design (CReM), AI-assisted retrosynthetic feasibility assessment, and in silico evaluation (docking, molecular dynamics, and ADMET profiling) to identify novel Donepezil derivatives as potential dual AChE/BChE inhibitors. A series of 10,000 derivatives were developed through computational methods and carefully assessed based on stringent drug-likeness, synthetic accessibility, and medicinal chemistry standards. This was succeeded by comprehensive ADMET profiling. Nine candidates were identified with predicted CNS pharmacokinetics, adequate toxicological profiles and reduced cytochrome P450 liabilities. Molecular docking yielded improved predicted binding affinities relative to Donepezil. Several derivatives, particularly D4 and D5, showed dual-site binding poses spanning both the catalytic gorge and the PAS. MD simulations indicated the stability of these poses over 100 ns. These computational results suggest that the proposed derivatives may preserve or improve upon Donepezil’s pharmacokinetic profile while offering potentially balanced AChE/BChE inhibition and anti-amyloidogenic activity, pending experimental validation. Full article

Background: Beta-blockers (BBs) remain a foundation of cardiovascular therapy. However, cumulative evidence suggests that metabolic adverse effects may differ significantly between individual sub-classes. While conventional BBs have been associated with changes in glucose and lipid metabolism, the comparative real-world reporting patterns of these events have not been comprehensively evaluated. Objective: We investigated the association between selected BBs and metabolic diseases using a large pharmacovigilance database and compared the reporting profiles of metoprolol (MET), carvedilol (CAR), bisoprolol (BIS), and nebivolol (NEB). Methods: A descriptive and disproportionality analysis was performed using Individual Case Safety Reports (ICSRs) submitted to the EudraVigilance database up to 26 April 2026. Metabolic adverse events were grouped into pathophysiological categories, including dysglycemia and type 2 diabetes mellitus (T2DM), lipid disorders, obesity-related disorders, inflammatory biomarkers, and hepatic steatosis. Reporting odds ratios (RORs) with 95% confidence intervals (CI) were calculated to identify disproportional reporting signals. To improve clinical reliability, a stratified analysis restricted to healthcare professional (HP)-submitted reports was conducted. Results: A total of 63.744 ICSRs were identified for the four BBs, including 27.169 for MET, 21.860 for BIS, 9487 for CAR, and 5228 for NEB. Dysglycemic events represented the most frequently reported metabolic category, with hyperglycemia and T2DM accounting for 155 reports each. MET was associated with the highest number of reports for T2DM, obesity, hepatic steatosis, and elevated triglycerides. In HP-submitted reports, MET showed significantly higher reporting odds of increased triglycerides, obesity, inflammation, and T2DM than BIS and/or CAR. CAR showed higher reporting odds for hyperglycemia and obesity compared with BIS, whereas BIS and, particularly, NEB presented comparatively lower reporting frequencies for metabolic diseases. No significant differences were observed for hepatic steatosis, decreased high density lipoprotein cholesterol (HDL-C), or impaired glucose tolerance. Conclusions: This large-scale pharmacovigilance study highlights substantial heterogeneity in the reporting of metabolic adverse events among commonly prescribed BBs. MET and to a lesser extent CAR were associated with higher reporting odds of metabolic diseases, whereas BIS and especially NEB demonstrated more favorable reporting profiles. Although causality cannot be established from spontaneous reporting data, these findings support individualized BB selection and closer metabolic monitoring in patients with cardiometabolic risk factors. Full article

Magnesium is an essential mineral involved in numerous physiological and neurobiological processes. However, the biological effects of distinct Mg forms remain insufficiently characterized. This study compared the systemic and neurobiological effects of a multi-form Mg supplement (Magnesium Breakthrough™, Mg BT™, Reno, NV, USA) with commonly used single-form Mg compounds in a rat model. Sixty-day-old male Wistar rats were assigned to a control group or to groups receiving Mg BT™ or individual Mg compounds (oxide, citrate or glycinate). Treatments were administered by gastric gavage for 30 days at 50 mg/kg/day of elemental Mg. A comprehensive panel of endpoints was evaluated, including Mg distribution in biological fluids and tissues, metabolic markers, glucose tolerance, synaptic protein expression (synaptophysin, PSD95, phospho-PSD95, drebrin), cortical gene expression (NR2B, BDNF), behavioral outcomes, and liver and kidney histology. Magnesium from the multi-form supplement increased serum Mg without affecting glucose homeostasis and modulated proteins involved in synaptic plasticity, accompanied by mild anxiolytic-like effects without changes in locomotion. No adverse histological alterations were observed, while preserved renal CLDN-19 expression indicated maintained tubular integrity. These findings suggest that supplementation with the multi-form Mg BT™ supplement influences multiple evaluated biological domains, including systemic, behavioral and molecular parameters, with effects comparable to those observed with individual magnesium compounds under the experimental conditions applied. Full article

Background/Objectives: Aquatic therapy is widely used in pediatric rehabilitation because buoyancy and water resistance facilitate movement practice under reduced gravitational load. The Halliwick Method is a prominent approach; however, its effects on balance, motor function, and neuromuscular performance in children and young adults with disabilities have not been comprehensively synthesized. This systematic review summarized the effects of Halliwick aquatic therapy and aquatic exercise on balance, strength, and functional mobility in this population. Methods: This review followed Cochrane and PRISMA 2020 guidelines and was registered in PROSPERO (CRD42025635215). PubMed, MEDLINE Complete, PEDro, Web of Science, and Google Scholar were searched from inception to November 2025. Randomized controlled trials (≥2 weeks; ≥10 participants per trial) involving individuals aged 3–29 years with disabilities were included. Risk of bias was assessed using the Cochrane RoB2 tool. Results: Eight randomized controlled trials (involving 222 participants) met inclusion criteria. Despite heterogeneity in diagnoses and protocols (Halliwick-based hydrotherapy, swimming, strengthening, task-oriented balance training), most studies reported improvements in balance and postural control (BBS/PBS, WOTA2), gross motor function (GMFM), and functional mobility (6MWT, TUG, gait indices). Several trials demonstrated gains in strength, and one reported favorable changes in lower-limb electromyographic activation. Methodological limitations included small samples, limited blinding, variable dosing, and scarce follow-up. Due to heterogeneity in interventions and outcomes, findings were synthesized narratively. Conclusions: Halliwick aquatic therapy and aquatic exercise appear to improve balance, motor function, and neuromuscular performance in children and young adults with disabilities. However, evidence is limited by heterogeneity and methodological constraints. More robust, standardized RCTs with direct muscle and neuromuscular assessments are needed. Full article

Background/Objectives: This study investigated whether ultrasonographically assessed contractility of the transversus abdominis (TrA) and lumbar multifidus muscles predicts balance and postural control in stroke-related hemiplegia. Methods: This cross-sectional study included 36 patients with subacute or chronic stroke. Balance was assessed using the Berg Balance Scale (BBS) and the Postural Assessment Scale for Stroke Patients (PASS). Bilateral L2–3, L3–4, and L4–5 multifidus and bilateral TrA muscle thickness were measured ultrasonographically at rest and during contraction. The thickening fraction (TF, %), resting thickness ratio (RTR, %), and TF ratio (TFR, %) were calculated. Significant correlates were entered into hierarchical regression models to identify independent predictors of balance. Results: The mean BBS was 39.92 ± 13.67, and the mean PASS-Total was 30.06 ± 4.59 (Maintaining a Posture [MP]: 10.65 ± 2.56; Changing a Posture [CP]: 19.41 ± 2.52). Moderate positive correlations were found between paretic-side L2–3 (pL2–3) multifidus TF and BBS and PASS-MP, while weak positive correlations were observed between paretic-side TrA TF and PASS-CP and between TrA TFR and BBS, PASS-Total, and PASS-CP. In hierarchical regression models, pL2–3 multifidus TF was a significant independent predictor of both BBS (ΔR² = 0.102, p = 0.020, β = 0.340) and PASS-MP (ΔR² = 0.090, p = 0.020, β = 0.320). Muscle parameters did not independently predict PASS-Total or PASS-CP. Conclusions: Paretic-side lumbar multifidus activation was identified as a significant independent predictor of balance and postural control, whereas TrA parameters did not independently predict balance outcomes in this population. Full article

Background: Technological innovation in logistics (TIL), logistics capability (LC), and lean logistics (LL) are receiving wider attention in logistics and supply chain research. They are often examined in separate models and less often in relation to both business performance (BP) and market performance (MP). Their joint effects on organizational performance remain insufficiently examined in previous research. Methods: This study examined the effects of TIL, LC, and LL on BP and MP through a quantitative survey conducted among enterprises in Serbia, a transition economy with limited empirical evidence on these relationships. Data from 129 valid responses were analyzed through descriptive statistics, correlation analysis, linear regression analysis, and multicollinearity diagnostics. Results: The findings show that LC has a positive and significant effect on both BP and MP. LL has a positive and significant effect on BP, while TIL has a positive and significant effect on MP. The model explains a larger share of variance in BP than in MP. Conclusions: The results support a differentiated view of logistics transformation and indicate that BP and MP should be examined as related but distinct outcome dimensions. The study integrates TIL, LC, and LL within a unified performance framework. Full article

Background: Parkinson’s disease (PD) diagnosis is often delayed until signature motor symptoms manifest, at which point profound dopaminergic neuron loss has already occurred, necessitating advanced motor diagnostic biomarkers. Quantitative gait analysis is a promising tool, but phase-specific kinematic parameters remain underexplored. This study aims to identify novel, stage-divided Timed Up and Go (TUG) biomarkers not only to differentiate healthy controls (HCs) from patients with PD but also to objectively monitor and track disease progression across advancing severity stages, which are further validated against conventional clinical motor scales. Methods: A total of 81 participants (48 PD, 33 HCs) performed a 3 m TUG test using MotionCore (JEIOS Inc., Busan, Republic of Korea). The test was subdivided into three movement phases (Stage 1, sit-to-walk; Stage 2, turning; Stage 3, walk-to-sit). Results: PD patients exhibited significantly prolonged durations and altered turning metrics compared to HCs. Turning parameters including turning radius (ETR), area (EMA), and turning stability (FN) demonstrated strong correlations with disease severity and clinical scales. Notably, stage-specific analyses revealed that step counts, time, and speed metrics across Stages 1, 2, and 3 effectively differentiated disease severity, with transitional decelerating and seating metrics in Stage 3 showing the most pronounced clinical correlations. Discussion: This study confirms that the TUG test systematically deteriorates with increasing PD severity. The robust correlations with clinical scales (UPDRS, FOG-Q, BBS) validate TUG metrics as objective measures of motor and balance impairments. Utilizing novel, staging-specific indices significantly enhances the TUG test’s clinical utility for supporting diagnosis, accurate staging, and monitoring disease progression. Although the overall group comparisons demonstrated statistical significance, a data overlap remains between mild PD and HCs, underscoring the need for large-scale longitudinal studies to validate these metrics for early detection. Full article

Background/Objectives: This meta-analysis primarily aimed to evaluate the effects of the Otago Exercise Program (OEP) on physical function performance related to the risk of falls in the elderly. Methods: A literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science for studies on OEP interventions related to falls in older adults. Eligible studies were randomized controlled trials that reported at least one physical function outcome related to fall risk, including the Timed Up and Go test (TUG), Berg Balance Scale (BBS), Short Physical Performance Battery (SPPB), 30-Second Sit-to-Stand Test (30s-SST), Falls Efficacy Scale-International (FES-I), or 6-Minute Walk Test (6MWT). Subsequently, a risk of bias assessment, as well as data extraction and synthesis, was performed. Results: Data were synthesized from a total of 13 studies, involving 1278 participants from OEP (n = 660) and control (n = 618) trials. The results suggested that OEP was associated with improvements in TUG (WMD = −1.47; 95%CI: −2.44, −0.51), BBS score (WMD = 4.43; 95%CI: 2.50, 6.36), SPPB scores (WMD = 0.76; 95%CI: 0.43, 1.09), 30s-SST (WMD = 2.68; 95%CI: 0.86, 4.49), FES-I score (WMD = −1.74; 95%CI: −3.15, −0.33). However, no significant effect was observed for the 6MWT. Subgroup analysis suggested that group-based OEP appeared to provide greater improvements in TUG, BBS scores, and 30s-SST, whereas home-based OEP did not show significant effects. In addition, interventions lasting ≥4 months were associated with greater improvements for TUG, BBS scores, and the 30s-SST. Older adults aged ≥75 showed significant improvements in TUG and 30s-SST. However, substantial heterogeneity was observed across several outcomes, and evidence for SPPB, FES-I, and 6MWT was based on a limited number of studies. Conclusions: OEP may improve physical function performance related to fall risk in older adults, such as the TUG, BBS, SPPB, 30s-SST, and FES-I, while no significant effect was observed for the 6MWT. Importantly, the findings support improvements in physical function performance rather than a direct reduction in actual fall incidence. These findings should be interpreted cautiously due to substantial heterogeneity and the limited number of trials for some outcomes. A group-based OEP lasting at least 4 months may provide greater benefits for improving physical function related to fall risk, particularly among adults aged ≥75 years. Full article

Sucrose synthase plays a crucial role in sucrose metabolism and flower regulation. By using bioinformatics techniques, 13, 16 and 13 SUS members were identified in Brassica rapa, Brassica nigra, and Brassica oleracea, respectively. The SUS family can be divided into three subfamilies. The SUS II subfamily has three B. nigra genes with significantly reduced motif types. The SUS III subfamily has fewer motif 2 in Arabidopsis thaliana compared to the other species. The interspecific collinearity analysis revealed a “one-to-one, many-to-one” relationship between species. KEGG revealed that Brassica nigra showed significantly higher enrichment in the metabolism pathway, while Brassica rapa and Brassica oleracea exhibited higher significance in carbohydrate metabolism. GO indicated that Brassica nigra had more enriched biological process pathways than the other two species. It reveals that SUS has a higher degree of similarity between the AA genome and the CC genome, while its similarity to the BB genome is lower. The analysis of the response of BraSUSs to different light intensities revealed that the differentially expressed genes BraA07g028740.3C and BraA07g037520.3C had enhanced expression rhythms under high light intensity. Using three diploid basal species with different flowering traits (Chinese cabbage, cabbage, and black mustard) as experimental materials, we conducted a comparative analysis of the SUS gene family. This will lay the foundation for deciphering the molecular regulatory mechanism by which the SUS gene affects flowering through its influence on sucrose synthesis. Full article

Membrane-based processes have emerged as efficient alternatives to conventional separation methods because they enable protein fractionation under mild processing conditions while preserving protein functionality and bioactivity. Furthermore, whey, traditionally regarded as a by-product of cheese manufacture, is now recognized as a valuable source of proteins and bioactive compounds that can be recovered and valorized through membrane processing. Despite this, the literature on protein fractionation processes based on membrane technologies remains limited across different membrane technologies and operational scales. This systematic review evaluates microfiltration (MF), ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) in the context of milk protein fractionation, with a focus on industrial relevance, process limitations, and the resulting high-value protein fractions. Unlike previous narrative reviews, the study integrates comparative performance metrics, including pressure, protein recovery, purity, process limitations, and resulting products. Following the PRISMA guidelines for the selection and assessment of eligibility for a systematic review, 55 studies were included in the final qualitative synthesis. The analysis shows that UF consistently achieves high protein recovery (>90%) and represents the dominant industrial technology for the production of whey protein concentrates and isolates, although its efficiency is limited by concentration polarization and flow rate drop at elevated volumetric concentration factors. Consequently, future research should prioritize integrated performance reporting, quantitative measurement, and integration of sustainability indicators to enable more robust industrial application of membrane-based dairy technologies. Moreover, more reporting bases on standardized industrial performance indicators and commercial case studies are needed to support the wider adoption and optimization of membrane technologies in dairy processing. Full article

Background/Objectives: This study aims to evaluate the effectiveness of binaural beats (BB) on the autonomic nervous system (ANS), kinesiophobia of reinjury and fitness biomarkers in professional athletes with chronic musculoskeletal injuries. Methods: A total of 54 athletes aged 18–25 years, engaged in open-skill sports and experiencing chronic lower-limb injuries for over three months, will be recruited. They will be randomly assigned to one of three groups: an intervention group, a placebo group, and a control group. All athletes will undergo a 15 min auditory intervention five times per week for four weeks. The intervention group will listen to BB embedded in music at high beta and gamma frequencies (30–100 Hz) with guided instructions. The placebo group will receive placebo BB within the same music framework, while the control group will listen only to the music background. Assessments will be conducted at baseline, immediately post-intervention, and at a 4-week follow-up. The primary outcomes will be kinesiophobia of reinjury, ANS function, and heart rate variability (HRV), assessed using the Tampa Scale of Kinesiophobia (TSK-17), Sympathetic Skin Response (SSR), and HRV analysis, respectively. Secondary outcomes will include sport-related anxiety and pain beliefs, assessed using the Sport Competition Anxiety Test (SCAT-15) and the Pain Beliefs and Perceptions Inventory (PBPI-16), respectively; handgrip strength, assessed using the Hand Grip Test; and fitness-related biomarkers, including maximal oxygen uptake (VO₂max) and blood lactate concentration. Conclusions: These findings may provide evidence supporting BB as a complementary, non-invasive intervention to enhance psychological and physiological rehabilitation in injured athletes. Ethics and Dissemination: The study has received ethical approval and is registered on ClinicalTrials.gov. Findings will be disseminated through peer-reviewed publications, conferences, and academic presentations. Full article

The decentralized deployment of photovoltaic (PV) systems in urbanized polluted mountainous basins faces unique challenges due to complex topography, persistent cloud cover and winter smog conditions. This study quantifies the atmospheric impact of localized winter haze/smog and Saharan dust intrusions on PV performance in the intermontane basin of Ioannina, NW Greece. By integrating a Digital Twin (DT) methodology with real energy production data, two PV plants were evaluated, a ground-based and a rooftop installation, to isolate the energy deficits caused by aerosol attenuation. The DT model demonstrated high accuracy (R² = 0.847) against actual power generation data for Koutselio and R² = 0.865 for Mpafra PV plants, while MBE was near zero for both sites (−0.008 kWh and −0.139 kWh, respectively). Error analysis revealed that the highest modeling discrepancies occurred during scattered clouds and intense winter haze conditions, primarily due to low spatial resolution of CAMS that fails to adequately capture localized biomass burning (BB) events. Despite the reduction in direct sunlight during extreme winter BB events, results indicate that the overall energy loss is mild. This operational stability is primarily due to the ability of c-Si modules to effectively utilize near-infrared radiation, which penetrates the low-level haze layer, alongside the thermal efficiency gains provided by low early-morning temperatures. Crucially, the installation geometry may influence system vulnerability. Direct comparisons revealed a minor power deviation of −4.8% for the ground-based Koutselio plant, while for the Mpafra site, there was a +3.2% production surplus likely linked to the high sky-view factor the rooftop installation has, which manages to capture isotropic diffuse irradiance. However, the low CAMS resolution may misclassify the haze events within the basin, further contributing to these discrepancies. On the contrary, Saharan dust intrusions caused broadband light attenuation, dropping the power production significantly on both installations. Ultimately, this research provides critical insights into the resilience of solar systems under strong air pollution events within polluted valleys in Southern Balkans, highlighting the connection between panel design and atmospheric attenuation. Full article

This study investigated the potential of cellulose as a carrier for bioactive phenolic compounds from tart cherry juice. Using a freeze-drying method, encapsulates were prepared by varying cellulose content (2.5%, 5%, 7.5%, and 10%) and complexation times (15 and 60 min) while maintaining a constant juice volume. The prepared encapsulates were characterized by determining the concentrations of total phenols, monomeric anthocyanins, and proanthocyanidins, alongside antioxidant activity by spectrophotometric methods, individual polyphenols by HPLC, color parameters and structural changes via IR spectroscopy. Additionally, the stability of these parameters was evaluated after one year of storage at room temperature. Results indicated that the highest concentrations of phenolic compounds and the strongest antioxidant potential were achieved with 2.5% cellulose content (the lowest content) after 15 min of complexation (shorter time). Concentrations of polyphenols decreased as the cellulose contents increased. Although changes in chemical parameters occurred during storage, the results confirm that cellulose is a viable carrier for tart cherry phenolics, particularly at lower contents, offering a promising approach for formulating stable bioactive delivery systems. Full article

The ecological adaptations of insect pests, such as multi-niche colonization and physiological resistance to conventional chemicals, pose severe challenges to the sustainable production of sweet potato (Ipomoea batatas). The tobacco whitefly, Bemisia tabaci (Hemiptera: Aleyrodidae), and the sweet potato weevil, Cylas formicarius (Coleoptera: Brentidae), form a highly destructive, spatially separated pest complex. In this study, we evaluated the dual-niche pathogenicity of a Beauveria bassiana (Hypocreales: Cordycipitaceae) isolate, BbCF-2, generated via spaceflight mutagenesis, against C. formicarius and B. tabaci under controlled laboratory conditions. The mutated strain exhibited enhanced colony expansion and a high sporulation capacity (2.72 × 10⁸ conidia/mL). Bioassays revealed that BbCF-2 possesses significantly increased virulence compared to the wild-type strain, capable of overcoming the distinct physiological and physical barriers of both targeted pests. Against the highly sclerotized subterranean C. formicarius adults, BbCF-2 achieved 92.68% mortality at 15 days post-inoculation at 1 × 10⁸ conidia/mL, with an LC50 of 8.452 × 10³ conidia/mL and an LT50 of 6.305 days. Concurrently, against the canopy-dwelling B. tabaci, the isolate demonstrated rapid lethal mycosis with an LT50 of 6.718 days, effectively reducing the adult vector population prior to their typical dispersal timeframe. These results demonstrate that the spaceflight-mutated BbCF-2 strain exhibits broad pathogenicity. By simultaneously targeting both foliar and soil-dwelling pests, this single-agent biological control strategy shows potential for integrated pest management, pending greenhouse and field evaluation. Full article