Search Results (11,009)

This study investigates the effect of Hull Vane^® on the total resistance and propulsion performance of a patrol vessel using computational fluid dynamics (CFD). Utilizing SHIPFLOW software, multiple simulations were conducted to evaluate how Hull Vane^® position and angle of attack influence hydrodynamic performance. A patrol vessel hull form the MAXSURF’s library was selected to investigate resistance and propulsive performance. Nine (9) configurations (named Cases A to I) of the Hull Vane^® were examined based on variations in longitudinal position and angle of attack. A grid independence study was conducted to determine the optimal mesh configuration. Validation was performed using the Holtrop–Mennen power prediction method and MAXSURF. According to this study, results indicate that Hull Vane^® configurations significantly reduce total resistance and delivered power at higher vessel speeds, with the best improvement in resistance occurring in Case C and in propulsion power in Case B. Propulsive efficiency was maximized in Case E. Furthermore, the study also demonstrates the potential of Hull Vane^® as a practical retrofit for enhancing naval vessel performance and reducing energy consumption. Full article

Lipid nanoparticle (LNP)-based delivery systems are promising tools for advancing RNA-based therapies. However, there are underlying challenges for the oral delivery of LNPs. In this study, we optimized an LNP formulation, which we encapsulated in a pH-sensitive Eudragit^® S 100 (Eu) coating. LNPs were prepared using the DLin-MC3-DMA ionizable lipid, cholesterol, DMG-PEG, and DSPC at a molar ratio of 50:38.5:10:1.5. LNPs were coated with 1% Eu solution via nanoprecipitation using 0.25% acetic acid to get Eu-coated LNPs (Eu-LNPs). Particle characteristics of LNPs were determined by using dynamic light scattering (DLS). Ribogreen and agarose gel retardation assays were used to evaluate nucleic acid entrapment and stability. LNPs and Eu-LNPs were ~120 nm and 4.5 μm in size, respectively. Eu-LNPs decrease to an average size of ~191 ± 22.9 nm at a pH of 8. Phosphate buffer (PB)-treated and untreated Eu-LNPs and uncoated LNPs were transfected in HEK-293 cells. PB-treated Eu-LNPs showed significant transfection capability compared to their non-PB-treated counterparts. Eu-LNPs protected their nucleic acid payloads in the presence of a simulated gastric fluid (SGF) with pepsin and maintained transfection capacity following SGF or simulated intestinal fluid. Hence, Eu coating is a potentially promising approach for the oral administration of LNPs. Full article

Background: Temporomandibular disorders are a generic term referred to clinical conditions involving the jaw muscles and temporomandibular joint with multifactorial pattern and genetic background. The aim of this observational study was to investigate the correlation between craniomandibular disorders and the presence of occlusal alterations. A clinical evaluation of the occlusal and articular status of the patients was carried out, integrating the latter with the electromyographic recording the activity of the masseter and temporalis muscles. Methods: A clinical observational study on 20 adults assessed temporomandibular disorders using DC/TMD criteria, anamnesis, clinical exams, occlusal and electromyographic analyses. Occlusion was evaluated morphologically and functionally. Electromyography tested static/dynamic muscle activity. Data were statistically analyzed using t-tests and Pearson correlation (p < 0.05). Results: Electromyographic analysis revealed significant differences between subjects with and without visual correction, suggesting that visual input influences masticatory muscle activity. Correlations emerged between occlusal asymmetries and neuromuscular parameters. These findings highlight clinical implications for mandibular function, muscle symmetry, and the potential for therapeutic rebalancing through targeted interventions. Conclusions: The study demonstrates a significant correlation between visual–motor integration and masticatory muscle efficiency. It emphasizes lateralized neuromuscular activation’s influence on occlusal contact distribution. Moreover, it identifies mandibular torsion–endfeel inverse correlation as a potential diagnostic marker for craniomandibular dysfunctions via surface electromyography. Full article

The cosmetic industry is growing at an impressive rate worldwide. In the cosmetic field, natural-origin ingredients represent the new frontier in this industry. Among the main components of cosmetics, lipids, emulsifiers, rheological modifiers, preservatives, colorants, and antioxidants can be found. These compounds form emulsions, which are among the main cosmetic formulations. An important aspect in this regard is the evaluation of emulsions’ stability over time and emulsions’ production methodology. In this paper, a comparison is made between two emulsion production technologies, the Standard and the “One-Pot” methods, through the characterization of the raw material ABWAX^® Revomul, a multifunctional wax for cosmetic use which consists of a low-melting structuring wax of vegetal origin (Rhus wax) and a natural emulsifier (Polyglyceril-3 Stearate). First, we evaluated the affinity between the wax raw materials and emollients of different chemical nature; then, we analyzed the impact of the production method on the emulsions to identify similarities and differences. ABWAX^® Revomul demonstrated a high level of effectiveness in regard to stabilizing water-in-oil emulsions. This study suggests that from an industrial point of view, the application of the two procedures allows products with different characteristics to be obtained, consequently allowing a specific method to be chosen to obtain the desired product. Full article

Background: Prebiotics are selectively used by host microorganisms to promote health. Because effective prebiotic doses (1.5–30 g/day) often require inconvenient delivery formats, this study aims to explore whether capsule-compatible doses of galacto-oligosaccharides (GOS) can effectively modulate the gut microbiome. Methods: The impact of Bimuno^® GOS (Reading, UK) at 0.5, 0.75, 1.83, and 3.65 g on the adult gut microbiome was assessed using the ex vivo SIFR^® technology (n = 8), a clinically validated, bioreactor-based technology. Results: The GOS were rapidly fermented and significantly increased beneficial Bifidobacterium species (B. adolescentis, B. bifidum, and B. longum), even at the lowest tested dose. In doing so, GOS strongly promoted SCFA production, particularly acetate (significant from 0.5 g) and butyrate (significant from 0.75 g). Gas production only mildly increased, likely as Bifidobacterium species do not produce gases. Based on the ability of the SIFR^® technology to cultivate strictly anaerobic, hard-to-culture gut microbes, unlike in past in vitro studies, we elucidated that GOS also enriched specific Lachnospiraceae species. Besides Anaerobutyricum hallii, this included Bariatricus comes, Blautia species (B. massiliensis, Blautia_A, B. faecis), Oliverpabstia intestinalis, Mediterraneibacter faecis, and Fusicatenibacter species. Finally, GOS also promoted propionate (significant from 0.75 g), linked to increases in Phocaeicola vulgatus. Conclusions: GOS displayed prebiotic potential at capsule-compatible doses, offering greater flexibility in nutritional product formulation and consumer convenience. Notably, the strong response at the lowest dose suggests effective microbiome modulation at lower levels than previously expected. Full article

Polymerase-coupled nanopore sequencing requires DNA polymerases with strong strand displacement activity and high processivity to sustain continuous signal generation. In this study, we characterized two novel B family DNA polymerases, SRHS and BBum, isolated from Bacillus phages SRT01hs and BeachBum, respectively. Both enzymes exhibited robust strand displacement, 3′→5′ exonuclease activity, and maintained processivity under diverse reaction conditions, including across a broad temperature range (10–45 °C) and in the presence of multiple divalent metal cofactors (Mg²⁺, Mn²⁺, Fe²⁺), comparable to the well-characterized Phi29 polymerase. Through biochemical analysis of mutants designed using AlphaFold3-predicted structural models, we identified key residues (G96, M97, D486 in SRHS; S97, M98, A493 in BBum) that modulated exonuclease activity, substrate specificity and metal ion utilization. Engineered variants SRHS_F and BBum_Pro_L efficiently incorporated unnatural nucleotides in the presence of Mg²⁺—a function not observed in Phi29 and other wild-type strand-displacing B family polymerases. These combined biochemical features highlight SRHS and BBum as promising enzymatic scaffolds for nanopore-based long-read sequencing platforms. Full article

L-type Ca²⁺ channels, particularly Ca_V1.2, play a crucial role in cardiac excitation-contraction coupling and are known to exhibit mechanosensitivity. However, the mechanisms regulating their response to mechanical stress remain poorly understood. To investigate the mechanosensitivity and nitric oxide (NO)-dependent regulation of L-type Ca²⁺ channels in rat ventricular cardiomyocytes, we used RNA sequencing to assess isoform expression and whole-cell patch-clamp recordings to measure L-type Ca²⁺ current (I_Ca,L) under controlled mechanical and pharmacological conditions. RNA sequencing revealed predominant expression of Ca_V1.2 (TPM: 0.1170 ± 0.0075) compared to Ca_V1.3 (0.0021 ± 0.0002) and Ca_V1.1 (0.0002 ± 0.0002). Local axial stretch (6–10 μm) consistently reduced I_Ca,L in proportion to stretch magnitude. The NO donor SNAP (200 μM) had variable effects on basal I_Ca,L in unstretched cells (stimulatory, inhibitory, or biphasic) but consistently restored stretch-reduced I_Ca,L to control levels. Ascorbic acid (10 μM), which reduces S-nitrosylation, increased basal I_Ca,L and partially restored the reduction caused by stretch, implicating S-nitrosylation in channel regulation. The sGC inhibitor ODQ (5 μM) decreased I_Ca,L in both stretched and unstretched cells, indicating involvement of the NO–cGMP pathway. Mechanical stress modulates L-type Ca²⁺ channels through a complex interplay between S-nitrosylation and NO–cGMP signaling, with S-nitrosylation playing a predominant role in stretch-induced effects. This mechanism may represent a key component of cardiac mechanotransduction and could be relevant for therapeutic targeting in cardiac pathologies involving mechanically induced dysfunction. Full article

Physiological levels of reactive oxygen species (ROS) play a crucial role as intracellular signaling molecules, helping to maintain cellular homeostasis. However, when ROS accumulate excessively, they become toxic to cells, leading to damage to lipids, proteins, and DNA. This oxidative stress can impair cellular function and lead to various forms of cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, paraptosis, parthanatos, and oxeiptosis. Despite their significance, the role of ROS in autosis (an autophagy-dependent form of cell death) remains largely unexplored. In this review, we gather current knowledge on autotic cell death and summarize how oxidative stress influences the activity of Beclin-1 and the Na⁺,K⁺-ATPase pump, both of which are critical effectors of this pathway. Finally, we discuss the theoretical potential for ROS to modulate this type of cell death, proposing a possible dual role for these species in autosis regulation through effectors such as HIF-1α, TFEB, or the FOXO family, and highlighting the need to experimentally address cellular redox status when working on autotic cell death. 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: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, specifically its Main Protease (M^pro), in accelerating insulin resistance and metabolic dysfunction in HepG2 cells in vitro. Methods: HepG2 cells were treated with varying concentrations of M^pro (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to assess cytotoxicity and glucose uptake. Based on initial findings, subsequent assays focused on higher concentrations (40, 80, and 160 nmol/mL). The effects of M^pro on cell viability, protein kinase B (AKT) expression, matrix metallopeptidase-1 (MMP1), dipeptidyl peptidase 4 (DPP4), interleukin-6 (IL-6) expression, and lipid peroxidation were investigated. Results: Our findings reveal that the SARS-CoV-2 M^pro treatment led to a concentration-dependent reduction in glucose uptake in HepG2 cells. Additionally, the M^pro treatment was associated with reduced insulin-stimulated AKT activation, particularly at higher concentrations. Inflammatory markers such as IL-6 were elevated in the extracellular medium, while DPP4 expression was decreased. However, extracellular soluble DPP4 (sDPP4) levels did not show a significant change. Despite these changes, cell viability remained relatively unaffected, suggesting that the HepG2 cells were able to maintain overall metabolic functions under M^pro exposure. Conclusions: This study demonstrated the concentration-dependent impairment of hepatic glucose metabolism, insulin signaling, and inflammatory pathways in HepG2 cells acutely exposed to the SARS-CoV-2 M^pro. These findings warrant further investigation to explore the long-term metabolic effects of SARS-CoV-2 and its proteases in the liver and to develop potential therapeutic approaches for post-viral metabolic complications. Full article

Cardiovascular disease (CVD) and dementia may share common pathogenic factors such as atherosclerosis and hyperlipoproteinemia. Dyslipidemia-induced oxidative stress contributes to dementia comorbidity in CVD. Abelmoschus esculentus (AE, okra) potentiates in alleviating hyperlipidemia and diabetes-related cognitive impairment. This study evaluated the effects of AE in hyperlipidemic ApoE^−/− mice treated with streptozotocin (50 mg/kg) and fed a high-fat diet (17% lard oil, 1.2% cholesterol). AE fractions F1 or F2 (0.65 mg/kg) were administered for 8 weeks. AE significantly reduced serum LDL-C, HDL-C, triglycerides, and glucose, improved cognitive and memory function, and protected hippocampal neurons. AE also lowered oxidative stress markers (8-hydroxy-2′-deoxyguanosine, 8-OHdG) and modulated neuronal nuclei (NeuN) and doublecortin (DCX) expression. In vitro, AE promoted neurite outgrowth and neuronal differentiation in retinoic acid (RA)-differentiated human SH-SY5Y cells under metabolic stress (glucose and palmitate), alongside the upregulation of heme oxygenase-1 (HO-1), Nuclear factor-erythroid 2-related factor 2 (Nrf2), and brain-derived neurotrophic factor (BDNF). These findings suggest AE may counter cognitive decline via oxidative stress regulation and the enhancement of neuronal differentiation. Full article

The Research Integrity Risk Index (RI²), introduced as a tool to identify universities at risk of compromised research integrity, adopts an overly reductive methodology by combining retraction rates and delisted journal proportions into a single, equally weighted composite score. While its stated aim is to promote accountability, this commentary critiques the RI² index for its flawed assumptions, lack of empirical validation, and disproportionate penalization of institutions in low- and middle-income countries. We examine how RI² misinterprets retractions, misuses delisting data, and fails to account for diverse academic publishing environments, particularly in Indonesia, where many high-performing universities are unfairly categorized as “high risk” or “red flag.” The index’s uncritical reliance on opaque delisting decisions, combined with its fixed equal-weighting formula, produces volatile and context-insensitive scores that do not accurately reflect the presence or severity of research misconduct. Moreover, RI² has gained significant media attention and policy influence despite being based on an unreviewed preprint, with no transparent mechanism for institutional rebuttal or contextual adjustment. By comparing RI² classifications with established benchmarks such as the Scimago Institution Rankings and drawing from lessons in global development metrics, we argue that RI², although conceptually innovative, should remain an exploratory framework. It requires rigorous scientific validation before being adopted as a global standard. We also propose flexible weighting schemes, regional calibration, and transparent engagement processes to improve the fairness and reliability of institutional research integrity assessments. Full article

The numerical simulation of unsteady, high-Reynolds-number incompressible flows governed by the Navier–Stokes (NS) equations presents significant challenges in computational fluid dynamics, primarily concerning numerical stability and computational efficiency. Standard Galerkin finite element methods often suffer from non-physical oscillations in convection-dominated regimes, while the multiscale nature of these flows demands prohibitively high computational resources for uniformly refined meshes. This paper proposes an improved Galerkin framework that synergistically integrates a Variational Multiscale Stabilization (VMS) method with an adaptive mesh refinement (AMR) strategy to overcome these dual challenges. Based on the Ritz–Galerkin formulation with the stable Taylor–Hood ($P_2-P_1$) element, a VMS term is introduced, derived from a generalized $\theta$-scheme. This explicitly constructs a subgrid-scale model to effectively suppress numerical oscillations without introducing excessive artificial diffusion. To enhance computational efficiency, a novel a posteriori error estimator is developed based on dual residuals. This estimator provides the robust and accurate localization of numerical errors by dynamically weighting the momentum and continuity residuals within each element, as well as the flux jumps across element boundaries. This error indicator guides an AMR algorithm that combines longest-edge bisection with local Delaunay re-triangulation, ensuring optimal mesh adaptation to complex flow features such as boundary layers and vortices. Furthermore, the stability of the Taylor–Hood element, essential for stable velocity–pressure coupling, is preserved within this integrated framework. Numerical experiments are presented to verify the effectiveness of the proposed method, demonstrating its ability to achieve stable, high-fidelity solutions on adaptively refined grids with a substantial reduction in computational cost. Full article

Background: Despite its central role in pediatric pre-surgical evaluation of drug-resistant focal epilepsy, conventional analog ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT (aPET) systems often yield modest epileptogenic zone (EZ) detection rates (~50–60%). Silicon photomultiplier–based digital PET/CT (dPET) promises enhanced image quality, but its performance in pediatric epilepsy remains untested. Methods: We retrospectively analyzed 22 children (mean age 11.5 ± 2.6 years) who underwent interictal brain ¹⁸F-FDG PET/CT: 11 on an analog system (Discovery ST, 2018–2019) and 11 on a digital system (Biograph Vision 450, 2020–2021). Three blinded nuclear medicine physicians independently scored EZ localization and image quality (4-point scale); post-surgical histology and ≥1-year clinical follow-up served as reference. Results: The EZ was correctly identified in 8/11 analog scans (72.7%) versus 10/11 digital scans (90.9%). Average image quality was significantly higher with dPET (3.0 ± 0.9 vs. 2.1 ± 0.9; p < 0.05), and inter-reader agreement improved from good (ICC = 0.63) to excellent (ICC = 0.91). Conclusions: Our preliminary findings suggest that dPET enhances image clarity and reader consistency, potentially improving localization accuracy in pediatric epilepsy presurgical workups. Full article

Objective: We evaluated the feasibility of a machine-learning (ML) model based on clinical features and radiomics from [¹⁸F]FDG PET/CT images to differentiate between infected and non-infected intracavitary vascular grafts and endografts (iVGEI). Methods: Three ML models were developed: one based on pre-treatment criteria to diagnose a vascular graft infection (“MAGIC-light features”), another using radiomics features from diagnostic [¹⁸F]FDG-PET scans, and a third combining both datasets. The training set included 92 patients (72 iVGEI-positive, 20 iVGEI-negative), and the external test set included 20 iVGEI-positive and 12 iVGEI-negative patients. The abdominal aorta and iliac arteries in the PET/CT scans were automatically segmented using SEQUOIA and TotalSegmentator and manually adjusted, extracting 96 radiomics features. The best-performing models for the MAGIC-light features and PET-radiomics features were selected from 343 unique models. Most relevant features were combined to test three final models using ROC analysis, accuracy, sensitivity, and specificity. Results: The combined model achieved the highest AUC in the test set (mean ± SD: 0.91 ± 0.02) compared with the MAGIC-light-only model (0.85 ± 0.06) and the PET-radiomics model (0.73 ± 0.03). The combined model also achieved a higher accuracy (0.91 vs. 0.82) than the diagnosis based on all the MAGIC criteria and a comparable sensitivity and specificity (0.70 and 1.00 vs. 0.76 and 0.92, respectively) while providing diagnostic information at the initial presentation. The AUC for the combined model was significantly higher than the PET-radiomics model (p = 0.02 in the bootstrap test), while other comparisons were not statistically significant. Conclusions: This study demonstrated the potential of ML models in supporting diagnostic decision making for iVGEI. A combined model using pre-treatment clinical features and PET-radiomics features showed high diagnostic performance and specificity, potentially reducing overtreatment and enhancing patient outcomes. Full article