Search Results (4,444)

This study presents a computational and experimental aerodynamic characterisation of a full-scale 5.5 m diameter, six-sail horizontal-axis windmill of the traditional Cretan Lasithi type, equipped with flexible woven polyester sails that act as a passive load-control mechanism. Seventeen operating points spanning wind speeds of 2.3–18.3 m/s were simulated in OpenFOAM using a transient sliding-mesh Arbitrary Mesh Interface formulation with the k–ω SST turbulence closure on a 2.3 million cell grid, selected on the basis of a four-level grid convergence study. CFD simulations identify three distinct aerodynamic regimes: a drag-dominated high-TSR regime (λ > 2.1), a mixed lift–drag working range with peak loading near λ ≈ 1.4–1.5, and a deep-stall regime in which boundary-layer separation propagates from root to tip as λ falls below 1.0. Field measurements conducted at the Energy Systems Synthesis Lab of the Hellenic Mediterranean University in compliance with IEC 61400-12-1:2005(E) confirm that rotor speed stabilises passively at 55–58 RPM above 13 m/s without any active control mechanism; CFD predictions agree with measured power output within 8–12% across the 2–13 m/s attached-flow envelope. The combined evidence indicates that passive overspeed self-regulation is driven by aeroelastic sail deformation, reducing effective disc solidity at high wind speeds, a mechanism that rigid-geometry CFD correctly identifies in trend but cannot quantify in magnitude. The primary limitation of the present work is the rigid-sail assumption of the CFD model, which requires a two-way coupled fluid–structure interaction extension as a future step. Full article

Background: Thromboembolism is a serious complication in acute lymphoblastic leukemia (ALL). This systematic review and meta-analysis evaluated thrombosis incidence and risk factors across populations receiving asparaginase-based therapy. Methods: From 214 studies (1994–2026), 58 met inclusion criteria, totaling 23,655 adult, pediatric, and mixed-population patients. Searches included Ovid MEDLINE, Embase, Cochrane CENTRAL, PubMed Central, and Google Scholar. Eligible studies were observational cohorts or clinical trials reporting thrombosis in ALL patients treated with asparaginase. Risk factors assessed included study design, asparaginase formulation, immunophenotype, gender, treatment phase, corticosteroid use, mediastinal mass, ABO blood group, body weight, and age. Random-effects models were used for meta-analysis, and risk of bias was assessed using ROBINS-I and RoB-2. Results: Adults had significantly higher thrombosis rates than children (p < 0.0001). Study design, asparaginase formulation, immunophenotype, and treatment phase differed significantly across age groups (p < 0.0001). T-cell ALL showed higher thrombosis rates than B-cell ALL (p < 0.0001). Significant pediatric risk factors included age ≥ 10 years, mediastinal mass, non-O blood type, and overweight/obesity (all p ≤ 0.0004). Gender and corticosteroid use were not significant predictors. Findings were limited by substantial heterogeneity across included studies. Conclusions: Thrombosis risk was multifactorial. Adults and older children had higher risk, and pediatric patients with overweight/obesity, mediastinal mass, or non-O blood type were particularly vulnerable. Thromboprophylaxis is advised for high-risk groups. This review was not registered and received no external funding. Full article

Introduction: Temperature is a key environmental factor influencing the physiological and biochemical processes of aquatic organisms, including xenobiotic metabolism. Understanding how temperature modulates the toxicological effects of pollutants such as polycyclic aromatic hydrocarbons (PAHs) is crucial in the context of climate change. Among these compounds, benzo[a]pyrene (BaP) and benzo[a]anthracene (BaA) are priority pollutants in aquatic environments, resulting from incomplete combustion. Their relevance is attributed to persistence and metabolic bioactivation potential. Fish primary hepatocyte cultures represent a relevant in vitro model for studying combined effects of thermal stress and chemical exposures, while supporting the 3Rs principles (Replacement, Reduction, and Refinement). Objective: This study aims to assess temperature-dependent effects of BaP and BaA, and their mixtures in brown trout hepatocytes using cytochrome P450 1A (CYP1A) immunohistochemistry as an indicator of xenobiotic metabolism. Methodology: Primary hepatocytes were isolated using a two-step collagenase perfusion method and cultured in 24-well plates at 18 °C and 22 °C. Cells were exposed for 72 h to supplemented L-15 medium (control) or to 0.1% dimethyl sulfoxide in supplemented L-15 medium (solvent control), as well as to single exposures of 1 and 10 µM of BaP and BaA and to equimolar mixtures of both compounds (1 and 10 µM). Viability was assessed using the lactate dehydrogenase (LDH) assay. CYP1A immunostaining was quantified based on cytoplasmic staining intensity relative to background area. Results: No significant effects on cell viability were observed under any condition. Temperature significantly reduced CYP1A expression in single exposures at 22 °C compared to 18 °C. BaP induced a significant dose-dependent increase, while BaA differed from controls only at 10 µM. In mixtures, only treatment- and dose-dependent effects were observed, with no temperature influence detected. Conclusions: Overall, the data highlight temperature as a key modulator of biochemical responses to PAHs, with single and mixed exposures eliciting distinct effects and suggesting potential synergism in mixtures. Full article

Background: The clinical characteristics of pancreatic acinar cell carcinoma (ACC) remain poorly defined due to its rarity. This study aimed to evaluate the morphological features and clinical outcomes of pancreatic ACC. Method: This multicenter retrospective study analyzed clinical data from seven referral hospitals. Electronic medical records were comprehensively reviewed to extract patient data. Survival outcomes were calculated from the date of pathologic confirmation of ACC. Results: Of the 37 patients, 28 (75.7%) were male. The age distribution at diagnosis ranged widely from 12 to 86 years, with a median of 62.0 years; seven patients (18.9%) were aged under 50 years. Morphologically, 24 patients (64.9%) presented with solid masses, whereas four had cystic masses and four exhibited mixed solid and cystic components. Regarding tumor resectability, 19 patients (51.4%) had resectable disease, 7 (18.9%) were locally advanced, and 11 (29.7%) were metastatic. In terms of treatment, 22 patients (59.4%) underwent surgical resection, 12 (32.4%) received palliative chemotherapy, and the remainder received best supportive care. In the surgical resection group, the median OS was not reached, demonstrating significantly prolonged survival (mean OS, 7.6 years; 5-year OS rate, 51%). In contrast, the median OS was 0.9 years in the palliative chemotherapy group and 0.1 years in the best supportive care group (p = 0.040). Conclusions: Pancreatic ACC showed a broad age distribution, with approximately 20% of patients aged <50 years, and pleomorphic morphological features, including solid, cystic, and mixed patterns. Patients who underwent surgical resection demonstrated favorable long-term survival outcomes compared to historical data for pancreatic ductal adenocarcinoma. Full article

Blue honeysuckle (Lonicera caerulea L.) is a polyphenol-rich berry increasingly recognized as a functional food ingredient for postprandial glycemic management. However, it remains unclear whether its polyphenols can modulate intestinal glucose transport in addition to inhibiting carbohydrate-digesting enzymes. In this study, blue honeysuckle polyphenol extract (BHPE) was characterized by UPLC-QTOF-MS/MS, and its effects on α-glucosidase activity and intestinal glucose transport were evaluated using enzyme kinetics, fluorescence quenching, molecular docking, and differentiated Caco-2 monolayers. A total of 24 phenolic compounds were tentatively identified, with anthocyanins and chlorogenic acid derivatives as the major constituents. BHPE exhibited a mixed-type, static-quenching inhibition of α-glucosidase (IC₅₀ = 75.05 μg/mL). Furthermore, molecular docking revealed that key constituents, including cyanidin-3-O-glucoside, chlorogenic acid, and proanthocyanidin B1, bind the enzyme via hydrogen bonding and hydrophobic interactions. In Caco-2 cell monolayers, BHPE reduced glucose transport by up to 51.56% under simulated postprandial conditions and coordinately downregulated SGLT1 and GLUT2 mRNA expression to 0.58- and 0.51-fold, respectively. These findings extend the bioactivity profile of blue honeysuckle polyphenols from enzyme-level inhibition to functional regulation at the intestinal epithelial barrier, highlighting their potential as multi-target natural ingredients for the attenuation of postprandial hyperglycemia. Full article

Background: Most bladder cancer cases present as non-muscle-invasive bladder cancer (NMIBC), with the course of multiple recurrences leading to stage progression to muscle-invasive bladder cancer (MIBC) in 10–20% of cases, which is associated with higher morbidity and mortality. Accurate histopathologic classification of bladder cancer remains important for patient management. Methods: This retrospective–prospective observational cohort study was conducted on 244 transurethral resection specimens. Immunohistochemistry assessed CK5/6, CK20, and apoptosis-inducing factor (AIF) using three representations: intensity, percentage of positive cells, and multiplicative score. Discrimination between NMIBC (pTa/pT1) and MIBC (≥pT2), and between low-grade (LG) and high-grade (HG) tumors, was evaluated using ROC/AUC analysis and logistic regression. The main analysis focused on cross-sectional marker performance in primary/non-recurrent tumors. Recurrent tumors were analyzed only as an exploratory subgroup. Tumors were also categorized into basal, luminal, mixed/double-positive, and double-negative phenotypes using thresholds of 10% for CK5/6 and CK20. Results: For stage discrimination, all three markers showed modest separation. The best-performing representation was CK5/6 intensity (AUC 0.641; lower in MIBC). For grade discrimination, the AIF score showed the highest performance (AUC 0.729, higher in HG). Combining markers improved model performance (NMIBC vs. MIBC: AUC 0.784; strict LG vs. HG: AUC 0.778). Using the 10% cutoff in non-recurrent tumors, mixed/double-positive tumors had the lowest MIBC proportion (6.0%) and double-negative tumors the highest (46.7%). Conclusions: CK5/6, CK20, and AIF provide modest discrimination between stages, with lower CK5/6 and CK20, and higher AIF, in MIBC. The AIF score shows the highest separation between grades and may serve as a useful non-proliferation marker for grading, particularly when interpreted alongside CK5/6 and CK20 in a simple immunohistochemical panel. Full article

Background/objectives: Renal-cell carcinoma (RCC) accounts for approximately 4% of all solid tumours worldwide. Oligometastatic RCC, frequently defined as the presence of fewer than five metastatic lesions, is increasingly recognised as a clinically and prognostically distinct disease state, yet standardised treatment algorithms remain lacking. Method: This narrative review summarises current local and systemic treatment strategies for oligometastatic RCC and identifies patient populations most likely to benefit based on 26 studies published within the past ten years. Results: Stereotactic ablative radiotherapy (SABR) was the most frequently evaluated local modality, consistently demonstrating high local control rates with favourable toxicity profiles. Systemic therapies showed mixed efficacy and greater treatment-related adverse events, while evidence for radiofrequency ablation, cryoablation, and metastasectomy remains limited but suggests feasibility in selected patients. Conclusions: Overall, current evidence supports local therapy—particularly SABR—in appropriately selected patients with oligometastatic RCC, though most available evidence is retrospective and concentrated in favourable-risk ccRCC populations, limiting generalizability. Further prospective research is needed to refine patient selection criteria and optimise treatment sequencing. Full article

Octacosanol (OCT) is a natural bioactive compound with multiple physiological activities. However, its poor aqueous solubility limits its application in functional beverages, and existing delivery systems suffer from low loading and excessive emulsifier use. This study aimed to develop a food-grade OCT-loaded microemulsion (OCT-ME) with high loading capacity. The formulation was optimized via pseudo-ternary phase diagram analysis combined with particle size and polydispersity index (PDI) measurements, and the characterization and biocompatibility of the optimized OCT-ME were systematically evaluated. The optimal formulation (w/w) consisted of 2.4% corn oil, 16.2% mixed emulsifiers (Tween 80/Span 80, HLB = 13), 5.4% 1,2-propanediol (Km = 3:1), and 75.0% deionized water, achieving a high OCT loading capacity of 1.0% (w/w). The resulting OCT-ME displayed a uniform particle size of 10.37 nm with a low PDI and exhibited excellent stability, favorable gastric OCT protection, and superior biocompatibility (cell viability > 90% at 5–25 μg/mL). This work addresses the key limitations of existing OCT delivery systems, providing theoretical support for the efficient solubilization and delivery of OCT in functional beverages. Full article

Leukocyte recruitment from blood into tissues involves sequential adhesive steps, including rolling and integrin-dependent arrest. VLA-4 can support firm adhesion and, in some settings, rolling interactions, whereas CD44–hyaluronan interactions have also been implicated in leukocyte rolling. Here, we used adhesion assays and parallel-plate flow chamber experiments to analyze CD44–hyaluronan-dependent monocyte interactions on ECV304 monolayers and to compare them with α4-integrin-sensitive adhesion on endothelial monolayers. WEHI 78/24 monocytoid cells interacted with ECV304 monolayers in a CD44- and hyaluronan-dependent manner, whereas adhesion to HMEC-1 and bEnd.3 monolayers was sensitive to α4-integrin blockade. Blocking CD44, adding soluble hyaluronan, or treating ECV304 monolayers with hyaluronidase reduced adhesion and rolling. Mixed primary human monocyte preparations also showed CD44-dependent adhesion and rolling on ECV304 monolayers. ECV304 cells are interpreted here not as endothelial cells, but as T24-derived, hyaluronidase-sensitive cellular monolayers useful for functional analysis of CD44–hyaluronan-dependent interactions. These findings support a substrate-dependent functional hierarchy in which CD44–hyaluronan-dependent monocyte rolling becomes detectable when α4-integrin-dependent adhesion is not dominant, while emphasizing the cell-model-based nature of the assay. Full article

There is increasing interest in structured layered double hydroxide (LDH)-based catalysts because they combine tunable acid–base/redox chemistry with reactor architectures that can reduce diffusion lengths, improve heat management, and lower pressure-drop penalties. This review evaluates LDH, LDH-derived oxide (LDO/MMO), reduced metal/LDO, reconstructed hydroxide-rich, and mixed dynamic states integrated into honeycomb monoliths, open-cell foams, meshes/felts, thin films, washcoats, coated plates, microchannels, capillaries, and additively manufactured lattices. To move beyond descriptive comparison, the literature is assessed using unified evaluation dimensions: operative active state, support architecture, coating/integration route, active-phase loading, coating thickness and uniformity, reactor-volume-normalized productivity or STY, ΔP/L, axial/radial thermal gradients, time-on-stream, coating loss, regeneration recovery, and pilot-readiness. Representative benchmarks illustrate both the promise and reporting gaps of the field: NiFe-LDH-derived monoliths for CO₂ methanation have reached ~70% CO₂ conversion at 300 °C with >90% CH₄ selectivity and only 0.7% post-test mass loss; NiFe-LDH/iron-foam monoliths retained 85% ozone conversion after 168 h; high-entropy LDH-derived oxides showed T50/T90 values of 246/254 °C for toluene oxidation; and Au/LDH capillary films achieved 31.9% glycerol carbonate yield and 3.78 g h⁻¹ g⁻¹ productivity. The strongest current cases are pollution abatement and CO₂ methanation, whereas biomass upgrading, fine-chemical flow, high-entropy coatings, and photo/electrocatalytic films require deeper module-level validation. Overall, structured LDH catalysts should be treated as coupled chemistry–coating–reactor systems whose performance must be judged simultaneously by activity, accessible catalyst inventory, transport efficiency, pressure drop, thermal profile, durability, regeneration, and manufacturability. Full article

Ataxia–Telangiectasia (A-T) is a rare neurodegenerative multisystem disease caused by mutations in the A-T Mutated (ATM) gene resulting in cerebellar ataxia, immunodeficiency and an increased cancer risk. Copper and zinc play important roles in similar cellular processes as the ATM protein, such as cell growth, apoptosis, and oxidative stress. This study aimed to explore copper and zinc levels in individuals with A-T since imbalances in these trace elements may contribute to the clinical features commonly seen in A-T and therefore be a target for novel therapies; furthermore we aimed to assess the potential role of copper and zinc as disease biomarkers. In this retrospective cohort study, plasma copper and zinc levels were collected from 37 individuals with A-T and compared with age-related reference values. The results showed lower zinc levels in pediatric individuals with classic A-T, but no differences in copper levels. In adults, copper levels were lower in classic A-T, but not in variant A-T. These findings suggest that copper and zinc metabolisms are dysregulated in A-T, but since mixed model analysis showed minimal changes over time, copper and zinc do not appear to be reliable biomarkers for disease progression. Full article

Background/Objectives: Skeletal muscle adaptation to metabolic stress involves a coordinated regulation of inflammatory, bioenergetic, and anabolic signalling pathways. This study aimed to investigate the potential role of whey protein isolate (WPI; commercial name: Volapure) as a modulator of cellular responses to stress in an in vitro model of exercise-mimetic stress over time. Methods: Murine C2C12-differentiated cells were exposed to an Exercise–Mimetic Mix (ExM) to reproduce key biochemical features of muscle stress. Cells were treated with WPI (1 mg/mL) using Pre-exposure (Pre-ExM) and Post-exposure (Post-ExM) protocols at 8 and 24 h. Multiple endpoints were assessed, including cell viability, reactive oxygen species (ROS) production, cytokine release (TNF-α, IL-6, IL-17), intracellular signalling pathways (p38 MAPK, ERK, AMPK, mTOR), bioenergetic markers (ATP, glycogen, lactate), protein synthesis (OPP incorporation), and Ca²⁺/Mg²⁺ fluxes. Results: ExM exposure induced a stress phenotype characterised by increased oxidative and inflammatory markers, impaired bioenergetic status, and reduced anabolic signalling. WPI was associated with modulation of these responses, reducing ROS and pro-inflammatory cytokines, restoring ATP and glycogen levels, and changes in ERK and mTOR-related signalling. The Post-ExM protocol showed greater modulation compared to the Pre-ExM approach, particularly at 24 h. WPI was also associated with the normalisation of ExM-altered Ca²⁺/Mg²⁺ fluxes. These findings should be interpreted as associative rather than causal. Conclusions: WPI was associated with modulation of key pathways involved in cellular adaptation to metabolic stress, supporting recovery of bioenergetic balance and anabolic signalling in C2C12 cells. These findings suggest a potential role for WPI in influencing cellular responses to metabolic stress, supporting recovery of bioenergetic balance and anabolic signalling in C2C12-differentiated-cells. However, further studies are required to confirm the translational relevance of these observations. Full article

Florid cemento-osseous dysplasia (FCOD) is a benign fibro-osseous condition typically presenting as multifocal, sclerotic masses throughout the jaws. While often asymptomatic, the hypovascular nature of the dysplastic bone predisposes it to secondary infection, which can mimic more aggressive pathologies. We present a complex diagnostic challenge involving a 76-year-old female with a history of intravenous ibandronic acid therapy for 18 months. The patient presented with a purulent mandibular fistula and exposed bone, leading to an initial clinical suspicion of Stage 2 Medication-Related Osteonecrosis of the Jaw (MRONJ). Radiographic evaluation, however, revealed generalized “cotton-wool” opacities across all four quadrants, characteristic of FCOD, with multifocal mixed radiolucent–radiopaque changes and a localized demarcated sequestrum in the symptomatic area. Accordingly, the diagnostic reasoning progressed from an initial clinical suspicion of MRONJ, to radiologic consideration of infected FCOD, and finally to exclusion of plasma cell neoplasia by immunohistochemical evaluation. The diagnostic dilemma intensified during histopathological analysis, which revealed an unusually dense, sheet-like infiltration of plasma cells within the fibro-osseous stroma. This striking plasmacytosis initially raised suspicion for a plasma cell neoplasm, such as plasmacytoma or multiple myeloma. To differentiate reactive inflammation from malignancy, immunohistochemical staining for kappa and lambda light chains was performed, demonstrating a polyclonal pattern that confirmed a reactive process. The final diagnosis was determined as FCOD with superimposed secondary osteomyelitis. Following conservative surgical debridement and targeted antibiotic therapy, the patient showed clinical resolution and remained stable at a 6-month follow-up. Recognizing these overlaps is essential for preventing over-treatment and ensuring appropriate management in elderly patients with complex medical backgrounds. Full article

In electricity–hydrogen coupling systems (EHCSs), the uncertainty of renewable energy generation (REG) tends to impact electrolyzers (ELs) in the following ways: (1) input powers of ELs are prone to fluctuations; (2) ELs are forced to operate under variable load states. Consequently, both impacts will reduce the service life of ELs. In this paper, considering the start–stop characteristics and combined operation modes of multiple ELs, a two-stage multi-time-scale energy allocation strategy (MSEAS) is proposed to mitigate the impacts of REG uncertainty and optimize the energy allocation for EHCSs. First, five refined operating states of ELs, such as shutdown, cold standby, low-load, variable-load and overload, are formulated as mixed-integer constraints and embedded into the system-level energy optimization model. Second, to mitigate power fluctuations caused by REG, a day-ahead optimization is employed to plan the power allocations of ELs, lithium batteries, fuel cells, and the grid with a 1 h time step; and then an intra-day rolling optimization is employed to adjust the operating states and power outputs of the above units with a 4 h window and 15 min step. Third, by enabling multiple ELs to flexibly operate in a combined mode, power-sharing mode and switching mode, the proposed MSEAS can refine the operation powers of ELs and reduce their start-up frequency. Comparative case studies are conducted in the off-grid and grid-connected operation tests, and the relevant results verify that the proposed MSEAS can effectively prevent the frequent start–stop of ELs, which contributes to extending the service life of ELs and reducing the system operating cost. Full article

The present study evaluated the stability of candidate reference genes during adipogenic differentiation of 3T3-L1 cells cultured on different extracellular matrices. The aim was to investigate the effects of matrix composition and differentiation stage on the expression of candidate housekeeping genes and to compare validation strategies in dynamic in vitro models. Eleven candidate reference genes (18S, Actb, B2m, Gapdh, Hmbs, Hprt, Nono, Ppia, Rplp0, Tbp, and Ywhaz) were analyzed by RT-qPCR in 3T3-L1 cells cultured on TC, collagen, gelatin, and Matrigel at Days 7 and 14 of differentiation. Gene stability was assessed using geNorm, NormFinder, RefFinder, comparative ΔCt, BestKeeper, generalized linear model (GLM), linear mixed model (LMM), and correlation analyses with the adipogenic markers Pparg and Fasn. The results demonstrated that the expression of most housekeeping genes was influenced by matrix composition, differentiation stage, or their interaction. Actb and 18S exhibited the strongest condition-dependent variability and pronounced matrix sensitivity. Gapdh and Hprt showed significant correlations with both Pparg and Fasn, while Hmbs correlated with Fasn, suggesting that these reference genes may not be fully independent of adipogenic status. Ppia demonstrated markedly contrasting rankings across analytical approaches, highlighting limitations of single-method stability assessment. The findings confirm that universal housekeeping genes are unlikely to exist across different matrix conditions and differentiation stages. The results highlight the need for multi-level validation strategies and experimentally validated normalization panels to minimize normalization bias and avoid misleading RT-qPCR expression profiles. Functional validation identified B2m and Rplp0 as the most suitable two-gene normalization panel for the experimental model evaluated, whereas Tbp remained a strong complementary reference gene candidate. Full article