Search Results (19,444)

This study examines how mechanically activated fly ash (TF), a polycarboxylate superplasticizer (PC), and an air-entraining admixture (AE) affect the hydration, microstructure, pore structure, mechanical properties, and freeze–thaw resistance of fine-grained concrete. Mechanical activation increased the specific surface area of the untreated ash (UF) from 3710 to 6450 cm²/g and reduced its mean particle size to 6.06 μm. Replacing 5 wt.% of cement with TF accelerated the nucleation of hydration products and densified the microstructure, as confirmed by exothermic profiling, XRD, and SEM. PC delayed the exothermic peak yet produced the highest heat-release intensity, indicating more efficient wetting and dispersion of reactive surfaces. The TF–PC system reached 39.3 MPa at 28 days, while the ternary TF–PC–AE composition achieved 33.2 MPa with a refined pore-size distribution (mercury intrusion porosimetry). The combined use of PC and AE tripled the pore volume in the 0.01–0.10 μm range and increased it by 28.7% (0.1–1 μm) and 46.21% (1.0–10 μm). The calculated potential freeze–thaw resistance rose from 54.25 to 61.97 and 72.83, confirming the beneficial role of 3–10 μm pores. After 110 accelerated freeze–thaw cycles, the optimized ternary composition lost only 0.55% of its mass. Full article

Cancer nanomedicine has generated extensive preclinical evidence of improved drug delivery, pharmacokinetics, and tolerability, yet its clinical impact has often remained modest. This narrative review examines the interconnected biological, pharmacokinetic, manufacturing, regulatory, and clinical factors underlying this translational paradox. A structured literature search was conducted primarily in PubMed and Google Scholar, focusing on studies published between 2022 and 2026 while retaining seminal earlier reports. Major biological barriers include protein corona formation, mononuclear phagocyte system clearance, heterogeneous enhanced permeability and retention, complex tumor microenvironments, and intratumoral heterogeneity. These factors limit circulation, tumor accumulation, tissue penetration, drug release, and interpatient reproducibility. Translation is further constrained by off-target accumulation, uncertain long-term toxicity, non-standardized experimental methods, batch-to-batch variability, scale-up challenges, and fragmented regulatory pathways. Clinical experience shows that successful products are dominated by relatively established platforms and reformulations of known anticancer agents, whereas many actively targeted or structurally complex systems have failed to demonstrate sufficient efficacy or safety. Future progress will require mechanism-driven design, human-relevant preclinical models, harmonized characterization, quality-by-design manufacturing, early regulatory integration, biomarker-guided patient selection, and adaptive clinical trials. Aligning nanoparticle engineering with biological and clinical realities is essential for achieving meaningful patient benefit. Full article

This study investigated non-conventional crops as raw materials for plant-based fermented functional products with potential neuromodulatory properties, assessing antioxidant activity, amino acid composition, neuroactive metabolites, and aroma profile. Antioxidant activity depended not only on total phenolic content but also on the composition and extractability of other bioactive and reducing constituents released during processing. Free amino acid and γ-aminobutyric acid (GABA) profiles differed markedly from the raw grains, reflecting the effects of enzymatic hydrolysis, formulation, and microbial fermentation. The naked oat fermented product (NOFP) had the highest total, essential and branched-chain free amino acid contents and contained serotonin (811 µg/kg). The triticale fermented product (TFP) showed high phenylethylamine (440 µg/kg), proline and glutamine, and the highest diacetyl content (502 ng/g), potentially contributing to its nutritional and sensory properties. The amaranth fermented product (AFP) was distinguished by high GABA (648.9 mg/kg DW) and L-DOPA (15,272 µg/kg). Kynurenine, kynurenic acid, indole-3-lactic acid, tryptamine, and other tryptophan and tyrosine metabolites were also detected. Volatile profiles were strongly matrix-dependent; AFP was the most diverse, with high levels of aldehydes, pyrazines, furans, and sulfur-containing compounds. Overall, the grain matrix and the processing and formulation sequence strongly influence the nutritional, antioxidant, neuroactive, and aroma characteristics of the products. Full article

Waterborne polyurethane (WPU) has emerged as one of the most promising environmentally friendly coating materials owing to its low volatile organic compound (VOC) emissions, excellent film-forming ability, good adhesion, and versatility in formulation. However, WPU suffers from several intrinsic limitations including inadequate thermal stability, modest mechanical strength, poor flame retardancy, and a lack of inherent antibacterial activity. To address these deficiencies, phosphorylated microfibrillated cellulose (PMFC), prepared from beech wood sawdust via sequential steam explosion, phosphorylation, and superfine grinding, was employed as a substrate for in situ silver nanoparticle (AgNPs) synthesis and subsequent incorporation into WPU via aqueous blending and solvent casting. PMFC functions through a combined mechanism: the hydroxyl and phosphate groups coordinate Ag⁺ ions, providing nucleation sites, while the nanofibrillar network provides steric stabilization against post-synthesis aggregation. The influence of AgNPs loading (1–10 wt% relative to PMFC at a fixed 1 wt% PMFC content) on the morphology, antibacterial activity, silver release behavior, thermal stability, flame retardancy, and mechanical properties of the resulting composite films was comprehensively investigated using free-standing composite films as a model system. At the optimal Ag loading of 5 wt%, the composite exhibited strong antibacterial activity against Escherichia coli with silver release below 1.15 ppb after 96 h, while tensile strength and Young’s modulus increased by 80% and 298%, respectively, relative to neat WPU. At high Ag loadings (70–80 wt%), the composites achieved conductive-level surface resistivity (~3 log Ω) through percolation network formation, demonstrating antistatic functionality. This study provides an effective strategy for fabricating WPU composite films with combined antibacterial, mechanical reinforcement, and antistatic capabilities. Full article

Background: Postpartum hypogalactia is a prevalent obstetric complication worldwide, closely associated with excessive oxidative stress and impaired antioxidant defense in mammary tissue. Current hormone-based therapies carry endocrine disruption risks, while natural antioxidant bioactive agents such as extracellular vesicles (EVs) are largely limited by rapid in vivo clearance and poor tissue retention. Methods: We constructed an injectable gelatin methacryloyl (GelMA) hydrogel system to encapsulate chemically induced mammary epithelial cell-derived EVs (CiMECs-EVs) and systematically evaluated their antioxidant and lactogenic activities via multi-omics analysis, cellular functional assays and a bromocriptine-induced murine hypogalactia model. Results: CiMECs-EVs induced a functional mammary epithelial-like phenotype in fibroblasts in a dose-dependent manner with functional cargo enriched in glutathione metabolism and redox-regulatory miRNAs. The GelMA matrix protected EV integrity and enabled sustained release, and the composite system significantly ameliorated mammary duct structure and lactation function in vivo with specific mammary tropism and no systemic toxicity, outperforming free EV treatment. Conclusions: This study presents a safe protein biomacromolecule-based antioxidant delivery platform that effectively restores mammary redox balance and antioxidant defenses, providing a promising non-hormonal therapeutic strategy for postpartum hypogalactia. Full article

Background: Effective topical management of sensitive skin remains challenging because inadequate cutaneous delivery limits the therapeutic performance of many anti-inflammatory agents. Glycyrrhetinic acid (GA) possesses well-recognized anti-inflammatory and barrier-protective activities, yet its clinical potential is constrained by poor aqueous solubility and inefficient skin delivery. This study aimed to develop a hyaluronic acid (HA)-engineered ethosomal system to enhance the local delivery and therapeutic efficacy of GA for sensitive skin. Methods: HA-coated GA-loaded ethosomes (HAGA-ETs) were prepared by electrostatic adsorption of HA onto a cationic ethosomal template. The physicochemical properties, release behavior, storage stability, skin retention, cellular uptake, and biological activities of HAGA-ETs were systematically evaluated using TNF-α/IFN-γ-stimulated HaCaT cells and an SLS-induced 3D reconstructed skin model. Results: HAGA-ETs exhibited a mean particle size of 140.1 nm, encapsulation efficiency exceeding 95%, sustained drug release, and good storage stability. Compared with Free-GA and unmodified ethosomes, HAGA-ETs showed improved cytocompatibility, enhanced skin retention, greater keratinocyte uptake, and stronger anti-inflammatory activity. HA pre-saturation attenuated the enhanced cellular uptake of HAGA-ETs, supporting the involvement of HA receptor-mediated cellular interaction. HAGA-ETs also more effectively restored barrier-related markers, suppressed hyper-reactivity- and allergy-associated mediators, and inhibited the activation of MAPK/NF-κB, JAK1/STAT1, and TRPV1-related signaling pathways in both cellular and 3D skin models. Conclusions: HA surface engineering effectively improved the topical delivery and local therapeutic efficacy of GA by enhancing skin retention and keratinocyte interaction. HAGA-ETs represent a promising nanoplatform for the local management of sensitive skin. Full article

Opuntia ficus-indica flowers represent a valuable source of phenolic compounds with promising antioxidant properties, although their application is limited by the poor stability and bioavailability of these bioactives. This study aimed to identify the most effective extraction method for maximizing polyphenol recovery and to develop a spray-dried microparticulate delivery system capable of improving the stability and release of the freeze-dried extract. Different extraction techniques were compared by determining total phenolic content (TPC), antioxidant activity and individual phenolic compounds by HPLC-UV. Among the investigated methods, decoction proved to be the most efficient, exhibiting the highest TPC (27.59 mg GAE/g), antioxidant capacity (DPPH: 0.53 mmol TEAC/100 g d.e.; ABTS: 0.79 mmol TEAC/100 g d.e.; FRAP: 43.18 mg Fe²⁺/100 g d.e.) and the greatest overall recovery of polyphenols. HPLC analysis identified quercetin as the predominant flavonoid (57.07 mg/g), followed by kaempferol rhamnoside and quercetin-3-rhamnoside. The selected extract was successfully encapsulated by spray-drying, producing spherical microparticles (MPs) with a process yield of 64%. SEM, DSC and FT-IR analyses confirmed suitable morphology and enhanced thermal stability. In vitro dissolution and ex vivo permeation studies demonstrated a faster initial release and enhanced early quercetin permeation of MPs across porcine colon mucosa compared with the freeze-dried extract. These findings highlight spray-dried microparticles as a promising strategy for improving stability, bioaccessibility and nutraceutical potential of O. ficus-indica flower polyphenols. Full article

Silk fibroin (SF)- and silk sericin (SS)-based antibacterial hydrogels are increasingly engineered as local antimicrobial platforms, yet cross-study interpretation is limited by inconsistent material reporting and by conflation of bacterial inhibition with tissue repair. We performed a structured evidence-mapping and critical synthesis of a frozen 2020–July 2026 corpus of 94 references. The original 46-record core map was re-audited at the original-article level: 43 full-text-verified, non-retracted primary studies were retained for detailed evidence grading, 2 records available only at abstract/database level were retained descriptively but not graded, and 1 subsequently retracted study was excluded from quantitative synthesis. Among the 43 graded studies, metal-ion/nanozyme/catalytic systems were most common (12/43, 27.9%), followed by release-mediated (11/43, 25.6%), multimodal (9/43, 20.9%), contact-active/anti-adhesive (6/43, 14.0%), and light-responsive systems (5/43, 11.6%). Sixteen studies (37.2%) used deliberately infected animal models, whereas only 4 (9.3%) reached a biofilm or adherent-bacteria-level endpoint in the graded map. Biological claim ceilings (C0–C5) are assessed independently from translation gates spanning material identity, reproducibility, mechanism, host safety, sterilization/storage, resistance, long-term fate, and deployment. Across mechanisms, SF and SS most often function as structural, interfacial, or transport-regulating matrices; direct silk-dependent bactericidal causality remains uncommon. The central translational deficit is failure to quantitatively link silk molecular identity and network architecture to antimicrobial exposure, bacterial killing, host selectivity, and long-term material fate. Full article

Functionalizing textiles with nanoparticles is a promising strategy for developing sustainable materials with antimicrobial activity and reduced potential for resistance. This study aimed to develop antimicrobial cotton and polyester (PE) textiles functionalized with gold and silver nanoparticles (Au@UP and Ag@UP) biosynthesized using Undaria pinnatifida (UP) aqueous extracts. The nanoparticle-functionalized textiles were characterized by Ultraviolet–visible spectroscopy (UV-vis), scanning electron microscopy (SEM), and fourier transform infrared spectroscopy (FTIR), and nanoparticle attachment–detachment and stability were evaluated on both substrates. Antioxidant activity was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, while antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa and cytocompatibility using the L-929 cell line were determined. UV–vis spectroscopy revealed residual release, while SEM, UV–vis, and FTIR confirmed nanoparticle binding. Cotton exhibited higher nanoparticle affinity and stability (KS = 0.5007 for Au@UP and 0.4817 for Ag@UP), attributed to its abundance of reactive hydroxyl groups. Although antioxidant activity decreased after nanoparticle binding (<5%), functionalized cotton gauzes retained antimicrobial activity. Au@UP and Ag@UP textiles were non-cytotoxic (>80% cell viability) and inhibited the growth of S. aureus (~15% and 90%, respectively) and P. aeruginosa (~90% for both). These findings support the potential of UP-mediated nanoparticle-functionalized textiles, particularly Ag@UP-containing materials, as sustainable antimicrobial surfaces. Full article

Vaginal drug delivery offers a critical route for local treatments but is limited by short formulation residence times. This study describes a thermosensitive in situ gel prepared by the cold-dissolution method from a ternary blend of Pluronic F127, Carbopol 940, and HPMC for localized vaginal therapy. We used ibuprofen as a model drug selected for its reported anti-inflammatory and antiproliferative activity. The hydrogels exhibited a constant gelation temperature of 28 °C and high viscosity under simulated physiological conditions; ibuprofen incorporation further reduced susceptibility to gravitational leakage. FTIR, XRD, and DSC analyses confirmed stable physical cross-linking of the polymer network and amorphous molecular dispersion of ibuprofen. Peppas–Sahlin modelling revealed a controlled, sustained release profile (>50% over 24 h) predominantly governed by Fickian diffusion (69%). The blank hydrogel exhibited high biocompatibility (>75% viability). In contrast, the ibuprofen-loaded matrix exhibited a concentration-dependent cytotoxic effect on HeLa cervical cancer cells, reducing cell viability to ~12% at the full extract concentration. Overall, this ternary hydrogel platform represents a stable, promising vehicle for sustained local administration of ibuprofen in the vaginal microenvironment. Full article

Fenofibric acid-loaded microfibrous mats were produced by electrospinning using polyvinylpyrrolidone (PVP) as a carrier polymer. Fenofibric acid, obtained through alkaline hydrolysis of fenofibrate, was incorporated into PVP solutions and processed under optimized electrospinning conditions to obtain uniform, defect-free fibers. The morphology and average fiber diameter were examined by scanning electron microscopy, revealing homogeneous, continuous fibers. Thermal analysis revealed the disappearance of the characteristic melting endotherm of fenofibric acid following electrospinning, indicating a substantial alteration in its thermal behavior within the polymer matrix. In vitro dissolution tests in artificial saliva showed a markedly enhanced release rate of fenofibric acid from the fibrous mats compared with the pure crystalline form, indicating a significant improvement in apparent solubility. These findings highlight the potential of PVP-based electrospun fiber formulation as an efficient carrier for the active metabolite of fenofibrate. Full article

Programmed cell death pathways in Plasmodium falciparum remain conceptually fragmented. Over decades, researchers have applied metazoan apoptotic, autophagic, and necrotic markers to this deep-branching protozoan, frequently clashing with the reality that the parasite lacks the canonical genetic machinery (such as true caspases or death receptors) found in multicellular eukaryotes. In this work, we shift the focus from the parasite’s disputed intrinsic death machinery to the host–parasite interaction arena: the active manipulation of the host erythrocyte’s autonomous suicide program, eryptosis. The intraerythrocytic development of P. falciparum generates profound oxidative stress through hemoglobin digestion and free heme release, driving lipid peroxidation and the accumulation of reactive aldehydes such as 4-hydroxynonenal (4-HNE)—potent signaling molecules that can trigger eryptotic pathways. We integrate existing literature on membrane remodeling, protein export, and lipid raft dynamics to propose a novel Host Protein Sequestration Hypothesis. We suggest that P. falciparum evades splenic clearance by actively dismantling the host cell’s surface death signaling platforms—Clusters of Apoptotic Signaling Molecule-Enriched Rafts (CASMERs)—and pulling these host components inward. We suggest that human FAS (CD95) is internalized by the parasite and physically interacts with Plasmodium lipid-raft scaffolding proteins, preventing it from engaging FasL (CD178) that is either expressed on adjacent erythrocytes or presented within the local splenic microenvironment—an interaction that would otherwise precipitate eryptotic signaling. This perspective offers a fundamentally fresh conceptual framework for understanding malaria survival strategies and highlights a vulnerable, non-canonical therapeutic target. Full article

Staphylococcus aureus (S. aureus), a primary exacerbating factor in eczema, remains a prevalent pathogenic public-health threat. The mechanism of mast cell/basophil degranulation in the context of S. aureus-exacerbated eczema remains unclear. We sought to investigate the direct effect of mast cell/basophil activation by S. aureus isolated from patients with severe eczema undergoing topical steroid withdrawal (TSW) and understand the mechanism of berberine (BBR) in inhibiting this activation. Clinical S. aureus strains (N = 8) were isolated from skin swabs of severe eczema patients and confirmed by sequencing. Human basophils (KU812), rat basophils (RBL-2H3) and murine mast cells (MC/9) were pre-treated with BBR for 48 h. and stimulated with heat-killed standard S. aureus- and clinical strains for 45 min, and degranulation was measured. BBR’s molecular-targets on basophils were identified by computational modeling and validated by qRT-PCR. BBR prevented degranulation following standard S. aureus stimulation in KU812, RBL-2H3 and MC/9 cells. BBR dose-dependently inhibited degranulation in KU812. BBR inhibited TNF-α and IL-4 release, and markedly suppressed the expression of FcεR1 (α, β, γ), TNFα, MAPK1, MAPK3, AKT2, CASP9, and CCND1 following standard S. aureus stimulation. BBR dose-dependently inhibited KU812 cell degranulation, markedly reduced TNF-α, IL-4, and MAPK1 and enhanced NFκB1A expression following clinical S. aureus strain stimulation. BBR inhibition of S. aureus-induced KU812 activation was at least associated with inhibition of MAPK-associated gene expression. This study provides novel insights into BBR’s effect in preventing S. aureus and human basophil interaction. Full article

This exploratory study examined a dual-role artificial intelligence-supported programming environment that integrated human-in-the-loop item generation and on-demand AI debugging within a flipped cognitive apprenticeship framework. Programming tasks were initially generated by GPT-4o and were subsequently reviewed, revised, and approved by the instructor before release. Both instructional conditions completed the same instructor-approved tasks and received the same compiler and automated test-case feedback. Students in the AI Debug-enabled condition could additionally request diagnostic guidance after an unsuccessful submission, whereas students in the comparison condition did not have access to AI-generated debugging assistance. The analytic sample comprised 45 students in the AI Debug-enabled condition and 16 students in the comparison condition. Prior-semester programming achievement, operationalized as the total grade obtained in the preceding programming course, was used as an archival baseline covariate. The observed baseline difference was not statistically significant. Programming-task performance was recorded across 13 instructional weeks. A generalized estimating equation model controlling for prior-semester programming achievement showed no significant overall condition effect, but revealed significant effects of instructional week and the Condition × Week interaction. Prior-semester programming achievement significantly predicted weekly task performance. The comparison condition also obtained higher midterm and final examination scores after adjustment for prior achievement. The findings do not demonstrate a consistent programming-performance advantage associated with access to AI Debug. Instead, adjusted differences varied across instructional weeks and assessment contexts. Because the study used naturally occurring nonequivalent groups and did not retain AI Debug activation records, the results should be interpreted as exploratory associations concerning feature availability rather than causal effects of actual AI use. The primary contribution lies in documenting a human-supervised architecture that integrates instructor-facing AI item generation and student-facing debugging assistance while distinguishing AI-supported task performance from independent programming achievement. Full article

Objectives: To compare, in vitro, the marginal and internal fit and marginal microleakage of preformed metal crowns (PMCs) placed with the conventional, Hall, and modified Hall techniques and cemented with three ion-releasing, resin- or glass-ionomer-matrix luting materials: a bioactive resin-matrix cement (ACTIVA^™ BioACTIVE-CEMENT), a bioceramic calcium aluminate cement (Calibra^® Bio), and a resin-modified glass ionomer cement (RMGIC; Riva Luting Plus). Methods: Forty-five extracted human primary molars were randomly allocated to three preparation groups (n = 15), each subdivided by cement (n = 5). After thermocycling (500 cycles, 5–55 °C, dwell time: 15 s, transfer time: 10 s), specimens were immersed in 1% methylene blue for 24 h, sectioned buccolingually, and examined by image analysis (ImageJ). Microleakage was quantified as the percentage of the crown–tooth interface showing dye penetration; marginal and internal fit were measured at thirteen points across marginal, axial, angular, and occlusal regions. Results: Marginal gap did not differ significantly among techniques or cements (p > 0.05). A significant region × technique interaction (p = 0.025) localised the technique effect to the angular region, where the Hall technique produced a larger gap than conventional preparation (p = 0.004). Microleakage was significantly greater for the Hall than the conventional technique (p = 0.045), with the modified Hall being intermediate. Cement had no significant effect, and fit and microleakage were uncorrelated. Conclusions: Preparation technique, rather than cement, was the principal determinant of seal and angular fit; ACTIVA^™ BioACTIVE-CEMENT and Calibra^® Bio performed comparably to RMGIC under the conditions tested. Clinical studies of a modified Hall technique incorporating a defined occluso-axial bevel are warranted to confirm these findings. Full article