Search Results (92,000)

The valorisation of agro-industrial by-products through fermentation offers an opportunity to develop functional ingredients with targeted effects on gut microbiota. This study evaluates the impact of apple pomace fermented at a low temperature (15 °C) by cold-adapted yeast on the structure and metabolic activity of human gut microbiota, simulated using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®). The fermented apple pomace preparation was characterised by high stability under gastrointestinal conditions, supporting its potential applicability as a functional food ingredient. Supplementation with fermented apple pomace induced distinct changes in the composition and activity of gut microbiota compared to the non-fermented substrate, including increased abundance of the genera Akkermansia, Coriobacteriaceae, and Parabacteroides, and reduced abundance of Bifidobacterium, Klebsiella, Serratia, and Raoultella. The fermented preparation was associated with reduced accumulation of metabolites typically linked to proteolytic fermentation and a more stable metabolic profile throughout the supplementation and washout phases. Short-chain fatty acid analysis indicated that fermentation influenced both the quantity and proportional balance of microbial fermentation products, promoting profiles closer to physiological reference ranges. Overall, fermentation of apple pomace at 15 °C enhanced its functional properties and modulated gut microbiota metabolism in a manner consistent with improved ecosystem stability. These findings highlight the potential of fermented fruit by-products as sustainable ingredients for dietary strategies aiming to support gut microbial functionality. Full article

Background: Glioblastoma (GBM) remains the most aggressive primary brain tumor, and intraoperative frozen section analysis is the current standard for rapid histopathological assessment. However, this approach is time-consuming and resource-intensive. Stimulated Raman scattering (SRS) imaging has emerged as a label-free technique enabling near real-time microscopic evaluation of fresh tissue. This study compares the visualization of selected histopathological features in a newly developed intraoperative SRS system with conventional hematoxylin–eosin (HE) staining in confirmed GBM. Methods: Tumor samples from 30 patients with neuropathologically confirmed GBM were analyzed. For each case, both HE-stained frozen sections and SRS-generated virtual HE-like images were prepared from separate portions of the specimen. Twelve neuropathologists with varying levels of experience assessed 60 images according to seven predefined GBM criteria, resulting in 720 image evaluations. Feature detection was analyzed using cluster-adjusted generalized estimating equation models, and interobserver agreement was assessed using Fleiss’ κ. Results: Descriptively, hypercellularity and hypervascularization were identified at similar frequencies in both modalities, whereas pleomorphism, endothelial proliferation, mitotic activity, and necrosis were more often recognized in HE images. In cluster-adjusted analyses, SRS showed significantly lower detection rates for hypercellularity, pleomorphism, endothelial proliferation, and mitotic activity, while no significant difference was observed for hypervascularization, necrosis, or pseudopalisading after false discovery rate correction. Interobserver agreement was feature-dependent and generally higher for HE than SRS, particularly for hypercellularity. Conclusions: In this feature-level analysis of neuropathologically confirmed GBM, SRS imaging provided rapid, label-free morphological information and showed comparable visualization of selected histopathological features, particularly hypervascularization. While conventional HE-stained frozen sections remained superior for certain WHO-defining features, SRS represents a promising intraoperative adjunct that may complement established neuropathological workflows. Further studies including non-tumor tissue and a broader range of glioma grades are needed to determine the full diagnostic accuracy and clinical applicability of this technique. Full article

Environmental scientists are increasingly monitoring therapeutic drugs and their metabolites in water systems, requiring knowledge of human drug metabolism and excretion. Many published studies, however, rely on data from small-scale human metabolism trials, typically involving around six (healthy, young, male) volunteers. Their generalizability to real-world drug users may be limited, potentially biasing environmental monitoring efforts. Here, we leveraged untargeted LC-SWATH/MS pharmacometabolomics data from 283 potential living kidney donors and 688 kidney transplant recipients to characterize the 24 h urinary excretion profiles of two widely used diuretics frequently monitored in wastewater, hydrochlorothiazide and furosemide. Both are expected to be excreted largely unchanged, which our analyses confirmed. For hydrochlorothiazide, however, we also identified (using reference standards) the previously underreported transformation products chlorothiazide and salamide. These findings highlight the relevance and capability of using untargeted metabolomics data from human excreta to provide insights from large, real-world cohorts into which chemicals enter wastewater systems, with both drugs serving as exemplary case studies for analogous analyses of other drugs. In particular, the qualitative information obtained (e.g., accurate mass, retention time, fragment spectra) may inform targeted biomonitoring and highlight cases where consensus-based estimates of excreted drug or metabolite fractions are overestimated. Full article

Structure-based strategies are widely used in tuberculosis drug discovery; however, their translational impact remains limited. This review examines how structure-based virtual screening (SBVS) is applied in practice to Mycobacterium tuberculosis targets and explores why docking-derived predictions frequently fail to translate into measurable biological activity. Rather than treating docking scores as quantitative predictors of potency, representative case studies are analyzed to demonstrate that SBVS is most effective when employed as a prioritization framework integrated with appropriate target preparation, physicochemical filtering, and early experimental validation. Across diverse targets, molecular dynamics simulations emerge as a critical discriminator, enabling the identification of binding instability and false-positive hits that persist after static docking. Tuberculosis-specific constraints—including cofactor-dependent catalysis, resistance-associated mutations, membrane-rich environments, and permeability barriers—are discussed as key factors decoupling in silico affinity from whole-cell efficacy. Collectively, these observations support a workflow-oriented view of computational drug discovery in tuberculosis, in which iterative integration of structural modeling and experimental validation is required for meaningful lead identification. Full article

In this work, we demonstrate a functional and previously insufficiently explored route for converting cyclic olefin copolymer (COC) TOPAS^® thin films into antibacterial hybrid materials through a combination of solvent casting, plasma activation, noble-metal sputtering, and subsequent thermal or laser treatment. While COC is already well-known as a transparent, chemically resistant material for pharmaceutical and optical applications, its coupling with post-treated noble-metal nanostructures for antibacterial functionality has not been systematically described. The main contribution of this study lies in showing that COC can serve not only as a passive packaging substrate, but also as an active platform for the formation of biologically relevant surface nanostructures. Compared with previously reported metal/polymer systems, the present work provides clear evidence that noble-metal layers on COC undergo substantial structural evolution after thermal and excimer-laser treatment, resulting in regular nanoclustered morphologies. A particularly important finding is the detection of Au particle implantation below the COC surface during sputtering, as revealed by Rutherford backscattering spectrometry, which distinguishes this system from conventional surface-only metal coatings. Furthermore, we show that laser and thermal processing do not merely reshape the deposited layer, but significantly influence the final biological response of the material. Ag-based structures showed strong bactericidal behavior against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. The prepared samples were comprehensively characterized by AFM, DSC, RBS, SEM, and TGA, and their roughness and wettability were also evaluated, enabling direct correlation between physicochemical changes and antibacterial performance. These results introduce a new strategy for upgrading conventionally used pharmaceutical COC materials into multifunctional surfaces with added antibacterial value. Full article

The development of sustainable plant protection strategies requires stable and environmentally compatible delivery systems for beneficial microorganisms. In this study, Bacillus subtilis was encapsulated within chitosan-based cast films to evaluate bacterial viability, sustained biological activity, and antifungal efficacy. Films prepared from chitooligosaccharide (COS) and chitosans of low, medium, and high molecular weight (CS-LMW, CS-MMW, CS-HMW) were characterized in terms of morphology, mechanical performance, and pH-dependent swelling behavior. The viscosity of the chitosan solutions increased markedly with molecular weight from 73 cP (COS) to 614 cP (CS-HMW), while film thickness ranged from 34 ± 1.5 to 57 ± 2.3 µm. Mechanical performance improved significantly with increasing molecular weight, with maximum tensile stress exceeding 200 MPa for CS-HMW films, while swelling studies confirmed pronounced pH-dependent behavior consistent with the polyelectrolyte nature of chitosan. Encapsulation effectively preserved bacterial viability and metabolic activity over time. The intrinsic antifungal activity of chitosan synergized with the biocontrol activity of B. subtilis against Fusarium avenaceum and Alternaria solani. The highest antifungal performance was observed for CS-HMW films, which produced inhibition zones up to 84.6 ± 5.0 mm against A. solani. These findings demonstrate that chitosan-based cast films serve as effective carriers for beneficial microorganisms, providing environmental protection and regulated biological activity. The combination of a bioactive polymer matrix with a potent biocontrol agent represents a promising eco-friendly approach to sustainable plant protection. Full article

Background: Coxsackievirus B2 (CVB2) causes a range of diseases, including hand, foot, and mouth disease; myocarditis; acute flaccid paralysis; meningitis; and encephalitis. However, no specific antiviral drugs or vaccines are currently available for CVB2. Methods: We used plaque purification, virus titre determination, and serial passaging to screen and identify an inactivated CVB2 vaccine candidate strain, KM31-C05, which exhibited high viral titres and good genetic stability. Comprehensive biological characterization of this candidate strain was performed, including phylogenetic analysis, virulence assessment in BALB/c mice, one-step growth curve analysis, optimization of the multiplicity of infection, as well as determination of viral load, pathological evaluation, and immunohistochemical analysis in tissues of BALB/c suckling mice post-challenge. An experimental inactivated vaccine was prepared using KM31-C05 to evaluate its immunogenicity and protective efficacy. Results: The viral titres of KM31-C05 reached 10⁸ CCID50/mL. After 20 serial passages, only three amino acid mutations were identified (VP3-G165V, VP1-N84K, and VP1-D129N). Although the two VP1 mutations were located in surface-exposed loops, the strain maintained high neutralizing titres across passages, indicating good genetic stability. However, whether these sites affect virulence and replication requires further investigation. Phylogenetic analysis revealed that this strain belonged to genotype C, which is consistent with the strains circulating in mainland China in recent years. The experimental inactivated vaccine prepared from KM31-C05 induced effective neutralizing antibodies (1:128–1:256) in BALB/c mice and provided complete protection to suckling mice against lethal challenge with this CVB2 strain in maternal antibody protection experiments. Conclusions: KM31-C05 demonstrates potential as a CVB2 vaccine candidate in China and provides a theoretical basis for the development of a CVB2 vaccine. Full article

Periodontitis is a chronic inflammatory disease marked by the progressive destruction of periodontal tissues, where conventional therapies often fail to maintain adequate drug levels at the target site. This study reports the development and characterization of a thermosensitive gel containing nanostructured lipid carriers (NLC) for controlled local periodontal delivery. Apigenin (AP)-loaded NLC were prepared using AP as active agent and clove essential oil (CEO) as liquid lipid subsequently incorporated into Poloxamer 407 (5–15% w/w) hydrogels. The formulations were evaluated in relation to particle size, morphology, thermal and rheological behavior, mucoadhesion, in vitro release, antibacterial activity, and stability. Optimized nanoscale NLC showed a high entrapment efficiency, and uniform morphology. Raman analysis confirmed successful AP incorporation and homogeneous distribution in the gel without incompatibility. NLC-loaded gels exhibited sol–gel transition at physiological temperature with improved viscoelasticity and enhanced mucoadhesion. The drug release was sustained for 48 h and followed the Korsmeyer–Peppas model, indicating diffusion-based and anomalous transport. The antibacterial assessment demonstrated the pronounced inhibitory activity of the NLC formulations against key periodontal pathogens, with the formulation-dependent modulation of antimicrobial efficacy observed following the gel incorporation. Stability studies showed preserved nanoparticle structure and uniform dispersion. Overall, the thermoresponsive NLC-hydrogel system offers a promising strategy for prolonged, localized periodontal therapy. Full article

Blast furnace cement-dolomite mortars prepared from commercial cement (CEM-III/B) containing ~75% of slag and natural dolomite were aged under accelerated conditions at 60 °C in 1 M NaOH for 0–24 months. The hydration products and microstructure features of the mortars were studied using XRD, TGA and SEM-EDS methods, with blast furnace cement paste for comparison. The results showed that the presence of dolomite enhanced slag hydration, as the carbonates released during dedolomitisation promoted Ca and Si dissolution from the slag grains. After prolonged ageing, a multi-rim structure was observed around the slag particles: the inner rim primarily consisted of a hydrotalcite-like phase mixed with C-S(A)-H gel, while the outer rims were richer in C-S(A)-H gel, with varying calcium content. Monocarbonate phase was additionally detected at the slag–paste interface in the presence of dolomite. The observed increase in mechanical strength during ageing had to do with two reasons: (i) the increase in hydration product content and (ii) the densification of microstructure due to the formation of calcium carbonate, which filled pores and microcracks and the possible carbonation of C-S (A)-H gel in the binding paste. Under the investigated alkaline ageing conditions, dolomite acts as a chemically active component rather than an inert filler, influencing both slag hydration kinetics and the composition of the resulting hydration products. Full article

This study examined the effects of particle size blending and hybrid binder content on the structural properties and methane adsorption behavior of coconut shell-based activated carbon monoliths. Monoliths were prepared using activated carbon particles with two size ranges (212–250 µm and 26–53 µm), blending ratios of 1:9, 3:7, 5:5, and 7:3, and a hybrid binder containing styrene–butyl acrylate (SBA) and carboxymethylcellulose (CMC). Morphology and elemental composition were analyzed by SEM-EDS, specific surface area and pore structure were evaluated by BET analysis, and surface properties were examined by XPS. Structural density and compressive strength were also measured. Among the tested samples, M50ML showed the highest structural density (0.544 g/cm³), compressive strength (27.5 MPa), and methane uptake (3.06 mg/g). This result was related to improved packing by particle size blending while maintaining microporosity. These results indicate that particle size blending and binder content significantly affected the structural properties and methane adsorption behavior of the prepared monoliths. Full article

Donor–acceptor (D-A)-type conjugated porous polymers (CPPs) have emerged as highly competitive photocatalysts for aerobic oxidation reactions. Herein, we rationally design and synthesize a series of D-A structured photocatalysts by employing dibenzothiophene-S, S-dioxide (BTDO) as the acceptor unit, and 4,8-bis(thiophen-2-yl) benzo [1,2-b:4,5-b’] dithiophene (DBD) and pyrene (Py) as the donor units. The effects of acceptor content on the optoelectronic and photocatalytic properties are systematically investigated. With the gradual increase in BTDO proportion and the decrease in pyrene content, the photocatalysts exhibit gradually narrowed band gaps, significantly promoted charge separation efficiency, and broadened visible light absorption range. Among the five as-prepared photocatalysts, DBD-T displays superior catalytic performance toward blue light-driven aerobic oxidation. Under mild conditions, benzyl sulfide and benzyl amine are selectively converted into benzyl sulfoxide and benzyl imine with a high conversion efficiency up to 96%. Moreover, DBD-T shows good universality toward a wide range of substrates, together with excellent recyclability and long-term stability. This work demonstrates that enhancing the electron-withdrawing capability of the acceptor unit represents a feasible and effective strategy to boost the photocatalytic performance of D-A-type conjugated polymers. Full article

The effects of static magnetic field (SMF) treatment on the solid-state culture of Sanghuangporus vaninii (SV) were investigated to enhance metabolite production and bioactivity. SMF parameters including intensity, exposure duration, and temperature were optimized, and treatment at 4 mT for 2 h per day produced the most pronounced effects, increasing total flavonoid (TFC), polyphenol (TPC), and triterpenoid (TTC) contents by 61–438% compared with the control. Ultrasonic extraction and semi-preparative chromatography enabled the isolation of three key compounds: D-(+)-trehalose (1), 5,7-dihydroxy-3,4′-dimethoxyflavone (2), and pinolenic acid (3), all of which were elevated following SMF treatment. Importantly, SMF exposure was associated with enhanced inhibitory activities against enzymes relevant to chronic metabolic disorders. The overall inhibitory activities against α-amylase, α-glucosidase, pancreatic lipase, and xanthine oxidase increased by 6–28% compared with the control, reaching a maximum inhibition of 97.60 ± 0.17%. Preliminary in vitro screening at 100 μg/mL showed that compounds 1 and 2 inhibited both α-amylase and α-glucosidase, whereas compound 3 selectively inhibited pancreatic lipase. Subsequent IC₅₀ analysis confirmed that compound 2 under SMF treatment exhibited inhibitory activity comparable to acarbose against α-amylase (45.62 μg/mL vs. 52.18 μg/mL) and α-glucosidase (38.74 μg/mL vs. 35.42 μg/mL). In addition, compound 3 showed moderate inhibition of pancreatic lipase with an IC₅₀ value of 42.15 μg/mL. These findings suggest that SMF treatment may enhance metabolite production and in vitro enzyme inhibitory activity in S. vaninii. However, these results are limited to in vitro assays, and further studies including cellular and in vivo validation, toxicity assessment, and pharmacokinetic evaluation, are required before any therapeutic or industrial applications can be considered. Full article

Kinmen peanut (Arachis hypogaea L. cultivar Kinmen No. 1) is a unique crop used to produce local specialty “peanut candy”; however, the peanut skins (PSs) are treated as waste owing to the bitter taste. To support the valorization of this agro-industrial by-product, peanut skin ethanolic extract (PSE) was prepared and evaluated for its hypolipidemic potential in a cholesterol/fat-fed hamster model, together with its antioxidant capacity and chemical composition. Hamsters were fed a cholesterol/fat-enriched diet supplemented with PSE at 0.1%, 0.2%, or 0.4% (w/w) for 8 weeks. Serum lipid profiles were determined, and derived atherogenic indices were calculated. In parallel, antioxidant activity was assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing power assays, while chemical characterization included total phenolics, crude phytosterols, and HPLC profiling of representative phenolic compounds. PSE significantly reduced serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared with the cholesterol/fat-enriched control, whereas triglycerides were not significantly altered. The LDL-C/HDL-C ratio was also reduced in PSE-treated groups, with the greatest reduction observed in the 0.1% PSE group (0.33 ± 0.04 vs. 0.56 ± 0.12 in the negative control). In addition, PSE exhibited marked antioxidant activity, with IC₅₀ values of 141.3 and 76.2 μg/mL in the DPPH and ABTS assays, respectively. Chemical analyses showed that PS contained 1098 ± 189 µg β-sitosterol equivalents/g PS and 199.3 ± 4.6 mg gallic acid equivalent (GAE)/g PS, and HPLC identified p-coumaric acid, ferulic acid, gallic acid, chlorogenic acid, daidzein, catechin, and resveratrol as representative phenolic constituents. Collectively, these findings support Kinmen peanut skin as a promising value-added source of bioactives for functional ingredient development targeting cholesterol dysregulation and oxidative processes. Full article

This paper verifies a method for determining the luminance of a pavement surface made of SMA mixtures at the design stage under laboratory conditions. Tests were conducted on surfaces made of six types of SMA mixtures with varying grain sizes (between 8 and 11 mm) and coarse aggregate types like trachybasalt with a luminance coefficient in diffused light of Q_d—53 mcd/m²/lx, gabbro with Q_d—83 mcd/m²/lx, and granite with Q_d—115 mcd/m²/lx. The effect of the glassblasting process on the changes in the luminance coefficient in diffused light (Q_d) was analyzed while simultaneously monitoring parameters describing skid resistance and macrotexture. Additionally, it was decided that tests would be performed on two sets of specimens differing in their conditioning temperatures. It was found that conditioning at −15 °C significantly improved the binder film removal process from asphalt mixture surfaces compared to those conditioned at 22 °C. Differences were recorded between individual specimens conditioned at −15 °C at the end of the glassblasting. The lowest Q_d values were found for specimens with the darkest trachybasalt aggregate (SMA 8—53.0; SMA 11—51.7 mcd/m²/lx) and the highest for specimens with the lightest granite aggregate (SMA 8—63.9; SMA 11—59.8 mcd/m²/lx). However, considering the differences in Q_d between individual coarse aggregates, the differences between specimens with these aggregates are insignificant. Glassblasting is a cheap and quick procedure for removing a binder from the surface of specimens, preparing them for luminance determination in the laboratory. It should be noted that glassblasted surfaces should not be used to determine the skid resistance and macrotexture changes at the design stage of an asphalt mixture. Full article

Background/Objectives: Residual EDTA may persist after smear-layer removal and after the application of contact sealers during setting. This in vitro study compared the effect of 1 min of pre-setting surface contact with 17% EDTA (vs. distilled water) on a calcium silicate-based sealer (AH Plus Bioceramic Sealer) and an epoxy resin-based sealer (AH Plus). Methods: Discs were prepared (N = 108) in a 2 × 2 design (n = 27/group); per group; n = 12 were used for solubility followed by eluate pH using the same specimens/eluates after 24 h immersion in distilled water; n = 12 were used to test Vickers microhardness on an independent set after setting; and n = 3 were used for SEM/EDS. Results: Data were analyzed at α = 0.05 using Kruskal–Wallis tests followed by Bonferroni-adjusted pairwise Mann–Whitney U tests for solubility and eluate pH, and one-way ANOVA was performed followed by Tukey’s post hoc test to assess the microhardness. Solubility differed among groups (p < 0.001) and was higher for the bioceramic sealer than for the resin sealer; pre-setting EDTA exposure increased solubility for the AH Plus Bioceramic Sealer (0.86 ± 0.08% to 1.30 ± 0.16%) and decreased solubility for AH Plus (0.34 ± 0.04% to 0.22 ± 0.03%) (p < 0.05). The eluate pH also differed among groups (p = 0.001) and was higher for the bioceramic sealer (≈11.7) than for the resin sealer (≈8.7–9.3), with no within-material differences (p = 0.999 and p = 0.851). Microhardness differed among groups (p < 0.001) and was higher for AH Plus (239.70–246.92 HV) than for AH Plus Bioceramic (131.72–170.83 HV); EDTA reduced microhardness only for the bioceramic sealer (p < 0.001), with no significant change for AH Plus (p = 0.475). Descriptive SEM/EDS findings suggested increased surface irregularities and lower surface Ca for AH Plus Bioceramic after EDTA exposure (12.68 to 7.31 wt%). Conclusions: Pre-setting EDTA contact therefore produced material-dependent changes in early properties and adverse surface-related effects in the calcium silicate-based sealer, supporting thorough chelator removal before obturation. Full article