Search Results (20,033)

Bioactive glass (BAG) S53P4 is a clinically approved bone substitute with antibacterial, osteoconductive and osteostimulatory properties. Its antibacterial effect is associated with ion release, local pH elevation and osmolality, but the precise biochemical and biophysical mode-of-action is unclear. This study investigates the antibacterial mechanism of BAG S53P4 eluates. BAG eluates, collected at 2, 4, 8, and 24 h, eradicated Staphylococcus aureus. Elemental analysis revealed an early increase in concentrations of Si and Na, a later rise in Ca, depletion of P over time and rapid loss of Mg. Membrane disturbances occurred within 5 min, evident by permeability for SYTOX, aligning with time-kill kinetics for S. aureus and Bacillus subtilis. In B. subtilis, 2h-BAG-eluate induced rapid delocalization of marker proteins for cell division and DNA repair, signaling membrane potential collapse and nucleoid condensation. Transcriptomics revealed early transcription remodeling reflecting ionic and energetic imbalance, including disruption of central metabolism, redox homeostasis, and translational stability. Scanning electron microscopy revealed severe cell surface damage and particulate deposits on S. aureus. Transmission electron microscopy showed cell envelop disruptions and cytoplasmic leakage. Energy dispersive X-ray analysis identified Si on bacterial cell surface at 4 h and intracellular accumulation in punctured, empty cells at 24 h. Overall, BAG ionic dissolution products kill bacteria through a stepwise mechanism involving membrane damage, protein delocalization and metabolic impairment, accompanied by Si deposition on bacterial surfaces and loss of Mg. This finally leads to cell wall degradation, cytoplasmic content leakage and further Si deposition on the cells and inside cell ghosts. Full article

Ten substituted quinobenzothiazinium salts were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All the compounds inhibited AChE in the IC₅₀ range of 0.03–0.658 µM, with 5,8,10-trimethyl-12H-quinolino[3,4-b][¹,⁴]benzothiazin-5-ium chloride (3d) being the most potent inhibitor, with an IC₅₀ value significantly better than that of the clinically used rivastigmine and galantamine and comparable to that of tacrine and donepezil. The IC₅₀ values for BChE inhibition ranged from 0.34 to 4.25 µM; 5,9-dimethyl-12H-quinolino[3,4-b][¹,⁴]benzothiazin-5-ium chloride (3b) exhibited the strongest BChE inhibitory activity and in general, all the investigated compounds were more potent inhibitors than rivastigmine and galantamine. Based on the calculated selectivity index values, they are rather preferential inhibitors of AChE. Cytotoxicity tests performed on normal human dermal fibroblasts (HFF-1) did not demonstrate any significant cytotoxicity under the tested conditions. The distance-oriented structure distribution for the studied molecules was related with the activity data using principal component analysis and hierarchical clustering analysis. (SAR)-based evaluation is reported to predict activity cliffs using a similarity–activity landscape index for the AChE inhibitory response values. Moreover, direct protein-mediated in silico methods were utilized to identify factors that may be relevant for quantitative (Q)SAR modeling. In practice, target-oriented molecular docking was used to organize the spatial distribution of the ligand property space for the anti-AChE system. In general, this series of alkylated quinobenzothiazinium salts with potent inhibitory activity against cholinesterases fulfills Lipinski’s rule of five based on in silico predictions and is also expected to have high absorption in the human gastrointestinal tract. All active derivatives are also expected to penetrate the blood–brain barrier, making them promising compounds for further research and possible use in Alzheimer’s disease therapy. Full article

Stain variability in digital pathology affects both cross-center diagnostic consistency and the robustness of downstream computational analysis. In this work, we formulate stain normalization as a variational inverse problem and derive a Screened Poisson Normalization (SPN) model from the steady-state reaction–diffusion mechanism underlying histological staining. In the CIE $L^{*}{a}^{*}{b}^{*}$ space, the model couples a gradient-domain fidelity term with a chromatic anchoring term, yielding a screened Poisson equation that preserves tissue morphology while enforcing color consistency. We prove that the corresponding variational problem is well-posed in $H^1\left(\Omega \right)$ and stable with respect to perturbations of the input data. We further show that the screening term induces an intrinsic localization length ${\ell }_c\sim {\lambda }_c^{-1/2}$, so that boundary perturbations decay exponentially away from tile interfaces. Based on this locality, we develop a non-overlapping tiled DCT-based spectral solver for gigapixel whole-slide images, enabling consistent tile-wise stain normalization and seamless whole-slide reassembly without heuristic boundary blending. Experiments on multi-scanner, multi-protocol, and archival-fading pathology datasets show that SPN achieves stable stain normalization with competitive chromatic alignment and strong preservation of diagnostically relevant microstructure, particularly in full-slide and tiled reconstruction settings. Supplementary experiments on synthetic pathology-like images further support the robustness of SPN under controlled color perturbations and indicate good generalization across diverse staining variations. Full article

The efficacy of the host antiviral response against Influenza A virus (IAV), a leading cause of global pandemics, hinges upon the rapid recognition of the pathogen and the prompt activation of immune mechanisms. Nevertheless, the epigenetic landscape that orchestrates this antiviral response remains largely elusive. Here, we identify histone demethylase JMJD2D as a critical regulator in defense against IAV infection. A significant upregulation of JMJD2D expression was observed clinically in response to IAV infection, indicating that JMJD2D may play a role in regulating IAV infection. Indeed, JMJD2D-deficient mice exhibit increased susceptibility to IAV, characterized by elevated viral loads, severe lung tissue damage, and reduced survival rates, suggesting that JMJD2D plays an essential role in defense against IAV infection. Consistently, knockdown or pharmacological inhibition of JMJD2D in lung cells suppressed IAV replication and the IAV-triggered innate immune response. Mechanistically, JMJD2D suppressed IAV infection by removing H3K9me3 at the promoter region of retinoic acid inducible gene-I (RIG-I) and cooperating with NF-κB to enhance the expression of RIG-I, a critical sensor for IAV RNA. This study identifies JMJD2D as an epigenetic rheostat that governs RIG-I-mediated antiviral signaling, highlighting its potential as a therapeutic target for mitigating severe IAV infection. Full article

Background: We aimed to investigate the potential synergistic effect of ivacaftor combined with colistin against Pseudomonas aeruginosa and Klebsiella pneumoniae, and to elucidate the underlying molecular mechanisms through metabolomic analysis and its reproducibility in a murine model. Methods: Six colistin-susceptible and 2 colistin-resistant cystic fibrosis P. aeruginosa isolates, along with two colistin-resistant K. pneumoniae clinical isolates, were studied. Antimicrobial susceptibility was assessed by broth microdilution, and synergy by checkerboard assay. Metabolomic profiling was conducted via LC-HRMS with statistical analysis. A murine pneumonia model, induced by intranasal administration of colistin-resistant strains, was used to validate in vivo ivacaftor and colistin synergy after 24 h. Results: No previously described colistin resistance mutations were identified in P. aeruginosa strains, whereas K. pneumoniae carried mgrB variations. Ivacaftor restored colistin susceptibility at 16 mg/L concentration, and at 1–2 mg/L led to at least a twofold reduction in colistin MIC. Metabolomic analysis of colistin-resistant P. aeruginosa strains revealed that ivacaftor induced modifications in phosphoethanolamine groups of lipid A. However, no synergistic effects were observed in the short-term in vivo pneumonia model, regardless of the administration route. Conclusions: Ivacaftor exhibited no direct antimicrobial activity against P. aeruginosa and K. pneumoniae isolates in vitro but restored colistin susceptibility through synergistic interactions. The lack of synergy in the murine pneumonia model may reflect treatment time and challenges in standardizing in vivo conditions. These findings highlight the potential of ivacaftor as an adjunct to colistin therapy, warranting further investigation into its clinical applicability. Full article

Hydrophobic carbon quantum dots (hbCQDs) with tunable photoluminescence were synthesized via a solvothermal approach and further hybridized with Rhodamine B (RhB) to extend emission into the visible range. The hbCQDs exhibit quasi-spherical morphology with an average particle size of 8 nm and predominantly disordered graphitic structure, as confirmed by TEM and XRD analyses. FTIR and XPS characterizations reveal surface functional groups including C–N, C=O/C–O, and S–H, which govern the photoluminescence properties. Pure hbCQDs display blue emission at 453 nm under excitation, with a quantum yield (QY) of 6.2%. Incorporation of RhB leads to dual-emission behavior: the surface-state emission remains in the blue region, while molecular-state emission from RhB appears in the orange-red region. The 0.2 mL RhB–CQD composite exhibits optimal properties, including a QY of 13% and a production yield of 82%, emitting white light under 365 nm UV excitation. Increasing RhB loading to 0.4 mL results in a shift in emission peaks and a reduced QY (<9%), with weaker orange fluorescence. These findings demonstrate that controlled RhB hybridization effectively tunes the emission spectrum of hbCQDs, offering a simple and reproducible strategy to achieve dual-color and white-light emission. The optimized hbCQDs/RhB composites hold significant potential for applications in hydrophobic media-compatible organic optoelectronics, light-emitting devices, and bioimaging. Full article

Three Ni-based composite coatings with varying TiCN/h-BN contents were fabricated on the surface of Ti-6Al-4V (TC4) alloy by laser cladding. The coatings were formulated with a fixed 15% TiCN and 0%, 2% and 5% h-BN, corresponding to L1–L3 coatings. The microstructure and phase composition were fully characterized and investigated. In addition, the microhardness and wear resistance of the coating were evaluated too. The analysis revealed that the L1–L3 coatings primarily consisted of Ti, TiNi, Ti(C, N) and TiAl₃ phases. Microstructural analysis indicated that the top region of the coating was predominantly composed of granular crystals, while the middle and bonding regions featured a combination of dendrites and white granular crystals. The average microhardness values for the L1–L3 coatings were measured at 1203.8, 1216.8 and 1235.5 HV_0.2, respectively, while the corresponding wear volumes were 0.098, 0.094 and 0.086 mm³. As the h-BN content increased, the microstructure of the Ni-based composite coating became finer and finer. Some TiB particles were also generated in the coating, which made the average microhardness and wear resistance increase gradually. Notably, the coating with 5% h-BN demonstrated the highest average microhardness and optimal wear resistance. Compared with the substrate, 5% h-BN increased the wear resistance of the substrate by 47.6%. The primary wear mechanism observed was abrasive wear. Full article

Growing environmental and food security concerns have increased interest in circular strategies to valorize agri-food by-products. Sunflower-seed press cake (SSPC), a protein-rich residue from oil extraction, is largely underutilized despite its high nutritional and functional value. This study aimed to develop a fermented plant-based food prototype (PBFP) from SSPC using Lactococcus lactis B12 and Penicillium camemberti, evaluating microbiological safety, chemical characteristics, and sensory acceptability. A blend containing 40% SSPC and 60% water was autoclaved, inoculated, and ripened for 4 weeks under controlled temperatures. Microbial counts, pH evolution, free amino acids, biogenic amines, volatile organic compounds (VOCs), cyclopiazonic acid (CPA) content, and sensory attributes were evaluated using cultural techniques, HPLC, HS-SPME/GC-MS, LC–ESI–MS/MS (QTRAP 4000), and sensory evaluation. L. lactis efficiently acidified the matrix (pH ≈ 4.5–4.9), ensuring microbial food safety, with high LAB counts (~10⁹ CFU/g) and absence of pathogens (Listeria monocytogenes and Salmonella spp.) and hygienic markers < 2 log CFU/g (B. cereus, E. coli, and Enterobacteriaceae). Free amino acids decreased during fermentation, and no histamine or tyramine was detected. VOC analysis revealed diacetyl, acetoin, 2,3-butanediol, and 1-octen-3-ol, contributing to mild dairy-like notes. CPA was detected at 0.48 ng/g, well below levels reported in cheeses. Sensory evaluation showed no significant differences in overall intensity between inoculated and control blends, although qualitative descriptors indicated subtle changes in aroma and texture. These results demonstrate the feasibility of safely producing a fermented plant-based prototype from SSPC. Future studies should explore longer ripening times, additional microbial consortia, and strategies to enhance texture and aroma complexity. Full article

Background: Antimicrobial resistance is a One Health problem driven by the intricate interactions across human, animal, and environmental interfaces that enable microbial exchange and movement of mobile genetic elements encoding resistance and virulence. This study investigated the genomic epidemiology of ESBL and non-ESBL Escherichia coli across One Health interfaces in Oman. Methods: This prospective cross-sectional study analyzed 295 non-duplicate Escherichia coli isolates derived from 104 clinical, 173 animal [diseased (123) and healthy (50)], 14 sewage and four water sources. Antimicrobial susceptibility testing was performed phenotypically, and a representative subset of 50 ESBL and non-ESBL Escherichia coli from the three interfaces underwent whole genome sequencing to determine MLST, phylogroups, resistance genes, virulence determinants and plasmid replicons. Results: ESBL prevalence was highest in human isolates (73%), followed by sewage (28.6%) and animals (16.3% diseased; 8% healthy). blaCTX-M-15 predominated in humans, whereas blaCTX-M-55 dominated in animals and sewage, suggesting ecological partitioning with partial overlap. Quinolone resistance was lowest in the animal interface. Sewage isolates harbored the most complex resistome, including rmtB and plasmid-mediated quinolone resistance genes. MLST analysis revealed high diversity in human isolates, including globally recognized ExPEC lineages (ST10, ST38, ST73, ST127, ST131), while ST224 dominated in animals with evidence of possible spillover to humans. ST167 was confined to sewage, consistent with environmental maintenance of high-risk clones. Phylogroup structuring showed predominance of A, B2 and D among human isolates and A, B1, and E among animal and sewage isolates. Virulence profiling demonstrated broader virulome diversity in humans, but shared core determinants (fimH, sitA, traT) across all domains. IncFIB(AP001918) was the dominant plasmid replicon, particularly among ESBL isolates, underscoring its role in horizontal gene dissemination. Alarmingly, mutation in pmrB (V161G) was identified in a healthy animal isolate, pointing to a need for greater colistin restriction in animal husbandry. Conclusions: This study highlights plasmid-mediated resistance and shared virulence determinants linking reservoirs; although AMR profile was quite distinct across the three interfaces, human isolates demonstrated greater resistance than animal isolates, suggesting healthcare-driven AMR in Oman. Continued integrated genomic surveillance is essential to monitor gene flow and inform coordinated antimicrobial stewardship strategies. Full article

This work analyses the influence of hydrothermal treatment (steaming) on the color stability and photochemical degradation of beech wood (Fagus sylvatica L.) with false heartwood under the influence of UV radiation. Samples in the native state and after steaming at temperatures of 105 °C (Mode I) and 120 °C (Mode II) were exposed to simulated aging in a Xenotest device for 360 h. Color changes were assessed in the color space CIE L*a*b* and surface chemical changes using ATR-FTIR spectroscopy. The results showed that unsteamed wood darkens significantly under the influence of UV radiation (ΔL* = −10.2), while wood steamed at 120 °C shows the opposite trend—lightening (ΔL* = +8.8). The color difference ΔE* reached values of 12 to 16 units for unsteamed wood, which indicates a complete color change. Steaming at higher temperatures successfully homogenizes the color of the sapwood and false heartwood and ensures their subsequent uniform visual aging. Full article

The Fukushima nuclear accident highlighted that evacuation-related psychosocial harm can outweigh direct radiation risks, underscoring the need to define the health impacts of chronic low-dose-rate (LDR) radiation and evidence-based thresholds for intervention. This study investigated the effects of continuous, postnatal LDR gamma irradiation (1.2 mGy/h, cumulative dose: 5 Gy) in male mice. While no changes in body weight, hippocampal neurogenesis, or major glial and neuronal populations were observed, persistent DNA damage (γ-H2AX foci) in dentate gyrus granule cells occurred in both irradiated male and female mice. Irradiated male mice developed anxiety-like behaviour, a phenotype not observed in a previously published study of female mice subjected to an identical irradiation protocol. Molecular profiling revealed two novel, dysregulated miRNA/mRNA axes in the hippocampus linking DNA damage to behaviour: a maladaptive miR-466i-5p/Tfcp2l1 pathway associated with genomic instability, and a potentially adaptive miR-101a-5p/BMP6 pathway promoting neuronal survival. Venn analysis further identified miR-124b-3p and novel-miR489-3p as conserved exposure biomarkers, altered in both the hippocampus and blood of irradiated animals. Our results show that a high cumulative dose of chronic LDR induces markedly less severe hippocampal pathology than has been reported for equivalent acute doses. These findings support the concept of dose-rate-dependent threshold dose and contribute to the evidence base for developing countermeasures following nuclear incidents or other radiation exposures. Full article

Synthetic dyes frequently persist through conventional wastewater treatment, motivating the use of advanced oxidation processes capable of breaking down these stable molecules. Metal-doped carbon dots (CDs) offer a tuneable platform for catalytic dye degradation in water, although their performance varies strongly with operating conditions. The aim of this work was to determine how temperature, H₂O₂ dosage, and pH influence the catalytic behaviour of Fe-, Cu-, Zn-, and Mg-doped CDs during the degradation of methylene blue (MB) and rhodamine B (RB), optimised using a Taguchi L27 orthogonal array design. Temperature and oxidant loading were the dominant factors: higher temperatures accelerated reactions through Arrhenius-type kinetics, while increasing H₂O₂ availability improved removal until excessive levels began to suppress •OH generation. Across all condition sets, apparent rate constants spanned 7.0 × 10⁻⁴–2.65 × 10⁻² min⁻¹, with t₅₀ values of 26–217 min and t₉₀ extending from ~86 min to >700 min; final decolourisation ranged from ~17% to nearly 100%. pH played a secondary role, mainly affecting dye speciation and surface adsorption. Dopant identity shifted the optimum operating region for each catalyst: Fe- and Cu-CDs achieved complete or near-complete removal of both dyes at pH 7 and 50 °C with relatively low H₂O₂ dosage (0.5–1.0 mL); Zn-CDs reached equivalent performance at pH 7 and 25 °C but required higher oxidant loading (1.5 mL of H₂O₂), reflecting their photo-induced rather than thermally driven activation mechanism; Mg-CDs performed comparably under the same conditions as Fe- and Cu-CDs. The resulting condition–catalyst map highlights the operating regimes that maximise efficiency while minimising chemical input, providing a practical framework for selecting carbon-dot-based catalysts for water treatment applications. Full article

Background: Dental caries remains one of the most prevalent oral diseases worldwide, largely driven by the virulence of Streptococcus mutans. Although plant phenolics from green tea and pomegranate are known for their antimicrobial properties, their molecular mechanisms of action against key S. mutans virulence targets remain insufficiently characterized. Aim: This study investigated the antibacterial and anti-virulence properties of Viroelixir, a phenolic-rich formulation derived from green tea (Camellia sinensis) and pomegranate (Punica granatum), against S. mutans, with particular emphasis on predictive molecular docking interactions with critical virulence-associated proteins. Methods: Viroelixir phytochemical composition was characterized by LC–MS using a C18 reverse-phase column and negative electrospray ionization mode. Antibacterial activity was evaluated using growth kinetics, agar plating, and crystal violet assays. Acidogenicity, hemolytic activity, and biofilm formation were assessed using pH modulation, hemolysis assays, SEM, and biofilm biomass quantification. Virulence gene expression was analyzed by RT-qPCR. In silico molecular docking was performed to explore potential interactions between major LC–MS-supported phenolic constituents and S. mutans virulence proteins, including glucosyltransferase B (GtfB), LuxS, and SpaP. Biocompatibility was evaluated in human gingival epithelial cells. Results: The LC-MS analysis revealed a complex mixture of phenolic compounds consistent with catechins and ellagitannins. Compound identification was considered tentative and based on mass spectral range and chromatographic behavior. Viroelixir significantly inhibited S. mutans growth, acid production, hemolytic activity, and biofilm formation in a concentration-dependent manner. Key virulence genes were markedly downregulated. Docking analyses suggested stable binding of selected phenolics—particularly punicalagin, catechin, and epigallocatechin—within the active sites of GtfB, LuxS, and SpaP. Importantly, Viroelixir showed no cytotoxic effects on gingival epithelial cells. Conclusions: Viroelixir exerts potent antibacterial and anti-virulence effects against S. mutans through a multi-target mechanism combining transcriptional suppression and predictive molecular inhibition of virulence proteins, supporting its potential as a safe, natural therapeutic for caries prevention. Full article

Biological E’s BEVAC^® is a recombinant DNA hepatitis B vaccine that has been used in India for more than a decade in routine early-life immunization and has recently been prequalified by the World Health Organization (WHO). This multicentre, single-blind, parallel-group, randomized phase IV trial, conducted at seven study sites in India, compared the immunogenicity and safety of BEVAC^® with a licensed comparator vaccine (GeneVac-B^®, Serum Institute of India Pvt. Ltd, Pune, India.) in healthy term neonates and infants. Participants received three 0.5 mL doses administered intramuscularly at birth (within 24 h), 6 weeks of age, and 14 weeks of age. The primary endpoint was seroprotection (anti-HBs IgG ≥10 mIU/mL) at 28 days after the third dose (Day 126), compared using a non-inferiority margin of −10%. Secondary endpoints included safety and tolerability outcomes through Day 126. A total of 468 neonates were randomized (234 per group), of whom 44% were female. At Day 126, seroprotection rates were 98.2% (95% CI: 95.39, 99.50) with BEVAC^® and 99.1% (95% CI: 96.78, 99.89) with the comparator; the between-group difference was −0.9% (95% CI: −3.09, 1.24), meeting the prespecified non-inferiority criterion. Solicited adverse events within 7 days after any dose occurred in 29.1% (95% CI: 23.3, 35.3) of BEVAC^® recipients and 35.0% (95% CI: 28.9, 41.5) of comparator recipients, most commonly pyrexia, injection-site pain, and swelling; all were mild-to-moderate. No serious adverse events were reported. BEVAC^® demonstrated non-inferior immunogenicity to the licensed comparator and a comparable safety profile. Full article

Maize biomass production and quality are influenced by numerous factors, including fertilization, soil characteristics, and climatic conditions. The aim of our study was to evaluate how different fertilization treatments ((1) Control, (2) farmyard manure (FYM), (3) FYM with added mineral nitrogen (FYM + N), and (4) FYM with added NPK mineral fertilizers (FYM + NPK)) affect the biomass yield and quality parameters (crude protein (CP), fiber content (FC), neutral detergent fiber (NDF), starch content (STR), organic matter digestibility (OMD), and neutral detergent fiber digestibility (DNDF)) of silage maize under various soil and climatic conditions in the Czech Republic (Caslav—degraded Chernozem, Ivanovice na Hané–Chernozem, Lukavec–Cambisol). The experiment was conducted from 2020 to 2023. Additionally, the study analyzed the effects of fertilization on soil chemical properties (pH, P, K, Ca, Mg, C, N). The highest average biomass yields were recorded in Ivanovice (23.8 t ha⁻¹, A), followed by Lukavec (19.7 t ha⁻¹, B) and Caslav (18.1 t ha⁻¹, B). Comparing fertilizer treatments, no significant differences were observed among FYM, FYM + N, and FYM + NPK; however, all three treatments significantly outperformed the Control at all sites. Conversely, fertilization did not affect the quality parameters. For silage maize, FYM represents the optimal fertilization strategy, providing yields and quality comparable to the combined application of mineral N, P, and K, which are more costly (in terms of purchase and application) and, under certain conditions, may negatively impact the environment. Nevertheless, the application of mineral fertilizers increased soil nutrient content, thereby improving conditions for subsequent crops. Full article