Search Results (1,510)

Background/Objectives: Fungal colonization and biofilm formation on intrauterine device (IUD) strings are known to contribute to recurrent infections and decreased contraceptive efficacy. This study aims to develop a novel approach to prevent Candida reservoir and biofilm formation on IUD strings, thereby lowering the risk of IUD-associated vulvovaginal candidiasis (VVC). Methods: Cervicovaginal samples were collected from human cervix using a sterile cytobrush, avoiding microbial contamination. Cytological examination using the Papanicolaou method was performed to detect the presence of Candida. The antifungal effect of the essential oils (EOs) was determined by broth dilution and disk diffusion methods. Antifungal and biofilm inhibitory effects of Thymus zygis (Tz) EO-coated IUD strings were determined by agar diffusion and crystal violet binding assays, while fungal growth on the coated strings was assessed using Scanning Electron Microscopy (SEM) and Energy-Dispersive X-ray (EDX) analysis. Results: Tz EO exhibited significantly lower minimum inhibitory concentration (MIC ≤ 0.06 µL/mL) and minimum fungicidal concentration (MFC = 0.24 µL/mL) values compared to Melaleuca alternifolia (Ma) EO (MIC > 0.24 µL/mL, MFC = 1.95 µL/mL), along with larger zones of inhibition (ZOI) against both Candida albicans (110.0 ± 6.0 mm vs. 91.3 ± 7.0 mm) and Candida glabrata (84.0 ± 13.1 mm vs. 50.0 ± 9.2 mm), indicating a stronger antifungal potential. On IUD strings coated with 4% (40 μL/g) Tz EO in hypromellose ointment, the biofilm formation of both C. albicans and C. glabrata strains was inhibited by 58.9% and 66.7%, respectively, as confirmed by SEM and EDX. Conclusions: Tz EO-coated IUD strings effectively inhibit Candida growth, suggesting a promising natural strategy to reduce recurrent IUD-associated fungal infections. However, before these results can be translated to clinical practice, additional research is needed. Future investigations may encompass an extended number of Candida isolates, stability and release studies of the EO in relation to the formulation, toxicity to vaginal mucosa, epithelial cells and sperm motility, and the effect on vaginal microbiotia. Full article

Gout is a form of sterile inflammatory arthritis in which monosodium urate (MSU) crystals deposit and provoke a neutrophil-predominant response, primarily driven by activation of the NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Here, we show that auranofin, a Food and Drug Administration (FDA)-approved anti-rheumatic agent, exerts anti-inflammatory effects in both in vitro and in vivo models of gout. Auranofin inhibited NLRP3 inflammasome activation in human THP-1 cells and murine macrophages, leading to reduced cleavage of caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18). In MSU crystal-induced mouse models, auranofin treatment reduced paw swelling, serum cytokine levels, and tissue inflammation. Notably, auranofin suppressed neutrophil migration and decreased expression of C-X-C motif chemokine ligand 1 (CXCL1) in inflamed foot tissue and air-pouch exudates. Mechanistically, auranofin disrupted the interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) axis, a key signaling pathway promoting neutrophil recruitment. Overexpression of IL-33 abolished the anti-inflammatory effects of auranofin, highlighting the central role of IL-33 in gout pathogenesis. Together, our findings suggest that auranofin alleviates MSU-induced inflammation by concurrently inhibiting NLRP3 inflammasome activation and IL-33-mediated neutrophil recruitment, supporting its potential as a dual-action therapeutic candidate for gout. Full article

Background/Objectives: Urinary tract infections (UTIs) represent a major healthcare challenge due to antimicrobial resistance and biofilm formation. Our aim was to evaluate whether repurposed drugs and efflux pump inhibitors (EPIs) could provide alternative strategies by investigating their antibacterial, anti-biofilm, and resistance-modifying properties against Gram-negative uropathogens under varying pH conditions. Methods: Clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were tested. Minimum inhibitory concentrations (MICs) of thioridazine (TZ), promethazine (PMZ), fluoxetine (Fx), sertraline (Sr), phenylalanine arginine β-naphthylamide (PAβN), carbonyl cyanide m-chlorophenyl hydrazone (CCCP), and the glutamine uptake inhibitor V9302 were determined at pH 5–8. Biofilm inhibition was assessed by crystal violet staining, while MIC reduction assays tested antibiotic combinations. Efflux pump inhibition was examined using an ethidium bromide accumulation assay. Results: TZ reduced biofilm formation in sensitive K. pneumoniae at all pH levels and enhanced ciprofloxacin (CIP) activity, whereas PMZ showed a weaker effect, limited mainly to neutral pH. Fx and Sr exhibited pH-dependent anti-biofilm activity, with Fx particularly effective against P. mirabilis at alkaline pH. PAβN consistently decreased biofilm biomass in both sensitive and resistant K. pneumoniae and, at pH 7–8, potentiated CIP activity with a 16-fold MIC reduction in the sensitive strain. CCCP showed pH-dependent activity, with stronger effects under acidic conditions, notably in E. coli and P. mirabilis. V9302 was a potent biofilm inhibitor in K. pneumoniae and resistant E. coli and interfered with efflux activity, showing strong effects in acidic environments. Conclusions: Repurposed drugs and EPIs may be useful as antibiotic adjuvants or biofilm inhibitors in treating resistant UTIs. Full article

The rare earth (RE) aqua 4-nitrophenylacetate (4npa) complexes {[RE(4npa)₃(H₂O)₂]·2H₂O}_n (RE = La (1La), Nd (2Nd)), [Ce(4npa)₃(H₂O)₂]_n (3Ce), and {[RE₂(4npa)₆(H₂O)]·2H₂O}_n (RE = Gd (4Gd), Dy (5Dy), Y (6Y), Er (7Er), Yb (8Yb)) were synthesised by salt metathesis reactions of RE^III chlorides or nitrates with sodium 4-nitrophenylacetate Na(4npa) in aqueous ethanol. The structures of all the complexes were determined by single-crystal X-ray diffraction (SCXRD) except for RE = 4Gd, which was determined to be isomorphous with the 5Dy and 7Er complexes by X-ray powder diffraction (XRPD). All the complexes crystallise as one-dimensional polymers linked by bridging carboxylates. Complexes (1La–3Ce) have mononuclear repeating units with two coordinated waters and ten coordinate RE ions, 1La and 2Nd also have two waters of crystallization, but 3Ce has none. By contrast, complexes (4Gd–8Yb) have binuclear repeating units with a single coordinated water. Isomorphous 5Dy and 7Er have one nine coordinate and one eight coordinate metal ion, whilst isomorphous 6Y and 8Yb have two eight coordinate RE ions. In some cases, bulk powders have structures different from the corresponding single crystals. For example, bulk 1La is isomorphous with 3Ce owing to the loss of water of crystallization, and 8Yb exhibits coordination isomerism between single crystals and microcrystalline powder. Weight loss corrosion tests revealed that {[Dy₂(4npa)₆(H₂O)]·2H₂O}_n (5Dy) has the greatest inhibition efficiency (89%) of the complexes (1La–8Yb). The activities are comparable to those of the corresponding 4-hydroxyphenylacetates (4hpa) and far superior to those of 2-hydroxyphenylacetates (2hpa) and the unsubstituted phenylacetates. Whilst the coordination numbers generally decline with the lanthanoid contraction, there are deviations around 5Dy, 6Y, 7Er, and 8Yb, and the corrosion inhibition is optimised with a midrange size. Full article

This study focuses on the sandstone of the Kizil Grottoes as the research object. Sandstone samples reinforced with barium hydroxide nanoparticle (Ba(OH)₂) solutions at different concentrations were subjected to mass and deformation monitoring, wave velocity tests, triaxial shear tests, and conventional mercury intrusion porosimetry (MIP) to investigate the reinforcement mechanism and effectiveness of nano-Ba(OH)₂ on Kizil sandstone. The results indicate that after treatment with nano-Ba(OH)₂, the strength and wave velocity of the sandstone samples significantly increased, with the 15% concentration showing the optimal reinforcement effect. Nano-Ba(OH)₂ enhances the cementation between sandstone particles, alters pore morphology and size distribution, reduces capillary water rise height, and inhibits sulfate ion crystallization and recrystallization, thereby achieving the dual effects of strength reinforcement and deterioration prevention. Full article

Oral Candida infections result from the overgrowth of this opportunistic fungus in the oral mucosa. Risk factors include immunosuppression, antibiotic or corticosteroid use, xerostomia, and conditions such as diabetes mellitus. Fungal resistance in Candida spp. has become a significant challenge, especially due to the excessive use of conventional antifungals such as azoles, echinocandins, and polyenes. Therefore, this study aims to determine the spectrum of antifungal activity of Juglans regia and assess its cytotoxicity on hepatocytes. Thus, a broth microdilution test was conducted according to the CLSI (M27-A3) guidelines. After initial screening, biofilm tests were conducted using the crystal violet (CV) and metabolic activity assays (MTT). Cytotoxicity was evaluated on human hepatocytes (HEPG2). The J. regia extract showed dose-dependent antifungal activity. At a concentration of 200 mg/mL, inhibition was greater according to the CV test in Candida albicans (31%) and Candida tropicalis (30.4%), while the MTT assay indicated a greater reduction in viability in C. albicans (61%) and C. glabrata (53.5%). At 100 mg/mL, C. albicans remained sensitive (37.7% CV; 71.6% MTT), while C. krusei and C. dubliniensis showed low viability by MTT (18.4% and 11.8%, respectively). At 50 mg/mL, C. albicans remained affected (74.3% MTT), but C. krusei, C. dubliniensis, and C. guilliermondii showed the lowest viability values (≤19.4% MTT), suggesting greater sensitivity to lower concentrations. These results indicate variation in susceptibility between species, with C. albicans being consistently inhibited, while C. krusei and C. dubliniensis responded better to lower doses. The extract showed cytocompatibility when applied to human hepatoma cells (HEPG2) and therefore holds significant potential for developing a new therapeutic approach. Full article

Background: The treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections is extremely challenging due to its antibiotic resistance, and the combination of plant active ingredients with antibiotics represents a potential strategy to address this issue. Methods: We determined the combinatorial relationship between baicalin (BA) and kanamycin (KM) using the checkerboard dilution method. The antibacterial activity of the baicalin–kanamycin (BA/KM) combination was evaluated through growth curve determination assays and scanning electron microscopy (SEM). The effects of the BA/KM combination on the cell membrane and cell wall of MRSA were analyzed using reactive oxygen species (ROS) detection assays, intracellular protein leakage experiments, alkaline phosphatase (AKP) activity assays, laser scanning confocal microscopy (LSCM) observations, and molecular docking simulations. The antibiofilm activity and related mechanisms of the BA/KM combination were elucidated via crystal violet staining, MTT assay, phenol-sulfuric acid method, congo red staining, staphyloxanthin determination assays, and quantitative real-time polymerase chain reaction (qPCR). The safety of the BA/KM combination was assessed through hemolytic activity analysis, and its anti-MRSA efficacy was evaluated on lettuce. Results: BA/KM combination showed a synergistic antibacterial effect on MRSA USA300. Mechanistic studies revealed that BA may interact with amino acid residues of peptidoglycan synthetase PBP2a to hinder peptidoglycan synthesis, thereby facilitating KM penetration through the cell wall. Subsequently, BA binds to amino acid residues of the membrane transporter NorA, leading to disruption of cell membrane homeostasis and enhancing KM’s ability to induce intracellular ROS accumulation in MRSA. Furthermore, the BA/KM combination reduced MRSA biofilm formation by 77.85% and decreased the metabolic activity of biofilm cells by 42.93% through inhibiting the synthesis of biofilm components EPS and PIA. Additionally, this combination suppressed the synthesis of staphyloxanthin and downregulated the expression of agrA and agrC genes. When 1/8 MIC BA was combined with 1/4 MIC KM, the count of MRSA on lettuce surfaces was reduced by 0.88 log CFU/cm², an effect comparable to that of 0.2% (v/v) hydrogen peroxide. Conclusions: According to these findings, the BA/KM combination may offer a promising option for enhancing antibacterial efficacy through synergism, reducing antibiotic usage concentrations, and limiting MRSA transmission in fresh agricultural products. Full article

Background/Objectives: The study developed, characterized, and evaluated the toxicity, antibacterial and antibiofilm activity of quercetin encapsulated in chitosan-coated zein nanoparticles (QUER-ZNP-CH). Methods: QUER-ZNP-CH were prepared by the nanoprecipitation method and characterized by physicochemical analyses, stability (12 months), and release kinetics. Toxicity was evaluated through hemocompatibility and a Tenebrio molitor larval model. Antibacterial activity (MIC/MBC, CLSI) and antibiofilm potential (crystal violet assay) were tested against resistant Klebsiella pneumoniae strains. Results: The nanoparticles were prepared, and physicochemical analyses revealed chemical interactions, efficient encapsulation of the drug, and thermal stability. The formulations remained stable over 12 months, and the release kinetics demonstrated controlled release for 72 h. No hemotoxic profile was observed and there was 95% survival of Tenebrio molitor larvae after treatment with QUER-ZNP-CH. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of QUER-ZNP-CH revealed enhanced antibacterial activity of QUER, as indicated by a 32 to 64-fold reduction in the MIC and MBC values. The biofilm inhibition potential of QUER-ZNP-CH showed 60–100% inhibition and 25–95% eradication in concentrations from 0.12 to 62.5 μg/mL. Conclusions: Thus, this nanotechnology-based formulation suggests potential for the treatment of bacterial infections caused by multidrug-resistant K. pneumoniae strains. Full article

The coordination chemistry of a hydrazinylpyrazine-derived Schiff base ligand (L1), formed in situ from salicylaldehyde and 2-hydrazinopyrazine, with Fe(III) salts has been systematically investigated under varied synthetic conditions. Six discrete Fe(III) complexes (1a–1e and 2) were isolated and structurally characterised via single-crystal X-ray diffraction, revealing diverse coordination geometries ranging from five-coordinate pseudo-trigonal bipyramidal to six-coordinate pseudo-octahedral environments. The supramolecular architectures are governed by a rich interplay of non-covalent interactions, including hydrogen bonding, halogen bonding, and π–π stacking, which significantly influence the crystallisation pathways and final solid-state structures. Continuous shape measure (CShM) analysis highlights substantial geometric distortion in the bis-tridentate complexes, attributed to the steric and electronic constraints imposed by the ligand. Powder X-ray diffraction and infrared spectroscopy confirm the presence of multiple phases in bulk samples, underscoring the kinetic competition between crystallisation and coordination. The results demonstrate that supramolecular stabilisation of monoligated species can kinetically inhibit bis-ligation, with ligand excess and solvent polarity serving as key parameters to direct complex speciation. These findings provide insight into the delicate balance between coordination geometry, ligand strain, and supramolecular assembly in Fe(III) Schiff base complexes. Full article

In order to enhance the performance of 20# steel, this study successfully fabricated AlCoCrFeNi high-entropy alloy coatings with different WC contents (x = 0, 10, 20, 30 wt%) on its surface using plasma cladding technology. The effects of WC content on the microstructure, mechanical properties, and corrosion resistance of the coatings were systematically investigated. The results indicate that without WC addition, the coating consists of a dual-phase structure comprising BCC and FCC phases. With the incorporation of WC, the FCC phase disappears, and the coating evolves into a composite structure based on the BCC matrix, embedded with multiple carbide phases such as W₂C, M₇C₃, M_xC_γ, and Co₆W₆C. These carbides are predominantly distributed along grain boundaries. As the WC content increases, significant grain refinement occurs and the volume fraction of carbides rises. The coating exhibits a mixed microstructure of equiaxed and columnar crystals, with excellent metallurgical bonding to the substrate. The microhardness of the coating increases markedly with higher WC content; however, the rate of enhancement slows when WC exceeds 20 wt%. The hardness of 1066.36 HV is achieved at 30 wt% WC. Wear test results show that both the friction coefficient and wear rate first decrease and then increase with increasing WC content. The optimal wear resistance is observed at 20 wt% WC, with a friction coefficient of 0.549 and a wear mass loss of only 0.25 mg, representing an approximately 40% reduction compared to the WC-free coating. Electrochemical tests demonstrate that the coating with 20 wt% WC facilitates the formation of a dense and stable passive film in NaCl solution, effectively inhibiting Cl⁻ ion penetration. This coating exhibits the best corrosion resistance, characterized by the lowest corrosion current density of 1.349 × 10⁻⁶ A·cm⁻² and the highest passive film resistance of 2764 Ω·cm². Full article

Natural product-derived drugs represent a cornerstone of modern pharmacotherapy, with many serving as essential therapeutic agents across diverse medical conditions. Recent advances in structural biology have provided unprecedented insights into the molecular mechanisms underlying their biological activities. This review presents a comprehensive structural analysis of five representative natural product-derived drugs: digoxin, simvastatin, morphine, paclitaxel, and penicillin. Through an examination of high-resolution crystal structures and cryo-electron microscopy (cryo-EM) data, we elucidate how these compounds interact with their respective protein targets and modulate biological functions. The structural data reveal diverse binding mechanisms—ranging from competitive inhibition and covalent modification to allosteric modulation via conformational selection and induced fit—demonstrating how natural products achieve their therapeutic effects through precise molecular recognition. These structural insights provide a molecular foundation for understanding natural product pharmacology and offer valuable guidance for structure-based drug design approaches in developing next-generation therapeutics. Full article

Biofilm formation by pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Escherichia coli, represents a major clinical challenge due to the high resistance of biofilms to conventional antimicrobial therapy. In this in vitro study, we investigated the antimicrobial and antibiofilm activity of synthetic peptides R23I^T, R23L^P, V31K^T, R44K^S, R44K^P, V31K^S, and I31K^P against methicillin-resistant S. aureus (MRSA, SA180-F strain), S. aureus (129B), P. aeruginosa (2943), and E. coli (MG1655). In liquid medium, peptides R23L^P and R44K^S exhibited the broadest and most potent antimicrobial activity against all tested strains. On solid agar, these peptides demonstrated comparable activity, with notable effects particularly against E. coli. We further assessed the peptides’ impact on both early-stage and mature biofilms using crystal violet staining for total biomass and the MTT assay for cellular metabolic activity. Peptide R44K^S showed a strong dose-dependent inhibitory effect on early MRSA biofilm formation, while most peptides unexpectedly enhanced biofilm formation by S. aureus and E. coli. Peptides R44K^P and V31K^S at 10 mg/mL significantly reduced both biomass and metabolic activity of early P. aeruginosa biofilms. None of the peptides inhibited mature biofilm biomass across species; however, several, particularly I31K^P, significantly reduced the metabolic activity of MRSA within mature biofilms. These findings underscore the strain- and stage-specific effects of antimicrobial peptides and highlight R23L^P, R44K^S, R44K^P, V31K^S, and I31K^P as promising candidates for targeted biofilm control in vitro, especially against MRSA. Full article

The effects of Cu content on the microstructure, texture, precipitates, and magnetic and mechanical properties of 0.20 mm-thick non-oriented silicon steel (3.0% Si-0.8% Al-0.5% Mn) were systematically investigated using optical microscopy, X-ray diffraction, electron backscatter diffraction, and transmission electron microscopy. The strengthening mechanisms of Cu-bearing high-strength non-oriented silicon steel were further elucidated. Increasing Cu content inhibited grain growth and suppressed the development of the α*-fiber texture in annealed sheets, while promoting the formation of γ-fiber texture. As a result, the P_1.0/400 and B₅₀ values deteriorated. The P_1.0/400 and B₅₀ values of 1.47% Cu non-oriented silicon steel were 13.930 W/kg and 1.614 T, respectively. However, due to the solid solution strengthening effect of 0.5% Cu and partial precipitation strengthening, the R_p0.2 increased by 43 MPa. After aging treatment at 550 °C for 20 min, the P_1.0/400 values of the aged sheets slightly increased, while the B₅₀ values remained almost unchanged. In the aged sheets containing 1.0–1.5% Cu, clustered Cu-rich precipitates with average sizes of 2.71 nm and 13.28 nm were observed. The crystal structure of these precipitates transitioned from the metastable B2-Cu to the stable FCC-Cu. These precipitates enhanced the R_p0.2 of the non-oriented electrical steel to 241 MPa and 269 MPa through cutting and bypass mechanisms, respectively. A high-strength non-oriented silicon steel with balanced magnetic and mechanical properties was developed for driving motors of new energy vehicles by utilizing nanoscale Cu-rich precipitates formed through aging treatment. The optimized steel exhibits a yield strength of 708 MPa, a magnetic induction B₅₀ of 1.639 T, and high-frequency iron loss P_1.0/400 of 14.77 W/kg. Full article

Poly(butylene adipate-co-terephthalate) (PBAT) possesses mechanical properties and processing advantages comparable to low-density polyethylene (LDPE). However, its poor water vapor barrier properties (~2 orders of magnitude lower than LDPE) limit its applications in agricultural films and packaging. In this study, dodecenyl succinic anhydride (DDSA) was employed as a functional comonomer to synthesize DDSA-modified PBAT-based copolyesters (PBADT) with varying compositions via co-esterification and melt polycondensation, and the effects of the hydrophobic alkylene side chain on surface hydrophobicity, water vapor barrier property, and other physical and mechanical properties of PBADT were systematically investigated. Results indicate that the introduction of DDSA significantly enhanced the surface hydrophobicity and water vapor barrier properties of PBAT. As the DDSA content increased from 0 to 55 mol%, the water contact angle increased from 79° to 101°, and the water vapor barrier performance improved by nearly three times. Crucially, due to the chemical bonding of hydrophobic side chains to the main chains, the PBADT films exhibited excellent stability in its water vapor barrier performance under external mechanical friction. Furthermore, DDSA introduction markedly reduced haze and increased light transmittance, demonstrating improved optical clarity. On the other hand, the existence of the long alkylene side chain of DDSA also significantly inhibited the crystallization and mechanical properties of the copolyesters. Full article

The present study concentrates on the role and underlying mechanisms of in situ crystallization (employed for nanocrystal formation) in influencing the solidification microstructure and properties of aluminum alloys. By systematically analyzing the effects on α-Al refinement, silicon phase modification, and secondary phase control, as well as exploring the impact on room-temperature mechanical properties, high-temperature deformation behavior, and fatigue performance, this work reveals the potential physical mechanisms of improving mechanical properties by providing nucleation sites and inhibiting grain growth, such as fine-grain strengthening and dispersion strengthening. Moreover, stabilization of the second phase optimizes high-temperature deformation behavior, and a reduction in stress concentration improves fatigue performance. Compared with traditional microstructure control methods, in situ crystallization can achieve deeper grain refinement from micron to nanometer scale, ensuring high uniformity of grain distribution and showing good compatibility with existing processes. By defining the regulation of in situ crystallization on the microstructure and properties of aluminum alloy, the existing research provides a feasible material solution for high stress, high temperature, and high reliability. Its core significance lies in breaking through the performance bottlenecks of traditional modification technology, such as unstable refining effect, element segregation, and so on. The co-promotion of “strength–plasticity–stability” of aluminum alloys and the consideration of process compatibility and cost controllability lay a theoretical and technical foundation for the industrialization of high-performance aluminum alloys. Full article