Search Results (2,075)

Arthrogenic muscle inhibition (AMI), neurophysiological suppression of voluntary quadriceps activation triggered by joint effusion and inflammation, is consistently initiated within hours of any form of knee surgery. If not actively counteracted during the first two postoperative weeks, AMI may drive a cascade of neuromuscular, morphological, and biomechanical deficits that can persist for years, substantially increasing the risk of post-traumatic osteoarthritis, reinjury, and long-term functional disability. Emerging evidence indicates that preoperative patient-related factors, including baseline quadriceps strength, age, body mass index, and physical fitness, further modulate the rehabilitation response and should be considered in planning early postoperative protocols. This narrative review, which was not designed as a systematic review or meta-analysis and therefore does not include formal quality assessment or pooled statistical analysis, evaluates evidence for seven early-phase (0–2 weeks postoperative) knee muscle activation interventions: neuromuscular electrical stimulation (NMES), isometric quadriceps exercise, blood flow restriction (BFR) training, electromyographic (EMG) biofeedback, open and closed kinetic chain (OKC/CKC) exercise, cryotherapy, and continuous passive motion (CPM). Findings are synthesized against six clinically relevant dimensions, safety in the 0–2 week window, home-based usability, capacity to overcome AMI, requirement for volitional effort, objective monitoring capability, and progressive resistance, to characterize a consistent pattern: no single existing modality simultaneously meets all combined requirements for home deployment, volitional engagement, objective monitoring, and progressive resistance from postoperative day one. This collective unmet need provides direction for future device development and clinical research. Full article

Background/Objective: Bisphenol AF (BPAF), a fluorinated analogue of bisphenol A, is an environmental contaminant associated with hepatotoxicity and metabolic disruption. However, the systematic molecular mechanisms linking early transcriptional events to metabolic dysfunction in the liver remain poorly defined. The aim of this study is to elucidate the association between BPAF exposure and hepatic lipid accumulation by integrating transcriptomics, cellular metabolomics, and targeted phenotypic assays. Methods: We performed RNA-sequencing on livers from mice exposed to BPAF (0.1–10 mg/kg/day, 28 days), and performed non-targeted metabolomics on AML12 murine hepatocytes co-cultured with RAW264.7 macrophages in a Transwell system (0–2500 nM BPAF, 48 h). Key metabolic pathways were identified through integrated bioinformatics and validated using enzymatic assays, qRT-PCR, Western blotting, and phenotypic staining (lipid droplets, ROS). Results: Multi-omics integration revealed significant disruption of PPAR signaling and the tricarboxylic acid (TCA) cycle. A striking dose-dependent accumulation of succinate was observed in exposed cells, concomitant with a significant inhibition of succinate dehydrogenase (SDH) activity (52% reduction at 2500 nM, p < 0.001). Transcriptomic data confirmed the downregulation of mitochondrial fatty acid β-oxidation genes. Phenotypic validation indicated that BPAF exposure is associated with oxidative stress, pro-inflammatory cytokine release (TNF-α, IL-6), and pronounced intracellular lipid droplet accumulation in hepatocytes. Conclusions: This study suggests that BPAF exposure is associated with SDH dysfunction, TCA cycle arrest, and lipid dysregulation. Whether BPAF directly inhibits SDH or acts through upstream mitochondrial targets warrants further structural and kinetic investigation. Full article

Background/Objectives: Anthracycline-induced cardiotoxicity remains a major challenge in cancer treatment, and researchers are showing interest in artificial intelligence (AI) to improve the prediction and detection of cancer therapy-related cardiac dysfunction (CTRCD). Current surveillance strategies rely mainly on left ventricular ejection fraction and, more recently, global longitudinal strain. Methods: The present study was designed to evaluate cardiac performance in a rat model of doxorubicin-induced cardiotoxicity and empagliflozin-mediated cardioprotection using a machine learning-based analytical framework. Eighteen adult male Sprague–Dawley rats were assigned to five experimental groups. We aimed to quantify ventricular wall dynamics and contractility using an advanced image-processing and object-detection model that has not been previously used to distinguish normal from impaired cardiac kinetics. During real-time recording, simultaneous electrocardiogram monitoring was performed, enabling direct correlation between deep learning-based ventricular wall motion metrics and cardiac electrical activity. The cardioprotective effects of empagliflozin were further validated by immunofluorescence staining (cTnI, vimentin, α-SMA, and Cx43) of rat cardiomyocytes and paraffin-embedded cardiac tissue, demonstrating attenuation of cellular injury and structural remodeling. Results: The integrated analysis of cardiac kinetic patterns derived via machine learning distinguishes not only extreme cardiotoxicity, but also tracks a graded pattern consistent with ECG-derived severity and treatment-related functional preservation. These findings indicate that the algorithm captures the gradient of empagliflozin’s cardioprotective effect within this internally validated preclinical setting. Additionally, immunofluorescence results validated the benefits of SGLT2 inhibition on myocardial integrity. Conclusions: The novelty of the present work lies at the intersection of advanced cardiac kinetic analysis using AI, preclinical modeling, and SGLT2-mediated cardioprotection in cardio-oncology. Full article

CO₂ methanation with renewable hydrogen is a promising strategy for carbon valorization and synthetic natural gas (SNG) production. However, the molecular mechanisms behind catalyst-dependent adsorption and mass transport in zeolite-confined spaces are still not fully elucidated. Herein, we performed comparative molecular simulations on HZSM-5, Ni/ZSM-5 and Ru/ZSM-5 by combining density functional theory (DFT), grand canonical Monte Carlo (GCMC) and molecular dynamics (MD) methods, aiming to clarify the thermodynamic and mass transport mechanisms of reactant enrichment and product desorption in CO₂ methanation. The electronic structures of the three systems were systematically evaluated via Mulliken charge analysis, differential charge density mapping, and frontier molecular orbital calculations. We further quantified the adsorption thermodynamics and diffusion kinetics of reactants and products, focusing specifically on the effects of temperature and framework Si/Al ratio for Ni/ZSM-5. The results show that Ni doping greatly modulates the local electronic environment of the ZSM-5 framework, enhancing the adsorption of CO₂ (−121.9 kJ·mol⁻¹) and H₂ (−81.6 kJ·mol⁻¹) and weakening the adsorption of CH₄ and H₂O. A higher Si/Al ratio reduces CO₂ adsorption capacity, while elevated temperatures inhibit reactant adsorption and lower the diffusion selectivity of CH₄. This demonstrates that moderately low temperatures and moderate Si/Al ratios can optimize the adsorption and diffusion behaviors of reactants and products. This work provides molecular-level insights into the adsorption and diffusion behaviors of Ni/ZSM-5 and offers theoretical references for the rational development of high-performance CO₂ methanation catalysts. Full article

Background/Objectives: Fraxetin (7,8-dihydroxy-6-methoxycoumarin), a coumarin constituent of Cortex Fraxini (Qinpi) used in traditional Chinese medicine, is metabolised mainly by UGT1A9, but its potential to inhibit UGT enzymes and cause herb–drug interactions (HDIs) is largely unstudied. Methods: Fraxetin and four related coumarins were screened against 11 recombinant human UGTs; isoforms inhibited ≥80% underwent full kinetic analysis with 4-methylumbelliferone as probe. Binding was examined by molecular docking on AlphaFold structures with PLIP, triplicate 100 ns molecular dynamics, and MM/GBSA and MM/PBSA free-energy calculations, and interaction risk by FDA 2020 in vitro–in vivo extrapolation (IVIVE). Results: Fraxetin alone inhibited both UGT1A1 and UGT1A9 by >80% and was characterised in detail, acting as a mainly competitive mixed-type inhibitor (UGT1A1 IC₅₀ 15.99 μM, K_i 8.32 μM; UGT1A9 IC₅₀ 8.44 μM, K_i 5.90 μM). A structure–activity comparison identified a dual-element pharmacophore comprising the C-6 methoxy group and the 7,8-dihydroxycoumarin aglycone. MM/GBSA favoured UGT1A9 over UGT1A1 (ΔΔG = −4.06 kcal/mol, p = 0.005), concordant with the kinetic ranking. IVIVE predicted a borderline systemic signal (R₁ > 1.02) but an intestinal R_1,gut approximately five- to seven-fold above the high-risk threshold of 11 after capping the luminal concentration at fraxetin aqueous solubility. Conclusions: This is the first characterisation of fraxetin as a moderate-potency inhibitor of UGT1A1 and UGT1A9 and points to a previously under-recognised herb–drug interaction risk concentrated in the intestinal lumen rather than systemically; the finding constitutes an interaction signal requiring clinical confirmation rather than an established risk. Full article

Invasive candidiasis remains a major cause of morbidity and mortality worldwide, with increasing relevance of non-Candida albicans species, particularly Pichia kudriavzevii, which is associated with high mortality and intrinsic resistance to fluconazole. This study evaluated the effect of voriconazole (VRC) on P. kudriavzevii growth, biofilm formation, and metabolic activity under different nutritional conditions. Planktonic growth and biofilm development were analyzed in Sabouraud dextrose broth (SDB), RPMI-1640, and RPMI-1640 supplemented with glucose (20 g·L⁻¹). Antifungal activity was assessed by optical density (OD₅₇₀) and XTT reduction assays, and biofilm morphology was examined by light microscopy. Glucose consumption was also determined during growth. VRC showed dose-dependent inhibition in SDB, reducing growth and biofilm metabolic activity by up to 94% and 98%, respectively. In contrast, in RPMI-1640, inhibition was significantly lower (≤27% growth and ≤77% biofilm reduction). Glucose supplementation partially restored antifungal susceptibility and increased biofilm metabolic activity. Growth kinetics confirmed VRC-induced delays in proliferation and impaired glucose utilization. These results demonstrate that VRC activity against P. kudriavzevii is strongly dependent on environmental nutrient availability, particularly glucose, which modulates fungal metabolism, biofilm development, and antifungal susceptibility, highlighting the importance of standardized antifungal susceptibility testing conditions and the role of metabolic state in azole efficacy. Full article

Glycolysis of poly(ethylene terephthalate) (PET) offers a promising route for chemical recycling, yet conventional homogeneous catalysts often suffer from low selectivity, severe side reactions (especially diethylene glycol, DEG formation), and detrimental metal residues that compromise the quality of recycled products. To address these challenges, we herein develop dipotassium phenylphosphonate (PPOA-K) as an efficient homogeneous catalyst for PET glycolysis. Under optimized conditions (1 wt% catalyst, 197 °C, EG/PET mass ratio 3:1, 90 min, atmospheric pressure), PPOA-K achieves 100% PET depolymerization and a high BHET yield of 86.0%, and the reaction follows apparent first-order kinetics with an activation energy of 70.3 kJ·mol⁻¹. Beyond its high catalytic activity, PPOA-K effectively suppresses the acid-catalyzed etherification of ethylene glycol to DEG, a common side reaction that reduces monomer purity and degrades recycled polyester properties. Remarkably, the trace amount of PPOA-K remaining in the recovered BHET (17.3 ppm) is not detrimental; instead, it continues to inhibit DEG formation during repolymerization and acts as a thermal stabilizer, improving the melting point and thermal stability of recycled PET. The advantages of PPOA-K are further demonstrated in a partial (in situ) glycolysis–repolymerization process, where it reduces the DEG content in the final rPET to 1.78% (vs. 2.25% for conventional Zn(OAc)₂), yielding rPET with a higher melting point, higher crystallinity, and better color. This work demonstrates that dipotassium phenylphosphonate uniquely combines high catalytic activity, side reaction suppression, and beneficial residue effects, offering a new catalyst design strategy for high-quality PET recycling. Full article

Mercury (Hg) is a global pollutant that poses a serious threat to ecosystems and human health. Biochar has shown great potential for mercury removal due to its porous structure and abundant surface functional groups. However, redox-active moieties on biochar can reduce adsorbed Hg²⁺ to volatile Hg⁰, leading to secondary mercury dispersion. To suppress this reduction, this study proposes a strategy of co-pyrolyzing coal gangue with rice husk to prepare composite biochars (RHB/CG), leveraging the abundant metal oxides in coal gangue to tailor the surface chemistry of biochar. The materials were characterized by FTIR, Raman, and XRD; static adsorption, mercury speciation analysis, and kinetic experiments were conducted. The results show that coal gangue incorporation significantly enhances the Hg²⁺ adsorption capacity of biochar, with the equilibrium adsorption capacity calculated by the pseudo-second-order kinetic model, increasing from 20.6 mg/g for pristine RHB to 38.7 mg/g for RHB/CG-1:1. More importantly, RHB/CG composites effectively suppress the reduction of Hg²⁺ to Hg⁰, and the amount of Hg⁰ accumulated in the system is 57.1% lower than that of pristine RHB. Mechanistic studies reveal that coal-gangue-derived basic functional groups (e.g., C–O–C, Si–O–M) inhibit reduction via sequestering Hg²⁺ through coordination and disruption of electron transfer pathways. PHREEQC simulations (pe = 6.0) confirm the decreased tendency of Hg²⁺ reduction to Hg⁰ with increasing pH, in good agreement with the experimental results showing reduced Hg²⁺ reduction. The corresponding results provide a green and sustainable solution for mercury-contaminated water and soil remediation. Full article

Background/Objectives: Oral candidiasis is an infection of the oral cavity caused by Candida albicans. Mucoadhesive buccal films could adhere to the buccal mucosa for prolonged periods, improving the therapeutic outcomes of patients with oral candidiasis. This study aimed to develop and evaluate the properties of fluconazole containing sodium alginate/methylcellulose-based buccal films for potential treatment of oral candidiasis. Methods: Drug-polymer compatibility was investigated using FT-IR spectrophotometry. Three optimised fluconazole films (F1 to F3) containing 1–1.6% sodium alginate and methylcellulose (1.6%) were formulated using the solvent-casting method. Their physicomechanical properties were characterised using standard protocols. Drug content and in vitro drug release profiles were evaluated using UV-visible spectroscopy; in vitro/ex vivo mucoadhesion studies were conducted using the shaking water bath technique, and their antifungal activity against Candida albicans was evaluated using the agar ditch method. Results: FT-IR data analysis revealed that sodium alginate, methylcellulose and fluconazole were compatible in the films. The films were off-white, smooth, peelable, thin, with satisfactory pH values, folding endurance, drug content, excellent zones of inhibition against Candida albicans (40 mm), controlled drug release profile (3.6–4.1 mg/cm² after 6 h), and they displayed Korsmeyer–Peppas drug release kinetics. Film F3 containing 1.6% sodium alginate and 1.6% of methylcellulose exhibited superior swelling index (70 ± 1%), tensile strength (0.68 ± 0.04 MPa) and in vitro/ex vivo mucoadhesion time (5.5 ± 0.3 h; 2.3 ± 0.3 h) relative to other studied films. Conclusions: The sodium alginate content of the films influenced their tensile and mucoadhesive properties. Film F3 was the most promising formulation for potential treatment of oral candidiasis. Full article

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

Temperature and pressure are critical controlling parameters in the in situ conversion process (ICP) of oil shale. Clarifying the mechanisms governing organic matter pyrolysis is essential for reliably extrapolating laboratory findings to geological conditions. This review systematically summarizes the effects of temperature and pressure on shale pyrolysis and on hydrocarbon generation kinetics. Temperature is the primary factor controlling pyrolysis rates and product distribution, with an optimal temperature window enhancing shale oil yield while suppressing secondary cracking. Low heating rates favor thorough pyrolysis, although their influence on reaction pathways is generally overlooked in current kinetic models. Pressure effects are stage-dependent: during organic matter conversion, they are minor, whereas, in the product expulsion stage, high pressure inhibits hydrocarbon expulsion, prolongs residence time, and promotes secondary cracking, thereby reducing overall oil yield while increasing light fractions. Discrepancies in reported pressure effects arise from variations in experimental systems, sample forms, and medium conditions. The coupling of temperature and pressure is synergistic rather than additive. Given that current kinetic models largely neglect pressure and heating-rate effects, and that temperature–pressure coupling mechanisms remain unclear, future research should focus on thermal simulation experiments across wide ranges of pressures and heating rates, complemented by ReaxFF molecular dynamics to elucidate reaction pathways and guide kinetic model development. Further in situ experiments under high-temperature and high-pressure conditions are needed to characterize coupled pore evolution and fluid migration. Ultimately, integrated thermo-hydro-mechanical-chemical (THMC) models should be developed to capture hydrocarbon generation, retention, and expulsion, providing a robust theoretical framework for optimizing ICP technology. Full article

Biosurfactants are surface-active microbial molecules with increasing industrial relevance as sustainable alternatives to synthetic surfactants. Among them, lipopeptides produced by Bacillus species, particularly surfactin, exhibit strong interfacial activity and biological functionality. In this study, rhizospheric soils from the La Araucanía region, Chile, were explored as a source of biosurfactant-producing bacteria. Eighteen strains were isolated, and two high-performing strains, Solo 1 and Solo 4, were identified as Bacillus amyloliquefaciens and Bacillus subtilis, respectively. Both strains harbored the srfAA gene and produced surfactin isoforms confirmed by MALDI-TOF MS. Kinetic analysis revealed distinct production profiles, with Solo 1 reaching a maximum of 90 mg L⁻¹ at 24 h, whereas Solo 4 showed continuous production up to 224.4 mg L⁻¹ at 72 h. Both biosurfactants exhibited high emulsification capacity (>80%) and stability across wide ranges of temperature, pH, and salinity. Importantly, cell-free supernatants from both strains showed antibacterial and antibiofilm activity against Staphylococcus aureus, with Solo 4 reaching 81% biofilm inhibition. In addition, surfactin-enriched extracts inhibited the pathogenic bacterium Pseudomonas syringae and the filamentous fungus Fusarium oxysporum, with Solo 4 consistently showing stronger antimicrobial performance. Overall, these findings identify Solo 4 as a promising native Bacillus strain for future development of biosurfactant-based systems aimed at antimicrobial control, biofilm management, agricultural pathogen suppression, surface sanitation, and environmentally compatible biotechnological processes. Full article

The performance of drug-loaded electrospun nanofibres is governed not only by drug content but also by the spatial distribution of the drug within the fibre matrix, which determines release kinetics and biological response. Here, we demonstrate that dose-dependent surface crystallisation of dexamethasone (DEX) in electrospun polycaprolactone (PCL)/gelatin nanofibres controls drug release behaviour and subsequent macrophage-mediated inflammation. Nanofibre mats containing 0, 1, and 2 wt% DEX (PG0, PG1, PG2) were fabricated and systematically characterised. Scanning electron microscopy revealed a change from homogeneous fibres (PG0) to surface-decorated crystalline domains with increasing drug loading, which indicates a supersaturation-driven phase separation during electrospinning. This morphological evolution directly governs the transport behaviour: PG2 exhibits a pronounced burst release due to surface-localised drug, whereas PG1 shows a balanced release profile with both surface-accessible and matrix-embedded drug fractions. Release characteristics result in different biological outcomes. PG1 and PG2 strongly inhibit pro-inflammatory cytokines (TNF-α and IL-6) in LPS-stimulated macrophages (~70–75% reduction), confirming retained drug bioactivity. However, higher drug loading (PG2) leads to lower fibroblast viability and compromised mechanical integrity. Importantly, PG1 shows a desirable balance of controlled drug release, cytocompatibility (>90% viability) and mechanical performance (~8 MPa) with effective anti-inflammatory activity. Degradation studies also show controlled structural evolution without destabilisation upon pH change, demonstrating suitability for wound environments. These results reveal surface crystallisation as an important design parameter for electrospun drug delivery systems and demonstrate that optimal therapeutic performance is controlled by intermediate drug loading, not maximum loading, providing a mechanistic framework for the rational design of immunomodulatory wound dressings. Full article

Hierarchical ZnO–SiO₂/carbon composites (C-Zn1, C-Zn2, C-Zn3) were synthesised via the carbonisation of resorcinol–formaldehyde gels in the presence of ZnO-modified fumed silica, and characterised by N₂ adsorption–desorption, FTIR, XRD, SEM, and zeta potential analysis. The composites exhibited hierarchical micro–mesoporous structures with BET surface areas of 467–499 m² g⁻¹; the non-microporous volume fraction increased from 0.09 (reference carbon RFC, 545 m² g⁻¹) to 0.54–0.63 upon ZnO–SiO₂ incorporation. Adsorption of methylene blue (MB), crystal violet (CV), and rhodamine 6G (R6G) followed the Marczewski–Jaroniec isotherm model. Maximum adsorption capacities for the best-performing composite (C-Zn1) reached 1.22 mmol g⁻¹ for MB, 1.04 mmol g⁻¹ for CV, and 0.63 mmol g⁻¹ for R6G, compared to 1.32, 1.17, and 0.67 mmol g⁻¹ for unmodified RFC. Kinetic analysis revealed up to 3.5-fold faster adsorption rates for C-Zn1 relative to RFC (for CV and R6G), attributed to enhanced diffusion through mesoporous channels while preserving the micropore-driven capacity. Agar well-diffusion assays against four bacterial strains showed no inhibition zones for any composite, indicating that no biologically active concentration of zinc species was released under the assay conditions. The proposed approach yields composites with enhanced adsorption kinetics, preserved capacity, and confirmed non-leaching character, positioning them as effective candidates for water purification. Full article

Multidrug-resistant bacterial pathogens pose a critical global health challenge, necessitating safe and effective antimicrobial alternatives. Plant-derived nanoparticles represent promising candidates due to their bioactivity and biocompatibility. Magnesium nitrate nanoparticles were synthesized using Momordica charantia peel extract through green chemistry. Phytochemical screening identified flavonoids, phenolics, tannins, and terpenoids that facilitated nanoparticle formation and stability. Characterization via scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy confirmed polydisperse size distribution (1–100 nm), crystalline structure, and functional group capping. Disc diffusion assays demonstrated concentration-dependent antibacterial activity against multidrug-resistant strains, with maximum inhibition zones of 17.6 ± 1.1 mm against Gram-positive bacteria. Minimum inhibitory concentration and minimum bactericidal concentration assays revealed high bactericidal activity, particularly against Gram-positive bacteria. Time-kill kinetic studies showed concentration- and time-dependent killing with ≥3 log₁₀ reduction in viable bacterial counts at higher concentrations. Nanoparticle–antibiotic combinations exhibited markedly enhanced activity against multidrug-resistant strains compared to free antibiotics, indicating synergistic effects. Toxicity assessment using Brine Shrimp Lethality Assay revealed low toxicity (LC₅₀ > 1000 µg/mL). Green-synthesized magnesium nitrate nanoparticles demonstrate potent antibacterial properties and effectively enhance antibiotic potency against multidrug-resistant bacteria. Further studies are required to validate therapeutic applicability. Full article