Search Results (8,371)

Skin aging is closely related to mitochondrial dysfunction and cell cycle abnormalities, and developing intervention strategies targeting mitochondrial quality control is an important direction for anti-aging research. In this study, we investigated the anti-aging mechanism of Camellia japonica flower (CJF) extract and its active ingredient hyperoside based on a doxorubicin (DOX)-induced endogenous senescence model in human skin fibroblasts (HSFs). LC-MS proteomics analysis revealed that CJF extract and hyperoside specifically activated the FUNDC1-mediated mitochondrial autophagy pathway, significantly ameliorated the DOX-induced decrease in mitochondrial membrane potential and the accumulation of reactive oxygen species (ROS), and alleviated the cellular S-phase blockade and reversed the high expression of senescence-associated β-galactosidase (SA-β-gal). Further studies showed that the two cleared damaged mitochondria by enhancing mitochondrial autophagy and restoring cellular energy metabolism homeostasis while promoting type III collagen and elastin synthesis and repairing the expression of Claudin 1 related to skin barrier function. For the first time, the present study reveals the molecular mechanism of CJF extract in delaying skin aging by regulating the FUNDC1-dependent mitochondrial autophagy pathway, which provides a theoretical basis and a candidate strategy for developing novel anti-aging agents targeting mitochondrial quality control. Full article

Antibiotic misuse accelerates resistance dissemination via plasmid conjugation, but quorum sensing (QS) regulatory mechanisms remain undefined. Using Escherichia coli (E. coli) MG1655 conjugation models (RP4-7/EC600 plasmids), we demonstrate that long-chain acyl-homoserine lactones (C10/C12-HSL) enhance transfer frequency by up to 7.7-fold (200μM C12-HSL; p < 0.001), while quorum-quenching by sub-inhibitory vanillin suppressed this effect by 95% (p < 0.0001). C12-HSL compromised membrane integrity via ompF upregulation (4-fold; p < 0.01) and conjugative pore assembly (trbBp upregulated by 1.38-fold; p < 0.05), coinciding with ROS accumulation (1.5-fold; p < 0.0001) and SOS response activation (recA upregulated by 1.68-fold; p < 0.001). Crucially, rpoS and rmf deletion mutants reduced conjugation by 65.5% and 55.8%, respectively (p < 0.001), exhibiting attenuated membrane permeability (≤65.5% reduced NPN influx; p < 0.0001), suppressed ROS (≤54% downregulated; p < 0.0001), and abolished transcriptional induction of conjugation/stress genes. Reciprocal RpoS–RMF (ribosomal hibernation factor) crosstalk was essential for AHL responsiveness, with deletions mutually suppressing expression (≤65.9% downregulated; p < 0.05). We establish a hierarchical mechanism wherein long-chain AHLs drive resistance dissemination through integrated membrane restructuring, stress adaptation, and RpoS–RMF-mediated genetic plasticity, positioning QS signaling as a viable target for curbing resistance spread. Full article

Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short half-life, toxic side effects, and increasingly severe drug resistance issues. This study aimed to develop a biomimetic nano-drug delivery system to enhance targeting ability, prolong blood circulation, and mitigate resistance of DAP. Methods: DAP-loaded chitosan nanocomposite particles (DAP-CS) were prepared by electrostatic self-assembly. Macrophage membrane vesicles (MM) were prepared by fusion of M1-type macrophage membranes with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). A biomimetic nano-drug delivery system (DAP-CS@MM) was constructed by the coextrusion process of DAP-CS and MM. Key physicochemical parameters, including particle diameter, zeta potential, encapsulation efficiency, and membrane protein retention, were systematically characterized. In vitro immune escape studies and in vivo zebrafish infection models were employed to assess the ability of immune escape and antibacterial performance, respectively. Results: The particle size of DAP-CS@MM was 110.9 ± 13.72 nm, with zeta potential +11.90 ± 1.90 mV, and encapsulation efficiency 70.43 ± 1.29%. DAP-CS@MM retained macrophage membrane proteins, including functional TLR2 receptors. In vitro immune escape assays, DAP-CS@MM demonstrated significantly enhanced immune escape compared with DAP-CS (p < 0.05). In the zebrafish infection model, DAP-CS@MM showed superior antibacterial efficacy over both DAP and DAP-CS (p < 0.05). Conclusions: The DAP-CS@MM biomimetic nano-drug delivery system exhibits excellent immune evasion and antibacterial performance, offering a novel strategy to overcome the clinical limitations of DAP. Full article

Background/Objectives: Antimicrobial resistance (AMR) contributes to millions of deaths globally each year, creating an urgent need for new therapeutic agents. Antimicrobial peptides (AMPs) have emerged as promising candidates due to their potential to combat AMR pathogens. This study aimed to evaluate the antimicrobial activity of an AMP from a soil-derived bacterial isolate against Gram-negative bacteria. Method: Soil bacteria were isolated and screened for antimicrobial activity. The bioactive peptide was purified and determined its structure and antimicrobial efficacy. Genomic analysis was conducted to predict the biosynthetic gene clusters (BGCs) responsible for AMP production. Results: Genomic analysis identified the isolate as Paenibacillus sp. Na14, which exhibited low genomic similarity (61.0%) to other known Paenibacillus species, suggesting it may represent a novel species. The AMP from the Na14 strain exhibited heat stability up to 90 °C for 3 h and retained its activity across a broad pH range from 3 to 11. Structural analysis revealed that the Na14 peptide consisted of 14 amino acid residues, adopting an α-helical structure. This peptide exhibited bactericidal activity at concentrations of 2–4 µg/mL within 6–12 h, and its killing rate was concentration-dependent. The peptide was found to disrupt the bacterial membranes. The Na14 peptide shared 64.29% sequence similarity with brevibacillin 2V, an AMP from Brevibacillus sp., which also belongs to the Paenibacillaceae family. Genomic annotation identified BGCs associated with secondary metabolism, with a particular focus on non-ribosomal peptide synthetase (NRPS) gene clusters. Structural modeling of the predicted NRPS enzymes showed high similarity to known NRPS modules in Brevibacillus species. These genomic findings provide evidence supporting the similarity between the Na14 peptide and brevibacillin 2V. Conclusions: This study highlights the discovery of a novel AMP with potent activity against Gram-negative pathogens and provides new insight into conserved AMP biosynthetic enzymes within the Paenibacillaceae family. Full article

In vitro cartilage explant culture has been used to assess nutraceuticals on cartilage responses to inflammatory stimuli. However, applying extracts of nutraceuticals directly to cartilage explants does not account for effects of digestion and hepatic biotransformation, or selective exclusion of product metabolites from joint fluid by the synovial membrane. The current study produced a simulated biological extract of a common nutraceutical (glucosamine; G_sim) by exposing it to a simulated upper gastrointestinal tract digestion, hepatic biotransformation by liver microsomes, and purification to a molecular weight cut-off of 50 kDa. This extract was then used to condition cartilage explants cultured for 120 h in the presence or absence of an inflammatory stimulus (lipopolysaccharide). Media samples were analyzed for prostaglandin E₂ (PGE₂), glycosaminoglycan (GAG), and nitric oxide (NO). Tissue was digested and analyzed for GAG content and stained for viability. Conditioning of explants with G_sim significantly reduced media GAG in stimulated and unstimulated explants and reduced nitric oxide production in unstimulated explants. These data provide evidence for the value of glucosamine in protecting cartilage from deterioration following an inflammatory challenge, and the model improves applicability of these in vitro data to the in vivo setting. Full article

The increasing depletion of fossil fuels and their environmental impact have led to the development of fuel cell hybrid electric vehicles. By combining fuel cells with batteries, these vehicles offer greater efficiency and zero emissions. However, their energy management remains a challenge requiring advanced strategies. This paper presents a comparative study of two developed energy management strategies: a deterministic rule-based approach and a fuzzy logic approach. The proposed system consists of a proton exchange membrane fuel cell (PEMFC) as the primary energy source and a lithium-ion battery as the secondary source. A comprehensive model of the hybrid powertrain is developed to evaluate energy distribution and system behaviour. The control system includes a model predictive control (MPC) method for fuel cell current regulation and a PI controller to maintain DC bus voltage stability. The proposed strategies are evaluated under standard driving cycles (UDDS and NEDC) using a simulation in MATLAB/Simulink. Key performance indicators such as fuel efficiency, hydrogen consumption, battery state-of-charge, and voltage stability are examined to assess the effectiveness of each approach. Simulation results demonstrate that the deterministic strategy offers a structured and computationally efficient solution, while the fuzzy logic approach provides greater adaptability to dynamic driving conditions, leading to improved overall energy efficiency. These findings highlight the critical role of advanced control strategies in improving FCHEV performance and offer valuable insights for future developments in hybrid-vehicle energy management. Full article

Background/Objective: This study explores a novel approach for diagnosing common middle ear pathologies using Pressure-Less Acoustic Immittance (PLAI™), a non-invasive alternative to conventional tympanometry. Methods: A total of 516 ear measurements were collected and stratified into three age groups: 0–3, 3–12, and 12+ years, reflecting key developmental stages. PLAI™-derived acoustic parameters, including resonant frequency, peak admittance, canal volume, and resonance peak frequency boundaries, were analyzed using Random Forest classifiers, with SMOTE addressing class imbalance and SHAP values assessing feature importance. Results: Age-specific models demonstrated superior diagnostic accuracy compared to non-stratified approaches, with macro F1-scores of 0.79, 0.84, and 0.78, respectively. Resonant frequency, ear canal volume, and peak admittance consistently emerged as the most informative features. Notably, age-based stratification significantly reduced false negative rates for conditions such as Otitis Media with Effusion and tympanic membrane retractions, enhancing clinical reliability. These results underscore the relevance of age-aware modeling in pediatric audiology and validate PLAI™ as a promising tool for early, pressure-free middle ear diagnostics. Conclusions: While further validation on larger, balanced cohorts is recommended, this study supports the integration of machine learning and acoustic immittance into more accurate, developmentally informed screening frameworks. Full article

In scientific research and engineering practice, the design of deep spiking neural network (DSNN) architectures remains a complex task that heavily relies on the expertise and experience of professionals. These architectures often require repeated adjustments and modifications based on factors such as the DSNN’s performance, resulting in significant consumption of human and hardware resources. To address these challenges, this paper proposes an innovative evolutionary membrane algorithm for optimizing DSNN architectures. This algorithm automates the construction and design of promising network models, thereby reducing reliance on manual tuning. More specifically, the architecture of DSNN is transformed into the search space of the proposed evolutionary membrane algorithm. The proposed algorithm thoroughly explores the impact of hyperparameters, such as the candidate operation blocks of DSNN, to identify optimal configurations. Additionally, an early stopping strategy is adopted in the performance evaluation phase to mitigate the time loss caused by objective evaluations, further enhancing efficiency. The optimal models identified by the proposed algorithm were evaluated on the CIFAR-10 and CIFAR-100 datasets. The experimental results demonstrate the effectiveness of the proposed algorithm, showing significant improvements in accuracy compared to the existing state-of-the-art methods. This work highlights the potential of evolutionary membrane algorithms to streamline the design and optimization of DSNN architectures, offering a novel and efficient approach to address the challenges in the applications of automated parameter optimization for DSNN. Full article

Background: Local anesthesia is essential for most dental procedures, but its parenteral administration is often painful. Topical anesthetics are commonly used to minimize local anesthesia pain; however, commercial formulations fail to fully prevent the discomfort of local anesthetic injection. Methods: We developed and characterized a novel lidocaine and epinephrine co-loaded liquid crystalline precursor system (LCPS) for topical anesthesia. The formulation was structurally characterized using polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). Rheological behavior was assessed through continuous and oscillatory rheological analyses. Texture profile analysis, in vitro mucoadhesive force evaluation, in vitro drug release and permeation studies, and an in vivo toxicity assay using the chicken chorioallantoic membrane (CAM) model were also conducted. Results: PLM and SAXS confirmed the transition of the LCPS from a microemulsion to a lamellar liquid crystalline structure upon contact with artificial saliva. This transition enhanced formulation consistency by over 100 times and tripled mucoadhesion strength. The LCPS also provided controlled drug release, reducing permeation flow by 93% compared to the commercial formulation. Importantly, the CAM assay indicated that the LCPS exhibited similar toxicity to the commercial product. Conclusions: The developed LCPS demonstrated promising physicochemical and biological properties for topical anesthesia, including enhanced mucoadhesion, controlled drug delivery, and acceptable biocompatibility. These findings support its potential for in vivo application and future clinical use to reduce pain during dental anesthesia procedures. Full article

Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt and NF-κB signaling pathways, and by inducing mitochondrial apoptosis through reactive oxygen species generation and cytochrome c release. However, its clinical application is hindered by its systemic and hemolytic toxicity, rapid degradation in plasma, poor pharmacokinetics, and immunogenicity, necessitating the development of targeted delivery strategies to enable safe and effective treatment. Nanoparticle-based delivery systems have emerged as a promising strategy for overcoming these challenges, offering improved tumor targeting, reduced off-target effects, and enhanced stability. This review provides a comprehensive overview of the mechanisms through which melittin exerts its anticancer effects and evaluates the development of various melittin-loaded nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, micelles, and inorganic systems. It also summarizes the preclinical evidence for melittin nanotherapy across a wide range of cancer types, highlighting both its cytotoxic and immunomodulatory effects. The potential of melittin nanoparticles to overcome multidrug resistance and synergize with chemotherapy, immunotherapy, photothermal therapy, and radiotherapy is discussed. Despite promising in vitro and in vivo findings, its clinical translation remains limited. Key barriers include toxicity, manufacturing scalability, regulatory approval, and the need for more extensive in vivo validation. A key future direction is the application of computational tools, such as physiologically based pharmacokinetic modeling and artificial-intelligence-based modeling, to streamline development and guide its clinical translation. Addressing these challenges through focused research and interdisciplinary collaboration will be essential to realizing the full therapeutic potential of melittin-based nanomedicines in oncology. Overall, this review synthesizes the findings from over 100 peer-reviewed studies published between 2008 and 2025, providing an up-to-date assessment of melittin-based nanomedicine strategies across diverse cancer types. Full article

Morus alba L. (MA) is a member of the Moraceae family, known as “white mulberry”. Due to the high levels of bioactive compounds, mulberry plants can be considered a good source of nutrients and antioxidant compounds. Our study aims to analyze the effect of MA extract leaves on erythrocytes, focusing on its action on metabolism and membrane integrity. The choice of erythrocytes as a study model is based on their metabolic simplicity and their easy availability. Cell viability, following exposure of the cells to the extract, was evaluated by hemolysis, methemoglobin, caspase 3 activity and flow cytofluorimetric analysis; in addition, the effect of the pretreatment with the MA was detected after incubation of erythrocytes with different stressors. The impact on cell metabolism was evaluated by measuring anion flux kinetics, ATP levels and phosphatase activity. The results obtained show a peculiar (double) effect of the extract, which, on the one hand, probably by exploiting its component with antioxidant properties, protects the cell membrane by accumulating on the bilayer. On the other hand, the alteration of anion exchange could lead to the triggering of apoptosis and consequent cell death. The hypotheses, although excluded by our data, all point toward a beneficial and protective action of the extract on the health and vitality of RBCs. Full article

Albumin-binding agents enhance tumor uptake of radiopharmaceuticals targeting prostate-specific membrane antigens (PSMAs) in radiotherapy. We synthesized PSMA-NARI-56, a molecule with both PSMA targeting activity and albumin-binding moiety, labeled with ¹⁷⁷Lu as the therapeutic agent. The aim of this study was to determine the specific binding of ¹⁷⁷Lu-PSMA-NARI-56 towards PSMA, assess its biodistribution, and evaluate therapeutic effectiveness by tumor-bearing mice. The effect of ¹⁷⁷Lu-PSMA-NARI-56 viability of PSMA-positive cell (LNCaP) was evaluated. Biodistribution and endoradiotherapy studies were utilized to determine the distribution, targeting, and anti-tumor efficacy by tumor-bearing mice identified by ¹¹¹In-PSMA-NARI-56. ¹⁷⁷Lu-PSMA-NARI-56 exhibited a significant impact on the viability of the LNCaP cell. Biodistribution results revealed the maximum tumor uptake of ¹⁷⁷Lu-PSMA-NARI-56 occurring within 24 h, reaching 40.56 ± 10.01%ID/g. In radionuclide therapy, at 58 days post-injection (p.i.), ¹⁷⁷Lu-PSMA-NARI-56 demonstrated superior tumor inhibition (98%) compared to ¹⁷⁷Lu-PSMA-617 (58%), and the mouse survival rate after 90 days of radiotherapy (90%) was also higher than that of ¹⁷⁷Lu-PSMA-617 (30%) in LNCaP tumor-bearing mice. In the PSMA-positive animal model, ¹⁷⁷Lu-PSMA-NARI-56 shows higher potential radiotheranostic and prolonged accumulation (identify by ¹¹¹In-PSMA-NARI-56/nanoSPECT/CT image), offering the potential for improved treatment effectiveness and increased survival rates when compared to ¹⁷⁷Lu-PSMA-617. Full article

This work presents the experimental and numerical investigation of a novel acoustic metamaterial based on sustainable and biodegradable components: cork membranes and honeycomb cores made from treated aramid paper. The design exploits the principle of localized resonance induced by tensioned membranes coupled with subwavelength cavities, aiming to achieve high sound absorption at low (250–500 Hz) and mid frequencies (500–1400 Hz) with minimal thickness and environmental impact. Three configurations were analyzed, varying the number of membranes (one, two, and three) while keeping a constant core structure composed of three stacked honeycomb layers. Acoustic performance was measured using an impedance tube (Kundt’s tube), focusing on the normal-incidence sound absorption coefficient in the frequency range of 250–1400 Hz. The results demonstrate that increasing the number of membranes introduces multiple resonances and broadens the effective absorption bandwidth. Numerical simulations were performed to predict pressure field distributions. The numerical model showed good agreement with the experimental data, validating the underlying physical model of coupled mass–spring resonators. The proposed metamaterial offers a low-cost, modular, and fully recyclable solution for indoor sound control, combining acoustic performance and environmental sustainability. These findings offer promising perspectives for the application of bio-based metamaterials in architecture and eco-design. Further developments will address durability, high-frequency absorption, and integration in hybrid soundproofing systems. Full article

This paper presents a theoretical model of a thin, penny-shaped piezoelectric actuator bonded to an isotropic thermo-elastic substrate under coupled electrical-thermal-diffusive loading. The problem is assumed to be axisymmetric, and the peeling stress of the film is neglected in accordance with membrane theory, yielding a simplified equilibrium equation for the piezoelectric film. By employing potential theory and the Hankel transform technique, the surface strain of the substrate is analytically derived. Under the assumption of perfect bonding, a governing integral equation is established in terms of interfacial shear stress. The solution to this integral equation is obtained numerically using orthotropic Chebyshev polynomials. The derived results include the interfacial shear stress, stress intensity factors, as well as the radial and hoop stresses within the system. Finite element analysis is conducted to validate the theoretical predictions. Furthermore, parametric studies elucidate the influence of material mismatch and actuator geometry on the mechanical response. The findings demonstrate that, the performance of the piezoelectric actuator can be optimized through judicious control of the applied electrical-thermal-diffusive loads and careful selection of material and geometric parameters. This work provides valuable insights for the design and optimization of piezoelectric actuator structures in practical engineering applications. Full article

Climate change has a significant negative impact on agriculture and food production. This trend requires technological development and the adaptation of new technologies in both the grapevine production and winemaking sectors. High temperatures and heat accumulation during the growing season result in faster ripening and a higher sugar content, leading to a higher alcohol content during fermentation. The negative consequences are an imbalanced wine character and consumer reluctance, as lower alcoholic beverages are now in high demand. Over the last decade, several methods have been developed to handle this impact and reduce the alcohol content of wines. In this study, we used the MASTERMIND^® REMOVE membrane-based dealcoholization system to reduce the alcohol concentration in of Pinot gris wines from 12.02% v/v to 10.69% v/v and to investigate the effect on analytical parameters in three steps (0.5%, 1%, and 1.5% reductions) along the treatment. To evaluate the impact of the partial alcohol reduction and identify correlations between the wine chemical parameters, data were analyzed with ANOVA, PCA, multivariate linear regression and cluster analysis. The results showed that except for the extract, sugar content and proline content, the treatment had a significant effect on the chemical parameters. Both free and total SO₂ levels were significantly reduced as well as volatile acid, glycerol and succinic acid levels. It must be highlighted that some parameters were not differing significantly between the untreated and the final wine, while the change was statistically verified in the intermediate steps of the partial alcohol reduction. This was the case for example for n-Propanol, i-Amylalcohol, Acetaldehyde, and Ethyl acetate. The multivariate linear regression model explained 18.84% of the total variance, indicating a modest but meaningful relationship between the alcohol content and the investigated analytical parameters. Our results showed that even if the applied instrument significantly modified some of the wine chemical parameters, those changes would not influence significantly the wine sensory attributes. Full article