Search Results (9,265)

This study focused on elucidating the effects of chitosan (Ch), hyaluronic acid (HA), and titanium dioxide nanoparticles (nano-TiO₂) on the physicochemical characteristics of a model bacterial membrane (layer) composed of the phospholipid DPPG (1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt). The membrane was prepared on mica using the Langmuir–Blodgett (LB) technique from an aqueous subphase containing Ch, HA and/or TiO₂. Its surface properties were subsequently characterized by optical profilometry and surface free energy estimation. The nanoscale topography of the DPPG layer provided a biomimetic platform that reflects the organization of bacterial membranes, enabling a precise evaluation of how external agents, such as Ch, HA, and nano-TiO₂, modify the surface’s structural and energetic properties. The results showed that the LB films exhibit mildly heterogeneous topography, which can be attributed to lipid domains with distinct molecular packing densities. Depending on the type of biopolymer employed with TiO₂, distinct topographic architectures of the DPPG monolayers were obtained. Furthermore, the presence of nano-TiO₂ was clearly manifested as a topographic irregularity, while the analysis of hydrophilic–hydrophobic properties revealed a structurally perturbed lipid film. The results provide detailed insight into how these specific molecules (Ch, HA, nano-TiO₂) interact at the molecular level with model bacterial membranes, offering a comprehensive picture of cell–microenvironment interactions. Full article

Acute myocardial infarction (AMI) results from a lack of oxygen supply to the myocardium, leading to the loss of cardiomyocytes and their replacement with fibrotic scar tissue. This process is closely associated with the development of heart failure. Regenerative medicine has emerged as a promising strategy to enhance treatment outcomes in severe cases of heart failure. This study aimed to evaluate myocardial regeneration after AMI using a biomaterial composed of mononuclear stem cells and human amniotic membrane. A total of 120 Wistar rats were subjected to experimentally induced AMI. On the 7th day post-infarction, rats with an ejection fraction of <50% on echocardiography were randomized into four groups: (1) control; (2) stem cells; (3) amniotic membrane; and (4) amniotic membrane combined with stem cells. On the 30th day, the surviving animals underwent a second echocardiographic evaluation and were subsequently euthanized. The group treated with the combination of amniotic membrane and stem cells showed reduced systolic and diastolic ventricular volumes. Histological analysis revealed that these animals exhibited less fibrosis and a lower percentage of type I collagen. Based on the results of the study, it was concluded that the combination of human amniotic membrane and mononuclear stem cells decreased ventricular volumes and myocardial fibrosis, suggesting more favorable ventricular remodeling in this experimental model. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells when the spike receptor-binding domain (RBD) engages angiotensin-converting enzyme 2 (ACE2). Cannabinoid scaffolds have recently been reported to bind S1/RBD, block spike-mediated membrane fusion, and modulate host inflammatory pathways, making them attractive candidates for entry inhibition. Here, we applied an integrated computational pipeline to prioritize cannabis-derived compounds as interfacial blockers of the RBD–ACE2 complex across variants. Eleven phytocannabinoids were docked into the wild-type (WT) RBD–ACE2 interface, identifying three cavities, with ligands preferentially occupying pocket 1. Complexes were subjected to triplicate 200 ns all-atom molecular dynamics (MD) simulations for WT, Delta, and Omicron BA.1 RBD–ACE2. Binding energetics were quantified using molecular mechanics/generalized Born surface area (MM/GBSA) and solvated interaction energy (SIE), and per-residue contributions were analyzed together with solvent-accessible surface area (SASA) and residue interaction networks. Among all compounds, cannabidiol (CBD) and cannabinol (CBN) were the only ligands that remained stably bound in pocket 1 for all variants. CBN showed the most favorable ligand–complex binding in WT, whereas CBD preserved favorable binding in Omicron BA.1 despite reduced interface burial, indicating that van der Waals/electrostatic complementarity and solvation, rather than surface coverage alone, govern affinity. Both ligands weakened modeled RBD–ACE2 binding by perturbing hot-spot residues centered on Y505 or N501Y in RBD and E37, A387, and R393 in ACE2. Overall, our results highlight CBD and CBN as tractable, variant-spanning interface disruptors and illustrate how MD-based free-energy calculations can support computational drug discovery against evolving viral protein–protein interfaces. Full article

Low temperature critically influences cellular metabolism by impairing processes such as membrane fluidity, enzyme activity, and protein folding. However, the comprehensive genetic landscape and regulatory mechanisms governing cold acclimation remain poorly understood. Here, we performed high-throughput, pooled genetic screening in the model alga Chlamydomonas reinhardtii (C. reinhardtii) to identify genes essential for cold acclimation. Our screening revealed numerous candidate genes implicated not only in early cold response pathways but also in core cellular processes, including DNA dynamics, protein homeostasis, metabolic regulation, and substrate transport. Notably, we identified a member of the RUS (ROOT UVB SENSITIVE) family, encoding a conserved DUF647 domain protein, designated CrRUS1. CRISPR-generated rus1 mutant alleles in C. reinhardtii display a phenotype consistent with our screening: the mutants did not exhibit any visible growth defects, but show severe growth defects at low temperature. Interestingly, the cold-induced phenotypic changes in rus1 can be reversed by dark conditions, suggesting that CrRUS1 likely promotes cold acclimation in C. reinhardtii through a light-dependent pathway. Our work provides novel genetic resources and mechanistic insights into cold acclimation in C. reinhardtii, with potential translational relevance for enhancing cold tolerance in crop species. Full article

Background/Objectives: Fungal keratitis remains a vision-threatening infection, and current amphotericin B (AmphB) eye drops suffer from low corneal residence time, poor aqueous solubility, and the need for frequent dosing. This study develops electrospun nanofiber-based ophthalmic inserts combining polyvinyl alcohol (PVA), gamma-cyclodextrin (γ-CD), and sodium taurocholate (STC) to enhance AmphB solubility and provide a non-invasive, rapidly dissolving ophthalmic dosage form. Methods: γ-CD and STC-enhanced AmphB-loaded PVA nanofiber-based ophthalmic inserts with varying γ-CD and STC concentrations were prepared by electrospinning and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Drug content, in vitro release (Weibull modeling), antifungal activity against Candida albicans, Fusarium solani, and Aspergillus fumigatus, ocular cytocompatibility using the Hen’s Egg Test on Chorioallantoic Membrane (HET-CAM), and accelerated stability (40 ± 2 °C, 75 ± 5% relative humidity, 4 weeks) were evaluated. Results: Bead-free nanofibers with mean diameters between 216 ± 33 nm and 310 ± 35 nm were obtained, and XRD confirmed complete amorphization of AmphB within the PVA nanofiber matrix, forming an amorphous solid dispersion. All formulations showed rapid and nearly complete AmphB release (≈100% within 60 min), with Weibull β values < 0.75, indicating Fickian diffusion-controlled release. AmphB-loaded PVA nanofiber-based ophthalmic inserts produced inhibition zones and broth susceptibility profiles comparable to AmphB in dimethyl sulfoxide (DMSO), demonstrating preserved antifungal activity. HET-CAM scores (0–0.9) classified the inserts as practically non-irritant, and SEM/FTIR after accelerated storage showed no relevant morphological or physicochemical changes. Conclusions: These γ-CD and STC-enhanced AmphB-loaded PVA nanofiber-based ophthalmic inserts provide a non-invasive, rapidly dissolving ophthalmic dosage form that combines amorphous AmphB, immediate drug availability, and good ocular tolerance, supporting their further development as a patient-friendly treatment option for fungal keratitis. Full article

Microalgae dewatering is a major bottleneck for the industrial deployment of microalgal biorefineries due to its high energy and water requirements. This study investigates the optimization and modeling of an industrial-scale aerated submerged ultrafiltration (UF) system for microalgae pre-concentration under real operating conditions. A submerged hollow-fibre Koch LE8 UF module (348 m², 0.03 µm) was operated directly on Chlorella sp. cultures produced in an 800 m² outdoor photobioreactor. Filtration–backwash cycles were experimentally optimized, identifying an optimal sequence of 8.33 min filtration and 1 min backwash, enabling up to 80% net water removal per cycle while maintaining fouling largely reversible under the tested conditions. Long-term trials (6–7 h) achieved stable concentration factors of 3.6–4.3 with complete biomass retention and sustained permeate flux despite increasing solids concentration. Reuse of permeate for backwashing eliminated freshwater consumption without compromising membrane performance. A dynamic resistance-in-series (RIS) model, incorporating mass balances and an empirically derived concentration-polarisation resistance, accurately reproduced permeate flux and biomass concentration dynamics (R² > 0.83) using a single fitted parameter. The validated model was further applied as a digital twin to simulate operation up to the theoretical concentration factor of 10, quantifying the associated energy and water demands. The system exhibited a low estimated specific energy consumption of 1.25 kWh·kg⁻¹ biomass and a water demand of 0.30 m³·kg⁻¹, demonstrating that aerated submerged UF is a robust, scalable, and energy-efficient solution for industrial microalgae harvesting. Full article

Fuel cell technologies are increasingly investigated as alternatives to conventional auxiliary diesel generators in order to enhance shipboard energy efficiency and reduce greenhouse gas emissions. This study presents a unified and uncertainty-driven system-level assessment of solid oxide fuel cell (SOFC) and proton exchange membrane fuel cell (PEMFC) systems operating as auxiliary power sources on a 200 m bulk carrier. Both technologies are evaluated under identical vessel characteristics, operating profiles, auxiliary load levels (360–600 kW), and cost assumptions, and are benchmarked directly against a conventional three–diesel-generator configuration. A modular numerical framework is developed to model propulsion–auxiliary interactions for ship speeds between 10 and 14 knots. SOFC systems are assessed using grey, bio-derived, and green natural gas pathways, while PEMFC systems are examined under grey, blue, and green hydrogen supply routes. Performance indicators include annual fuel consumption, carbon dioxide (CO₂) emission reduction, net present value (NPV), internal rate of return (IRR), payback period (PBP), and marginal abatement cost (MAC). Economic uncertainty is explicitly embedded in the framework through Monte Carlo simulation, where fuel prices (±20%) and capital costs are sampled across defined ranges, generating probabilistic distributions rather than single deterministic estimates. This uncertainty-centred approach enables assessment of robustness, downside risk, and probability of profitability. Results show that replacing a single operating 600 kW diesel generator with fuel cell systems reduces auxiliary fuel energy demand by 25–35% for SOFC and approximately 15–25% for PEMFC relative to the diesel benchmark. Annual CO₂ reductions range from 1.1 to 1.3 kt for SOFC systems and 1.8–2.8 kt for PEMFC configurations. Under grey fuel pathways, median NPVs reach approximately 2–4.5 M$ for SOFC and 9–17 M$ for PEMFC as load increases, with IRRs exceeding 15% and 30%, respectively. Transitional pathways exhibit narrower margins, while renewable pathways remain more sensitive to fuel price variability. The findings demonstrate that fuel pathway cost dominates lifecycle outcomes under uncertainty and that hydrogen-based PEMFC systems exhibit the strongest economic resilience within the examined market ranges. The framework provides structured, uncertainty-aware decision support and establishes a foundation for integration into model-based systems engineering (MBSE) environments for early stage ship energy system design. Full article

Gamma-tocotrienol (GT3) is one of the constituents of vitamin E that demonstrated significant radioprotective efficacy in murine and nonhuman primate (NHP) models. Considering the antioxidant activity of GT3 and its role in terminating lipid peroxidation, we hypothesize that mechanism of radioprotective effect of GT3 may involve the inhibition of irradiation-induced ferroptosis—a form of regulated cell death characterized by excessive, iron-dependent, peroxidation of lipids in cellular membranes. To test this hypothesis, the metabolomic and proteomic data from serum samples of GT3- or vehicle-treated NHPs exposed to 12 Gy (partial- or total-body) radiation was analyzed with focus on lipid peroxidation markers and proteins involved in iron metabolism. Four secondary lipid peroxidation products were identified including 4-oxo-2-nonenal (4-ONE), 4-hydroperoxy-2-nonenal (4-HPNE), 3,4-epoxynonanal (3,4-ENA), and trans-4,5-epoxy-(2E)-decenal (4,5-EDE). In vehicle-treated animals, their concentrations increased significantly as soon as 4 h after irradiation and then gradually declined. GT3 treatment mitigated this radiation-induced increase. In addition to lipid peroxidation products, similar patterns of change were observed for several polyunsaturated, monounsaturated, and saturated fatty acids as well as amino acids such as lysine and its derivatives. Taken together, these metabolomic changes suggest that irradiation induces cellular membrane damage through enhanced lipid peroxidation, while GT3 exerts a protective effect against this process. In addition, GT3 increased serum levels of haptoglobin and hemopexin—two plasma scavenger proteins that play complementary protective roles in iron and heme homeostasis. Although the present study does not conclusively demonstrate that GT3 mediates radioprotection via inhibition of ferroptosis, the data suggest that GT3 limits membrane damage and reduces susceptibility to ferroptosis by enhancing iron and heme scavenging. Further investigation into the interaction between GT3 and key components of ferroptosis following exposure to ionizing radiation is therefore warranted. Full article

Mitochondrial dysfunction plays a central role in the pathogenesis of bronchopulmonary dysplasia (BPD). Solute carrier family 25 member 28 (SLC25A28) is an iron transporter located in the inner mitochondrial membrane. In this study, we aimed to explore the role and underlying molecular mechanisms of SLC25A28 in BPD. Hyperoxia (85% O₂) was used to establish a neonatal murine model of BPD, and mouse lung epithelial cells (MLE-12 cells) were used in vitro. SLC25A28 expression and activity were downregulated under hyperoxic conditions, both in vivo and in vitro. SLC25A28 overexpression restored hyperoxia-induced mitochondrial oxidative phosphorylation (OXPHOS) dysfunction, and further enhanced the proportion of Ki67-positive cells by 37% (p < 0.05) and increased migration by 33% (p < 0.01) in MLE-12 cells. In contrast, SLC25A28 knockdown exacerbated these impairments in MLE-12 cells, with reduced the proportion of Ki67 positive cells by 71% (p < 0.01) and a 35% reduction in the migration rate. SLC25A28 was also knocked down in vivo, which further aggravated alveolar simplification in BPD mice. Furthermore, the mitochondrial-targeted peptide SS-31 could potentially interact with SLC25A28 and preserve its protein abundance. SS-31 administration mitigated hyperoxia-induced alveolar simplification, with the radical alveolar count (RAC) increasing by 28% (p < 0.05) and the mean linear intercept (MLI) decreasing by 20% (p < 0.001). In summary, this study revealed that SLC25A28 ameliorated hyperoxic lung injury by improving mitochondrial OXPHOS in alveolar epithelial cells, suggesting that it may serve as a potential therapeutic target for BPD. Full article

Bovine mastitis is a multifactorial inflammatory disease primarily characterized by inflammatory cell infiltration and the destruction of mammary alveoli. It is a major cause of reduced milk yield and quality. The imbalance between antioxidant defenses and the generation of reactive oxygen species (ROS), which occurs due to the high metabolic activity of the mammary gland during the periparturient period, increases the incidence of mastitis. During early lactation, especially in high-yielding dairy cows, the massive synthesis and secretion of milk increase the energy demand of mammary tissue, leading to excessive ROS accumulation. This results in cell membrane disruption and, ultimately, antioxidant dysfunction in the mammary tissue. This study established an in vitro oxidative stress model by treating bovine mammary epithelial cells (BMECs) with 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH). The optimal concentration of 1000 μmol/L AAPH was determined using the CCK-8 assay. Model validation showed that, compared to the control group, ROS levels were significantly elevated (p < 0.001) and mitochondrial membrane potential was significantly decreased (p < 0.001) in the AAPH-treated group. Transmission electron microscopy (TEM) analysis revealed that AAPH treatment caused ultrastructural damage, including reduced microvilli, mitochondrial swelling, disappearance of cristae, and vacuolization. Mechanistic studies demonstrated that AAPH treatment significantly upregulated the mRNA and protein expression of AMPK, HMOX-1, mTOR, NOS, and SOD (p < 0.001), while significantly downregulating CYP1A1 expression (p < 0.001). Pretreatment with N-acetylcysteine (NAC) effectively alleviated the oxidative stress damage caused by AAPH. This study successfully established an in vitro AAPH-induced oxidative stress model in BMECs and revealed its molecular mechanism of cellular damage. The damage occurs through modulation of the AMPK/mTOR signaling pathway and the regulation of antioxidant-related gene expression. Full article

The potential of water-soluble membrane proteins (wsMPs) has not been fully realized. In this article, we exploit the nearly identical functionality of wsMPs with their membrane-bound counterparts and show that we can create water-soluble membrane proteins that incorporate into the plasma membranes of cells and alter their fate. As a proof of concept, we demonstrate the functional properties of water-soluble engineered pore-forming proteins, K⁺ ionic channels (MthK), and constitutively active GPCRs—among them frizzled receptors—both in vitro and in vivo. We call this method in vivo deployment of recombinant viable MPs, iDRIVE. Furthermore, we demonstrate that our strategy mediates the unidirectional insertion of MPs into the plasma membrane, and through constitutively active receptors, we present evidence for similar signaling pathway activation between small molecules and our water-soluble proteins using model phenotypes and molecular signaling assays. We present three examples where wsMPs are functional in dictating cellular fate, both in vitro and in vivo. Lastly, we show the induction of similar differential methylation via the activation of the Wnt signaling pathway using the conventional small molecule agonist, CHIR99021, or our wsFrizzled receptors (iDRIVE-FZD) in human embryonic kidney (HEK 293) embryoid spheroids (ESs). Additionally, we show that Wnt activation via wsFrizzled receptors results in even more biologically relevant epigenetic changes than via the small molecule CHIR99021. Future work will employ iDRIVE to differentiate stem cells in the production of research and clinically relevant organoids. Full article

To address the inaccurate scheduling of electric–hydrogen integrated stations (EHISs) caused by the limited accuracy of conventional mechanistic models for proton exchange membrane (PEM) electrolyzers, this study proposes a deep reinforcement learning (DRL)-based scheduling strategy incorporating a data-driven electrolyzer model. First, a deep XGBoost model is developed to characterize the hydrogen production behavior of the PEM electrolyzer, thereby replacing the traditional mechanistic model and reducing prediction errors. Second, the EHIS scheduling problem is formulated as a constrained Markov decision process (CMDP) that explicitly considers user demand and carbon emission constraints. Third, an improved deep Q-network (DQN) algorithm integrating Lagrangian relaxation and the template policy-based reinforcement learning (TPRL) method is designed to solve the scheduling problem, which enhances convergence speed and generalization performance under similar operating scenarios. The simulation results demonstrate that the proposed method can effectively alleviate the decision-making risks introduced by model inaccuracies and significantly improve the operational profitability of the station while satisfying user demand and carbon emission constraints. Full article

Cyclodextrins (CDs) have gained increasing attention as versatile platforms for enhancing drug delivery to the central nervous system, particularly in overcoming the restrictive properties of the blood–brain barrier (BBB). Owing to their unique cyclic oligosaccharide structure, CDs are capable of forming inclusion complexes with a wide range of therapeutic agents, thereby improving their solubility, stability, and bioavailability. In addition to their role as excipients, growing evidence indicates that CDs can actively modulate biological processes, including membrane fluidity and cholesterol homeostasis, which are critical factors in neurological disorders. This review explores the application of CDs in facilitating drug transport across the BBB through multiple mechanisms, including carrier-mediated transport, receptor-mediated transcytosis, and nanoparticle-based delivery systems. Special emphasis is placed on their use in the treatment of neurodegenerative and neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, Niemann–Pick type C disease, and other central nervous system disorders. In these contexts, CD-based formulations have demonstrated the ability to enhance brain targeting, reduce pathological protein aggregation, and improve therapeutic outcomes in preclinical models. This review uniquely integrates cyclodextrin’s physicochemical properties with specific blood–brain barrier transport mechanisms, proposing a structure–transport–therapy framework that enables a more predictive understanding of brain-targeted drug delivery. Full article

This study introduces a novel, simplified, and scalable two-step process for generating bioactive eggshell membrane (ESM) formulations by combining jet-O-mizer ultra-fine milling of ESM (yielding JEM biomaterial) with KOH-mediated hydrolysis, achieving ~50% solubilization of proteins and peptides and enabling the first evaluation of ESM-derived bioactives for gut health applications. The soluble protein fraction (SJ) was separated from the whole hydrolysate (WJ), and subjected to simulated gastrointestinal digestion to assess stability and bioavailability. The antioxidant capacities of the JEM-derived material showed a significant 15-fold increase compared to soluble non-hydrolyzed JEM (NJEM). SJ inhibited E. coli bacterial growth by 50% within 24 h, compared to the untreated bacterial culture. The formulations demonstrated superior anti-inflammatory properties with lipopolysaccharide (LPS)-induced RAW macrophages, resulting in a 80% reduction in NO production compared to untreated cells. Proteomics analysis of SJ revealed key anti-inflammatory (YBX1, YWHAE) and antimicrobial (OCX36, OC-17, TENP, and histones) effectors whose coordinated activities could modulate gut microbial composition. The permeability of the intestinal barrier model Caco-2 monolayer was not significantly affected by treatment with any JEM-derived formulation, thereby predicting maintenance of intestinal integrity. This study provides safe, novel ESM derivatives with high bioavailability and multifunctional bioactivities, including antibacterial, antioxidant, and anti-inflammatory effects, positioning them as promising candidates for dietary supplements to promote gut health. Full article

Organophosphorus pesticide residues (OPPs) pose significant threats to ecological systems and human health, and conventional detection techniques are cumbersome, time-consuming, and costly. Herein, a facile electrochemical biosensor has been constructed based on a methyl green/chitosan (MG/Chi) composite membrane-modified electrode for the selective detection of OPPs, using isazofos (Isa) as the model analyte. Experimental results demonstrated that Isa significantly decreases the redox peak current of the modified electrode in buffer solution, and a good linear relationship was observed between the change in peak current and Isa concentration within a specific range. This biosensor exhibits excellent anti-interference capability and high sensitivity, with a limit of detection (LOD) as low as 0.60 μM. Furthermore, it was successfully applied for the quantitative determination of OPPs in real food and environmental samples, which confirms its reliable practical applicability and potential for on-site monitoring. Full article