The morphological changes that can be induced in a dry ionomer by application of a strong electric field have been studied by means of computer simulation. The internal energy of the membrane at first slowly decreases with increasing field, but then rapidly increases after a certain threshold field is reached. This effect is interpreted as the reorganization of interacting head group dipoles in response to the external perturbation. The resulting morphology contains continuous channels of hydrophilic material capable of facilitating proton conduction. Upon removal of the poling field, the system does not return to its original morphology, but retains the anisotropic structure of the poled material. The poled structure appears to be thermodynamically stable, as confirmed by calculations of the Helmholtz energy of the original and poled samples.
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http://dx.doi.org/10.1088/0953-8984/23/23/234105 | DOI Listing |
Med Chem
January 2025
Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune 70000, Morocco.
Background: Oxidative stress is strongly linked to neurodegeneration through the activation of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate (PARIS) and aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2). This activation, triggered by ataxia-telangiectasia mutated (ATM) kinase, leads to dopaminergic neuron loss and α-synuclein aggregation, a critical pathophysiological aspect of Parkinson's disease (PD). To halt PD progression, pharmacological inhibition of c-Abl kinase is essential.
View Article and Find Full Text PDFMed Chem
January 2025
Laboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences of Agadir, Ibn Zohr University, Agadir, Morocco.
Background: We continue to struggle with the prevention and treatment of the influenza virus. The 2009 swine flu pandemic, caused by the H1N1 strain of influenza A, resulted in numerous fatalities. The threat of influenza remains a significant concern for global health, and the development of novel drugs targeting these viruses is highly desirable.
View Article and Find Full Text PDFMol Pharm
January 2025
Department of Pharmacy, National and Kapodistrian University of Athens, Zografou 15771, Greece.
The simulation of antral conditions for estimating drug apparent equilibrium solubility after a high-calorie, high-fat meal is challenging. In this study, (1) we measured the apparent equilibrium solubility of two model lipophilic drugs, ketoconazole and danazol, in antral aspirates collected at various time points after a minced high-calorie, high-fat meal and a glass of water 30 min after initiation of meal administration, and we designated one point estimate for ketoconazole and one point estimate for danazol; (2) we evaluated the usefulness of FeSSGF-V2 and FEDGAS pH = 3 in reproducing the two point estimates; (3) we evaluated potential compositions of FeSSGF-V3 that simulate the pH, the buffer capacity toward both less acidic and more acidic values, and the antral lipid and protein contents with easily accessible, commercially available products, and (4) we identified the most useful composition of FeSSGF-V3 for reproducing the two point estimates. For both model drugs, apparent solubility in FeSSGF-V2 and in FEDGAS pH 3 deviated substantially from the corresponding point estimate.
View Article and Find Full Text PDFSmall
January 2025
Department of Surgical Oncology and General Surgery Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Current in vitro models for gastric cancer research, such as 2D cell cultures and organoid systems, often fail to replicate the complex extracellular matrix (ECM) found in vivo. For the first time, this study utilizes a gelatin methacryloyl (GelMA) hydrogel, a biomimetic ECM-like material, in 3D bioprinting to construct a physiologically relevant gastric cancer model. GelMA's tunable mechanical properties allow for the precise manipulation of cellular behavior within physiological ranges.
View Article and Find Full Text PDFMol Inform
January 2025
Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Corrensstr. 48, 48149, Muenster, Germany.
Primary carnitine deficiency (PCD) is a rare autosomal recessive genetic disorder caused by missense mutations in the SLC22A5 gene encoding the organic carnitine transporter novel type 2 (OCTN2). This study investigates the structural consequences of PCD-causing mutations, focusing on the N32S variant. Using an alpha-fold model, molecular dynamics simulations reveal altered interactions and dynamics suggesting potential mechanistic changes in carnitine transport.
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