Search Results (7,645)

Diabetes mellitus represents a major global health challenge, which has generated ongoing interest in developing enzymatic strategies to modulate carbohydrate digestion. Phlorizin, a dihydrochalcone found predominantly in plants of the genus Malus, has been extensively investigated for its antidiabetic potential; however, its practical application is limited by its low water solubility. Enzymatic fructosylation represents an effective biocatalytic approach to overcome this limitation and modulate the functional properties of phenolic compounds. In this study, the inhibitory activity of an enzymatically fructosylated phlorizin-enriched fraction, containing 4-O-mono-fructosyl phlorizin (4PHF) as its main component, was evaluated against key carbohydrate-digesting enzymes using in vitro assays complemented by in silico molecular docking analyses. The 4PHF-enriched fraction showed potent inhibition of α-amylase in vitro, with an IC₅₀ value of 2.69 µg/mL. However, no significant inhibition of α-glucosidase was observed within the analyzed concentration range, indicating a selective inhibitory profile. Molecular docking analyses supported the experimental findings, revealing favorable binding orientations and predicted affinities of 4PHF for α-amylase and α-glucosidase, stabilized primarily by hydrogen bond interactions. Overall, the combined in vitro and in silico results demonstrate that enzymatic fructosylation effectively reprograms the enzyme interaction profile of phlorizin, highlighting 4PHF as a structurally optimized modulator of carbohydrate-digesting enzymes, with potential relevance for applied research on enzyme inhibition related to metabolic diseases. Full article

Background: The growing recognition of shared molecular pathways and molecular signatures between cardiovascular diseases and cancer has motivated interest in exploring antihypertensive-associated chemical space for oncological applications. Concurrently, artificial intelligence (AI)-driven molecular generation has enabled the rapid creation of virtual lead candidates for specific therapeutic indications, although their broader biological interaction profiles often remain unexplored. Methods: In this paper, we explore the computational screening of a library of AI-generated antihypertensive virtual lead compounds to evaluate their polypharmacological anticancer potential. The compounds were originally designed and prioritized for modulating $\mathsf{\beta }$-adrenergic receptors but are here re-evaluated in a cancer-focused context using a multi-stage in silico approach. We chose five (5) known cancer target proteins and performed compound profiling for drug-likeness, pharmacokinetic suitability, and safety. Docking simulations, binding free energy estimates, molecular interaction mapping, and pharmacophore modeling were used to evaluate the molecules’ interactions with the cancer-linked protein targets. We employed the binding free energy estimates of the ligand–protein complexes to determine compounds with polypharmacological anticancer potential. In addition, molecular dynamics simulations of some of the compounds with polypharmacological anticancer potential were employed to evaluate binding stability and dynamic behavior of selected ligand–target complexes. Results: Several compounds showed good docking scores, physicochemical characteristics, and pharmacokinetic profiles. Also, the results reveal that several AI-generated antihypertensive virtual leads exhibit favorable multi-target binding profiles, with consistent docking affinities and stable interaction networks across multiple cancer-related targets. Conclusions: Our findings suggest that several of the hypothetically evaluated compounds exhibit favorable physicochemical properties, acceptable predicted pharmacokinetic and safety profiles, and consistent predicted binding affinities across multiple cancer-relevant targets. Full article

Mechanosensitive ion channels (MSCs) are fundamental transducers that convert mechanical forces into electrochemical signals, enabling cells to regulate processes such as Ca²⁺ homeostasis, migration, proliferation, and adhesion. Located in both plasma and organellar membranes, MSCs, including Piezos, TRPs, K2Ps, MscL, and MscS families exhibit diverse ion selectivity, gating mechanisms and physiological roles. Emerging evidence demonstrates that lipids are dynamic regulators of MSC activation, sensitivity, and kinetics. Endogenous membrane lipids such as cholesterol, phospholipids, sphingolipids and fatty acids modulate MSC behavior by altering bilayer tension, curvature, stiffness and protein–lipid interactions. Exogenous lipids, including dietary fatty acids and lipid-derived metabolites, influence MSCs by modifying membrane physical properties or engaging specific lipid-binding sites on channel proteins. These interactions shape fundamental biological processes and contribute to disease mechanisms in cardiovascular dysfunction, neurological disorders, metabolic disease, and cancer. Despite significant progress, the molecular principles by which lipids regulate MSC conformational transitions and force sensing remain incompletely defined. This review synthesizes current knowledge on endogenous and exogenous lipid modulation of MSCs, integrating structural, computational and electrophysiological insights to highlight emerging therapeutic opportunities targeting lipid–mechanotransduction interfaces. Full article

Because prostate cancer proliferates in an androgen-dependent manner, various inhibitors of androgen production and antagonists of the androgen receptor (AR) are used as therapeutic agents. However, the emergence of castration-resistant prostate cancer has prompted the development of additional treatment strategies. In this study, we focused on the antiprostate cancer effects of vitamin D3 and examined novel antiproliferative effects through the crosstalk with androgen signaling. In human prostate cancer LNCaP cells, homeobox C9 (HOXC9) was identified as a common regulated target gene by dihydroxytestosterone and 1α,25-dihydroxyvitamin D3, but in opposite directions. Ligand-stimulated AR and vitamin D receptor competitively shared binding sites in the HOXC9 regulatory region, but dihydroxytestosterone stimulation preferentially suppressed HOXC9 expression due to the stronger binding properties of AR and the induction of DNA methylation. Forced expression of HOXC9 inhibited androgen signaling to eliminate the androgen-dependent proliferation by associating with the AR transcription complex, in part due to interference with AR binding to some of its targets in LNCaP cells. In summary, this study provides evidence for the involvement of HOXC9 in antiproliferative effects through a regulatory mechanism mediated by a crosstalk between vitamin D receptor and AR. Full article

Canine distemper virus (CDV) remains a highly contagious and lethal pathogen, posing a severe global threat to domestic dogs and wild carnivores. To address the urgent need for effective interventions, we utilized a proprietary Vero-SLAM cell platform to isolate a wild-type CDV strain and generate neutralizing polyclonal antibodies. Subsequently, phage display technology was employed to screen for single-chain variable fragments (scFvs) targeting the CDV hemagglutinin protein (CDV-H). This approach led to the identification of a specific scFv with virus-binding affinity comparable to commercial antibodies, which effectively blocks CDV infection in Vero-SLAM cells. Molecular docking and molecular dynamics simulations were conducted to elucidate the interaction mechanism, suggesting that this scFv binds to a novel and unique epitope on the CDV-H. These findings not only expand our understanding of the antigenic properties of the CDV H protein but also provide a theoretical foundation and a promising candidate molecule for the development of future CDV diagnostics and antiviral strategies. Full article

In this work, we investigate the effect of ligand chemistry on the optical and electrical properties of copper indium disulphide (CuInS₂) quantum dots (QDs) and evaluate their suitability for photodetection with simple device structures. CuInS₂ QDs capped with dodecanethiol (DDT) ligands were synthesized, followed by processes to exchange the DDT with thioglycolic acid (TGA), mercaptopropionic acid (MPA), or thioacetamide (TAA) ligands. Photoluminescence (PL) and UV-Visible absorption studies revealed that while TGA- and MPA-capped QDs retained strong emission, TAA-capped QDs exhibited significant quenching, indicating surface defect formation due to poor ligand binding. Metal–semiconductor–metal (MSM) test structures were fabricated using the QD films as the active layer to study their electrical properties under dark and UV-illuminated conditions. Devices based on MPA- and TGA-capped QD films demonstrated currents that were 7–9 times higher than those of devices with native DDT ligands, with significantly enhanced photocurrent-to-dark current ratios of 2.6 and 1.7, respectively, highlighting the effective charge transport pathways enabled by the shorter ligands. The device with TGA-capped QD film also responded well to 20 kHz pulsed UV excitation, underscoring the strong potential of this simple MSM structure for photodetection and optical switching applications. Full article

Ion channels are fundamental membrane proteins that mediate selective ion flow across biological membranes and thereby govern excitability, signaling, and homeostasis in virtually all cell types. Although channel function is determined by intrinsic structural features, the surrounding lipid milieu is now recognized as a decisive regulatory layer. Lipids tune ion channel activity through complementary mechanisms: they can bind directly to channel proteins, reshape bilayer physical properties, or act as signaling messengers that couple extracellular cues to channel gating. In addition, the organization of membranes into lipid microdomains such as rafts and caveolae can cluster channels with receptors and scaffolds, enhancing signaling specificity and efficiency. Recent advances in cryo-electron microscopy and molecular simulations have expanded our understanding of these lipid–channel interactions, revealing lipids as active modulators rather than passive structural components. This review provides a comprehensive overview of the principles by which lipids regulate ion channel function and highlights the biological and potential clinical significance of this fundamental interplay. Full article

The intrinsic electronic and structural properties of the transition metal rhenium (Re) endow it with substantial application potential in electrocatalysis. However, the high cost of Re requires the development of Re-based materials to reduce cost and optimize the performance at the same time. Herein, a one-step high-pressure and high-temperature (HPHT) synthetic strategy is proposed for fabricating Re-C phase gradient composites, presenting a facile and efficient pathway to develop high-performance hydrogen evolution reaction (HER) electrocatalysts. By studying the structural evolution of Re toward ReC and uncovering its intrinsic mechanism, the regulation of the material’s electrocatalytic activity was successfully realized. Experimental results confirm that HPHT conditions of 5 GPa and 1400 °C effectively induce the formation of multiple crystalline phases of Re-C solid solution and ReC in the Re-C composite. These phases have coherent phase boundaries and form the phase gradient composites. Compared with element Re, the synergistic effect of phase gradient composites broadens the electronic state range by increasing electron transfer from Re to C in ReC (increasing the binding energy) and reduces the binding energy in Re-C solid solution. The broad electronic states range in the phase gradient composites exhibits optimal HER overpotentials of 150 mV (acidic electrolyte) and 166 mV (alkaline electrolyte) at 10 mA cm⁻². These findings provide a promising strategy to boost catalysts’ electrocatalytic performance via constructing phase gradient composites. Full article

The product quality of freeze-dried pear slices is limited by moisture absorption, texture softening, and color deterioration. This study evaluated the effects of sugar impregnation using glucose, fructose, and sucrose at 2 M and 3 M concentrations on key quality attributes. Sugar impregnation improved the product’s appearance, texture, and flavor by reducing moisture absorption, reinforcing the cell wall, and forming a surface sugar layer, exceeding the benefits of osmotic dehydration. Among all groups, 3 M sucrose-treated samples exhibited the highest glass transition temperature (Tg), lowest moisture uptake, and most compact structure, indicating enhanced stability and reduced hygroscopicity. Further analyses revealed that sugar impregnation regulated microstructure and water-binding behavior, contributing to better physical properties. These findings suggest that high-concentration sucrose impregnation is an effective strategy to improve structural integrity and extend the shelf life of freeze-dried fruits and vegetables, offering promising applications in food preservation. Full article

Three novel metal complexes of the tridentate ligand 4-nitro-2-(quinolin-8-yliminomethyl)phenol (NQP) were synthesized and fully characterized using elemental analysis, TGA, magnetic susceptibility, FT-IR, NMR, and UV–Vis spectroscopy. Stoichiometric studies and characterization data proposed square-planar Pd(II), tetrahedral Zn(II), and octahedral Fe(III) geometries. Density functional theory calculations (B3LYP and B3LYP/6-311G(d,p) with LANL2DZ for metals) showed good agreement with experimental findings and revealed enhanced nonlinear optical properties, as evidenced by increased polarizability and hyperpolarizability values. Biological studies demonstrated significant antimicrobial activity, with the Pd–NQP complex exhibiting superior efficacy against bacterial and fungal strains compared to ofloxacin and fluconazole, following the order NQP < Zn < Fe < Pd. Cytotoxicity assays against Hep-G2, MCF-7, and HCT-116 cell lines revealed strong anticancer activity, particularly for the Pd(II) complex (IC₅₀ = 6.35–12.95 μ_g/μL), comparable to cisplatin. All complexes showed higher DPPH radical scavenging activity than ascorbic acid and strong DNA-binding affinity. Antimicrobial activity was further validated experimentally, while molecular docking studies elucidated favorable binding interactions with microbial proteins and cancer-related targets. Full article

The present study aims to evaluate the interaction of gliclazide with proteins related to inflammation—{inhibitor of nuclear factor kappa-B kinase subunit beta (IKKα) and NF-kappa-B-inducing kinase (NIK)}; oxidative stress—{kelch domain of Kelch-like ECH-associated protein 1 (KKeap1)} and ER stress—{inositol-requiring enzyme-1alpha (IRE1α)}. X-ray crystal structure of IKKα, (PDB ID: 5EBZ), KKeap1 (PDB ID: 4L7B), NIK (PDB ID: 8YHW) and IRE1α (PDB ID: 4YZ9) were obtained from Protein Data Bank and Open Babel 3.1.1 was used to prepare the ligands. Prior to docking, protein structures were prepared by removing water molecules, adding hydrogen atoms, and optimizing side chain conformations using Maestro (Schrödinger Suite, version 2024-2) along with the OPLS4 force field. Ligand docking was performed using the Glide application. Molecular dynamics simulation was performed with Desmond (Schrödinger Suite) within the Maestro interface for 100 ns for the NPT ensemble at 300 K and 1 atm pressure. Physicochemical and pharmacokinetics properties were analyzed using ADMETlab 3.0 and SwissADME. The binding energies of gliclazide with IKKα, NIK, KKeap1 and IRE1α were −8.3, −7.9, −8.4 and −8.8, respectively. Root mean square displacement (RMSD), root mean square fluctuation (RMSF) and radius of gyration analyses predicted relatively strong and stable interactions between gliclazide and the proteins, with favourable pharmacokinetic properties. It was also observed that CYP3A4 metabolizes gliclazide, in addition to CYP2C9 and CYP2C19. The activity of gliclazide against inflammation, oxidative stress and endoplasmic reticulum stress might be via interaction with these proteins. Full article

Background: Skin cancer progression is driven by the dysregulation of key oncogenic signaling pathways, including EGFR, BRAF V600E, and TGF-β, which collectively promote tumor proliferation, invasion, and metastatic progression. Targeting these pathways using multitarget natural modulators represents a promising therapeutic strategy. Methods: In this study, forty-nine phytoconstituents from Cannabis sativa were evaluated using an integrated computational approach to explore their inhibitory potential against EGFR, BRAF V600E, and the TGF-β receptor. Molecular docking was performed to assess binding affinities and interaction profiles, followed by ADMET analysis to evaluate pharmacokinetic and safety properties. The top-ranked compounds were further investigated using 200 ns molecular dynamics simulations and MM-GBSA binding free energy calculations to assess the stability and strength of protein–ligand interactions. Results: Several phytoconstituents exhibited strong binding affinities toward the target proteins, formed stable interactions with key active-site residues, and demonstrated favorable pharmacokinetic profiles with acceptable safety characteristics. Molecular dynamics simulations confirmed the structural stability of the selected protein–ligand complexes, while MM-GBSA analysis supported their favorable binding energetics. Conclusions: These findings suggest that Cannabis sativa phytoconstituents may represent a promising source of multitarget modulators capable of attenuating EGFR, BRAF V600E, and TGF-β driven oncogenic signaling in skin cancer. This study provides a mechanistic framework that supports further in vitro validation and the development of cannabis-derived therapeutic candidates for targeted skin cancer management. Full article

Chemosensory proteins (CSPs) are found in the olfactory sensory organs (antennae and maxillary palps) and/or gustatory sensory organs (labellum and legs) and have long been accepted to function through the binding of odorants. However, the same CSPs are also expressed in many tissues other than olfactory and gustatory organs, such as the gut, brain, fat body, wing, epidermis, Corpora allata, salivary gland, pheromone gland, prothoracic gland, etc. In this report, we suggest renaming the “chemosensory protein (CSP)” the “4-Cysteine Soluble Protein (4CSP)”. This paradigm and nomenclature shift is based on molecular characteristics, genomic mining, tissue distribution, and functional roles beyond those related to olfaction. We examined prior studies on this protein gene family to bolster the renaming, highlighting the most recent findings that we ascribe to “pleiotropic properties” and evolutionary relevance rather than smell. The scope of the report, per se, is broad, and this is especially true given the volume of data that has been gathered on 4CSP expressed in ways that are not consistent with the olfactory paradigm. Statements outlining the many chemosensory properties of 4CSPs, particularly how they activate olfactory receptor neurons (ORNs), are currently scarce, if they exist at all. Many debates currently focus on 4CSPs’ non-chemosensory functions, which are backed by a multitude of evidence, from gene evolution to tissue distribution. Therefore, strong arguments in favor of renaming chemosensory proteins are becoming evident here, outweighing the drawbacks. Full article

In response to the growing challenges of climate change and environmental degradation, the European Union announced the Green Deal on 11 December 2019, aiming for climate neutrality by 2050. To achieve this, a series of regulatory measures have been introduced to promote sustainability in the construction sector. This paper examines key EU regulations that, while not explicitly mandating wood, create conditions favorable to timber and wood-based products due to their low-carbon and renewable properties. The Carbon Removal Certification Framework (CRCF) encourages timber adoption through voluntary carbon removal incentives, whereas the new Construction Products Regulation (CPR) represents a mandatory intervention, embedding environmental and climate criteria directly into market standards. Additional regulations, including the Ecodesign for Sustainable Products Regulation (ESPR), the Energy Performance of Buildings Directive (EPBD), the Carbon Border Adjustment Mechanism (CBAM), the Nature Restoration Law (NRL), and the Regulation on Deforestation-Free Products (EUDR), further support wood by promoting resource efficiency, responsible sourcing, energy performance, and long-term carbon storage. Together, these measures form a multi-layered framework in which voluntary and binding instruments interact, indirectly supporting sustainable construction practices. Given its ability to store carbon over extended periods and achieve a net negative footprint in life cycle assessments, wood emerges as a strategic material for advancing the EU’s climate objectives. Full article

Cancer remains the second leading cause of death worldwide, highlighting the urgent need for novel therapeutic agents. In this work, twenty derivatives of N-benzyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides were synthesized and spectroscopically analyzed using FT-IR, NMR (¹H and ¹³C), and elemental analysis. Substitution of benzyl moiety with o-CH₃ (8), p-OCH₃ (10), m-CH₃ (18), p-CH₃ (19), and p-CF₃ (21) demonstrated three-fold distinct cytotoxicity against human colon cancer (HCT-116) cells with IC_50s of 72.0, 100.0–112.0 µM. The cheminformatics calculations disclosed that the analogues possess diverse physicochemical properties and invariable predictions across six drug-likeness scoring models, supporting their potential cytotoxicity profile against colorectal cancer cell lines (Caco-2 and HCT-116). The docking studies against both wild-type and mutant PI3Kα clarified binding interactions, implying that particular functionalities improve efficacy and selectivity. This study provides further evidence for the therapeutic promise of quinolones in targeting cancer-specific pathways and expedites the process for developing potent anticancer agents. Full article