Search Results (4,711)

Bisphenol S (BPS), an environmental endocrine disruptor, has been implicated in polycystic ovary syndrome (PCOS), but its underlying molecular targets remain largely uncharacterized. Here, this study integrated network toxicology, molecular simulations and in vitro cellular assays to identify key mediators of BPS-associated PCOS. A total of 199 overlapping target genes between BPS exposure and PCOS were screened from public databases, predicted hub genes were extracted via protein–protein interaction (PPI) network construction and 30 core hub genes were enriched in oxidative stress, hormone response, inflammation, cell-cycle regulation, and PI3K-Akt, FoxO, AGE-RAGE, and endocrine resistance pathways by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Using molecular docking simulations found that the top 15 hub proteins exhibited favorable binding affinities for BPS, with binding free energies below −5.0 kcal/mol. Molecular dynamics simulations revealed that BPS binding induced only minor conformational perturbations in EGFR and ESR1, with negligible effects on backbone stability, core domain flexibility, global compactness and surface properties. In contrast, BPS association effectively dampened global backbone fluctuations and the residue-level mobility of IGF1, and the intermolecular hydrogen bond strength followed the order IGF1 > EGFR > ESR1. In KGN cells, BPS suppressed cell viability and proliferation in a time- and dose-dependent manner while upregulating the protein levels of EGFR, ESR1 and IGF1; notably, IGF1 was most sensitive to low-dose BPS exposure. These findings suggest that BPS may exacerbate PCOS progression by upregulating EGFR, ESR1 and IGF1 to inhibit granulosa cell growth, and thereby disrupt ovarian oxidative homeostasis, hormone signaling, insulin metabolism and cell-cycle regulation via the PI3K-Akt and FoxO pathways. This study provides a theoretical framework for assessing the reproductive health risks of BPS, and lays a foundation for further experimental validation and population-based epidemiological research. Full article

Water plays an active role in organic chemistry, yet the number of explicit water molecules required to describe the local solvation environment of small organic substrates remains poorly established. Herein, we examine the solvation of five small polar hydrogen-bond (HB) acceptors using explicit molecular clusters containing two to twelve water molecules. Conformational searches, electronic structure calculations, and Interacting Quantum Atoms (IQA) energy decomposition were combined to assess energetic convergence and the nature of solute–water interactions. Binding and water deformation energies converge at approximately ten water molecules, defining a practical minimum hydration shell for these substrates. Solute–water interactions are largely confined to the first solvation shell, within ca. 3.5 Å of the heteroatom of the organic substrate, while more distant water molecules recover a bulk-like local environment. Except for trimethylamine, the strongest solute–water contact is weaker than the average HB among water molecules. IQA further shows that differences among interaction energies are governed mainly by the exchange-correlation component, revealing an important covalent contribution to hydrogen bonding. Multiacceptor hydrogen-bonded sites preferentially form water networks around only one HB acceptor rather than bridged independent hydration spheres around each HB acceptor. These results provide practical criteria for constructing compact, chemically meaningful explicit solvation models in aqueous organic chemistry. Full article

This study aimed to determine how insulin’s pharmaceutical form governs release from a topical matrix and to provide a molecular-level rationale for the observed behavior. A hybrid hydrogel of Carbopol^® Ultrez™ 10 and sodium alginate (1:2) was loaded with human insulin in two clinically distinct forms: a soluble solution (Actrapid^®) and an isophane/NPH suspension (Insulatard^®). Insulin release from the CU10:SA (1:2) hybrid hydrogel is continuous, without any sudden surge in release (the so-called *burst* effect), and follows diffusion according to Fick’s law. The soluble formulation released more insulin than the suspension, although the two profiles were similar in shape (f₁ = 13.39; f₂ = 97.54). The two CU10/SA insulin hydrogels were pseudoplastic fluids with pronounced shear-stress hysteresis and did not differ in hardness, cohesiveness, adhesiveness, or elasticity. Two rheological models, including the Carreau–Yasuda (CY) model and Santesarti’s shear rate-based model (SRB), described the recorded shear stress vs. shear rate curves fairly well. To explore this behavior at the molecular level, cavity-guided blind docking (CB-Dock2/AutoDock Vina) was performed on both the insulin monomer and the assembled zinc hexamer, using deprotonated oligomer models of the polymers. The alginate and Carbopol fragments converged on a single B-chain surface patch, where a carboxylate–Arg-B22 salt bridge supported by hydrogen bonding appeared to be the main anchoring motif, with weak docking scores (−4.5 to −4.9 kcal/mol on the insulin monomer) indicative of reversible physisorption rather than tight binding; the same patch was also engaged on the hexamer, which suggests that the proposed interaction motif does not depend on the insulin association state. These docking results are hypothesis-generating and complement, rather than prove, the experimental findings. The greater release of soluble insulin is attributed mainly to its pharmaceutical form, since the larger, less mobile protamine–zinc microcrystals of NPH insulin are likely to be more strongly entrapped in the matrix, rather than to differences in interaction chemistry. Together, the results link interaction chemistry, formulation state, and diffusion-controlled release. Full article

This study investigated the effects of a combination of κ-carrageenan (CRG), konjac glucomannan (KGM) and a sodium caseinate-stabilized camellia oil emulsion on the quality attributes of surimi. The results demonstrated that adding the emulsion alone enhanced the textural properties but failed to increase the water-holding capacity (WHC) or reduce cooking loss. In contrast, incorporating both polysaccharides with the emulsion reduced cooking loss to 7.3% of that of the control (2.3 ± 1.0% vs. 31.4 ± 1.4%) and increased the WHC to 97.7 ± 1.3%, representing a 47.8% improvement over the control (66.1 ± 1.2%). Furthermore, this ternary composite system yielded substantial enhancements in the textural profile of the gels. These improvements were attributed primarily to the formation of hydrogen bonds between the polysaccharides and surimi proteins, which strengthened intermolecular interactions. Microstructural observations corroborated this mechanism, revealing that the composite system promoted the formation of a denser and more uniform network, which improved the freeze–thaw stability of the surimi. Sensory evaluation indicated that the combined treatment enhanced the flavor profile and acceptability of surimi gels. Thus, KGM and CRG can be combined with sodium caseinate-stabilized camellia oil emulsion to improve the quality of surimi gels. These results offer valuable theoretical guidance for advancing surimi-based foods. Full article

The coexistence of dyes and phosphate in industrial effluents creates a treatment challenge because both contaminants can occur as negatively charged species while interacting differently with adsorbent surfaces. To explore a potential solution, this study evaluated magnesium oxysulfite/sulfate (MgOS) for methyl orange (MO) and phosphate adsorption under single- and binary-solute conditions. MgOS was characterized by complementary physicochemical and surface analyses, and adsorption equilibrium, kinetics, thermodynamics, pH effects, and competitive behavior were examined. MgOS exhibited a mesoporous, chemically heterogeneous structure and maintained effective adsorption over a broad pH range with an apparent pH-regulating effect. Adsorption capacities reached 50.6 mg g⁻¹ for MO and 16.3 mg g⁻¹ for phosphate in single-solute systems. MO reached equilibrium within 7–45 min and was generally described by pseudo-first-order kinetics. Phosphate required 150–360 min and showed concentration-dependent kinetic behavior, with PSO and Elovich models providing the best fits depending on the fitting approach and initial concentration. MO adsorption was spontaneous and exothermic, while phosphate adsorption was spontaneous and endothermic. Surface characterization supported electrostatic interactions, hydrogen bonding, and Mg-site coordination for MO, whereas phosphate removal involved ligand exchange, inner-sphere coordination, and Mg-O-P/Mg-phosphate-like species. Phosphate reduced MO adsorption by 11.9–30.7% in binary systems, while phosphate adsorption remained comparatively stable. MgOS therefore showed potential for simultaneous MO and phosphate removal under competitive conditions. Full article

The Gibbs equation describes the relationship between the enthalpy (∆H), entropy (∆S), and Gibbs energy (∆G) changes in physicochemical processes: ∆G = ∆H − T∆S. It remains a cornerstone of chemical thermodynamics, yet it has features that need to be understood. The linear correlations between ∆S and ∆H (or ∆G and ∆H) are often found across various series of processes. These correlations do not follow from the laws of thermodynamics, thus meaning that there may be additional restrictions on the variation in the thermodynamic potentials. In this study, we attempted to establish the quantitative principles governing the ∆G vs. ∆H relationship across various processes involving non-covalent interactions at 298.15 K, from solvation and vaporization to molecular complexation and supramolecular recognition. The baseline for the analysis was the linear ∆G vs. ∆H correlation for solvation in non-associated solute–solvent systems, first noted by Barclay and Butler. The classification of the solute–solvent systems enabled quantification of the deviations associated with conformational flexibility, complexation and solvophobic effects upon solvation. These regularities necessarily meant that the ∆G vs. ∆H for solution- and gas-phase molecular complexation processes should be described by similar linear relationships, having the same slope as the Barclay–Butler baseline. Furthermore, this framework was applied to α-cyclodextrin host–guest systems. The validity of the established relationships was checked against more than 4500 experimental thermodynamic values. They enable the calculation of the enthalpy change from a single equilibrium constant measurement at 298.15 K, with the deviation comparable to an experimental uncertainty. The predictive power does not depend on the process (solvation, vaporization, and complexation), the phase it takes place in (gas, liquid), or the dominating interaction type (collective/pairwise, van der Waals forces/hydrogen bonding/charge transfer), highlighting the uniform character of the discussed relationships. Full article

Ziziphus seeds, an abundant and low-cost lignocellulosic residue generated across the value chains of Z. mauritiana, Z. spina-christi, and Z. jujuba in arid and semi-arid regions, have emerged as a promising but under-synthesized feedstock for adsorption-based water treatment. This review provides a critical, mechanism-focused assessment of Ziziphus seed-derived adsorbents—raw biomass, biochars, activated carbons, and magnetic or nanocomposite hybrids—covering preparation routes, physicochemical characterization, adsorption mechanisms, and environmental performance for dye and heavy metal remediation. Comparative analysis of the literature (2020–2025) shows that adsorption capacity is dictated primarily by the intensity and nature of thermochemical/chemical modification rather than by botanical origin alone: chemical activation with H₃PO₄, H₂SO₄, or ZnCl₂ and alkali or magnetic functionalization yield specific surface areas ranging from approximately 100 to 1900 m² g⁻¹ and substantially enhance dye and metal uptake relative to unmodified biomass. Mechanistic evidence indicates that dye removal is governed predominantly by electrostatic attraction, hydrogen bonding, π–π interactions, and pore filling, whereas heavy metal sequestration (particularly Cr(VI), Cd(II), and Pb(II)) proceeds via surface complexation, ion exchange, and, in some systems, redox transformation, with markedly pollutant-specific pH optima. Kinetic and equilibrium data are best described by pseudo-second-order and Freundlich models for heterogeneous carbons and metal systems, while pseudo-first-order and Langmuir behavior are more prevalent for rapidly adsorbing dyes and structurally hybridized materials; thermodynamic parameters confirm spontaneous, but mechanistically variable (endothermic or exothermic), adsorption. Despite promising bench-scale capacities, including magnetic biochars achieving >98% Cr(VI) removal, the field remains constrained by an overreliance on idealized single-solute batch systems and negligible data on the removal of nutrients, pharmaceuticals, and per- and polyfluoroalkyl substances. Future research should prioritize application-specific functionalization, continuous-flow and multicomponent testing, long-term regeneration studies, and integrated sustainability assessment to advance Ziziphus-derived adsorbents toward field-scale deployment. Full article

To enhance the comprehensive service performance of road asphalt mastic, untreated bamboo fiber (UBF), acid-treated bamboo fiber (ABF), and alkali-treated bamboo fiber (NBF) were prepared for asphalt modification. Basic physical test, contact angle surface energy test, dynamic shear rheometer (DSR), linear amplitude sweep (LAS) fatigue test, and bending beam rheometer (BBR) low-temperature test were conducted to characterize macro-performance, interfacial bonding, high-temperature deformation resistance, fatigue durability, and low-temperature cracking performance. Compared with neat base asphalt, the adhesion energy of NBF-modified asphalt mastic increased by 88.1%, and the 64 °C rutting factor (G*/sin δ) was elevated by 41.3%. At 2.5% strain amplitude, the fatigue life of NBF mastic was 3.2 times that of UBF mastic and 8.3 times that of ABF mastic. Meanwhile, NBF yielded lower BBR creep stiffness modulus S and higher m-value, indicating improved low-temperature crack-resistance performance. Alkali treatment stripped hemicellulose and wax on the fiber surface to expose abundant hydroxyl groups, forming hydrogen bonding interactions with asphalt polar components. Its adhesion energy was 36.2% higher than that of UBF mastic. Acid etching increased fiber surface roughness but failed to form effective polar bonding, leading to only 22.6% improvement in rutting factor and limited fatigue promotion. Comprehensive weighted scoring demonstrated that the comprehensive performance of NBF modified asphalt was 23.9% higher than UBF and 36.2% higher than ABF. Alkali-modified bamboo fiber is a sustainable plant fiber modifier with an excellent effect on multiple performance indices for pavement asphalt. Full article

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, and obesity and type 2 diabetes (T2D) are recognized metabolic risk factors for its development. In this study, disease-associated gene lists for T2D and obesity were integrated with differentially expressed genes from the Cancer Genome Atlas Liver Hepatocellular Carcinoma cohort (TCGA-LIHC). Analysis of 371 primary HCC and 50 solid-tissue normal samples identified 2123 differentially expressed genes, including 715 upregulated and 1408 downregulated genes. The intersection of the 715 upregulated genes with 2055 T2D-associated and 1944 obesity-associated protein-coding genes identified 29 common candidates. Functional annotation identified 14 extracellular-region genes, which were evaluated using protein–protein interaction analysis and ranked using the maximal clique centrality algorithm. SPP1, encoding Osteopontin (OPN), was the highest-ranked candidate. SPP1 expression distinguished HCC from non-tumor tissues with an area under the receiver operating characteristic curve of 0.714 (95% confidence interval: 0.666–0.760). High SPP1 expression was associated with poorer overall survival, and continuous log2-transformed SPP1 expression remained independently associated with survival after adjustment for age, sex, and pathological stage. OPN was subsequently subjected to structural modeling, molecular dynamics simulation, B-cell epitope prediction, and the structure-guided optimization of anti-OPN monoclonal antibodies. Molecular docking and binding affinity analyses revealed that optimized mAbs exhibited predicted Kd values corresponding to approximately 10- to 650-fold stronger binding affinity and increased predicted hydrogen bonding at the interface. These findings support SPP1 as a promising immunotherapeutic target in metabolically driven HCC, warranting further experimental validation. Full article

In the absence of electronic reasons for distortion and with its ligands idealized as spherical, the hexaaquanickel(II) cation may be regarded as a simple example for octahedral metal coordination. In structurally characterized derivatives, the cation must adopt a lower symmetry in which it may well be distorted. We investigate hexaaquanickel(II) 3-carboxy-4-hydroxybenzenesulfonate dihydrate, a solid in which the cation occupies a center of inversion and subtends classical O–H···O hydrogen bonds with anions and co-crystallized water. Based on high-resolution X-ray diffraction, we analyze the resulting experimental electron density in order to understand why one of the three independent Ni–O coordinative bonds is significantly shorter than the others. The electron density and its derived properties in the bond critical points do not indicate correlation between hydrogen and coordinative bonds. The electrostatic potential derived from the experimental density reflects the electron distribution in the d orbitals and suggests that intra-cation repulsions and attractions are responsible for the distorsion of the cation. The quality of our experimental results is further underlined by a very good match between the measured electron density in the bond critical points of the Ni–O coordinative bonds and a previous report in the literature. Full article

The reaction of Cd(NO₃)₂·4H₂O with the fluorescent ditopic N-donor ligand 2,5-bis[(pyridin-3-yl)ethynyl]thiophene (L) afforded the new coordination polymer {[Cd(L)(H₂O)₂(NO₃)₂]∙1.25H₂O}_n (1). Single-crystal X-ray diffraction analysis revealed that the Cd^II centre is heptacoordinated and adopts a distorted pentagonal-bipyramidal coordination geometry, with two bridging L ligands in the axial positions and water molecules and nitrate anions occupying the equatorial plane. The antiperiplanar conformation of L promotes the formation of zigzag polymeric chains, which are further assembled through O–H···O hydrogen bonds and π–π stacking interactions into a 3D supramolecular network containing solvent-accessible channels. Compound 1 was further characterised by FT-IR spectroscopy, melting point determination, and solid-state absorption and emission spectroscopy. Full article

Background: DNase I inhibitors may be useful as biochemical tools and as potential leads for investigating pathological processes associated with excessive DNA degradation. Squaramides represent attractive scaffolds for drug discovery owing to their rigid, highly polarized structure and versatile hydrogen-bonding properties. Methods: Four novel pyridine-containing squaramides (5a–5d), comprising two symmetric and two asymmetric derivatives, were synthesized and structurally characterized by spectroscopic methods and, for 5a and 5b, single-crystal X-ray diffraction. Their DNase I inhibitory activity and cytotoxicity were evaluated experimentally. Comparative structure–activity analysis, molecular docking, molecular descriptor calculations, and in silico ADME profiling were additionally performed. Results: All compounds inhibited bovine pancreatic DNase I, with IC₅₀ values ranging from 34.42 ± 5.86 to 61.95 ± 9.61 μM. Compound 5a showed the highest inhibitory activity within the present series (IC₅₀ = 34.42 ± 5.86 μM). Comparison with five previously reported structurally related derivatives identified preliminary structure–activity trends, with 5a exhibiting the highest activity among the nine compounds considered. Molecular docking predicted a common preferred binding region within the major DNA-contact/catalytic region of DNase I and suggested possible noncovalent ligand–enzyme interactions. Molecular descriptor calculations revealed differences in the electronic properties of selected compounds, while in silico ADME analysis predicted generally favorable physicochemical and absorption-related properties together with potential pharmacokinetic liabilities. No measurable cytotoxicity was observed against the investigated cancer cell lines at the tested concentrations. Conclusions: Pyridine-containing squaramides represent a promising scaffold for further investigation as DNase I inhibitors, with 5a providing a useful starting point for subsequent structural optimization and mechanistic studies. Full article

Chlorogenic acid (CA), the principal bioactive constituent of honeysuckle, is conventionally extracted by time-consuming methods using toxic organic solvents, which carry the risk of thermal degradation. This study provides a rapid and efficient microwave-assisted deep eutectic solvent (DES-MAE) method for CA extraction and elucidates its mechanism at the molecular level. Eight DESs were systematically screened, and extraction parameters were optimized via single-factor experiments and response surface methodology (RSM). Density functional theory (DFT) calculations were performed to reveal the DES-CA interaction mechanism. Benzyltrimethylammonium chloride–ethylene glycol with 40% water content was identified as optimal. Under the optimized conditions (640 W, 78 s, and 9.35 mg/mL), the quadratic model (R² = 0.9879) predicted a CA yield of 39.851 mg/g, which was consistent with the experimental value of 39.431 ± 0.068 mg/g (1.1% relative deviation). DFT calculations revealed four hydrogen bonds and π-π stacking between DES1 and CA, with a binding energy of −25.641 kcal/mol, which far exceeded those of water (−5.277 kcal/mol) and ethanol (−8.946 kcal/mol). The DES-MAE method achieved the highest extraction yield within merely 78 s, compared with 60 min for HRE and 30 min for the pharmacopoeial method. This work provides a rapid, efficient, and mechanistically validated strategy for extracting bioactive compounds from traditional Chinese medicinal materials. Full article

Chitosan films have attracted increasing attention as biodegradable packaging materials; however, their relatively low stiffness and limited mechanical stability restrict their practical application. In this study, ramie elementary fiber-reinforced chitosan composite films were prepared using ramie elementary fiber suspensions at concentrations of 0, 0.5, 1.0, and 1.5 g/L. The mechanical properties, chemical interactions, crystalline structure, and surface morphology of the composite films were systematically investigated by tensile testing, Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The results showed that the incorporation of ramie elementary fibers significantly affected the mechanical behavior of chitosan films. Among the tested concentrations, the composite film with 0.5 g/L ramie elementary fibers exhibited the best overall performance, with the elastic modulus increasing by 130% from 67.46 MPa to 155.14 MPa compared with the pure chitosan film. FTIR analysis indicated that the formation of hydrogen-bonding between ramie elementary fibers and the chitosan matrix, while XRD results showed that the incorporation of ramie elementary fibers enhanced the structural ordering of the chitosan-based composite films without forming a new crystalline phase. SEM observations further confirmed that an appropriate fiber content promoted uniform dispersion and good interfacial bonding, whereas excessipve fiber addition led to aggregation, surface roughening, and interfacial defects. These findings demonstrate that low-content ramie elementary fibers can effectively improve the stiffness and structural stability of chitosan composite films, providing a potential strategy for developing biodegradable fiber-reinforced packaging materials. Full article

Jujube polysaccharides (ZJPA) and cyclic adenosine monophosphate (cAMP) are bioactive compounds with antioxidant and health-promoting potential, and their combination exhibits enhanced antioxidant activity. However, their limited stability and susceptibility to gastrointestinal environmental stresses restrict their applications in functional foods. In this study, a pH-responsive composite hydrogel bead delivery system was developed using chitosan (CS) and sodium alginate (SA) as wall materials to co-encapsulate ZJPA and cAMP, aiming to protect these bioactive compounds during gastrointestinal digestion while maintaining their enhanced functionality. The hydrogel beads were fabricated via the ionotropic gelation method, and the formulation parameters were optimized using single-factor experiments combined with response surface methodology (RSM). The optimized hydrogel beads were obtained under the conditions of calcium chloride concentration of 3%, CS concentration of 0.5%, SA concentration of 3%, and core-to-wall ratio of 1:6, with a cAMP microencapsulation yield (MEY) of 97.79%. Structural characterization confirmed that ZJPA and cAMP were successfully incorporated into the CS-SA network through electrostatic interactions and intermolecular hydrogen bonding without the formation of new covalent bonds. Furthermore, the hydrogel beads exhibited distinct pH-responsive swelling and gastrointestinal release behaviors, providing effective protection under acidic gastric conditions and enabling sustained release under intestinal conditions. Importantly, the DPPH radical scavenging assay demonstrated that the co-encapsulation strategy preserved the enhanced antioxidant activity between ZJPA and cAMP. Overall, this study establishes a multifunctional hydrogel bead delivery strategy integrating enhanced bioactivity preservation, gastrointestinal protection, and controlled release, providing new opportunities for the application of jujube-derived bioactive compounds in functional foods. Full article