Search Results (380)

To address the challenges of zwitterionic dissociation and steric hindrance in the esterification of α-aromatic amino acids, this study prepared the solid superacid catalyst SO₄²⁻/TiO₂/HZSM-5 (STH) and its plasma-modified derivative SO₄²⁻/TiO₂/HZSM-5 (STH-RF) via an aging-impregnation method. Systematic characterization revealed that plasma modification optimizes the crystal morphology and particle dispersion of the catalyst, while also achieving pore clearance and an increase in the specific surface area. Furthermore, it gradationally enhances acidic properties by increasing the abundance of strong acid and Lewis acid sites, and promotes uniform loading and stable bonding of the SO₄²⁻ active component. Performance evaluation using the synthesis of L-phenylalanine methyl ester as a model reaction demonstrated that STH-RF exhibits optimal catalytic activity, affording a product yield of 85.7%, which is significantly higher than that of unmodified STH (19%) and the homogeneous catalyst H₂SO₄ (63%). This superior performance originates from a “structure–acidity” synergistic effect, combining the thermodynamic advantage of a lower energy barrier for the rate-determining step (12.6 Kcal·mol⁻¹) with efficient kinetics under optimal process conditions (1.0 MPa, 2000 rpm, 170 °C). Moreover, STH-RF maintained a yield above 80% after four consecutive reaction cycles, indicating excellent stability. This work provides a novel catalytic system for the green and efficient synthesis of highly hindered α-amino acid derivatives, holding significant theoretical and practical implications. Full article

Fyn is a Src-family tyrosine kinase implicated in synaptic dysfunction and neuroinflammation across multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Saracatinib (AZD0530) is a potent Src-family inhibitor that has been explored as a repurposed therapeutic; however, its clinical utility is limited by poor kinase selectivity caused by high sequence conservation within Src-family ATP-binding sites. Here, we combine surface plasmon resonance (SPR) and X-ray crystallography to define saracatinib recognition by the Fyn kinase domain (KD). SPR single-cycle kinetics shows that saracatinib binds the isolated Fyn KD and full-length Fyn with low-nanomolar affinity, whereas dasatinib binds with subnanomolar affinity and markedly slower dissociation. We determined the crystal structure of the Fyn KD-saracatinib complex at 2.22 Å resolution. The kinase adopts an active-like conformation with the DFG motif and αC-helix in the ‘in’ state and a conserved β3 αC Lys-Glu salt bridge. Saracatinib occupies the adenine and ribose pockets, and engages the hinge through direct and water-mediated hydrogen bonding while complementing a hydrophobic back pocket by van der Waals contacts. Comparison with reported saracatinib-bound structures of other kinases suggests that the active-state geometry observed for Fyn creates a pocket not observed in inactive-like complexes, providing a structural handle for designing Fyn-selective inhibitors. Comparison with all saracatinib-bound kinase co-structures currently available in the PDB (ALK2 and PKMYT1) indicates a conserved monodentate hinge binding mode but kinase-dependent αC-helix conformations, providing a structural rationale for designing Fyn-selective analogues. Full article

Alkaline water electrolysis remains one of the leading and most mature technologies for large-scale hydrogen production. Its advantages stem from the use of inexpensive, earth-abundant materials and well-established industrial deployment, yet the technology continues to face challenges, including sluggish hydrogen evolution reaction (HER) kinetics and energy-efficiency limitations compared with acidic electrolysis systems. This review provides a comprehensive overview of the fundamental principles governing alkaline electrolysis, encompassing electrolyte chemistry, electrode materials, electrochemical mechanisms, and the roles of overpotentials, cell resistances, and surface morphology in determining system performance. Key developments in catalytic materials are discussed, highlighting both noble-metal and non-noble-metal electrocatalysts, as well as advanced approaches to surface modification and nanostructuring designed to enhance catalytic activity and long-term stability. Particular emphasis is placed on the emerging strategy of in situ ionic activation, wherein transition-metal ions and oxyanions are introduced directly into the operating electrolyte. These species dynamically interact with electrode surfaces under polarization, inducing real-time surface reconstruction, improving water dissociation kinetics, tuning hydrogen adsorption energies, and extending electrode durability. Results derived from polarization measurements, electrochemical impedance spectroscopy, and surface morphology analyses consistently demonstrate that ionic activators, such as Ni–Co–Mo systems, significantly increase the HER performance through substantial increase in surface roughness and increased intrinsic electrocatalytic activity through synergy of d-metals. By integrating both historical context and recent research findings, this review underscores the potential of ionic activation as a scalable and cost-effective way toward improving the efficiency of alkaline water electrolysis and accelerating progress toward sustainable, large-scale green hydrogen production. Full article

The hydrogen gasochromic phenomenon offers a new strategy for real-time sensing technologies for hydrogen leakage to ensure hydrogen safety. However, the limited recovery kinetics impede the cycling and further practical applications. Herein, we designed a series of PtAg-decorated WO₃ nanowires via the chemical reduction deposition method, which could exhibit obvious and reversible color changes for H₂ detection. With the assistance of Ag, the oxygen adsorption and dissociation were accelerated; then, the sample could exhibit a constant rapid recovery rate. The crystalline Pt-Ag/WO₃ nanowires could attain a 50% recovery degree within 52 s, and the recovery time of the Pt-Ag/WO₃ sample was reduced to one fifth that of Pt/WO₃. This study provides a fundamental solution to the challenge of slow recovery kinetics in H₂ gasochromic crystalline materials. Full article

We present a mathematical analysis of the sterol regulatory element-binding protein 2 (SREBP-2) pathway, a key regulator of intracellular cholesterol homeostasis. Using a compartment model formulated as a nonlinear system of ordinary differential equations, we investigate stability via M-matrix theory and norm-based criteria. We show that the Frobenius norm ${\parallel B\parallel }_F\ge 1$ cannot ensure stability, whereas the infinity norm condition ${\parallel B\parallel }_{\infty }<1$ provides a practical guarantee that the spectral radius $\rho \left(B\right)<1$. The spectral norm ${\parallel B\parallel }_2$ yields sharper intermediate bounds. Numerical simulations confirm these results, highlighting parameter regions of stability and showing that the dissociation rate $k_{-1}$ has the strongest influence on system behavior. These findings demonstrate the robustness of the ${\mathsf{\ell }}_{\infty }$ criterion, clarify the role of dissociation kinetics in cholesterol regulation, and provide a rigorous framework for assessing homeostatic control in the SREBP-2 pathway. Full article

Bioactive compounds are widely recognized for their ability to enhance health and prevent diseases due to their various biological activities. However, these compounds are very sensitive to environmental factors, which can reduce their solubility, bioavailability, permeability, and stability, necessitating carriers to protect and ensure targeted delivery. To develop an effective delivery system, it is essential to assess the key factors that influence the release behaviour of bioactive compounds. Therefore, the primary aim of this study is to evaluate how the conditions of the release media, the attributes of hydrogels, and the characteristics of the entrapped bioactive compounds regulate the release kinetics of these compounds. Prior to create suitable carriers, it is essential to comprehend the mechanisms of digestion and absorption of these compounds. Consequently, absorption and the factors influencing stability and bioavailability of bioactives were reviewed first. The conditions of release media, especially the pH, ionic characteristics, temperature, and the nature of solvent served as a critical determinant in the release of bioactive substances by affecting the functional groups, electrostatic interactions between carrier and entrapped bioactive compound, dissociation and conformational changes in polymers. The properties of delivery systems can be controlled using polymers, crosslinkers, plasticizers, and specific environmental factors. The application of dual crosslinkers or a combination of physical and chemical crosslinkers enhanced the efficiency of the crosslinking process, subsequently improving the overall release profile of bioactive compounds from the matrices. Therefore, this review explored several options for enhancing the delivery system. Full article

Plant protease inhibitors (PPI) play a significant role against microbes, insects, and, to a considerable extent, human pathogens. PPIs inactivate hydrolase enzymes or depolarize the plasma membrane of the pathogens, thereby inhibiting their growth, replication, and invasion. Here, an active serine protease inhibitor was isolated and purified from the seeds of Cleome viscosa. The purified inhibitor was homogenous and exhibited a molecular weight of around 12 kDa as a monomer. The secondary structure analysis indicated that the inhibitor was predominantly composed of α-helical content. The kinetics experiments demonstrated a noncompetitive mode of inhibition towards serine protease when casein was used as the enzyme substrate. The inhibitor formed a stable complex with serine protease, having a likely 1:1 stoichiometry, as inferred from ITC, and the dissociation constant was examined to be K_d = 1.9 × 10⁻⁶ M with a Gibbs free energy of ΔG = −8.079 (kcal/mol). The inhibitor exhibits stable protease inhibition up to 90 °C. Further, in vitro preliminary studies revealed its inhibitory effects against HSV-2 function, evidence that it may have a role in the treatment of viral infections. Full article

Utilizing microfluidic models, this review synthesizes experimental and simulation insights into the pore-scale behavior of hydrates during formation and decomposition in porous media. It outlines the fundamental characteristics of CO₂ hydrates and their significance in porous media, with a focus on major advancements in hydrate nucleation, growth, distribution, and decomposition kinetics. This study details various porous media systems, visualization experimental setups, and observation techniques employed in experimental research. Key factors, including temperature, pressure, salinity, and pore characteristics, are analyzed to determine their influence on hydrate formation (nucleation, growth kinetics, and phase equilibrium) and decomposition (dissociation kinetics and efficiency) behaviors. In terms of numerical simulation, we distinguishes multiscale numerical simulation methods for the molecular scale, the pore scale, and then the reactor scale, including molecular dynamics simulation, the phase field model, the pore network model, and the macroscopic kinetics model, and discusses the role of simulation in revealing the micro-mechanisms and predicting macroscopic behaviors. This article also summarizes the application of relevant numerical simulation methods (such as MD, CFD, and LBM) in revealing the micro-mechanism of hydrates. Therefore, this review offers critical insights into the micro-mechanisms of carbon dioxide hydrate behavior in porous media, thereby undergirding the theoretical basis for optimizing related engineering designs. Full article

With the increasing adoption of traveling grate machines, increasing the proportion of pellets in blast furnace burdens has become a key strategy for reducing carbon emissions in ironmaking. Magnetite (Fe₃O₄) is not only the core raw material for pellet production but also serves as an important transition metal oxide catalyst, widely used in various fields due to its unique electronic structure and surface activity. This study employed density functional theory (DFT) and ab initio molecular dynamics (AIMD) to simulate the oxidation process of a Ca-doped Fe₃O₄ (110) surface at 1073 K, revealing the inhibition mechanism of the gangue element Ca and its impact on surface catalytic activity at the atomic scale. The results demonstrate that Ca segregates on the Fe₃O₄ surface, where it adsorbs and activates O₂ molecules, thereby delaying O₂ migration to active iron bridge sites and subsequent dissociation, which ultimately inhibits the oxidation kinetics. Electronic structure analysis indicates that the breakage of the O–O bond is accompanied by a sharp decrease in system energy (stabilizing at approximately −509 eV); it also clearly elucidates the charge transfer process and the mechanism of Fe-O bond formation during this exothermic reaction. This research provides a theoretical foundation for the development of fluxed pellets and high-temperature-resistant catalysts. Full article

In this study, we report the preparation of platinum nanoparticles (Pt NPs) deposited on HTiNbO₅ and the application of the resultant material in the catalytic decomposition of sodium borohydride (NaBH₄) to generate hydrogen. The starting material, KTiNbO₅, was prepared through a solid-state process involving Nb₂O₅, K₂CO₃, and TiO₂. The subsequent treatment with HNO₃ resulted in the exchange of potassium by protons, rendering HTiNbO₅. This material served as support for Pt nanoparticles (3.6 ± 0.7 nm), producing Pt NPs/HTiNbO₅. All compounds were characterized using TGA, FTIR, XRD, Raman, SEM-EDS, and HRTEM. The influence of different factors on the reaction kinetics was evaluated, resulting in a hydrogen generation rate (HGR) of 22,790.18 $\mathrm{m}\mathrm{L} {\mathrm{m}\mathrm{i}\mathrm{n}}^{-1}{\mathrm{g}}_{\mathrm{c}\mathrm{a}\mathrm{t}}^{-1}$ at 50 °C. The activation energy (41.83 kJ mol⁻¹) was also determined. A mechanistic study with deuterated water revealed a kinetic isotopic effect (KIE) value of 1.27, indicating the dissociation of B-H from BH₄⁻ as the rate-determining step of the process. Furthermore, the reuse and durability of the material were evaluated, revealing a catalyst performance close to 100% over the 10 tested cycles. Therefore, it can be concluded that the synthesized material, Pt-nanoparticles dispersed on HTiNbO₅, exhibits excellent performance and is suitable for hydrogen evolution from NaBH₄. Full article

Background/Objectives: The cell surface proteoglycan glypican-3 (GPC3) is reportedly overexpressed in hepatocellular carcinoma (HCC) tissues, but not in benign liver tissues, rendering this protein a potential target for radionuclide theranostic approaches. Peptides are generally a promising class of targeting molecules for the development of radioligands because they combine straightforward synthetic access with favorable pharmacokinetics. Among the published peptides with disclosed structures, one of the most promising radioligands is [¹⁸F]AlF-NOTA-TJ12P2, which has a reported comparably high binding affinity to GPC3 and a high hydrophilicity. In this study, we aimed to design novel GPC3-targeting radioligands based on the TJ12P2 peptidic scaffold. Methods: Peptides were synthesized on solid phase using an Fmoc protecting group strategy. For comparative investigations, the reference nanobody HN3 was expressed in E. coli, isolated and subsequently modified with NODA-GA or SulfoCy3. The binding of native peptides, scrambled variants and reference nanobodies to GPC3 was investigated by surface plasmon resonance (SPR) interaction analysis, and fluorescently labeled versions of peptides and nanobodies were used for fluorescence microscopy in HepG2 (GPC3+) or SK Hep1 (GPC3−) cells. The chelator-bearing peptides were radiolabeled with gallium-67 and their stability towards radiolysis and in human serum was investigated. The binding of radiolabeled peptides and nanobodies to HepG2 cells was assessed in real-time ligand binding experiments. Results: The synthesized native peptides did not exhibit binding towards GPC3 in SPR interaction analyses, and the observed response was comparable to that of the scrambled variants at equal concentrations. Additionally, no binding to or uptake of the fluorescent constructs into cells was observed with fluorescence microscopy regardless of cellular GPC3 expression level. In real-time radioligand binding experiments, very fast association and dissociation of the gallium-67 labeled peptides to GPC3 positive HepG2 cells was observed, suggesting either extremely fast binding kinetics or unspecific binding of the peptides. Conclusions: Taken together, these findings suggest that the peptide TJ12P2 lacks specific binding to GPC3 in vitro and might not serve as a basis for the development of radioligands targeting GPC3. Full article

New compostable materials have been developed to replace single-use soft materials such as polyurethane foams (PUR). To this end, eco-friendly systems have been formulated on the basis of agar gels prepared in mixed solvent (glycerol/water) to meet specifications, i.e., stiffness of several hundred kPa, reasonable extensibility, and good stability when exposed to open air. While the addition of glycerol slows down gelation kinetics, mechanical properties are improved up to a glycerol content of 80 wt%, with enhanced extensibility of the gels while maintaining high Young’s moduli. Swelling analyses of mixed gels, in water or pure glycerol, demonstrate the preservation of an energetic network, with no change in volume, in pure water and the transition towards an entropic network in glycerol related to the partial dissociation of helix bundles. Dimensional and mechanical analysis of gels aged in an open atmosphere at room temperature shows that the hygroscopic character of glycerol enables sufficient water retention to maintain the physical network, with antagonistic effects linked to relative increases in glycerol, which tends to weaken the network, and agar, which on the contrary strengthens it. Complementary analyses carried out on aged agar gels formulated with an initial glycerol/water mass composition of 60/40, the most suitable for the targeted development, enabled the comparison of the properties of agar gels favorably with those of PURs and verified their stability during long-term storage, as well as their non-toxicity and compostability. Full article

Developing high-activity and high-durability Pd-based electrocatalysts is an important strategy to promote their commercial application. Herein, a smaller particle size and ultrathin sheet-like PdCu alloy metallene (PdCuene) were successfully prepared by using a one-pot wet chemistry method for FAOR. Experimental measurements indicated that the introduction Cu into Pd lattice induces a significant compressive strain effect through lattice mismatch between Pd and Cu, and the strain effect optimizes the electronic structure of Pd, as well as the high electrochemical surface area, increased exposure of active sites, and appropriate lattice strain have been demonstrated as factors that influence the enhancement of intrinsic activity and the acceleration of kinetics, thereby improving FAOR performance. Moreover, the stronger lattice strain of 0.85% would facilitate surface adsorption and dissociation of formic acid. Specifically, the optimized PdCuene exhibits enhanced mass activity and specific activity with current densities of 2.31 A mg_Pd⁻¹ and 4.09 mA cm⁻², respectively, which transcend the activities of Pd metallene (1.44 A mg_Pd⁻¹ and 2.73 mA cm⁻²) and commercial Pd/C (0.6 A mg_Pd⁻¹ and 1.53 mA cm⁻²). Meanwhile, PdCuene displayed obvious enhanced durability. The work provides an approach to modulate the lattice strain engineering, which represents a highly promising strategy for designing efficient FAOR electrocatalysts. Full article

Anecdotal reports have recently circulated suggesting that intramuscular injection of bacteriostatic saline (BS)—which contains benzyl alcohol (BnOH)—can reverse botulinum toxin type A (BoNTA)-induced brow ptosis. Given the well-established intracellular persistence of BoNTA’s light chain and its irreversible cleavage of SNAP-25, such rapid functional recovery challenges existing pharmacological understanding. This study employed high-resolution pharmacokinetic/pharmacodynamic (PK/PD) modelling using the AesthetiSim™ platform to systematically evaluate this hypothesis. A total of 30,000 virtual patients were randomized to receive BoNTA alone, BoNTA followed by BS injection, or BoNTA followed by normal saline (NS) at Day 7. The model incorporated BoNTA diffusion, internalization, SNAP-25 cleavage, neuromuscular output, and transient BS effects on membrane permeability and endosomal trafficking. Simulated recovery trajectories were tracked over 90 days. The primary outcome, time to 80% restoration of baseline frontalis muscle force (T₈₀), averaged 42.0 days in the BoNTA-only group and 35.5 days in the BS group (Δ = −6.5 days; p < 0.001). Only 13.9% of BS-treated patients reached the T₈₀ threshold by Day 30. Partial reactivation (T₃₀) occurred earlier with BS (21.8 ± 5.3 days vs. 27.3 ± 4.9 days), and the area under the effect curve (AUEC) was increased by 9.7%, reflecting higher overall muscle function over time. In molecular simulations, BnOH produced a minor rightward shift in the BoNTA–SNAP-25 dissociation curve, but receptor occupancy remained above 90% at therapeutic toxin concentrations, suggesting no meaningful impairment of binding affinity. A global Sobol sensitivity analysis demonstrated that the primary driver of recovery kinetics was intracellular LC degradation (49% of T₈₀ variance), while BS-modulated extracellular parameters collectively contributed less than 20%. These findings indicate that BS does not reverse the molecular action of BoNTA but may transiently influence recovery kinetics via non-receptor-mediated pathways such as increased membrane permeability or altered vesicular trafficking. The magnitude and variability of this effect do not support the notion of a true pharmacologic reversal. Instead, these results emphasize the need for mechanistic scrutiny when evaluating rapid-reversal claims, particularly those propagated through anecdotal or social media channels without supporting biological plausibility. Full article

The Long Interspersed Element-1 (L1) retrotransposon is an ancient genetic parasite that comprises a significant part of the human genome. ORF2p is a multifunctional enzyme with endonuclease (EN) and reverse transcriptase (RT) activities that mediate target-primed reverse transcription of RNA into DNA. Structural studies of LINE-1 ORF2p consistently show a single Mg²⁺ cation in the reverse transcriptase active site, conflicting with the common DNA polymerase mechanism which involves two divalent cations. We explored a reaction pathway of the DNA elongation based on the recent high-resolution ternary complex structure of the ORF2p. The combined quantum and molecular mechanics approach at the QM (PBE0-D3/6-31G**)/MM (CHARMM) level is employed for biased umbrella sampling molecular dynamics simulations followed by umbrella integration utilized to obtain the free energy profile. The nucleotidyl transfer reaction proceeds in a single step with a free energy barrier of 15.1 ± 0.8 kcal/mol, and 7.8 ± 1.2 kcal/mol product stabilization relative to reagents. Concerted nucleophilic attack by DNA O3′ and proton transfer to Asp703 occur without a second catalytic metal ion. Estimated rate constant ∼60 s⁻¹ aligns with RT kinetics, while analysis of the Laplacian of the electron density along the cleaving P-O bond identifies a dissociative mechanism. Full article