Search Results (1,944)

This study was designed to systematically identify novel umami peptides in lager beer, clarify their molecular interactions with the T1R1/T1R3 receptor, and determine their specific effects on multidimensional sensory attributes. The peptides were characterized by LC-MS/MS combined with de novo sequencing, and 906 valid sequences were obtained. Machine-learning models (UMPred-FRL, Tastepeptides-Meta, and Umami-MRNN) predicted 76 potential umami peptides. These candidates were docked to T1R1/T1R3 with the CDOCKER protocol, producing 57 successful complexes. Six representative peptides—KSTEL, DELIK, DIGISSK, IEKYSGA, DEVR, and PVPL—were selected for 100 ns molecular-dynamics simulations and MM/GBSA binding-energy calculations. All six peptides stably occupied the narrow cleft at the T1R1/T1R3 interface. Their binding free energies ranked as DEVR (−44.09 ± 5.47 kcal mol⁻¹) < KSTEL (−43.21 ± 3.45) < IEKYSGA (−39.60 ± 4.37) ≈ PVPL (−39.53 ± 2.52) < DELIK (−36.14 ± 3.11) < DIGISSK (−26.45 ± 4.52). Corresponding taste thresholds were 0.121, 0.217, 0.326, 0.406, 0.589, and 0.696 mmol L⁻¹ (DEVR < KSTEL < IEKYSGA < DELIK < PVPL < DIGISSK). TDA-based sensory validation with single-factor additions showed that KSTEL, DELIK, DEVR, and PVPL increased umami scores by ≈21%, ≈22%, ≈17%, and ≈11%, respectively, while DIGISSK and IEKYSGA produced marginal changes (≤2%). The short-chain peptides thus bound with high affinity to T1R1/T1R3 and improved core taste and mouthfeel but tended to amplify certain off-flavors, and the long-chain peptides caused detrimental impacts. Future formulation optimization should balance flavor enhancement and off-flavor suppression, providing a theoretical basis for targeted brewing of umami-oriented lager beer. Full article

In this study, we present a comprehensive theoretical analysis of modifications in the physical and chemical properties of MoSe₂ upon the introduction of substitutional transition metal impurities, specifically, Ti, V, Cr, Fe, Co, Ni, Cu, W, Pd, and Pt. Wet systematically calculated the adsorption enthalpies for various representative analytes, including O₂, H₂, CO, CO₂, H₂O, NO₂, formaldehyde, and ethanol, and further evaluated their free energies across a range of temperatures. By employing the formula for probabilities, we accounted for the competition among molecules for active adsorption sites during simultaneous adsorption events. Our findings underscore the importance of integrating temperature effects and competitive adsorption dynamics to predict the performance of highly selective sensors accurately. Additionally, we investigated the influence of temperature and analyte concentration on sensor performance by analyzing the saturation of active sites for specific scenarios using Langmuir sorption theory. Building on our calculated adsorption energies, we screened the catalytic potential of doped MoSe₂ for CO₂-to-methanol conversion reactions. This paper also examines the correlations between the electronic structure of active sites and their associated sensing and catalytic capabilities, offering insights that can inform the design of advanced materials for sensors and catalytic applications. Full article

Fissure swarms and dike swarms in Iceland constitute the main parts of volcanic systems that are 40–150 km long, 5–20 km wide, extend to depths of 10–20 km, and contain 2 × 10¹⁴ outcrop-scale (≥0.1 m) and 10^22–23 down to grain-scale (≥1 mm) fractures, suggesting that statistical physics is an appropriate method of analysis. Length-size distributions of 565 outcrop-scale Holocene fissures (tension fractures and normal faults) and 1041 Neogene dikes show good to excellent fits with negative power laws and exponential laws. Here, the Helmholtz free energy is used to represent the energy supplied to the swarms and to derive the Gibbs–Shannon entropy formula. The calculated entropies of 12 sets and subsets of fissures and 3 sets and subsets of dikes all show strong positive correlations with sets/subsets length ranges and scaling exponents. Statistical physics considerations suggest that, at a given time, the probability of the overall state of stress in a crustal segment being heterogeneous is much greater than the state of stress being homogeneous and favourable to the propagation of a fissure or a dike. In a heterogeneous stress field, most fissures/dikes become arrested after a short propagation—which is a formal explanation of the observed statistical size-length distributions. As the size of the stress-homogenised rock volume increases larger fissures/dikes can form, increasing the length range of the distribution (and its entropy) which may, potentially, transform from an exponential distribution into a power-law distribution. Full article

Background: Antibacterial resistance (ABR) poses a major challenge to global health, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the prominent multidrug-resistant strains. MRSA has developed resistance through the expression of Penicillin-Binding Protein 2a (PBP2a), a key transpeptidase enzyme involved in bacterial cell wall biosynthesis. Objectives: The objective was to design and characterize a novel small-molecule inhibitor targeting PBP2a as a strategy to combat MRSA. Methods: We synthesized a new indole triazole conjugate (ITC) using eco-friendly and click chemistry approaches. In vitro antibacterial tests were performed against a panel of strains to evaluate the ITC antibacterial potential. Further, a series of in silico evaluations like molecular docking, MD simulations, free energy landscape (FEL), and principal component analysis (PCA) using the crystal structure of PBP2a (PDB ID: 4CJN), in order to predict the mechanism of action, binding mode, structural stability, and energetic profile of the 4CJN-ITC complex. Results: The compound ITC exhibited noteworthy antibacterial activity, which effectively inhibited the selected strains. Binding score and energy calculations demonstrated high affinity of ITC for the allosteric site of PBP2a and significant interactions responsible for complex stability during MD simulations. Further, FEL and PCA provided insights into the conformational behavior of ITC. These results gave the structural clues for the inhibitory action of ITC on the PBP2a. Conclusions: The integrated in vitro and in silico studies corroborate the potential of ITC as a promising developmental lead targeting PBP2a in MRSA. This study demonstrates the potential usage of rational drug design approaches in addressing therapeutic needs related to ABR. Full article

Recent research on the design and synthesis of new and upgraded materials for secondary batteries is growing to fulfill future energy demands around the globe. Herein, by using DFT calculations, the thermodynamic and electrochemical properties of Na/Na⁺@C₁₂ complexes and then halogens (X⁻ = Br⁻, Cl⁻, and F⁻) as counter anions are studied for the enhancement of Na-ion battery cell voltage and overall performance. Isolated C₁₂ nanorings showed a lower cell voltage (−1.32 V), which was significantly increased after adsorption with halide anions as counter anions. Adsorption of halides increased the Gibbs free energy, which in turn resulted in higher cell voltage. Cell voltage increased with the increasing electronegativity of the halide anion. The Gibbs free energy of Br⁻@C₁₂ was −52.36 kcal·mol⁻¹, corresponding to a desirable cell voltage of 2.27 V, making it suitable for use as an anode in sodium-ion batteries. The estimated cell voltage of these considered complexes ensures the effective use of these complexes in sodium-ion secondary batteries. Full article

Finite-time thermodynamics (FTT) describes the study of thermodynamic processes that take place in finite time. Due to the finite-time requirement, in general the system cannot move from equilibrium state to equilibrium state. As a consequence, excess entropy is generated, available work is reduced, and/or the maximally achievable efficiency is not achieved; minimizing these negative side-effects constitutes an optimal control problem. Particularly challenging are processes and cycles that involve phase transitions of the working fluid material or the target material of a synthesis process, especially since most materials reside on a highly complex energy landscape exhibiting alternative metastable phases or glassy states. In this perspective, we discuss the issues and challenges involved in dealing with such materials when performing thermodynamic processes that include phase transitions in finite time. We focus on thermodynamic cycles with one back-and-forth transition and the generation of new materials via a phase transition; other systems discussed concern the computation of free energy differences and the general applicability of FTT to systems outside the realm of chemistry and physics that exhibit cost function landscapes with phase transition-like dynamics. Full article

This study investigates how phospholipid headgroups influence passive membrane penetration and structural impact of four nitrogen-, sulfur-, and oxygen-containing heterocycles (NSO-HETs)—N-methyl-2-pyrrolidone (PIR), 1,4-dioxane (DIOX), oxane (OXA), and phenol (PHE). Using all-atom molecular dynamics simulations combined with Accelerated Weight Histogram free energy calculations, the passive transport of NSO-HETs across DPPC, DPPE, DPPA, and DPPG bilayers was characterized. DPPG showed the highest membrane affinity, increasing permeability (logP_memb/bulk) by 27–64% compared to DPPE, associated with the lowest permeability and tightest lipid packing. Free energy barriers are also decreased in DPPG relative to DPPE; PIR’s central barrier dropped from 19.2 kJ/mol (DPPE) to 16.6 kJ/mol (DPPG), while DIOX’s barrier decreased from 7.2 to 5.2 kJ/mol. OXA exhibited the lowest central barriers (1.2–2.2 kJ/mol) and uniquely accumulated at higher concentrations in the bilayer center than in bulk water, with free energy ranging from −3.4 to −5.9 kJ/mol. PHE and OXA caused significant bilayer thinning (up to 11%) and reduced lipid tail order, especially in DPPE and DPPA. Concentration effects were most pronounced in DPPE, where high solute loading disrupted lipid order and altered free energy profiles. These results highlight the crucial role of headgroup identity in modulating NSO-HET membrane permeability and structural changes. Full article

Background: Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies worldwide, characterized by remarkable molecular heterogeneity and poor clinical outcomes. Despite advancements in diagnosis and treatment, the prognosis for HCC remains dismal, largely due to late-stage diagnosis and limited therapeutic efficacy. Therefore, there is a critical need to identify novel therapeutic targets and explore alternative strategies, such as drug repurposing, to improve patient outcomes. Methods: In this study, we employed network pharmacology, molecular docking, and molecular dynamics (MD) simulations to explore the potential therapeutic targets of Nirmatrelvir in HCC. Results: Nirmatrelvir targets were predicted through SwissTarget (101 targets), SuperPred (1111 targets), and Way2Drug (38 targets). Concurrently, HCC-associated genes (5726) were retrieved from DisGeNet. Cross-referencing the two datasets identified 29 overlapping proteins. A protein–protein interaction (PPI) network constructed from the overlapping proteins was analyzed using CytoHubba, identifying 10 hub genes, with HDAC1, HDAC3, and STAT3 achieving the highest degree scores. Molecular docking revealed a strong binding affinity of Nirmatrelvir to HDAC1 (docking score = −7.319 kcal/mol), HDAC3 (−6.026 kcal/mol), and STAT3 (−6.304 kcal/mol). Moreover, Nirmatrelvir displayed stable dynamic behavior in repeated 200 ns simulation analyses. Binding free energy calculations using MM/GBSA showed values of −23.692 kcal/mol for the HDAC1–Nirmatrelvir complex, −33.360 kcal/mol for HDAC3, and −21.167 kcal/mol for STAT3. MM/PBSA analysis yielded −17.987 kcal/mol for HDAC1, −27.767 kcal/mol for HDAC3, and −16.986 kcal/mol for STAT3. Conclusions: The findings demonstrate Nirmatrelvir’s strong binding affinity towards HDAC3, underscoring its potential for future drug development. Collectively, the data provide computational evidence for repurposing Nirmatrelvir as a multi-target inhibitor in HCC therapy, warranting in vitro and in vivo studies to confirm its clinical efficacy and safety and elucidate its mechanisms of action in HCC. Full article

The overall efficiency of combining denitrification and volatile organic compound (VOC) removal through selective catalytic reduction (SCR) technology is currently mainly limited by the VOC removal aspect. However, existing studies have not studied the microscopic mechanism of the interaction between VOCs and catalysts, failing to provide a theoretical basis for catalysts. Therefore, this work explored the interaction mechanisms between SCR catalysts doped with different additives and typical VOCs (acetone and toluene) in flue gas based on density functional theory (DFT) calculations. The results showed that the VNi-TiO₂ surface exhibited a high adsorption energy of −0.80 eV for acetone and a high adsorption energy of −1.02 eV for toluene on the VMn-TiO₂ surface. Electronic structure analysis revealed the VMn-TiO₂ and VNi-TiO₂ surfaces exhibited more intense orbital hybridization with acetone and toluene, promoting charge transfer between the two and resulting in stronger interactions. The analysis of temperature on adsorption free energy showed that VMn-TiO₂ and VNi-TiO₂ still maintained high activity at high temperatures. This work contributes to clarifying the interaction mechanism between SCR and VOCs and enhancing the VOC removal efficiency. Full article

Background: There is little information about the effectiveness of oral nutritional supplements (ONS) in combatting nutrient inadequacies in primary care, where most malnutrition exists. Aim: To examine the extent to which readymade ONS add or displace the nutrients consumed in the diet and their impact on combatting dietary inadequacies. Methods: 308 free-living people >50 years with medium + high risk of malnutrition (Malnutrition Universal Screening Tool) were randomised to receive readymade low volume (2.4 kcal/mL), liquid ONS plus dietary advice (ONS + DA) or dietary advice alone (DA). Intake was assessed at baseline (24 h recall) and 4-weekly for 12 weeks (3-day diet record). Total nutrient intake was benchmarked against UK and European dietary reference values (DRVs). The proportion of energy and nutrients from the ONS that added or displaced those from the diet (net addition/displacement) was calculated. Results: ONS + DA led to significantly greater total energy and nutritional intakes, with 25/29 nutrient intakes significantly higher than with DA alone. There were no significant differences in dietary energy and nutrient intakes from food between the groups. There was little or no displacement of nutrients from the diet, with over 90% of the energy and nutrients consumed in the ONS additive to the diet. ONS + DA more than halved the number of people with nutrient intakes that failed to meet DRVs and the number of nutrients per person that did not meet DRVs compared to DA alone. Conclusions: Supplementation with readymade, low volume (2.4 kcal/mL) liquid ONS overcomes most nutrient intake inadequacies in malnourished older people in primary care without significantly reducing intake from the diet. This makes ONS an effective way to improve nutritional intakes above dietary advice alone to improve the outcomes for the management of older people at risk of malnutrition. Full article

Experimental and theoretical studies were applied to investigate the adsorption properties of testagen (KEDG) peptide on copper surfaces in sodium chloride solution and, implicitly, its inhibition efficiency (IE) on metal corrosion. The tetrapeptide synthesized from the amino acids lysine (Lys), glutamic acid (Glu), aspartic acid (Asp), and glycine (Gly), named as H-Lys-Glu-Asp-Gly-OH, achieved an inhibition efficiency of around 86% calculated from electrochemical measurements, making KEDG a promising new copper corrosion inhibitor. The experimental data were best fitted to the Freundlich adsorption isotherm. The standard free energy of adsorption ($\mathsf{\Delta }{\mathrm{G}}_{\mathrm{a}\mathrm{d}\mathrm{s}}^{\mathrm{o}}$) reached the value of −30.86 kJ mol⁻¹, which revealed a mixed action mechanism of tetrapeptide, namely, chemical and physical spontaneous adsorption. The copper surface characterization was performed using optical microscopy and SEM/EDS analysis. In the KEDG presence, post-corrosion, SEM images showed a network surface morphology including microdeposits with an acicular appearance, and EDS analysis highlighted an upper surface layer consisting of KEDG, sodium chloride, and copper corrosion compounds. The computational study based on DFT and Monte Carlo simulation confirmed the experimental results and concluded that the spontaneous adsorption equilibrium establishment was the consequence of the contribution of noncovalent (electrostatic, van der Waals) interactions and covalent bonds. Full article

Background: The introduction of cystic fibrosis transmembrane conductance regulator modulators, especially the triple therapy elexacaftor, tezacaftor, ivacaftor (ETI), has improved outcomes in people with cystic fibrosis (pwCF), reducing underweight but increasing overweight rates. Objectives: This study investigates the effect of ETI on appetite control, body composition, and energy balance during a 3-week inpatient rehabilitation programme with regular exercise. Methods: In 54 pwCF (38 on ETI, 16 without ETI), changes in body composition (fat mass index, FMI; fat-free mass index, FFMI) and energy balance (calculated from body composition changes) were assessed. Appetite control was evaluated via plasma peptide YY (PYY) levels and post-exercise meal energy intake. Results: The programme significantly increased BMI (+0.3 ± 0.1 kg/m²; CI 0.1–0.4) and energy balance (+4317 ± 1976 kcal/3 weeks), primarily through FFMI gains (+0.3 ± 0.1 kg/m²; CI 0.1–0.4). Despite higher post-exercise meal energy intake and a tendency towards lower PYY levels in the ETI group, changes in body composition and energy balance did not differ between groups. This is explained by a higher prevalence of exocrine pancreatic insufficiency in the ETI group (92% vs. 50%, p < 0.001). Small sample sizes limit the interpretation of data on appetite control and energy intake. Conclusions: A 3-week inpatient rehabilitation programme improved body composition in pwCF, without resulting in a more positive energy balance with ETI therapy. This is due to a higher prevalence of pancreatic insufficiency in this group. Full article

In order to explore the essence of the anticoccidiosis of anticoccidial drugs under bioelectric currents, the intermolecular double-proton transfer and conformational transformation of 4-pyridone-3-carboxylic acid were investigated by quantum chemistry calculations (at the M06-2X/6-311++G**, M06-2X/aug-cc-pVTZ and CCSD(T)/aug-cc-pVTZ levels) and finite temperature string (FTS) under external electric fields. The solvent effect of H₂O on the double-proton transfer was evaluated by the integral equation formalism polarized continuum model. The results indicate that the influences of the external electric fields along the direction of the dipole moment on double-proton transfer are significant. The corresponding products are controlled by the direction of the external electric field. Due to the first-order Stark effect, some good linear relationships form between the changes of the structures, atoms in molecules (AIMs) results, surface electrostatic potentials, barriers of the transition state, and the external electric field strengths. From the gas to solvent phase, the barrier heights increased. The spatial order parameters (ϕ, ψ) of the conformational transformation could be quickly converged through the umbrella sampling and parameter averaging, and thus the free-energy landscape for the conformational transformation was obtained. Under the external electric field, there is competition between the double-proton transfer and conformational transformation. The external electric field greatly affects the cooperativity transfer, while it has little effect on the conformational transformation. This study is helpful in the selection and updating of anticoccidial drugs. Full article

This study provides a novel experimental setup and methodology for the quantitative investigation of evaporation-induced foaming behaviors in a polymer/small-molecule solution system (PSMS). In traditional dynamic test methods, it is difficult to precisely describe the evaporation-induced foaming process of a multicomponent solution because the concentration of light components in solution continuously decreases during ebullition, causing undesired changes in foaming behavior. In this study, a precisely controlled condensation reflux module was introduced into the setup to maintain pressure, temperature, and concentration of the PSMS at constant levels during the entire ebullition process, allowing dynamic test methods to quantify the evaporation-induced foamability. With this newly proposed device, experimental data of typical PSMS, polyolefin elastomer (POE)/n-hexane solution system, were obtained and modeled to illustrate the foam growth profile, thereby characterizing the dynamic foaming process based on a logistic growth function. The corresponding dimensionless number Σevap was calculated to evaluate evaporation-induced foam stability by analyzing the foam growth profile under varying pressure, concentration, and energy input levels. Furthermore, given that the PSMS represents a highly non-ideal system, the bubble nucleation rate J was modified in this work by introducing a correction coefficient δ to account for the non-ideal effects of macromolecules present in solutions. Additionally, another correction coefficient λ was incorporated into the Gibbs free energy term to adjust for supersaturation of liquid during nucleation. The experiment’s data align well with the modified bubble nucleation rate mechanism proposed herein. Full article

With the continuous expansion of data center scales worldwide, the problem of energy consumption has become increasingly prominent. To address the multi-parameter control challenge in environmental temperature regulation for large data center computer rooms, achieve precise control of hot-aisle temperatures in data centers, and reduce energy waste, this paper designs a multi-parameter model-free adaptive control (MMFAC) algorithm suitable for computer room environmental temperatures. The algorithm integrates the model-free adaptive control (MFAC) algorithm with a weight matrix to perform scaling transformations. Considering the large parameter space of the MFAC controller and the dynamic complexity of data center temperature control systems, compact-form dynamic linearization (CFDL) technology and optimization mathematical methods are used to simplify the parameter identification of the pseudo-Jacobian matrices and the calculation of control quantities for the regulation devices. Simulation experiments based on measured data from a data center show that the proposed algorithm can calculate control quantities for equipment such as air conditioners according to real-time environmental parameter measurements and drive each device based on these control quantities. Meanwhile, the algorithm can reduce errors in key parameters by adjusting the weight matrix. Comparative tests with other control algorithms show that the algorithm has faster response in temperature control and smaller control errors, verifying the effectiveness and application prospects of the algorithm in data center temperature control. Full article