Intestinal absorption of compounds is significant in drug research and development. To evaluate this efficiently, a method combining mathematical modeling and molecular simulation was proposed, from the perspective of molecular structure. Based on the quantitative structure-property relationship study, the model between molecular structure and their apparent permeability coefficients was successfully constructed and verified, predicting intestinal absorption of drugs and interpreting decisive structural factors, such as AlogP98, Hydrogen bond donor and Ellipsoidal volume. The molecules with strong lipophilicity, less hydrogen bond donors and receptors, and small molecular volume are more easily absorbed. Then, the molecular dynamics simulation and molecular docking were utilized to study the mechanism of differences in intestinal absorption of drugs and investigate the role of molecular structure. Results indicated that molecules with strong lipophilicity and small volume interacted with the membrane at a lower energy and were easier to penetrate the membrane. Likewise, they had weaker interaction with P-glycoprotein and were easier to escape from it and harder to export from the body. More in, less out, is the main reason these molecules absorb well.

This study investigated the gelling properties, rheological behaviour, and microstructure of heat-induced, low-salt myofibrillar protein (MP) gels containing different levels (2%, 4%, 6%, and 8%, w/w) of cross-linked (CTS) or acetylated (ATS) tapioca starch. The results indicated that either CTS or ATS significantly enhanced the gel strength and water-holding capacity of low-salt MP gels (P < 0.05), an outcome verified by the rheological behaviour test results under different modes. Furthermore, iodine-staining images indicated that the MP-dominated continuous phase gradually transited to a starch-dominated phase with increasing CTS or ATS levels, and 4% was the critical point for this phase transition. In addition, hydrophobic interactions and disulphide bonds constituted the major intermolecular forces of low-salt MP gels, effectively promoting phase transition. In brief, modified tapioca starches possess considerable potential application value in low-salt meat products.

Food comprises proteins, lipids, sugars and various other molecules that constitute a multicomponent biological system. It is challenging to investigate microscopic changes in food systems solely by performing conventional experiments. Molecular dynamics (MD) simulation serves as a crucial bridge in addressing this research gap. The Groningen Machine for Chemical Simulations (GROMACS) is an open-source, high-performing molecular dynamics simulation software that plays a significant role in food science research owing to its high flexibility and powerful functionality; it has been used to explore the molecular conformations and the mechanisms of interaction between food molecules at the microcosmic level and to analyze their properties and functions. This review presents the workflow of the GROMACS software and emphasizes the recent developments and achievements in its applications in food science research, thus providing important theoretical guidance and technical support for obtaining an in-depth understanding of the properties and functions of food.

OBJECTIVE: Elucidation of the micro-mechanisms of sol-gel transition of gelling glucans with different glycosidic linkages is crucial for understanding their structure-property relationship and for various applications. Glucans with distinct molecular chain structures exhibit unique gelation behaviors. The disparate gelation phenomena observed in two methylated glucans, methylated (1,3)-β-d-glucan of curdlan (MECD) and methylated (1,4)-β-d-glucan of cellulose (MC), notwithstanding their equivalent degrees of substitution, are intricately linked to their unique molecular architectures and interactions between glucan and water.
METHODS: Density functional theory and molecular dynamics simulations focused on the electronic property distinctions between MECD and MC, alongside conformational variations during thermal gelation. Inline attenuated total reflection Fourier transform infrared spectroscopy tracked secondary structure alterations in MECD and MC. To corroborate the simulation results, additional analyses including circular dichroism, rheology, and micro-differential scanning calorimetry were performed.
RESULTS: Despite having similar thermally induced gel networks, MECD and MC display distinct physical gelation patterns and molecular-level conformational changes during gelation. The network of MC gel was formed via a \"coil-to-ring\" transition, followed by ring stacking. In contrast, the MECD gel comprised compact irregular helices accompanied by notable volume shrinkage. These variations in gelation behavior are ascribed to heightened hydrophobic interactions and diminished hydrogen bonding in both systems upon heating, resulting in gelation. These findings provide valuable insights into the microstructural changes during gelation and the thermo-gelation mechanisms of structurally similar polysaccharides.

Multiple sclerosis (MS) is a common disease in young women of reproductive age, characterized by demyelination of the central nervous system (CNS). Understanding how genes related to MS are expressed during pregnancy can provide insights into the potential mechanisms by which pregnancy affects the course of this disease. This review article presents evidence-based studies on these patients\' gene expression patterns. In addition, it constructs interaction networks using bioinformatics tools, such as STRING and KEGG pathways, to understand the molecular role of each of these genes. Bioinformatics research identified 25 genes and 21 signaling pathways, which allows us to understand pregnancy patients\' genetic and biological phenomena and formulate new questions about MS during pregnancy.

OBJECTIVE: Targeted therapies have markedly improved the prognosis of lung cancer patients; nevertheless, challenges persist, including limited beneficiary populations and the emergence of drug resistance. This study investigates the molecular mechanisms of mutant TP53 in lung cancer, aiming to contribute to novel strategies for targeted therapy.
METHODS: The TCGA database was employed to delineate the mutational landscape of TP53 in lung cancer patients. Differential gene expression between TP53-mutant and wild-type patients was analyzed, followed by functional enrichment. DSG3 protein expression in lung cancer patients was assessed using IHC, and its impact on prognosis was analyzed in the TCGA database. The influence of TP53 on the downstream gene DSG3 was investigated using qPCR, ChIP-qPCR, and luciferase reporter gene assays. Protein enrichment in the DSG3 promoter region was examined through IP-MS, and the regulatory role of the HIF1-α/TP53 complex on DSG3 was explored using Co-IP, luciferase assays, and ChIP-qPCR. Molecular interactions between TP53 (R273H) and HIF1-α were detected through immunoprecipitation and molecular docking. The effects and mechanisms of DSG3 on lung cancer phenotypes were assessed through WB, transwell, and wound healing assays.
RESULTS: TP53 mutations were present in 47.44% of patients, predominantly as missense mutations. DSG3 exhibited high expression in TP53-mutant lung cancer patients, and this elevated expression correlated with a poorer prognosis. TP53 interference led to a reduction in DSG3 mRNA expression, with TP53 mutant P53 enriching at the P2 site of the DSG3 promoter region, a recruitment facilitated by HIF1-α. The DBD region of TP53 (R273H) demonstrated interaction with HIF1-α. DSG3, activated through Ezrin phosphorylation, played a role in promoting invasion and metastasis.
CONCLUSIONS: Mutant TP53 facilitates lung cancer cell invasion by modulating desmoglein 3.

The rise in dengue cases in tropical and sub-tropical areas has become a significant health concern. At present, there is no definitive cure for dengue fever, which underscores the importance of identifying potent inhibitors. Dengue NS2B-NS3 protease is the prime drug target due to its vital function for replication. Quercetin, a flavone, has anti-dengue virus properties but is limited by low bioavailability. Previous studies have shown that methoxy substitution in flavones improves bioavailability and metabolic stability. Azaleatin is a derivative of quercetin with a methoxy substitution at the C5 position, however its ability to inhibit dengue is unknown. In this study, azaleatin was investigated for its inhibition against dengue NS2B-NS3 protease using in vitro and in silico techniques. The fluorescence assay was used to determine the IC50 value and inhibition kinetics. The molecular interaction between azaleatin and NS2B-NS3 was studied using CB-Dock2 and AutoDock Vina. The complex\'s stability was then analysed using GROMACS. Besides, the ADMETlab 2.0 was utilized to predict pharmacokinetic of the azaleatin. Results showed that azaleatin inhibits dengue NS2B-NS3 protease non-competitively with a Ki of 26.82 µg/ml and an IC50 of 38 µg/ml. Molecular docking indicated binding of the azaleatin to the allosteric pocket of NS2B-NS3 with a docking score of -8.2 kcal/mol. Azaleatin was found stable in the pocket along 100 ns, supporting its inhibitory mode. The compound has favourable pharmacokinetic profiles and conformed to Lipinski\'s Rule of Five. Taken together, azaleatin inhibits NS2B-NS3 protease in a non-competitive mode, suggesting its potential as safer anti-dengue compound.Communicated by Ramaswamy H. Sarma.

Eugenol (EU), a natural bioactive compound found in various plants, offers numerous health benefits, but its application in the food and pharmaceutical industry is limited by its high volatility, instability, and low water solubility. Therefore, this study aimed to utilize the surface coating technique to develop zein-tween-80-fucoidan (Z-T-FD) composite nanoparticles for encapsulating eugenol using a nozzle simulation chip. The physicochemical characteristics of the composite nanoparticles were examined by varying the weight ratios of Z, T, and FD. Results showed that the Z-T-FD weight ratio of 5:1:15 exhibited excellent colloidal stability under a range of conditions, including pH (2-8), salt concentrations (10-500 mmol/L), heating (80 °C), and storage (30 days). Encapsulation of EU into Z-T-FD nanoparticles (0.5:5:1:15) resulted in an encapsulation efficiency of 49.29 ± 1.00%, loading capacity of 0.46 ± 0.05%, particle size of 205.01 ± 3.25 nm, PDI of 0.179 ± 0.006, and zeta-potential of 37.12 ± 1.87 mV. Spherical structures were formed through hydrophobic interaction and hydrogen bonding, as confirmed by Fourier transform infrared spectroscopy and molecular docking. Furthermore, the EU-Z-T-FD (0.5:5:1:15) nanoparticles displayed higher in vitro antioxidant properties (with DPPH and ABTS radical scavenging properties at 75.28 ± 0.16% and 39.13 ± 1.22%, respectively), in vitro bioaccessibility (64.78 ± 1.37%), and retention rates under thermal and storage conditions for EU compared to other formulations. These findings demonstrate that the Z-T-FD nanoparticle system can effectively encapsulate, protect, and deliver eugenol, making it a promising option for applications in the food and pharmaceutical industries.

UNASSIGNED: Rice starch has high digestibility due to its large carbohydrate content. Synergistic modification of hot-melt extrusion (HME) and additives such as flavonoids, hydrocolloids, proteins, lipids, and other additives has the tendency to retard the rate of starch hydrolysis. Hence, the current investigation aimed to study the combined effect of the HME-assisted addition of nobiletin (NOB, 0, 2, 4, and 6%) on the multi-scale structures, interactions, thermal, and digestibility characteristics of rice starch.
UNASSIGNED: The study employed density functional theory calculations and an infrared second derivative of an Fourier-transform infrared (FTIR) spectrometer to analyze the interactions between NOB and starch. The physicochemical properties of the starch extrudates were characterized by FTIR, 13C nuclear magnetic resonance, X-ray diffraction, and differential scanning calorimetry, while the digestibility was evaluated using an in vitro digestion model.
UNASSIGNED: HME was found to disrupt the crystalline structure, helix structure, short-ordered structure, and thermal properties of starch. The interaction between NOB and starch involved hydrophobic interactions and hydrogen bonds, effectively preventing the molecular chains of starch from interacting with each other and disrupting their double helix structure. The addition of NOB led to the formation of a highly single-helical V-type crystalline structure, along with the formation of ordered structural domains. Consequently, the combined treatment significantly enhanced the ordered structure and thermal stability of starch, thus effectively leading to an increase in resistant starch and slowly digestion starch.
UNASSIGNED: The study underscores that synergistic modification of HME and NOB holds promise for enhancing both the nutritional value and functional properties of rice starch. These findings offer valuable insights for developing high-quality rice starch products with broader applications.

The study aimed to create a low loading, high retention, easier to apply O/W mometasone furoate (MF) cream using a chemical enhancer (CE) approach to provide more options for patients with atopic dermatitis (AD) and to investigate molecular mechanisms of its increased release and retention. A Box-Behnken design determined the optimal formulation based on stability and in vitro skin retention. Evaluations included appearance, rheological properties, irritation, in vivo tissue distribution and pharmacodynamics. Molecular mechanisms of enhanced release were studied using high-speed centrifugation, molecular dynamics and rheology. The interaction between the CE, MF and skin was studied by tape stripping, CLSM, ATR-FTIR and SAXS. The formulation was optimized to contain 0.05% MF and used 10% polyglyceryl-3 oleate (POCC) as the CE. There was no significant difference from Elocon® cream in in vivo retention and pharmacodynamics but increased in vivo retention by 3.14-fold and in vitro release by 1.77-fold compared to the basic formulation. POCC reduced oil phase cohesive energy density, enhancing drug mobility and release. It disrupted skin lipid phases, aiding drug entry and formed hydrogen bonds, prolonging retention. This study highlights POCC as a CE in the cream, offering insights for semi-solid formulation development.