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[Display omitted] 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. 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. 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. [ABSTRACT FROM AUTHOR]

The small GTPase Rho family are the major factors in mediating actin cytoskeleton dynamics. Rho-specific guanine nucleotide dissociation inhibitors (RhoGDIs) serve as important negative regulators by complexing with inactive Rho into the cytoplasm. However, how these two molecules interact still needs experimental verification. Based on fluorescence resonance energy transfer (FRET) measurements, we would demonstrate crucial sites in RhoGDI and RhoA for this regulatory role. Cotransfection of RhoGDI markedly reduced RhoA or Cdc42 activity in airway smooth muscle (ASM) cells, while D185R-RhoGDI mutant reversed this decrease, indicating that RhoGDI Asp185 residue is essential for the molecular interaction. R68D-RhoA (mutation in the switch II region) resulted in a deficiency in RhoGDI regulation, while TV37/38NG-RhoA (in the switch I region) displayed low RhoA activity. Hence, the Arg68 site in RhoA is indispensable for regulation by RhoGDI, and Thr37Val38 site is important for maintaining RhoA activity. Additionally, microtubule but not actin cytoskeleton showed inhibitory role in RhoA activity, while the dissolution of either cytoskeleton did not change the regulatory role of RhoGDI. In checking the downstream effect, reduction of RhoA activity induced by PDGF stimulation or RhoGDI decreased cellular stress fibers. In this study, FRET visualization was applied to have experimentally demonstrated the interaction sites and crucial role of RhoGDI in regulating RhoA activity. Highlights: • This study used FRET visualization to demonstrate the interaction sites and crucial role of RhoGDI in negatively regulating RhoA activity; • The Asp185 residue in RhoGDI is essential for molecular interaction between RhoGDI and RhoA; • The Arg68 site in RhoA is indispensable for regulation by RhoGDI, while Thr37Val38 site important for normal RhoA activity; • Microtubule showed inhibitory role in RhoA, and decreased RhoA activity induced by PDGF stimulation or RhoGDI reduced cellular stress fibers. [ABSTRACT FROM AUTHOR]

Carbohydrate digestive enzymes like α-amylase and α-glucosidase can be used to treat and manage diabetes. By inhibiting these enzymes, carbohydrate digestion slowed down, lowering the level of glucose entry into the bloodstream and preventing postprandial hyperglycemia. However, the effectiveness of current antidiabetic agents is limited due to their adverse effects. Therefore, the current study explored natural inhibitors from the methanol extract of rice to combat this issue. Through an integrated approach, four different rice cultivars were analysed and found that red rice methanol extract compounds stigmasterol and 1,2-benzenedicarboxylic acid interacted with α-amylase and α-glucosidase. Additionally, further research on stigmasterol directs the structure-activity relationship studies that aid in managing diabetic conditions. [ABSTRACT FROM AUTHOR]

The protein structure, gel changes, and chewing properties of low‐sodium myofibrillar protein (MP) prepared by compound chloride salts (KCl/MgCl2, KCl/CaCl2, and KCl/MgCl2/CaCl2) and different substitution degrees (10%, 25%, and 40%) at same ionic strength (0.6 M) were investigated. The results revealed that the low‐sodium MP gels containing CaCl2 manifested more liquid loss and less moisture content accompanied by obvious morphological shrinkage, while KCl/MgCl2 contributed to the gel juiciness. At high substitution degree of 40%, KCl/CaCl2 substitution rendered the gel with dense structure and highest strength, but worse water retention capacity. Using other compound chloride salts influenced the chewing efficiency, and CaCl2 substitution made the gel relatively hard to chew. The inhomogeneous structure accompanied by cluster blocks in KCl/CaCl2‐substituted MP gel accelerated the overall fracture rate. During heating process, more proteins in CaCl2‐substituted MP did not participate in gel formation, intervening the final gel properties. The chloride salt mixtures containing MgCl2, rather than CaCl2, avoided or alleviated the liquid loss and shrinkage of low‐sodium MP gel within the substitution degree of 10%–40%, and substitution degree not exceeding 25% was more reasonable for the controlled qualities. [ABSTRACT FROM AUTHOR]

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The investigation of the interplay between complex coacervate microdroplets and amphiphilic molecules offers valuable insights into the processes of prebiotic compartmentalization on the early Earth and presents a promising avenue for future advancements in biotechnology. Herein, the interaction between complex coacervate microdroplets and amphiphilic molecule (decanoic acid) is systematically investigated by varying charge strengths of negatively charged polyelectrolytes (DNA and PAA) and positively charged polyelectrolytes (PDDA and DEAE‐Dextran). It is found that the interaction between amphiphilic molecule and complex coacervate microdroplets depended on the delicate balance between the interaction between decanoic acid and polyelectrolyte and the interaction between two polyelectrolytes. The different spatial distribution of amphiphilic molecule can result in differences in the internal microenvironment, which can further alter the uptake or exclusion of small molecules and biomolecules with different charges and polarities and functional biological process. [ABSTRACT FROM AUTHOR]

The study analyzed the impact of adding Moringa oleifera dietary fiber (MDF) on the gel strength, color, water-holding capacity, protein secondary structure, microstructure, rheology, and texture properties of silver carp surimi. The results showed that incorporating 0.1%, 0.3% and 0.6% MDF into silver carp surimi resulted in enhanced gel strength, water-holding capacity and texture compared with pure silver carp surimi. The addition of 0.9% MDF significantly reduced the whiteness of silver carp surimi. For all surimi gels, the storage modulus (G’) was higher than the loss modulus (G”), confirming the gel structure of the surimi. Fourier transform infrared (FTIR) spectroscopy showed that the addition of MDFs had little effect on the protein secondary structure of the surimi. Compared with the pure surimi group, the ionic bonding and hydrophobic interaction in the surimi gel with 0.6% MDF addition significantly increased (P < 0.05), indicating enhanced intermolecular interaction in the gel. Therefore, the addition of 0.6% MDF in silver carp surimi resulted in more uniform network structure and an increase in the dietary fiber content. This study provides an effective approach to improve the processing performance and nutritional quality of silver carp surimi, and provides a reference for the development and utilization of M. oleifera dietary fiber.

ABSTRACTThis study addresses the crucial protein Internalin A in the development of a possible vaccination against Listeria monocytogenes. A meticulous in silico strategy was used which included physiochemical analysis, epitope prediction, and molecular interaction studies. Computational techniques shed light on potential development of a vaccine candidate against Listeria, with a focus on the Internalin A protein along with its immune simulations. Insights into molecular interactions and physiochemical features aid in understanding of prospective Listeria vaccine candidates. Ultimately, the computational analysis in this study sets the groundwork for the creation of a possible vaccination against Listeria. The discovered epitopes and insights into molecular interactions are useful for experimental validation. In vitro and in vivo investigations should be conducted in the future to confirm the effectiveness of these anticipated epitopes. These findings advanced our understanding of vaccine design by providing insights into battling Listeria infections and perhaps guiding tactics for other diseases.

Background: Recently, the substitution R1051Q in VEGFR2 has been described as a cancer-associated "gain of function" mutation. VEGFR2R1051Q phosphorylation is ligand-independent and enhances the activation of intracellular pathways and cell growth both in vitro and in vivo. In cancer, this mutation is found in heterozygosity, suggesting that an interaction between VEGFR2R1051Q and VEGFR2WT may occur and could explain, at least in part, how VEGFR2R1051Q acts to promote VEGFR2 signaling. Despite this, the biochemical/biophysical mechanism of the activation of VEGFR2R1051Q remains poorly understood. On these bases, the aim of our study is to address how VEGFR2R1051Q influences the biophysical behavior (dimerization and membrane dynamics) of the co-expressed VEGFR2WT. Methods: We employed quantitative FLIM/FRET and FRAP imaging techniques using CHO cells co-transfected with the two forms of VEGFR2 to mimic heterozygosity. Results: Membrane protein biotinylation reveals that VEGFR2WT is more exposed on the cell membrane with respect to VEGFR2R1051Q. The imaging analyses show the ability of VEGFR2WT to form heterodimers with VEGFR2R1051Q and this interaction alters its membrane dynamics. Indeed, when the co-expression of VEGFR2WT/VEGFR2R1051Q occurs, VEGFR2WT shows reduced lateral motility and a minor pool of mobile fraction. Conclusions: This study demonstrates that active VEGFR2R1051Q can affect the membrane behavior of the VEGFR2WT. [ABSTRACT FROM AUTHOR]

In order to improve fuel economy to meet the standard for passenger car oil, a new formulation with good viscosity–temperature performance for gasoline engine oil is required. In this study, coal-to-liquid (CTL) base oil, with a high viscosity index and good low-temperature performance, was selected as the base oil to develop the gasoline engine oil. A systematic study on the molecular interaction between the CTL base oil and the viscosity index improver (VII), including three kinds of hydrogenated styrene diene copolymers (HSD-type) and four kinds of ethylene propylene copolymers (OCP-type), was conducted. It was found that in general, in CTL base oil, the HSD-type VII exhibited a much higher viscosity index, a significantly lower shear stability index, a higher thickening ability, and a lower cold-cranking simulator (CCS) viscosity than that of OCP-type VII. Moreover, when comparing CTL base oil with mineral oil 150N, the combination of CTL base oil and the VII displayed a lower CCS viscosity than that of mineral oil, suggesting it had better low-temperature performance and was able to quickly form a protective oil film on the surface, which was beneficial for the cold start. The functional group distribution state of the VII in base oil was analyzed using synchrotron radiation micro-infrared microscope (SR Micro-IR) technology, which revealed that HSD-1 had a better molecular interaction with CTL6 than 150N because of the better uniformity of the C=C group distribution. Based on this, a SP 0W-20 gasoline engine oil was developed by the combination of CTL base oil and the HSD-1 viscosity index improver, together with an additive package, a polymethacrylate pour point depressant, and a non-silicone defoamer, which showed excellent low-temperature performance, thermal oxidation stability, and detergency performance compared to the reference oil. [ABSTRACT FROM AUTHOR]

This study aims to explore the relationship between 4-Hydroxycinnamic Acid, a compound found in broccoli fruit (Brassica oleracea var. italica), and Estrogen Receptor Beta Protein through in silico analysis. The research was conducted using Pymol, MOE 2015, Discovery Studio 2016, and Lepinski Rule software. These tools were employed to model the structure of both the compound and protein, as well as to evaluate their interaction. The results revealed a significant interaction with a Binding Affinity of -6.4182. Moreover, the Root Mean Square Deviation (RMSD) measurements yielded a value of 3.8907, indicating the degree of agreement between the compound and protein structures. Analysis using the Lepinski Rule disclosed the characteristics of the compound 4-Hydroxycinnamic Acid, including a mass of 164, two hydrogen bond donors, three hydrogen bond acceptors, a log P value of 1.490, and a molar reactivity of 44.776. These findings provide valuable insights into the potential of 4-Hydroxycinnamic Acid in interacting with Estrogen Receptor Beta Protein, which could serve as a foundation for further research on the health benefits and therapeutic applications of this compound, contributing to the goal of good health and well-being. [ABSTRACT FROM AUTHOR]

Phytophthora palmivora, a hemibiotrophic oomycete, causes diseases in several economically important tropical crops, such as oil palm, which it is responsible for a devastating disease called bud rot (BR). Despite recent progress in understanding host resistance and virulence mechanisms, many aspects remain unknown in P. palmivora isolates from oil palm. Model pathosystems are useful for understanding the molecular interactions between pathogens and hosts. In this study, we utilized detached leaves and whole seedlings of Arabidopsis thaliana Col-0 to describe and evaluate the infection process of three P. palmivora isolates (CPPhZC-05, CPPhZC-04, CPPhZOC-01) that cause BR in oil palm. Two compatible isolates (CPPhZC-05 and CPPhZOC-01) induced aqueous lesions at 72 h post-inoculation (hpi), with microscopic visualization revealing zoospore encysting and appressorium penetration at 3 hpi, followed by sporangia generation at 72 hpi. In contrast, an incompatible isolate (CPPhZC-04) exhibited cysts that could not penetrate tissue, resulting in low leaf colonization. Gene expression of ten P. palmivora infection-related genes was quantified by RT-qPCR, revealing overexpression in compatible isolates, but not in the incompatible isolate. Additionally, key genes associated with salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) in Arabidopsis exhibited regulation during interaction with the three isolates. These findings demonstrate that P. palmivora can infect Arabidopsis Col-0, and variability is observed in the interaction between Arabidopsis-Col-0 and P. palmivora isolates. Establishing this pathosystem is expected to enhance our understanding of P. palmivora's pathology and physiology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Understanding the interaction between drugs and human serum albumin (HSA) is crucial for drug development. This study investigates the binding of a COVID‐19 drug, nirmatrelvir (NIR), to HSA through a computational approach. Molecular docking was employed to identify potential NIR binding site on HSA, and revealed distinct clusters at Sites I, II, and III. However, Site III exhibited a preference for NIR based on the lowest binding energy. Molecular dynamics simulation over 100 ns confirmed the stability of the NIR−HSA complex, with consistent binding at Site III. The compactness of HSA was maintained throughout the simulation period, as indicated by the radius of gyration, while structural flexibility analysis revealed typical fluctuations around some residues. Root‐mean‐square deviation (RMSD) patterns illustrated stability of the complex, and hydrogen bond analysis suggested four stable hydrogen bonds between NIR and HSA. These investigations offer insightful information on molecular interactions governing the stability of the NIR−HSA complex. [ABSTRACT FROM AUTHOR]

Purpose: 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. [ABSTRACT FROM AUTHOR]

The utilization of ionic liquids as versatile reaction media and catalysts has garnered significant attention in the field of green and sustainable chemistry. In this study, sum frequency generation vibrational spectroscopy (SFG-VS) is employed to investigate the interactions between l-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF4]) and styrene oxide (SO) at the air/liquid interface. Spectral analysis in the range of 1000 cm−1 to 3700 cm−1 reveals that only vibrational modes of C–H bonds are observed. Notably, the orientation of the epoxy ring of SO is found to be towards the bulk phase, while the three C–H groups on the imidazolium ring of the cation are parallel to the surface. Consequently, there are no observed interactions between the cation and SO. However, in the vibrational spectra of C–H bonds, interactions between the anion BF4- and the CH2 group of the epoxy ring result in blue shifts in the vibrations of CH (SO) and CH3 (cation). These findings support a proposed reaction mechanism where the ionic liquid catalyzes SO first and subsequently reacts with CO2 providing valuable insights into intermolecular interactions and molecular orientations at reaction interfaces. [ABSTRACT FROM AUTHOR]

Summary: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe inflammatory condition that remains refractory; however, its molecular mechanisms are largely unknown. Previous studies have shown numerous compounds containing 4-indolyl-2-aminopyrimidine that display strong anti-inflammatory properties. In our research, we identified that a 4-Indole-2-Arylaminopyrimidine derivative named “IAAP” suppressed lipopolysaccharide (LPS)-induced inflammation. Immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified that IAAP interacts with a lysosomal cysteine protease, cathepsin L (CTSL), and restrains its activity. The nuclear factor kappa B (NF-κB) family plays a central role in controlling innate immunity. Canonical NF-κB activation, such as stimulation with lipopolysaccharide (LPS), typically involves the degradation of A20. We observed that IAAP suppression of CTSL prevented the LPS-induced degradation of A20, thereby ameliorating NF-κB activation. This study identifies CTSL as a crucial regulator of A20/NF-κB signaling and suggests IAAP as a potential lead compound for developing drugs to treat ALI/ARDS.

Summary: Lysine lactylation (Kla), an epigenetic mark triggered by lactate during glycolysis, including the Warburg effect, bridges metabolism and gene regulation. Enzymes such as p300 and HDAC1/3 have been pivotal in deciphering the regulatory dynamics of Kla, though questions about additional regulatory enzymes, their specific Kla substrates, and the underlying functional mechanisms persist. Here, we identify SIRT1 and SIRT3 as key ''erasers'' of Kla, shedding light on their selective regulation of both histone and non-histone proteins. Proteomic analysis in SIRT1/SIRT3 knockout HepG2 cells reveals distinct substrate specificities toward Kla, highlighting their unique roles in cellular signaling. Notably, we highlight the role of specific Kla modifications, such as those on the M2 splice isoform of pyruvate kinase (PKM2), in modulating metabolic pathways and cell proliferation, thereby expanding Kla’s recognized functions beyond epigenetics. Therefore, this study deepens our understanding of Kla’s functional mechanisms and broadens its biological significance.

Summary: P16INK4A expression is inversely associated with RB1 expression in cancer cells, and P16INK4A inhibits CDK4-catalyzed RB1 phosphorylation. How P16INK4A and RB1 coordinately express and regulate the cell cycle remains to be studied. In the present study, we found that P16INK4A upregulated the E3 ligase UTP14A, which led to the ubiquitination of RB1 at K810 and RB1 degradation. P16INK4A loss consistently disrupted the UTP14A-mediated degradation of RB1 and caused RB1 accumulation. Functionally, P16INK4A loss inhibited RB1 ubiquitination in a cell cycle progression-independent fashion and inhibited proteome-scale ubiquitination in a cell cycle progression-dependent manner. Our findings indicate that there is a negative feedback loop between P16INK4A and RB1 expression and that disruption of this loop may partially rescue the biological outcomes of P16INK4A loss. We also revealed a hitherto unknown function for P16INK4A in regulating proteome-scale ubiquitination by inhibiting cell proliferation, which may be useful for the development of anticancer drugs.

Summary: The abnormal expression of circular RNAs (circRNAs) is emerging as a critical cause in regulation of pathological changes of hypoxic pulmonary hypertension (PH), in which ferroptosis is a new pathological change reported recently. However, how circRNAs regulate ferroptosis remains unclear. Here, we proved a significant decrease in circMyst4 expression in hypoxia. In vitro assays revealed that circMyst4 alleviated hypoxic pulmonary artery smooth muscle cell (PASMC) ferroptosis through directly combing with DDX5 in the nucleus to promote GPX4 mRNA processing and inhibiting the formation of the Eef1a1/ACSL4 complex in the cytoplasm. Additionally, superenhancer (SE) was verified to drive the generation of circMyst4. In vivo assays revealed that circMyst4 inhibited the progression of hypoxic PH. Overall, SE-driven circMyst4 may be a new potential therapeutic target for mediating PASMC ferroptosis through promoting DDX5-regulated GPX4 mRNA processing and inhibiting the binding between Eef1a1 and ACSL4.

Summary: Lamins A and C are components of the lamina at the nuclear periphery and associate with heterochromatin. A distinct, relatively mobile pool of lamin A/C in the nuclear interior associates with euchromatic regions and with lamin-associated polypeptide 2α (LAP2α). Here we show that phosphorylation-dependent impairment of lamin assembly had no effect on its chromatin association, while LAP2α depletion was sufficient to increase chromatin association of lamins. This suggests that complex interactions between LAP2α, chromatin, and lamins regulate lamin chromatin binding. Both the C terminus of LAP2α and its N-terminal LAP2-Emerin-MAN1 (LEM) domain, mediating interaction with lamin A/C indirectly via barrier-to-autointegration factor (BAF), are required for binding to lamins. The N-terminal LEM-like domain of LAP2α, but not its LEM domain, mediates chromatin association of LAP2α and requires LAP2α dimerization via its C terminus. Our data suggest that formation of several LAP2α-, lamin A/C-, and BAF-containing complexes in the nucleoplasm and on chromatin affects lamin chromatin association.

Summary: Etomoxir has been used for decades as a popular small molecule inhibitor of carnitine palmitoyltransferase I, Cpt1, to block mitochondrial fatty acid β-oxidation. To test the specificity of etomoxir, we generated click chemistry–enabled reagents to label etomoxir binding proteins in situ. Etomoxir bound to Cpt1, but also bound to a large array of diverse proteins that metabolize and transport fatty acids in the cytoplasm, peroxisome, and mitochondria. Many of the most abundant proteins identified in primary hepatocytes were peroxisomal proteins. The loss of Pex5, required for the import of peroxisomal matrix proteins, eliminated many of these etomoxir-labeled proteins. By utilizing the promiscuous, covalent, and fatty acid mimetic properties of etomoxir, etomoxir targets of fatty acid ω-oxidation were revealed following the loss of Pex5. These data demonstrate that etomoxir is not specific for Cpt1 and is not appropriate as a tool to distinguish the biological effects of fatty acid oxidation.

Summary: Mitochondria-endoplasmic reticulum (ER) contact sites (MERCs) emerged to play critical roles in numerous cellular processes, and their dysregulation has been associated to neurodegenerative disorders. Mutations in the SPG4 gene coding for spastin are among the main causes of hereditary spastic paraplegia (HSP). Spastin binds and severs microtubules, and the long isoform of this protein, namely M1, spans the outer leaflet of ER membrane where it interacts with other ER-HSP proteins. Here, we showed that overexpressed M1 spastin localizes in ER-mitochondria intersections and that endogenous spastin accumulates in MERCs. We demonstrated in different cellular models that downregulation of spastin enhances the number of MERCs, alters mitochondrial morphology, and impairs ER and mitochondrial calcium homeostasis. These effects are associated with reduced mitochondrial membrane potential, oxygen species levels, and oxidative metabolism. These findings extend our knowledge on the role of spastin in the ER and suggest MERCs deregulation as potential causes of SPG4-HSP disease.

Poly (ethylene oxide) (PEO)‐based polymer electrolytes show the prospect in all‐solid‐state lithium metal batteries; however, they present limitations of low room‐temperature ionic conductivity, and interfacial incompatibility with high voltage cathodes. Therefore, a salt engineering of 1, 1, 2, 2, 3, 3‐hexafluoropropane‐1, 3‐disulfonimide lithium salt (LiHFDF)/LiTFSI system was developed in PEO‐based electrolyte, demonstrating to effectively regulate Li ion transport and improve the interfacial stability under high voltage. We show, by manipulating the interaction between PEO matrix and TFSI−‐HFDF−, the optimized solid‐state polymer electrolyte achieves maximum Li+ conduction of 1.24 × 10−4 S cm−1 at 40 °C, which is almost 3 times of the baseline. Also, the optimized polymer electrolyte demonstrates outstanding stable cycling in the LiFePO4/Li and LiNi0.8Mn0.1Co0.1O2/Li (3.0–4.4 V, 200 cycles) based all‐solid‐state lithium batteries at 40 °C. [ABSTRACT FROM AUTHOR]

A novel chitosan-whey protein composite film containing persimmon leaf extract (PLE) was prepared, and its application for the preservation of chicken breast meat was investigated. The results showed that, all fillers, including whey protein, PLE, and glycerol were well mixed and homogeneously dispersed in the chitosan-polymer substrate, forming a uniform composite film material. The intermolecular interactions between the fillers involved hydrogen bonding and electrostatic interactions. Notably, the incorporation of PLE significantly improved the mechanical properties, water and light barrier properties, and antioxidant activity of chitosan-whey protein based film. Among them, the chitosan-whey protein composite film incorporated with 0.2% (w/v) PLE (CWP-4) had a lower solubility, water content, water vapor permeability, and higher mechanical properties, light barrier properties, and antioxidant activity. Moreover, the actual application of composite films on chicken breast meat preservation indicated that this novel composite film can effectively delay chicken breast meat spoilage and the lipid oxidation process, and thus, prolong the shelf life of chicken breast meat. [ABSTRACT FROM AUTHOR]

Mentha spicata is a popular herb used in foods, cosmetics, and medicines. In the present study, liquid chromatography-mass spectrometry-based metabolomics analysis and the zebrafish model were used to investigate the potential biomarkers of M. spicata growing in Shanghe County (Shandong Province, China) and their anti-inflammatory properties. Network pharmacology and molecular docking were performed to screen the main targets of the characteristic compounds to understand their mechanisms of action. Nine potential markers including sugars (1,2), polyphenolic acids (3–5), and flavonoids (6–9) were identified from the species. The inhibitory effects on leukocyte migration confirmed that compounds 1 and 3–9 played a positive role in the protective effect of Shanghe M. spicata (SM) extract against inflammation. Akt (protein kinase B), EGFR (epidermal growth factor receptor), and MMP9 (matrix metalloproteinase 9) were the core target proteins of the identified compounds in the anti-inflammatory process. The most significant Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment terms were response to abiotic stimulus (Biological Process), carbohydrate derivative binding (Molecular Function), and pathways in cancer. In docking simulations, 3-p-coumaroylquinic acid (3-PC, 4) and cirsimaritin (CN, 7) exhibited the highest potential affinity to the active sites of Akt and EGFR proteins, respectively; additionally, 5-demethylsinensetin (5-DS, 9) and luteolin (LN, 6) were considered the most suitable ligands for the MMP9 protein. The present study highlighted the use of SM resources as functional products with health benefits.

Summary: Compartmentalization of proteins by liquid-liquid phase separation (LLPS) is used by cells to control biochemical reactions spatially and temporally. Among them, the recruitment of proteins to DNA foci and nucleolar trafficking occur by biomolecular condensation. Within this frame, the oncoprotein SET/TAF-Iβ plays a key role in both chromatin remodeling and DNA damage response, as does nucleophosmin (NPM1) which indeed participates in nucleolar ribosome synthesis. Whereas phase separation by NPM1 is widely characterized, little is known about that undergone by SET/TAF-Iβ. Here, we show that SET/TAF-Iβ experiences phase separation together with respiratory cytochrome c (Cc), which translocates to the nucleus upon DNA damage. Here we report the molecular mechanisms governing Cc-induced phase separation of SET/TAF-Iβ and NPM1, where two lysine-rich clusters of Cc are essential to recognize molecular surfaces on both partners in a specific and coordinated manner. Cc thus emerges as a small, globular protein with sequence-encoded heterotypic phase-separation properties.

Summary: Despite recent advances in the mechanism of oxidized DNA activating NLRP3, the molecular mechanism and consequence of oxidized DNA associating with NLRP3 remains unknown. Cytosolic NLRP3 binds oxidized DNA which has been released from the mitochondria, which subsequently triggers inflammasome activation. Human glycosylase (hOGG1) repairs oxidized DNA damage which inhibits inflammasome activation. The fold of NLRP3 pyrin domain contains amino acids and a protein fold similar to hOGG1. Amino acids that enable hOGG1 to bind and cleave oxidized DNA are conserved in NLRP3. We found NLRP3 could bind and cleave oxidized guanine within mitochondrial DNA. The binding of oxidized DNA to NLRP3 was prevented by small molecule drugs which also inhibit hOGG1. These same drugs also inhibited inflammasome activation. Elucidating this mechanism will enable the design of drug memetics that treat inflammasome pathologies, illustrated herein by NLRP3 pyrin domain inhibitors which suppressed interleukin-1β (IL-1β) production in macrophages.

Summary: Tel1/ataxia telangiectasia mutated (ATM) kinase plays multiple functions in response to DNA damage, promoting checkpoint-mediated cell-cycle arrest and repair of broken DNA. In addition, Saccharomyces cerevisiae Tel1 stabilizes replication forks that arrest upon the treatment with the topoisomerase poison camptothecin (CPT). We discover that inactivation of the Exo1 nuclease exacerbates the sensitivity of Tel1-deficient cells to CPT and other agents that hamper DNA replication. Furthermore, cells lacking both Exo1 and Tel1 activities exhibit sustained checkpoint activation in the presence of CPT, indicating that Tel1 and Exo1 limit the activation of a Mec1-dependent checkpoint. The absence of Tel1 or its kinase activity enhances recombination between inverted DNA repeats induced by replication fork blockage in an Exo1-dependent manner. Thus, we propose that Exo1 processes intermediates arising at stalled forks in tel1 mutants to promote DNA replication recovery and cell survival.

Summary: PU.1 (SPI1) is pivotal in hematopoiesis, yet its role in human endothelial-to-hematopoietic transition (EHT) remains unclear. Comparing human in vivo and in vitro EHT transcriptomes revealed SPI1’s regulatory role. Knocking down SPI1 during in vitro EHT led to a decrease in the generation of hematopoietic progenitor cells (HPCs) and their differentiation potential. Through multi-omic analysis, we identified KLF1 and LYL1 - transcription factors specific to erythroid/myeloid and lymphoid cells, respectively - as downstream targets of SPI1. Overexpressing KLF1 or LYL1 partially rescues the SPI1 knockdown-induced reduction in HPC formation. Specifically, KLF1 overexpression restores myeloid lineage potential, while LYL1 overexpression re-establishes lymphoid lineage potential. We also observed a SPI1-LYL1 axis in the regulatory network in in vivo EHT. Taken together, our findings shed new light on the role of SPI1 in regulating lineage commitment during EHT, potentially contributing to the heterogeneity of hematopoietic stem cells (HSCs).

Metal nanoparticles offer promising prospects in agriculture, enhancing plant growth and ensuring food security. Silver, gold, copper, and zinc nanoparticles possess unique properties making them attractive for plant applications. Understanding molecular interactions between metal nanoparticles and plants is crucial for unlocking their potential to boost crop productivity and sustainability. This review explores metal nanoparticles in agriculture, emphasizing the need to understand these interactions. By elucidating mechanisms, it highlights the potential for enhancing crop productivity, stress tolerance, and nutrient-use efficiency, contributing to sustainable agriculture and food security. Quantifying benefits and risks reveal significant advantages. Metal nanoparticles enhance crop productivity by 20% on average and reduce disease incidence by up to 50% when used as antimicrobial agents. They also reduce nutrient leaching by 30% and enhance soil carbon sequestration by 15%, but concerns about toxicity, adverse effects on non-target organisms, and nanoparticle accumulation in the food chain must be addressed. Metal nanoparticles influence cellular processes including sensing, signaling, transcription, translation, and post-translational modifications. They act as signaling molecules, activate stress-responsive genes, enhance defense mechanisms, and improve nutrient uptake. The review explores their catalytic role in nutrient management, disease control, precision agriculture, nano-fertilizers, and nano-remediation. A bibliometric analysis offers insights into the current research landscape, highlighting trends, gaps, and future directions. In conclusion, metal nanoparticles hold potential for revolutionizing agriculture, enhancing productivity, mitigating environmental stressors, and promoting sustainability. Addressing risks and gaps is crucial for their safe integration into agricultural practices.

Summary: Deleted in liver cancer 3 (DLC3) is a Rho GTPase-activating protein (RhoGAP) that plays a crucial role in maintaining adherens junction integrity and coordinating polarized vesicle transport by modulating Rho activity at the plasma membrane and endomembranes. By employing bioinformatical sequence analysis, in vitro experiments, and in cellulo assays we here identified a polybasic region (PBR) in DLC3 that facilitates the association of the protein with cellular membranes. Within the PBR, we mapped two serines whose phosphorylation can alter the electrostatic character of the region. Consequently, phosphomimetic mutations of these sites impaired the membrane association of DLC3. Furthermore, we found a new PBR-dependent localization of DLC3 at the midbody region, where the protein locally controlled Rho activity. Here, the phosphorylation-dependent regulation of DLC3 appeared to be required for proper cytokinesis. Our work thus provides a novel mechanism for spatiotemporal termination of Rho signaling by the RhoGAP protein DLC3.

Thermo-dynamical analyses of organic mixtures are essential across industries. Ultrasonic sound velocity (U) measurements in the ternary organic mixtures of Toluene, Chloroform, and Cyclohexane have been conducted between 303.15, 308.15 and 313.15 K. The experimental/derived data were utilised to compute deviations for their excess values such as adiabatic compressibility (βE), free length (LfE), free volume (VfE), impedance (ZE), internal pressure (πiE) and enthalpy (HE) to investigate and confirm the types of interactions. Using these derived parameters, excess parameters were calculated to further reaffirm the type, strength, magnitude, and potential interactions such as complex formation, dipole-dipole, and dispersive types. Moreover, both ideal and nonideal behaviours were analysed. The ultrasonic velocity data were validated against some contemporary and well-known models like Namoto’s relation (NR), Ideal mixture relation (IMR), Impedance dependence relation (IDR), Collision factor theory (CFT) and Nutch-Kunkies (NK) theorem. From the IMR and IDR are gives well approach to experimental one. And a comparative study of these models was conducted to ascertain the possible types of interactions within the mixtures through their molecular interaction parameter, percentage deviation, standard percentage error deviation.

Summary: YAP/TEAD signaling is essential for organismal development, cell proliferation, and cancer progression. As a transcriptional coactivator, how YAP activates its downstream target genes is incompletely understood. YAP forms biomolecular condensates in response to hyperosmotic stress, concentrating transcription-related factors to activate downstream target genes. However, whether YAP forms condensates under other signals, how YAP condensates organize and function, and how YAP condensates activate transcription in general are unknown. Here, we report that endogenous YAP forms sub-micron scale condensates in response to Hippo pathway regulation and actin cytoskeletal tension. YAP condensates are stabilized by the transcription factor TEAD1, and recruit BRD4, a coactivator that is enriched at active enhancers. Using single-particle tracking, we found that YAP condensates slowed YAP diffusion within condensate boundaries, a possible mechanism for promoting YAP target search. These results reveal that YAP condensate formation is a highly regulated process that is critical for YAP/TEAD target gene expression.

Diah Lia Aulifa,1 Adnan Aly Al Shofwan,2 Sandra Megantara,1 Taufik Muhammad Fakih,3 Arif Budiman2 1Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 2Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 3Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Bandung, IndonesiaCorrespondence: Diah Lia Aulifa, Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Sumedang, 45363, Indonesia, Email diah.lia@unpad.ac.idIntroduction: Amorphous drug dispersion is frequently used to enhance the solubility and dissolution of poorly water-soluble drugs, thereby improving their oral bioavailability. The dispersion of these drugs into polymer matrix can inhibit their recrystallization. The inter-molecular interactions between drug and polymer plays a role in the improvement of the dissolution rate, solubility, and physical stability of drug.Aim: This study aims to investigate the formation and interactions of ritonavir (RTV)/poloxamer (PLX) amorphous formulation using a computational approach via molecular dynamics (MD) simulations, which mimicked solvent evaporation and melt-quenching method.Methods: TheRoot Mean Square Deviation (RMSD) value, Root Mean Square Fluctuation (RMSF), Radial Distribution Function (RDF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA), and hydrogen bond interactions were analyzed to determine interaction mechanisms between RTV and PLX in amorphous solid dispersion.Results: The pi-alkyl bonds between RTV and PLX were formed after simulations of solvent evaporation, while the hydrogen bond interactions of RTV-PLX was observed during melt method simulations. These results indicate the successful formulation of amorphous solid dispersion (ASD) from RTV and PLX. The RMSD values obtained from the solvent evaporation, melt-cooling-A, melt-cooling-B, and melt-cooling-C methods were 3.33 Å, 1.97 Å, 1.30 Å, and 1.29 Å, respectively, while the average RMSF values were 2.65 Å, 1.04 Å, 1.05 Å, and 1.07 Å, respectively. This indicates that the suppression of translational motion of RTV from the melt method can be stronger than solvent evaporation caused by the intermolecular interactions of RTV-PLX.Conclusion: MD simulations helped in understanding the formation and interaction mechanisms of ASD formulations that were difficult to detect by experimental approaches.Keywords: amorphous solid dispersion, molecular interaction, molecular dynamics simulations, ritonavir, poloxamer

Fertilization is a complex process that depends on the fusion of the cell membrane of sperm with that of oocyte, and it involves sperm-oocyte recognition, binding, and fusion, which are mediated by multiple proteins. Among those proteins, IZUMO1 and its receptor JUNO have been identified as essential factors for sperm-oocyte recognition and fusion. However, the interaction between IZUMO1 and JUNO alone does not lead to cell membrane fusion, suggesting the involvement of additional proteins in sperm-oocyte membrane fusion. In this study, we have discovered that a protein called WDR54, which consists of WD-repeat modules, is located on the cell membrane of sperm, as well as on the cell membrane and in the cytoplasm of the oocyte. We have found that WDR54 is involved in sperm-oocyte fertilization. When sperm and oocyte were treated with anti-WDR54 ascites, the in vitro fertilization (IVF) rate significantly decreased. Furthermore, our research has shown that WDR54 interacts with both IZUMO1 and JUNO, and it colocalizes with IZUMO1 on the surface of the sperm head and with JUNO on the oocyte surface. Through structural analysis of the putative complexes of WDR54-IZUMO1 and WDR54-JUNO, we infer that these three proteins could form a complex of JUNO-WDR54-IZUMO1-JUNO (referred to as the "JWIJ complex") on the oocyte surface. Our findings suggest that WDR54 is an important factor involved in sperm-oocyte adhesion and fusion. This discovery provides new insight into the mechanisms of mammalian sperm-oocyte adhesion and fusion. • WDR54 is located on the surface of sperm and oocyte, and colocalizes with IZUMO1 and JUNO, on sperm head and oocyte surface, respectively. • The IVF rate was significantly inhibited when rat sperm and oocytes were treated with mouse anti-rat WDR54 ascites. • WDR54 is a candidate for mediating the interactions between sperm and egg plasma membranes. [ABSTRACT FROM AUTHOR]

Streptococcus mutans, the primary cause of dental caries, relies on its ability to create and sustain a biofilm (dental plaque) for survival and pathogenicity in the oral cavity. This study was focused on the antimicrobial biofilm formation control and biofilm dispersal potential of Coumaric acid (CA) against Streptococcus mutans on the dentin surface. The biofilm was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay, microtiter plate assay, production of extracellular polymeric substances (EPSs), florescence microscopy (surface coverage and biomass μm2) and three-dimensional (3D) surface plots. It was observed that CA at 0.01 mg/mL reduced bacterial growth by 5.51%, whereases at 1 mg/mL, a significant (p < 0.05) reduction (98.37%) was observed. However, at 1 mg/mL of CA, a 95.48% biofilm formation reduction was achieved, while a 73.45% biofilm dispersal (after 24 h. treatment) was achieved against the preformed biofilm. The MTT assay showed that at 1 mg/mL of CA, the viability of bacteria in the biofilm was markedly (p < 0.05) reduced to 73.44%. Moreover, polysaccharide (EPS) was reduced to 24.80 μg/mL and protein (EPS) to 41.47 μg/mL. ImageJ software (version 1.54 g) was used to process florescence images, and it was observed that the biofilm mass was reduced to 213 (μm2); the surface coverage was reduced to 0.079%. Furthermore, the 3D surface plots showed that the untreated biofilm was highly dense, with more fibril-like projections. Additionally, molecular docking predicted a possible interaction pattern of CA (ligand) with the receptor Competence Stimulating Peptide (UA159sp, PDB ID: 2I2J). Our findings suggest that CA has antibacterial and biofilm control efficacy against S. mutans associated with dental plaque under tested conditions. [ABSTRACT FROM AUTHOR]

Thermo-acoustical parameters of solutions of (2-[(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)methyl]-1H-benzo[d]imidazol-1-yl)(phenyl)methanone, (AS2-13) and (2-[(5-(4-aminophenyl)-1,3,4-oxadiazol-2-ylthiomethyl]-1H-benzo[d]imidazol-1-yl)(phenyl)methanone, (AS2-14) in dimethyl sulfoxide (DMSO) and N, N-dimethylformamide (DMF) have been evaluated. Various acoustical and thermodynamic parameters, including density (ρ), viscosity (η), and ultrasonic sound velocity (U), have been measured at three different temperatures, namely (298.15 K, 308.15 K and 318.15 K at atmospheric pressure. These results have been explained by considering the molecular interactions of the liquid mixture's components. [ABSTRACT FROM AUTHOR]

Drug delivery insights were provided by performing density functional theory (DFT) calculations to investigate the adsorption of a non-steroidal anti-inflammatory drugs; ibuprofen (IBU), by an iron-doped silicon carbide (FSiC) graphene monolayer. In this regard, the single models of IBU, SiC, and FSiC were optimized to obtain their stabilized geometries and features, in which a remarkable achievement was found for the enhanced FSiC graphene monolayer towards the original SiC graphene monolayer for interacting with the IBU substance. Subsequently, the formation of interacting complex of IBU and each of SiC and FSiC graphene monolayers was investigated by re-optimizing the bimolecular models to obtain IBU@SiC and IBU@FSiC complexes with interaction energies of -1.44 kcal/mol and -43.14 kcal/mol, respectively. Additionally, a remarkable role of iron-doped region for managing the interactions between FSiC and IBU counterparts was found. The existence of O…Fe interaction in the formation IBU@FSiC complex was affirmed by the results of quantum theory of atoms in molecules (QTAIM) analyses. The electronic molecular orbitals results indicated a softer FSiC graphene monolayer than SiC graphene monolayer for a better participation in interactions with the IBU substance. Comparing the changes of density of states (DOS) diagrams and energy gap (GAP) distances of frontier molecular orbital levels from the single graphene monolayer to the complex state have been revealed an easier IBU detection by the FSiC than the SiC. As a final note, a suitability of IBU@FSiC complex formations was found for working as a proposed drug delivery platform upon further investigation in this field. [ABSTRACT FROM AUTHOR]

The gel prepared using Nemipterus virgatus (N. virgatus) surimi alone still has some defects in texture and taste. Complexing with polysaccharides is an efficient strategy to enhance its gel properties. The main objective of this study was to analyze the relationship between the gel quality and molecular interaction of N. virgatus surimi gel after complexing with tapioca starch. The results make clear that the gel strength, hardness, and chewiness of surimi gel were increased by molecular interaction with tapioca starch. At the appropriate addition amount (12%, w/w), the surimi gel had an excellent gel strength (17.48 N), water-holding capacity (WHC) (89.01%), lower cooking loss rate (CLR) (0.95%), and shortened T2 relaxation time. Microstructure analysis indicated that the addition of tapioca starch facilitated even distribution in the gel network structure, resulting in a significant reduction in cavity diameter, with the minimum diameter reduced to 20.33 μm. In addition, tapioca starch enhanced the hydrogen bonding and hydrophobic interaction in the gel system and promoted the transformation of α-helix to β-sheet (p < 0.05). Correlation analysis showed that the increased physicochemical properties of surimi gel were closely related to the enhanced noncovalent interactions. In conclusion, noncovalent complexation with tapioca starch is an efficient strategy to enhance the quality of surimi gel. [ABSTRACT FROM AUTHOR]

Die molekulardynamische Simulation ist eine weit verbreitete Methode, die Einblicke in die submikroskopische Ebene von Vielteilchensystemen erlaubt und die Berechnung makroskopischer und struktureller Eigenschaften ermöglicht. Sie kann auch didaktisch hilfreich zur Vermittlung von Wechselwirkungen und den daraus resultierenden molekularen Prozessen sein. Der Umgang mit der Frage, wie eine solche Simulation abläuft, kann zum Verständnis chemischer Inhalte beitragen. Dieses „Wie" erfordert eine Auseinandersetzung mit den Simulationsmethoden und den molekularen Modellen auf der Grundlage einsehbarer Programmcodes. Bei solchen Glass‐Box Simulationen ist der Code Teil der Behandlung chemischer Inhalte. Dabei wird informatisches Denken genutzt, um mit Algorithmen molekulare Vorgänge zu erläutern. In diesem Artikel werden die van der Waals‐Wechselwirkung, die Geschwindigkeitsverteilung sowie die Struktur von Fluiden und Feststoffen behandelt. Neben einer Visualisierung der submikroskopischen Prozesse ermöglicht dieser Ansatz auch Erkenntnisse über die Natur von Modellen. Hinzu kommt, dass Programmierfähigkeiten in den Naturwissenschaften von großer Bedeutung sind und auch im schulischen Bereich für die damit verbundenen Möglichkeiten sensibilisiert werden sollte. [ABSTRACT FROM AUTHOR]

In this study, an amorphous solid dispersion containing the poorly water-soluble drug, bisacodyl, was prepared by hot-melt extrusion to enhance its therapeutic efficacy. First, the miscibility and interaction between the drug and polymer were investigated as pre-formulation strategies using various analytical approaches to obtain information for selecting a suitable polymer. Based on the calculation of the Hansen solubility parameter and the identification of the single glass transition temperature ( T g ), the miscibility between bisacodyl and all the investigated polymers was confirmed. Additionally, the drug–polymer molecular interaction was identified based on the comprehensive results of dynamic vapor sorption (DVS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and a comparison of the predicted and experimental values of T g . In particular, the hydroxypropyl methylcellulose (HPMC)-based solid dispersions, which exhibited large deviation between the calculated and experimental values of T g and superior physical stability after DVS experiments, were selected as the most appropriate solubilized bisacodyl formulations due to the excellent inhibitory effects on precipitation based on the results of the non-sink dissolution test. Furthermore, it was shown that the enteric-coated tablets containing HPMC–bisacodyl at a 1:4 ratio (w/w) had significantly improved in vivo therapeutic laxative efficacy compared to preparations containing un-solubilized raw bisacodyl in constipation-induced rabbits. Therefore, it was concluded that the pre-formulation strategy, using several analyses and approaches, was successfully applied in this study to investigate the miscibility and interaction of drug–polymer systems, hence resulting in the manufacture of favorable solid dispersions with favorable in vitro and in vivo performances using hot-melt extrusion processes. [ABSTRACT FROM AUTHOR]

Compared with aqueous single‐ion batteries, rechargeable aqueous hybrid ion batteries, especially Li+/Zn2+hybrid ion batteries, are receiving extensive interest owing to their low cost, high operating voltage, and energy density. However, their working voltage and lifespan are limited by the decomposition of water and the growth of Zn dendrites. Herein, detrimental side reactions induced by the water reduction and the Zn dendrite growth are successfully suppressed by a poly(propylene glycol) (PPG)‐based hybrid ion electrolyte [(1 m Zn(TFSI)2 + 10 m LiTFSI) in PPG/H2O]. The addition of PPG in the electrolyte can not only enhance the bonding strength of hydrogen‐bond in water but also tailor the solvation sheath of Zn2+ as revealed by synchrotron X‐rays. The participated solvation of PPG with Zn2+ can weaken Zn−H2O interactions and redistribute Zn2+ flux on the surface of the Zn anode, thus inducing favorably even deposition of Zn. In addition, the decomposition of TFSI− contributes a ZnF2 ‐enriched solid electrolyte interface at the Zn anode to further prevent water decomposition and restrain Zn dendrites. The PPG‐based electrolyte enables 2.1 V LiMnO2//Zn batteries to deliver high specific capacities (121.7 mAh g−1 for a coin cell and 90 mAh g−1 for a pouch cell), and maintain 80% of the capacity over 700 cycles at 0.5 C, suggesting a promising pathway for highly reversible aqueous hybrid ion batteries. [ABSTRACT FROM AUTHOR]

BackgroundRice 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.MethodsThe 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.ResultsHME 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.DiscussionThe 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.

DNA methylation is well-accepted as a bridge to unravel the complex interplay between genome and environmental exposures, and its alteration regulated the cellular metabolic responses towards pollutants. However, the mechanism underlying site-specific aberrant DNA methylation and metabolic disorders under pollutant stresses remained elusive. Herein, the multilevel omics interferences of sulfonamides (i.e., sulfadiazine and sulfamerazine), a group of antibiotics pervasive in farmland soils, towards rice in 14 days of 1 mg/L hydroponic exposure were systematically evaluated. Metabolome and transcriptome analyses showed that 57.1–71.4 % of mono- and disaccharides were accumulated, and the differentially expressed genes were involved in the promotion of sugar hydrolysis, as well as the detoxification of sulfonamides. Most differentially methylated regions (DMRs) were hypomethylated ones (accounting for 87–95 %), and 92 % of which were located in the CHH context (H = A, C, or T base). KEGG enrichment analysis revealed that CHH-DMRs in the promoter regions were enriched in sugar metabolism. To reveal the significant hypomethylation of CHH, multi-spectroscopic and thermodynamic approaches, combined with molecular simulation were conducted to investigate the molecular interaction between sulfonamides and DNA in different sequence contexts, and the result demonstrated that sulfonamides would insert into the minor grooves of DNA, and exhibited a stronger affinity with the CHH contexts of DNA compared to CG or CHG contexts. Computational modeling of DNA 3D structures further confirmed that the binding led to a pitch increase of 0.1 Å and a 3.8° decrease in the twist angle of DNA in the CHH context. This specific interaction and the downregulation of methyltransferase CMT2 (log2FC = –4.04) inhibited the DNA methylation. These results indicated that DNA methylation-based assessment was useful for metabolic toxicity prediction and health risk assessment.