Despite the significant amount of denim waste and its potential as a cellulose source, its use has been neglected. This study uses N-methyl morpholine-N-oxide, an eco-friendly solvent, to dissolve denim (including 100 % cotton) and create a denim film. Achieving a 10 % denim record solubility, a cellulosic film was also fabricated for comparison. Characterisation techniques were applied, and molecular dynamics simulations explored intramolecular interactions and the influence of indigo dye on dissolution process. FTIR spectra indicated no chemical reactions during dissolution and regeneration, though a shift in OH stretching suggested a change in crystallinity, confirmed by XRD results showing decreased crystallinity and a structural shift from cellulose I to cellulose II. 13C NMR analysis revealed disruptions in interchain hydrogen bonds after regeneration. TGA results showed lower decomposition temperatures for both films compared to the powders. Testing mechanical properties showed the denim film had higher elongation at break but lower tensile strength than the cellulose film. MD simulations indicated indigo dye did not significantly affect fundamental interactions but decreased denim solubility by reducing the diffusion coefficient. Rheological tests supported the simulation results, showing higher viscosity and molecular weight for the denim solution compared to cellulose.

Boron neutron capture therapy (BNCT) is a highly targeted, selective and effective technique to cure various types of cancers, with less harm to the healthy cells. In principle, BNCT treatment needs to distribute the 10boron (10B) atoms inside the tumor tissues, selectively and homogeneously, as well as to initiate a nuclear fission reaction by capturing sufficient neutrons which releases high linear energy particles to kill the tumor cells. In BNCT, it is crucial to have high quality boron agents with acceptable bio-selectivity, homogeneous distribution and deliver in required quantity, similar to chemotherapy and other radiotherapy for tumor treatment. Nevertheless, boron drugs currently used in clinical trials yet to meet the full requirements. On the other hand, BNCT processing has opened up the era of renaissance due to the advanced development of the high-quality neutron source and the global construction of new BNCT centers. Consequently, there is an urgent need to use boron agents that have increased biocapacity. Artificial intelligence (AI) tools such as molecular docking and molecular dynamic simulation technologies have been utilized to develop new medicines. In this work, the in silico assessments including bioinformatics assessments of BNCT related tumoral receptor proteins, computational assessments of optimized small molecules of boron agents, are employed to speed up the screening process for boron drugs. The outcomes will be applicable to pave the way for future BNCT that utilizes artificial intelligence. The in silico molecular docking and dynamic simulation results of the optimized small boron agents, such as 4-borono-l-phenylalanine (BPA) with optimized proteins like the L-type amino acid transporter 1 (LTA1, also known as SLC7A5) will be examined. The in silico assessments results will certainly be helpful to researchers in optimizing druggable boron agents for the BNCT application. The clinical status of the optimized proteins, which are highly relevant to cancers that may be treated with BNCT, has been assessed using bioinformatics technology and discussed accordingly. Furthermore, the evaluations of cytotoxicity (IC50), boron uptake and tissue distribution of the optimized ligands 1 and 7 have been presented.

Molecularly imprinted polymers (MIPs) are a growing highlight in polymer chemistry. They are chemically and thermally stable, may be used in a variety of environments, and fulfill a wide range of applications. Computer-aided studies of MIPs often involve the use of computational techniques to design, analyze, and optimize the production of MIPs. Limited information is available on the computational study of interactions between the epinephrine (EPI) MIP and its target molecule. A rational design for EPI-MIP preparation was performed in this study. First, density functional theory (DFT) and molecular dynamic (MD) simulation were used for the screening of functional monomers suitable for the design of MIPs of EPI in the presence of a crosslinker and a solvent environment. Among the tested functional monomers, acrylic acid (AA) was the most appropriate monomer for EPI-MIP formulation. The trends observed for five out of six DFT functionals assessed confirmed AA as the suitable monomer. The theoretical optimal molar ratio was 1:4 EPI:AA in the presence of ethylene glycol dimethacrylate (EGDMA) and acetonitrile. The effect of temperature was analyzed at this ratio of EPI:AA on mean square displacement, X-ray diffraction, density distribution, specific volume, radius of gyration, and equilibrium energies. The stability observed for all these parameters is much better, ranging from 338 to 353 K. This temperature may determine the processing and operating temperature range of EPI-MIP development using AA as a functional monomer. For cost-effectiveness and to reduce time used to prepare MIPs in the laboratory, these results could serve as a useful template for designing and developing EPI-MIPs.

Using plant extracts as photosensitizers in photodynamic therapy (PDT) represents a significant green approach toward sustainability. This study investigates beetroot juice (BRJ), betanin, and their liposomal formulations (Lip-BRJ, Lip-Bet) as photosensitizers in cancer PDT. BRJ was prepared, and its betanin content was quantified via HPLC. The p-nitrosodimethylaniline (RNO)/imidazole technique monitored the singlet oxygen formation. BRJ and betanin decreased the RNO absorbance at 440 nm by 12% and 9% after 45 min of irradiation, respectively. Furthermore, betanin interaction with Bcl-2 proteins was examined using binding free energy analysis and molecular dynamic simulation. The results revealed favorable interactions with ΔG values of -40.94 kcal/mol. Then, BRJ, betanin, Lip-BRJ, and Lip-Bet were tested as photosensitizers on normal (HEK 293) and human lung cancer (A549) cell lines. Irradiation significantly enhanced the cytotoxicity of Lip-Bet on HEK 293 cells (20% cell viability at 2000 µg/mL) and A549 cells (13% cell viability at 1000 µg/mL). For Lip-BRJ, irradiation significantly enhanced the cytotoxicity on HEK 293 cells at lower concentrations and on A549 cells at all tested concentrations. These results proved the positive effect of light and liposomal encapsulation on the anticancer activity of betanin and BRJ, suggesting the efficiency of liposomal beetroot pigments as green photosensitizers.

3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) is an explosive with excellent performance, and the use of DNTF as a high-energy component is of great significance for improving the comprehensive performance of weapons. To explore the effect of DNTF on low-melting-point molten carrier explosives, the compatibility between DNTF and other low-melting-point explosives was analyzed by differential scanning calorimetry, and mechanical sensitivity was tested. The compatibility and cohesive energy density between DNTF and other low-melting-point explosives were calculated by Materials Studio. The results showed that DNTF has good compatibility with most low-melting-point explosives, and the peak temperature change of the mixed system formed by melt-casting is not obvious. Among them, DNTF has the best compatibility with MTNP, TNT, and DNAN; moderate compatibility with DFTNAN and DNP; and the worst compatibility with DNMT. The sensitivity test results indicate that the combination of DNTF and TNT has the most significant reduction in mechanical sensitivity. DFTNAN and MTNP have better stability than DNTF and can generate strong interaction forces with DNTF. Other low-melting-point explosives mixed with DNTF have lower intermolecular forces than DNTF. The DNTF/MTNP system requires the most energy to phase change when heated compared to other mixed systems and is the least sensitive to heat. The DNTF/DNMT system has the lowest cohesive energy density and is the most sensitive to heat.

An H-bond involves the sharing of a hydrogen atom between an electronegative atom to which it is covalently bound (the donor) and another electronegative atom serving as an acceptor. Such bonds represent a critically important geometrical force in biological macromolecules and, as such, have been characterized extensively. H-bond formation invariably leads to a weakening within the acceptor moiety due to the pulling exerted by the donor hydrogen. This phenomenon can be compared to a spring connecting two masses; pulling one mass stretches the spring, similarly affecting the bond between the two masses. Herein, we describe the opposite phenomenon when investigating the energetics of the C-H···O=C bond. This bond underpins the most prevalent protein transmembrane dimerization motif (GxxxG) in which a glycine Cα-H on one helix forms a hydrogen bond with a carbonyl in a nearby helix. We use isotope-edited FT-IR spectroscopy and corroborating computational approaches to demonstrate a surprising strengthening of the acceptor C=O bond upon binding with the glycine Cα-H. We show that electronic factors associated with the Cα-H bond strengthen the C=O oscillator by increasing the s-character of the σ-bond, lowering the hyperconjugative disruption of the π-bond. In addition, a reduction of the acceptor C=O bond\'s polarity is observed upon the formation of the C-H···O=C bond. Our findings challenge the conventional understanding of H-bond dynamics and provide new insights into the structural stability of inter-helical protein interactions.

The rise in drug-resistant fungal infections poses a significant public health concern, necessitating the development of new antifungal therapies. We aimed to address this challenge by targeting a yeast casein kinase of Candida albicans for antifungal drug development. The compound library contained 589 chemical structures similar to the previously identified kinase inhibitor GW461484A. Through virtual screening, four compounds with the PubChem IDs 102583821, 12982634, 102487860, and 86260205 were selected based on their binding energies. Hydrophobic bonds and van der Waals interactions stabilised the docked complexes. Comprehensive interaction studies and a 200-nanosecond molecular dynamics simulation suggested that these molecules can maintain stable interactions with the target, as evidenced by satisfactory RMSD and RMSF values. The Rg-RMSD-based Free Energy Landscape of these complexes indicated thermodynamic stability due to the presence of conformers with global minima. These promising findings highlight the potential for developing novel antifungal therapies targeting Yck2 in C. albicans. Further experimental validation is required to assess the efficacy of these compounds as antifungal agents. This research provides a significant step towards combating antifungal resistance and opens up a new avenue for drug discovery.

Hsp27 is a member of the small heat-shock proteins (sHSPs) - the known cellular line of defence against abnormal protein folding behaviors. Nevertheless, its upregulation is linked to a variety of pathological disorders, including several types of cancers. The ceramide synthases (CerS) mediate the synthesis of ceramide, a critical structural and signaling lipid. Functionally, downstream ceramide metabolites are implicated in the apoptosis process and their abnormal functionality has been linked to anticancer resistance. Studies showed that CerS1 are possibly inhibited by Hsp27 leading to biochemical anticancer effects in vitro. Nevertheless, the nature of such protein-protein interaction (PPI) has not been considerably investigated in molecular terms, hence, we present the first description of the dynamics CerS1-Hsp27 interaction landscapes using molecular dynamics simulations. Time-scale molecular dynamics simulation analysis indicated a system-wide conformational events of decreased stability, increased flexibility, reduced compactness, and decreased folding of CerS1. Analysis of binding energy showed a favorable interaction entailing 56 residues at the interface and a total stabilizing energy of -158 KJ/mol. The CerS1 catalytic domain experienced an opposite trend compared to the protein backbone. Yet, these residues adopted a highly compact conformation as per DCCM and DSSP analysis. Furthermore, conserved residues (SER 212, ASP 213, ALA 240, GLY 243, ASP 319) comprising the substrate shuttling machinery showed notable rigidity implying a restrained ceramide precursor access and assembly; hence, a possible inhibitory mechanism. Findings from this report would streamline a better molecular understanding of CerS1-Hsp27 interactions and decipher its potential avenue toward unexplored anti-cancer mechanisms and therapy.

This study investigates the toxic effects of the insecticide spinetoram on the model organism Bombyx mori (Linnaeus) and explores the potential ameliorative properties of O-Vanillin. Sub-lethal concentrations of spinetoram were given to silkworm larvae via oral feed, resulting in reduced body weight, larval length, and impaired cocoon characteristics. A study of the enzymatic and non-enzymatic antioxidants revealed oxidative stress in the gut, fat body, and silk gland tissues, characterized by decreased antioxidants and increased lipid peroxidation. However, post-treatment with O-Vanillin effectively mitigated these toxic effects, preserving antioxidant capacities and preventing lipid peroxidation. Additionally, O-Vanillin prevented the loss of body weight and improved cocoon characteristics. At the histological level, spinetoram exposure caused mild histological damage in the gut, fat body, and silk gland. However, O-Vanillin post-treatment had ameliorative effects and mitigated the histological damages. To delve deeper into the mechanism of amelioration of O-Vanillin, in silico studies were used to study the interaction between an important xenobiotic metabolism protein of the Bombyx mori, i.e., Cytochrome p450, specifically CYP9A19, and O-Vanillin. We performed blind molecular docking followed by molecular dynamic simulation, and the results demonstrated stable binding interactions between O-Vanillin and CYP9A19, a cytochrome P450 protein in silkworm, belonging to the subfamily CYP9A, suggesting a potential role for O-vanillin in modulating xenobiotic metabolism.

Anaplastic lymphoma kinase (ALK)-driven lung cancer represents a critical therapeutic target, demanding innovative approaches for the identification of effective inhibitors. Anaplastic lymphoma kinase (ALK), a key protein involved in the pathogenesis of ALK-driven lung cancers, has been the focus of extensive drug discovery efforts. This study employed a comprehensive computational drug discovery approach, integrating virtual screening with the Lipinski filter, re-docking, molecular dynamics (MD) simulations, and free energy calculations to identify potential inhibitors from a natural compound library. Utilizing the MTiOpenScreen web server, we screened for compounds that exhibit favorable interactions with ALK, resulting in 1227 compounds with virtual screening scores ranging from - 10.2 to - 3.7 kcal/mol. Subsequent re-docking of three selected compounds (ZINC000059779788, ZINC000043552589, and ZINC000003594862) and one reference compound against ALK yielded docking scores - 10.4, - 10.2, - 10.2, and - 10.1 kcal/mol, respectively. These compounds demonstrated promising interactions with ALK, suggesting potential inhibitory effects. Advanced analyses, including MD simulation and binding free energy calculations, further supported the potential efficacy of these compounds. MD simulations, particularly the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses, revealed that compounds ZINC000059779788 and ZINC000003594862 achieved better stability compared to compound ZINC000043552589. These stable conformations suggest effective binding over time. Free energy calculations using the MM/GBSA method showed that ZINC000059779788 had the most favorable binding energy, indicating a strong and stable interaction with the ALK protein. The promising computational findings from this study emphasize the necessity for additional experimental testing to verify the therapeutic efficacy of these natural compounds for treating lung cancers.