Structural analysis and insight into novel MMP-13 inhibitors from natural chemiome as disease-modifying osteoarthritis drugs

Purpose: To identify natural chemiome that inhibits matrix-metalloproteinases (MMPs) with a view to discovering novel disease-modifying osteoarthritis drugs (DMOADs).Methods: Computer-aided drug design (CADD) with virtual screening, ADME/Tox, molecular docking, molecular dynamics simulation, and MM-PBSA calculations were used in search of novel natural compounds that inhibit MMPs.Results: From more than fifty thousand compounds, a single lead compound (IBS ID: 77312) was shortlisted using bias based on binding energy and drug-likeness. This lead compound synergistically bound to the S1 domain of MMP-13 protein through five hydrogen bonds. The interactions became stable within 100-nanosecond molecular dynamics simulation run. The in vitro data for the lead compound showed that its minimal non-lethal dose increased collagen content but decreased aggrecan level in chondrocytes.Conclusion: This study has identified a natural lead compound that may pave the way for a novel DMOAD of natural origin against OA.Keywords: Osteoarthritis, MMP-13, Natural chemiome, Disease-modifying osteoarthritis drug, Molecular dockin

Effect of Liquid Crystalline Acrylates on the Electro-Optical Properties and Micro-Structures of Polymer-Dispersed Liquid Crystal Films

Polymer-dispersed liquid-crystal (PDLC) films have wide applications in light shutters, smart windows for cars and buildings, dimming glasses, and smart peep-proof films due to their switchable optical states under electrical fields as well as large area processibility. They are usually prepared with liquid crystals (LCs) and non-liquid crystalline monomers (NLCMs). Introduction of liquid crystalline monomers (LCMs) into PDLCs might spark new functionality or high-performance devices such as polymer-dispersed and -stabilized liquid crystals. In this study, the effect of molecular structures and doping concentrations of acrylate LCMs on the electro-optical properties and micro-structures of PDLC films is systematically studied. The pore size of polymer networks and the driving voltage of the PDLC films are affected by the molecular polarity and degree of functionality of the LCMs. The electro-optical properties of the PDLC films are affected by the synergistic influence of molecular structure of LCMs and micro-structures of PDLCs. These results might provide the experimental and theoretical basis for constructing the relationship between the molecular structure of LCM, micro-structure and electro-optical response of PDLC films

Phenotypic and Transcriptomics Analyses Reveal Underlying Mechanisms in a Mouse Model of Corneal Bee Sting

Corneal bee sting (CBS) is one of the most common ocular traumas and can lead to blindness. The ophthalmic manifestations are caused by direct mechanical effects of bee stings, toxic effects, and host immune responses to bee venom (BV); however, the underlying pathogenesis remains unclear. Clinically, topical steroids and antibiotics are routinely used to treat CBS patients but the specific drug targets are unknown; therefore, it is imperative to study the pathological characteristics, injury mechanisms, and therapeutic targets involved in CBS. In the present study, a CBS injury model was successfully established by injecting BV into the corneal stroma of healthy C57BL/6 mice. F-actin staining revealed corneal endothelial cell damage, decreased density, skeletal disorder, and thickened corneal stromal. The terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay showed apoptosis of both epithelial and endothelial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that cytokine–cytokine interactions were the most relevant pathway for pathogenesis. Protein–protein interaction (PPI) network analysis showed that IL-1, TNF, and IL-6 were the most relevant nodes. RNA-seq after the application of Tobradex® (0.3% tobramycin and 0.1% dexamethasone) eye ointment showed that Tobradex® not only downregulated relevant inflammatory factors but also reduced corneal pain as well as promoted nerve regeneration by repairing axons. Here, a stable and reliable model of CBS injury was successfully established for the first time, and the pathogenesis of CBS and the therapeutic targets of Tobradex® are discussed. These hub genes are expected to be biomarkers and therapeutic targets for the diagnosis and treatment of CBS

Colored PDLC Films with Wide Gamut Range

Due to the discoloration properties under different applied voltages, dye-doped polymer-dispersed liquid crystal (PDLC) films are widely used as camouflage nets and invisibility cloaks. However, the range of the discoloration has an intuitive effect on their applications. In this work, we studied the gamut range of PDLC film doped with dyes of red, green, blue, and yellow, with the concentration corresponding to the minimum haze of these dyes. The influence of the applied voltage on the color range of single-layer and double-layer films with different backgrounds was studied. The relationship of the voltage with the color was set from 0 V to 60 V at steps of 5 V, to characterize the discoloration of the PDLC films. The results showed that the films could cover 42.48% of the sRGB gamut and even exceed the range

Effect of Curing Temperature on the Properties of Electrically Controlled Dimming Film with Wide Working Temperature Range

In this paper, a polymer dispersed liquid crystal (PDLC) film with good electro-optical properties and wide working temperature range was prepared by the UV-polymerization induced phase separation (PIPS) method by optimizing the curing temperature using a LC with wide temperature range. The investigation found that when the polymerization temperature was at the clearing point of the prepolymer/LC mixture, the film had better electro-optical properties and a high contrast ratio of 51 at 90 °C, and the rise time and decay time were respectively as fast as 241.5 ms and 1750 ms at −20 °C. This study provides further methodological guidance for the curing process of PDLC film, and promotes its application in outdoor smart windows

Tailoring of Porous Structure in Macro-Meso-Microporous SiC Ultrathin Fibers <i>via</i> Electrospinning Combined with Polymer-Derived Ceramics Route

<p>Porous SiC has attracted extensive attention for its wide applications, especially in harsh environment, due to its unique properties. In the present paper, novel macro-meso-microporous SiC ultrathin fibers (MMM-SFs) were synthesized through electrospinning process associated with polymer-derived ceramics route, and the porous structure in the SFs can be conveniently tailored by tuning the composition of the spinning solvents and the concentration of the precursor (polycarbosilane). The surface features and microstructures of the resultant MMM-SFs were characterized in detail. These fibers presented a high specific surface area of 86.1–128.2 m² g⁻¹. The formation mechanism of hierarchically porous structure was discussed as well. <i>N,N</i>′-dimethylformamide (DMF) played a critical role in forming macropores, while the decomposition of SiO_<i>x</i>C_<i>y</i> phase was responsible for the meso-/micropores. Our method utilized to synthesize hierarchically porous SFs is easily capable of designing other ceramic fibers.</p