The Effect of Epoxidation on Strain-Induced Crystallization of Epoxidized Natural Rubber.

The effect of epoxidation on strain-induced crystallization (SIC) of epoxidized natural rubber (ENR) and mechanism are studied with synchrotron radiation wide-angle X-ray diffraction (SR-WAXD) and polarized infrared spectroscopy (P-IR). WAXD results reveal that appropriate epoxidation, for example, ENR-25 epoxidized with ≈25% isoprene units, can unexpectedly enhance the SIC of natural rubber (NR), resulting in the improvement of tear resistance. On the other hand, exorbitant epoxidation, for example, ENR-40 epoxidized with ≈40% isoprene units, depresses the SIC and weakens the mechanical properties of NR remarkably. P-IR studies reveal that epoxidation can promote the orientation of chain segments along the stretching direction, which plays a determining role on SIC of NR. Accordingly, hierarchical multiscale schematic models are proposed. This insight into epoxidation on SIC of ENR strongly suggests that ENR with appropriate epoxidation degree is a promising candidate material for the fabrication of high-performance engineering rubber products.

Gene structure, expression and function analysis of the MyoD gene in the Pacific white shrimp Litopenaeus vannamei.

The Pacific white shrimp Litopenaeus vannamei is a representative species of decapod crustacean and an economically important marine aquaculture species worldwide. However, research on the genes involved in muscle growth and development in shrimp is still lacking. MyoD is recognized as a crucial regulator of myogenesis and plays an essential role in muscle growth and differentiation in various animals. Nonetheless, little information is available concerning the function of this gene among crustaceans. In this study, we identified a sequence of the MyoD gene (LvMyoD) with a conserved bHLH domain in the L. vannamei genome. Phylogenetic analysis revealed that both the overall protein sequence and specific functional sites of LvMyoD are highly conserved with those of other crustacean species and that they are evolutionarily closely related to vertebrate MyoD and Myf5. LvMyoD expression is initially high during early muscle development in shrimp and gradually decreases after 40 days post-larval development. In adults, the muscle-specific expression of LvMyoD was confirmed through RT-qPCR analysis. Knockdown of LvMyoD inhibited the growth of the shrimp in body length and weight. Histological observation and transcriptome sequencing of muscle samples after RNA interference (RNAi) revealed nuclear agglutination and looseness in muscle fibers. Additionally, we observed significant effects on the expression of genes involved in heat shock proteins, myosins, actins, protein synthesis, and glucose metabolism. These findings suggest that LvMyoD plays a critical role in regulating muscle protein synthesis and muscle cell differentiation. Overall, this study highlights the involvement of LvMyoD in myogenesis and muscle growth, suggesting that it is a potentially important regulatory target for shrimp breeding efforts.

Discovery, SAR Study of GST Inhibitors from a Novel Quinazolin-4(1H)-one Focused DNA-Encoded Library.

The DNA-encoded library (DEL) is a powerful hit-generation tool in drug discovery. This study describes a new DEL with a privileged scaffold quinazolin-4(3H)-one developed by a robust DNA-compatible multicomponent reaction and a series of novel glutathione S-transferase (GST) inhibitors that were identified through affinity-mediated DEL selection. A novel inhibitor 16 was subsequently verified with an inhibitory potency value of 1.55 ± 0.02 µM against SjGST and 2.02 ± 0.20 µM against hGSTM2. Further optimization was carried out via various structure-activity relationship studies. And especially, the co-crystal structure of the compound 16 with the SjGST was unveiled, which clearly demonstrated its binding mode was quite different from the known GSH-like compounds. This new type of probe is likely to play a different role compared with the GSH, which may provide new opportunities to discover more potent GST inhibitors.

In crystallo-screening for discovery of human norovirus 3C-like protease inhibitors.

Outbreaks of human epidemic nonbacterial gastroenteritis are mainly caused by noroviruses. Viral replication requires a 3C-like cysteine protease (3CLpro) which processes the 200 kDa viral polyprotein into six functional proteins. The 3CLpro has attracted much interest due to its potential as a target for antiviral drugs. A system for growing high-quality crystals of native Southampton norovirus 3CLpro (SV3CP) has been established, allowing the ligand-free crystal structure to be determined to 1.3 Å in a tetrameric state. This also allowed crystal-based fragment screening to be performed with various compound libraries, ultimately to guide drug discovery for SV3CP. A total of 19 fragments were found to bind to the protease out of the 844 which were screened. Two of the hits were located at the active site of SV3CP and showed good inhibitory activity in kinetic assays. Another 5 were found at the enzyme's putative RNA-binding site and a further 11 were located in the symmetric central cavity of the tetramer.