Based on the excellent biocompatibility of collagen, collagen was extracted from pig skin by acid-enzymatic method. The films were prepared by the self-aggregation behavior of collagen, and the catalase was immobilized by adsorption, cross-linking and embedding. The experiment investigated the effects of glutaraldehyde on the mechanical properties, external sensory properties, and denaturation temperature of the films. The results showed that self-aggregating material could maintain the triple helix structure of pig skin collagen. The self-aggregation treatment and cross-linking treatment can improve the mechanical properties to 53 MPa, while the glutaraldehyde cross-linking agent can increase the denaturation temperature of the pig skin collagen self-aggregating membrane by 20.35% to 84.48 C.This means that its application to immobilized catalase has better stability. The comparison shows that the catalase immobilized by the adsorption method has strong activity and high operational stability, and the cross-linking agent glutaraldehyde and the initial enzyme concentration have a significant effect on the immobilization, and the activity can reach 175 U g À1 . After 16 uses of the film, the catalase was completely inactivated. This study provides a reference for the preparation of a catalase sensor that can be used to detect hydrogen peroxide in food by a catalase sensor.

A developmentally retarded mutant (drm1) was identified from ethyl methanesulfonate (EMS)-mutagenized M2 seeds in Columbia (Col-0) genetic background. The drm1 flowers 109 d after sowing, with a whole life cycle of about 160 d. It also shows a pleiotropic phenotype, e.g., slow germination and lower germination rate, lower growth rate, curling leaves and abnormal floral organs. The drm1 mutation was a single recessive nuclear mutation, which was mapped to the bottom of chromosome 5 and located within a region of 20-30 kb around MXK3.1. There have been no mutants with similar phenotypes reported in the literature, suggesting that DRM1 is a novel flowering promoting locus. The findings that the drm1 flowered lately under all photoperiod conditions and its late flowering phenotype was significantly restored by vernalization treatment suggest that the drm1 is a typical late flowering mutant and most likely associated with the autonomous flowering pathway. The conclusion was further confirmed by the revelation that the transcript level of FLC was constantly upregulated in the drm1 at all the developmental phases examined, except for a very early stage. Moreover, the transcript levels of two other important repressors, EMF and TFL1, were also upregulated in the drm1, implying that the two repressors, along with FLC, seems to act in parallel pathways in the drm1 to regulate flowering as well as other aspects of floral development in a negatively additive way. This helps to explain why the drm1 exhibits a much more severe late-flowering phenotype than most late-flowering mutants reported. It also implies that the DRM1 might act upstream of these repressors.

We successfully synthesized {BiW8}, a 10‐nuclear heteroatom cluster modified {BiW8O30}. At 24 h post‐incubation, the IC50 values of {BiW8} against HUVEC, MG63, RD, Hep3B, HepG2, and MCF7 cells were 895.8, 127.3, 344.3, 455.0, 781.3, and 206.3 μM, respectively. The IC50 value of {BiW8} on the MG63 cells was more than 2‐fold lower than that of the other raw materials. Through morphological and functional features, we demonstrated pyroptosis as a newly identified mechanism of cell death induced by {BiW8}. {BiW8} increased 2‐fold reactive oxygen species (ROS) levels in MG63 cells at 24 h post‐incubation. Compared with 0 h, the glutathione (GSH) content decreased by 59, 65, 75, 94, and 97 % at 6, 12, 24, 36 and 48 h post‐incubation, respectively. Furthermore, multiple antitumor mechanisms of {BiW8} were identified via transcriptome analysis and chemical simulation, including activation of pyroptosis, suppression of GSH generation, depletion of GSH, and inhibition of DNA repair.

No abstract

Glucocorticoid receptor (GR) regulates various cellular functions. Given its broad influence on metabolic activities, it has been the target of drug discovery for decades. However, how drugs induce conformational changes in GR has remained elusive. Herein, we used five GR agonists (dex, AZ938, pred, cor, and dibC) with different efficacies to investigate which aspect of the ligand induced the differences in efficacy. We performed molecular dynamics simulations on the five systems (dex-, AZ938-, pred-, cor-, and dibC-bound systems) and observed a distinct discrepancy in the conformation of the cofactor TIF2. Moreover, we discovered ligand-induced differences regarding the level of conformational changes posed by the binding of cofactor TIF2 and identified a pair of essential residues D590 and T39. We further found a positive correlation between the efficacies of ligands and the interaction of the two binding pockets’ domains, where D590 and T739 were involved, implying their significance in the participation of allosteric communication. Using community network analysis, two essential communities containing D590 and T739 were identified with their connectivity correlating to the efficacy of ligands. The potential communication pathways between these two residues were revealed. These results revealed the underlying mechanism of allosteric communication between the ligand-binding and cofactor-binding pockets and identified a pair of important residues in the allosteric communication pathway, which can serve as a guide for future drug discovery.