Discovering New Metallo-Deubiquitinase CSN5 Inhibitors by a Non-Catalytic Activity Assay Platform.

COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, CFP-1, that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5. By using this platform, we identified 2-aminothiazole-4-carboxylic acids as new CSN5 inhibitors, which inhibited CSN5 but slightly downregulated PD-L1 in cancer cells. Furthermore, through the integration of deep learning-enabled virtual screening, we discovered that shikonins are nanomolar CSN5 inhibitors, which can upregulate PD-L1 in HCT116 cells. The binding modes of these structurally distinct inhibitors with CSN5 were explored by using microsecond-scale molecular dynamics simulations and tryptophan quenching assays.

[Medicinal plant biodiversity in Jilin province based on big data of the fourth national survey of traditional Chinese medicine resources].

Using Origin2022Pro, PAST4.09, GraphPad, and ArcGIS, this study analyzed the big data of the fourth national survey of traditional Chinese medicine resources in Jilin province from five dimensions: differences in resource quantity, taxonomic group, family, and genus, regional distribution, and spatiotemporal distribution, aiming to fully elucidate the biodiversity of medicinal plants in Jilin province. The results indicated that 2 241 species of medicinal plants existed in Jilin province, belonging to 881 genera of 243 families, with 20 dominant families and 3 dominant genera. There were 1 901 species of medicinal plants(belonging to 778 genera of 227 families) in the eastern mountainous region, 1 503 species(belonging to 690 genera of 225 families) in the mid-mountainous areas of the central mountainous region, and 811 species(belonging to 436 genera of 136 families) in the western plain region. The biodiversity of medicinal plants in Jilin province was high and presented a trend of high in the east and low in the west. The medicinal plant resources were mainly concentrated in the eastern mountainous region, and the number of medicinal plant groups had significant diffe-rences between regions, following the trend of western region > central region > eastern region. The species richness was in the order of eastern region > western region > central region. The species diversity structure in the central region was similar to that in the eastern and western regions, while it was significantly different between the western and eastern regions. Compared with the third national survey of traditional Chinese medicine resources, the fourth survey showed an increase of 1 417 species, a decrease of 580 species, and 824 common species, indicating significant changes in the biodiversity of medicinal plants in Jilin province. The reasons for these changes need to be further explored. This article elucidates the background and biodiversity changes of medicinal plant resources in Jilin province, laying a foundation for the protection, utilization, and industrial development of traditional Chinese medicine resources in Jilin province.

Expression changes of brain natriuretic peptide in brain tissues of rats after focal cerebral ischemia-reperfusion / 中华神经医学杂志

Objective To investigate the changes of brain natriuretic peptide (BNP) level in the　brain tissues of rats after focal ischemia-reperfusion. Methods Mature male Wistar rats were　randomly divided into sham-operated and ischemia-reperfusion groups. Focal cerebral　ischemia-reperfusion rat models in the ischemia-reperfusion group were established using Longa's　suture-occluded method.And the 2 groups were sub-grouped into 0,3,6,9,12,24,48 and 72 h,and 1and 2 w observation groups according to different times after ischemia-reperfusion. The pathological　changes in the brain tissues were observed by HE staining and immunohistochemistry. Results HE　staining indicated that neuron degeneration,necrosis and tissue edema could be seen in the brain tissues　of rats after ischemic-reperfusion. The BNP levels in the ischemic-reperfusion sub-groups were　significantly higher than those in the sham-operative sub-groups at corresponding time points (P＜0.05);and the peak level of edema and BNP expression appeared at 48 h after reperfusion. Conclusion The　expression of BNP in the brain tissues of rats after focal cerebral ischemia-reperfusion increases,which　might be related to the cerebral edema.