Due to the high homology of the ATP sites of the JAK family, the development of selective inhibitors for a certain JAK isoform is extremely challenging. Our strategy to achieve high selectivity for TYK2 relies on targeting the TYK2 pseudokinase (JH2) domain. Based on the clinical compound BMS-986165, through structure-activity relationship studies, a class of acyl compounds with excellent TYK2 inhibitory activity and selectivity to other subtypes of the JAK family was discovered.
Alpine lakes play a significant role in improving watershed ecology, adjusting water storage, and managing regional water resources. They are also a valuable freshwater reservoir, flood storage, and species gene pool in Central Asia. This article validated the accuracy of the CryoSat-2 footprints altimetry dataset for the Lake Bosten and Lake Issyk-Kul ranges. The time series for the surface elevations of the Central Asian alpine lakes Karakul and Chatyrkul were established, based on footprints altimetry data. The lake hydrological drivers were analyzed using remote sensing meteorological reanalysis data of the lake basins. The following main conclusions were reached. The CryoSat-2 footprints altimetry dataset has high confidence in lake surface elevation monitoring. Compared with Hydroweb monitoring results, the agreement between the monitoring results in the range between Lake Bosten and Lake Issyk-Kul are 0.96 and 0.84. The surface elevation of Lake Karakul shows an overall increasing trend with a variation rate of +7.7 cm/yr from 2010 to 2020, which has a positive correlation with the temperature in the basin. This indicates that the increased temperature, which results in the increased snow and ice meltwater in the basin, is the main driving force of the increased lake evolution. The lake surface elevation of Lake Chatyrkul shows an overall decreasing trend, with a variation rate of −9.9 cm/yr from 2010 to 2020, which has a negative correlation with the temperature in the basin. This suggests that Lake Chatyrkul is poorly recharged by snow and ice meltwater. The main driving force of its evolution is the increased evaporative output of the lake due to the increase in temperature. These conclusions prove that temperature and alpine glacial variability within the lake basin play an important role in lake surface elevation variations in alpine regions of Central Asia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.