A Natural Compound Containing a Disaccharide Structure of Glucose and Rhamnose Identified as Potential N-Glycanase 1 (NGLY1) Inhibitors.

N-glycanase 1 (NGLY1) is an essential enzyme involved in the deglycosylation of misfolded glycoproteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which could hydrolyze N-glycan from N-glycoprotein or N-glycopeptide in the cytosol. Recent studies indicated that NGLY1 inhibition is a potential novel drug target for antiviral therapy. In this study, structure-based virtual analysis was applied to screen candidate NGLY1 inhibitors from 2960 natural compounds. Three natural compounds, Poliumoside, Soyasaponin Bb, and Saikosaponin B2 showed significantly inhibitory activity of NGLY1, isolated from traditional heat-clearing and detoxifying Chinese herbs. Furthermore, the core structural motif of the three NGLY1 inhibitors was a disaccharide structure with glucose and rhamnose, which might exert its action by binding to important active sites of NGLY1, such as Lys238 and Trp244. In traditional Chinese medicine, many compounds containing this disaccharide structure probably targeted NGLY1. This study unveiled the leading compound of NGLY1 inhibitors with its core structure, which could guide future drug development.

[Risk Assessment Method of Non-point Source Pollution Output for Watershed Using High Resolution Data].

In recent years, non-point source pollution has become the main cause of water quality deterioration in some reservoirs in China. Taking the Panjiakou Reservoir as an example, the classical output risk model was improved by introducing a precipitation factor and terrain factor. Combined with high-resolution satellite precipitation products (GPM) and GF-6 satellite images, a high-resolution data-driven risk assessment method for non-point source pollution output was established to study the temporal and spatial distribution characteristics of non-point source pollution output risk in the Panjiakou Reservoir basin. The results showed that the non-point source pollution output risk was high in the study area in 2018. The areas with higher and highest risk of nitrogen pollution output accounted for approximately 70.6% of the total watershed area, whereas the higher risk of phosphorus pollution output accounted for approximately 21.9%. The temporal and spatial distribution characteristics of non-point source pollution output risk in the Panjiakou Reservoir basin were analyzed. It was found that the non-point source pollution output risk in the Panjiakou Reservoir basin increased first and then decreased from April to September. This was consistent with the spatial and temporal distribution of precipitation in the basin. Combined with the analysis of land use distribution characteristics, the upstream area of the basin was mainly cultivated land, whereas cities were concentrated in the downstream portion of the basin. Affected by agricultural production and human activities, the risk of non-point source pollution output was higher in these regions. In view of the temporal and spatial distribution characteristics of non-point source pollution output risk, it is necessary to formulate a reasonable agricultural fertilization method, plan the landscape layout of source-sinks, and construct vegetation buffer zones.