LPE-1, an orally active pyrimidine derivative, inhibits growth and mobility of human esophageal cancers by targeting LSD1.

Histone lysine specific demethylase 1 (LSD1) plays an important role in epigenetic modifications, and aberrant expression of LSD1 predicts tumor progression and poor prognosis in human esophageal cancers. In this study, a series of LSD1 inhibitors were synthesized and proved to be highly potent against human esophageal squamous cell carcinoma (ESCC). Our data showed that these LSD1 inhibitors selectively suppressed the viability of esophageal cancer cell line (EC-109) bearing overexpressed LSD1. Among these, compound LPE-1 (LSD1 IC50=0.336±0.003µM) significantly suppressed proliferation, induced apoptosis, arrested cell cycle of EC109 cells at G2/M phase, and caused changes of the associated protein markers correspondingly. We also found that compound LPE-1 potently inhibited the migration and invasion of EC-109 cells. Docking studies showed that the cyano group formed hydrogen bonds with Val811 and Thr810. Additionally, the thiophene moiety formed arene-H interaction with Trp761 residue. In vivo studies showed that compound LPE-1 inhibited tumor growth of xenograft models bearing EC-109 without obvious toxicity. Collectively, our findings indicate that LSD1 may be a potential therapeutic target in ESCC, and compound LPE-1 could serve as a lead compound for further development for anti-ESCC drug discovery.

[Migration Characteristics of Manganese During Rainfall Events and Its Impacts on Water Quality in a Drinking Water Source Reservoir].

In view of the problem of excessive manganese concentrations in the Xi'an Jinpen Reservoir during the flood season in 2017, the vertical distribution of manganese in density currents and its occurrence pattern were monitored at multiple monitoring sections along the upstream reaches to the main basin. The influences of density currents plunging into the reservoir on the migration and transformation of Mn were studied, and sedimentation, output, and deposition of manganese in the reservoir water were also specifically estimated during a single, typical storm runoff process. Devices for avoiding high turbidity and high load inflows in rainfall events were proposed. The results showed that significant increases of total manganese were induced by high-turbidity inflows, which largely degraded water quality during rainfall events. From 12 to 14 October, 9.11 tons of total manganese were transported into the reservoir during a single rainfall event, and the pollution conditions were largely remitted by flood discharges with an output of 6.22 tons; thus, the net deposition (manganese) was 1.47 tons. The manganese content and morphological changes along the upper reaches of the reservoir indicated that soil erosion occurred during the continuous rainfall process, and this caused a large amount of particulate pollutants to flow into the water body with the runoff. More than 70% of the total manganese in the water was in the iron-manganese oxide bound state. Correlation analysis was conducted with particles of different particle size ranges, and granular manganese particle sizes were about 2-20 µm. The findings indicate that when flood discharges with turbidity currents occur, this can effectively reduce the load of pollutants and the safety risks of water.

[Sources and Distribution of Phosphorus in Sediments of the Jinpen Reservoir].

In order to explore the sources and distribution of phosphorus in sediments of a stratified water source reservoir, the total phosphorus (TP) content and distribution of phosphorus fractions in sedimentation particles and sediments of the Jinpen Reservoir of Xi'an were analyzed from March to November in 2017. The results showed that the TP content in the surface sediments of the Jinpen Reservoir was obviously affected by the deposition of particulate phosphorus (PP), and the correlation coefficient was 0.8775. Besides, this TP pool was also affected by the biogeochemistry of sediments. From June to August, algae in the Jinpen Reservoir propagated intensely, and a large number of dead algae were deposited on the bottom of the water body, which resulted in a type of endogenous pollution dominated by algae. The concentration of PP reached (753.51±17.11) mg·kg-1, and the content of TP increased, with NaOH-nrP as the main component. During the flood season of the Jinpen Reservoir from September to November, the runoff water carried a large amount of sediments with large pollutant loads, which resulted in increases of the concentration of PP in the water body. However, the TP content in the sediment per unit mass was relatively small. As a result, the TP content of surface sediments decreased, with inorganic Ca-P and rest-P as the main forms, which accounted for 55.8%-66.2% of the TP in sediment, and were influenced by particle sedimentation. The SRP, BD-P, and NaOH-srP, the most active fractions, underwent a series of transport and transformation processes under the changing environmental conditions (mainly redox conditions), and these forms were obviously affected by the biochemical processes in sediments and minimally affected by the sedimentation processes of the reservoir.