Scanning electron microscope (SEM), transmission electron microscope (TEM) and X-ray diffraction (XRD) were employed to study the phase in a directionally solidified experimental nickel base alloy. It was observed that the phase distribute at interdendritic area and precipitate mainly from the 0 phase in this experimental alloy. Orientation relationship between the 0 and the phase was found as ð111Þ 0 k ð0001Þ and h " 1 110i 0 k h11 " 2 20i . Detrimental effect of the phase on oxidation resistance of the alloys was also found.
Disruption of EZH2−embryonic ectoderm development (EED) protein−protein interaction (PPI) is a new promising cancer therapeutic strategy. We have previously reported the discovery of astemizole, a small-molecule inhibitor targeting the EZH2−EED PPI. Herein, we report the cocrystal structure of EED in complex with astemizole at 2.15 Å. The structure elucidates the detailed binding mode of astemizole to EED and provides a structure-guided design for the discovery of a novel EZH2−EED interaction inhibitor, DC-PRC2in-01, with an affinity K d of 4.56 μM. DC-PRC2in-01 destabilizes the PRC2 complex, thereby leading to the degradation of PRC2 core proteins and the decrease of global H3K27me3 levels in cancer cells. The proliferation of PRC2-driven lymphomas cells is effectively inhibited, and the cell cycle is arrested in the G0/G1 phase. Together, these data demonstrate that DC-PRC2in-01 could be an effective chemical probe for investigating the PRC2-related physiology and pathology and providing a promising chemical scaffold for further development.
Excessive nitrogen (N) discharge from agriculture causes widespread problems in aquatic ecosystems. Knowledge of spatiotemporal patterns and source attribution of N pollution is critical for nutrient management programs but is poorly studied in headwaters with various small water bodies and mini-point pollution sources. Taking a typical small watershed in the low mountains of Southeastern China as an example, N pollution and source attribution were studied for a multipond system around a village using the Hydrological Simulation Program-Fortran (HSPF) model. The results exhibited distinctive spatio-seasonal variations with an overall seriousness rank for the three indicators: total nitrogen (TN) > nitrate/nitrite nitrogen (NO-N) > ammonia nitrogen (NH-N), according to the Chinese Surface Water Quality Standard. TN pollution was severe for the entire watershed, while NO-N pollution was significant for ponds and ditches far from the village, and the NH-N concentrations were acceptable except for the ponds near the village in summer. Although food and cash crop production accounted for the largest source of N loads, we discovered that mini-point pollution sources, including animal feeding operations, rural residential sewage, and waste, together contributed as high as 47% of the TN and NH-N loads in ponds and ditches. So, apart from eco-fertilizer programs and concentrated animal feeding operations, the importance of environmental awareness building for resource management is highlighted for small farmers in headwater agricultural watersheds. As a first attempt to incorporate multipond systems into the process-based modeling of nonpoint source (NPS) pollution, this work can inform other hydro-environmental studies on scattered and small water bodies. The results are also useful to water quality improvement for entire river basins.
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