Potent and selective chemical probes are valuable tools for discovery of novel treatments for human diseases. NF-κB-inducing kinase (NIK) is a key trigger in the development of liver injury and fibrosis. Whether inhibition of NIK activity by chemical probes ameliorates liver inflammation and injury is largely unknown. In this study, a small-molecule inhibitor of NIK, B022, was found to be a potent and selective chemical probe for liver inflammation and injury. B022 inhibited the NIK signaling pathway, including NIK-induced p100-to-p52 processing and inflammatory gene expression, both in vitro and in vivo Furthermore, in vivo administration of B022 protected against not only NIK but also CCl-induced liver inflammation and injury. Our data suggest that inhibition of NIK is a novel strategy for treatment of liver inflammation, oxidative stress, and injury.-Ren, X., Li, X., Jia, L., Chen, D., Hou, H., Rui, L., Zhao, Y., Chen, Z. A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury.
Rice cultivation has been challenged by increasing food demand and water scarcity. We examined the responses of water use, grain yield, and water productivity to various modes of field water managements in Chinese double rice systems. Four treatments were studied in a long-term field experiment (1998–2015): continuous flooding (CF), flooding—midseason drying—flooding (F-D-F), flooding—midseason drying—intermittent irrigation without obvious standing water (F-D-S), and flooding—rain-fed (F-RF). The average precipitation was 483 mm in early-rice season and 397 mm in late-rice season. The irrigated water for CF, F-D-F, F-D-S, and F-RF, respectively, was 263, 340, 279, and 170 mm in early-rice season, and 484, 528, 422, and 206 mm in late-rice season. Grain yield for CF, F-D-F, F-D-S, and F-RF, respectively, was 4,722, 4,597, 4,479, and 4,232 kgha-1 in early-rice season, and 5,420, 5,402, 5,366, and 4,498 kgha-1 in late-rice season. Compared with CF, F-D-F consumed more irrigated water, which still decreased grain yield, leading to a decrease in water productivity by 25% in early-rice season and by 8% in late-rice season. Compared with F-D-F, F-D-S saved much irrigated water with a small yield reduction, leading to an increase in water productivity by 22% in early-rice season and by 26% in late-rice season. The results indicate that CF is best for early-rice and FDS is best for late-rice in terms of grain yield and water productivity.
The cold shock domain (CSD) is an evolutionarily conserved nucleic acid binding domain that exhibits binding activity to RNA, ssDNA, and dsDNA. Mammalian CRHSP-24 contains CSD, but its structure-functional relationship has remained elusive. Here we report the crystal structure of human CRHSP-24 and characterization of the molecular trafficking of CRHSP-24 between stress granules and processing bodies in response to oxidative stress. The structure of CRHSP-24 determined by single-wavelength anomalous dispersion exhibits an ␣-helix and a compact -barrel formed by five curved anti-parallel  strands. Ligand binding activity of the CSD is orchestrated by residues Ser 41 to Leu 43 . Interestingly, a phosphomimetic S41D mutant abolishes the ssDNA binding in vitro and causes CRHSP-24 liberated from stress granules in vivo without apparent alternation of its localization to the processing bodies. This new class of phosphorylation-regulated interaction between the CSD and nucleic acids is unique in stress granule plasticity. Importantly, the association of CRHSP-24 with stress granules is blocked by PP4/ PP2A inhibitor calyculin A as PP2A catalyzes the dephosphorylation of Ser 41 of CRHSP-24. Therefore, we speculate that CRHSP-24 participates in oxidative stress response via a dynamic and temporal association between stress granules and processing bodies.
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