The rice SUB1A-1 gene, which encodes a group VII ethylene response factor (ERFVII), plays a pivotal role in rice survival under flooding stress, as well as other abiotic stresses. In Arabidopsis, five ERFVII factors play roles in regulating hypoxic responses. A characteristic feature of Arabidopsis ERFVIIs is a destabilizing N terminus, which functions as an N-degron that targets them for degradation via the oxygen-dependent N-end rule pathway of proteolysis, but permits their stabilization during hypoxia for hypoxia-responsive signaling. Despite having the canonical N-degron sequence, SUB1A-1 is not under N-end rule regulation, suggesting a distinct hypoxia signaling pathway in rice during submergence. Herein we show that two other rice ERFVIIs gene, ERF66 and ERF67, are directly transcriptionally up-regulated by SUB1A-1 under submergence. In contrast to SUB1A-1, ERF66 and ERF67 are substrates of the N-end rule pathway that are stabilized under hypoxia and may be responsible for triggering a stronger transcriptional response to promote submergence survival. In support of this, overexpression of ERF66 or ERF67 leads to activation of anaerobic survival genes and enhanced submergence tolerance. Furthermore, by using structural and protein-interaction analyses, we show that the C terminus of SUB1A-1 prevents its degradation via the N-end rule and directly interacts with the SUB1A-1 N terminus, which may explain the enhanced stability of SUB1A-1 despite bearing an N-degron sequence. In summary, our results suggest that SUB1A-1, ERF66, and ERF67 form a regulatory cascade involving transcriptional and N-end rule control, which allows rice to distinguish flooding from other SUB1A-1–regulated stresses.

The apical sodium-dependent bile acid transporter (ASBT) transports bile salts from the lumen of the gastrointestinal (GI) tract to the liver via the portal vein. Multiple pharmaceutical companies have exploited the physiological link between ASBT and hepatic cholesterol metabolism, which led to the clinical investigation of ASBT inhibitors as lipid-lowering agents. While modest lipid effects were demonstrated, the potential utility of ASBT inhibitors for treatment of type 2 diabetes has been relatively unexplored. We initiated a lead optimization effort that focused on the identification of a potent, nonabsorbable ASBT inhibitor starting from the first-generation inhibitor 264W94 (1). Extensive SAR studies culminated in the discovery of GSK2330672 (56) as a highly potent, nonabsorbable ASBT inhibitor which lowers glucose in an animal model of type 2 diabetes and shows excellent developability properties for evaluating the potential therapeutic utility of a nonabsorbable ASBT inhibitor for treatment of patients with type 2 diabetes.

PURPOSE: We systematically reviewed the literature in order to determine whether evidence indicated that preoperative stoma site marking reduces the occurrence of postoperative stoma and peristomal complications. DESIGN: Systematic review with meta-analysis of pooled findings. SUBJECTS/SETTING: We systematically reviewed 6 electronic databases including PubMed, MEDLINE, CINAHL, Cochrane Library for English language articles, along with the Airiti Library and Wanfang Data for Chinese articles for evidence related to the effects of stoma site marking on stoma and peristomal complications. We sought articles published from their inception to January 31, 2018. METHODS: Ten studies that included 2109 participants, each comparing 2 groups of patients who did and did not undergo preoperative stoma site marking, were retrieved and analyzed. RESULTS: In patients who underwent stoma site marking, the marking was associated with reduced stoma and peristomal complications in all stoma types (odds ratio [OR] = 0.52; 95% CI, 0.42-0.64; P < .001). Patients who underwent stoma and had fecal ostomies experienced fewer complications (OR = 0.34; 95% CI, 0.25-0.47; P < .001) than patients with unmarked stomas. In contrast, patients with urostomies did not experience fewer complications when compared to those with unmarked ostomies (OR = 0.531; 95% CI, 0.23-1.21; P = .132). Persons with fecal ostomies also had fewer hernias and peristomal skin complications (ORs = 0.25 and 0.30; 95% CIs, 0.09-0.71 and 0.20-0.44, respectively; both Ps < .001). The results revealed that stoma site marking was associated with reduced early and late stoma and peristomal complications (ORs = 0.76 and 0.38; 95% CIs, 0.61-0.94 and 0.32-0.46; P = .010 and P < .001, respectively). CONCLUSIONS: Preoperative stoma site marking is associated with a reduced occurrence of stoma and peristomal complications and should be considered as a standard of preoperative care.

There is a great appeal to develop an omnipotent player combining lithium-ion batteries (LIBs) with the capacitive storage communities. Hybrid capacitors as a kind of promising energy storage device are attracting increasing attention in the main playground in recent years. Unlike supercapacitors (SCs) and LIBs, hybrid capacitors combine a capacitive electrode with a Faradaic battery electrode. In these hybrid cells, the capacitive electrode brings the power while the energy mainly comes from the Faradaic one. Numerous efforts have been conducted in the past decades; however, the research about hybrid capacitors is still at its infancy stage, and it is not expected to replace LIBs or SCs in the near future utterly. Here, the advances of hybrid capacitors, including insertiontype materials, lithium-ion capacitors, and sodium-ion capacitors, are reviewed. This review aims to offer useful guidance for the design of faradic battery electrodes and hybrid cell construction. Brief challenges and opportunities for future research on hybrid capacitors are finally presented.

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Wild tomatoes (Solanum peruvianum) are important genomic resources for tomato research and breeding. Development of a foreign DNA-free CRISPR-Cas delivery system has potential to mitigate public concern about genetically modified organisms. Here, we established a DNA-free CRISPR-Cas9 genome editing system based on an optimized protoplast regeneration protocol of S. peruvianum, an important resource for tomato introgression breeding. We generated mutants for genes involved in small interfering RNAs (siRNA) biogenesis, RNA-DEPENDENT RNA POLYMERASE 6 (SpRDR6) and SUPPRESSOR OF GENE SILENCING 3 (SpSGS3); pathogen-related peptide precursors, PATHOGENESIS-RELATED PROTEIN-1 (SpPR-1) and PROSYSTEMIN (SpProSys); and fungal resistance (MILDEW RESISTANT LOCUS O, SpMlo1) using diploid or tetraploid protoplasts derived from in vitro-grown shoots. The ploidy level of these regenerants was not affected by PEG-Ca2+-mediated transfection, CRISPR reagents, or the target genes. By karyotyping and whole genome sequencing analysis, we confirmed that CRISPR-Cas9 editing did not introduce chromosomal changes or unintended genome editing sites. All mutated genes in both diploid and tetraploid regenerants were heritable in the next generation. spsgs3 null T0 regenerants and sprdr6 null T1 progeny had wiry, sterile phenotypes in both diploid and tetraploid lines. The sterility of the spsgs3 null mutant was partially rescued, and fruits were obtained by grafting to wild-type stock and pollination with wild-type pollen. The resulting seeds contained the mutated alleles. Tomato yellow leaf curl virus proliferated at higher levels in spsgs3 and sprdr6 mutants than in the wild type. Therefore, this protoplast regeneration technique should greatly facilitate tomato polyploidization and enable the use of CRISPR-Cas for S. peruvianum domestication and tomato breeding.

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