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A high-quality rice activation tagging population has been developed and screened for drought-tolerant lines using various water stress assays. One drought-tolerant line activated two rice glutamate receptor-like genes. Transgenic overexpression of the rice glutamate receptor-like genes conferred drought tolerance to rice and Arabidopsis. Rice (Oryza sativa) is a multi-billion dollar crop grown in more than one hundred countries, as well as a useful functional genetic tool for trait discovery. We have developed a population of more than 200,000 activation-tagged rice lines for use in forward genetic screens to identify genes that improve drought tolerance and other traits that improve yield and agronomic productivity. The population has an expected coverage of more than 90 % of rice genes. About 80 % of the lines have a single T-DNA insertion locus and this molecular feature simplifies gene identification. One of the lines identified in our screens, AH01486, exhibits improved drought tolerance. The AH01486 T-DNA locus is located in a region with two glutamate receptor-like genes. Constitutive overexpression of either glutamate receptor-like gene significantly enhances the drought tolerance of rice and Arabidopsis, thus revealing a novel function of this important gene family in plant biology.

Through screening a library of nitrile hydratases developed inhouse, NHT-120 was selected to catalyze the hydration of 3-cyanopyridine for production of nicotinamide. After reaction optimization, a fed-batch method was used to alleviate the substrate inhibition. Under this approach, 200 g/L of 3-cyanopyridine could be converted to nicotinamide in 5.5 h, and no nicotinic acid was produced. Under a substrate to enzyme ratio of 100:1 (w/w), nicotinamide in the reaction solution could reach 230 g/L.

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Thien-2-yl 1S,2R-milnacipran analogues were synthesized and characterized as norepinephrine/serotonin transporter inhibitors. These compounds possessed higher potencies than 1S,2R-milnacipran (2R-1) while maintaining low molecular weight and moderate lipophilicity, which are the important features for the pharmacological and pharmacokinetic characteristics of milnacipran (1). Thus, compound 5c exhibited IC50 values of 2.3 and 32 nM, respectively, at NET and SERT, which were more than 10-fold better than those of 1 (NET IC50 = 77 nM, SERT IC50 = 420 nM). Moreover, 5c achieved the same efficacy as 1, but with much lower doses, in a rodent spinal nerve ligation pain model. In addition, 5c displayed desirable pharmacokinetic properties in several species, including high oral availability and significant brain penetration.

Background: Esophageal cancer is one of the most common cancers with significant morbidity and mortality. It is important to predict the prognosis of patients. The purpose of this study was to comprehensively assess the prognostic and clinicopathologic significance of NLR in patients with esophageal cancer. Methods: A systematic literature search was performed using PubMed, Cochrane Library, Embase, Web of Science, MEDLINE, and CNKI. This meta-analysis was conducted in accordance with PRISMA guidelines. Hazard ratio (HR) with 95% confidence interval (CI) was used as the effect estimation to evaluate the prognostic role of NLR. Odds ratio (OR) was used to evaluate the relation between NLR and clinicopathologic characteristics. Results: A total of 8431 patients from 32 studies were included in this meta-analysis. The pooled results showed that elevated NLR might predict poor prognosis: The factors considered included overall survival (OS) (HR, 1.57; 95% CI, 1.40-1.75; P < .001), cancer-specific survival (CSS) (HR, 1.28; 95% CI, 1.09-1.49; P < .001), progression-free survival (PFS) (HR, 1.45; 95% CI, 1.29-1.72; P < .001), and disease-free survival (DFS) (HR,1.58; 95% CI, 1.27-1.97; P < .001). High NLR was also associated with tumor differentiation, tumor length, tumor invasion depth, lymph node metastasis, and clinical stage. No significant association was observed between NLR and metastasis stage (OR, 1.69; 95% CI, 0.98-2.98; P = .058). Conclusions: The results of this meta-analysis suggest that elevated NLR value might predict poor prognosis (OS, CSS, PFS, and DFS), according to abnormal clinicopathologic parameters.

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MYH9 encodes the heavy chain of nonmuscle myosin IIA, a ubiquitously expressed cytoplasmic myosin that regulates the actin cytoskeleton, cell migration, cell polarization, and signal transduction in cancer cells. Here, we investigated the role of MYH9 in cancer stem cells (CSCs) associated with esophageal cancer (EC). The subcellular localization of MYH9 was investigated in SKGT-4 cells through immunofluorescent analysis. MYH9+ and MYH9− spheroid cells were derived from SKGT-4 cells by flow cytometry and compared for self-renewal capacity, tumorigenicity, CD133 positivity, cisplatin resistance, and phosphatidylinositol-3kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) activity. MYH9 messenger RNA expression was assessed in 30 EC patients by quantitative reverse transcription-polymerase chain reaction. Kaplan-Meier curves were plotted to explore the influence of MYH9 on EC survival. MYH9 localized to the plasma membrane, cytoplasm, and nucleus of SKGT-4 cells. Spheroid cells displayed higher MYH9 expression and positivity compared to parental SKGT-4 cells. MYH9+ cells showed strong CSC characteristics, including in vivo tumorigenicity, migration, invasion, cisplatin resistance, and CD133+ positivity. MYH9 activated the PI3K/ AKT/mTOR axis in CSCs and was upregulated in EC patients with poor survival. Collectively, these data show that MYH9 significantly promotes tumorigenesis by regulating PI3K/AKT/mTOR signaling in EC. MYH9 expression remarkably correlates with poor prognosis and represents a novel biomarker and drug target for the diagnosis and treatment of EC.