Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 (HLA-DRA and DPB1), 17q12 (ORMDL3), 3q13.33 (CD80), 2q32.3 (STAT1/STAT4), 3q25.33 (IL12A), 4q24 (NF-κB) and 22q13.1 (RPL3/SYNGR1). We also identified variants in IL21, IL21R, CD28/CTLA4/ICOS, CD58, ARID3A and IL16 as novel PBC risk loci. These new findings and histochemical studies showing enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic portal tracks) support a disease mechanism in which the deregulation of the IL21 signalling pathway, in addition to CD4 T-cell activation and T-cell co-stimulation are critical components in the development of PBC.

MicroRNAs (miRNAs) are frequently dysregulated in glioblastoma (GBM) patients. It has been discovered that highly stable extracellular miRNAs circulate in the blood of both healthy individuals and patients. miRNAs in serum of patients with GBM and normal controls were analyzed by microarray analysis. The relevant bioinformatic analysis of the predicted target genes (gene ontology, pathway, gene network analysis) were performed. The miRNA microarray reveals differentially expressed miRNAs in serum between the GBM and normal controls. Of the 752 miRNAs, 115 miRNAs were upregulated in the GBM group, and 24 miRNAs were downregulated (fold change ≥2.0, P<0.01). By further analysis, we found that miR-576-5p, miR-340 and miR-626 were significantly overexpressed, but miR-320, let-7g-5p and miR-7-5P showed significantly low expression in GBM patients. By further bioinformatic analysis, we found that they possibly play important roles in the regulation of glioma signaling pathways. In summary, the six miRNAs are significant distinct in the peripheral blood of patients with GBM pathologies. These data suggest that the miRNA profile of the peripheral blood may serve as a new biomarker for glioma diagnosis with high specificity and sensitivity.

MicroRNA (miR)-486-5p expression is often reduced in human cancers. However, its expression in gastric carcinoma and its relation to clinicopathological features and prognosis are unclear. Tissue microarrays were constructed from 84 patients with gastric adenocarcinoma (GC) who were undergoing radical resection. miR-486-5p expression was detected by miRNA-locked nucleic acid in situ hybridization, and its correlations with clinicopathological features and overall survival were analyzed. Bioinformatic studies predict that fibroblast growth factor 9 (FGF9) is a potential target gene of miR-486-5p. miR-486-5p was mainly located in the cytoplasm of GC cells and neighboring normal tissues. Compared with paracancerous normal tissue, miR-486-5p expression was decreased in 63.1% (53/84) of the GC samples, increased in 32.1% (27/84) and unchanged in 4.8% (4/84). FGF9 expression was decreased in 69.0% (58/84) of GC samples and increased in 31.0% (26/84) compared with normal paracancerous tissues using immunohistochemical analysis. Low or unchanged miR-486-5p expression (P = 0.002), tumor stage (P = 0.001), tumor status (P = 0.001), node status (P = 0.001), tumor size (P = 0.004), and depth of tumor invasion (P = 0.013) were significant negative prognostic predictors for overall survival in patients with GC. After stratification according to American Joint Committee on Cancer (AJCC) stage, low/unchanged miR-486-5p expression remained a significant predictor of poor survival in stage II (P = 0.024) and stage III (P = 0.003). Cox regression analysis identified the following predictors of poor prognosis: tumor status (hazard ratio [HR], 7.19; 95% confidence interval [CI], 1.75–29.6; P = 0.006), stage (HR, 2.62; 95%CI, 1.50–4.59; P = 0.001), lymph node metastasis (HR, 2.52; 95% CI, 1.27–4.99; P = 0.008), low/unchanged miR-486-5p (HR, 2.47; 95% CI, 1.35–4.52; P = 0.003), high level of FGF9 (HR, 2.41; 95% CI, 1.42–4.09; P = 0.001) and tumor size (HR, 2.50; 95% CI, 1.30–4.82; P = 0.006). Low or unchanged expression of miR-486-5p compared with neighboring normal tissues was associated with a poor prognosis, while high expression was associated with a good prognosis in GC. miR-486-5p may thus be useful for evaluating prognosis and may provide a novel target treatment in patients with GC.

No abstract

There is limited information about the combined effect of shading time and nitrogen (N) on grain filling and quality of rice. Therefore, two japonica super rice cultivars, Nanjing 44 and Ningjing 3, were used to study the effect of shading time and N level on the characteristics of rice panicle and grain filling as well as the corresponding yield and quality. At a low N level (150 kg N ha-1 , 150N), grain yield decreased (by 21.07-26.07%) under the treatment of 20 days of shading before heading (BH) compared with the no shading (NS) treatment. These decreases occurred because of shortened panicle length, decreased number of primary and secondary branches, as well as the grain number and weight per panicle. At 150N, in the treatment of 20 days of shading after heading (AH), grain yield also decreased (by 9.46-10.60%) due to the lower grain weight per panicle. The interaction of shading and N level had a significant effect on the number of primary and secondary branches. A high level of N (300 kg N ha-1 , 300N) could offset the negative effect of shading on the number of secondary branches and grain weight per panicle, and consequently increased the grain yield in both shading treatments. In superior grains, compared with 150N NS, the time to reach 99% of the grain weight (T 99) was shortened by 1.6 to 1.7 days, and the grain weight was decreased by 4.18-5.91% in 150N BH. In 150N AH, the grain weight was 13.39-13.92% lower than that in 150N NS due to the slow mean and the maximum grain-filling rate (GR mean and GR max). In inferior grains, grain weight and GR mean had a tendency of 150N NS>150N BH>150N AH. Under shaded conditions, 300N decreased the grain weight due to lower GR mean both in superior and inferior grains. Compared with 150N NS, the milling and appearance qualities as well as eating and cooking quality were all decreased in 150N BH and 150N AH. Shading with the high level of 300N improved the milling quality and decreased the number of chalky rice kernels, but the eating and cooking quality was reduced with increased chalky area and overall chalkiness. Therefore, in the case of short term shading, appropriate N fertilizer could be used to improve the yield and milling quality of rice, but limited application of N fertilizer is recommended to achieve good eating and cooking quality of rice.