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Anthocyanins in cornflower (Centaurea cyanus) is catalysed by a set of biosynthesis genes, however, the potential mechanism of transcriptional regulation remains unclear. In the present study, we traced the dynamic changes of petal colour development from white to violet and finally to blue on the same petal in cornflower. Pigment analysis showed that anthocyanin accumulation dramatically increased with petal colour development. Subsequently, nine libraries from above three colour regions were constructed for RNA-seq and 105,506 unigenes were obtained by de novo assembling. The differentially expressed genes among three colour regions were significantly enriched in the phenylpropanoid biosynthesis and flavonoid biosynthesis pathways, leading to the excavation and analysis of 46 biosynthesis genes involved in this process. Furthermore, four R2R3-CcMYBs clustered into subgroup 4 or subgroup 6 and one CcbHLH1 clustered into IIIf subgroup were screened out by phylogenetic analysis with Arabidopsis homologues. The promoters of flavanone 3-hydroxylase (CcF3H) and dihydroflavonol 4-reductase (CcDFR) were further isolated to investigate upstream regulation mechanism. CcMYB6-1 significantly upregulated the activity of above two promoters and stimulated anthocyanin accumulation by dual luciferase assay and transient expression in tobacco leaves, and its activity was obviously enhanced when co-infiltrated with CcbHLH1. Moreover, both yeast two-hybrid and bimolecular fluorescence complementation assays indicated the protein-protein interaction between these two activators. read more Based on these obtained results, it reveals that CcMYB6-1 and CcbHLH1 are two novel transcription factors synergistically involved in regulating anthocyanin biosynthesis. This study provides insights into the regulatory mechanism of anthocyanin accumulation in cornflower. BACKGROUND Youth who experience puberty earlier than their peers are at heightened risk for substance use during adolescence. However, little is known about whether pubertal timing exacerbates effects of relevant early risk factors, such as family substance use history, as predicted by the "accentuation hypothesis". Using longitudinal data from youth with and without a family history of alcohol use disorder (AUD FHx), we evaluated whether pubertal timing intensifies preexisting familial risk effects on late adolescent substance use. METHODS Participants were 568 males and 245 females from the Michigan Longitudinal Study. Pubertal timing was indexed by fitting mixed-effects linear models to repeated measures of self-reported Tanner stage. Multilevel models then tested (a) whether AUD FHx predicted pubertal timing, and (b) whether AUD FHx, pubertal timing, or their interaction predicted alcohol and marijuana use at ages 16-18. RESULTS AUD FHx was unrelated to pubertal timing in either males or females. In males, alcohol and marijuana use in late adolescence were predicted by AUD FHx and timing, but not their interaction. In females, AUD FHx predicted alcohol-related outcomes, but there were no main or interaction effects of timing. CONCLUSIONS Pubertal timing does not moderate the link between AUD FHx and late adolescent substance use, in contrast to the accentuation hypothesis. In males, measures of pubertal maturation and familial risk provide unique information for prediction of use. Females displayed no link between pubertal timing and use, which may suggest different risk pathways, or may have been due to the female sample's smaller size. BACKGROUND Population aging is dynamic process of increasing proportion of older adults in the total population, which is an inescapable result of decline in fertility rate and extension in life expectancy. Inevitably, age-related metabolic diseases, for example obesity, type 2 diabetes, metabolic syndrome, dyslipidemia, and nonalcoholic fatty liver disease, are becoming epidemic globally along with the demographic transition. CONTENT The review examines the literatures related to 1) the epidemiology of age related metabolic diseases including obesity, type 2 diabetes, metabolic syndrome, dyslipidemia, and nonalcoholic fatty liver disease; and 2) the risk factors of age related metabolic diseases including genetic factors, diet, smoking, Physical activity, intestinal microbiota and environmental factors. CONCLUSION Population aging is becoming epidemic worldwide, resulting in increasing incidence and prevalence of a serious of age-related metabolic diseases. Both genetic and environmental factors contribute to the diseases, thus interventions targeting on these factors may have beneficial effect on the development of age-related metabolic diseases. BACKGROUND Graft-versus-host disease (GVHD) is a leading cause of death in patients after hematopoietic stem-cell transplantation (HSCT). Previous studies have shown different efficacy of GVHD prophylaxis therapies. METHODS We reviewed 46 randomized controlled trials (including 8050 participants) systematically from Jun 20, 2004 to Aug 20, 2019. These investigations compared the following drugs or their combination at therapeutic dose range for GVHD after HSCT. The main results were based on the proportion of patients who respond to these therapies. RESULTS Cyclosporine + methotrexate + Anti-T cell globulin (ATG), tacrolimus + methotrexate + ATG, tacrolimus + bortezomib + sirolimus and cyclosporine + marrow mesenchymal stem cells (MMSCs) were significantly more efficacious than corticosteroids alone (OR 12.15, 6.71, 6.25, 3.73). corticosteroids alone were less efficacious than all the other GVHD prophylaxis therapies tested. CONCLUSION Cyclosporine + methotrexate + ATG may be the best choice when starting treatment for GVHD. INTRODUCTION Optimal placement of Deep Brain Stimulation (DBS) lead is critical to ensure an adequate therapeutic benefit and minimize stimulation-induced side effects. METHODS We reviewed data from 2004 to 2018 of all cases of essential tremor treated with thalamic DBS at the University of Cincinnati. All procedures were performed with the patient awake. Change in parallel trajectory was classified as major repositioning, whereas a change in depth of electrode classified as minor repositioning. The following data were compared between groups (no vs. minor vs. major repositioning) age at surgery, sex, AC-PC length, third ventricle width, cerebral atrophy, small vessel disease burden, and intraoperative tremor control. Univariate and multivariate analyses were conducted to identify factors associated with intraoperative repositioning. RESULTS Of the 127 encounters with essential tremor, 71 required repositioning (33 major and 38 minor). Comparing procedures with major, minor, and no repositioning, mean number of changes per procedure (4 vs.