Design, synthesis and identification of N, N-dibenzylcinnamamide (DBC) derivatives as novel ligands for α-synuclein fibrils by SPR evaluation system.

PET imaging of α-synuclein (α-syn) deposition in the brain will be an effective tool for earlier diagnosis of Parkinson's disease (PD) due to α-syn aggregation is the widely accepted biomarker for PD. However, the necessary PET radiotracer for imaging is clinically unavailable until now. The lead compound discovery is the first key step for the study. Herein, we initially established an efficient biologically evaluation system well in highthroughput based on SPR technology, and identified a novel class of N, N-dibenzylcinnamamide (DBC) compounds as α-syn ligands through the assay. These compounds were proved to have high affinities against α-syn aggregates (KD < 10 nM), which well met the requirement of binding activity for the PET probe. These DBC compounds were firstly reported as α-syn ligands herein and the preliminary obtained structure has been further modified into F-labeled ones. Among them, a high-affinity tracer (5-41) with 1.03 nM (KD) has been acquired, indicating its potential as a new lead compound for developing PET radiotracer.

Clinical risk factors for new-onset atrial fibrillation in acute myocardial infarction: A systematic review and meta-analysis.

New-onset atrial fibrillation (NOAF) remains common arrhythmia in acute myocardial infarction (AMI), and is closely associated with increased subsequent cardiovascular mortality. Our meta-analysis aims to summarize more clinical risk factors for NOAF.Comprehensive systematic search of MEDLINE, EMBASE, and the Cochrane Library were carried out to find relevant studies inception to December 2017. Pooled mean difference (MD) and 95% confidence interval (CI) were calculated to evaluate the value of clinical risk factors in the prediction of NOAF after AMI.Eleven studies containing 9570 patients were included in the meta-analysis. Overall, older age and increased heart rate (HR) levels had a significant positive association with NOAF in patients with AMI. The MD in age between the patients with, and those without NOAF, was 8.22 units (95% confidence interval [CI]: 7.44-9.01), test for overall effect z score = 20.51 (P < .00001, I = 0%). Moreover, the MD in a subgroup analysis for HR levels between the patients with, and those without NOAF was 4.34 units (95% Cl: 2.56-6.11), test for overall effect z score = 4.78 (P < .00001, I = 31%).In patient with AMI, our meta-analysis demonstrated that older age and increased HR levels on admission are related to greater risk of NOAF.

RsmA regulates biofilm formation in Xanthomonas campestris through a regulatory network involving cyclic di-GMP and the Clp transcription factor.

Biofilm formation and dispersal in the black rot pathogen Xanthomonas campestris pathovar campestris (Xcc) is influenced by a number of factors. The extracellular mannanase ManA has been implicated in biofilm dispersal whereas biofilm formation requires a putative glycosyl transferase encoded by the xag gene cluster. Previously we demonstrated that the post-transcriptional regulator RsmA exerts a negative regulatory influence on biofilm formation in Xcc. Here we address the mechanisms by which RsmA exerts this action. We show that RsmA binds to the transcripts of three genes encoding GGDEF domain diguanylate cyclases to influence their expression. Accordingly, mutation of rsmA leads to an increase in cellular levels of cyclic di-GMP. This effect is associated with a down-regulation of transcription of manA, but an upregulation of xag gene transcription. Mutation of clp, which encodes a cyclic di-GMP-responsive transcriptional regulator of the CRP-FNR family, has similar divergent effects on the expression of manA and xag. Nevertheless Clp binding to manA and xag promoters is inhibited by cyclic di-GMP. The data support the contention that, in common with other CRP-FNR family members, Clp can act as both an activator and repressor of transcription of different genes to influence biofilm formation as a response to cyclic di-GMP.