Late-stage cascade of oxidation reactions during the biosynthesis of oxalicine B in Penicillium oxalicum

Oxalicine B ( 1) is an α-pyrone meroterpenoid with a unique bispirocyclic ring system derived from Penicillium oxalicum. The biosynthetic pathway of 15-deoxyoxalicine B ( 4) was preliminarily reported in Penicillium canescens, however, the genetic base and biochemical characterization of tailoring reactions for oxalicine B ( 1) has remained enigmatic. In this study, we characterized three oxygenases from the metabolic pathway of oxalicine B ( 1), including a cytochrome P450 hydroxylase OxaL, a hydroxylating Fe(II)/α-KG-dependent dioxygenase OxaK, and a multifunctional cytochrome P450 OxaB. Intriguingly, OxaK can catalyze various multicyclic intermediates or shunt products of oxalicines with impressive substrate promiscuity. OxaB was further proven via biochemical assays to have the ability to convert 15-hydroxdecaturin A ( 3) to 1 with a spiro-lactone core skeleton through oxidative rearrangement. We also solved the mystery of OxaL that controls C-15 hydroxylation. Chemical investigation of the wild-type strain and deletants enabled us to identify 10 metabolites including three new compounds, and the isolated compounds displayed potent anti-influenza A virus bioactivities exhibiting IC50 values in the range of 4.0-19.9 μmol/L. Our studies have allowed us to propose a late-stage biosynthetic pathway for oxalicine B ( 1) and create downstream derivatizations of oxalicines by employing enzymatic strategies.

Changes of Electrocardiogram after Acute Stroke / 中国康复理论与实践

@#Objective To investigate the feature and mechanism of electrocardiogram (ECG) changes in different onset parts after different types of acute stroke.MethodsA retrospective analysis about ECG was performed according to data of 163 acute stroke patients.ResultsThe abnormal ratio of ECG had no significant difference between hemorrhagic stroke and ischemic stroke. Moreover, the patients with onset areas on basal ganglia and thalamus had a higher rate of abnormal ECG.ConclusionThe patients with acute stroke have a higher incidence of abnormal ECG. The changes of ECG are associate with types and areas of injury.