Nocarbenzoxazoles A–G, Benzoxazoles Produced by Halophilic Nocardiopsis lucentensis DSM 44048

Seven new benzoxazole derivatives, nocarbenzoxazoles A–G (<b>1</b>–<b>7</b>), were isolated from the halophilic strain Nocardiopsis lucentensis DSM 44048. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic data, HRESIMS, and X-ray single-crystal diffraction. The isolated compounds were assayed for their cytotoxicity against a panel of human tumor cell lines (HepG2, MDA-MB-231, MDA-MB-435, HeLa, and PC3). Compounds <b>1</b>–<b>6</b> were found to have modest or no activity. Compound <b>7</b> showed selective activity against HepG2 and HeLa with IC₅₀ values of 3 and 1 μM, respectively

Characterization of Protein Lysine Propionylation in <i>Escherichia coli</i>: Global Profiling, Dynamic Change, and Enzymatic Regulation

Propionylation at protein lysine residue is characterized to be present in both eukaryotic and prokaryotic species. However, the majority of lysine propionylation substrates still remain largely unknown. Using affinity enrichment and mass-spectrometric-based proteomics, we identified 1467 lysine propionylation sites in 603 proteins in <i>E. coli</i>. Quantitative propionylome analysis further revealed that global lysine propionylation level was drastically increased in response to propionate treatment, a carbon source for many microorganisms and also a common food preservative. The results indicated that propionylation may play a regulatory role in propionate metabolism and propionyl-CoA degradation. In contrast with lysine acetylation and succinylation, our results revealed that the lysine propionylation level of substrates showed an obvious decrease in response to high glucose, suggesting a distinct role of propionylation in bacteria carbohydrate metabolism. This study further showed that bacterial lysine deacetylase CobB and acetyltransferase PatZ could also have regulatory activities for lysine propionylation in <i>E. coli</i>. Our quantitative propionylation substrate analysis between <i>cobB</i> wild-type and <i>cobB</i> knockout strain led to the identification of 13 CobB potentially regulated propionylation sites. Together, these findings revealed the broad propionylation substrates in <i>E. coli</i> and suggested new roles of lysine propionylation in bacterial physiology

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke

BackgroundTreatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain.MethodsWe randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event.ResultsA total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 158 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60).ConclusionsIn this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.)