Cytotoxic phenyl polyketides from Hypericum curvisepalum N. Robson.

(±)-Hypecurvone A (1) and B (2), two new undescribed phenyl polyketides, along with seven known analogues (3-9) were isolated from the whole plant of Hypericum curvisepalum. Chiral separation of 1 and 2 yielded two pairs of enantiomers 1a/1b and 2a/2b, respectively. The structures of these compounds were elucidated by extensive spectroscopic analyses and ECD spectra simulations. All isolates exhibited moderate cytotoxicity against human hepatocellular carcinoma SMMC-7721 cells, and compound 3 also showed weak cytotoxicity toward MGC-803 cells. The cytotoxicity of these compounds was found to be related to enhanced mitochondria-mediated apoptosis and inhibition of the G2/M phase of the cell cycle.

Three New Xanthones from Hypericum scabrum and Their Quorum Sensing Inhibitory Activities against Chromobacterium violaceum.

Quorum sensing (QS) plays an important role in the production of virulence factors and pathogenicity in pathogenic bacteria and is, therefore, a hopeful target to fight against bacterial infections. During our search for natural QS inhibitors, two new xanthonolignoids (1 and 2), each existing as a racemic mixture, one new simple oxygenated xanthone (7), and eight known analogs (3-6, 8-11) were isolated from Hypericum scabrum Linn. Chiral separation of 1 yielded a pair of enantiomers 1a and 1b. The structures of these compounds were elucidated by spectroscopic analysis and ECD (electrostatic circular dichroism) calculations. All isolates were evaluated for their QS inhibitory activity against Chromobacterium violaceum. Both 9 and 10 exhibited the most potent QS inhibitory effects with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 31.25 and 62.5 µM, respectively. Crystal violet staining was used to further evaluate the biofilm inhibition potential of compounds 7, 9 and 10, and the formation of biofilms increased with decreasing drug concentration in a classic dose-dependent manner. The results of a cytotoxicity assay revealed that compounds 7, 9 and 10 exhibited no cytotoxic activity on PC-12 cells at the tested concentration.

Robust Optimal Control for the Vehicle Suspension System With Uncertainties.

The suspension system is an important unit that affects vehicle performance, including handling stability and riding comfort. In order to improve vehicle performances, a novel robust optimal control strategy for the active suspension system in vehicles is proposed. To handle the parameter uncertainties and external random disturbances, the proposed optimal control strategy is designed by using the combination of the linear quadratic regulator (LQR) optimal control and sliding-mode control. First, by using the nominal model of the active suspension system without the uncertain parameters and the external random disturbances, an optimal control performance index is given, and the initial optimal controller is designed by using the LQR control strategy. Then, to handle the parameter uncertainties and the external disturbances, a robust optimal integral sliding-mode control strategy based on the initial optimal controller is designed, which not only can achieve the optimal control objective but also has good robustness to the uncertain parameters and external disturbances. By using the Lyapunov stability theory, stability analysis of the proposed robust optimal integral sliding-mode control strategy is performed. Finally, the collaborative simulation platform based on the Carsim and MATLAB/Simulink is developed. The simulation results illustrate the advantage of the proposed robust optimal control strategy for the suspension system.

Impact of Percutaneous Transhepatic Biliary Drainage on Clinical Outcomes of Patients with Malignant Obstructive Jaundice Undergoing Laparoscopic Pancreaticoduodenectomy.

Preoperative biliary drainage may increase the morbidity and mortality of pancreaticoduodenectomy. Studies on percutaneous transhepatic biliary drainage (PTBD) before laparoscopic pancreaticoduodenectomy (LPD), however, are scarce. The aim of this study was to examine the impact of PTBD on clinical outcomes of patients with malignant obstructive jaundice undergoing LPD. Clinical data of 172 patients who had malignant obstructive jaundice and underwent LPD from 2014 to 2017 in our hospital were retrospectively analyzed. Demographics, catheter-related complications, postoperative complications, and oncological outcomes were collected and analyzed. Propensity score matching was performed to minimize selection bias associated with the comparison of data between patients who underwent PTBD and then LPD (PTBD group), and those given LPD alone (LPD group). The results showed that, in the PTBD group relative to the LPD group, the operating time was significantly shortened (250.28±69.95 vs. 278.58±86.51 min, P=0.0196), the intraoperative blood loss was markedly reduced (271.96±403.47 vs. 429.72±482.47 mL, P=0.022), and overall rates of complications (16.33% vs. 36.49%, P=0.0025) including postoperative haemorrhage (2.04% vs. 12.16%, P=0.0072) and delayed gastric emptying (4.08% vs. 13.51%, P=0.0251) were greatly decreased. The propensity score-matched analysis, with 48 patients enrolled in each group, revealed no statistically significant differences in operating duration (262.71±68.64 vs. 280.25±83.52 min, P=0.264), intraoperative blood loss (290.21±407.71 vs. 373.75±422.33 mL, P=0.327) and delayed gastric emptying (4.17% vs. 12.50%, P=0.1396). PTBD group had lower incidences in overall complications (22.92% vs. 39.58%, P=0.0481) and postoperative haemorrhage (2.08% vs. 12.50%, P=0.0497) than LPD group. In conclusion, patients with malignant obstructive jaundice may benefit from PTBD procedure before LPD in terms of perioperative outcomes.

Screening Study on the Anti-Angiogenic Effects of Traditional Chinese Medicine - Part II: Wild Chrysanthemum.

Background and Aims: Part 2 of our ongoing research with anti-angiogenic effects focuses on Wild chrysanthemum; a heat-clearing and detoxicating Traditional Chinese Medicine (TCM). We screened six heat-clearing and detoxicating TCM and noticed that wild chrysanthemum has a potent anti-angiogenic effect in zebrafish. This study aims to determine the genetic mechanisms underlying the anti-angiogenic effects of wild chrysanthemum. Methods: Wild chrysanthemum was decocted, concentrated, sieved and desiccated to attain the water extract. 200µg/mL wild chrysanthemum water extract (WCWE) was diluted in 0.1% dimethyl sulfoxide (DMSO) and given to zebrafish via fish water. 48h post-fertilization (hpf) fli1a-EGFP transgenic zebrafish were used to assay angiogenesis. mRNA-seq, qRT-PCR assay and a parallel reaction monitor (PRM) were carried out to reveal the underlying mechanisms. Results: WCWE showed a significant anti-angiogenic effect in zebrafish. The results of mRNA-seq showed that there were 1119 genes up-regulated and 1332 genes down-regulated by WCWE. The bioinformatic analysis based on mRNA-seq demonstrated that the proteasome signaling pathway was significantly down-regulated. The results of the qRT-PCR assay were consistent with those of the mRNA-seq assay. The results of the PRM assay showed that nine proteins involved in proteasome signaling and the protein expression level of ctnnb2 were significantly down-regulated. The results of the KEGG pathway analysis based on PRM assay demonstrated that WCWE may have an inhibitory action on the regulatory particle of the proteasome. Conclusion: Wild chrysanthemum has a significant anti-angiogenic effect in zebrafish and it may have an inhibitory action on the regulatory particle of the proteasome. The mechanisms underlying the anti-angiogenic effects of wild chrysanthemum may be related to the down-regulation of proteasome/ß-catenin signaling in zebrafish.