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(±)-Patulinervones A (

The transcriptional repressor Snail trriggers epithelial-mesenchymal transition (EMT), the process allowing cancer cells with invasive and metastasis properties. In this study, we screened medicinal plants for the Snail inhibitory active components by high content screen (HCS) and found that the crude extract of Xylopia vielana leaves showed potential activity. Subsequently, bioassay-guided isolation of the extract of Xylopia vielana was performed to obtain twenty-four dimeric guaianes (1-24), including 16 new analogues (1-5, 8-11, 13-15, 17, 18, 21, and 22). Their structures were elucidated by the comprehensive application of multiple spectroscopic methods. Compounds 1, 11, 12, and 16 were initially identified as the active compounds. Wound healing assay, transwell migration assay and western blot experiments verified that compounds 1 and 12 inhibited the expression of Snail in a concentration-dependent manner, and compound 12 was verified as a potent tumor migration inhibitory agent. This work showed a practical strategy for the discovery of new Snail inhibitors from natural products and provided potential insights for dimeric guaianes as anticancer lead compounds specifically targeting Snail protein.

BACKGROUND To assess the non-adherence rate among pulmonary tuberculosis (TB) patients in Anhui Province, eastern China and to explore the influential factors, so as to identify targets for intervention. MATERIAL AND METHODS A total of 339 TB patients were recruited from TB dispensaries in 8 counties of Anhui Province, eastern China using a stratified sampling method. All study subjects were surveyed using a structured questionnaire. Differences between groups involving categorical data were analyzed using the chi-square test. RESULTS Overall, of the 339 patients, 33.63% missed medication. Divorced and widowed patients were more likely to miss medication compared with those who were married or unmarried (P0.01). Regarding the knowledge related to topics such as transmission route, preventive measures, and suspicious symptoms, the awareness rate in the group with good medication compliance was higher than in the group with poor compliance (P0.05). We found that compliance was not significantly associated with seeking medical treatment in professional institutions, the national free TB treatment policy, or discrimination (P0.05). The rate of non-compliance under supervision (26.10%) was lower than that without supervision (64.18%) (P0.001). CONCLUSIONS The anti-TB treatment non-adherence rate in TB patients is relatively high in Anhui Province, eastern China, and is associated with marital status, annual income, TB knowledge, and medical staff visits.

Five new prenylated acetophenones, melicoptelins A-E (1–5), along with one known congener (6) were isolated from the roots of Melicope ptelefolia. Among them, compounds 2a/2b, 3a/3b, and 4a/4b were obtained as inseparable interconverting mixtures of keto and enol tautomers. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D, 2D NMR and HRESIMS. Compouds 2a/2b, 4a/4b and 5 exhibit protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with IC50 values of 34.4, 55.2 and 66.6 μM, respectively.

A synthesis-inspired chemical investigation of the leaves of Melicope ptelefolia led to the isolation of evodialones A–D (1–4), four rearranged acetophenone stereoisomers possessing a prenylated acylcyclopentenone skeleton with three stereogenic carbons. Evodialones C and D (3 and 4) are new minor constituents. The chiral-phase HPLC resolution gave (+)-1–4 and (−)-1–4, eight enantiomers forming a complete stereoisomer library. Their absolute configurations were elucidated via extensive spectroscopic data and a modified Mosher’s method. The relationship between the chiral structures and their NMR and ECD data is discussed. Compounds (±)-1, -2, and -4 have significant protective effects on high-glucose-induced oxidative stress in human vein endothelial cells.

The ability to separate bioactive compounds from herbal medicines, which contain abundant components, is crucial for drug discovery. Conventional Countercurrent chromatography (CCC) methods for separating bioactive compounds are labor intensive and show low efficiency. Here, we present a novel integrative CCC method for separating lysine-specific demethylase 1 (LSD1) inhibitors from the roots of Salvia miltiorrhiza (RSM). The methanol extracts of RSM were separated into hydrosoluble and liposoluble fractions, which were online stored in coils. Subsequently, the targeting LSD1 constituents were isolated using isocratic, gradient, or recycling elution mode. All separation processes could be accomplished using one CCC apparatus. Using our separation strategy, two phenylpropanoids and four tanshinones were isolated, which were determined to be new classes of natural LSD1 inhibitors. Salvianolic acid B, which showed the most potent inhibitory activity with an IC50 of 0.11 μM, exhibiting a considerable potential as an anticancer agent. Promisingly, the integrative CCC could be a crucial tool for the target separation of enzyme inhibitors from herbal medicines.

Nine new spirocyclic acylphloroglucinol derivatives, hyperpatulols A-I (1-9), were characterized from the flowers of Hypericum patulum. Their structures were elucidated by the basic analysis of the obtained spectroscopic data, and their absolute configurations were assigned by both the electronic circular dichroism (ECD) exciton chirality method and ECD calculation. The evaluation of their anti-migration effects on U2-OS human osteosarcoma cells showed that compound 4 exhibited moderate inhibitory activity in a dose-dependent manner. Further pharmacological studies revealed that 4 could regulate the expression of the proteins Vimentin and E-cadherin.

Thirteen undescribed dimeric guaianes were isolated from the leaves of Xylopia vielana Pierre. Their structures were elucidated by NMR spectroscopy and mass spectrometry, and the absolute configurations of vielanins G-Q were determined by a combination of the circular dichroism (CD) exciton chirality method, chemical conversion, and electronic CD (ECD) spectroscopy analysis. Vielaninors A and B are the first examples of trinor-guaiane-dimers. Multidrug resistance reversal activity assay of the isolates was evaluated in doxorubicin-resistant human breast cancer cells. Vielanins H, K-M, P, and Q were noncytotoxic and enhanced the cytotoxicity of doxorubicin by 2.1–41.6-fold at 10 μM.

Experiments based on Froude scaling law were conducted in a 1/10 reduced-scale model tunnel to investigate the effect of slope on critical velocity in tunnel with longitudinal ventilation under fire. Methanol pool fire was used as the fire source. Smoke movement in the model tunnel with different combination of tunnel slope (−3%, −1.8%, −1%, 0%, 1%, 1.8% and 3%) and longitudinal ventilation velocity was studied. The longitudinal distribution of temperature and velocity were measured. Critical longitudinal ventilation velocity for arresting smoke back flowing in the model tunnel was investigated. Critical velocity in horizontal tunnel obtained in this study was used to compare with that of previous studies. The experimental results agreed well with the model proposed by Wu and Bakar. Correlation between the critical velocity and the slope of the tunnel is proposed based on the experiment results. As the tunnel slope increases from downhill to uphill, critical velocity decreases nearly at a rate independent of the heat release rate of the fire source. The correlation proposed in this studied agrees well with the equation adopted in the Subway Environment Simulation Computer Program (SES). However, it has some discrepancy with the expressions proposed by Atkinson and Ko et al. based on their experimental results. The cause of the discrepancy is attributed to different configuration of the experiments.

Exhaust efficiency in tunnel fires with mechanical means was discussed. Heat exhaust efficiency and smoke exhaust efficiency were defined and studied under two different exhaust modes (longitudinal exhaust and transverse exhaust) respectively. Exhaust efficiency depends on smoke generation rate, exhaust rate, heat loss through walls of tunnel, configuration of extraction installations and so on. Under smoke extraction, smoke exhaust efficiency equals 1 if a quasi-steady vented stage without upstream outflow forms, otherwise smoke exhaust efficiency is less than 1. Heat exhaust efficiency is always less than 1 since part of the heat released by the fire is lost through the solid boundaries of tunnel by radiative and convective heat transfer between the smoke and ceiling lining. Based on experimental data obtained from a series of fire tests in a model tunnel, heat exhaust efficiency was estimated and influencing factors were discussed. In tunnel fires with transverse mechanical exhaust system, heat exhaust efficiency varies from 20% to 50%. Heat exhaust efficiency increases along with the reduction of the number of exhaust inlets turned on while extracting and decreases along with the increase of the area of exhaust inlet. However, quantitative influence of inlet position on exhaust efficiency still need further study and will be reported later.

e15124 Background: To compare the clinical effects of microwave ablation (MWA) and surgical resection in the treatment of small hepatocellular carcinoma (SHCC). Methods: 65 SHCC patients with intac...