Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease.

Fifteen chalcone derivatives 3a-3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aß1-42 aggregation effectively ranged from 45.9-94.5 % at 20 µM, and acted as potential antioxidants. Their structure-activity relationships were summarized. In particular, (2E)-3-[4-(dimethylamino)phenyl]-1-(pyridin-2-yl)prop-2-en-1-one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 µM, and it could disassemble the self-induced Aß1-42 aggregation fibrils with ratio of 57.1 % at 20 µM concentration. In addition, compound 3g displayed good chelating ability for Cu2+ , and could effectively inhibit and disaggregate Cu2+ -induced Aß aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aß1-42 -induced SH-SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine-induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.

Prophylactic noninvasive positive pressure ventilation in the weaning of difficult-weaning tracheotomy patients.

BACKGROUND: Prophylactic noninvasive positive pressure ventilation (NPPV) reduces reintubation in endotracheal intubation patients. However, the efficacy of using the prophylactic NPPV in the weaning of tracheotomy patients is unclear. METHODS: We performed prophylactic NPPV in 11 tracheotomy patients who passed a spontaneous breathing trial (SBT), removed the tracheotomy tube, and closed the incision (intervention group). We matched another 11 tracheotomy patients who also passed an SBT but weaning and removing of tracheotomy tube were managed as conventional methods (control group). RESULTS: Patients in the control group had reinstitution of mechanical ventilation 36 times after the initial SBT success. Compared with the control group, the interventional group had fewer weaning days (3.0±2.1 vs. 11.3±9.2, P=0.01) from initial SBT success to successful weaning and shorter intensive care unit (ICU) length of stay (11.6±4.2 vs. 20.3±11.6, P=0.03) after initial SBT success. The interventional group had lower nosocomial pneumonia rates after initial SBT success (0/11 vs. 2/11), lower ICU mortality (0/11 vs. 2/11), lower hospital mortality (0/11 vs. 3/11), and higher successful weaning rate (11/11 vs. 8/11), but it didn't reach significant difference. Also, there was no significant difference between groups in total duration of ventilation (25.5±13.3 vs. 34.7±24.2 days), hospital stay after initial SBT success (24.0±22.3 vs. 37.4±31.3 days), total ICU stay (35.7±15.3 vs. 45.0±29.5 days), and total hospital stay (48.7±33.1 vs. 68.6±52.6 days). CONCLUSIONS: Prophylactic NPPV may be useful to accelerate weaning, and shorten ICU stay after initial SBT success in tracheotomy patients.

Piezo1 induced apoptosis of type II pneumocytes during ARDS.

OBJECTIVE: The mechanisms of lung injury in acute respiratory distress syndrome (ARDS) are not well understood.Piezo1 was recently identified as a mechanotransduction protein. The present study found the expression of Piezo1 in type II pneumocytes and investigated its role in mediating ARDS-related lung injury. METHODS: Sprague-Dawley rats were used to establish an ARDS model, the expression of Piezo1,lung injuries, apoptosis as well as calcium influx were assessed. RESULTS: Piezo1 was expressed in type II pneumocytes as shown by immunofluorescence staining and expression was increased in the ARDS model. Knockdown of Piezo1 reduced apoptosis which was related to the elevation of Bcl-2.Calcium influx played a vital role in Piezo1-induced apoptosis. CONCLUSION: Piezo1 was expressed in type II pneumocytes. Mechanical stretch of alveoli during ARDS induced activation of the Piezo1 channel,which resulted in calcium influx. The increased intracellular Ca2+ induced the apoptosis of type II pneumocytes, which may be related to the Bcl-2 pathway.

[Soil nitrogen content and enzyme activities in rhizosphere and non-rhizosphere of summer maize under different nitrogen application rates.] / æ–½æ°®é‡å¯¹å¤çŽ‰ç±³æ ¹é™ å’Œéžæ ¹é™ åœŸå£¤é ¶æ´»æ€§åŠæ°®å«é‡çš„å½±å“.

A field experiment was conducted on fluvo-aquic soil in the North China Plain to study the effects of nitrogen application rate on soil nitrogen contents and enzyme activities in rhizosphere and non-rhizosphere of summer maize. The results showed that the soil enzyme activities under different nitrogen application rates showed similar seasonal patterns. In comparison to no nitrogen ferti-lizer treatment, all nitrogen application treatments significantly increased NO3--N contents in rhizosphere and non-rhizosphere soils, NH4+-N content in rhizosphere soil and the activities of ß-N-acetylglucosaminidase, ß-glucosidase, ß-xylosidase and Cellobiohyrolase. During the whole summer maize growing season, the NO3--N content in non-rhizosphere soil was significantly higher than that in rhizosphere soil. The NH4+-N content in non-rhizosphere soil was also significantly higher than that in rhizosphere soil at filling stage but significantly lower at seedling and maturity stages. Furthermore, soil enzyme activities in rhizosphere soil were significantly higher than those in non-rhizosphere soil. Effect of nitrogen application on soil organic carbon content was not significant. Soil total nitrogen content increased significantly when the nitrogen application rate was 0-180 kg·hm-2 but decreased significantly when the rate was higher than 180 kg·hm-2. Generally, a proper rate of nitrogen fertilizer application could significantly increase soil enzyme activities and total nitrogen content, and then improve soil biochemistry properties.