The binding model of 3-（2-chloropyrid-5-ylmethylamino）-2-cyanoacrylate photosystem Ⅱ （PSⅡ） electron transport inhibitors with the D 1 protein of PSII was built. The high herbicidal activity of this kind of inhib...The binding model of 3-（2-chloropyrid-5-ylmethylamino）-2-cyanoacrylate photosystem Ⅱ （PSⅡ） electron transport inhibitors with the D 1 protein of PSII was built. The high herbicidal activity of this kind of inhibitors was explained by docking studies： in addition to usual factors, the N atom on the pyridine ring could form an H-bond with the backbone amide of Phe265 on the D1 protein. 3D-QSAR analysis on sixteen 3-（2-chloropyrid-5-yl- methylamino）-2-cyanoacrylate compounds was performed using CoMFA method to explain the nature of interactions between the compounds and D1 protein. These studies may provide useful insights for designing new PSII electron transport inhibitors.展开更多
AIM To evaluate the effect on cardiovascular outcomes of sodium-glucose co-transporter-2(SGLT2) inhibitors in a real world setting by analyzing electronic medical records.METHODS We used Tri Net X, a global federated ...AIM To evaluate the effect on cardiovascular outcomes of sodium-glucose co-transporter-2(SGLT2) inhibitors in a real world setting by analyzing electronic medical records.METHODS We used Tri Net X, a global federated research network providing statistics on electronic health records(EHR). The analytics subset contained EHR from approximately 38 Million patients in 35 Health Care Organizations in the United States. The records of 46,909 patients who had taken SGLT2 inhibitors were compared to 189,120 patients with dipeptidyl peptidase(DPP) 4 inhibitors. We identified five potential confounding factors and built respective strata: elderly, hypertension, chronic kidney disease(CKD), and co-medication with either insulin or metformin. Cardiovascular events were countedas stroke(ICD10 code: I63) or myocardial infarction(ICD10: I21) occurring within three years after the first instance of the respective medication in the patients' records.RESULTS Of the 46909 patients with SGLT2 inhibitors in their EHR, 1667 patients(3.6%) had an ICD code for stroke or for myocardial infarction within the first three years after the first instance of the medication. In the control group, there were 10680 events of 189120 patients(5.6%), which represents a risk ratio of 0.63(95%CI: 0.60-0.66). The overall incidence of stroke or myocardial infarction in the strata with a potential confounding risk factor reached from 4.9% in patients taking metformin to 12.5% in the stratum with the highest risk(concomitant CKD). In all strata, the difference in risk of experiencing a cardiovascular event was similarly in favor of SGLT2 vs control, with Risk Ratio ranging from 0.62 to 0.81.CONCLUSION Real world data replicated the results from randomized clinical trials, confirmed the cardiovascular advantages of SGLT2 inhibitors, and showed its applicability to the US population.展开更多
Three series of novel 2-cyanoacrylates 7a--7f, 9a-9f, 10a--10f containing 1,3,4-thiadiazole ring moieties were synthesized as herbicidal inhibitors of photosystem II （PS II） electron transportation. Their structures...Three series of novel 2-cyanoacrylates 7a--7f, 9a-9f, 10a--10f containing 1,3,4-thiadiazole ring moieties were synthesized as herbicidal inhibitors of photosystem II （PS II） electron transportation. Their structures were clearly verified by lH NMR, 13C NMR, elemental analysis （or HRMS analysis） and single-crystal X-ray diffraction analysis. Bioassay showed that a suitable group at the 3-position of acrylates was essential for high herbicidal activ- ity. In particular, compound 7e showed the best herbicidal activities and gave 100% inhibitory activity against rape and amaranth pigweed at a dose of 1.5 kg/ha. Introduction of substituent with higher polarity such as sulfinyl or sulfonyl to the 5-position of 1,3,4-thiadiazole decreased herbicidal activities.展开更多
: The “oxygen burst” phenomenon that appeared during the light-induction period of intact leaves could be monitored using a photoacoustic technique high time resolution. The relationship between oxygen bursts and da...: The “oxygen burst” phenomenon that appeared during the light-induction period of intact leaves could be monitored using a photoacoustic technique high time resolution. The relationship between oxygen bursts and dark-adapted time, far-red light pretreatment, photothermal signal, and chlorophyll a (Chl a) fluorescence kinetics were investigated in the present study. Using extraneous inhibitors or cofactors of electron transport, a modified vacuum-infiltration method was undertaken to locate directly the site at which oxygen bursts of intact leaves occurred. We found that the photothermal signal showed little evidence of oscillation during the light-induction period. The oxygen burst was resolved into two components if dark-adapted time lasted longer than 20 min. Methyl viologen (MV) or far-red light could not eliminate the first component, whereas formate-Na (pH 7.0,20 μmol/L) eliminated the first component but had no effect on the second one. Furthermore, the photochemical quenching, the electron transport rate of Chl a fluorescence, and the first component of the oxygen bursts approached lowest values simultaneously. This evidence indicates that the site at which the first component of oxygen bursts occurred was located between photo-system (PS)I and PSII (i.e. the PQ pool). The formate-Na experiment also showed a linkage between the first component and the S state of oxygen evolution at the donor side of PSII. Furthermore, elimination of the second component by far-red light and absorption of the second component by MV indicated that the site at which the second component of oxygen bursts may be located at the acceptor side of PSII.展开更多
文摘The binding model of 3-（2-chloropyrid-5-ylmethylamino）-2-cyanoacrylate photosystem Ⅱ （PSⅡ） electron transport inhibitors with the D 1 protein of PSII was built. The high herbicidal activity of this kind of inhibitors was explained by docking studies： in addition to usual factors, the N atom on the pyridine ring could form an H-bond with the backbone amide of Phe265 on the D1 protein. 3D-QSAR analysis on sixteen 3-（2-chloropyrid-5-yl- methylamino）-2-cyanoacrylate compounds was performed using CoMFA method to explain the nature of interactions between the compounds and D1 protein. These studies may provide useful insights for designing new PSII electron transport inhibitors.
文摘AIM To evaluate the effect on cardiovascular outcomes of sodium-glucose co-transporter-2(SGLT2) inhibitors in a real world setting by analyzing electronic medical records.METHODS We used Tri Net X, a global federated research network providing statistics on electronic health records(EHR). The analytics subset contained EHR from approximately 38 Million patients in 35 Health Care Organizations in the United States. The records of 46,909 patients who had taken SGLT2 inhibitors were compared to 189,120 patients with dipeptidyl peptidase(DPP) 4 inhibitors. We identified five potential confounding factors and built respective strata: elderly, hypertension, chronic kidney disease(CKD), and co-medication with either insulin or metformin. Cardiovascular events were countedas stroke(ICD10 code: I63) or myocardial infarction(ICD10: I21) occurring within three years after the first instance of the respective medication in the patients' records.RESULTS Of the 46909 patients with SGLT2 inhibitors in their EHR, 1667 patients(3.6%) had an ICD code for stroke or for myocardial infarction within the first three years after the first instance of the medication. In the control group, there were 10680 events of 189120 patients(5.6%), which represents a risk ratio of 0.63(95%CI: 0.60-0.66). The overall incidence of stroke or myocardial infarction in the strata with a potential confounding risk factor reached from 4.9% in patients taking metformin to 12.5% in the stratum with the highest risk(concomitant CKD). In all strata, the difference in risk of experiencing a cardiovascular event was similarly in favor of SGLT2 vs control, with Risk Ratio ranging from 0.62 to 0.81.CONCLUSION Real world data replicated the results from randomized clinical trials, confirmed the cardiovascular advantages of SGLT2 inhibitors, and showed its applicability to the US population.
基金Project supported by the National Natural Science Foundation of China （NNSFC） （No. 20772068） and the National Key Project of Scientific and Technical Supporting Programs Funded by Ministry of Science ＆ Technology of China （No. 2006BAE01A01-5）.
文摘Three series of novel 2-cyanoacrylates 7a--7f, 9a-9f, 10a--10f containing 1,3,4-thiadiazole ring moieties were synthesized as herbicidal inhibitors of photosystem II （PS II） electron transportation. Their structures were clearly verified by lH NMR, 13C NMR, elemental analysis （or HRMS analysis） and single-crystal X-ray diffraction analysis. Bioassay showed that a suitable group at the 3-position of acrylates was essential for high herbicidal activ- ity. In particular, compound 7e showed the best herbicidal activities and gave 100% inhibitory activity against rape and amaranth pigweed at a dose of 1.5 kg/ha. Introduction of substituent with higher polarity such as sulfinyl or sulfonyl to the 5-position of 1,3,4-thiadiazole decreased herbicidal activities.
文摘: The “oxygen burst” phenomenon that appeared during the light-induction period of intact leaves could be monitored using a photoacoustic technique high time resolution. The relationship between oxygen bursts and dark-adapted time, far-red light pretreatment, photothermal signal, and chlorophyll a (Chl a) fluorescence kinetics were investigated in the present study. Using extraneous inhibitors or cofactors of electron transport, a modified vacuum-infiltration method was undertaken to locate directly the site at which oxygen bursts of intact leaves occurred. We found that the photothermal signal showed little evidence of oscillation during the light-induction period. The oxygen burst was resolved into two components if dark-adapted time lasted longer than 20 min. Methyl viologen (MV) or far-red light could not eliminate the first component, whereas formate-Na (pH 7.0,20 μmol/L) eliminated the first component but had no effect on the second one. Furthermore, the photochemical quenching, the electron transport rate of Chl a fluorescence, and the first component of the oxygen bursts approached lowest values simultaneously. This evidence indicates that the site at which the first component of oxygen bursts occurred was located between photo-system (PS)I and PSII (i.e. the PQ pool). The formate-Na experiment also showed a linkage between the first component and the S state of oxygen evolution at the donor side of PSII. Furthermore, elimination of the second component by far-red light and absorption of the second component by MV indicated that the site at which the second component of oxygen bursts may be located at the acceptor side of PSII.
