Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogeno...Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogenous esters and xenobiotic esters. Herein, to real-time monitor the activities of CES1 in various biological systems, a practical and iso form-specific fluorescent probe was developed on the basis of the substrate preference of CES1, as well as the structural and optical properties of BODIPY dyes. After screening of a panel of BODIPY ester derivatives, probe 1 displayed the best combination of specificity,sensitivity, enzymatic kinetics and applicability for monitoring CES1 activities in real samples. This probe was successfully used to detect CESl activities in several biological systems including tissue preparations,living cells, tissue slices and zebrafish. Furthermore, the biomedical applications of probe 1 for screening of CES1 inhibitors were also demonstrated using tissue preparations or living cells as enzyme sources. In summary, a practical and broadly applicable tool for real-time monitoring CES1 in biological systems was developed and well-characterized, which held great promise for further investigations on CES1-associated drug discovery, clinical practice and fundamental research.展开更多
Evaluating the correlation between hypoxia inducible factor 1(HIF-1) and nitric oxide(NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activ...Evaluating the correlation between hypoxia inducible factor 1(HIF-1) and nitric oxide(NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet(LD). The probe shows excellent selectivity to NO and high sensitivity with 6000-fold fluorescence enhancement. Live cell imaging experiments revealed the probe’s capability of imaging exogenous and endogenous NO with specific in LDs of Hep G2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situ visualization of NO-dependent HIF-1 upregulation through LD accumulation.展开更多
α1-Adrenoceptors（α1-ARs）, including at least three subtypes, α（1A）, α（1B） and α（1D）, which play essential roles in G protein-coupled receptors（GPCRs）, can convey multiple pivotal extracellular signals i...α1-Adrenoceptors（α1-ARs）, including at least three subtypes, α（1A）, α（1B） and α（1D）, which play essential roles in G protein-coupled receptors（GPCRs）, can convey multiple pivotal extracellular signals in varied tissues and organs. In this research, a series of napthalimide-based small-molecule fluorescent probes（1a-1f） for α1-ARs, including two parts, a pharmacophore（quinazoline and phenylpiperazine） for α1-AR recognition and a fluorophore（naphthalimide） for visualization, were designed and synthesized successfully. These compounds display excellent fluorescence property and high affinity to receptors,which were used successfully for in vitro visualization of α1-adrenoceptors.展开更多
The effect of the positive bias on Reynolds stress （RS） and its effect on the radial turbulent transport at the edge plasma （r/a =0.9） and scrape-off layer （SOL） region of plasma in tokamak are investigated. The...The effect of the positive bias on Reynolds stress （RS） and its effect on the radial turbulent transport at the edge plasma （r/a =0.9） and scrape-off layer （SOL） region of plasma in tokamak are investigated. The radial and poloidal electric fields （Sr, Ep） and ion saturation current （Is） are measured by multi-purpose probe （MPP）. This probe is fabricated and constructed for the first time in the IR-T1 tokamak. The most advantage of this probe is that the variations of Er and Ep can be measured in different radii at the single shot. Thus the information of different radii can be compared with high precision. The bias voltage is fixed at Vbias = 200 V and it has been applied with the limiter bias that is fixed in r/a = 0.9. Moreover, the phase difference between radial and poloidal electric fields, and temporal evolution of the RS .spectrum detected by MPP are calculated. RS magnitude on the edge （r/a = 0.9） is more than its value in the SOL （r/a = 1.02）. With the applied bias 200 V, ItS and the magnitude of the phase difference between Er and Ep are increased, while the radial turbulent transport is decreased simultaneously. Thus it can be concluded that RS affects radial turbulence. Temporal evolution of the RS spectrum shows that the frequency of RS is increased and reaches its highest value at r/a=0.9 in the presence of bias.展开更多
By means of total energy calculations within the framework of the local density approximation (LDA), the interactions between a silicon Si(001) surface and a scanning probe are investigated. The tip of the probe, comp...By means of total energy calculations within the framework of the local density approximation (LDA), the interactions between a silicon Si(001) surface and a scanning probe are investigated. The tip of the probe, comprising 4 Si atoms scans along the dimer lines above an asymmetric p(2 × 1) surface, at a distance where the chemical interaction between tip-surface is dominant and responsible for image resolution. At that distance, the tip causes the dimer to toggle when it scans above the lower atom of a dimer. The toggled dimers create an alternating pattern, where the immediately adjacent neighbours of a toggled dimer remain unchanged. After the tip has fully scanned across the p(2 × 1) surface, causes the dimers to arrange in a p(2 × 2) reconstruction, reproducing the images obtained in scanning probe experiments. Our modelling methodology includes simulations that reveal the energy input required to overcome the barrier to the onset of dimer toggling. The results show that the energy input to overcome this barrier is lower for the p(2 × 1) surface than that for the p(2 × 2) or c(4 × 2) surfaces.展开更多
A novel fluorescent probe 9-（4-（1,2-diamine）benzene-N1-phenyl）acridine（DABPA） was synthesized for the detection of nitric oxide（NO） and characterized by IR, 1H-NMR and EI-MS spectroscopy. Based on a photoelect...A novel fluorescent probe 9-（4-（1,2-diamine）benzene-N1-phenyl）acridine（DABPA） was synthesized for the detection of nitric oxide（NO） and characterized by IR, 1H-NMR and EI-MS spectroscopy. Based on a photoelectron transfer mechanism, the fl uorescence intensities of DABPA were investigated with the different concentrations of NO. Under the optimal experimental conditions, the fl uorescence intensity of DABPA had a good linear relationship（R2=0.9977） with NO concentration in the range from 1×10-7 to 1.5×10-6 mol/L with a detection limit of 1×10-8 mol/L. The cytotoxicity induced by DABPA was evaluated by the MTT（3-（4,5-dimethylthiazol-2-yl）-2,5diphenyl tetrazolium bromide） assay for biological application. Furthermore, the probe DABPA had also been successfully applied to real-time image NO produced in PC12 cells in the presence of L-arginine.展开更多
基金supported by the National Natural Science Foundation of China(Nos. 21572029, 31600641,81703604, 81773687, 81672961 and 81573501)the National Key Research and Development Program of China (Nos. 2017YFC1700200 and 2017YFC1702000)+2 种基金Program of Shanghai Academic/Technology Research Leader(No. 18XD1403600)Shuguang Program (No. 18SG40)supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission and the Innovative Entrepreneurship Program of High-level Talents in Dalian (Nos. 2016RQ025 and 2017RQ121)
文摘Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogenous esters and xenobiotic esters. Herein, to real-time monitor the activities of CES1 in various biological systems, a practical and iso form-specific fluorescent probe was developed on the basis of the substrate preference of CES1, as well as the structural and optical properties of BODIPY dyes. After screening of a panel of BODIPY ester derivatives, probe 1 displayed the best combination of specificity,sensitivity, enzymatic kinetics and applicability for monitoring CES1 activities in real samples. This probe was successfully used to detect CESl activities in several biological systems including tissue preparations,living cells, tissue slices and zebrafish. Furthermore, the biomedical applications of probe 1 for screening of CES1 inhibitors were also demonstrated using tissue preparations or living cells as enzyme sources. In summary, a practical and broadly applicable tool for real-time monitoring CES1 in biological systems was developed and well-characterized, which held great promise for further investigations on CES1-associated drug discovery, clinical practice and fundamental research.
基金financially supported by National Natural Science Foundation of China (Nos. 21971023, 22074007 and 21525206)。
文摘Evaluating the correlation between hypoxia inducible factor 1(HIF-1) and nitric oxide(NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet(LD). The probe shows excellent selectivity to NO and high sensitivity with 6000-fold fluorescence enhancement. Live cell imaging experiments revealed the probe’s capability of imaging exogenous and endogenous NO with specific in LDs of Hep G2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situ visualization of NO-dependent HIF-1 upregulation through LD accumulation.
基金supported by grants from the Fok Ying Tong Education Foundation (No. 122036)the Program of New Century Excellent Talents in University (No. NCET-11-0306)+1 种基金the Shandong Natural Science Foundation (No. JQ201019)the Independent Innovation Foundation of Shandong University, IIFSDU (No. 2010JQ005)
文摘α1-Adrenoceptors（α1-ARs）, including at least three subtypes, α（1A）, α（1B） and α（1D）, which play essential roles in G protein-coupled receptors（GPCRs）, can convey multiple pivotal extracellular signals in varied tissues and organs. In this research, a series of napthalimide-based small-molecule fluorescent probes（1a-1f） for α1-ARs, including two parts, a pharmacophore（quinazoline and phenylpiperazine） for α1-AR recognition and a fluorophore（naphthalimide） for visualization, were designed and synthesized successfully. These compounds display excellent fluorescence property and high affinity to receptors,which were used successfully for in vitro visualization of α1-adrenoceptors.
文摘The effect of the positive bias on Reynolds stress （RS） and its effect on the radial turbulent transport at the edge plasma （r/a =0.9） and scrape-off layer （SOL） region of plasma in tokamak are investigated. The radial and poloidal electric fields （Sr, Ep） and ion saturation current （Is） are measured by multi-purpose probe （MPP）. This probe is fabricated and constructed for the first time in the IR-T1 tokamak. The most advantage of this probe is that the variations of Er and Ep can be measured in different radii at the single shot. Thus the information of different radii can be compared with high precision. The bias voltage is fixed at Vbias = 200 V and it has been applied with the limiter bias that is fixed in r/a = 0.9. Moreover, the phase difference between radial and poloidal electric fields, and temporal evolution of the RS .spectrum detected by MPP are calculated. RS magnitude on the edge （r/a = 0.9） is more than its value in the SOL （r/a = 1.02）. With the applied bias 200 V, ItS and the magnitude of the phase difference between Er and Ep are increased, while the radial turbulent transport is decreased simultaneously. Thus it can be concluded that RS affects radial turbulence. Temporal evolution of the RS spectrum shows that the frequency of RS is increased and reaches its highest value at r/a=0.9 in the presence of bias.
基金supported by the Fundamental Research Funds for the Central Universities(No.WJ1014005)the Natural Science Foundation of Shanghai Municipality(No.11ZR1408800)+2 种基金Innovation Program of Shanghai Municipal Education Commission(No. 12ZZ047)Doctoral Fund of Ministry of Education of China(No. 20110074120008)the National Natural Science Foundation of China(No.21106043)
文摘A convenient and scalable synthesis of 1-amino-5-cyanonaphthalene was described.
文摘By means of total energy calculations within the framework of the local density approximation (LDA), the interactions between a silicon Si(001) surface and a scanning probe are investigated. The tip of the probe, comprising 4 Si atoms scans along the dimer lines above an asymmetric p(2 × 1) surface, at a distance where the chemical interaction between tip-surface is dominant and responsible for image resolution. At that distance, the tip causes the dimer to toggle when it scans above the lower atom of a dimer. The toggled dimers create an alternating pattern, where the immediately adjacent neighbours of a toggled dimer remain unchanged. After the tip has fully scanned across the p(2 × 1) surface, causes the dimers to arrange in a p(2 × 2) reconstruction, reproducing the images obtained in scanning probe experiments. Our modelling methodology includes simulations that reveal the energy input required to overcome the barrier to the onset of dimer toggling. The results show that the energy input to overcome this barrier is lower for the p(2 × 1) surface than that for the p(2 × 2) or c(4 × 2) surfaces.
基金Funded by the National Natural Science Foundation of China(Nos.50802069,81100890,51272191)the Fundamental Research Funds for the Central Unversities(WUT:2013-IV-010)the Students Innovation and Entrepreneurship Training Program of WHUT(20141049701012)
文摘A novel fluorescent probe 9-（4-（1,2-diamine）benzene-N1-phenyl）acridine（DABPA） was synthesized for the detection of nitric oxide（NO） and characterized by IR, 1H-NMR and EI-MS spectroscopy. Based on a photoelectron transfer mechanism, the fl uorescence intensities of DABPA were investigated with the different concentrations of NO. Under the optimal experimental conditions, the fl uorescence intensity of DABPA had a good linear relationship（R2=0.9977） with NO concentration in the range from 1×10-7 to 1.5×10-6 mol/L with a detection limit of 1×10-8 mol/L. The cytotoxicity induced by DABPA was evaluated by the MTT（3-（4,5-dimethylthiazol-2-yl）-2,5diphenyl tetrazolium bromide） assay for biological application. Furthermore, the probe DABPA had also been successfully applied to real-time image NO produced in PC12 cells in the presence of L-arginine.
