This study investigates the end-burning hybrid rocket motors with polyethylene fuel by the numerical simulation and experiment.Based on computational fluid dynamics,a numerical model is developed.The model is validate...This study investigates the end-burning hybrid rocket motors with polyethylene fuel by the numerical simulation and experiment.Based on computational fluid dynamics,a numerical model is developed.The model is validated by two firing tests in this hybrid rocket motor,which uses oxygen and polyethylene as propellants.The results show that the numerical and experimental data are in good agreement,and the error of the chamber pressure is less than 2.63%.Based on the simulation mode,the blowoff limit of the end-burning hybrid rocket motors is investigated.When the nozzle throat diameter and the inner diameter of grain are large,it is more difficult for the hybrid rocket motor to achieve end-burning mode,i.e.,the flame spreading is prevented in the narrow duct.The main reason is that when the nozzle throat and the grain port are large,chamber pressure and oxidizer flow velocity are low.Therefore,the friction velocity considering the pressure and flow velocity is proposed.The critical friction velocity is about 4.054–4.890 m/s in the hybrid rocket motors.When the friction velocity exceeds the critical friction velocity,the combustion mode in hybrid rocket motors changes from the flame spreading mode to the end-burning mode.Moreover,the regression rate formula is obtained by fitting,which shows that the regression rate has a good correlation with combustion chamber pressure.The critical friction velocity and regression rate formula can provide an important reference for end-burning hybrid rocket motors.展开更多
Estrogen sulfotransferase(SULT1E1),an essential conjugative enzyme in mammals,plays a crucial role in both estrogen homeostasis and xenobiotic metabolism.Deciphering the dynamic changes in SULT1E1function under specif...Estrogen sulfotransferase(SULT1E1),an essential conjugative enzyme in mammals,plays a crucial role in both estrogen homeostasis and xenobiotic metabolism.Deciphering the dynamic changes in SULT1E1function under specific physiological or pathological conditions and discovering SULT1E1 modulators require practical and highly efficient tools for sensing SULT1E1 in biological context.Herein,we showcase a scaffold-seeking and structural optimization strategy for the rational engineering of isoform-specific fluorescent substrates for SULT1E1.First,docking-based virtual screening coupled with biochemical assays suggested that N–butyl–4-hydroxyphenyl-1,8-naphthalimide(HPN) was a suitable scaffold for constructing the fluorescent substrates for SULT1E1,but this fluorophore could be metabolized by multiple SULT isoforms.To develop isoform-specific substrates for SULT1E1,various substituents were introduced on the north part of HPN to explore the structure-enzyme specificity relationships of HPN derivatives as SULT1E1substrates.After molecular docking and experimental validation,an isoform-specific fluorescent substrate(HPN10) for SULT1E1 was successfully engineered.HPN10 demonstrated exceptional isoform-specificity,ultra-high sensitivity,and favorable signal-to-noise ratio(212).HPN10 excelled in the precise sensing of SULT1E1 activities in complex biological matrices,including cellular specimens and liver preparations.HPN10 immensely facilitated the discovery and characterization of SULT1E1 inhibitors,while tetrabromobisphenol A(TBBPA,half inhibitory concentration(IC_(50)) = 31.5 ± 3.4 nmol/L) was identified as a potent SULT1E1 inhibitor that could strongly block SULT1E1 activities in living cells.Collectively,this work presents a practical and efficient strategy for the rational engineering of isoform-specific fluorescent substrates for target conjugative enzyme(s),while HPN10 emerges as a reliable SULT1E1-activatable tool for functional sensing and drug discovery.展开更多
Bile salt hydrolase(BSH),a gatekeeper enzyme in bile acid metabolism,regulates the host's bile acid profile and is closely associated with various metabolic diseases.However,suitable methods for measuring its acti...Bile salt hydrolase(BSH),a gatekeeper enzyme in bile acid metabolism,regulates the host's bile acid profile and is closely associated with various metabolic diseases.However,suitable methods for measuring its activity in living systems remain scarce.Herein,a novel far-red fluorogenic substrate(CA-ABEI)for BSH was designed and developed by conjugating cholic acid with an aminocoumarin fluorophore.Under physiological conditions,CA-ABEI can be rapidly hydrolyzed by BSH from various bacterial sources to form ABEI,triggering strong fluorescence enhancement at 620 nm.Specifically activated by BSH,CA-ABEI enables accurate detection of BSH activity in biospecimens,including pure enzymes,bacteria and intact fecal slurries,and the first bioimaging of BSH activity in both BSH-expressing engineered Escherichia coli and natural intestinal microbiota.Moreover,a high-throughput screening platform was established using CA-ABEI,enabling the evaluation of BSH inhibitory effects from 96 herbal extracts.Pu-erh tea emerged as a potent BSH inhibitor and its active components were subsequently characterized,aiding the discovery of novel BSH inhibitors.Collectively,CA-ABEI proved to be a powerful tool for monitoring BSH activity in complex biological systems with value for exploring physiological functions and rapid screening of inhibitors.展开更多
基金supported by the National Natural Science Foundation of China(No.U20B2034)the Academic Excellence Foundation of Beihang University for PhD Students,China.
文摘This study investigates the end-burning hybrid rocket motors with polyethylene fuel by the numerical simulation and experiment.Based on computational fluid dynamics,a numerical model is developed.The model is validated by two firing tests in this hybrid rocket motor,which uses oxygen and polyethylene as propellants.The results show that the numerical and experimental data are in good agreement,and the error of the chamber pressure is less than 2.63%.Based on the simulation mode,the blowoff limit of the end-burning hybrid rocket motors is investigated.When the nozzle throat diameter and the inner diameter of grain are large,it is more difficult for the hybrid rocket motor to achieve end-burning mode,i.e.,the flame spreading is prevented in the narrow duct.The main reason is that when the nozzle throat and the grain port are large,chamber pressure and oxidizer flow velocity are low.Therefore,the friction velocity considering the pressure and flow velocity is proposed.The critical friction velocity is about 4.054–4.890 m/s in the hybrid rocket motors.When the friction velocity exceeds the critical friction velocity,the combustion mode in hybrid rocket motors changes from the flame spreading mode to the end-burning mode.Moreover,the regression rate formula is obtained by fitting,which shows that the regression rate has a good correlation with combustion chamber pressure.The critical friction velocity and regression rate formula can provide an important reference for end-burning hybrid rocket motors.
基金supported by Natural Science Foundation of China (Nos.U23A20516,82273897,81922070)Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine (No.2023YZZ02)+3 种基金the State Key Laboratory of Fine Chemicals,Dalian University of Technology (Nos.KF2202,KF2414)Shanghai Municipal Health Commission’s TCM research project (No.2022CX005)Future Plan for Traditional Chinese Medicine development of Science and Technology of Shanghai Municipal Hospital of TCM (Nos.WL-XJRY-2021010 K,WLGNDBZPY-2022001 K)Shanghai Jing’an District Health Commission (No.2024QT03)。
文摘Estrogen sulfotransferase(SULT1E1),an essential conjugative enzyme in mammals,plays a crucial role in both estrogen homeostasis and xenobiotic metabolism.Deciphering the dynamic changes in SULT1E1function under specific physiological or pathological conditions and discovering SULT1E1 modulators require practical and highly efficient tools for sensing SULT1E1 in biological context.Herein,we showcase a scaffold-seeking and structural optimization strategy for the rational engineering of isoform-specific fluorescent substrates for SULT1E1.First,docking-based virtual screening coupled with biochemical assays suggested that N–butyl–4-hydroxyphenyl-1,8-naphthalimide(HPN) was a suitable scaffold for constructing the fluorescent substrates for SULT1E1,but this fluorophore could be metabolized by multiple SULT isoforms.To develop isoform-specific substrates for SULT1E1,various substituents were introduced on the north part of HPN to explore the structure-enzyme specificity relationships of HPN derivatives as SULT1E1substrates.After molecular docking and experimental validation,an isoform-specific fluorescent substrate(HPN10) for SULT1E1 was successfully engineered.HPN10 demonstrated exceptional isoform-specificity,ultra-high sensitivity,and favorable signal-to-noise ratio(212).HPN10 excelled in the precise sensing of SULT1E1 activities in complex biological matrices,including cellular specimens and liver preparations.HPN10 immensely facilitated the discovery and characterization of SULT1E1 inhibitors,while tetrabromobisphenol A(TBBPA,half inhibitory concentration(IC_(50)) = 31.5 ± 3.4 nmol/L) was identified as a potent SULT1E1 inhibitor that could strongly block SULT1E1 activities in living cells.Collectively,this work presents a practical and efficient strategy for the rational engineering of isoform-specific fluorescent substrates for target conjugative enzyme(s),while HPN10 emerges as a reliable SULT1E1-activatable tool for functional sensing and drug discovery.
基金supported by the National Natural Science Foundation of China(Nos.82274011,U23A20516,U24A20793 and 82260843)the National Key Research and Development Program of China(No.2022YFC3502000)the Traditional Chinese Medicine Guangdong Provincial Laboratory Scientific Research and Development Incubation Project(No.HQL2024PZ004)。
文摘Bile salt hydrolase(BSH),a gatekeeper enzyme in bile acid metabolism,regulates the host's bile acid profile and is closely associated with various metabolic diseases.However,suitable methods for measuring its activity in living systems remain scarce.Herein,a novel far-red fluorogenic substrate(CA-ABEI)for BSH was designed and developed by conjugating cholic acid with an aminocoumarin fluorophore.Under physiological conditions,CA-ABEI can be rapidly hydrolyzed by BSH from various bacterial sources to form ABEI,triggering strong fluorescence enhancement at 620 nm.Specifically activated by BSH,CA-ABEI enables accurate detection of BSH activity in biospecimens,including pure enzymes,bacteria and intact fecal slurries,and the first bioimaging of BSH activity in both BSH-expressing engineered Escherichia coli and natural intestinal microbiota.Moreover,a high-throughput screening platform was established using CA-ABEI,enabling the evaluation of BSH inhibitory effects from 96 herbal extracts.Pu-erh tea emerged as a potent BSH inhibitor and its active components were subsequently characterized,aiding the discovery of novel BSH inhibitors.Collectively,CA-ABEI proved to be a powerful tool for monitoring BSH activity in complex biological systems with value for exploring physiological functions and rapid screening of inhibitors.
