Genetic divergence was studied in selected 36 genotypes of Dalbergia sissoo Roxb. on the basis of seven morphological parameters. The divergence among genotypes was estimated by Mahalanobis method and genotypes were g...Genetic divergence was studied in selected 36 genotypes of Dalbergia sissoo Roxb. on the basis of seven morphological parameters. The divergence among genotypes was estimated by Mahalanobis method and genotypes were grouped into clusters by Tocher's method. All the genotypes were classified into seven distinct clusters on the basis of seven morphological traits. Cluster 1 was the largest with 25 genotypes followed by Cluster 2 (four genotypes). Cluster 3, 5, 6 and 7 were the divergent clusters. The D2 analysis revealed that D2 value (39.42) between clone 5040 and clone 201 was recorded maximum. The intra-cluster distance ranged from 0.00 (Cluster 3, 5, 6 and 7) to 3.89 (Cluster 1), the Cluster 3 (clone 33) was the most divergent cluster with maximum inter cluster distance (13.97) with the Cluster 7. By the divergence analysis, the parents for hybridization from diverse clusters could be selected for heterotic hybrids.展开更多
In order to consider the influence of temperature and underground water movement, an elastoplastic model and a 2D FEM stress fields on the migration of radioactive nuclide with code for analysis of coupled thermo-hyd...In order to consider the influence of temperature and underground water movement, an elastoplastic model and a 2D FEM stress fields on the migration of radioactive nuclide with code for analysis of coupled thermo-hydro-mechanical (THM) processes in saturated and unsaturated porous media were extended and improved through introducing the percolation and migration equation, so that the code can be used for solving the temperature field, flow field, stress field and nuclide concentration field simultaneously. The states of temperatures, pore pressures and nuclide concentrations in the near field of a hypothetical nuclear waste repository were investigated. The influence of the half life of the radioactive nuclide on the temporal change of nuclide concentration was analyzed considering the thermo-hydro-mechanical-migratory coupling. The results show that, at the boundary of the vitrified waste, the concentration of radioactive nuclide with a half life of 10 a falls after a period of rising, with the maximum value of 0.182 mol/m3 and the minimum value of 0.181 mol/m^3 at the end of computation. For a half life of 1 000 a, the concentration of radioactive nuclide always increases with the increase of the time during the computation period; and the maximum value is 1.686 mol/m^3 at the end of the computation. Therefore, under the condition of THM coupling, the concentration of radioactive nuclide with a shorter half life will decrease more quickly with water flow; but for the radioactive nuclide with a longer half life, its concentration will keep at a higher level for a longer time in the migration process.展开更多
This paper deals with the iterative learning control (ILC) design for multiple-input multiple-output (MIMO),time-delay systems (TDS).Two feedback ILC schemes are considered using the so-called two-dimensional ...This paper deals with the iterative learning control (ILC) design for multiple-input multiple-output (MIMO),time-delay systems (TDS).Two feedback ILC schemes are considered using the so-called two-dimensional (2D) analysis approach.It shows that continuous-discrete 2D Roesser systems can be developed to describe the entire learning dynamics of both ILC schemes,based on which necessary and sufficient conditions for their stability can be provided.A numerical example is included to validate the theoretical analysis.展开更多
A 2D analytical electrostatics analysis for the cross-section of a FinFET (or tri-gate MOSFET) is performed to calculate the threshold voltage.The analysis results in a modified gate capacitance with a coefficient H i...A 2D analytical electrostatics analysis for the cross-section of a FinFET (or tri-gate MOSFET) is performed to calculate the threshold voltage.The analysis results in a modified gate capacitance with a coefficient H introduced to model the effect of tri-gates and its asymptotic behavior in 2D is that for double-gate MOSFET.The potential profile obtained analytically at the cross-section agrees well with numerical simulations.A compact threshold voltage model for FinFET,comprising quantum mechanical effects,is then proposed.It is concluded that both gate capacitance and threshold voltage will increase with a decreased height,or a decreased gate-oxide thickness of the top gate,which is a trend in FinFET design.展开更多
Functional multiblock poly(ether-b-amide)(PEBA)copolymers,comprised of PA1212(polyamide 1212)as hard segments and Jeffamine ED-2003 as soft segments,were successfully prepared via two-step melt polycondensation withou...Functional multiblock poly(ether-b-amide)(PEBA)copolymers,comprised of PA1212(polyamide 1212)as hard segments and Jeffamine ED-2003 as soft segments,were successfully prepared via two-step melt polycondensation without any amidation catalyst.Here,using diamino-terminated poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide)(PPO-PEO-PPO),Jeffamine ED-2003,enhances the compatibility between polyamide oligomer and polyether,which is better than the traditional route using hydroxyl-terminated polyether.The chemical structure of multiblock PEBAs,as well as the microphase separated structure with crystalline phase of polyamide and polyether,were confirmed by heteronuclear multiple-bond correlation spectrum,heteronuclear multiple quantum correlation spectrum,Fourier transform infrared spectroscopy(FT-IR),differential scanning calorimetry and dynamic mechanical analysis.The hydrophilic PEBA copolymers showed water adsorption ranging from 87.3%to 17.1%depending on the polyether content,and specially showed moisture responsive behavior within seconds when exposed to moisture.The corresponding mechanism was studied using time-resolved attenuated total reflectance FT-IR spectroscopy in the molecular level and the water diffusion coefficient was estimated to be 1.07×10^(–8)cm^(2)∙s^(-1).Two-dimensional correlation FT-IR spectra analysis was performed to confirm that the interaction between water and polyether phase was in preference to that between water and polyamide matrix,and water molecule only forms hydrogen bond with the polyether segment.Due to the incorporation of PEO segments,the PEBAs have the surface resistivity varying from 5.6×10^(9)to 6.5×10^(10)Ω,which makes PEBA potential candidate as permanent antistatic agent.展开更多
Rockfalls are one of the most dangerous natural events in hilly terrains, and they substantially threaten residential areas and transport corridors in these environments. This study is aimed to analyze the risk of roc...Rockfalls are one of the most dangerous natural events in hilly terrains, and they substantially threaten residential areas and transport corridors in these environments. This study is aimed to analyze the risk of rockfall from a slope to nearby houses in a historical settlement with past rockfall histories. It contains numerous applications to study rockfall danger from different points of view(e.g., kinematics,numerical stability analysis, risk assessment, 2D trajectory). The rockfall kinematics revealed the statistics for different structurally controlled failure modes among the surveyed slope discontinuities,especially wedge type and block toppling were the most significant ones. Finite element analysis showed that the slope was stable under the natural condition with a safety factor of 2.19. The rockfall risk rating system calculated a medium risk for the houses downstream. Based on the field measurements, a possible rockfall profile was determined and located as an input in the 2D rockfall trajectory program. The rigid-body impact model runs utilized various shapes and sizes of blocks to simulate the rockfall events realistically. According to the 2D trajectory model results, there was no rockfall danger for the investigated downslope houses. The study showed the importance of using different analysis techniques to solve rockfall risk in protected areas based on scientific and rational approaches.展开更多
The generalized two-dimensional correlation analysis based on time-resolved light scattering patterns (2D TRLS) has been employed to study the phase separation process of an epoxy-amine-polyethersulfone blend in whi...The generalized two-dimensional correlation analysis based on time-resolved light scattering patterns (2D TRLS) has been employed to study the phase separation process of an epoxy-amine-polyethersulfone blend in which the secondary phase separation takes place. The results of the 2D TRLS provided more detailed information that was not readily observed in the 1D TRLS patterns. (i) During the first process of phase separation, the sequential order of coarsening in size of the domains among the larger and smaller ones has been reversed between the diffusion regime and the hydrodynamic regime. (ii) The change of the larger domains in size, due to the hydrodynamic flow in the late stage of the first phase separation process, keeps on taking place earlier than that of the new domains appeared in the secondary phase separation process. (iii) During the secondary phase separation process the size growth of the smaller domains takes place earlier than that of the larger ones, probably due to the assumption that the coarsening mode could decrease the interface tension more quickly.展开更多
A new compound {[Bi(trans-DAM)(cis-DAM)(H2O)]NO3·H2O}n 1 derived from bismuth and the flexible ligand N,N'-diacetic acid imidazolium chloride (H2DAMCl) was obtained by hydrothermal synthesis and characte...A new compound {[Bi(trans-DAM)(cis-DAM)(H2O)]NO3·H2O}n 1 derived from bismuth and the flexible ligand N,N'-diacetic acid imidazolium chloride (H2DAMCl) was obtained by hydrothermal synthesis and characterized by single-crystal X-ray diffraction. Compound 1 crystallizes in the monoclinic P21/c space group with a = 9.2298(18), b = 13.339(3), c = 17.090(3) , β = 105.38(2)°, V = 2028.7(7)A^3, Z = 4, C14H18N5O13Bi, Mr = 673.31, Dc = 2.204 g/cm^3, F(000) = 1296, μ = 8.772 mm-1, the final R = 0.0472 and wR = 0.1441 for 4129 observed reflections (I 〉 2σ(I)). In 1, the carboxylic groups from DAM- ligands adopt a cheating mode to link bismuth ions to form a 2D sheet network. These sheets are further connected by hydrogen bonding interactions to give an interesting 3D supramolecular framework. 2D correlation analysis of IR of 1 with thermal and magnetic perturbation was introduced to ascertain the characteristic adsorption of the groups overlapped in the 1D IR spectrum. Additionally, compound 1 exhibits fluorescent emission at room temperature.展开更多
This paper first suggests the use of the Fourier frequency transmission method of two dimensions function ( 2D FFT) to analyze radial rotating errors that occurred in a rotor. Based on this method a magnetic rotor i...This paper first suggests the use of the Fourier frequency transmission method of two dimensions function ( 2D FFT) to analyze radial rotating errors that occurred in a rotor. Based on this method a magnetic rotor is measured. The authors point out that the main cause to affect radial rotating accuracy of the rotating shaft at a high speed is the dynamic imbalance of the shaft itself. Finally the feedforward control scheme is suggested to improve the accuracy of the shaft in an active magnetic bearing ( AMB ) system.展开更多
Regard for the fuzziness and the randomness in some acoustic fields,a method for the numerical analysis of the 2D acoustic field with Fuzzy-Random parameters was proposed based on the equivalent conversion of informat...Regard for the fuzziness and the randomness in some acoustic fields,a method for the numerical analysis of the 2D acoustic field with Fuzzy-Random parameters was proposed based on the equivalent conversion of information entropy.In the proposed method,a fuzzyrandom acoustic field was treated as a pure fuzzy acoustic field or a pure random acoustic field by transforming all the variables into fuzzy variables or random variables.Perturbation finite element methods for analyzing the two-dimensional acoustic fuzzy and random field are deduced.The sound pressure response of a 2D acoustic tube and the 2D acoustic cavity of a car with fuzzy-random parameters were analyzed by the proposed method and the Monte Carlo method,the results show that the proposed method can be well applied to the numerical analysis of the 2D acoustic field with fuzzy-random parameters,and has good prospect of engineering application.展开更多
Aiming at the problem that the epistemic uncertain parameters exist in an acoustic field, an evidence theory-based finite element method (ETFEM) is proposed by introducing the evidence theory, in which the focal ele...Aiming at the problem that the epistemic uncertain parameters exist in an acoustic field, an evidence theory-based finite element method (ETFEM) is proposed by introducing the evidence theory, in which the focal element and basic probability assignment (BPA) are used to describe the epistemic uncertainty. In order to reduce the computational cost, the interval analysis technique based on perturbation method is adopted to acquire the approximate sound pressure response bounds for each focal element. The corresponding formulations of intervals of expectation and standard deviation of the sound pressure response with epistemic uncertainty are deduced. The sound pressure response of a 2D acoustic tube and a 2D car acoustic cavity with epistemic uncertain parameters are analyzed by the proposed method. The proposed method is verified through the comparison of the analysis results of random acoustic field with that of epistemic uncertain acoustic field. Numerical analysis results show that the proposed method can analyze the 2D acoustic field with epistemic uncertainty effectively, and has good prospect of engineering application.展开更多
Lianhuaqingwen(LHQW)capsule,a herb medicine product,has been clinically proved to be effective in coronavirus disease 2019(COVID-19)pneumonia treatment.However,human exposure to LHQW components and their pharmacologic...Lianhuaqingwen(LHQW)capsule,a herb medicine product,has been clinically proved to be effective in coronavirus disease 2019(COVID-19)pneumonia treatment.However,human exposure to LHQW components and their pharmacological effects remain largely unknown.Hence,this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities.Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach,leading to detection of 132 LHQW prototype and metabolite components,which were absorbed via the gastrointestinal tract and formed via biotransformation in human,respectively.Together with data from screening by comprehensive 2 D angiotensin-converting enzyme 2(ACE2)biochromatography,8 components in LHQW that were exposed to human and had potential ACE2 targeting ability were identified for further pharmacodynamic evaluation.Results show that rhein,forsythoside A,forsythoside I,neochlorogenic acid and its isomers exhibited high inhibitory effect on ACE2.For the first time,this study provides chemical and biochemical evidence for exploring molecular mechanisms of therapeutic effects of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to human.It also demonstrates the utility of the human exposure-based approach to identify pharmaceutically active components in Chinese herb medicines.展开更多
文摘Genetic divergence was studied in selected 36 genotypes of Dalbergia sissoo Roxb. on the basis of seven morphological parameters. The divergence among genotypes was estimated by Mahalanobis method and genotypes were grouped into clusters by Tocher's method. All the genotypes were classified into seven distinct clusters on the basis of seven morphological traits. Cluster 1 was the largest with 25 genotypes followed by Cluster 2 (four genotypes). Cluster 3, 5, 6 and 7 were the divergent clusters. The D2 analysis revealed that D2 value (39.42) between clone 5040 and clone 201 was recorded maximum. The intra-cluster distance ranged from 0.00 (Cluster 3, 5, 6 and 7) to 3.89 (Cluster 1), the Cluster 3 (clone 33) was the most divergent cluster with maximum inter cluster distance (13.97) with the Cluster 7. By the divergence analysis, the parents for hybridization from diverse clusters could be selected for heterotic hybrids.
基金Project(2010CB732101) supported by the National Basic Research Program of China Project(SKLQ 008) supported by the Research Fund of State Key Laboratory of Geomechanics and Geotechnical Engineering of China
文摘In order to consider the influence of temperature and underground water movement, an elastoplastic model and a 2D FEM stress fields on the migration of radioactive nuclide with code for analysis of coupled thermo-hydro-mechanical (THM) processes in saturated and unsaturated porous media were extended and improved through introducing the percolation and migration equation, so that the code can be used for solving the temperature field, flow field, stress field and nuclide concentration field simultaneously. The states of temperatures, pore pressures and nuclide concentrations in the near field of a hypothetical nuclear waste repository were investigated. The influence of the half life of the radioactive nuclide on the temporal change of nuclide concentration was analyzed considering the thermo-hydro-mechanical-migratory coupling. The results show that, at the boundary of the vitrified waste, the concentration of radioactive nuclide with a half life of 10 a falls after a period of rising, with the maximum value of 0.182 mol/m3 and the minimum value of 0.181 mol/m^3 at the end of computation. For a half life of 1 000 a, the concentration of radioactive nuclide always increases with the increase of the time during the computation period; and the maximum value is 1.686 mol/m^3 at the end of the computation. Therefore, under the condition of THM coupling, the concentration of radioactive nuclide with a shorter half life will decrease more quickly with water flow; but for the radioactive nuclide with a longer half life, its concentration will keep at a higher level for a longer time in the migration process.
基金supported by the National Natural Science Foundation of China(No.60727002,60774003,60921001,90916024)the COSTIND(No.A2120061303)the National 973 Program(No.2005CB321902)
文摘This paper deals with the iterative learning control (ILC) design for multiple-input multiple-output (MIMO),time-delay systems (TDS).Two feedback ILC schemes are considered using the so-called two-dimensional (2D) analysis approach.It shows that continuous-discrete 2D Roesser systems can be developed to describe the entire learning dynamics of both ILC schemes,based on which necessary and sufficient conditions for their stability can be provided.A numerical example is included to validate the theoretical analysis.
文摘A 2D analytical electrostatics analysis for the cross-section of a FinFET (or tri-gate MOSFET) is performed to calculate the threshold voltage.The analysis results in a modified gate capacitance with a coefficient H introduced to model the effect of tri-gates and its asymptotic behavior in 2D is that for double-gate MOSFET.The potential profile obtained analytically at the cross-section agrees well with numerical simulations.A compact threshold voltage model for FinFET,comprising quantum mechanical effects,is then proposed.It is concluded that both gate capacitance and threshold voltage will increase with a decreased height,or a decreased gate-oxide thickness of the top gate,which is a trend in FinFET design.
基金financially supported by the National Natural Science Foundation of China (21978089 and 21878256)the Fundamental Research Funds for the Central Universities (22221818010)+1 种基金the 111 Project (B20031)the Program of Shanghai Subject Chief Scientist (21XD1433000)
文摘Functional multiblock poly(ether-b-amide)(PEBA)copolymers,comprised of PA1212(polyamide 1212)as hard segments and Jeffamine ED-2003 as soft segments,were successfully prepared via two-step melt polycondensation without any amidation catalyst.Here,using diamino-terminated poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide)(PPO-PEO-PPO),Jeffamine ED-2003,enhances the compatibility between polyamide oligomer and polyether,which is better than the traditional route using hydroxyl-terminated polyether.The chemical structure of multiblock PEBAs,as well as the microphase separated structure with crystalline phase of polyamide and polyether,were confirmed by heteronuclear multiple-bond correlation spectrum,heteronuclear multiple quantum correlation spectrum,Fourier transform infrared spectroscopy(FT-IR),differential scanning calorimetry and dynamic mechanical analysis.The hydrophilic PEBA copolymers showed water adsorption ranging from 87.3%to 17.1%depending on the polyether content,and specially showed moisture responsive behavior within seconds when exposed to moisture.The corresponding mechanism was studied using time-resolved attenuated total reflectance FT-IR spectroscopy in the molecular level and the water diffusion coefficient was estimated to be 1.07×10^(–8)cm^(2)∙s^(-1).Two-dimensional correlation FT-IR spectra analysis was performed to confirm that the interaction between water and polyether phase was in preference to that between water and polyamide matrix,and water molecule only forms hydrogen bond with the polyether segment.Due to the incorporation of PEO segments,the PEBAs have the surface resistivity varying from 5.6×10^(9)to 6.5×10^(10)Ω,which makes PEBA potential candidate as permanent antistatic agent.
文摘Rockfalls are one of the most dangerous natural events in hilly terrains, and they substantially threaten residential areas and transport corridors in these environments. This study is aimed to analyze the risk of rockfall from a slope to nearby houses in a historical settlement with past rockfall histories. It contains numerous applications to study rockfall danger from different points of view(e.g., kinematics,numerical stability analysis, risk assessment, 2D trajectory). The rockfall kinematics revealed the statistics for different structurally controlled failure modes among the surveyed slope discontinuities,especially wedge type and block toppling were the most significant ones. Finite element analysis showed that the slope was stable under the natural condition with a safety factor of 2.19. The rockfall risk rating system calculated a medium risk for the houses downstream. Based on the field measurements, a possible rockfall profile was determined and located as an input in the 2D rockfall trajectory program. The rigid-body impact model runs utilized various shapes and sizes of blocks to simulate the rockfall events realistically. According to the 2D trajectory model results, there was no rockfall danger for the investigated downslope houses. The study showed the importance of using different analysis techniques to solve rockfall risk in protected areas based on scientific and rational approaches.
基金supported by the National Natural Science of Foundation of China(NSFC)(Nos.20674014, 20425415,20274010,50103003,20221402)
文摘The generalized two-dimensional correlation analysis based on time-resolved light scattering patterns (2D TRLS) has been employed to study the phase separation process of an epoxy-amine-polyethersulfone blend in which the secondary phase separation takes place. The results of the 2D TRLS provided more detailed information that was not readily observed in the 1D TRLS patterns. (i) During the first process of phase separation, the sequential order of coarsening in size of the domains among the larger and smaller ones has been reversed between the diffusion regime and the hydrodynamic regime. (ii) The change of the larger domains in size, due to the hydrodynamic flow in the late stage of the first phase separation process, keeps on taking place earlier than that of the new domains appeared in the secondary phase separation process. (iii) During the secondary phase separation process the size growth of the smaller domains takes place earlier than that of the larger ones, probably due to the assumption that the coarsening mode could decrease the interface tension more quickly.
基金supported by the National Natural Science Foundation of China (No. 20873021)the State Key Laboratory of Structure Chemistry and the Young Talent Programmed of Fujian Province (No. 2006F3072)
文摘A new compound {[Bi(trans-DAM)(cis-DAM)(H2O)]NO3·H2O}n 1 derived from bismuth and the flexible ligand N,N'-diacetic acid imidazolium chloride (H2DAMCl) was obtained by hydrothermal synthesis and characterized by single-crystal X-ray diffraction. Compound 1 crystallizes in the monoclinic P21/c space group with a = 9.2298(18), b = 13.339(3), c = 17.090(3) , β = 105.38(2)°, V = 2028.7(7)A^3, Z = 4, C14H18N5O13Bi, Mr = 673.31, Dc = 2.204 g/cm^3, F(000) = 1296, μ = 8.772 mm-1, the final R = 0.0472 and wR = 0.1441 for 4129 observed reflections (I 〉 2σ(I)). In 1, the carboxylic groups from DAM- ligands adopt a cheating mode to link bismuth ions to form a 2D sheet network. These sheets are further connected by hydrogen bonding interactions to give an interesting 3D supramolecular framework. 2D correlation analysis of IR of 1 with thermal and magnetic perturbation was introduced to ascertain the characteristic adsorption of the groups overlapped in the 1D IR spectrum. Additionally, compound 1 exhibits fluorescent emission at room temperature.
文摘This paper first suggests the use of the Fourier frequency transmission method of two dimensions function ( 2D FFT) to analyze radial rotating errors that occurred in a rotor. Based on this method a magnetic rotor is measured. The authors point out that the main cause to affect radial rotating accuracy of the rotating shaft at a high speed is the dynamic imbalance of the shaft itself. Finally the feedforward control scheme is suggested to improve the accuracy of the shaft in an active magnetic bearing ( AMB ) system.
基金supported by the Independent Subject of State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body in Hunan University(60870002)
文摘Regard for the fuzziness and the randomness in some acoustic fields,a method for the numerical analysis of the 2D acoustic field with Fuzzy-Random parameters was proposed based on the equivalent conversion of information entropy.In the proposed method,a fuzzyrandom acoustic field was treated as a pure fuzzy acoustic field or a pure random acoustic field by transforming all the variables into fuzzy variables or random variables.Perturbation finite element methods for analyzing the two-dimensional acoustic fuzzy and random field are deduced.The sound pressure response of a 2D acoustic tube and the 2D acoustic cavity of a car with fuzzy-random parameters were analyzed by the proposed method and the Monte Carlo method,the results show that the proposed method can be well applied to the numerical analysis of the 2D acoustic field with fuzzy-random parameters,and has good prospect of engineering application.
基金supported by the National Natural Science Foundation of China(11572121)Independent Research Project of State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body(71375004)
文摘Aiming at the problem that the epistemic uncertain parameters exist in an acoustic field, an evidence theory-based finite element method (ETFEM) is proposed by introducing the evidence theory, in which the focal element and basic probability assignment (BPA) are used to describe the epistemic uncertainty. In order to reduce the computational cost, the interval analysis technique based on perturbation method is adopted to acquire the approximate sound pressure response bounds for each focal element. The corresponding formulations of intervals of expectation and standard deviation of the sound pressure response with epistemic uncertainty are deduced. The sound pressure response of a 2D acoustic tube and a 2D car acoustic cavity with epistemic uncertain parameters are analyzed by the proposed method. The proposed method is verified through the comparison of the analysis results of random acoustic field with that of epistemic uncertain acoustic field. Numerical analysis results show that the proposed method can analyze the 2D acoustic field with epistemic uncertainty effectively, and has good prospect of engineering application.
基金supported by Natural Science Foundation of China,China,(Grant Nos.81773688,U1903119,81973291,and 81973275)Zhejiang University Special Scientific Research Fund for COVID-19 Prevention and Control,China+1 种基金“Phospherus”Project of Shanghai Science and Technology Committee,China,(Grant Nos.19QA1411500)National Major Scientific and Technological Special Project for"Significant New Drugs Development",China,(Grant No.2020ZX09201005)
文摘Lianhuaqingwen(LHQW)capsule,a herb medicine product,has been clinically proved to be effective in coronavirus disease 2019(COVID-19)pneumonia treatment.However,human exposure to LHQW components and their pharmacological effects remain largely unknown.Hence,this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities.Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach,leading to detection of 132 LHQW prototype and metabolite components,which were absorbed via the gastrointestinal tract and formed via biotransformation in human,respectively.Together with data from screening by comprehensive 2 D angiotensin-converting enzyme 2(ACE2)biochromatography,8 components in LHQW that were exposed to human and had potential ACE2 targeting ability were identified for further pharmacodynamic evaluation.Results show that rhein,forsythoside A,forsythoside I,neochlorogenic acid and its isomers exhibited high inhibitory effect on ACE2.For the first time,this study provides chemical and biochemical evidence for exploring molecular mechanisms of therapeutic effects of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to human.It also demonstrates the utility of the human exposure-based approach to identify pharmaceutically active components in Chinese herb medicines.