Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid ...Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.展开更多
The study presents a comprehensive coupled thermo-bio-chemo-hydraulic(T-BCH)modeling framework for stabilizing soils using microbially induced calcite precipitation(MICP).The numerical model considers relevant multiph...The study presents a comprehensive coupled thermo-bio-chemo-hydraulic(T-BCH)modeling framework for stabilizing soils using microbially induced calcite precipitation(MICP).The numerical model considers relevant multiphysics involved in MICP,such as bacterial ureolytic activities,biochemical reactions,multiphase and multicomponent transport,and alteration of the porosity and permeability.The model incorporates multiphysical coupling effects through well-established constitutive relations that connect parameters and variables from different physical fields.It was implemented in the open-source finite element code OpenGeoSys(OGS),and a semi-staggered solution strategy was designed to solve the couplings,allowing for flexible model settings.Therefore,the developed model can be easily adapted to simulate MICP applications in different scenarios.The numerical model was employed to analyze the effect of various factors,including temperature,injection strategies,and application scales.Besides,a TBCH modeling study was conducted on the laboratory-scale domain to analyze the effects of temperature on urease activity and precipitated calcium carbonate.To understand the scale dependency of MICP treatment,a large-scale heterogeneous domain was subjected to variable biochemical injection strategies.The simulations conducted at the field-scale guided the selection of an injection strategy to achieve the desired type and amount of precipitation.Additionally,the study emphasized the potential of numerical models as reliable tools for optimizing future developments in field-scale MICP treatment.The present study demonstrates the potential of this numerical framework for designing and optimizing the MICP applications in laboratory-,prototype-,and field-scale scenarios.展开更多
An elastoplastic constitutive model based on the Modified Cam Clay(MCC)model is developed to describe the mechanical behaviour of soils cemented via microbially induced calcite precipitation(MICP).It considers the inc...An elastoplastic constitutive model based on the Modified Cam Clay(MCC)model is developed to describe the mechanical behaviour of soils cemented via microbially induced calcite precipitation(MICP).It considers the increase of the elastic stiffness,the change of the yield surface due to MICP cementation and the degradation of calcium carbonate bonds during shearing.Specifically,to capture the typical contraction-dilation transition in MICP soils,the original volumetric hardening rule in the MCC model is modified to a combined deviatoric and volumetric hardening rule.The model could reproduce a series of drained triaxial tests on MICP-treated soils with different calcium carbonate contents.Further,we carry out a parametric study and observe numerical instability in some cases.In combination with an analytical analysis,our numerical modelling has identified the benefits and limitations of using MCCbased models in the simulation of MICP-cemented soils,leading to suggestions for further model development.展开更多
In this study,we carried out a comparative study of two different numerical strategies for the modeling of the biogeochemical processes in microbially induced calcite precipitation(MICP)process.A simplified MICP model...In this study,we carried out a comparative study of two different numerical strategies for the modeling of the biogeochemical processes in microbially induced calcite precipitation(MICP)process.A simplified MICP model was used,which is based on the mass transport theory.Two numerical strategies,namely the operator splitting(OS)and the global implicit(GI)strategies,were adopted to solve the coupled reactive mass transport problems.These two strategies were compared in the aspects of numerical accuracy,convergence property and computational efficiency by solving the presented MICP model.To look more into the details of the model,sensitivity analysis of some important modeling parameters was also carried out in this paper.展开更多
Background:The importance of biodiversity in maintaining multiple ecosystem functions has been widely accepted.However,the specific mechanisms affecting biodiversity and ecosystem multifunctionality(BEMF)relationships...Background:The importance of biodiversity in maintaining multiple ecosystem functions has been widely accepted.However,the specific mechanisms affecting biodiversity and ecosystem multifunctionality(BEMF)relationships in forests are largely unknown.This is particularly evident for the macroscale of a large forested landscape.Methods:Based on 412 one-tenth hectare field plots distributed over forested areas across northeastern China,we evaluated three alternative hypotheses explaining the relationships between BEMF,namely:niche complementarity,mass ratio,and vegetation quantity effect.We used Rao's quadratic entropy and community weighted mean trait values to quantify forest“biodiversity”.These two variables represent two complementary aspects of functional properties,which are in line with niche complementary and mass ratio effects,respectively.Results:Ecosystem multifunctionality was negatively associated with the community weighted mean values of acquisitive traits(a proxy of mass ratio effect).Rao's quadratic entropy(a proxy of niche complementarity)had no relationship with ecosystem multifunctionality.Higher stand biomass greatly increased ecosystem multifunctionality,which is in line with the vegetation quantity effect.Our results confirm that in the temperate forests of northeastern China,the relationship of BEMF was primarily affected by vegetation quantity,followed by mass ratio effects.Conclusions:The results of this study contribute to a better understanding of the main drivers of ecosystem multifunctionality in forest ecosystems.The results of this study provide additional evidence to support the vegetation quantity and mass ratio hypotheses in forest ecosystems.展开更多
Helium(He)is commercially produced from natural gas by low-temperature condensation.The process is energy extensive because of the extremely low He concentration(<0.3%)and the operation at cryogenic temperature.Her...Helium(He)is commercially produced from natural gas by low-temperature condensation.The process is energy extensive because of the extremely low He concentration(<0.3%)and the operation at cryogenic temperature.Herein we demonstrated DD3R zeolite membrane was efficient to extract He from natural gas at atmosphere temperature.The membrane performance was evaluated in terms of temperature,pressure and molar fractions.The overall membrane performance was dominated by the diffusivity selectivity.The single He permeance and ideal He/CH_(4) selectivity were 5.8×10^(-9)mol·m^(-2)·s^(-1)·Pa^(-1)and 79 under a feed pressure of 1.3 MPa.Even though He concentration was as low as 0.22%,the He permeance and He/CH_(4) mixture selectivity were 3.0×10^(-9)mol·m^(-2)·s^(-1)·Pa^(-1)and 44 at 0.7 MPa.During the longterm operation(~130 h)the membrane performance was stable even the feed mixture containing3.6%ethane as contaminations.The results approved the feasibility of DD3R zeolite membranes for He extraction from natural gas.展开更多
This work presents the design of hollow fiber T-type zeolite membrane modules with different geometric configurations. The module performances were evaluated by pervaporation dehydration of ethanol/water mixtures. Str...This work presents the design of hollow fiber T-type zeolite membrane modules with different geometric configurations. The module performances were evaluated by pervaporation dehydration of ethanol/water mixtures. Strong concentration polarization was found for the modules with big membrane bundles. The concentration polarization was enhanced at high temperature due to the higher water permeation flux. The increase of feed flow could improve water permeation flux for the membrane modules with small membrane bundle.Computational fluid dynamics was used to visualize the flow field distribution inside of the modules with different configurations. The membrane module with seven bundles exhibited highest separation efficiency due to the uniform distribution of flow rate. The packing density could be 10 times higher than that of the tubular membrane module. The hollow fiber membrane module exhibited good stability for ethanol dehydration.展开更多
As is known, high-level radioactive waste (HLW) is commonly heat-emitting. Heat output from HLWwilldissipate through the surrounding rocks and induce complex thermo-hydro-mechanical-chemical(THMC) processes. In hi...As is known, high-level radioactive waste (HLW) is commonly heat-emitting. Heat output from HLWwilldissipate through the surrounding rocks and induce complex thermo-hydro-mechanical-chemical(THMC) processes. In highly consolidated clayey rocks, thermal effects are particularly significantbecause of their very low permeability and water-saturated state. Thermal impact on the integrity of thegeological barriers is of most importance with regard to the long-term safety of repositories. This studyfocuses on numerical analysis of thermal effects on hydro-mechanical properties of clayey rock using acoupled thermo-mechanical multiphase flow (TH2M) model which is implemented in the finite elementprogramme OpenGeoSys (OGS). The material properties of the numerical model are characterised by atransversal isotropic elastic model based on Hooke's law, a non-isothermal multiphase flow model basedon van Genuchten function and Darcy's law, and a transversal isotropic heat transport model based onFourier's law. In the numerical approaches, special attention has been paid to the thermal expansion ofthree different phases: gas, fluid and solid, which could induce changes in pore pressure and porosity.Furthermore, the strong swelling and shrinkage behaviours of clayey material are also considered in thepresent model. The model has been applied to simulate a laboratory heating experiment on claystone.The numerical model gives a satisfactory representation of the observed material behaviour in thelaboratory experiment. The comparison of the calculated results with the laboratory findings verifies thatthe simulation with the present numerical model could provide a deeper understanding of the observedeffects. 2014 Institute of Rock and Soil Mechanics, Chinese Academy of Sciences. Production and hosting byElsevier B.V. All rights reserved.展开更多
Membrane gas separation is considered an energy-saving technique to extract He from natural gas due to no phase change and room temperature operation.However,the membrane performance was strongly limited by the trade-...Membrane gas separation is considered an energy-saving technique to extract He from natural gas due to no phase change and room temperature operation.However,the membrane performance was strongly limited by the trade-off between permeance and selectivity.Herein,novel 4,4′-(hexafluoroisopropylidene)diphthalic anhydride(6FDA)-2,2′-bis(3-amino-4-hydroxyphenyl)hexafluoropropane(APAF)-5-amino-2-(4-aminobenzene)benzimidazole(BIA)asymmetric membranes with a thickness of 300 nm were successfully prepared by the non-solvent induced phase separation method.The membrane performance was modulated by regulating dope solution compositions(e.g.,tetrahydrofuran and polymer concentration).The ideal He/CH_(4) selectivity was 124 and the optimized He permeance reached 87 GPU,beyond the current upper bound.He/CH_(4) selectivity was 75 and He permeance was 73 GPU for the binary mixture feed containing 0.2 mol%He.The membrane showed good resistance to CO_(2) and C_(2)H_(6),which are the typical impurities in natural gas.The 6FDA-APAF-BIA membranes have good stability(>160 h),which can provide great potential in He extraction from natural gas.展开更多
Heart failure is the leading cause of death worldwide.Compound Danshen Dripping Pill(CDDP)or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular di...Heart failure is the leading cause of death worldwide.Compound Danshen Dripping Pill(CDDP)or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China.However,the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown.We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E(ApoE)and LDL receptor(LDLR)dual deficient(ApoE^(–/–)LDLR^(–/–))mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure.CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis.Mechanistically,both Wnt and lysine-specific demethylase 4A(KDM4A)pathways were significantly activated in mice with heart injury.Conversely,CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors.While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity.In addition,CDDP attenuated simvastatin-induced myolysis in skeletal muscle.Taken together,our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.展开更多
基金supported by the National Natural Science Foundation of China(NSFC)(81973316,82173807)the China Postdoctoral Science Foundation(2020M681914)+1 种基金the Fund from Tianjin Municipal Health Commission(ZC200093)the Open Fund of Tianjin Central Hospital of Obstetrics and Gynecology/Tianjin Key Laboratory of human development and reproductive regulation(2021XHY01)。
文摘Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.
基金support from the OpenGeoSys communitypartially funded by the Prime Minister Research Fellowship,Ministry of Education,Government of India with the project number SB21221901CEPMRF008347.
文摘The study presents a comprehensive coupled thermo-bio-chemo-hydraulic(T-BCH)modeling framework for stabilizing soils using microbially induced calcite precipitation(MICP).The numerical model considers relevant multiphysics involved in MICP,such as bacterial ureolytic activities,biochemical reactions,multiphase and multicomponent transport,and alteration of the porosity and permeability.The model incorporates multiphysical coupling effects through well-established constitutive relations that connect parameters and variables from different physical fields.It was implemented in the open-source finite element code OpenGeoSys(OGS),and a semi-staggered solution strategy was designed to solve the couplings,allowing for flexible model settings.Therefore,the developed model can be easily adapted to simulate MICP applications in different scenarios.The numerical model was employed to analyze the effect of various factors,including temperature,injection strategies,and application scales.Besides,a TBCH modeling study was conducted on the laboratory-scale domain to analyze the effects of temperature on urease activity and precipitated calcium carbonate.To understand the scale dependency of MICP treatment,a large-scale heterogeneous domain was subjected to variable biochemical injection strategies.The simulations conducted at the field-scale guided the selection of an injection strategy to achieve the desired type and amount of precipitation.Additionally,the study emphasized the potential of numerical models as reliable tools for optimizing future developments in field-scale MICP treatment.The present study demonstrates the potential of this numerical framework for designing and optimizing the MICP applications in laboratory-,prototype-,and field-scale scenarios.
基金funded by the German Research Foundation(DFG)(Grant No.NA 330/20e1).
文摘An elastoplastic constitutive model based on the Modified Cam Clay(MCC)model is developed to describe the mechanical behaviour of soils cemented via microbially induced calcite precipitation(MICP).It considers the increase of the elastic stiffness,the change of the yield surface due to MICP cementation and the degradation of calcium carbonate bonds during shearing.Specifically,to capture the typical contraction-dilation transition in MICP soils,the original volumetric hardening rule in the MCC model is modified to a combined deviatoric and volumetric hardening rule.The model could reproduce a series of drained triaxial tests on MICP-treated soils with different calcium carbonate contents.Further,we carry out a parametric study and observe numerical instability in some cases.In combination with an analytical analysis,our numerical modelling has identified the benefits and limitations of using MCCbased models in the simulation of MICP-cemented soils,leading to suggestions for further model development.
基金financial support from the German Research Foundation(DFG)(Grant No.NA 330/20-1)the DFG under grant No.FE 1962/1-1(426819984)for financial supportthe Open Research Fund of State Key Laboratory of Geomechanics and Geotechnical Engineering,Institute of Rock and Soil Mechanics,Chinese Academy of Sciences(Grant No.Z019002)。
文摘In this study,we carried out a comparative study of two different numerical strategies for the modeling of the biogeochemical processes in microbially induced calcite precipitation(MICP)process.A simplified MICP model was used,which is based on the mass transport theory.Two numerical strategies,namely the operator splitting(OS)and the global implicit(GI)strategies,were adopted to solve the coupled reactive mass transport problems.These two strategies were compared in the aspects of numerical accuracy,convergence property and computational efficiency by solving the presented MICP model.To look more into the details of the model,sensitivity analysis of some important modeling parameters was also carried out in this paper.
基金supported by the Program of National Natural Science Foundation of China(No.31971650)the Key Project of National Key Research and Development Plan(No.2017YFC0504005)the National Natural Science Foundation of China(No.31800362).
文摘Background:The importance of biodiversity in maintaining multiple ecosystem functions has been widely accepted.However,the specific mechanisms affecting biodiversity and ecosystem multifunctionality(BEMF)relationships in forests are largely unknown.This is particularly evident for the macroscale of a large forested landscape.Methods:Based on 412 one-tenth hectare field plots distributed over forested areas across northeastern China,we evaluated three alternative hypotheses explaining the relationships between BEMF,namely:niche complementarity,mass ratio,and vegetation quantity effect.We used Rao's quadratic entropy and community weighted mean trait values to quantify forest“biodiversity”.These two variables represent two complementary aspects of functional properties,which are in line with niche complementary and mass ratio effects,respectively.Results:Ecosystem multifunctionality was negatively associated with the community weighted mean values of acquisitive traits(a proxy of mass ratio effect).Rao's quadratic entropy(a proxy of niche complementarity)had no relationship with ecosystem multifunctionality.Higher stand biomass greatly increased ecosystem multifunctionality,which is in line with the vegetation quantity effect.Our results confirm that in the temperate forests of northeastern China,the relationship of BEMF was primarily affected by vegetation quantity,followed by mass ratio effects.Conclusions:The results of this study contribute to a better understanding of the main drivers of ecosystem multifunctionality in forest ecosystems.The results of this study provide additional evidence to support the vegetation quantity and mass ratio hypotheses in forest ecosystems.
基金sponsored by the National Natural Science Foundation of China(21908097,22035002)the National Key Research and Development Program of China(2021YFC2101203)+1 种基金Jiangsu Specially-Appointed Professors Program and"333 Talent Project"of Jiangsu ProvinceState Key Laboratory of Materials-Oriented Chemical Engineering(ZK202002)。
文摘Helium(He)is commercially produced from natural gas by low-temperature condensation.The process is energy extensive because of the extremely low He concentration(<0.3%)and the operation at cryogenic temperature.Herein we demonstrated DD3R zeolite membrane was efficient to extract He from natural gas at atmosphere temperature.The membrane performance was evaluated in terms of temperature,pressure and molar fractions.The overall membrane performance was dominated by the diffusivity selectivity.The single He permeance and ideal He/CH_(4) selectivity were 5.8×10^(-9)mol·m^(-2)·s^(-1)·Pa^(-1)and 79 under a feed pressure of 1.3 MPa.Even though He concentration was as low as 0.22%,the He permeance and He/CH_(4) mixture selectivity were 3.0×10^(-9)mol·m^(-2)·s^(-1)·Pa^(-1)and 44 at 0.7 MPa.During the longterm operation(~130 h)the membrane performance was stable even the feed mixture containing3.6%ethane as contaminations.The results approved the feasibility of DD3R zeolite membranes for He extraction from natural gas.
基金Supported by the National Natural Science Foundation of China(21222602,21490585 and 21176117)National High-tech R&D Program of China(2015AA03A602)+4 种基金the Key Project of Chinese Ministry of Education(212060)the Outstanding Young Fund of Jiangsu Province(BK2012040)Young Fund of Jiangsu Province(BK20130915)the "Six Top Talents" and "333 Talent Project" of Jiangsu Province,a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Innovation Project for Graduate Student of Jiangsu Province(KYLX15-0790)
文摘This work presents the design of hollow fiber T-type zeolite membrane modules with different geometric configurations. The module performances were evaluated by pervaporation dehydration of ethanol/water mixtures. Strong concentration polarization was found for the modules with big membrane bundles. The concentration polarization was enhanced at high temperature due to the higher water permeation flux. The increase of feed flow could improve water permeation flux for the membrane modules with small membrane bundle.Computational fluid dynamics was used to visualize the flow field distribution inside of the modules with different configurations. The membrane module with seven bundles exhibited highest separation efficiency due to the uniform distribution of flow rate. The packing density could be 10 times higher than that of the tubular membrane module. The hollow fiber membrane module exhibited good stability for ethanol dehydration.
基金supported by BMWi (Bundesministerium für Wirtschaft und Energie,Berlin)
文摘As is known, high-level radioactive waste (HLW) is commonly heat-emitting. Heat output from HLWwilldissipate through the surrounding rocks and induce complex thermo-hydro-mechanical-chemical(THMC) processes. In highly consolidated clayey rocks, thermal effects are particularly significantbecause of their very low permeability and water-saturated state. Thermal impact on the integrity of thegeological barriers is of most importance with regard to the long-term safety of repositories. This studyfocuses on numerical analysis of thermal effects on hydro-mechanical properties of clayey rock using acoupled thermo-mechanical multiphase flow (TH2M) model which is implemented in the finite elementprogramme OpenGeoSys (OGS). The material properties of the numerical model are characterised by atransversal isotropic elastic model based on Hooke's law, a non-isothermal multiphase flow model basedon van Genuchten function and Darcy's law, and a transversal isotropic heat transport model based onFourier's law. In the numerical approaches, special attention has been paid to the thermal expansion ofthree different phases: gas, fluid and solid, which could induce changes in pore pressure and porosity.Furthermore, the strong swelling and shrinkage behaviours of clayey material are also considered in thepresent model. The model has been applied to simulate a laboratory heating experiment on claystone.The numerical model gives a satisfactory representation of the observed material behaviour in thelaboratory experiment. The comparison of the calculated results with the laboratory findings verifies thatthe simulation with the present numerical model could provide a deeper understanding of the observedeffects. 2014 Institute of Rock and Soil Mechanics, Chinese Academy of Sciences. Production and hosting byElsevier B.V. All rights reserved.
基金sponsored by the National Key Research and Development Program of China(Grant No.2021YFC2101203)the National Natural Science Foundation of China(Grant Nos.22178164 and U22B20148)+2 种基金the Jiangsu Provincial Carbon Peak Carbon Neutral Science and Technology Innovation Special Fund(Grant No.BE2022033)the Jiangsu Specially-Appointed Professors Programthe State Key Laboratory of Materials-Oriented Chemical Engineering(Grant No.ZK202002).
文摘Membrane gas separation is considered an energy-saving technique to extract He from natural gas due to no phase change and room temperature operation.However,the membrane performance was strongly limited by the trade-off between permeance and selectivity.Herein,novel 4,4′-(hexafluoroisopropylidene)diphthalic anhydride(6FDA)-2,2′-bis(3-amino-4-hydroxyphenyl)hexafluoropropane(APAF)-5-amino-2-(4-aminobenzene)benzimidazole(BIA)asymmetric membranes with a thickness of 300 nm were successfully prepared by the non-solvent induced phase separation method.The membrane performance was modulated by regulating dope solution compositions(e.g.,tetrahydrofuran and polymer concentration).The ideal He/CH_(4) selectivity was 124 and the optimized He permeance reached 87 GPU,beyond the current upper bound.He/CH_(4) selectivity was 75 and He permeance was 73 GPU for the binary mixture feed containing 0.2 mol%He.The membrane showed good resistance to CO_(2) and C_(2)H_(6),which are the typical impurities in natural gas.The 6FDA-APAF-BIA membranes have good stability(>160 h),which can provide great potential in He extraction from natural gas.
基金supported by the China NSFC grants 82173807 to Yajun Duan and 81973316 to Jihong HanTianjin Municipal Science and Technology Commission of China Grant 20JCZDJC00710the Fundamental Research Funds for the Central Universities(Nankai University,China)63211045 to Jihong Han.
文摘Heart failure is the leading cause of death worldwide.Compound Danshen Dripping Pill(CDDP)or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China.However,the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown.We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E(ApoE)and LDL receptor(LDLR)dual deficient(ApoE^(–/–)LDLR^(–/–))mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure.CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis.Mechanistically,both Wnt and lysine-specific demethylase 4A(KDM4A)pathways were significantly activated in mice with heart injury.Conversely,CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors.While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity.In addition,CDDP attenuated simvastatin-induced myolysis in skeletal muscle.Taken together,our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.