In order to study the influence of three-grid assembly thermal deformation caused by heat accumulation on breakdown times and an ion extraction process,a hot gap test and a breakdown time test are carried out to obtai...In order to study the influence of three-grid assembly thermal deformation caused by heat accumulation on breakdown times and an ion extraction process,a hot gap test and a breakdown time test are carried out to obtain thermal deformation of the grids when the thruster is in 5 k W operation mode.Meanwhile,the fluid simulation method and particle-in-cell-Monte Carlo collision(PICMCC) method are adopted to simulate the ion extraction process according to the previous test results.The numerical calculation results are verified by the ion thruster performance test.The results show that after about 1.2 h operation,the hot gap between the screen grid and the accelerator grid reduce to 0.25–0.3 mm,while the hot gap between the accelerator grid and the decelerator grid increase from 1 mm to about 1.4 mm when the grids reach thermal equilibrium,and the hot gap is almost unchanged.In addition,the breakdown times experiment shows that 0.26 mm is the minimal safe hot gap for the grid assembly as the breakdown times improves significantly when the gap is smaller than this value.Fluid simulation results show that the plasma density of the screen grid is in the range 6?×10^(17)–6?×?10^(18) m^(13) and displays a parabolic characteristic,while the electron temperature gradually increases along the axial direction.The PIC-MCC results show that the current falling of an ion beam through a single aperture is significant.Meanwhile,the intercepted current of the accelerator grid and the decelerator grid both increase with the change in the hot gap.The ion beam current has optimal perveance status without thermal deformation,and the intercepted current of the accelerator grid and the decelerator grid are 3.65 m A and 6.26 m A,respectively.Furthermore,under the effect of thermal deformation,the ion beam current has over-perveance status,and the intercepted current of the accelerator grid and the decelerator grid are 10.46 m A and 18.24 m A,respectively.Performance test results indicate that the breakdown times increase obviously.The intercepted current of the accelerator grid and the decelerator grid increases to 13 m A and 16.5 m A,respectively,due to the change in the hot gap after 1.5 h operation.The numerical calculation results are well consistent with performance test results,and the error comes mainly from the test uncertainty of the hot gap.展开更多
A 2D hybrid-PIC simulation model is proposed to investigate the beam extraction phenomena of the ion thruster. In which the electrons of the plasma sheath upstream the accelerator grid are assumed as particles while t...A 2D hybrid-PIC simulation model is proposed to investigate the beam extraction phenomena of the ion thruster. In which the electrons of the plasma sheath upstream the accelerator grid are assumed as particles while the downstream are fluid for improving the calculation efficiency. The ion transparency, plasma sheath formation, ion beam extraction characteristic of a two- and three-grid system have been compared in detail in this paper. From the comparison of the appearing time of the under-perveance phenomena in the two- and three-grid system, it illustrated that the two grid system has the wider operation range of the plasma densities than the three-grid one.展开更多
Beam flatness is an important parameter that determines the performance and the lifetime of a gridded ion thruster.To improve the beam flatness of the 30 cm(LIPS-300)ion thruster,variable aperture ion optics that adap...Beam flatness is an important parameter that determines the performance and the lifetime of a gridded ion thruster.To improve the beam flatness of the 30 cm(LIPS-300)ion thruster,variable aperture ion optics that adapts to the decreasing ion density as the radius increases is proposed.It is the ion optics that the screen grid surface is divided into several zones,where the aperture diameter in each zone is determined by the ion density and the electron temperature upstream of the screen grid.The beam current density in the central area is artificially reduced.A particle in cell-Monte Carlo collision model is applied in this work to investigating the effect of variable aperture on the perveance and the maximum beam current per aperture by simulating the extraction,focusing and acceleration processes of ions.Taking into account the engineering implementability,the screen grid surface is divided into four zones.The hole diameter in each zone is decreased from 1.95 mm to 1.8 mm,1.9 mm,1.8 mm and 1.7 mm,respectively.The simulation results show that the maximum ion density in the center area of grid is decreased by10.6%and 6.99%,while it is increased by 6.49%and 22.3%in the edge region,respectively.The beam flatness of the variable aperture ion optics is improved from 0.69 to 0.88.The erosion rate is decreased by 31.9%,but the total beam current is also decreased by 7.15%.The simulation results can provide a valuable reference of the development of the ion thruster.展开更多
Both the long-life and multi-mode versions of LIPS-200 ion thruster are under investigation in LIP(Lanzhou Institute of Physics).To confirm the feasible ranges of the beam current and accel(abbreviation for accelarati...Both the long-life and multi-mode versions of LIPS-200 ion thruster are under investigation in LIP(Lanzhou Institute of Physics).To confirm the feasible ranges of the beam current and accel(abbreviation for accelaration)grid potential to apply to the thruster,the wide-range beam perveance(the state of beam focus)and saddle point potential(the lowest potential along beamlet centerline)characteristics of LIPS-200 are studied with a test-verified PIC-MCC(Particle in Cell-Monte Carlo Collisions)model.These characteristics are investigated with both the initial and the eroded states of the accel grid aperture diameter.The results show that the feasible ranges of these parameters with respect to perveance/crossover(overfocused)limit extend as the operating time accumulates,while the feasible range of accel grid potential narrows due to a reduced EBSF(electron backstreaming failure)margin.The feasible ranges determined by the initial condition are:(i)the beam current up to 0.981 A,and(ii)the accel grid potential up to−85 V.A 23%enlargement of the aperture diameter would bring up to 48 V of EBSF margin loss.展开更多
A two-dimensional particle-in-cell plasma model is built in the R-Z plane to investigate the low- frequency plasma oscillations in the discharge channel of a 5 kW LHT-140 Hall thruster. In addition to the elastic, exc...A two-dimensional particle-in-cell plasma model is built in the R-Z plane to investigate the low- frequency plasma oscillations in the discharge channel of a 5 kW LHT-140 Hall thruster. In addition to the elastic, excitation, and ionization collisions between neutral atoms and electrons, the Coulomb collisions between electrons and electrons and between electrons and ions are analyzed. The sheath characteristic distortion is also corrected. Simulation results indicate the capability of the built model to reproduce the low-frequency oscillation with high accuracy. The oscillations of the discharge current and ion density produced by the model are consistent with the existing conclusions. The model predicts a frequency that is consistent with that calculated by the zero-dimensional theoretical model.展开更多
Electric propulsion technology is the most active professional technology in the field of space propulsion in recent years.China began the research of electric propulsion technology in the 1970s,and entered the stage ...Electric propulsion technology is the most active professional technology in the field of space propulsion in recent years.China began the research of electric propulsion technology in the 1970s,and entered the stage of rapid development after 2000.It has successively completed the principle research,technical breakthrough and ground test verification.Driven by the increasing demand for space missions,various new types of electric propulsion are emerging.展开更多
Chronic diabetic wounds remain a globally recognized clinical challenge.They occur due to high concentrations of reactive oxygen species and vascular function disorders.A promising strategy for diabetic wound healing ...Chronic diabetic wounds remain a globally recognized clinical challenge.They occur due to high concentrations of reactive oxygen species and vascular function disorders.A promising strategy for diabetic wound healing is the delivery of exosomes,comprising bioactive dressings.Metformin activates the vascular endothelial growth factor pathway,thereby improving angiogenesis in hyperglycemic states.However,multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported,and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains unclear.Here,we engineered dual-loaded hydrogels possessing tissue adhesive,antioxidant,self-healing and electrical conductivity properties,wherein 4-armed SH-PEG cross-links with Ag^(+),which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound repair.Multiwalled carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group,creating a stable three-dimensional structure for exosome and metformin loading.The diabetic wound model of the present study suggests that the PEG/Ag/CNT-M+E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular injury.The mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission,thereby protecting F-actin homeostasis and alleviating microvascular dysfunction.Hence,we propose a drug-bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.展开更多
Background:Acute lung injury(ALI)is a common complication following severe burns.The underlying mechanisms of ALI are incompletely understood;thus,available treatments are not sufficient to repair the lung tissue afte...Background:Acute lung injury(ALI)is a common complication following severe burns.The underlying mechanisms of ALI are incompletely understood;thus,available treatments are not sufficient to repair the lung tissue after ALI.Methods:To investigate the relationship between the Notch pathway and burn-induced lung injury,we established a rat burn injury model by scalding and verified lung injury via lung injury evaluations,including hematoxylin and eosin(H&E)staining,lung injury scoring,bronchoalveolar lavage fluid and wet/dry ratio analyses,myeloperoxidase immunohistochemical staining and reac-tive oxygen species(ROS)accumulation analysis.To explore whether burn injury affects Notch1 expression,we detected the expression of Notch1 and Hes1 after burn injury.Then,we extracted pulmonary microvascular endothelial cells(PMVECs)and conducted Notch pathway inhibition and activation experiments,via aγ-secretase inhibitor(GSI)and OP9-DLL1 coculture,respectively,to verify the regulatory effect of the Notch pathway on ROS accumulation and apoptosis in burn-serum-stimulated PMVECs.To investigate the regulatory effect of the Notch pathway on ROS accumulation,we detected the expression of oxidative-stress-related molecules such as superoxide dismutase,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase(NOX)2,NOX4 and cleaved caspase-3.NOX4-specific small interfering RNA(siRNA)and the inhibitor GKT137831 were used to verify the regulatory effect of the Notch pathway on ROS via NOX4.Results:We successfully established a burn model and revealed that lung injury,excessive ROS accumulation and an inflammatory response occurred.Notch1 detection showed that the expression of Notch1 was significantly increased after burn injury.In PMVECs challenged with burn serum,ROS and cell death were elevated.Moreover,when the Notch pathway was suppressed by GSI,ROS and cell apoptosis levels were significantly increased.Conversely,these parameters were reduced when the Notch pathway was activated by OP9-DLL1.Mechanistically,the inhibition of NOX4 by siRNA and GKT137831 showed that the Notch pathway reduced ROS production and cell apoptosis by downregulating the expression of NOX4 in PMVECs.Conclusions:The Notch pathway reduced ROS production and apoptosis by downregulating the expression of NOX4 in burn-stimulated PMVECs.The Notch-NOX4 pathway may be a novel therapeutic target to treat burn-induced ALI.展开更多
Background:MicroRNA-101(miR-101)is a tumor suppressor microRNA(miRNA)and its loss is associated with the occurrence and progression of various diseases.However,the biological function and target of miR-101 in the path...Background:MicroRNA-101(miR-101)is a tumor suppressor microRNA(miRNA)and its loss is associated with the occurrence and progression of various diseases.However,the biological function and target of miR-101 in the pathogenesis of hypertrophic scars(HS)remains unknown.Methods:We harvested HS and paired normal skin(NS)tissue samples from patients and cultured their fibroblasts(HSF and NSF,respectively).We used quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),fluorescence in situ hybridization(FISH),enzyme-linked immunosorbent assays(ELISA)and Western blot analyses to measure mRNA levels and protein expression of miR-101,enhancer of zeste homolog 2(EZH2),collagen 1 and 3(Col1 and Col3)andα-smooth muscle actin(α-SMA)in different in vitro conditions.We also used RNA sequencing to evaluate the relevant signaling pathways and bioinformatics analysis and dual-luciferase reporter assays to predict miR-101 targets.We utilized a bleomycin-induced fibrosis mouse model in which we injected miR-101 mimics to evaluate collagen deposition in vivo.Results:We found low expression of miR-101 in HS and HSF compared to NS and NSF.Overexpressing miR-101 decreased Col1,Col3 andα-SMA expression in HSF.We detected high expression of EZH2 in HS and HSF.Knockdown of EZH2 decreased Col1,Col3 andα-SMA in HSF.Mechanistically,miR-101 targeted the 3-untranslated region(3UTR)of EZH2,as indicated by the decreased expression of EZH2.Overexpressing EZH2 rescued miR-101-induced collagen repression.MiR-101 mimics effectively suppressed collagen deposition in the bleomycin-induced fibrosis mouse model.Conclusions:Our data reveal that miR-101 targets EZH2 in HS collagen production,providing new insight into the pathological mechanisms underlying HS formation.展开更多
Background:Population-based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent.This prospective cohort study aimed to investigate th...Background:Population-based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent.This prospective cohort study aimed to investigate the association between fruit and vegetable intake and the risk of new-onset hypertension.Methods:Based on the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR),58,981 Chinese adults without hypertension at baseline were included.Information on fruit and vegetable intake was collected using a food-frequency questionnaire.Cox proportional hazards models were performed to estimate the hazard ratios(HRs)and 95%confidence intervals(CIs)of incident hypertension.Results:During 640,795 person-years of follow-up,21,008 new cases of hypertension were recorded.Compared with participants in the lowest quintile(Q1)of total fruit and vegetable(TFV)intake,the HRs(95%CIs)of incident hypertension were 0.90(0.86-0.95),0.85(0.81-0.90),0.82(0.78-0.86),and 0.83(0.78-0.88)for the Q2 to Q5 group(ptrend<0.001),respectively.In further analyses categorizing participants according to the recommended intake level(500 g/day),we found that increasing the intake of TFV,even though it was still insufficient for the recommendation,also had a protective effect against the incident hypertension.When considering the intake of fruit or vegetable separately,we found similar trends as the TFV intake.Conclusion:These results suggest that a higher intake of fruit and vegetable is beneficial for preventing hypertension in Chinese adults.展开更多
基金supported by the National Key Laboratory Fund of Science and Technology on Vacuum Technology & Physics (Grant No.6142207030103)National Natural Science Foundation of China (Grant No.11702123)
文摘In order to study the influence of three-grid assembly thermal deformation caused by heat accumulation on breakdown times and an ion extraction process,a hot gap test and a breakdown time test are carried out to obtain thermal deformation of the grids when the thruster is in 5 k W operation mode.Meanwhile,the fluid simulation method and particle-in-cell-Monte Carlo collision(PICMCC) method are adopted to simulate the ion extraction process according to the previous test results.The numerical calculation results are verified by the ion thruster performance test.The results show that after about 1.2 h operation,the hot gap between the screen grid and the accelerator grid reduce to 0.25–0.3 mm,while the hot gap between the accelerator grid and the decelerator grid increase from 1 mm to about 1.4 mm when the grids reach thermal equilibrium,and the hot gap is almost unchanged.In addition,the breakdown times experiment shows that 0.26 mm is the minimal safe hot gap for the grid assembly as the breakdown times improves significantly when the gap is smaller than this value.Fluid simulation results show that the plasma density of the screen grid is in the range 6?×10^(17)–6?×?10^(18) m^(13) and displays a parabolic characteristic,while the electron temperature gradually increases along the axial direction.The PIC-MCC results show that the current falling of an ion beam through a single aperture is significant.Meanwhile,the intercepted current of the accelerator grid and the decelerator grid both increase with the change in the hot gap.The ion beam current has optimal perveance status without thermal deformation,and the intercepted current of the accelerator grid and the decelerator grid are 3.65 m A and 6.26 m A,respectively.Furthermore,under the effect of thermal deformation,the ion beam current has over-perveance status,and the intercepted current of the accelerator grid and the decelerator grid are 10.46 m A and 18.24 m A,respectively.Performance test results indicate that the breakdown times increase obviously.The intercepted current of the accelerator grid and the decelerator grid increases to 13 m A and 16.5 m A,respectively,due to the change in the hot gap after 1.5 h operation.The numerical calculation results are well consistent with performance test results,and the error comes mainly from the test uncertainty of the hot gap.
基金supported by National Natural Science Foundation of China (No. 11702123)Technology Based Research Projects of SASTIND (No. JSZL2017203B008)Fund for Distinguished Young Talents of CAST (No. 9140C550206130C55003)
文摘A 2D hybrid-PIC simulation model is proposed to investigate the beam extraction phenomena of the ion thruster. In which the electrons of the plasma sheath upstream the accelerator grid are assumed as particles while the downstream are fluid for improving the calculation efficiency. The ion transparency, plasma sheath formation, ion beam extraction characteristic of a two- and three-grid system have been compared in detail in this paper. From the comparison of the appearing time of the under-perveance phenomena in the two- and three-grid system, it illustrated that the two grid system has the wider operation range of the plasma densities than the three-grid one.
基金supported by Top Young Talents of China Aerospace ScienceTechnology Corporation,Innovation Group Project of Gansu ProvinceNational Natural Science Foundation of China(No.11802111)。
文摘Beam flatness is an important parameter that determines the performance and the lifetime of a gridded ion thruster.To improve the beam flatness of the 30 cm(LIPS-300)ion thruster,variable aperture ion optics that adapts to the decreasing ion density as the radius increases is proposed.It is the ion optics that the screen grid surface is divided into several zones,where the aperture diameter in each zone is determined by the ion density and the electron temperature upstream of the screen grid.The beam current density in the central area is artificially reduced.A particle in cell-Monte Carlo collision model is applied in this work to investigating the effect of variable aperture on the perveance and the maximum beam current per aperture by simulating the extraction,focusing and acceleration processes of ions.Taking into account the engineering implementability,the screen grid surface is divided into four zones.The hole diameter in each zone is decreased from 1.95 mm to 1.8 mm,1.9 mm,1.8 mm and 1.7 mm,respectively.The simulation results show that the maximum ion density in the center area of grid is decreased by10.6%and 6.99%,while it is increased by 6.49%and 22.3%in the edge region,respectively.The beam flatness of the variable aperture ion optics is improved from 0.69 to 0.88.The erosion rate is decreased by 31.9%,but the total beam current is also decreased by 7.15%.The simulation results can provide a valuable reference of the development of the ion thruster.
基金Group independent research and development projects(No.YF-ZZYF-2021-132).
文摘Both the long-life and multi-mode versions of LIPS-200 ion thruster are under investigation in LIP(Lanzhou Institute of Physics).To confirm the feasible ranges of the beam current and accel(abbreviation for accelaration)grid potential to apply to the thruster,the wide-range beam perveance(the state of beam focus)and saddle point potential(the lowest potential along beamlet centerline)characteristics of LIPS-200 are studied with a test-verified PIC-MCC(Particle in Cell-Monte Carlo Collisions)model.These characteristics are investigated with both the initial and the eroded states of the accel grid aperture diameter.The results show that the feasible ranges of these parameters with respect to perveance/crossover(overfocused)limit extend as the operating time accumulates,while the feasible range of accel grid potential narrows due to a reduced EBSF(electron backstreaming failure)margin.The feasible ranges determined by the initial condition are:(i)the beam current up to 0.981 A,and(ii)the accel grid potential up to−85 V.A 23%enlargement of the aperture diameter would bring up to 48 V of EBSF margin loss.
文摘A two-dimensional particle-in-cell plasma model is built in the R-Z plane to investigate the low- frequency plasma oscillations in the discharge channel of a 5 kW LHT-140 Hall thruster. In addition to the elastic, excitation, and ionization collisions between neutral atoms and electrons, the Coulomb collisions between electrons and electrons and between electrons and ions are analyzed. The sheath characteristic distortion is also corrected. Simulation results indicate the capability of the built model to reproduce the low-frequency oscillation with high accuracy. The oscillations of the discharge current and ion density produced by the model are consistent with the existing conclusions. The model predicts a frequency that is consistent with that calculated by the zero-dimensional theoretical model.
文摘Electric propulsion technology is the most active professional technology in the field of space propulsion in recent years.China began the research of electric propulsion technology in the 1970s,and entered the stage of rapid development after 2000.It has successively completed the principle research,technical breakthrough and ground test verification.Driven by the increasing demand for space missions,various new types of electric propulsion are emerging.
基金supported by National Natural Science Foundation of China Youth Science Fund Project(No.82002039)National Natural Science Foundation of China(81530064)+1 种基金National Natural Science Foundation of China(81772071)National Natural Science Foundation of China(No.82172210).
文摘Chronic diabetic wounds remain a globally recognized clinical challenge.They occur due to high concentrations of reactive oxygen species and vascular function disorders.A promising strategy for diabetic wound healing is the delivery of exosomes,comprising bioactive dressings.Metformin activates the vascular endothelial growth factor pathway,thereby improving angiogenesis in hyperglycemic states.However,multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported,and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains unclear.Here,we engineered dual-loaded hydrogels possessing tissue adhesive,antioxidant,self-healing and electrical conductivity properties,wherein 4-armed SH-PEG cross-links with Ag^(+),which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound repair.Multiwalled carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group,creating a stable three-dimensional structure for exosome and metformin loading.The diabetic wound model of the present study suggests that the PEG/Ag/CNT-M+E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular injury.The mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission,thereby protecting F-actin homeostasis and alleviating microvascular dysfunction.Hence,we propose a drug-bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.
基金supported by grants from the National Natural Science Foundation of China(81601680 and 81671910).
文摘Background:Acute lung injury(ALI)is a common complication following severe burns.The underlying mechanisms of ALI are incompletely understood;thus,available treatments are not sufficient to repair the lung tissue after ALI.Methods:To investigate the relationship between the Notch pathway and burn-induced lung injury,we established a rat burn injury model by scalding and verified lung injury via lung injury evaluations,including hematoxylin and eosin(H&E)staining,lung injury scoring,bronchoalveolar lavage fluid and wet/dry ratio analyses,myeloperoxidase immunohistochemical staining and reac-tive oxygen species(ROS)accumulation analysis.To explore whether burn injury affects Notch1 expression,we detected the expression of Notch1 and Hes1 after burn injury.Then,we extracted pulmonary microvascular endothelial cells(PMVECs)and conducted Notch pathway inhibition and activation experiments,via aγ-secretase inhibitor(GSI)and OP9-DLL1 coculture,respectively,to verify the regulatory effect of the Notch pathway on ROS accumulation and apoptosis in burn-serum-stimulated PMVECs.To investigate the regulatory effect of the Notch pathway on ROS accumulation,we detected the expression of oxidative-stress-related molecules such as superoxide dismutase,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase(NOX)2,NOX4 and cleaved caspase-3.NOX4-specific small interfering RNA(siRNA)and the inhibitor GKT137831 were used to verify the regulatory effect of the Notch pathway on ROS via NOX4.Results:We successfully established a burn model and revealed that lung injury,excessive ROS accumulation and an inflammatory response occurred.Notch1 detection showed that the expression of Notch1 was significantly increased after burn injury.In PMVECs challenged with burn serum,ROS and cell death were elevated.Moreover,when the Notch pathway was suppressed by GSI,ROS and cell apoptosis levels were significantly increased.Conversely,these parameters were reduced when the Notch pathway was activated by OP9-DLL1.Mechanistically,the inhibition of NOX4 by siRNA and GKT137831 showed that the Notch pathway reduced ROS production and cell apoptosis by downregulating the expression of NOX4 in PMVECs.Conclusions:The Notch pathway reduced ROS production and apoptosis by downregulating the expression of NOX4 in burn-stimulated PMVECs.The Notch-NOX4 pathway may be a novel therapeutic target to treat burn-induced ALI.
基金supported by the National Natural Science Foundation of China(81772071 to DHH).
文摘Background:MicroRNA-101(miR-101)is a tumor suppressor microRNA(miRNA)and its loss is associated with the occurrence and progression of various diseases.However,the biological function and target of miR-101 in the pathogenesis of hypertrophic scars(HS)remains unknown.Methods:We harvested HS and paired normal skin(NS)tissue samples from patients and cultured their fibroblasts(HSF and NSF,respectively).We used quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),fluorescence in situ hybridization(FISH),enzyme-linked immunosorbent assays(ELISA)and Western blot analyses to measure mRNA levels and protein expression of miR-101,enhancer of zeste homolog 2(EZH2),collagen 1 and 3(Col1 and Col3)andα-smooth muscle actin(α-SMA)in different in vitro conditions.We also used RNA sequencing to evaluate the relevant signaling pathways and bioinformatics analysis and dual-luciferase reporter assays to predict miR-101 targets.We utilized a bleomycin-induced fibrosis mouse model in which we injected miR-101 mimics to evaluate collagen deposition in vivo.Results:We found low expression of miR-101 in HS and HSF compared to NS and NSF.Overexpressing miR-101 decreased Col1,Col3 andα-SMA expression in HSF.We detected high expression of EZH2 in HS and HSF.Knockdown of EZH2 decreased Col1,Col3 andα-SMA in HSF.Mechanistically,miR-101 targeted the 3-untranslated region(3UTR)of EZH2,as indicated by the decreased expression of EZH2.Overexpressing EZH2 rescued miR-101-induced collagen repression.MiR-101 mimics effectively suppressed collagen deposition in the bleomycin-induced fibrosis mouse model.Conclusions:Our data reveal that miR-101 targets EZH2 in HS collagen production,providing new insight into the pathological mechanisms underlying HS formation.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Grant/Award Number: 2021-I2M-1-010)National Key Research and Development Program of China(Grant/Award Number: 2018YFE0115300)+2 种基金National Natural Science Foundation of China(Grant/Award Numbers: 82030102, 82070473)National High Level Hospital Clinical Research Funding(Grant/Award Numbers: 2022-GSP-GG-1, 2022-GSP-GG-2)National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences(Grant/Award Number: NCRC2020006).
文摘Background:Population-based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent.This prospective cohort study aimed to investigate the association between fruit and vegetable intake and the risk of new-onset hypertension.Methods:Based on the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR),58,981 Chinese adults without hypertension at baseline were included.Information on fruit and vegetable intake was collected using a food-frequency questionnaire.Cox proportional hazards models were performed to estimate the hazard ratios(HRs)and 95%confidence intervals(CIs)of incident hypertension.Results:During 640,795 person-years of follow-up,21,008 new cases of hypertension were recorded.Compared with participants in the lowest quintile(Q1)of total fruit and vegetable(TFV)intake,the HRs(95%CIs)of incident hypertension were 0.90(0.86-0.95),0.85(0.81-0.90),0.82(0.78-0.86),and 0.83(0.78-0.88)for the Q2 to Q5 group(ptrend<0.001),respectively.In further analyses categorizing participants according to the recommended intake level(500 g/day),we found that increasing the intake of TFV,even though it was still insufficient for the recommendation,also had a protective effect against the incident hypertension.When considering the intake of fruit or vegetable separately,we found similar trends as the TFV intake.Conclusion:These results suggest that a higher intake of fruit and vegetable is beneficial for preventing hypertension in Chinese adults.