At high cycles of steam huff&puff,oil distribution in reservoirs becomes stronger heterogeneity due to steam channeling.Thermal solidification agent can be used to solve this problem.Its solution is a lowviscosity...At high cycles of steam huff&puff,oil distribution in reservoirs becomes stronger heterogeneity due to steam channeling.Thermal solidification agent can be used to solve this problem.Its solution is a lowviscosity liquid at normal temperature,but it can be solidified above 80℃.The plugging degree is up to 99%at 250℃.The sweep efficiency reaches 59.2%,which is 7.3%higher than pure steam injection.In addition,simultaneous injection of viscosity reducer and/or nitrogen foams can further enhance oil recovery.The mechanism of this technology depends on its strong plugging ability,which changes the flowing pattern of steam to effectively mobilize remaining oil.Viscosity reducer and nitrogen foams further expand the sweep range and extends the effective period.Therefore,thermal solidification agent can plug steam channeling paths and adjust steam flowing direction to significantly enhance oil recovery at high cycles of steam huff&puff.展开更多
The ultra-fine grained(UFG)pure titanium was prepared by equal channel angular pressing(ECAP)and rotary swaging(RS).The strain controlled low cycle fatigue(LCF)test was carried out at room temperature.The fatigue life...The ultra-fine grained(UFG)pure titanium was prepared by equal channel angular pressing(ECAP)and rotary swaging(RS).The strain controlled low cycle fatigue(LCF)test was carried out at room temperature.The fatigue life prediction model and mean stress relaxation model under asymmetrical stress load were discussed.The results show that the strain ratio has a significant effect on the low cycle fatigue performance of the UFG pure titanium,and the traditional Manson-coffin model can not accurately predict the fatigue life under asymmetric stress load.Therefore,the SWT mean stress correction model and three-parameter power curve model are proposed,and the test results are verified.The final research shows that the threeparameter power surface model has better representation.By studying the mean stress relaxation phenomenon under the condition of R≠-1,it is revealed that the stress ratio and the strain amplitude are the factors that significantly afiect the mean stress relaxation rate,and the mean stress relaxation model with the two variables is calculated to describe the mean stress relaxation phenomenon of the UFG pure titanium under different strain ratios.The fracture morphology of the samples was observed by SEM,and it was concluded that the final fracture zone of the fatigue fracture of the UFG pure titanium was a mixture of ductile fracture and quasi cleavage fracture.The toughness of the material increases with the increase of strain ratio at the same strain amplitude.展开更多
Friction stir welding was used to join two AA2060-T8 plates,and then the effect of precipitate evolution on microstructure and corrosion behavior of the joint was investigated.The evolution of precipitates on the top ...Friction stir welding was used to join two AA2060-T8 plates,and then the effect of precipitate evolution on microstructure and corrosion behavior of the joint was investigated.The evolution of precipitates on the top surface of the joint was characterized by scanning electron microscopy and transmission electron microscopy.The corrosion behaviors of different regions in the joint were investigated by an electrochemistry method and an alternating salt spray exposure.The corrosion was mainly dependent on the nature of precipitates in each region of the joint.The shoulder affected zone had the worst corrosion resistance as a result of the re-dissolved ofθ′(Al2Cu),T1(Al2CuLi)andδ′(Al3Li)phases,the formation of intergranular precipitates and precipitate-free zones.However,the thermomechanically affected zone had a slightly improved corrosion resistance because it had no intergranular precipitates.The heat affected zone and base metal had the best corrosion resistance.展开更多
This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma co...This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma concentration-time curve(AUC)of cilastatin were significantly increased,while renal clearance and cumulative urinary excretion of cilastatin were decreased.At the same time,imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1(hOAT1)-HEK293 and human OAT3(hOAT3)-HEK293 cells.Probenecid,p-aminohippurate,and benzylpenicillin inhibited the uptake of imipenem and cilastatin in rat kidney slices and in hOAT1-and hOAT3-HEK 293 cells,respectively.The uptakes of imipenem and cilastatin in hOAT1-and hOAT3-HEK 293 cells were significantly higher than that in mock-HEK-293 cells.Moreover,the K m values of cilastatin were increased in the presence of imipenem with unchanged V max,indicating that imipenem inhibited the uptake of cilastatin in a competitive manner.When imipenem and cilastatin were co-administered,the level of imipenem was higher compared with imipenem alone both in vivo and in vitro.But,cilastatin significantly inhibited the uptake of imipenem when dehydropeptidase-1(DPEP1)was silenced by RNAi technology in hOAT1-and hOAT3-HEK 293 cells.In conclusion,imipenem and cilastatin are the substrates of OAT1 and OAT3.OAT1 and OAT3 mediate the DDI between imipenem and cilastatin.Meanwhile,cilastatin also reduces the hydrolysis of imipenem by inhibiting the uptake of imipenem mediated by OAT1 and OAT3 in the kidney as a complement.展开更多
To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam,renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats.A b...To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam,renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats.A bacteremia model was established to investigate the pharmacokinetic properties of piperacillin and tazobactam under different conditions.Renal slices were taken to examine the uptake of piperacillin and tazobactam.Pharmacokinetic studies ofβ-lactamase in rats were performed to study the contribution of rOat1/3 to the inhibition of tazobactam onβ-lactamase.The AUC(from 2.93±0.58 to 6.52±1.44 mg·min/ml)and the plasma clearance(CL P)(from 2.41±1.20 to 0.961±0.212 ml/min/kg)of tazobactam were both altered after the intravenous coadministration of piperacillin and tazobactam in the bacteremia rats.The renal clearance(CL R)of tazobactam decreased from 1.30±0.50 to 0.361±0.043 ml/min/kg.In summary,there was a beneficial interaction between piperacillin and tazobactam mediated by rOat1 and rOat3.Piperacillin enhances the inhibitory effect of tazobactam onβ-lactamase through the inhibition of rOat1 and rOat3 in rats.The contribution rate of rOat1/3 for the synergistic effect was 20%when the two drugs were coadministered.展开更多
This study presents a detailed investigation into the soil arching effects within deep foundation pits(DFPs),focusing on their mechanical behavior and implications for structural design.Through rigorous 3D finite elem...This study presents a detailed investigation into the soil arching effects within deep foundation pits(DFPs),focusing on their mechanical behavior and implications for structural design.Through rigorous 3D finite element modeling and parameter sensitivity analyses,the research explores the formation,geometric characteristics,and spatial distribution of soil arching phenomena.The investigation encompasses the influence of key parameters such as elastic modulus,cohesion,and internal friction angle on the soil arching effect.The findings reveal that soil arching within DFPs exhibits distinct spatial characteristics,with the prominent arch axis shifting as excavation depth progresses.Optimal soil arching is observed when the pile spacing approximates three times the pile diameter,enhancing soil retention and minimizing deformation risks.Sensitivity analyses highlight the significant impact of soil parameters on soil arching behavior,underscoring the critical role of cohesive forces and internal friction angles in shaping arching characteristics.By elucidating the interplay between soil parameters and soil arching effects,the research provides insights for optimizing pile spacing and structural stability.展开更多
Pharmacokinetics(PK)is the study of the absorption,distribution,metabolism,and excretion(ADME)processes of a drug.Understanding PK properties is essential for drug development and precision medication.In this review w...Pharmacokinetics(PK)is the study of the absorption,distribution,metabolism,and excretion(ADME)processes of a drug.Understanding PK properties is essential for drug development and precision medication.In this review we provided an overview of recent research on PK with focus on the following aspects:(1)an update on drug-metabolizing enzymes and transporters in the determination of PK,as well as advances in xenobiotic receptors and noncoding RNAs(ncRNAs)in the modulation of PK,providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy;(2)current status and trends in assessing drug-drug interactions,especially interactions between drugs and herbs,between drugs and therapeutic biologies,and microbiota-mediated interactions:(3)advances in understanding the effects of diseases on PK,particularly changes in metabolizing enzymes and transporters with disease progression;(4)trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies:(5)emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes,especially non-P450s.Existing challenges and perspectives on future directions are discussed,and may stimulate the development of new research models,technologies,and strategies towards the development of better drugs and improved clinical practice.展开更多
Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I(DHP-I),was developed. In present stud...Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I(DHP-I),was developed. In present study, the potential roles of renal organic anion transporters(OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated in vitro and in rabbits. Our results indicated that imipenem and cilastatin were substrates of h OAT1 and h OAT3. Cilastatin inhibited h OAT1/3-mediated transport of imipenem with IC50 values comparable to the clinical concentration, suggesting the potential to cause a clinical drug–drug interaction(DDI). Moreover,imipenem exhibited h OAT1/3-dependent cytotoxicity, which was alleviated by cilastatin and probenecid. Furthermore, cilastatin and probenecid ameliorated imipenem-induced rabbit acute kidney injury, and reduced the renal secretion of imipenem. Cilastatin and probenecid inhibited intracellular accumulation of imipenem and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells. Renal OATs, besides DHP-I, was also the target of interaction between imipenem and cilastatin, and contributed to the nephrotoxicity of imipenem. This therefore gives in part the explanation about the mechanism by which cilastatin protected against imipenem-induced nephrotoxicity. Thus, OATs can potentially be used as a therapeutic target to avoid the renal adverse reaction of imipenem in clinic.展开更多
Universal challenge lies in torque feedback accuracy for steer-by-wire systems,especially on uneven and low-friction road.Therefore,this paper proposes a fusion method based on Kalman filter that combines a dynamics-r...Universal challenge lies in torque feedback accuracy for steer-by-wire systems,especially on uneven and low-friction road.Therefore,this paper proposes a fusion method based on Kalman filter that combines a dynamics-reconstruction method and disturbance observer-based method.The dynamics-reconstruction method is designed according to the vehicle dynamics and used as the prediction model of the Kalman filter.While the disturbance observer-based method is performed as an observer model of the Kalman filter.The performance of all three methods is comprehensively evaluated in a hardware-in-the-loop system.Experimental results show that the proposed fusion method outperforms dynamics reconstruction method and disturbance observer-based method.Specifically,compared with the dynamics-reconstruction method,the root mean square error is reduced by 36.58%at the maximum on the flat road.Compared with the disturbance observer-based method,the root mean square error is reduced by 39.11%at the maximum on different-friction and uneven road.展开更多
In this work, 20-mm-thick aluminum-alloy plates were joined via friction stir welding. The temperature gradient was reduced by reducing the surface welding heat input to achieve uniformity of the mechanical properties...In this work, 20-mm-thick aluminum-alloy plates were joined via friction stir welding. The temperature gradient was reduced by reducing the surface welding heat input to achieve uniformity of the mechanical properties across the thick plate joints. The welding temperature was measured using thermocouples. The microstructures were observed via electron backscatter diff raction and transmission electron microscopy. The tensile properties of the samples sliced along the thickness direction of the joint were evaluated. The results show that the highest welding peak temperature is 430℃ on the advancing side on the top surface of the joint. The grain size gradually decreased along the thickness direction, and grain refi nement was due to the combination of continuous, discontinuous, and geometric dynamic recrystallization. The tensile properties of the sliced samples were found to be uniform, and the ultimate tensile strength reached 62% of that of the base metal. The main strengthening mechanism of the Al–Zn–Mg–Cu alloy joints consists of precipitation strengthening. In addition, the η ` → η phase transition and grain coarsening in the heat-affected zone were found to be responsible for the fracture of the joints.展开更多
For an electrical six-degree-of-freedom Stewart platform,it is difficult to compute the equivalent inertia of each motor in real time,as the inertia is time-varying.In this study,an analysis using Kane's equation ...For an electrical six-degree-of-freedom Stewart platform,it is difficult to compute the equivalent inertia of each motor in real time,as the inertia is time-varying.In this study,an analysis using Kane's equation is undertaken of the driven torque of the movements of motor systems(including motor friction,movements of motor systems along with the actuators,rotation around axis of rotors and snails),as well as driven torque of the platform and actuators.The electromagnetic torque was calculated according to vector-controlled permanent magnet synchronous motor(PMSM) dynamics.By equalizing the driven torque and electromagnetic torque,a model was established.This method,taking into consideration the influence of counter electromotive force(EMF) and motor friction,could be applied to the real-time dynamic control of the platform,through which the calculation of the time-varying equivalent inertia is avoided.Finally,simulations with typically desired trajectory inputs are presented and the performance of the Stewart platform is determined.With this approach,the multi-body dynamics of the electrical Stewart platform is better understood.展开更多
This paper reported a wine-derived lactic acid bacterium,Lactiplantibacillus plantarum XJ25,which exhibited higher cell viability under acid stress upon methionine supplementation.Cellular morphology and the compositi...This paper reported a wine-derived lactic acid bacterium,Lactiplantibacillus plantarum XJ25,which exhibited higher cell viability under acid stress upon methionine supplementation.Cellular morphology and the composition of the cytomembrane phospholipids revealed a more solid membrane architecture presented in the acid-stressed cells treated with methionine supplementation.Transcriptional analysis showed L.plantarum XJ25 reduced methionine transport and homocysteine biosynthesis under acid stress.Subsequent overexpression assays proved that methio-nine supplementation could alleviate the cell toxicity from homocysteine accumulation under acid stress.Finally,L.plantarum XJ25 employed energy allocation strategy to response environmental changes by balancing the uptake methionine and adjusting saturated fatty acids(SFAs)in membrane.These data support a novel mechanism of acid resistance involving methionine utilization and cellular energy distribution in LAB and provide crucial theoretical clues for the mechanisms of acid resistance in other bacteria.展开更多
基金supported by National Natural Science Foundation of China(52074321)Natural Science Foundation of Beijing Municipality,China(3192026)。
文摘At high cycles of steam huff&puff,oil distribution in reservoirs becomes stronger heterogeneity due to steam channeling.Thermal solidification agent can be used to solve this problem.Its solution is a lowviscosity liquid at normal temperature,but it can be solidified above 80℃.The plugging degree is up to 99%at 250℃.The sweep efficiency reaches 59.2%,which is 7.3%higher than pure steam injection.In addition,simultaneous injection of viscosity reducer and/or nitrogen foams can further enhance oil recovery.The mechanism of this technology depends on its strong plugging ability,which changes the flowing pattern of steam to effectively mobilize remaining oil.Viscosity reducer and nitrogen foams further expand the sweep range and extends the effective period.Therefore,thermal solidification agent can plug steam channeling paths and adjust steam flowing direction to significantly enhance oil recovery at high cycles of steam huff&puff.
基金Funded by National Natural Science Foundation of China(No.51474170)the Key Laboratory Project of Shaanxi Provincial Department of Education(No.20js075)。
文摘The ultra-fine grained(UFG)pure titanium was prepared by equal channel angular pressing(ECAP)and rotary swaging(RS).The strain controlled low cycle fatigue(LCF)test was carried out at room temperature.The fatigue life prediction model and mean stress relaxation model under asymmetrical stress load were discussed.The results show that the strain ratio has a significant effect on the low cycle fatigue performance of the UFG pure titanium,and the traditional Manson-coffin model can not accurately predict the fatigue life under asymmetric stress load.Therefore,the SWT mean stress correction model and three-parameter power curve model are proposed,and the test results are verified.The final research shows that the threeparameter power surface model has better representation.By studying the mean stress relaxation phenomenon under the condition of R≠-1,it is revealed that the stress ratio and the strain amplitude are the factors that significantly afiect the mean stress relaxation rate,and the mean stress relaxation model with the two variables is calculated to describe the mean stress relaxation phenomenon of the UFG pure titanium under different strain ratios.The fracture morphology of the samples was observed by SEM,and it was concluded that the final fracture zone of the fatigue fracture of the UFG pure titanium was a mixture of ductile fracture and quasi cleavage fracture.The toughness of the material increases with the increase of strain ratio at the same strain amplitude.
基金Beijing Natural Science Foundation (Grant No. 3194048)China Friction Stir Welding Center and to Beijing Key Laboratory of Pipeline Critical Technology and Equipment for Deepwater Oil & Gas Development (Grant No. BIPT2018006) for the financial support
文摘Friction stir welding was used to join two AA2060-T8 plates,and then the effect of precipitate evolution on microstructure and corrosion behavior of the joint was investigated.The evolution of precipitates on the top surface of the joint was characterized by scanning electron microscopy and transmission electron microscopy.The corrosion behaviors of different regions in the joint were investigated by an electrochemistry method and an alternating salt spray exposure.The corrosion was mainly dependent on the nature of precipitates in each region of the joint.The shoulder affected zone had the worst corrosion resistance as a result of the re-dissolved ofθ′(Al2Cu),T1(Al2CuLi)andδ′(Al3Li)phases,the formation of intergranular precipitates and precipitate-free zones.However,the thermomechanically affected zone had a slightly improved corrosion resistance because it had no intergranular precipitates.The heat affected zone and base metal had the best corrosion resistance.
基金supported by a grant from the National Natural Science Foundation of China (No. 81874324,81473280,U1608283)the Natural Science Foundation of Liaoning (No. 20170540293)Dalian Science and technology innovation fund (No. 2018J12SN065).
文摘This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma concentration-time curve(AUC)of cilastatin were significantly increased,while renal clearance and cumulative urinary excretion of cilastatin were decreased.At the same time,imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1(hOAT1)-HEK293 and human OAT3(hOAT3)-HEK293 cells.Probenecid,p-aminohippurate,and benzylpenicillin inhibited the uptake of imipenem and cilastatin in rat kidney slices and in hOAT1-and hOAT3-HEK 293 cells,respectively.The uptakes of imipenem and cilastatin in hOAT1-and hOAT3-HEK 293 cells were significantly higher than that in mock-HEK-293 cells.Moreover,the K m values of cilastatin were increased in the presence of imipenem with unchanged V max,indicating that imipenem inhibited the uptake of cilastatin in a competitive manner.When imipenem and cilastatin were co-administered,the level of imipenem was higher compared with imipenem alone both in vivo and in vitro.But,cilastatin significantly inhibited the uptake of imipenem when dehydropeptidase-1(DPEP1)was silenced by RNAi technology in hOAT1-and hOAT3-HEK 293 cells.In conclusion,imipenem and cilastatin are the substrates of OAT1 and OAT3.OAT1 and OAT3 mediate the DDI between imipenem and cilastatin.Meanwhile,cilastatin also reduces the hydrolysis of imipenem by inhibiting the uptake of imipenem mediated by OAT1 and OAT3 in the kidney as a complement.
基金supported by the National Natural Science Foundation of China(Nos.81874324,81473280,U1608283,81603186)
文摘To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam,renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats.A bacteremia model was established to investigate the pharmacokinetic properties of piperacillin and tazobactam under different conditions.Renal slices were taken to examine the uptake of piperacillin and tazobactam.Pharmacokinetic studies ofβ-lactamase in rats were performed to study the contribution of rOat1/3 to the inhibition of tazobactam onβ-lactamase.The AUC(from 2.93±0.58 to 6.52±1.44 mg·min/ml)and the plasma clearance(CL P)(from 2.41±1.20 to 0.961±0.212 ml/min/kg)of tazobactam were both altered after the intravenous coadministration of piperacillin and tazobactam in the bacteremia rats.The renal clearance(CL R)of tazobactam decreased from 1.30±0.50 to 0.361±0.043 ml/min/kg.In summary,there was a beneficial interaction between piperacillin and tazobactam mediated by rOat1 and rOat3.Piperacillin enhances the inhibitory effect of tazobactam onβ-lactamase through the inhibition of rOat1 and rOat3 in rats.The contribution rate of rOat1/3 for the synergistic effect was 20%when the two drugs were coadministered.
基金supported by Key R&D Program of Shandong Province,China(Grant No.2021CXGC011203).
文摘This study presents a detailed investigation into the soil arching effects within deep foundation pits(DFPs),focusing on their mechanical behavior and implications for structural design.Through rigorous 3D finite element modeling and parameter sensitivity analyses,the research explores the formation,geometric characteristics,and spatial distribution of soil arching phenomena.The investigation encompasses the influence of key parameters such as elastic modulus,cohesion,and internal friction angle on the soil arching effect.The findings reveal that soil arching within DFPs exhibits distinct spatial characteristics,with the prominent arch axis shifting as excavation depth progresses.Optimal soil arching is observed when the pile spacing approximates three times the pile diameter,enhancing soil retention and minimizing deformation risks.Sensitivity analyses highlight the significant impact of soil parameters on soil arching behavior,underscoring the critical role of cohesive forces and internal friction angles in shaping arching characteristics.By elucidating the interplay between soil parameters and soil arching effects,the research provides insights for optimizing pile spacing and structural stability.
基金supported by National Natural Science Foundation of China(grants:81573489,81522047,81730103,81320108027,81660618,and 81773808)the National Key Research and Development Program(grant:2017YFE0109900 and 2017YFC0909303,China)+5 种基金the 111 project(grant:B16047,China)the Key Laboratory Foundation of Guangdong Province(grant:2017B030314030,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y093,China)National Engineering and Technology Research Center for New drug Druggability Evaluation(Seed Program of Guangdong Province,2017B090903004,China)Natural Science Foundation of Guangdong(grant:2017A030311018 and 2015A030313124,China)National Institutes of Health(grants No.R01CA225958 and R01GM113888 to Ai-Ming Yu,USA).
文摘Pharmacokinetics(PK)is the study of the absorption,distribution,metabolism,and excretion(ADME)processes of a drug.Understanding PK properties is essential for drug development and precision medication.In this review we provided an overview of recent research on PK with focus on the following aspects:(1)an update on drug-metabolizing enzymes and transporters in the determination of PK,as well as advances in xenobiotic receptors and noncoding RNAs(ncRNAs)in the modulation of PK,providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy;(2)current status and trends in assessing drug-drug interactions,especially interactions between drugs and herbs,between drugs and therapeutic biologies,and microbiota-mediated interactions:(3)advances in understanding the effects of diseases on PK,particularly changes in metabolizing enzymes and transporters with disease progression;(4)trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies:(5)emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes,especially non-P450s.Existing challenges and perspectives on future directions are discussed,and may stimulate the development of new research models,technologies,and strategies towards the development of better drugs and improved clinical practice.
基金supported by a grant from the National Natural Science Foundation of China,China(Nos.81874324,81473280,and U1608283)Dalian Science and technology innovation found,China(No.2018J12SN065)
文摘Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I(DHP-I),was developed. In present study, the potential roles of renal organic anion transporters(OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated in vitro and in rabbits. Our results indicated that imipenem and cilastatin were substrates of h OAT1 and h OAT3. Cilastatin inhibited h OAT1/3-mediated transport of imipenem with IC50 values comparable to the clinical concentration, suggesting the potential to cause a clinical drug–drug interaction(DDI). Moreover,imipenem exhibited h OAT1/3-dependent cytotoxicity, which was alleviated by cilastatin and probenecid. Furthermore, cilastatin and probenecid ameliorated imipenem-induced rabbit acute kidney injury, and reduced the renal secretion of imipenem. Cilastatin and probenecid inhibited intracellular accumulation of imipenem and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells. Renal OATs, besides DHP-I, was also the target of interaction between imipenem and cilastatin, and contributed to the nephrotoxicity of imipenem. This therefore gives in part the explanation about the mechanism by which cilastatin protected against imipenem-induced nephrotoxicity. Thus, OATs can potentially be used as a therapeutic target to avoid the renal adverse reaction of imipenem in clinic.
文摘Universal challenge lies in torque feedback accuracy for steer-by-wire systems,especially on uneven and low-friction road.Therefore,this paper proposes a fusion method based on Kalman filter that combines a dynamics-reconstruction method and disturbance observer-based method.The dynamics-reconstruction method is designed according to the vehicle dynamics and used as the prediction model of the Kalman filter.While the disturbance observer-based method is performed as an observer model of the Kalman filter.The performance of all three methods is comprehensively evaluated in a hardware-in-the-loop system.Experimental results show that the proposed fusion method outperforms dynamics reconstruction method and disturbance observer-based method.Specifically,compared with the dynamics-reconstruction method,the root mean square error is reduced by 36.58%at the maximum on the flat road.Compared with the disturbance observer-based method,the root mean square error is reduced by 39.11%at the maximum on different-friction and uneven road.
基金supported by the National Natural Science Foundation of China(Nos.U1760201,51974220,52034005)the Innovation Capacity Support Project of Shaanxi Province(No.2020KJXX-077)+4 种基金the National Key Research and Development Program of China(No.2017YFB0306202)the Key Research and Development Program of Shaanxi Province(Grant No.2020ZDLGY13-06)the Key Industrial Research Program of Shaanxi Province(Grant No.2017ZDXM-GY-037)the Natural Science Basic Research Program of Shaanxi Province(Grant Nos.2019JQ-111,2019JQ-769)the Xi’an Science and Technology Project(Grant No.201805033YD11CG17(8))。
文摘In this work, 20-mm-thick aluminum-alloy plates were joined via friction stir welding. The temperature gradient was reduced by reducing the surface welding heat input to achieve uniformity of the mechanical properties across the thick plate joints. The welding temperature was measured using thermocouples. The microstructures were observed via electron backscatter diff raction and transmission electron microscopy. The tensile properties of the samples sliced along the thickness direction of the joint were evaluated. The results show that the highest welding peak temperature is 430℃ on the advancing side on the top surface of the joint. The grain size gradually decreased along the thickness direction, and grain refi nement was due to the combination of continuous, discontinuous, and geometric dynamic recrystallization. The tensile properties of the sliced samples were found to be uniform, and the ultimate tensile strength reached 62% of that of the base metal. The main strengthening mechanism of the Al–Zn–Mg–Cu alloy joints consists of precipitation strengthening. In addition, the η ` → η phase transition and grain coarsening in the heat-affected zone were found to be responsible for the fracture of the joints.
文摘For an electrical six-degree-of-freedom Stewart platform,it is difficult to compute the equivalent inertia of each motor in real time,as the inertia is time-varying.In this study,an analysis using Kane's equation is undertaken of the driven torque of the movements of motor systems(including motor friction,movements of motor systems along with the actuators,rotation around axis of rotors and snails),as well as driven torque of the platform and actuators.The electromagnetic torque was calculated according to vector-controlled permanent magnet synchronous motor(PMSM) dynamics.By equalizing the driven torque and electromagnetic torque,a model was established.This method,taking into consideration the influence of counter electromotive force(EMF) and motor friction,could be applied to the real-time dynamic control of the platform,through which the calculation of the time-varying equivalent inertia is avoided.Finally,simulations with typically desired trajectory inputs are presented and the performance of the Stewart platform is determined.With this approach,the multi-body dynamics of the electrical Stewart platform is better understood.
基金supported by the National Natural Science Foundation of China(32072206)the National Key R&D Program of China(2019YFD1002503)the China Technology Agriculture Research System(CARS-29-jg-3).
文摘This paper reported a wine-derived lactic acid bacterium,Lactiplantibacillus plantarum XJ25,which exhibited higher cell viability under acid stress upon methionine supplementation.Cellular morphology and the composition of the cytomembrane phospholipids revealed a more solid membrane architecture presented in the acid-stressed cells treated with methionine supplementation.Transcriptional analysis showed L.plantarum XJ25 reduced methionine transport and homocysteine biosynthesis under acid stress.Subsequent overexpression assays proved that methio-nine supplementation could alleviate the cell toxicity from homocysteine accumulation under acid stress.Finally,L.plantarum XJ25 employed energy allocation strategy to response environmental changes by balancing the uptake methionine and adjusting saturated fatty acids(SFAs)in membrane.These data support a novel mechanism of acid resistance involving methionine utilization and cellular energy distribution in LAB and provide crucial theoretical clues for the mechanisms of acid resistance in other bacteria.