Effect of Strain Ratio on Fatigue Model of Ultra-fine Grained Pure Titanium

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.

析出相演变对2060-T8铝合金搅拌摩擦焊接头腐蚀行为的影响（英文）

采用搅拌摩擦焊对2060-T8铝合金板材进行焊接,研究析出相演变对接头显微组织和腐蚀行为的影响。在采用扫描电镜和透射电镜表征2060-T8铝合金搅拌摩擦焊接头上表面析出相演变行为的基础上,通过电化学试验和交变盐雾腐蚀试验研究接头各区域的腐蚀行为。研究表明,腐蚀行为与各区析出相的特性密切相关,由于θ′(Al_2Cu)相、T1(Al_2CuLi)相和δ′(Al_3Li)相的回溶,以及晶界相和无沉淀析出带的出现,轴肩影响区是腐蚀最敏感的区域;因为不存在晶界析出相,相比轴肩影响区,热机械影响区的抗腐蚀性能略有提高;热影响区和母材的抗腐蚀性能最好。

纯锆的动态力学行为及绝热剪切带

使用分离式霍普金森压杆装置(SHPB)对纯锆在室温下进行动态压缩实验,应变速率为800～4000 s-1。采用金相显微镜和Quanta200型扫描电子显微镜对绝热剪切带及压缩断口进行观察。结果表明,纯锆具有较低的应变速率敏感性,由于高应变条件下产生了高密度的孪晶,材料硬化显著增强,真应力-真应变曲线随应变增加呈上升趋势,最大抗压强度为843 MPa。纯锆试样中观察到明显的绝热剪切带,且沿剪切带出现裂纹,压缩断口呈韧性断裂。绝热剪切带的出现和发展是材料失效的主要原因。对剪切带内部的温度进行了估算,结果表明,纯锆剪切带内部最高温度为1564℃。

润滑气体对箔片动压止推气体轴承静特性的影响分析

以新型鼓泡箔片动压止推气体轴承为研究对象,采用有限差分法和Newton-Raphson迭代法通过Matlab软件编程求解流固耦合的数值模型,得到了同一温度下不同润滑气体以及同一润滑气体在不同温度下的轴承气膜压力分布、厚度分布和承载能力;研究了润滑气体物性参数对航空涡轮冷却器中箔片动压止推气体轴承静特性的影响规律。结果表明:动力黏度较大的润滑气体形成较大的气膜压力和气膜厚度分布,并产生较高的承载能力;随着轴承长时间高速运行产生的高温导致的润滑气体物性参数的改变有利于提高轴承的承载能力。

Organic anion transporters also mediate the drug–drug interaction between imipenem and cilastatin

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.

Piperacillin enhances the inhibitory effect of tazobactam on β-lactamase through inhibition of organic anion transporter 1/3 in rats

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.

基于SSR-HRM技术的4种药用天麻变型遗传多样性及遗传结构分析

目的比较乌天麻Gastrodia elata f.glauca、绿天麻G.elata f.viridis、红天麻G.elata f.elata和黄天麻G.elata f.flavida 4种药用天麻变型的遗传多样性、遗传结构和遗传信息差异,为天麻新品种选育提供依据。方法从不同产地收集了40份不同天麻变型的花茎。应用简单重复序列(simple sequence repeat,SSR)分子标记与高分辨率熔解曲线(high-resolution melting,HRM)相结合技术,通过聚丙烯酰胺凝胶电泳,从80对引物中筛选出15对多态性高的SSR引物。对这些天麻花茎样品进行实时荧光定量PCR扩增,统计遗传多样性参数,分析群体遗传结构,结合40份天麻的HRM数据进行聚类分析。结果从15对SSR引物检测到114个等位基因,平均每对引物7.6个。天麻样品的观测杂合度(observed heterozygosity,Ho)、期望杂合度(expected heterozygosity,He)、和Nei’s多样性指数(Nei's diversity index,Nei)的平均值分别为0.9813、0.8019和0.8121,表明天麻的遗传多样性丰富。这4种天麻变型的遗传多样性不同,从高到低依次为乌天麻、绿天麻、红天麻和黄天麻。SSR-HRM分析将这40份天麻样品分为4个基因型,各天麻变型的大多数样品分布在不同的基因型中。这4种天麻变型之间的遗传距离不同,乌天麻与绿天麻遗传距离最近,与黄天麻遗传距离最远。结论SSR-HRM技术对天麻基因分型更准确。这4种天麻变型的遗传信息不同,但存在基因交流现象。乌天麻与绿天麻亲缘关系最近,与红天麻次之,与黄天麻亲缘关系最远。可利用不同天麻变型遗传信息差异进行新品种选育。

室温ECAP变形纯钛孪生行为研究

室温下对纯钛进行多道次等径弯曲通道变形(ECAP),分别采用光学显微镜(OM)、透射电镜(TEM)、电子背散射衍射仪(EBSD)、室温拉伸和显微硬度观察,测试纯钛变形过程组织演变和力学性能变化规律,探讨纯钛室温变形机制和孪生行为。结果表明,纯钛ECAP变形过程中出现■拉伸孪晶和■压缩孪晶,随着挤压道次的增大,孪晶数量先增大后减小。孪晶的出现有效改变晶格取向,激发进一步位错滑移,辅助塑性变形过程,使纯钛显微组织有效细化,经过4道次ECAP变形,平均晶粒尺寸由约63.79μm细化至约2.81μm。1道次变形后晶粒细化效果最显著,平均晶粒尺寸比变形前减小约94%;随着变形道次的增加,晶粒细化效果减弱,4道次变形后平均晶粒尺寸累积减小约95.6%。同时,大量位错、孪晶和亚晶的形成,使得位错、孪晶以及亚晶之间的相互作用加强,显著提高了纯钛的屈服强度和显微硬度,4道次变形后,屈服强度从215 MPa增加到600 MPa,增幅为179%;显微硬度从HV 129增加到HV 200。由于1道次变形后晶粒细化效果最显著,并且出现大量孪晶和位错,屈服强度与硬度的增幅也最大。

ECAP制备超细晶生物医用钛及钛合金的研究进展

钛及钛合金由于质轻、弹性模量低、生物相容性佳和骨整合性优异,已成为应用最广泛的生物医学金属材料之一。然而,较低的塑性、耐腐蚀性能和耐磨损性能限制了其发展和应用。剧烈塑性变形被认为是对金属材料最有效的晶粒细化方法之一,其中,等通道转角挤压(ECAP)是制备块状超细晶(UFG)/纳米晶金属材料的常用技术。通过ECAP变形,可以制备具有优异综合性能的UFG钛及钛合金。本文综述了生物医用UFG钛及钛合金的ECAP制备方式,着重讨论了ECAP变形对钛及钛合金的组织、力学性能、耐腐蚀性能和耐磨损性能的影响,分析了钛及钛合金的ECAP变形机制和晶粒细化机制,提出了通过ECAP变形结合传统塑性加工和变形后热处理来进一步优化钛及钛合金综合性能的想法。

原始晶粒尺寸对ECAP变形纯钛组织性能的影响

室温下,对923及1023 K退火1 h所得的不同原始晶粒尺寸的工业纯钛进行ECAP变形。通过TEM、EBSD、室温拉伸和显微硬度测试研究原始晶粒尺寸对ECAP变形纯钛组织性能的影响。探讨纯钛ECAP变形孪生行为和变形机制。结果表明,退火温度越高,原始晶粒尺寸越大。1道次变形后,1023 K退火纯钛的晶粒细化效果更显著。4道次变形后,923 K退火纯钛的组织更细小均匀。随着变形道次的增加,屈服强度不断增大,1道次变形后增幅最大,约为100%,且原始晶粒尺寸越大,强度增幅越大。纯钛ECAP变形机制包括位错滑移和孪生,原始晶粒尺寸越大,孪晶数量越多。

纯钛的热变形行为及显微组织演变

用Gleeble-3500热模拟试验机对退火态纯钛试样,在变形温度298-723 K、应变速率10^-4-10-1s^-1下进行热压缩试验,研究变形温度和应变速率对其热变形行为及组织演变的影响。结果表明：纯钛的压缩行为与变形温度和应变速率存在相关性;当应变速率一定时,流变应力随变形温度的升高而减小;当变形温度一定时,流变应力随应变速率的增大而增大。显微组织观察结果显示：在低温或高应变速率下变形时,形变组织主要为大尺寸等轴晶和孪晶,随着温度的升高或应变速率的降低,再结晶晶粒逐渐增多,孪晶数量减少,直至消失。

Current trends in drug metabolism and pharmacokinetics

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.

Cilastatin protects against imipenem-induced nephrotoxicity via inhibition of renal organic anion transporters(OATs)

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.

Kalman Filter-Based Fusion Estimation Method of Steering Feedback Torque for Steer-by-Wire Systems

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.

Microstructure and Mechanical Properties in Friction Stir Welded Thick Al–Zn–Mg–Cu Alloy Plate

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.

Dynamic modeling of a 6-degree-of-freedom Stewart platform driven by a permanent magnet synchronous motor

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.

Methionine addition improves the acid tolerance of Lactiplantibacillus plantarum by altering cellular metabolic flux,energy distribution,lipids composition

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.