DMA选择性激动心力衰竭大鼠离体心室肌细胞Na^(+)/Ca^(2+)交换体提高心肌变力

目的二甲基氨氯吡咪(DMA)作为强效的选择性Na^(+)/H^(+)交换体抑制剂,可以特异性增强大鼠心肌细胞的Na^(+)/Ca^(2+)交换(NCX)电流。NCX是治疗心力衰竭(心衰)的一个有潜力的靶点。本研究拟验证DMA是否增强NCX电流(INa/Ca),诱导Ca^(2+)内流,产生对心衰大鼠心室肌细胞的正性肌力作用。方法采用腹主动脉缩窄法诱导大鼠心衰模型,胶原酶法急性分离正常和心衰大鼠心室肌细胞;采用膜片钳全细胞记录方法测定细胞的I_(Ca-L),I_(Na),I _(K1),I_(to),和I_(Na/Ca),膜电流大小以电流强度表示,在正常和心衰大鼠离体心室肌细胞中观察DMA对主要离子电流的影响。结果DMA(0.1、0.3、1和3μmol/L)对正常和心衰大鼠心室肌细胞NCX内向和外向电流均呈浓度依赖性增加,心衰大鼠心室肌细胞在电位+50mV的外向INa/Ca密度分别增大了(10.78±4.73)%、(31.47±5.47)%、(55.60±16.84)%、(75.01±19.74)%,在电位-100mV的内向INa/Ca密度分别增大了(19.00±6.29)%、(33.51±20.17)%、(55.49±22.56)%、(94.77±15.75)%。DMA诱导的向内NCX电流的增强作用大于对外向NCX电流作用,但DMA对ICa-L、INa、I K1和Ito无明显影响。结论DMA可以双向激动心衰大鼠心肌细胞,DMA的正性肌力作用可能与INa/Ca升高相关。DMA作为一种新的NCX激动剂,为治疗心衰提供新思路。

过饱和度理论及过饱和药物递送系统

在药物研发领域,如何有效提高难溶性药物的溶解与吸收是一个极具挑战的难题。目前,过饱和药物递送系统(Supersaturating drug delivery systems,SDDS)利用药物溶液处于过饱和态的优势,可同时提高难溶性药物的表观溶解度与渗透性。本文对过饱和度的理论及其在药物研发领域中的实际应用进行了系统的综述,介绍了过饱和度的产生与维持、及其与药物吸收的关系,归纳了常用的SDDS技术,并对无定形固体分散体、共晶、无定形/共无定形产生过饱和进行重点阐述。

Preliminary analysis on the source properties and seismogenic structure of the 2017 M_s7.0 Jiuzhaigou earthquake

At GMT time 13：19, August 8, 2017, an M1.0 earthquake struck the Jiuzhaigou region in Sichuan Province, China, causing severe damages and casualties. To investigate the source properties, seismogenic structures, and seismic hazards, we systematically analyzed the tectonic environment, crustal velocity structure in the source region, source parameters and rupture process, Coulomb failure stress changes, and 3-D features of the rupture plane of the Jiuzhaigou earthquake. Our results indicate the following： （1） The Jiuzhaigou earthquake occurred on an unmarked fault belonging to the transition zone of the east Kunlun fault system and is located northwest of the Huya fault. （2） Both the mainshock and aftershock rupture zones are located in a region where crustal seismic velocity changes dramatically. Southeast to the source region, shear wave velocity at the middle to lower crust is significantly low, but it rapidly increases northeastward and lies close to the background velocity across the rupture fault. （3） The aftershock zone is narrow and distributes along the northwest-southeast trend, and most aftershocks occur within a depth range of 5-20 km. （4） The focal mechanism of the Jiuzhaigou earthquake indicates a left-lateral strike-slip fault, with strike, dip, and rake angles of 152~, 74~ and 8~, respectively. The hypocenter depth measures 20 km, whereas the centroid depth is about 6 kin. The co-seismic rupture mainly concentrates at depths of 3-13 km, with a moment magnitude （Mw） of 6.5. （5） The co-seismic rupture also strengthens the Coulomb failure stress at the two ends of the rupture fault and the east segment of the Tazang fault. Aftershocks relocation results together with geological surveys indicate that the causative fault is a near vertical fault with notable spatial variations： dip angle varies within 660-89~ from northwest to southeast and the average dip angle measures -84~. The results of this work are of fundamental importance for further studies on the source characteristics, tectonic environment, and seismic hazard evaluation of the Jiuzhaigou earthquake.

Microstructure and Mechanical Properties of Multilayertextured 2D Carbon/Carbon Composites

Two-dimensional（2D） carbon/carbon（C/C） composites with multilayered texture, especially with different thickness of high-textured（HT） pyrocarbon layer, were prepared by isothermal, isobaric chemical vapor infiltration（CVI） technique. The influence of matrix microstructure on mechanical properties of C/C composites was investigated by polarized light microscopy, scanning electron microscopy and three-point bending test. The results show that the samples with multilayer-textured pyrocarbon matrix own a higher flexural strength than the one with pure medium-textured structure, which is attributed to multiple crack deflection and interfacial sliding between different textured pyrocarbon layers and between sub-layers within HT layer. The increase in thickness of HT pyrocarbon layer improves the plasticity of the samples and renders the fracture in pseudo-plastic behavior.

Misalignment Tolerance in One-side and Symmetric Loading Hopkinson Pressure Bar Experiments

The split-Hopkinson pressure bar(SHPB)is a widely used experimental technique for studying the mechanical properties of materials at high strain rates.There are two kinds of loading methods applied in the SHPB technique,namely one-side loading and symmetric loading.However,the experimental accuracy of the two loading methods is affected by the interface contact.The present study focused on the inadequate contact caused by the misalignment of the pressure bars.The commercial software ABAQUS was used for simulations.The result shows that the inadequate contact caused by the alignment of the bars has a non-negligible effect on the calculated results.Compared with the one-side loading Hopkinson pressure bar,the symmetric loading Hopkinson pressure bar has a more relaxed requirement for the alignment of the bars.The conclusion arrived at in this paper can help researchers to make a reasonable choice between one-side and symmetric loading Hopkinson pressure bars according to actual requirements.

Experimental research of condensate blockage and mitigating effect of gas injection

The condensate blockage causes a substantial decrease in well productivity for gas condensate reservoirs.Based on the previous studies,a novel experimental method was designed to evaluate condensate blockage and the mitigating effect of gas injection.The method considers the stacking effect in the near wellbore region and the gas flow in the far wellbore region.There is an intermediate vessel containing condensate gas at the entrance of core holder in the experimental apparatus.In the process of pressure depletion experiment in a long core model,the vessel is connected to the core and the pressure of the vessel remains above the dew point pressure.The seriousness of condensate blockage is investigated by this research.When pressure drops to maximum retrograde condensation pressure,the gas permeability decreases by 80%compared with the initial gas permeability.Contrastive experiments were conducted to study the removal effect of different injection fluids and different injection volumes.The results show that CO2 injection is more effective than methanol in mitigating condensate blockage and the optimal CO2 injection volume is around 0.15 HCPV。