联用多步骤虚拟筛选方法发现具有新母核的GABAA受体正性变构调节剂

GABAA受体主要介导哺乳动物中枢神经系统的抑制性信号传递,是镇静催眠药的关键靶点。在寻找具有新母核的镇静催眠药的过程中,计算机辅助药物设计(CADD)方法显示出巨大的优势。在这项研究中,首先,我们通过机器学习模型、分子对接模型和分子力学广义玻恩比表面积(MMGBSA)方法筛选了来自于商业数据库中的41112种化合物。经过筛选,我们得到了16个化合物,然后我们通过全细胞膜片钳电生理学实验验证了4个结构新颖的化合物确实为有效的GABAA受体正性变构调节剂。其中,化合物GPR120在细胞水平和动物水平都得到了实验验证。在重组表达α1β2γ2型受体的皮层神经元中,在10和50µmol∙L^(−1)浓度下,GPR120可将GABA EC3-10电流分别增强71.5%和163.8%。通过全分解贡献分析和点突变实验,我们发现GPR120与GABAA受体结合的关键位点是H102,与阳性药物地西泮相似。为了进一步验证GPR120在动物水平上的功能,我们进行了运动活动测试和翻正反射消失(LORR)实验。GPR120对小鼠的运动活动有抑制作用,6 h后可恢复,说明GPR120是一种中度镇静剂。在戊巴比妥钠(PB)诱导的翻正反射消失实验中,与生理盐水组相比,GPR120(20 mg∙kg^(−1))可显著缩短开始LORR的时间并延长LORR的持续时间。综上所述,通过联用多种虚拟筛选方法,我们发现了GPR120是一种具有新型母核的中度强度镇静剂。

Using restored two-dimensional X-ray images to reconstruct the three-dimensional magnetopause

Astronomical imaging technologies are basic tools for the exploration of the universe,providing basic data for the research of astronomy and space physics.The Soft X-ray Imager(SXI)carried by the Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)aims to capture two-dimensional(2-D)images of the Earth’s magnetosheath by using soft X-ray imaging.However,the observed 2-D images are affected by many noise factors,destroying the contained information,which is not conducive to the subsequent reconstruction of the three-dimensional(3-D)structure of the magnetopause.The analysis of SXI-simulated observation images shows that such damage cannot be evaluated with traditional restoration models.This makes it difficult to establish the mapping relationship between SXIsimulated observation images and target images by using mathematical models.We propose an image restoration algorithm for SXIsimulated observation images that can recover large-scale structure information on the magnetosphere.The idea is to train a patch estimator by selecting noise–clean patch pairs with the same distribution through the Classification–Expectation Maximization algorithm to achieve the restoration estimation of the SXI-simulated observation image,whose mapping relationship with the target image is established by the patch estimator.The Classification–Expectation Maximization algorithm is used to select multiple patch clusters with the same distribution and then train different patch estimators so as to improve the accuracy of the estimator.Experimental results showed that our image restoration algorithm is superior to other classical image restoration algorithms in the SXI-simulated observation image restoration task,according to the peak signal-to-noise ratio and structural similarity.The restoration results of SXI-simulated observation images are used in the tangent fitting approach and the computed tomography approach toward magnetospheric reconstruction techniques,significantly improving the reconstruction results.Hence,the proposed technology may be feasible for processing SXI-simulated observation images.

Large-scale spatial data visualization method based on augmented reality

Background A task assigned to space exploration satellites involves detecting the physical environment within a certain space.However,space detection data are complex and abstract.These data are not conducive for researchers'visual perceptions of the evolution and interaction of events in the space environment.Methods A time-series dynamic data sampling method for large-scale space was proposed for sample detection data in space and time,and the corresponding relationships between data location features and other attribute features were established.A tone-mapping method based on statistical histogram equalization was proposed and applied to the final attribute feature data.The visualization process is optimized for rendering by merging materials,reducing the number of patches,and performing other operations.Results The results of sampling,feature extraction,and uniform visualization of the detection data of complex types,long duration spans,and uneven spatial distributions were obtained.The real-time visualization of large-scale spatial structures using augmented reality devices,particularly low-performance devices,was also investigated.Conclusions The proposed visualization system can reconstruct the three-dimensional structure of a large-scale space,express the structure and changes in the spatial environment using augmented reality,and assist in intuitively discovering spatial environmental events and evolutionary rules.

Research advances of magnesium and magnesium alloys worldwide in 2022

More than 4600 papers in the field of Mg and Mg alloys were published and indexed in the Web of Science(WoS)Core Collection database in 2022.The bibliometric analyses indicate that the microstructure,mechanical properties,and corrosion of Mg alloys are still the main research focus.Bio-Mg materials,Mg ion batteries and hydrogen storage Mg materials have attracted much attention.Notable contributions to the research and development of magnesium alloys were made by Chongqing University(>200 papers),Chinese Academy of Sciences,Shanghai Jiao Tong University,and Northeastern University(>100 papers)in China,Helmholtz Zentrum Hereon in Germany,Ohio State University in the USA,the University of Queensland in Australia,Kumanto University in Japan,and Seoul National University in Korea,University of Tehran in Iran,and National University of Singapore in Singapore,etc.This review is aimed to summarize the progress in the development of structural and functional Mg and Mg alloys in 2022.Based on the issues and challenges identified here,some future research directions are suggested.

Optimization on microstructure,mechanical properties and damping capacities of duplex structured Mg–8Li–4Zn–1Mn alloys

Optimizing the mechanical properties and damping capacity of the duplex-structured Mg–Li–Zn–Mn alloy by tailoring the microstructure via hot extrusion was investigated.The results show that the Mg–8Li–4Zn–1Mn alloy is mainly composed ofα-Mg,β-Li,Mg–Li–Zn and Mn phases.The microstructure of the test alloy is refined owing to dynamic recrystallization(DRX)during hot extrusion.After hot extrusion,the crushed precipitates are uniformly distributed in the test alloy.The yield strength(YS),ultimate tensile strength(UTS),and elongation(EL)of as-extruded alloy reach 156 MPa,208 MPa,and 32.3%,respectively,which are much better than that of as-cast alloy.Furthermore,the as-extruded and as-cast alloys both exhibit superior damping capacities,with the damping capacity(Q^(-1))of 0.030 and 0.033 at the strain amplitude of 2×10^(-3),respectively.The mechanical properties of the test alloy can be significantly improved by hot extrusion,whereas the damping capacities have no noticeable change,which indicates that the duplex-structured Mg–Li alloys with appropriate mechanical properties and damping properties can be obtained by alloying and hot extrusion.

Applications of magnesium alloys for aerospace:A review

With the increasingly excellent performance of magnesium alloy materials, magnesium alloys are increasingly widely used under the urgent need for weight reduction in aerospace applications. However, due to the severe aviation environment, the strength, corrosion resistance and electrical conductivity of magnesium alloy materials need to be further improved. Many scholars are committed to studying higher comprehensive mechanical properties. Besides, they have studied surface treatment processes with space application characteristics, such as high emissivity oxidation and high anti-corrosion electroplating. To further improve the safety and reliability of magnesium alloys and expand their applications, this paper discusses several kinds of magnesium alloys and summarizes their research progress. The whole manuscript should be revised by an expert who has more experience on English writing. At the same time, the surface treatments of magnesium alloy materials for aerospace are analyzed. Besides, the application of magnesium alloy in aerospace field is summarized. With the in-depth research of many scholars, the improvement of material properties and the development of surface protection and functional technology, it is believed that magnesium alloys will be used in more and more aerospace applications and make more contributions to the aerospace field.

4D打印技术的研究进展

3D打印技术具有能够方便廉价地实现从3D虚拟模型到实体化的优点,在产品设计、快速成型、先进材料等领域得到了广泛的应用。近年来,"4D打印"概念的提出引起了社会和学术界广泛的关注。4D打印技术是在3D打印的基础上引入时间维度,在一定外界刺激的作用下,4D打印刺激响应材料的形状、结构和功能能够随着时间的推移而不断变化。文中对4D打印进行了概述,着重介绍了4D打印材料及其形状记忆效应,总结了4D打印技术在各个领域的应用前景,并结合4D打印研究现状探讨了4D打印技术的发展趋势。

Research advances in magnesium and magnesium alloys worldwide in 2020

Research on magnesium alloys continues to attract great attention,with more than 3000 papers on magnesium and magnesium alloys published and indexed in SCI in 2020 alone.The results of bibliometric analyses show that microstructure control and mechanical properties of Mg alloys are continuously the main research focus,and the corrosion and protection of Mg alloys are still widely concerned.The emerging research hot spots are mainly on functional magnesium materials,such as Mg ion batteries,hydrogen storage Mg materials,and bio-magnesium alloys.Great contributions to the research and development of magnesium alloys in 2020 have been made by Chongqing University,Chinese Academy of Sciences,Central South University,Shanghai Jiaotong University,Northeastern University,Helmholtz Zentrum Geesthacht,etc.The directions for future research are suggested,including:1)the synergistic control of microstructures to achieve high-performance magnesium alloys with concurrent high strength and superior plasticity along with high corrosion resistance and low cost;2)further development of functional magnesium materials such as Mg batteries,hydrogen storage Mg materials,structural-functional materials and bio-magnesium materials;3)studies on the effective corrosion protection and control of degradation rate of magnesium alloys;4)further improvement of advanced processing technology on Mg alloys.

Research advances of magnesium and magnesium alloys worldwide in 2021

More than 4000 papers in the field of Mg and Mg alloys were published and indexed in Web of Science(WoS)Core Collection database in 2021.The bibliometric analyses indicate that the microstructure,mechanical properties,and corrosion of Mg alloys still are the main research focus.Mg ion batteries and hydrogen storage Mg materials have attracted much attention.Significant contributions to the research and development of magnesium alloys were made by Chongqing University,Shanghai Jiaotong University,and Chinese Academy of Sciences in China,Helmholtz Zentrum Hereon in Germany,Ohio State University in the United States,the University of Queensland in Australia,Kumanto University in Japan,and Seoul National University in Korea,University of Tehran in Iran,etc..This review is aimed to summarize the progress in the development of structural and functional Mg and Mg alloys in 2021.Based on the issues and challenges identified here,some future research directions are suggested.

Overview of advancement and development trend on magnesium alloy

Magnesium alloys are characterized by their low density(approximately 1.8g/cm3 for magnesium alloys),high strength,large modulus of elasticity,good heat dissipation,good shock absorption,greater ability to withstand impact load than aluminum alloys,good corrosion resistance to organic matter and alkalinity.According to the statistical analysis of literature data collected by Web of Science Core Collection,it can be found that the growth rate of publications on magnesium alloy during 2008-2018 is significantly higher than the overall growth rate of alloy research papers.In the past 11 years,the Web of Science Core Collection has collected 21,440 papers on magnesium alloys,averaging nearly 2000 papers annually,of which 2768 papers were collected in 2018,an increase of 206%over 2008,accounting for more than one fifth o f the total literature on alloy research.Magnesium alloys have become an important lightweight metallic structural material and have been widely studied worldwide.As the only journal focusing on magnesium alloy research which devoted to the coverage and dissemination of global research on magnesium alloys.This article statistically analyzes all the academic articles published by Journal of Magnesium and Alloys(JMA)from 2013 to 2018 and compares them with all the articles containing magnesium alloy in their titles on the Web of Science during this period.The development trends of magnesium alloys are summarized based on these articles,and the influence and academic value of the articles published by JMA are summarized as well.This paper hopes to better realize the value of JMA,help better spread the academic research of magnesium alloys,and promote the development of global magnesium alloy research.©2019 Published by Elsevier B.V.on behalf of Chongqing University.

Microstructural evolution and enhanced mechanical properties of Mg?Gd?Y?Zn?Zr alloy via centrifugal casting, ring-rolling and aging

A ring-shaped Mg?8.5 Gd?4 Y?1 Zn?0.4 Zr(wt%) alloy was manufactured via centrifugal casting and ring-rolling process. The effects of accumulative ring-rolling reduction amount on the microstructure, texture, and tensile properties of the alloy were investigated. The results indicate that the microstructure of centrifugal cast alloy consists of equiaxed grains and network-like eutectic structure present at grain boundaries. The ring-rolled alloy exhibits a characteristic bimodal microstructure composed of fine dynamic recrystallized(DRXed) grains with weak basal texture and coarse un-DRXed grains with strong basal texture, along with the presence of LPSO phase. With increasing amount of accumulative ring-rolling reduction, the coarse un-DRXed grains are refined via the formation of increasing amount of fine DRXed grains. Meanwhile, the dynamic precipitation of Mg5 RE phase occurs, generating a dispersion strengthening effect. A superior combination of strength and ductility is achieved in the ring-rolled alloy after an accumulative rolling reduction of 80%. The tensile strength of this ring-rolled alloy after peak aging is further enhanced, reaching 511 MPa, while keeping a reasonable ductility. The salient strengthening mechanisms identified include the grain boundary strengthening of fine DRXed grains, dispersion strengthening of dynamic precipitated Mg;RE phase, short fiber strengthening of LPSO lamellae/rods, and precipitation strengthening of nano-sized prismatic β precipitates and basal γ precipitates.

Magnesium-Based Materials for Energy Conversion and Storage

The development of materials for energy conversion and storage systems is essential for the realization of the sustainable and low-carbon society for which China pledged the long-term strategic target to reach peak carbon dioxide(CO_(2))emissions before 2030 and achieve carbon neutrality by 2060.Because the progress in this field can improve the utilization of the intermittent harvested renewable energy.

Research on the microstructure and properties of a multi-pass friction stir processed 6061Al coating for AZ31 Mg alloy

A 6061 Al coating for AZ31 Mg alloy was prepared by multi-pass friction stir welding(FSW)with different travel speeds.The mi-crostructure,mechanical properties of the interfacial region and the corrosion behavior of the coating were investigated systematically.The results indicate that the interfacial intermetallic compounds formed in the stir zone(SZ)consist of mainly Al12Mg17 and Al3Mg2.The inter-metallic compounds in the SZ are significantly increased when the travel speed is increased from 30 mm/min to 60 mm/min.Microhardness measurements and results of shear-tensile tests show that the mechanical properties are influenced by the intermetallic compounds formed in the SZ during FSW.Corrosion tests indicate that the 6061 Al coating can significantly improve the corrosion resistance of AZ31 plate.The 6061 Al coating obtained with a travel speed of 30 mm/min has a maximum corrosion potential E corr of-0.503 V VSE.

A New Method to Determine the Grid Directions in Reservoir Numerical Simulation

Grid direction selection and grid size design are two important elements that need to be considered in the grid direction design in reservoir numerical simulation. Reservoir engineers normally utilize geological data (such as the distribution of fractures, low permeability zones, faults and major stress) and simulation experiences to design the grid direction of simulation model qualitatively. The research of the paper indicates that the key to determine the grid direction is to determine the principal permeability direction. Under the circumstances of few static materials, a new grid direction determination method has been developed by using field data (well location map and inter-well permeability) on the bases of Darcy’s law and tensor analysis theory. The grid direction of WZ11-7 Oilfield simulation model has been determined using four production wells and two production zones (L1 and L3) in WZ11-7-2 well group, the results are in conformity with the geological studied major stress. Therefore, this method can give insights into the numerical simulation study.

Study on S-shaped region of pump turbine based on Omega vortex analysis method and entropy production theory

In order to comprehensively analyze the operation instability of the pump turbine S-shaped region,this paper uses DDES turbulence model to calculate the model pump turbine from the perspective of the evolution law of runner vortex and draft tube vortex rope and entropy production rate,combined with experiments.The results show that the numerical simulation is in good agreement with the experiment.Omega vortex analysis method is more accurate than other vortex recognition methods because it is not affected by the threshold value.The vortices at the runner region under the runaway condition and the turbine brake condition develop towards the vaneless space and the blade pressure surface respectively,which will cause the flow obstruction and blade separation.The overall vorticity of the reverse pump condition is the largest.The vortex rope of the draft tube under runaway and turbine brake conditions is columnar in shape and has very high rotational strength.The vortex rope under reverse pump conditions is prone to fracture and form scattered vortices,impeding the normal movement of the fluid.The entropy production rate of the spanwise surface near the upper ring and the lower crown is greater than the middle spanwise surface due to the boundary layer effect.And the energy dissipation in the runner under reverse pump conditions is characterized by high at both ends of the runner and low in the middle.The energy dissipation near the wall of the straight cone section of the draft tube is large due to the squeezing effect of the vortex rope on the flow.

Microstructure and strengthening mechanism of hot-extruded ultralight Mg-Li-Al-Sn alloys with high strength

Duplex-structured Mg-7Li-2Al-1.5Sn alloys with high strength were fabricated and their strengthening mechanism was investigated.The Mg-7Li-2Al-1.5Sn alloys were prepared by casting and extruded at the temperature of 533 K with an extrusion ratio of 25:1.The microstructure and mechanical properties of Mg-7Li-2Al-1.5Sn alloys were systematically investigated by OM,XRD,SEM,TEM,and tensile tests.The results show that Mg-7Li-2Al-1.5Sn alloys are mainly composed ofα-Mg,β-Li,LiMgAl_(2),Mg_(2)Sn and Li_(2)MgSn phases.The yield strength(YS),ultimate tensile strength(UTS)and elongation(EL)of the extruded alloy at room temperature reach 250 MPa,324 MPa and 11.9%,respectively.A lot of Sn-rich precipitates(Mg_(2)Sn and Li_(2)MgSn)are precipitated during extrusion with an average size of∼14 nm,which is beneficial to the grain refinement.Dynamic recrystallization occurs during hot deformation and the nanoprecipitates effectively refine the dynamic recrystallized(DRXed)grains.Besides,the residual dislocations existed in DRXed and un-DRXed grains result in the dislocation strengthening in the extruded alloy.Mg7Li-2Al-1.5Sn alloys possess excellent high-temperature mechanical properties with the YS,UTS and EL of 200 MPa,237 MPa and 26.7%at 423 K,respectively.Sn-rich precipitates with good thermal stability can effectively prevent grain growth,which is good for the improvement of the high-temperature performance of Mg-Li-Al-Sn alloy.

Constitutive Modeling and Hot Deformation Behavior of Duplex Structured Mg–Li–Al–Sr Alloy

Hot deformation behavior of an as-extruded duplex structured Mg-9Li-3Al-2.5Sr alloy is investigated via hot compression tests conducted at 200-350℃ with strain rate of 0.001-1 s^-1.The flow behavior of Mg-9Li-3Al-2.5Sr alloy can be described accurately by hyperbolic sine constitutive equation and the average activation energy for deformation is calculated as 143.5 k J/mol.Based on a dynamic materials model,the processing maps of Mg-9Li-3Al-2.5Sr alloy which describe the variation of power dissipation efficiency are constructed as a function of temperature and strain rate.The processing maps exhibit an area of discontinuous dynamic recrystallization occurring at 280-300℃ with strain rate of 0.001-0.01 s^-1,which corresponds to the optimum hot working conditions.

Microstructure and Corrosion Properties of Duplex-Structured Extruded Mg-6Li-4Zn-xMn Alloys

The extruded Mg-6 Li-4 Zn-xMn(x=0,0.4,0.8,1.2 wt%)alloys were prepared,and the microstructure of the test alloys was investigated by optical microscopy,scanning electron microscopy and transmission electron microscopy.The corrosion properties were determined by electrochemical measurements and immersion measurements in 3.5%NaCl solution.The results indicate that the extruded Mg-6 Li-4 Zn-xMn alloys are mainly composed ofα-Mg phase,β-Li phase,Mn precipitates and some intermetallic compounds(MgLi_(2)Zn).With the addition of Mn,stable corrosion products were formed on the surface of the test alloy,which can effectively inhibit further corrosion progress and improve the corrosion resistance.Mg-6 Li-4 Zn-1.2 Mn alloy exhibits the best corrosion resistance,attributed to grain refinement,the improvement of the stability of corrosion product film and uniform distribution of fine second phases.