基于IP联合蛋白质组学探讨ENG互作蛋白在bEnd.3细胞中的作用

目的本研究拟筛选并验证在脑微血管内皮细胞(bEnd.3)中Endoglin(ENG)的互作蛋白及其作用。方法采用蛋白质组学和生物信息学技术鉴定并富集ENG互作蛋白,对这些互作蛋白进行亚细胞定位、GO功能注释、IPR注释和蛋白互作网络等分析。将以上分析筛选出的ENG互作蛋白,采用免疫共沉淀(IP)实验、细胞免疫荧光(IF)和蛋白免疫印迹(WB)技术进行验证和对比,探究ENG互作蛋白在棕榈酸(PA)、基因沉默和过表达ENG处理bEnd.3细胞中的表达变化及作用。结果通过蛋白质组学分析,bEnd.3细胞中ENG互作蛋白在亚细胞定位分析中细胞骨架相关成分呈现出较高的占比;通过GO注释和IPR注释进一步发现,是细胞骨架中的中间纤维和微丝蛋白呈现较高的富集状态。ENG与细胞骨架蛋白互作热力图结果显示,与对照组相比,PA处理的bEnd.3细胞中微丝蛋白Filamin B(Flnb)数值显著降低。IP和IF结果显示,bEnd.3细胞中ENG与Flnb存在蛋白互作和共定位情况。WB结果显示,bEnd.3细胞在PA处理条件下,ENG和Flnb蛋白表达均下降;在ENG沉默条件下,Flnb蛋白随ENG表达的减少而降低;在ENG过表达条件下,Flnb蛋白随ENG表达的增加而升高。结论ENG互作蛋白广泛参与到多种相关的生物途径以及信号通路之中,ENG在bEnd.3细胞中与Flnb蛋白存在相互作用且二者具有共定位现象,ENG还能够调控PA处理的bEnd.3细胞Flnb蛋白表达水平。

Experimental,Numerical,and Analytical Studies on the Bending of Mechanically Lined Pipe

Mechanically lined pipe(MLP)is often used for offshore oil and gas transport because of its low cost and corrosion resistance.During installation and operation,the pipe may undergo severe bending deformation,which causes the liner to separate from the outer pipe and buckles,affecting the stability of the whole line.In this paper,the buckling response of MLP subjected to bending is investigated to clarify its bending characteristics by employing both experiments,numerical simulation,as theoretical methods.Two types of MLPs were manufactured with GB 45 carbon steel(SLP)and Al 6061(ALP)used as the outer pipe material,respectively.The hydraulic expansion and bending experiments of small-scale MLPs are conducted.In addition to the ovalized shape of the cross-section for the SLP specimens,the copper liner was found to wrinkle on the compressive side.In contrast,the liner of ALP remains intact without developing any wrinkling and collapse mode.In addition,a dedicated numerical framework and theoretical models were also established.It was found both the manufacturing and bending responses of the MLP can be well reproduced,and the predicted maximum moment and critical curvatures are in good agreement with the experimental results.

Effect of characteristics and distribution of Mg_(17)Al_(12)precipitates on tensile and bending properties of high-Al-containing Mg alloys

This study investigates the effect of characteristics and distribution of Mg_(17)Al_(12)precipitates on the uniaxial tensile and three-point bending properties of extruded Mg alloys containing high Al contents.The extruded Mg–9Al–1Zn–0.3Mn(AZ91)alloy contains lamellar-structured Mg_(17)Al_(12)discontinuous precipitates along the grain boundaries,which are formed via static precipitation during natural air cooling.The extruded Mg–11Al–1Zn–0.3Mn(AZ111)alloy contains spherical Mg_(17)Al_(12)precipitates at the grain boundaries and inside the grains,which are formed via dynamic precipitation during extrusion.Due to inhomogeneous distribution of precipitates,the AZ111 alloy consists of two different precipitate regions:precipitate-rich region with numerous precipitates and finer grains and precipitate-scarce region with a few precipitates and coarser grains.The AZ111 alloy exhibits a higher tensile strength than the AZ91 alloy because its smaller grain size and more abundant precipitates result in stronger grain-boundary hardening and precipitation hardening effects,respectively.However,the tensile elongation of the AZ111 alloy is lower than that of the AZ91 alloy because the weak cohesion between the dynamic precipitates and the matrix facilitates the crack initiation and propagation.During bending,a macrocrack initiates on the outer surface of bending specimen in both alloys.The AZ111 alloy exhibits higher bending yield strength and lower failure bending strain than the AZ91 alloy.The bending specimens of the AZ91 alloy have similar bending formability,whereas those of the AZ111 alloy exhibit considerable differences in bending formability and crack propagation behavior,depending on the distribution and number density of precipitates in the specimen.In bending specimens of the AZ111 alloy,it is found that the failure bending strain(ε_(f,bending))is inversely proportional to the area fraction of precipitates in the outer zone of bending specimen(A_(ppt)),with a relationship ofε_(f,bending)=–0.1A_(ppt)+5.86.

Discharge evolution law of debris flow based on a sharp bend physical modeling test

For the basins with debris flow development,its channel terrain exhibits a tortuous shape,which significantly restricts the movement of debris flows and leads to severe erosion effects on the concave bank.Therefore,this study aims to analyze the shear force of debris flows within the bend channel.We established the relationship between the shear force and bend curvature through laboratory experiments.Under the long-term erosion by debris flows,the curvature radius of bends gradually increases,however,when this increasing trend reaches an equilibrium state with the intensity of debris flow discharge,there will be no significant change in curvature radius.In general,the activity pattern and discharges of debris flows would remain relatively stable.Hence,we can infer the magnitude of debris flow discharges from the terrain parameters of the bend channel.

Bending Failure Mode and Prediction Method of the Compressive Strain Capacity of A Submarine Pipeline with Dent Defects

A dent is a common type of defects for submarine pipeline.For submarine pipelines,high hydrostatic pressure and internal pressure are the main loads.Once pipelines bend due to complex subsea conditions,the compression strain capacity may be exceeded.Research into the local buckling failure and accurate prediction of the compressive strain capacity are important.A finite element model of a pipeline with a dent is established.Local buckling failure under a bending moment is investigated,and the compressive strain capacity is calculated.The effects of different parameters on pipeline local buckling are analyzed.The results show that the dent depth,external pressure and internal pressure lead to different local buckling failure modes of the pipeline.A higher internal pressure indicates a larger compressive strain capacity,and the opposite is true for external pressure.When the ratio of external pressure to collapse pressure of intact pipeline is greater than 0.1,the deeper the dent,the greater the compressive strain capacity of the pipeline.And as the ratio is less than 0.1,the opposite is true.On the basis of these results,a regression equation for predicting the compressive strain capacity of a dented submarine pipeline is proposed,which can be referred to during the integrity assessment of a submarine pipeline.

Bending Strength of Glass Materials under Strong Dynamic Impact and Its Strain Rate Effects

Based on the structural characteristics of the high-speed loading tester,a four-point bending test device was designed to carry out the four-point bending strength test of glass under the action of static load and different impact velocities,and the formulae for calculating the maximum dynamic stress and strain rate of glass specimens under the action of impact loads were derived.The experimental results show that the bending strength values of the glass under dynamic impact loading are all higher than those under static loading.With the increase of impact speed,the bending strength value of glass specimens generally tends to increase,and the bending strength value increases more obviously when the impact speed exceeds 0.5 m/s or higher.By increasing the impact velocity,higher tensile strain rate of glass specimens can be obtained because the load action time becomes shorter.The bending strength of the glass material increases with its tensile strain rate,and when the tensile strain rate is between 0 and 2 s^(-1),the bending strength of the glass specimen grows more obviously with the strain rate,indicating that the glass bending strength is particularly sensitive to the tensile strain rate in this interval.As the strain rate increases,the number of cracks formed after glass breakage increases significantly,thus requiring more energy to drive the crack formation and expansion,and showing the strain rate effect of bending strength at the macroscopic level.The results of the study can provide a reference for the load bearing and structural design of glass materials under dynamic loading.

Analysis of deformation mechanisms in magnesium single crystals using a dedicated four-point bending tester

In this study,we explored the deformation mechanisms of Mg single crystals using a combination of scanning electron microscopy and electron backscattered diffraction in conjunction with a dedicated four-point bending tester.We prepared two single-crystal samples,oriented along the<1120>and<1010>directions,to assess the mechanisms of deformation when the initial basal slip was suppressed.In the<1120>sample,the primary{1012}twin(T1)was confirmed along the<1120>direction of the sample on the compression side with an increase in bending stress.In the<1010>sample,T1 and the secondary twin(T2)were confirmed to be along the<1120>direction,with an orientation of±60°with respect to the bending stress direction,and their direction matched with(0001)in T1 and T2.This result implies that crystallographically,the basal slip occurs readily.In addition,the<1010>sample showed the double twin in T1 on the compression side and the tertiary twin along the<1010>direction on the tension side.These results demonstrated that the maximum bending stress and displacement changed significantly under the bend loading because the deformation mechanisms were different for these single crystals.Therefore,the correlation between bending behavior and twin orientation was determined,which would be helpful for optimizing the bending properties of Mg-based materials.

Bending strength degradation of a cantilever plate with surface energy due to partial debonding at the clamped boundary

This paper investigates the bending fracture problem of a micro/nanoscale cantilever thin plate with surface energy,where the clamped boundary is partially debonded along the thickness direction.Some fundamental mechanical equations for the bending problem of micro/nanoscale plates are given by the Kirchhoff theory of thin plates,incorporating the Gurtin-Murdoch surface elasticity theory.For two typical cases of constant bending moment and uniform shear force in the debonded segment,the associated problems are reduced to two mixed boundary value problems.By solving the resulting mixed boundary value problems using the Fourier integral transform,a new type of singular integral equation with two Cauchy kernels is obtained for each case,and the exact solutions in terms of the fundamental functions are determined using the PoincareBertrand formula.Asymptotic elastic fields near the debonded tips including the bending moment,effective shear force,and bulk stress components exhibit the oscillatory singularity.The dependence relations among the singular fields,the material constants,and the plate's thickness are analyzed for partially debonded cantilever micro-plates.If surface energy is neglected,these results reduce the bending fracture of a macroscale partially debonded cantilever plate,which has not been previously reported.

A Light and Simplified Branch Bending Method for Young Pear Trees

Aiming at high cost and low efficiency of conventional branch bending method in the modern intensive planting and labor-saving cultivation mode of young pear trees,this paper provides a new branch bending method with wide source of raw materials,cheap price and simple operation,which is also suitable for the management of low-age branches in the process of high grafting and upgrading of traditional big trees.

The Effects of the Longitudinal Axis of Loading upon Bending, Shear and Torsion of a Thin-Walled Cantilever Channel Beam

Three aluminium channel sections of US standard extruded dimension are mounted as cantilevers with x-axis symmetry. The flexural bending and shear that arise with applied axial torsion are each considered theoretically and numerically in terms of two longitudinal axes of loading not coincident with the shear centre. In particular, the warping displacements, stiffness and stress distributions are calculated for torsion applied to longitudinal axes passing through the section’s centroid and its web centre. The stress conversions derived from each action are superimposed to reveal a net sectional stress distribution. Therein, the influence of the axis position upon the net axial and shear stress distributions is established compared to previous results for each beam when loading is referred to a flexural axis through the shear centre. Within the net stress analysis is, it is shown how the constraint to free warping presented by the end fixing modifies the axial stress. The latter can be identified with the action of a ‘bimoment’ upon each thin-walled section.

基于p38MAPK-PPARγ/NF-κB信号通路探讨消肿止痛合剂对血管内皮细胞bEND-3凋亡的影响

目的从细胞及信号通路层面探讨消肿止痛合剂对皮瓣缺血再灌注损伤中血管内皮细胞凋亡的影响。方法血管内皮细胞bEND-3培养。TNF-α体外细胞凋亡诱导模型建立并将细胞分为:p38MAPK抑制剂组、PPARγ抑制剂组、NF-κB抑制剂组、模型对照组、空白组。微丝绿色荧光探针观察细胞骨架微丝。RT-PCR法检测血管内皮细胞bEND-3细胞中p38MAPK、PPARγ、IκBα、NF-κBmRNA的表达。结果空白组中p38MAPK、PPARγ、IκBα、NF-κB的表达量无明显差异,模型对照组中p38MAPK与NF-κB的表达量最高,与模型对照组相比,p38MAPK抑制剂组bEnd.3细胞中p38MAPK与NF-κB的表达被抑制,PPARγ、IκBα表达量升高(P<0.05);PPARγ抑制剂组中PPARγ、IκBα、NF-κB的表达被抑制,p38MAPK表达量升高(P<0.05),NF-κB抑制剂组中p38MAPK与NF-κB的表达被抑制,IκBα与PPARγ的表达量升高(P<0.05);与空白组相比,p38MAPK抑制剂组与NF-κB抑制剂组中p38MAPK、PPARγ、IκBα、NF-κB的表达量升高(P<0.05),PPARγ抑制剂组中p38MAPK与NF-κB表达量明显升高,PPARγ、IκBα表达被抑制(P<0.05)。结论消肿止痛合剂可抑制bEND-3细胞凋亡,其机制与影响可能与p38MAPK-PPARγ/NF-κB信号通路有关。

Flow measurement and parameter optimization of right-angled flow passage in hydraulic manifold block

This study was conducted to investigate the flow field characteristics of right-angled flow passage with various cavities in the typical hydraulic manifold block.A low-speed visualization test rig was developed and the flow field of the right-angled flow passage with different cavity structures was measured using 2D-PIV technique.Numerical model was established to simulate the three-dimensional flow field.Seven eddy viscosity turbulence models were investigated in predicting the flow field by comparing against the particle image relocimetry(PIV)measurement results.By defining the weight error function K,the S-A model was selected as the appropriate turbulence model.Then,a three-factor,three-level response surface numerical test was conducted to investigate the influence of flow passage connection type,cavity diameter and cavity length-diameter ratio on pressure loss.The results show that the Box-Benhnken Design(BBD)model can predict the total pressure loss accurately.The optimal factor level appeared in flow passage connection type II,14.64 mm diameter and 67.53%cavity length-diameter ratio.The total pressure loss decreased by 11.15%relative to the worst factor level,and total pressure loss can be reduced by 64.75%when using an arc transition right-angled flow passage,which indicates a new direction for the optimization design of flow passage in hydraulic manifold blocks.

Interaction of a circular cavity and a beeline crack in right-angle plane impacted by SH-wave

The problem of scattering of SH-wave by a circular cavity and an arbitrary beeline crack in right-angle plane was investigated using the methods of Green's function,complex variables and muti-polar coordinates.Firstly,we constructed a suitable Green's function,which is an essential solution to the displacement field for the elastic right-angle plane possessing a circular cavity while bearing out-of-plane harmonic line source load at arbitrary point.Secondly,based on the method of crack-division,integration for solution was established,then expressions of displacement and stress were obtained while crack and circular cavities were both in existence.Finally,the dynamic stress concentration factor around the circular cavity and the dynamic stress intensity factor at crack tip were discussed to the cases of different parameters in numerical examples.Calculation results show that the crack produces adverse engineering influence on both of the dynamic stress concentration factor and the dynamic stress intensity factor.

SCATTERING OF CIRCULAR CAVITY IN RIGHT-ANGLE PLANAR SPACE TO STEADY SH-WAVE

Complex function method and multi-polar coordinate transformation technology are used here to study scattering of circular cavity in right-angle planar space to SH-wave with out-of-plane loading on the horizontal straight boundary. At first, Green function of right-angle planar space which has no circular cavity is constructed; then the scattering solution which satisfies the free stress conditions of the two right-angle boundaries with the circular cavity existing in the space is formulated. Therefore, the total displacement field can be constructed using overlapping principle. An infinite algebraic equations of unknown coefficients existing in the scattering solution field can be gained using multi-polar coordinate and the free stress condition at the boundary of the circular cavity. It can be solved by using limit items in the infinite series which can give a high computation precision. An example is given to illustrate the variations of the tangential stress at the boundary of the circular cavity due to different dimensionless wave numbers, the location of the circular cavity, the loading center and the distributing range of the out-of-plane loading. The results show the efficiency and effectiveness of the mothod introduced here.

NLRP3炎症小体在bEnd.3细胞氧糖剥夺及复氧复糖后的表达观察

脑卒中具有高死亡率及高致残率的特点,其死亡率在全球范围内位居第二[1],其所导致的长期残疾为家庭和社会带来了沉重的负担。治疗缺血性脑卒中最有效的策略之一是立即恢复大脑的血流,尽管这会导致进一步的细胞坏死和神经损伤,即缺血再灌注损伤。

Electro-chemo-mechanical analysis of the effect of bending deformation on the interface of flexible solid-state battery

Flexible solid-state battery has several unique characteristics including high flexibility,easy portability,and high safety,which may have broad application prospects in new technology products such as rollup displays,power implantable medical devices,and wearable equipments.The interfacial mechanical and electrochemical problems caused by bending deformation,resulting in the battery damage and failure,are particularly interesting.Herein,a fully coupled electro-chemo-mechanical model is developed based on the actual solid-state battery structure.Concentration-dependent material parameters,stress-dependent diffusion,and potential shift are considered.According to four bending forms(k=8/mm,0/mm,-8/mm,and free),the results show that the negative curvature bending is beneficial to reducing the plastic strain during charging/discharging,while the positive curvature is detrimental.However,with respect to the electrochemical performance,the negative curvature bending creates a negative potential shift,which causes the battery to reach the cut-off voltage earlier and results in capacity loss.These results enlighten us that suitable electrode materials and charging strategy can be tailored to reduce plastic deformation and improve battery capacity for different forms of battery bending.

Comparison of Flow Characteristics Around Refractive and Right-angled Groins in Barotropic and Baroclinic Conditions

Groins are employed to prevent nearshore areas from erosion and to control the direction of flow. However, the groin structure and its associated flow characteristics are the main causes of local erosion. In this study, we investigate the flow patterns around refractive and right-angle groins. In particular, we analytically compare the flow characteristics around a refractive groin and study the degree of accuracy that can be achieved by using a right-angle groin of various projected lengths. To compare the flow characteristics, we replaced the right-angle groin with an approximation of a refractive groin. This replacement had the least effect on the maximum velocity of flow in the channel. Moreover, we investigated the distribution of the density variables of temperature and salinity, and their effects on the flow characteristics around the right-angle groin. A comparison of the flow analysis results in baroclinic and barotropic conditions reveals that the flow characteristic values are very similar for both the refractive and right-angle groins. The geometry of the groin, i.e., right-angle or refractive, has little effect on the maximum speed to relative average speed. Apart from the angular separation, the arm length of the groin in downstream refractive groins has less effect on other flow characteristics than do upstream refractive groins. We also correlated a number of non-dimensional variables with respect to various flow characteristics and groin geometry. These comparisons indicate that the correlation between the thalweg height and width of the channel and groin arm＇s length to projection length have been approximated using linear and nonlinear formulas regardless of inner velocity in the subcritical flow.

CXCL1通过促进蛋白激酶B磷酸化导致bEND.3小鼠脑微血管内皮细胞骨架收缩和通透性增加

目的探讨脓毒症脑病炎症中CXC趋化因子配体1(CXCL1)及其受体CXC趋化因子受体2(CXCR2)对脑内皮细胞骨架重排和通透性的影响及其相关机制。方法野生型小鼠腹腔注射脂多糖(LPS)(10 mg/kg)建立脓毒症脑病模型,ELISA检测全脑组织肿瘤坏死因子α(TNF-α)和CXCL1含量。使用500 ng/mL LPS和200 ng/mL TNF-α刺激bEND.3脑微血管内皮细胞后,Western blot法检测细胞CXCR2的表达。以150 ng/mL CXCL1刺激bEND.3细胞,免疫荧光染色观察脑内皮细胞骨架纤维型肌动蛋白(F-actin)重排的变化。脑内皮细胞通透性实验中,将bEND.3细胞随机分为PBS对照组、CXCL1组、CXCL1联合选择性CXCR2拮抗剂SB225002组,Transwell^(TM)小室检测各组通透性变化情况。CXCL1刺激bEND.3细胞后,Western blot法检测细胞中蛋白激酶B(AKT)和磷酸化AKT(p-AKT)蛋白表达。结果腹腔注射LPS导致小鼠全脑组织中TNF-α和CXCL1水平显著升高;LPS和TNF-α刺激可增高bEND.3细胞CXCR2蛋白的表达。CXCL1刺激bEND.3细胞使其细胞骨架收缩,细胞间隙形成增加,且细胞渗透性增加,而CXCR2拮抗剂SB225002预处理可显著抑制CXCL1引起的脑内皮细胞肌动蛋白应力纤维和细胞间隙的形成、以及通透性的增高,同时CXCL1(150 ng/mL)刺激使得脑内皮细胞AKT的磷酸化水平明显升高。结论CXCL1通过AKT磷酸化激活引起脑内皮细胞骨架收缩、细胞通透性增加,CXCR2拮抗剂SB225002可有效抑制CXCL1诱导的细胞骨架收缩和通透性升高。

Numerical analysis of bending property of bi-modulus materials and a new method for measurement of tensile elastic modulus

In nature,there are widely distributed bi-modulus materials with different deformation characteristics under compressive and tensile stress states,such as concrete,rock and ceramics.Due to the lack of constitutive model that could reasonably consider the bi-modulus property of materials,and the lack of simple and reliable measurement methods for the tensile elastic parameters of materials,scientists and engineers always neglect the effect of the bi-modulus property of materials in engineering design and numerical simulation.To solve this problem,this study utilizes the uncoupled strain-driven constitutive model proposed by Latorre and Montáns(2020)to systematically study the distributions and magnitudes of stresses and strains of bi-modulus materials in the three-point bending test through the numerical method.Furthermore,a new method to synchronously measure the tensile and compressive elastic moduli of materials through the four-point bending test is proposed.The numerical results show that the bi-modulus property of materials has a significant effect on the stress,strain and displacement in the specimen utilized in the three-point and four-point bending tests.Meanwhile,the results from the numerical tests,in which the elastic constitutive model proposed by Latorre and Montáns(2020)is utilized,also indicate that the newly proposed measurement method has a good reliability.Although the new measurement method proposed in this study can synchronously and effectively measure the tensile and compressive elastic moduli,it cannot measure the tensile and compressive Poisson’s ratios.

Accounting for speckle-scale beam bending in classical ray tracing schemes for propagating realistic pulses in indirect drive ignition conditions

We propose a semi-analytical modeling of smoothed laser beam deviation induced by plasma flows.Based on a Gaussian description of speckles,the model includes spatial,temporal,and polarization smoothing techniques,through fits coming from hydrodynamic simulations with a paraxial description of electromagnetic waves.This beam bending model is then incorporated into a ray tracing algorithm and carefully validated.When applied as a post-process to the propagation of the inner cone in a full-scale simulation of a National Ignition Facility(NIF)experiment,the beam bending along the path of the laser affects the refraction conditions inside the hohlraum and the energy deposition,and could explain some anomalous refraction measurements,namely,the so-called glint observed in some NIF experiments.