DAMPs和肾脏疾病

DAMPs是机体受到损伤后释放的内源性预警信号,可激活固有免疫系统,联系适应性免疫,介导无菌性炎症。近年来,DAMPs在肾脏疾病领域日益受到关注。为此,本文将对常见DAMPs、DAMPs受体、DAMPs与肾脏疾病的关系等作一综述。

炎症反应中巨噬细胞的Siglec-G分子对DAMPs和PAMPs的识别及调节作用

目的:探究巨噬细胞中唾液酸结合性免疫球蛋白样凝集素(Siglecs)家族的成员Siglec-G参与损伤相关分子模式(DAMPs)和病原相关分子模式(PAMPs)识别及其在炎症反应中的调节作用。方法:提取并纯化野生型小鼠腹腔巨噬细胞,用DAMPs中的高迁移率族蛋白Bl(HMGB1)和PAMPs中的脂多糖(LPS)分别刺激24 h,Real-time PCR方法检测细胞中Siglec-G基因的表达,ELISA方法检测野生型和Siglec-G基因敲除小鼠腹腔巨噬细胞培养上清中肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的分泌情况。结果:HMGB1能够使巨噬细胞中Siglec-G的表达明显升高,而LPS作用后Siglec-G的表达没有明显改变,同时发现,HMGB1作用于Siglec-G敲除小鼠的巨噬细胞后,TNF-α和IL-6的分泌明显增加,而LPS刺激后炎症因子的分泌没有明显改变。结论:巨噬细胞通过表达Siglec-G来识别DAMPs并发挥免疫抑制作用,而其对于PAMPs缺乏识别及调控作用。

DAMPs对人肝癌HepG2细胞增殖能力影响的机制研究

目的:探讨在损伤相关模式分子(DAMPs)诱导下人肝癌HepG2细胞增殖能力变化的发生机制。方法:将HepG2细胞分为对照组,DAMPs组,IL-6 siRNA组,IL-6 siRNA+DAMPs组;MTT比色法检测HepG2细胞增殖能力的变化;实时荧光定量PCR法检测IL-6及STAT3 mRNA的表达;Western blot法测定HepG2细胞STAT3蛋白和磷酸化STAT3蛋白的表达。结果:DAMPs组细胞增殖能力较对照组显著增强,IL-6 mRNA及STAT3 mRNA的表达较对照组显著上调,差异均有统计学意义(P<0.01);Western bot法检测出四组STAT3蛋白表达无明显差异,而DAMPs组磷酸化STAT3蛋白的表达高于对照组,差异有统计学意义(P<0.01)。结论:DAMPs可能通过IL-6/STAT3信号通路促进人肝癌HepG2细胞的增殖。

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

The combination of immunotherapy and chemotherapy is regarded as a promising approach for the treatment of certain types of cancer. However, the underlying mechanisms need to be fully investigated to guide the design of more efficient protocols for cancer chemoimmunotherapy. It is well known that danger-associated molecular patterns （DAMPs） can activate immune cells, including dendritic cells （DCs）, via Toll-like receptors （TLRs）; however, the role of DAMPs released from chemical drug-treated tumor cells in the activation of the immune response needs to be further elucidated. Here, we found that colorectal cancer （CRC） cells treated with oxaliplatin （OXA） and/or 5-fluorouracil （5-Fu） released high levels of high-mobility group box 1 （HMGB1） and heat shock protein 70 （HSP70）. After OXA/5-Fu therapy, the sera of CRC patients also exhibited increased levels of HMGB1 and HSP70, both of which are well-known DAMPs. The supernatants of dying CRC cells treated with OXA/5-Fu promoted mouse and human DC maturation, with upregulation of HLA-DR, CD80 and CD86 expression and enhancement of IL-lp, TNF-a, MIP-la, MIP-lp, RANTES and IP-IO production. Vaccines composed of DCs pulsed with the supernatants of chemically stressed CRC cells induced a more significant IFN-y-producing Thl response both in vitroand in vivo. However, the supernatants of chemically stressed CRC cells failed to induce phenotypic maturation and cytokine production in TLR4-deficient DCs, indicating an essential role of TLR4 in DAMP-induced DC maturation and activation. Furthermore, pulsing with the supernatants of chemically stressed CRC cells did not efficiently induce an IFN-y-producing Thl response in TLR4-deficient DCs. Collectively, these results demonstrate that DAMPs released from chemically stressed cancer cells can activate DCs viaTLR4 and enhance the induction of an anti-tumor T-cell immune response, delineating a clinically relevant immuno-adjuvant pathway triggered by DAMPs.

Aseismic performances of constrained damping lining structures made of rubber-sand-concrete

Flexible damping technology considering aseismic materials and aseismic structures seems be a good solution for engineering structures.In this study,a constrained damping structure for underground tunnel lining,using a rubber-sand-concrete(RSC)as the aseismic material,is proposed.The aseismic performances of constrained damping structure were investigated by a series of hammer impact tests.The damping layer thickness and shape effects on the aseismic performance such as effective duration and acceleration amplitude of time-domain analysis,composite loss factor and damping ratio of the transfer function analysis,and total vibration level of octave spectrum analysis were discussed.The hammer impact tests revealed that the relationship between the aseismic performance and damping layer thickness was not linear,and that the hollow damping layer had a better aseismic performance than the flat damping layer one.The aseismic performances of constrained damping structure under different seismicity magnitudes and geological conditions were investigated.The effects of the peak ground acceleration(PGA)and tunnel overburden depth on the aseismic performances such as the maximum principal stress and equivalent plastic strain(PEEQ)were discussed.The numerical results show the constrained damping structure proposed in this paper has a good aseismic performance,with PGA in the range(0.2-1.2)g and tunnel overburden depth in the range of 0-300 m.

Microstructure and damping properties of LPSO phase dominant Mg-Ni-Y and Mg-Zn-Ni-Y alloys

This work studied the microstructure,mechanical properties and damping properties of Mg_(95.34)Ni_(2)Y_(2.66) and Mg_(95.34)Zn_(1)Ni_(1)Y_(2.66)alloys systematically.The difference in the evolution of the long-period stacked ordered(LPSO)phase in the two alloys during heat treatment was the focus.The morphology of the as-cast Mg_(95.34)Ni_(2)Y_(2.66)presented a disordered network.After heat treatment at 773 K for 2 hours,the eutectic phase was integrated into the matrix,and the LPSO phase maintained the 18R structure.As Zn partially replaced Ni,the crystal grains became rounded in the cast alloy,and lamellar LPSO phases and more solid solution atoms were contained in the matrix after heat treatment of the Mg_(95.34)Zn_(1)Ni_(1)Y_(2.66)alloy.Both Zn and the heat treatment had a significant effect on damping.Obvious dislocation internal friction peaks and grain boundary internal friction peaks were found after temperature-dependent damping of the Mg_(95.34)Ni_(2)Y_(2.66)and Mg_(95.34)Zn_(1)Ni_(1)Y_(2.66)alloys.After heat treatment,the dislocation peak was significantly increased,especially in the alloy Mg_(95.34)Ni_(2)Y_(2).66.The annealed Mg_(95.34)Ni_(2)Y_(2.66)alloy with a rod-shaped LPSO phase exhibited a good damping performance of 0.14 atε=10^(−3),which was due to the difference between the second phase and solid solution atom content.These factors also affected the dynamic modulus of the alloy.The results of this study will help in further development of high-damping magnesium alloys.

Prediction of Damping Capacity Demand in Seismic Base Isolators via Machine Learning

Base isolators used in buildings provide both a good acceleration reduction and structural vibration control structures.The base isolators may lose their damping capacity over time due to environmental or dynamic effects.This deterioration of them requires the determination of the maintenance and repair needs and is important for the long-termisolator life.In this study,an artificial intelligence prediction model has been developed to determine the damage and maintenance-repair requirements of isolators as a result of environmental effects and dynamic factors over time.With the developed model,the required damping capacity of the isolator structure was estimated and compared with the previously placed isolator capacity,and the decrease in the damping property was tried to be determined.For this purpose,a data set was created by collecting the behavior of structures with single degrees of freedom(SDOF),different stiffness,damping ratio and natural period isolated from the foundation under far fault earthquakes.The data is divided into 5 different damping classes varying between 10%and 50%.Machine learning model was trained in damping classes with the data on the structure’s response to random seismic vibrations.As a result of the isolator behavior under randomly selected earthquakes,the recorded motion and structural acceleration of the structure against any seismic vibration were examined,and the decrease in the damping capacity was estimated on a class basis.The performance loss of the isolators,which are separated according to their damping properties,has been tried to be determined,and the reductions in the amounts to be taken into account have been determined by class.In the developed prediction model,using various supervised machine learning classification algorithms,the classification algorithm providing the highest precision for the model has been decided.When the results are examined,it has been determined that the damping of the isolator structure with the machine learning method is predicted successfully at a level exceeding 96%,and it is an effective method in deciding whether there is a decrease in the damping capacity.

Mechanical property of cylindrical sandwich shell with gradient core of entangled wire mesh

To explore the wide-frequency damping and vibration-attenuation performances in the application of aerospace components,the cylindrical sandwich shell structure with a gradient core of entangled wire mesh was proposed in this paper.Firstly,the gradient cores of entangled wire mesh in the axial and radial directions were prepared by using an in-house Numerical Control weaving machine,and the metallurgical connection between skin sheets and the gradient core was performed using vacuum brazing.Secondly,to investigate the mechanical properties of cylindrical sandwich shells with axial or radial gradient cores,quasi-static and dynamic mechanical experiments were carried out.The primary evaluations of mechanical properties include secant stiffness,natural frequency,Specific Energy Absorption(SEA),vibration acceleration level,and so on.The results suggest that the vibration-attenuation performance of the sandwich shell is remarkable when the high-density core layer is at the end of the shell or abuts the inner skin.The axial gradient material has almost no influence on the vibration frequencies of the shell,whereas the vibration frequencies increase dramatically when the high-density core layer approaches the skin.Moreover,compared to the conventional sandwich shells,the proposed functional grading cylindrical sandwich shell exhibits more potential in mass reduction,stiffness designing,and energy dissipation.

Capillary Property of Entangled Porous Metallic Wire materials and Its Application in Fluid Buffers:Theoretical Analysis and Experimental Study

Strong impact does serious harm to the military industries so it is necessary to choose reasonable cushioning material and design effective buffers to prevent the impact of equipment.Based on the capillary property entangled porous metallic wire materials(EPMWM),this paper designed a composite buffer which uses EPMWM and viscous fluid as cushioning materials under the low-speed impact of the recoil force device of weapon equipment(such as artillery,mortar,etc.).Combined with the capillary model,porosity,hydraulic diameter,maximum pore diameter and pore distribution were used to characterize the pore structure characteristics of EPMWM.The calculation model of the damping force of the composite buffer was established.The low-speed impact test of the composite buffer was conducted.The parameters of the buffer under low-speed impact were identified according to the model,and the nonlinear model of damping force was obtained.The test results show that the composite buffer with EPMWM and viscous fluid can absorb the impact energy from the recoil movement effectively,and provide a new method for the buffer design of weapon equipment(such as artillery,mortar,etc.).

Scattering of Water Waves by Dual Symmetric Inclined Floating Porous Barriers Using the DBEM

The scattering of normally incident water waves by two surface-piercing inclined perforated barriers in water with a uniform finite depth is investigated within the framework of linear water wave theory.Considering that thin barriers are zero-thickness,a novel numerical method involving the the coupling of the dual boundary element method(DBEM)with damping layers is applied.In order to effectively damp out the reflected waves,two damping layers,instead of pseudoboundaries are implemented near the two side boundaries of the computational domain.Thus,the modified linearized free surface boundary conditions are formulated and used for solving both the ordinary boundary integral equation as well as the hypersingular boundary integral equation for degenerate boundaries.The newly developed numerical method is validated against analytical methods using the matched eigenfunction expansion method for the special case of two vertical barriers or the inclined angle to the vertical being zero.The influence of the length of the two damping layers has been discussed.Moreover,these findings are also validated against previous results for several cases.After validation,the numerical results for the reflection coefficient,transmission coefficient and dissipation coefficient are obtained by varying the inclination angle and porosity-effect parameter.The effects of both the inclination angle and the porosity on the amplitudes of wave forces acting on both the front and rear barriers are also investigated.It is found that the effect of the inclination angle mainly shifts the location of the extremal values of the reflection and the transmission coefficients.Additionally,a moderate value of the porosity-parameter is quite effective at dissipating wave energy and mitigating the wave loads on dual barriers.

Influence of Trailing-Edge Wear on the Vibrational Behavior of Wind Turbine Blades

To study the impact of the trailing-edge wear on the vibrational behavior of wind-turbine blades,unworn blades and trailing-edge worn blades have been assessed through relevant modal tests.According to these experiments,the natural frequencies of trailing-edge worn blades-1,-2,and-3 increase the most in the second to fourth order,thefifth order increases in the middle,and thefirst order increases the least.The damping ratio data indi-cate that,in general,thefirstfive-order damping ratios of trailing-edge worn blades-1 and trailing-edge worn blades-2 are reduced,and thefirstfive-order damping ratios of trailing-edge worn blades-3 are slightly improved.The mode shape diagram shows that the trailing-edge worn blades-1 and-2 have a large swing in the tip and the blade,whereas the second-and third-order vibration shapes of the trailing edge-worn blade-3 tend to be improved.Overall,all these results reveal that the blade’s mass and the wear area are the main fac-tors affecting the vibration characteristics of wind turbine blades.

Research on the evolution law of dynamic performance of CR400BF EMU train based on stochastic dynamics simulation

Purpose–This paper aims to obtain the evolution law of dynamic performance of CR400BF electric multiple unit(EMU).Design/methodology/approach–Using the dynamic simulation based on field test,stiffness of rotary arm nodes and damping coefficient of anti-hunting dampers were tested.Stiffness,damping coefficient,friction coefficient,track gauge were taken as random variables,the stochastic dynamics simulation method was constructed and applied to research the evolution law with running mileage of dynamic index of CR400BF EMU.Findings–The results showed that stiffness and damping coefficient subjected to normal distribution,the mean and variance were computed and the evolution law of stiffness and damping coefficient with running mileage was obtained.Originality/value–Firstly,based on the field test we found that stiffness of rotary arm nodes and damping coefficient of anti-hunting dampers subjected to normal distribution,and the evolution law of stiffness and damping coefficient with running mileage was proposed.Secondly stiffness,damping coefficient,friction coefficient,track gauge were taken as random variables,the stochastic dynamics simulation method was constructed and applied to the research to the evolution law with running mileage of dynamic index of CR400BF EMU.

Damps’role in inflammatory bowel disease:a paradoxical player of mtDNA-STING signaling pathway in gut homeostasis

The inflammatory bowel disease(IBD),including Crohn’s disease(CD)and ulcerative colitis,are chronic,relapsing immune mediated disorders of the gastrointestinal homeostasis and intestinal inflammation[1].Failure to resolve mucosal inflammation and maintain gut barrier are notable shared clinical challenges in IBD,in particular when they activate immune cells within the gut lamia propria.Clinical trials and animal model studies aiming towards DAMPs have demonstrated that they can be effective therapeutic targets in mucosal inflammation of IBD.

基于Toll样受体通路与损伤相关分子模式分子炎症机制探讨扩张型心肌病中医药干预作用

随着Toll样受体(TLRs)通路与损伤相关分子模式(DAMPs)分子炎症机制研究深入,其对炎性反应、自我免疫等人体生理代谢活动所需路径产生影响等证据表明,心肌炎性活动与此有关。炎症是防御机体内外病原造成组织损伤的主要机制。TLRs通路可通过炎性反应参与心肌梗死后心脏肥大及心肌纤维化;DAMPs分子可促使心脏组织产生慢性炎性反应,从而导致心脏组织损伤、修复。近几年中医药的快速发展在治疗扩张型心肌病方面取得了重要突破并积累了丰富经验,而炎症机制可成为中医治疗扩张型心肌病的新靶点与新方向。

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.

Effect of ground motion duration on inelastic displacement ratio of SDOF systems

In this paper,the influence of ground motion duration on the inelastic displacement ratio,C_(1),of highly damped SDOF systems is studied.For this purpose,two sets of spectrally equivalent long and short duration ground motion records were used in an analysis to isolate the effects of ground motion duration on.The effect of duration was evaluated for observed values of C_(1) by considering six ductility levels,and different damping and post-yield stiffness ratios.A new predictive equation of C_(1) also was developed for long and short duration records.Results of non-linear regression analysis of the current study provide an expression with which to quantify the duration effect.Based on the average values of estimated C_(1) ratios for long duration records divided by C_(1) for a short duration set,it is concluded that the maximum difference between long and short duration records occurs when the damping ratio is 0.3 and the post-yield stiffness ratio is equal to zero.

巨噬细胞与肾移植

肾移植是终末期肾病患者的最佳治疗方案,但移植肾远期存活仍是临床上面临的重要难题。肾缺血-再灌注损伤(IRI)和移植肾排斥反应被认为是影响移植肾远期存活的重要因素,受固有免疫和适应性免疫细胞调控。巨噬细胞是固有免疫细胞中一种,可协助启动适应性免疫,分为M1型巨噬细胞、M2型巨噬细胞和调节性巨噬细胞。先前研究揭示M1型巨噬细胞加重肾IRI和急性T细胞介导的排斥反应(TCMR);而M2型巨噬细胞减轻肾IRI和急性TCMR,但与抗体介导的排斥反应(AMR)呈正相关;调节性巨噬细胞是巨噬细胞一种特殊亚群,可诱导移植免疫耐受,具有极大临床应用前景和基础科研价值。本文述评了巨噬细胞分型、巨噬细胞与肾IRI、移植肾排斥反应及调节性巨噬细胞与免疫耐受的关系,并分析了其可能作用机制,以期诱导巨噬细胞亚型改变或清除特定亚型巨噬细胞,进而改善移植预后及移植肾远期存活。

Damping performance of SiC nanoparticles reinforced magnesium matrix composites processed by cyclic extrusion and compression

This work dealt with the damping performance and its underlying mechanism in SiC nanoparticles reinforced AZ91D composite(SiC_(np)/AZ91D)processed by cyclic extrusion and compression(CEC).It was found that the CEC process significantly affects the damping performance of the composite due to alterations in the density of dislocations and grain boundaries in the matrix alloy.Although there would be dynamic precipitation of the Mg17Al12 phase during processing which increases the phase interface and limits the mobility of dislocations and grain boundaries.The results also showed that the damping capacity of 1%SiC_(np)/AZ91D composite continuously decreases with adding CEC pass number and it consistently increases with rising the applied temperature.Considering the first derivative of the tanδ-T curve,the dominant damping mechanism based on test temperature can be divided into three regions.These three regions are as follows(i)dislocation vibration of the weak pinning points(≤T_(cr)),(ii)dislocation vibration of the strong pinning points(T_(cr)∼T_(V)),and(iii)grain boundary/interface sliding(≥T_(V))

Study of the Judder Characteristics of Friction Material for an Automobile Clutch and Test Verification

The friction judder characteristics during clutch engagement have a significant influence on the NVH of a driveline.In this research,the judder characteristics of automobile clutch friction materials and experimental verification are studied.First,considering the stick-slip phenomenon in the clutch engagement process,a detailed 9-degrees-of-freedom(DOF)model including the body,each cylinder of the engine,clutch and friction lining,torsional damper,transmission and other driveline parts is established,and the calculation formula of friction torque in the clutch engagement process is determined.Second,the influence of the friction gradient characteristics on the amplification or attenuation of the automobile friction judder is analyzed,and the corresponding stability analysis and the numerical simulation of different friction gradient values are carried out with MATLAB/Simulink software.Finally,judder bench test equipment and a corresponding damping test program are developed,and the relationship between the friction coefficient gradient characteristics and the system damping is analyzed.After a large number of tests,the evaluation basis of the test is determined.The research results show that the friction lining with negative gradient characteristics of the friction coefficient will have a judder signal.When the friction gradient value is less than-0.005 s/m,the judder signal of the measured clutch cannot be completely attenuated,and the judder phenomenon occurs.When the friction gradient is greater than-0.005 s/m,the judder signal can be significantly suppressed and the system connection tends to be stable.

Thickness-dependent magnetic properties in Pt/[Co/Ni]_(n) multilayers with perpendicular magnetic anisotropy

We systematically investigated the Ni and Co thickness-dependent perpendicular magnetic anisotropy(PMA)coefficient,magnetic domain structures,and magnetization dynamics of Pt(5 nm)/[Co(t_(Co))/Ni(t_(Ni))]_(5)/Pt(1 nm)multilayers by combining the four standard magnetic characterization techniques.The magnetic-related hysteresis loops obtained from the field-dependent magnetization M and anomalous Hall resistivity(AHR)ρxy showed that the two serial multilayers with t_(Co)=0.2 nm and 0.3 nm have the optimum PMA coefficient K_(U) as well as the highest coercivity H_(C) at the Ni thickness t_(Ni)=0.6 nm.Additionally,the magnetic domain structures obtained by magneto-optic Kerr effect(MOKE)microscopy also significantly depend on the thickness and K_(U) of the films.Furthermore,the thickness-dependent linewidth of ferromagnetic resonance is inversely proportional to K_(U) and H_(C),indicating that inhomogeneous magnetic properties dominate the linewidth.However,the intrinsic Gilbert damping constant determined by a linear fitting of the frequency-dependent linewidth does not depend on the Ni thickness and K_(U).Our results could help promote the PMA[Co/Ni]multilayer applications in various spintronic and spin-orbitronic devices.