Exercise-induced modulation of miR-149-5p and MMP9 in LPS-triggered diabetic myoblast ER stress: licorice glycoside E as a potential therapeutic target

Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.

Coseismic Coulomb stress changes induced by a 2020-2021 M_(W)>7.0 Alaska earthquake sequence in and around the Shumagin gap and its influence on the Alaska-Aleutian subduction interface

Three M_(W)>7.0 earthquakes in 2020-2021 occurred in the Shumagin seismic gap and its adjacent area of the Alaska-Aleutian subduction zone,including the Mw7.8 Simeonof thrust earthquake on July 22,2020,the M_(W)7.6 Sand Point strike-slip earthquake on October 19,2020,and the M_(W)8.2 Chignik thrust earthquake on July 29,2021.The spatial and temporal proximity of these three earthquakes prompts us to probe stress-triggering effects among them.Here we examine the coseismic Coulomb stress change imparted by the three earthquakes and their influence on the subduction interface.Our results show that:(1)The Simeonof earthquake has strong loading effects on the subsequent Sand Point and Chignik earthquakes,with the Coulomb stress changes of 3.95 bars and 2.89 bars,respectively.The Coulomb stress change caused by the Sand Point earthquake at the hypocenter of the Chignik earthquake is merely around 0.01 bars,suggesting the negligible triggering effect on the latter earthquake;(2)The triggering effects of the Simeonof,Sand Point,and Chignik earthquakes on aftershocks within three months are not well pronounced because of the triggering rates of 38%,14%,and 43%respectively.Other factors may have played an important role in promoting the occurrence of these aftershocks,such as the roughness of the subduction interface,the complicated velocity structure of the lithosphere,and the heterogeneous prestress therein;(3)The three earthquakes caused remarkable coseismic Coulomb stress changes at the subduction interface nearby these mainshocks,with an average Coulomb stress change of 3.2 bars in the shallow region directly inwards the trench.

Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

The reliability of AlGaN/GaN high electron mobility transistors under step-electrical stresses

In spite of their extraordinary performance, AlGaN/GaN high electron mobility transistors （HEMTs） still lack solid reliability. Devices under accelerated DC stress tests （off-state, VDS = 0 state, and on-state step-stress） are investigated to help us identify the degradation mechanisms of the AlGaN/GaN HEMTs. All our findings are consistent with the degradation mechanism based on crystallographic-defect formation due to the inverse piezoelectric effects in Ref. [1] （Joh J and del Alamo J A 2006 IEEE IDEM Tech. Digest p. 415）. However, under the on-state condition, the devices are suffering from both inverse piezoelectric effects and hot electron effects, and so to improve the reliability of the devices both effects should be taken into consideration.

Inference and optimal design on step-stress partially accelerated life test for hybrid system with masked data

Under Type-Ⅱ progressively hybrid censoring, this paper discusses statistical inference and optimal design on stepstress partially accelerated life test for hybrid system in presence of masked data. It is assumed that the lifetime of the component in hybrid systems follows independent and identical modified Weibull distributions. The maximum likelihood estimations(MLEs)of the unknown parameters, acceleration factor and reliability indexes are derived by using the Newton-Raphson algorithm. The asymptotic variance-covariance matrix and the approximate confidence intervals are obtained based on normal approximation to the asymptotic distribution of MLEs of model parameters. Moreover,two bootstrap confidence intervals are constructed by using the parametric bootstrap method. The optimal time of changing stress levels is determined under D-optimality and A-optimality criteria.Finally, the Monte Carlo simulation study is carried out to illustrate the proposed procedures.

The soybean GmPUB21-interacting protein GmDi19-5 responds to drought and salinity stresses via an ABA-dependent pathway

Drought-induced protein 19(Di19) is a Cys2/His2 zinc-finger protein that functions in plant growth and development and in tolerance to abiotic stresses.Gm PUB21,an E3 ubiquitin ligase,negatively regulates drought and salinity response in soybean.We identified potential interaction target proteins of Gm PUB21by yeast two-hybrid c DNA library screening,Gm Di19-5 as a candidate.Bimolecular fluorescence complementation and glutathionine-S-transferase pull-down assays confirmed the interaction between Gm Di19-5 and Gm PUB21.Gm Di19-5 was induced by Na Cl,drought,and abscisic acid(ABA) treatments.Gm Di19-5 was expressed in the cytoplasm and nucleus.Gm Di19-5 overexpression conferred hypersensitivity to drought and high salinity,whereas Gm Di19-5 silencing increased drought and salinity tolerance.Transcripts of ABA-and stress response-associated genes including Gm RAB18 and Gm DREB2A were downregulated in Gm Di19-5-overexpressing plants under drought and salinity stresses.ABA decreased the protein level of Gm Di19-5 in vivo,whereas Gm PUB21 increased the decrease of Gm Di19-5 after exogenous ABA application.The accumulation of Gm PUB21 was also inhibited by Gm Di19-5.We conclude that Gm PUB21 and Gm Di19-5 collaborate to regulate drought and salinity tolerance via an ABA-dependent pathway.

Cracking behaviors and strength of rock-like samples with steps of different geometries under shear stress

Steps are distinctive features for estimating the movement of the upper and lower block of faults.However,studies about the influence of steps as a special type of discontinuity on cracking behaviors and strength of rock masses are limited.In this research,rock-like samples with steps and preexisting flaws were fabricated.Step height h and the inclination angle of gentle slope of the stepαwere set to different values.Direct shear tests were conducted on these samples under different normal stresses.The experimental results reveal that the inclination angle of the gentle slope of the stepα,step height h,and normal stress have an influence on the strength,crack initiation,and crack propagation of the samples.The experimental results show that crack behaviors and shear strength were affected by step inclination anglesαand step height h.As the normal stress increases,the improvement of the strength of samples with a large step height is larger than that of samples with a small step height,the improvement of the strength of samples withαof 10°is larger than that of samples withαof 0°and-10°.The discrete element method was used to simulate the shear test.Numerical results show five different types of displacement vectors,which can be used to determine whether the cracks are tensile cracks or shear cracks.The above conclusions can provide help for estimating mechanical properties and failure modes of rock masses with steps of different geometries.

基于Arrhenius-Weibull模型的ECU步进应力加速试验设计

文章基于Arrhenius-Weibull模型对ECU的加速寿命试验方法展开研究,基于加速模型试验原理选择步进应力施加方式。为满足产品的可靠度指标,通过分析Weibull分布情况计算最小试验样件数量。通过最大似然估计的方法确定产品的Arrhenius-Weibull模型参数,以便完成各个应力阶段的等效转换。通过对步进加速试验设计过程示例,提供一种满足产品寿命参数指标的判断依据,为后续从业者进行相关的加速试验设计提供依据。

Temperature and stress fields in electron beam welded Ti-15-3 alloy to 304 stainless steel joint with copper interlayer sheet

Electron beam welding of Ti-15-3 alloy to 304 stainless steel （STS） using a copper filler metal was carried out. The temperature fields and stress distributions in the Ti/Fe and Ti/Cu/Fe joint during the welding process were numerically simulated and experimentally measured. The results show that the rotated parabola body heat source is fit for the simulation of the electron beam welding. The temperature distribution is asymmetric along the weld center and the temperature in the titanium alloy plate is higher than that in the 304 STS plate. The thermal stress also appears to be in asymmetric distribution. The residual tensile stress mainly exists in the weld at the 304 STS side. The copper filler metal decreases the peak temperature and temperature grade in the joint as well as the residual stress. The longitudinal and lateral residual tensile strengths reduce by 66 MPa and 31 MPa, respectively. From the temperature and residual stress, it is concluded that copper is a good filler metal candidate for the electron beam welding of Ti-15-3 titanium alloy to 304 stainless steel.

一种新型SEPIC可拓展高增益DC-DC变换器

针对多串式并网光伏发电系统中的直流母线电压与太阳能光伏板的输出电压之间的电压水平不匹配问题,提出一种非隔离高增益DC-DC变换器。变换器在传统SEPIC变换器的基础上引入了开关电容网络,通过多个电容电压叠加实现了高增益,同时还降低了输入电流纹波,获得了更低的半导体器件电压应力。详细分析了变换器在连续导通模式和断续导通模式下的工作原理、电压增益以及半导体器件电压电流应力。此外,还探究了在连续导通模式下未考虑寄生元件与考虑寄生元件两种情况对变换器电压增益的影响程度。将变换器与其他6种升压变换器进行对比突显其性能优势。最后,搭建了一台200 W的实验样机进行验证,实验结果表明了所提变换器的正确性和可行性。

Application of observed strain steps to the study of remote earthquake stress triggering

A study of the Kunlunshan earthquake of MS = 8.1 based on observed coseismic strain steps from the borehole strain monitoring network over China has been carried out with some interesting results. Firstly, many recordings disagree with theoretic calculation using static dislocation model. Secondly, abnormally large strain steps are ob-served at quite a few stations in the tectonically active east-northern China, while in the relatively inactive east-southern China no obvious steps are recorded. It is inferred that seismic stress triggering may significantly affect remote seismic strain field. In other words, whether remote faulting be seismically triggered or not may de-termine the pattern of local seismic strain changes. Further comparison study results of March 11, 1999 Zhangbei earthquake and November 1, 1999 Datong earthquake show that the specific pattern of seismic zones has obvious influence on seismic strain changes in the region. This supports the idea that observed abnormal strain steps might be produced by coseismicly stress-triggered local faulting.

An Improved Method to Extract Generation of Interface Trap in Hot-Carrier-Stressed LDD n-MOSFET

A new improved technique,based on the direct current current voltage and charge pumping methods,is proposed for measurements of interface traps density in the channel and the drain region for LDD n MOSFET.This technique can be applied to virgin samples and those subjected to hot carrier stress,and the latter are known to cause the interface damage in the drain region and the channel region.The generation of interface traps density in the channel region and in the drain region can be clearly distinguished by using this technique.

Numerical simulation of flow separation over a backward-facing step with high Reynolds number

Large eddy simulation (LES) explicitly calculates the large-scale vortex field and parameterizes the small-scale vortices.In this study,LES and κ-ε models were developed for a specific geometrical configuration of backward-facing step (BFS).The simulation results were validated with particle image velocimetry (PIV) measurements and direct numerical simulation (DNS).This LES simulation was carried out with a Reynolds number of 9000 in a pressurized water tunnel with an expansion ratio of 2.00.The results indicate that the LES model can reveal largescale vortex motion although with a larger grid-cell size.However,the LES model tends to overestimate the top wall separation and the Reynolds stress components for the BFS flow simulation without a sufficiently fine grid.Overall,LES is a potential tool for simulating separated flow controlled by large-scale vortices.

Effects of bottom shear stresses on the wave-induced dynamic response in a porous seabed:PORO-WSSI (shear) model

When ocean waves propagate over the sea floor,dynamic wave pressures and bottom shear stresses exert on the surface of seabed.The bottom shear stresses provide a horizontal loading in the wave-seabed interaction system,while dynamic wave pressures provide a vertical loading in the system.However,the bottom shear stresses have been ignored in most previous studies in the past.In this study,the effects of the bottom shear stresses on the dynamic response in a seabed of finite thickness under wave loading will be examined,based on Biot＇s dynamic poro-elastic theory.In the model,an ＂u-p＂ approximation will be adopted instead of quasi-static model that have been used in most previous studies.Numerical results indicate that the bottom shear stresses has certain influences on the wave-induced seabed dynamic response.Furthermore,wave and soil characteristics have considerable influences on the relative difference of seabed response between the previous model（without shear stresses） and the present model（with shear stresses）.As shown in the parametric study,the relative differences between two models could up to 10% of p0,depending on the amplitude of bottom shear stresses.

Sensitivity analysis of pull-in voltage for RF MEMS switch based on modified couple stress theory

An approximate analytical model for calculating the pull-in voltage of a stepped cantilever-type radio frequency （RF） micro electro-mechanical system （MEMS） switch is developed based on the Euler-Bernoulli beam and a modified couple stress theory, and is validated by comparison with the finite element results. The sensitivity functions of the pull-in voltage to the designed parameters are derived based on the proposed model. The sensitivity investigation shows that the pull-in voltage sensitivities increase/decrease nonlinearly with the increases in the designed parameters. For the stepped cantilever beam, there exists a nonzero optimal dimensionless length ratio, where the pull-in voltage is insensitive. The optimal value of the dimensionless length ratio only depends on the dimensionless width ratio, and can be obtained by solving a nonlinear equation. The determination of the designed parameters is discussed, and some recommendations are made for the RF MEMS switch optimization.

Interfacial stress transfer behavior in a specially-shaped fiber/matrix pullout test

Specially designed fibers are widely used in engineering practice because the specially-designed shape can help to improve the bonding strength of the fiber and the interface. Studied in this paper is the interfacial shear stress transfer behavior on both sides of the specially designed fiber when it is being pulled out; in which automatic analysis of three-dimensional photoelasticity is employed and the finite element method is adopted. The results show that the stress transfer occurs mainly in the region near the fiber＇s embedded end where the stress reaches its critical point, leading to debonding of the interface. Before debonding, as the pullout loading increases, the peak value of shear stress transfers along the fiber from the embedded end to the interior of the matrix, and then stops at the hooked part of the fiber because of its impediment. When the interface begins to debond as the load increases, the shear stress can be transferred to the hooked part.

Lateral resonances in initial stressed 1-3 piezocomposites

A theoretical analysis of the lateral resonances in 1-3 piezocomposites with poling initial stress is conducted using the Bloch wave theory. Based on the linear piezoelectricity theory, theoretical formulations that include initial stress for the propagation of acoustic plane waves are made. Numerical calculations are performed to study the effects of the initial stress on the lateral mode frequencies and the stop band. It is found that lateral mode frequencies increase with the piezoelectricity of the piezocomposites, but decrease with the poling initial stress. The influence of the initial shear stress on the lateral mode frequencies is minimal, and can thus be neglected.

Thermoelastic stress analysis of multilayered films in a micro-thermoelectric cooling device

This paper presents an analytical solution for the thermoelastic stress in a typical in-plane＇s thin-film micro- thermoelectric cooling device under different operating con- ditions. The distributions of the permissible temperature fields in multilayered thin-films are analytically obtained, and the characteristics, including maximum temperature dif- ference and maximum refrigerating output of the thermo- electric device, are discussed for two operating conditions. Analytical expressions of the thermoelastic stresses in the layered thermoelectric thin-films induced by the tempera- ture difference are formulated based on the theory of mul- tilayer system. The results demonstrate that, the geometric dimension is a significant factor which remarkably affects the thermoelastic stresses. The stress distributions in layers of semiconductor thermoelements, insulating and support- ing membrane show distinctly different features. The present work may profitably guide the optimization design of high- efficiency micro-thermoelectric cooling devices.

Prediction of flow stress of Ti-15-3 alloy with artificial neural network

Hot compression experiments were conducted on Ti 15 3 alloy specimens using Gleeble 1500 Thermal Simulator.These tests were focused to obtain the flow stress data under various conditions of strain,strain rate and temperature. On the basis of these data, the predicting model for the nonlinear relation between flow stress and deformation strain,strain rate and temperature for Ti 15 3 alloy was developed with a back propagation artificial neural network method. Results show that the neural network can reproduce the flow stress in the sampled data and predict the nonsampled data well. Thus the neural network method has been verified to be used to tackle hot deformation problems of Ti 15 3 alloy. [

A fractional differential constitutive model for dynamic stress intensity factors of an anti-plane crack in viscoelastic materials

Fractional differential constitutive relationships are introduced to depict the history of dynamic stress inten- sity factors （DSIFs） for a semi-infinite crack in infinite viscoelastic material subjected to anti-plane shear impact load. The basic equations which govern the anti-plane deformation behavior are converted to a fractional wave-like equation. By utilizing Laplace and Fourier integral transforms, the fractional wave-like equation is cast into an ordinary differential equation （ODE）. The unknown function in the solution of ODE is obtained by applying Fourier transform directly to the boundary conditions of fractional wave-like equation in Laplace domain instead of solving dual integral equations. Analytical solutions of DSIFs in Laplace domain are derived by Wiener-Hopf technique and the numerical solutions of DSIFs in time domain are obtained by Talbot algorithm. The effects of four parameters α, β, b1, b2 of the fractional dif- ferential constitutive model on DSIFs are discussed. The numerical results show that the present fractional differential constitutive model can well describe the behavior of DSIFs of anti-plane fracture in viscoelastic materials, and the model is also compatible with solutions of DSIFs of anti-plane fracture in elastic materials.