Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

PDZK1 protects against mechanical overload-induced chondrocyte senescence and osteoarthritis by targeting mitochondrial function

Mechanical overloading and aging are two essential factors for osteoarthritis(OA)development.Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology,but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated.

Investigations of the mechanical response of dummy HTPB propellant grain under ultrahigh acceleration overload conditions using onboard flight-test measurements

In this paper,to study the mechanical responses of a solid propellant subjected to ultrahigh acceleration overload during the gun-launch process,specifically designed projectile flight tests with an onboard measurement system were performed.Two projectiles containing dummy HTPB propellant grains were successfully recovered after the flight tests with an ultrahigh acceleration overload value of 8100 g.The onboard-measured time-resolved axial displacement,contact stress and overload values were successfully obtained and analysed.Uniaxial compression tests of the dummy HTPB propellant used in the gunlaunched tests were carried out at low and intermediate strain rates to characterize the propellant's dynamic properties.A linear viscoelastic constitutive model was employed and applied in finite-element simulations of the projectile-launching process.During the launch process,the dummy propellant grain exhibited large deformation due to the high acceleration overload,possibly leading to friction between the motor case and propellant grain.The calculated contact stress showed good agreement with the experimental results,though discrepancies in the overall displacement of the dummy propellant grain were observed.The dynamic mechanical response process of the dummy propellant grain was analysed in detail.The results can be used to estimate the structural integrity of the analysed dummy propellant grain during the gun-launch process.

SiO_(2) Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed.Results SiO_(2) altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO_(2)-induced mitochondrial damage and myocardial injury.SiO_(2) inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO.Conclusion Iron overload-induced ferroptosis contributes to SiO_(2)-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO_(2) cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

Numerical Simulation-Based Analysis of the Impact of Overloading on Segmentally Assembled Bridges

Segmentally assembled bridges are increasinglyfinding engineering applications in recent years due to their unique advantages,especially as urban viaducts.Vehicle loads are one of the most important variable loads acting on bridge structures.Accordingly,the influence of overloaded vehicles on existing assembled bridge structures is an urgent concern at present.This paper establishes thefinite element model of the segmentally assembled bridge based on ABAQUS software and analyzes the influence of vehicle overload on an assembled girder bridge struc-ture.First,afinite element model corresponding to the target bridge is established based on ABAQUS software,and the load is controlled to simulate vehicle movement in each area of the traveling zone at different times.Sec-ond,the key cross-sections of segmental girder bridges are monitored in real time based on the force character-istics of continuous girder bridges,and they are compared with the simulation results.Finally,a material damage ontology model is introduced,and the structural damage caused by different overloading rates is compared and analyzed.Results show that thefinite element modeling method is accurate by comparing with on-site measured data,and it is suitable for the numerical simulation of segmental girder bridges;Dynamic sensors installed at 1/4L,1/2L,and 3/4L of the segmental girder main beams could be used to identify the dynamic response of segmental girder bridges;The bottom plate of the segmental girder bridge is mostly damaged at the position where the length of the precast beam section changes and the midspan position.With the increase in load,damage in the direction of the bridge develops faster than that in the direction of the transverse bridge.Thefindings of this study can guide maintenance departments in the management and maintenance of bridges and vehicles.

GNSS array receiver faced with overloaded interferences:anti-jamming performance and the incident directions of interferences

Anti-jamming solutions based on antenna arrays enhance the anti-jamming ability and the robustness of global navigation satellite system(GNSS)receiver remarkably.However,the performance of the receiver will deteriorate significantly in the overloaded interferences scenario.We define the overloaded interferences scenario as where the number of interferences is more than or equal to the number of antenna arrays elements.In this paper,the effect mechanism of interferences with different incident directions is found by studying the anti-jamming performance of the adaptive space filter.The theoretical analysis and conclusions,which are first validated through numerical examples,reveal the relationships between the optimal weight vector and the eigenvectors of the input signal autocorrelation matrix,the relationships between the interference cancellation ratio(ICR),the signal to interference and noise power ratio(SINR)of the adaptive space filter output and the number of interferences,the eigenvalues of the input signal autocorrelation matrix.In addition,two simulation experiments are utilized to further corroborate the theoretical findings through soft anti-jamming receiver.The simulation results match well with the theoretical analysis results,thus validating the effect mechanism of overloaded interferences.The simulation results show that,for a four elements circular array,the performance difference is up to 19 dB with different incident directions of interferences.Anti-jamming performance evaluation and jamming deployment optimization can obtain more accurate and efficient results by using the conclusions.

Correction of dynamic Brazilian disc tensile strength of rocks under preloading conditions considering the overload phenomenon and invoking the Griffith criterion

Dynamic tensile failure is a common phenomenon in deep rock practices,and thus accurately evaluating the dynamic tensile responses of rocks under triaxial pressures is of great significance.The Brazilian disc(BD)test is the suggested method by the International Society for Rock Mechanics and Rock Engineering(ISRM)for measuring both the static and dynamic tensile strengths of rock-like materials.However,due to the overload phenomenon and the complex preloading conditions,the dynamic tensile strengths of rocks measured by the BD tests tend to be overestimated.To address this issue,the dynamic BD tensile strength(BTS)of Fangshan marble(FM)under different preloading conditions were measured through a triaxial split Hopkinson pressure bar(SHPB).The fracture onset in BD specimen was captured through a strain gage around the disc center.The discrepancy between the traditional tensile strength(TTS,determined by the peak load P_(f) of the BD specimen)and the nominal tensile strength(NTS,obtained from the load P_(i) when the diametral fracture commences in the tested BD specimen)was applied to quantitatively evaluating the overload phenomenon.The Griffith criterion was used to rectify the calculation of the tensile stress at the disc center under triaxial stress states.The results demonstrate that the overload ratio(s)increases with the loading rate(σ)and decreases with the hydrostatic pressure(σ_(s)).The TTS corrected by the Griffith criterion is independent of theσ_(s)due to the overload phenomenon,while the NTS corrected by the Griffith criterion is sensitive to both the andσ.Therefore,it is essential to modify the tensile stress in dynamic confined BD tests using both the overload correction and the Griffith criterion rectification to obtain the accurate dynamic BTS of rocks.

Curcumin attenuates iron-overloaded stress to macrophages via up-regulation of SOD and Nrf2

Background:It is known to all that iron overload is a fatal adverse effect on cells and tissue.Herein,our study aimed to investigate the effects of curcumin on iron-overloaded stress in macrophages.Methods:Ferric ammonium citrate was added to the macrophage cell line(RAW264.7)to establish an iron-overloaded macrophage model.Cell counting kit 8 assay was used to detect cell viability.Superoxide dismutase,reactive oxygen species,malondialdehyde,and apoptosis were performed to analyze the severity of cellular oxidative damage.In addition,quantitative real-time polymerase chain reaction and western blot were used to detect the expression of nuclear factor erythroid 2-related factor 2.Results:The result showed that iron overload of macrophage was visualized by incubating in 40μM ferric ammonium citrate for 24 h.The curcumin significantly reversed the iron overload-induced apoptotic cells at low(10μM)and middle(20μM)concentrations.Additionally,the levels of malondialdehyde and reactive oxygen species activity in the groups of curcumin at low(10μM)and middle(20μM)concentrations were significantly decreased,while superoxide dismutase activity was obviously increased compared with that of the ferric ammonium citrate group alone.Finally,we found that low(10μM)and middle(20μM)dose curcumin up-regulated nuclear factor erythroid 2-related factor 2 expression at mRNA and protein levels compared with the ferric ammonium citrate group alone.Conclusion:Curcumin reduces iron-overloaded stress in macrophages by activating nuclear factor erythroid 2-related factor 2 and enhancing the superoxide dismutase activity,thereby protecting cell apoptosis.

铁死亡在非酒精性脂肪性肝病发病中作用的研究进展

铁死亡是近年提出的一种新型细胞死亡方式,其主要特征为铁过载及脂质过氧化。铁死亡参与非酒精性脂肪性肝病的发生发展。铁过载可通过芬顿反应产生大量活性氧,在脂氧合酶的作用下,肝细胞膜上的不饱和脂肪酸发生脂质过氧化,从而诱导肝细胞死亡,导致非酒精性脂肪性肝病/非酒精性脂肪性肝炎的发生。阻断铁死亡可能成为保护肝细胞的治疗策略之一。

再生障碍性贫血“瘀证”与铁过载的相关性探讨

铁过载和中医“血瘀证”在再生障碍性贫血(简称再障)的发生发展中发挥着重要作用。围绕再障“瘀证”的发生机制和临床特征,结合中医“取象比类”和相关临床基础研究进展,系统阐述了铁过载与再障中医“瘀证”潜在的相关性。铁螯合治疗契合“祛瘀生新”的中医理论,有利于改善造血,而从中医“补肾活血”着手,同样有助于疾病临床疗效的提升。

差异化授权型领导与知识型员工知识隐藏——基于跨层分析

基于团队和个体视角构建两个中介模型,探讨差异化授权型领导对知识型员工知识隐藏的内在作用机制。通过对67个团队的358位员工进行跨层检验,分析发现:在团队层面,差异化授权型领导通过降低团队信任,从而增强知识型员工知识隐藏动机;在个体层面,差异化授权型领导通过对知识型员工角色负荷、情绪耗竭的链式影响而诱发知识隐藏行为。上述结论丰富了差异化授权型领导影响后果研究,为促进团队成员知识分享与流动提供了重要的实践启示。

miRNA-208a-3p过表达致慢性心衰大鼠心肌细胞线粒体钙超载和功能障碍的机制研究

目的观察miRNA-208a-3p在慢性心力衰竭大鼠心肌中的表达水平,探讨其在线粒体钙稳态和线粒体功能方面的调节机制。方法35只健康SD大鼠,随机分为模型组(n=20)和对照组(n=15),模型组采用腹主动脉直径缩窄法建立慢性心衰模型,对照组行假手术。通过心功能和组织病理学检测评价模型,测定心肌miR-208a-3p表达,心肌线粒体去乙酰化酶3(SIRT3)蛋白和NADH脱氢酶亚基1(ND1)蛋白表达、线粒体Ca2+水平、心肌细胞活性氧(ROS)生成。结果模型组大鼠心肌miR-208a-3p表达水平显著高于对照组(P<0.05),SIRT3蛋白表达显著低于对照组(P<0.001),且miR-208a-3p与SIRT3表达呈显著负相关;模型组ND1蛋白表达显著低于对照组(P<0.05),且ND1与SIRT3表达呈显著正相关;模型组心肌细胞线粒体内Ca2+水平显著高于对照组(P<0.05),心肌细胞ROS生成也显著高于对照组(P<0.05)。结论慢性心衰心肌组织miR-208a-3p过度表达与SIRT3/ND1活性降低相关,抑制线粒体呼吸链活性,此外,心肌细胞出现线粒体钙超载和ROS生成增加,进一步加剧线粒体呼吸功能障碍,是慢性心衰线粒体功能障碍的重要机制。

一种套装式子母弹抛撒用燃气发生器的设计研究

为实现子母弹低过载抛撒功能,设计了一种套装式燃气发生器,通过在燃气发生器燃烧室外增加套装壳体形成降压增容辅助室,从而提高抛撒机构的初始作用容积,以达到降低抛撒过载的目的,并通过仿真和试验手段对基于套装式和典型结构燃气发生器的抛撒机构内弹道性能进行了对比研究。结果表明:在相同抛撒速度下,套装式燃气发生器产生的抛撒过载为16.2g,比典型结构燃气发生器的抛撒过载降低了10.4g,降比约39%,过载降低效果明显。本研究为低过载子弹抛撒用燃气发生器设计提供了新的思路。

基于冷流推力的变微过载控制方法研究

针对地面微重力环境下的变微过载控制方法,以不同冷流压力以及二次流入射位置等因素,开展了基于冷流推力的流场仿真,分析了二次射流对主流流场影响。并研制了冷流推力系统,通过测试验证了冷流推力与总压的相互关系。并通过微重力落舱开展了1s微重力环境下的变微过载试验,结果表明通过冷流流场型面设计,以及主流、二次流压力的控制可以控制作用于内舱的推力,从而改变内舱微重力环境下的微重力水平,满足在微重力环境下的变微过载控制能力。

小口径弹载遥测系统天线设计

天线是弹载遥测系统的核心器件。针对小口径弹载遥测系统的特殊需求,开展弹载天线设计。采用圆极化模式消除炮弹飞行过程中自旋对遥测信号的影响;通过扩展天线的波束宽度适应炮弹的曲线弹道;为满足小口径炮弹对天线小尺寸的需求,通过采用高介电常数介质基板并对辐射单元开槽实现天线小型化;天线和弹载遥测系统板卡之间采用插针相连以实现天线的抗过载要求。对所设计的天线进行试制加工,并测得其阻抗带宽为24 MHz,沿轴线±80°内的轴比均小于3 dB,且其顶点处增益为2.18 dBi。测试结果表明此天线的性能够满足实际使用需求。

装药过载环境力等效模拟实验技术研究

为解决装药安全可靠性能实验成本高、强过载环境测试难度大等瓶颈问题,以等效模拟弹体侵彻钢板时内部装药过载环境力为目标,基于数值模拟方法,设计了装药过载环境力等效模拟实验装置,并开展了等效模拟实验,突破了同时满足加载压力大于1 GPa和脉冲宽度大于100μs的技术难点。结果表明,弹丸侵彻钢板时装药受到的过载为正弦波单脉冲。在装置中采用波形调整器不仅能够调控加载到待测药表面的波形,还能对压力的衰减产生大幅影响。随着波形调整器厚度的增大,加载在待测药表面的压力逐渐减小,脉冲宽度显著增大;随着飞片厚度增大,飞片获得的驱动速度逐渐减小,加载在待测药表面的压力明显减小,脉冲宽度变化不明显。装药过载环境力模拟装置形成的脉冲特征值与弹丸侵彻钢靶过程的数值模拟结果对比,超压峰值误差最高为5.71%,脉宽误差最高为14.8%,均低于15%,验证了用该装置模拟弹体侵彻钢靶时装药加载状态的等效性。

地面超载下摩擦单桩负摩阻力的连续介质力学解

针对地面超载引起的摩擦单桩负摩阻力,提出了一种基于桩土相互作用和连续介质力学的竖向位移模型来模拟桩土系统位移,模型中包含了桩土轴线位移函数和沿径向的衰减函数;采用变分法得到了桩土系统的总势能,从而得到了位移模型中桩土位移和衰减函数的耦合控制方程;利用迭代法求解了这两个耦合函数,得到了桩身轴力、中性面、负摩阻力、下拉力和土弹簧等效刚度等关键参数的数学表达式;通过和原位试验及已有理论结果的对比,验证了所提方法的正确性。结果表明:桩土模量比对桩的负摩阻力和下拉力有显著影响,中性面位置与长细比密切相关,而与桩土模量比关系不大;随着桩土模量比增大和桩长细比减小,桩身同一位置处轴力增长明显,但增长速率变缓;地面超载作用下桩周土体位移最大沉降出现在地表处,且地表以下0.3倍桩长范围内为位移强烈影响区;桩长细比和桩土模量比的增加均会使桩周土体位移场影响范围增大。

舰船内高能量密度电容过载爆炸损伤分析

文中通过建立电容单元的过载爆炸能量等效模型,运用任意拉格朗日-欧拉(ALE)方法求解冲击波与结构的流固耦合过程,模拟电容组中电容单元的爆炸过程随不同电容单元间距,不同位置电容单元爆炸对整个电容组的损伤.分析不同工况下电容组的损伤结果,发现增加电容单元间距可以有效地降低电容组整体的损伤程度.在相同位置电容单元爆炸时,不同电容单元间距对正前方和正侧方的电容单元损伤不同:间距增加至2倍时,正前方最大位移约降低32.17%,正侧方电容单元的最大位移约降低24.19%;间距增至3倍时,正前方电容单元的最大位移约降低48.69%,正侧方电容单元的最大位移约降低41.13%.

开洞刚性墙后土体破坏模式运动单元上限分析

超载作用下开洞地下刚性连续墙后土体稳定性问题具有广泛的工程应用背景。考虑墙体矩形开洞宽度足够大,且刚性墙与土体完全光滑接触等条件,参考构造刚性多块体上限法思路,预设墙后土体极简破坏机构并转化为初始三角网格,提出交替循环式新增节点、单元缩减、对角互换及成层加密等网格更新措施,同步开展基于刚体平动运动单元上限方法的刚性墙后土体破坏分析,通过多层级非线性规划运算获得高精度临界超载系数σ_(s)/c上限解,界定墙后土体滑移线网破坏模式及其定量范围与扩展边界。进一步依前述流程计算获得多参数影响下的临界超载系数σ_(s)/c上限解图表,结果表明:1)刚性墙后土体典型破坏特征表现为土体上方和开洞处的整体下沉刚性区域,开洞前方核心区域以密集滑移线网区隔的刚性滑块群,以及外围主要滑动面;2)临界超载系数σ_(s)/c随土体内摩擦角ϕ增大而增大,且后续增幅显著增加;3)σ_(s)/c随开洞深度比C/D的增大呈现出近似线性增大的趋势;4)相较于ϕ和C/D,土体重度参数γD/c的变化对于σ_(s)/c的影响不甚明显,σ_(s)/c随γD/c增大呈现近似线性减小的趋势;5)σ_(s)/c受剪胀角参数ψ/ϕ的影响与ϕ的增大程度密切相关。本研究结果可为开洞地下刚性连续墙后土体失稳破坏模式定量分析、破坏机理研究及工程措施制定等工作提供有力的数据支持。