Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Correlation between the rock mass properties and maximum horizontal stress:A case study of overcoring stress measurements

Understanding the mechanical properties of the lithologies is crucial to accurately determine the horizontal stress magnitude.To investigate the correlation between the rock mass properties and maximum horizontal stress,the three-dimensional(3D)stress tensors at 89 measuring points determined using an improved overcoring technique in nine mines in China were adopted,a newly defined characteristic parameter C_(ERP)was proposed as an indicator for evaluating the structural properties of rock masses,and a fuzzy relation matrix was established using the information distribution method.The results indicate that both the vertical stress and horizontal stress exhibit a good linear growth relationship with depth.There is no remarkable correlation between the elastic modulus,Poisson's ratio and depth,and the distribution of data points is scattered and messy.Moreover,there is no obvious relationship between the rock quality designation(RQD)and depth.The maximum horizontal stress σ_(H) is a function of rock properties,showing a certain linear relationship with the C_(ERP)at the same depth.In addition,the overall change trend of σ_(H) determined by the established fuzzy identification method is to increase with the increase of C_(ERP).The fuzzy identification method also demonstrates a relatively detailed local relationship betweenσ_H and C_(ERP),and the predicted curve rises in a fluctuating way,which is in accord well with the measured stress data.

EFFECTS OF STRAIN RATIO ON THERMAL-MECHANICAL CYCLIC STRESS-STRAIN RESPONSE AND FATIGUE LIFE IN DS SUPERALLOY DZ125

The effects of strain ratio on thermal-mechanical cyclic stress-strain response and fatigue life in DS superalloy DZ125 have been studied by performing tests at various strain ratio experiments, under strain-controlled and temperature cycling from 550 to 1000℃. It is shown that thermal-mechanical cyclic stress-strain response behavior not only depend on magnitude of strain, and temperature-loading phase angle, but also strain ratio. Fatigue life at strain ratio Rε=-0.3 is longer than that of strain ratio Rε=-1.0, under in-phase thermal-mechanical loading. However, Fatigue life at strain ratio Rε=-0.3 is shorter than that of strain ratio Rε=-1.0, under out-of-phase thermal-mechanical loading. The thermal-mechanical fatigue (TMF) damage model was discussed. Results of fractography show that fatigue, creep and oxidation damage always occur during TMF. The main damage mode depends on loading wave, strain ratio and magnitude of strain.

Dip2a regulates stress susceptibility in the basolateral amygdala

Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.

Thermal-Mechanical Simulation and Analysis on Structural Caused Package Induced Stress in Stacked Chip Scale Package

Stacked chip scale package(SCSP) attracts more and more attentions in advanced packages application with light weight,thin and small size,high reliability,low power and high storage capability.However,more and more physical and electrical issues being caused by package-induced stress in SCSP were reported recently.The effect of structural factors,including die thickness,die attach film thickness,die attach film type,and spacer size on package induced stress,was investigated.Analyses were given based on simulation results and provide important suggestion for package design.

Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

Thermal-mechanical response of microscale functional film for infrared window

Infrared window in hypersonic missile usually suffers complex aerodynamic force/heat during high-speed flight.A finite element method was adopted to simulate the thermal and stress response of microscale functional film for infrared window under different aerodynamic heats/forces conditions.Temperature and stress distribution were obtained with different heat fluxes.There is almost constant stress distribution along the film thickness except a sudden decrease near the substrate.The maximum stresses are located at the points which are 0.3 mm away from the edges.Different film materials result in different stress values.The temperature and stress in ZrN are larger than those in Y2O3.Besides the numerical simulation,an oxygen propane flame jet impingement test was performed to investigate thermal shock failure of the infrared window.Some place of the window surface has spots damage and some place has line crack damage after thermal shock.

Cracked elastic substrate strip with functionally graded coating under thermal-mechanical loading

This paper investigates the functionally graded coating bonded to an elastic strip with a crack under thermal- mechanical loading. Considering some new boundary conditions, it is assumed that the temperature drop across the crack surface is the result of the thermal conductivity index which controls heat conduction through the crack region. By the Fourier transforms, the thermal-elastic mixed boundary value problems are reduced to a system of singular integral equations which can be approximately solved by applying the Chebyshev polynomials. The numerical computation methods for the temperature, the displacement field and the thermal stress intensity factors （TSIFs） are presented. The normal temperature distributions （NTD） with different parameters along the crack surface are analyzed by numerical examples. The influence of the crack position and the thermal-elastic non- homogeneous parameters on the TSIFs of modes I and 11 at the crack tip is presented. Results show that the variation of the thickness of the graded coating has a significant effect on the temperature jump across the crack surfaces when keeping the thickness of the substrate constant, and the thickness of functionally graded material （FGM） coating has a significant effect on the crack in the substrate. The results can be expected to be used for the purpose of gaining better understanding of the thermal-mechanical behavior of graded coatings.

Thermal-mechanical properties of short carbon fiber reinforced geopolymer matrix composites subjected to thermal load

Short carbon fiber preform reinforced geopolymer composites containing different contents of α-Al2O3 filler （Cr（a-Al2O3）/geopolymer composites） were fabricated, and the effects of heat treatment temperatures up to 1 200 ℃ on the thermal-mechanical properties were studied. The results show that the thermal shrinkage in the direction perpendicular to the lamination of the composites gradually increases with the increase of the heat treatment temperatures from room temperature （25 ℃ ） to 1000 ℃. However, the composites in the direction parallel to the lamination show an expansion behavior. Beyond 1 000℃, in the two directions the composites exhibit a larger degree of shrinkage due to the densification and crystallization. The mechanical properties of the composites show the minimum values in the temperature range from 600 to 800 ℃ as the hydration water of geopolymer matrix is lost. The addition of α-Al2O3 particle filler into the composites clearly increases the onset crystalline temperature of leucite （KAlSi2O6） from the amorphous geopolymer matrix. In addition, the addition of α-Al2O3 particles into the composites can not only help to keep volume stable at high temperatures but also effectively improve the mechanical properties of the composites subjected to thermal load to a certain extent. The main toughening mechanisms of the composites subjected to thermal load are attributed to fiber pulling-out.

Fatigue behaviour of coke drum materials under thermal-mechanical cyclic loading

Coke drums are vertical pressure vessels used in the delayed coking process in petroleum refineries. Significant temperature variation during the delayed coking process causes damage in cracking. There were some studies on coke drums in the form of bulging and the fatigue life estimation for the coke drums, but most of them were based on strain-fatigue life curves at constant temperatures, which do not consider simultaneous cyclic temperature and mechanical loading conditions. In this study, a fatigue testing system is successfully devel- oped to allow performing thermal-mechanical fatigue （TMF） test similar to the coke drum loading condition. Two commonly used base and one clad materials of coke drums are then experimentally investigated. In addition, a comparative study between isothermal and TMF lives of these materials is conducted. The experimental findings lead to better understanding of the damage mechanisms occurring in coke drums and more accurate prediction of fatigue life of coke drum materials.

Thermal-Mechanical Fatigue Behavior and Life Analysis of Cast Ni-base Superalloy K417

In-phase (IP) and out-of-phase (OP) thermal-mechanical fatigue (TMF) behavior of cast Ni-base superalloy K417 was studied. All experiments were carried out under total strain control with temperature cycling between 400-850℃. Both in-phase and out-of-phase TMF specimens exhibited cyclic hardening followed by cyclic softening at the minimum temperature. Besides, they cyclically hardened in the early stage of life followed by cyclic softening at the maximum temperature. OP TMF life was longer than that of IP TMF. Various damage mechanisms operating in different controlled strain ranges and phasing were discussed. A few life prediction methods for isothermal fatigue were used to handle TMF fatigue and their applicability to superalloy K417 was evaluated. The SEM analysis of the fracture surface showed that transgranular fracture was the principal cracking mode for both IP and OP TMF. Oxidation was the main damage mechanism in causing shorter fatigue life for IP TMF compared with OP TMF.

Numerical simulation of a sheet metal extrusion process by using thermal-mechanical coupling EAS FEM

The thermal-mechanical coupling finite element method(FEM)was usedto simulate a non-isothermal sheet metal extrusion process. On thebasis of the finite plasticity consistent with multiplicativedecomposition of the deformation gradient, the enhanced as- sumedstrain(EAS)FEM was applied to carry out the numerical simulation. Inorder to make the computation reliable ad avoid hour- glass mode inthe EAS element under large compressive strains, an alterative formof the original enhanced deformation gradient was employed. Inaddition, reduced factors were used in the computation of the elementlocal internal parameters and the enhanced part of elementalstiffness.

Ferroptosis and endoplasmic reticulum stress in ischemic stroke

Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron metabolism.The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum,and the progression of inflammatory diseases can trigger endoplasmic reticulum stress.Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival.Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke.However,there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke.This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke,aiming to provide a reference for developing treatments for ischemic stroke.

Grain Yield,Biomass Accumulation,and Leaf Photosynthetic Characteristics of Rice under Combined Salinity-Drought Stress

Simultaneous stresses of salinity and drought often coincide during rice-growing seasons in saline lands,primarily due to insufficient water resources and inadequate irrigation facilities.Consequently,combined salinity-drought stress poses a major threat to rice production.In this study,two salinity levels(NS,non-salinity;HS,high salinity)along with three drought treatments(CC,control condition;DJ,drought stress imposed at jointing;DH,drought stress imposed at heading)were performed to investigate their combined influences on leaf photosynthetic characteristics,biomass accumulation,and rice yield formation.Salinity,drought,and their combination led to a shortened growth period from heading to maturity,resulting in a reduced overall growth duration.Grain yield was reduced under both salinity and drought stress,with a more substantial reduction under the combined salinity-drought stress.The combined stress imposed at heading caused greater yield losses in rice compared with the stress imposed at jointing.Additionally,the combined salinity-drought stress induced greater decreases in shoot biomass accumulation from heading to maturity,as well as in shoot biomass and nonstructural carbohydrate(NSC)content in the stem at heading and maturity.However,it increased the harvest index and NSC remobilization reserve.Salinity and drought reduced the leaf area index and SPAD value of flag leaves and weakened the leaf photosynthetic characteristics as indicated by lower photosynthetic rates,transpiration rates,and stomatal conductance.These reductions were more pronounced under the combined stress.Salinity,drought,and especially their combination,decreased the activities of ascorbate peroxidase,catalase,and superoxide dismutase,while increasing the contents of malondialdehyde,hydrogen peroxide,and superoxide radical.Our results indicated a more significant yield loss in rice when subjected to combined salinity-drought stress.The individual and combined stresses of salinity and drought diminished antioxidant enzyme activities,inhibited leaf photosynthetic functions,accelerated leaf senescence,and subsequently lowered assimilate accumulation and grain yield.

Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

First Cycle Effect of Polycrystalline CuZnAl Shape Memory Alloy during Thermal-Mechanical Cycling

The thermal-mechanical (T-M) cycles at constant strain of a polycrystalline CuZnAl alloy have been studied in the. present work. In-situ optical microscopic observations have been made to reveal the features of the phase transitions during T-M cycling. The variation of stress-temperature (S-T) curves and electrical resistance-temperature (R-T) curves accompanying with T-M cycling have been measured by tensile test and electrical resistance measurements. It has been found that the polycrystalline CuZnAl alloy shows apparent morphology changes and properties variations in the first cycle during T-M cycling which is called the first cycle effect in the present work. The stable transformation procedure in the T-M cycle is: martensiteparent phase +residual acicular martensite. This residual martensite possesses the character of stress-induced martensite.

Impact of effective stress on permeability for carbonate fractured-vuggy rocks

To gain insight into the flow mechanisms and stress sensitivity for fractured-vuggy reservoirs,several core models with different structural characteristics were designed and fabricated to investigate the impact of effective stress on permeability for carbonate fractured-vuggy rocks(CFVR).It shows that the permeability performance curves under different pore and confining pressures(i.e.altered stress conditions)for the fractured core models and the vuggy core models have similar change patterns.The ranges of permeability variation are significantly wider at high pore pressures,indicating that permeability reduction is the most significant during the early stage of development for fractured-vuggy reservoirs.Since each obtained effective stress coefficient for permeability(ESCP)varies with the changes in confining pressure and pore pressure,the effective stresses for permeability of four representative CFVR show obvious nonlinear characteristics,and the variation ranges of ESCP are all between 0 and 1.Meanwhile,a comprehensive ESCP mathematical model considering triple media,including matrix pores,fractures,and dissolved vugs,was proposed.It is proved theoretically that the ESCP of CFVR generally varies between 0 and 1.Additionally,the regression results showed that the power model ranked highest among the four empirical models mainly applied in stress sensitivity characterization,followed by the logarithmic model,exponential model,and binomial model.The concept of“permeability decline rate”was introduced to better evaluate the stress sensitivity performance for CFVR,in which the one-fracture rock is the strongest,followed by the fracture-vug rock and two-horizontalfracture rock;the through-hole rock is the weakest.In general,this study provides a theoretical basis to guide the design of development and adjustment programs for carbonate fractured-vuggy reservoirs.