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.

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.

Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

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.

Residual elastic stress strain field and geometrically necessary dislocation density distribution around nano-indentation in TA15 titanium alloy

Nanoindentation and high resolution electron backscatter diffraction（EBSD） were combined to examine the elastic modulus and hardness of α and β phases,anisotropy in residual elastic stress strain fields and distributions of geometrically necessary dislocation（GND） density around the indentations within TA15 titanium alloy.The nano-indention tests were conducted on α and β phases,respectively.The residual stress strain fields surrounding the indentation were calculated through crosscorrelation method from recorded patterns.The GND density distribution around the indentation was calculated based on the strain gradient theories to reveal the micro-mechanism of plastic deformation.The results indicate that the elastic modulus and hardness for α p hase are 129.05 GPas and 6.44 GPa,while for β phase,their values are 109.80 GPa and 4.29 GPa,respectively.The residual Mises stress distribution around the indentation is relatively heterogeneous and significantly influenced by neighboring soft β phase.The region with low residual stress around the indentation is accompanied with markedly high a type and prismatic-GND density.

Finite element analysis of stress distribution and burst failure of SiC_f/Ti-6Al-4V composite ring

A three-dimensional cyclic symmetry finite element model of titanium-matrix composites（TMCs） ring was developed to investigate the stress distribution and burst failure. The effects of fiber volume fractions, reinforced areas, thermal residual stresses and two different temperatures on stress distribution were studied. The burst speed was obtained through analyzing the hoop tensile stresses under a series of rotating speeds. The results indicate that at the two different temperatures, the influences of fiber volume fractions and reinforced areas on stress level and distribution are different. Some proposals are provided for the structure design of the TMCs ring. With regard to thermal residual stresses, a larger reinforced area is an advisable choice for design of the ring at higher temperature.

Absorption and Distribution of Na^+, K^+ and Chlorophyll Fluorescence in Castor under Salt Stress

[Objective] The aim of this study is to reveal the salt resistance of castor. [Method] Under salt stress, the growth, osmotic potential, chlorophyll fluorescence parameters, Na^+ and K^+ uptakes and transports in the seedlings of two Ricinus communis varieties (cultivar castor ‘Zibi 6’ and wild castor which grew naturally in coastal saline-alkali land), were comparatively studied. [Result] Wild castor preformed better in halophilism than that of cultivar castor Zibi 6 under the NaCl treatment. One of the salt tolerant mechanisms of castor is to improve K^+ uptake and transport to overground portion, thus to maintain K^+/Na^+ homeostasis in leaves; on the other hand, the high stability of Photoreaction System Ⅱ (PS Ⅱ) plays a key role in maintaining the leaf photosynthetic rate under salt stress. [Conclusion] The results of this study provided theoretical basis for the extension and application of castor in saline beach.

Nonlinear Analysis of Axial-load and Stress Distribution for Threaded Connection

Analytical method for the distributions of axial-load and stress is based on elastic assumption, but the threaded connections are often in plastic deformation stage in practice. Meanwhile the strain in the threaded connection is difficult to measure. So it is necessary to study the reliable numerical method. At present neither the convergence analysis of the computational results nor the elastic-plastic analysis in the loading-unloading process are studied. In this paper, von Mises plasticity and kinematic hardening model is used to describe the material response. A new convergence criterion for nonlinear finite element analysis of the loading-unloading process is proposed. An axisymmetric finite element model according to the proposed convergence criterion is developed and used to analyze the distributions of axial-load and stress. It can be conclude that the stress distribution analysis is more dependent on the mesh density than the axial-load distribution analysis. The stress distribution result indicates that with increasing of applied load, the engaged threads close to the nut-bearing surface become plastic firstly. The axial-load distribution result reveals that the load percentage carried by single thread depends on the position of thread and load intensity. When the load is relatively small, the applied load is mainly carried by the engaged threads near the nut-bearing surface, when the load is larger, the differences of percentages for all threads become small. The proposed convergence analyzing procedure is applicable for other nonlinear analyses. The obtained distributions of axial-load and stress can be a reference of engineering application.

Analytical model and application of stress distribution on mining coal floor

Given the analysis of underground pressure, a stress calculation model of coal floor stress has been established based on a theory of elasticity. The model presents the law of stress distribution on the relatively fixed position of the mining coal floor： the extent of stress variation in a fixed floor position decreases gradually along with depth, the decreasing rate of the vertical stress is clearly larger than that of the horizontal stress at a specific depth. The direction of the maximum principal stress changes gradually from a vertical direction to a horizontal direction with the advance of the working face. The deformation and permeability of the rock mass of the coal floor are obtained by contrasting the difference of the principal stress established from theoretical calculations with curves of stress-strain and permeability-strain from tests, which is an important mechanical basis for preventing water inrush from confined aauifers.

Predicting the present-day in situ stress distribution within the Yanchang Formation Chang 7 shale oil reservoir of Ordos Basin, central China

The Yanchang Formation Chang 7 oil-bearing layer of the Ordos Basin is important in China for producing shale oil.The present-day in situ stress state is of practical implications for the exploration and development of shale oil;however,few studies are focused on stress distributions within the Chang 7 reservoir.In this study,the present-day in situ stress distribution within the Chang 7 reservoir was predicted using the combined spring model based on well logs and measured stress data.The results indicate that stress magnitudes increase with burial depth within the Chang 7 reservoir.Overall,the horizontal maximum principal stress(SHmax),horizontal minimum principal stress(Shmin) and vertical stress(Sv) follow the relationship of Sv≥SHmax>Shmin,indicating a dominant normal faulting stress regime within the Chang 7 reservoir of Ordos Basin.Laterally,high stress values are mainly distributed in the northwestern parts of the studied region,while low stress values are found in the southeastern parts.Factors influencing stress distributions are also analyzed.Stress magnitudes within the Chang 7 reservoir show a positive linear relationship with burial depth.A larger value of Young's modulus results in higher stress magnitudes,and the differential horizontal stress becomes higher when the rock Young's modulus grows larger.

Characteristics of stress distribution in floor strata and control of roadway stability under coal pillars

Given the difficulties encountered in roadway support under coal pillars,we studied the characteristics of stress distribution and their effect on roadway stability,using theoretical analysis and numerical simulation.The results show that,under a coal pillar,vertical stress in a floor stratum increases while horizontal stress decreases.We conclude that the increased difference between vertical and horizontal stress is an important reason for deformation of the surrounding rock and failures of roadways under coal pillars.Based on this,we propose control technologies of the surrounding rock of a roadway under a coal pillar,such as high strength and high pre-stressed bolt support,cable reinforcement support single hydraulic prop with beam support and reinforcement by grouting of the surrounding rock,which have been successfully applied in a stability control project of a roadway under a coal pillar.

Study of electromagnetic characteristics of stress distribution and sudden changes in the mining of gob-surrounded coal face

The incidence of dynamic coal or rock disasters is closely related to the distribution of stress in the surrounding rock. Our experiments show that electromagnetic radiation （EMR） signals are related to the state of stress of a coal body. The higher the stress, the more intense the deformation and fractures of a coal body and the stronger the EMR signals. EMR signals reflect the degrees of concentrated stress of a coal body and danger of a rock burst. We selected EMR intensity as the test index of the No.237 gob-surrounded coal face in the Nanshan coal mine. We tested the EMR characteristics of the stress distribution on the strike, on the incline and in the interior of the coal body. The EMR rule of rock bursts, caused by sudden changes in stress, is analyzed. Our research shows that EMR technology can be not only used to test qualitatively the stress distribution of the surrounding rock, but also to predict a possible occurrence of rock burst. Based on this, effective distress measures are used to eliminate or at least weaken the incidence of rock bursts. We hooe that safetv in coalmines will be enhanced.

Study of Stress and Strain Distributions of First Pass Conventional Spinning Under Different Roller-trace

Based on simplified axisymmetrical forming model, a elasto-plastic FEM simulation system of multi-pass conventional spinning is developed. Taking the typical draw-spinning as the study object, and establishing reasonable mechanics model, research on the first pass of spinning process is carried out with FEM system developed. The distributions of the stress and strain are obtained by three types of roller-trace curves: straight line, involute curves and quadratic curves. The results are as follows: (1) The values of equivalent stress and strain are the lowest under involute curve compared to other two curves, and they change relatively small and decrease with the increase of radius. The values of equivalent stress and strain is the highest under quadratic curves, and increase with the increase of radius. (2) The value of radial stress is smallest under involute curve, and is the largest under straight line. Value of radial stress is often used as the criterion of cracking limit, so its distribution laws can provide references for studying the condition of cracking in multi-pass conventional spinning under different roller-trace. (3) Tangential stress is compressive stress. Absolute value of tangential stress is the smallest under involute curve, and values of tangential stress are close between other two curves. The distribution laws of tangential stress can serve as a significant guide to research the critical condition of wrinkling in multi-pass conventional spinning under different roller-trace. (4) The reduction of thickness is the smallest under involute curve. The distribution of the thickness strain is very unequal under quadratic curves. The results obtained can provide references for selecting reasonable roller-trace in multi-pass conventional spinning.

Numerical analysis of stress distribution in the upper arm tissues under an inflatable cuff：Implications for noninvasive blood pressure measurement

An inflatable cuff wrapped around the upper arm is widely used in noninvasive blood pressure measurement.However, the mechanical interaction between cuff and arm tissues, a factor that potentially affects the accuracy of noninvasive blood pressure measurement, remains rarely addressed. In the present study, finite element（FE） models were constructed to quantify intra-arm stresses generated by cuff compression, aiming to provide some theoretical evidence for identifying factors of importance for blood pressure measurement or explaining clinical observations. Obtained results showed that the simulated tissue stresses were highly sensitive to the distribution of cuff pressure on the arm surface and the contact condition between muscle and bone. In contrast, the magnitude of cuff pressure and small variations in elastic properties of arm soft tissues had little influence on the efficiency of pressure transmission in arm tissues. In particular, it was found that a thickened subcutaneous fat layer in obese subjects significantly reduced the effective pressure transmitted to the brachial artery, which may explain why blood pressure overestimation occurs more frequently in obese subjects in noninvasive blood pressure measurement.

Thermal residual stresses and stress distributions under tensile and compressive loadings of short fiber reinforced metal matrix composites

The thermal residual stresses and the stress distributions of short fiber reinforced metal matrix composite under tensile and compressive loadings were studied using large strain axisymmetric elasto plastic finite element method. It is demonstrated that the thermal residual stresses can result in asymmetrical stress distributions and matrix plasticity. The thermal residual stresses decrease the stress transfer in tension and enhance the stress transfer in compression. The fiber volume fraction has more important effects on the thermal residual stresses and the stress distributions under tensile and compressive loadings than the fiber aspect ratio and the fiber end distance. [

Effects of Rock Bolting on Stress Distribution around Tunnel Using the Elastoplastic Model

To ensure the stability of a tunnel during construction, rock bolts are usually installed, which affects the stress distribution around the tunnel. Therefore, it is necessary to study the effects of rock bolting on the stress distribution around the tunnel. In this article, the effects of rock bolting on the stress distribution around the tunnel, including the pesition and orientation of bolts, the overburden depths, and the bolt lengths, are simulated using the ANSYS software with an elnstoplastic model. The effect of multiple bolts of 2 m and 1 m lengths on the stress distribution in the roof and on the lateral sides of a tunnel and at different overburden depths is considered. An important finding is that the tensile stress region that is very dangerous for rock in the bottom of the tunnel grows rapidly with increasing overburden depths when rock bolts are installed only in the roof or on the lateral sides of a tunnel. The determination of the length of the rock bolt used around a tunnel is dependent on the loads and the integrity of the rock mass around the tunnel. In addition, rock bolting around the tunnel can obviously reduce the coefficients and the size of the region of stress concentration, especially when installed in high-stress areas. This fact is very important and essential for the design of tunnels and ensures engineering safety in tunnel engineering.