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.

A thermo-mechanical damage constitutive model for deep rock considering brittleness-ductility transition characteristics

This paper developed a statistical damage constitutive model for deep rock by considering the effects of external load and thermal treatment temperature based on the distortion energy.The model parameters were determined through the extremum features of stress−strain curve.Subsequently,the model predictions were compared with experimental results of marble samples.It is found that when the treatment temperature rises,the coupling damage evolution curve shows an S-shape and the slope of ascending branch gradually decreases during the coupling damage evolution process.At a constant temperature,confining pressure can suppress the expansion of micro-fractures.As the confining pressure increases the rock exhibits ductility characteristics,and the shape of coupling damage curve changes from an S-shape into a quasi-parabolic shape.This model can well characterize the influence of high temperature on the mechanical properties of deep rock and its brittleness-ductility transition characteristics under confining pressure.Also,it is suitable for sandstone and granite,especially in predicting the pre-peak stage and peak stress of stress−strain curve under the coupling action of confining pressure and high temperature.The relevant results can provide a reference for further research on the constitutive relationship of rock-like materials and their engineering applications.

Physical and Thermo-Mechanical Properties of Composite Materials Based on Raw Earth and Crushed Palm Leaf Fibers (Borassus aethiopum)

The objective of this study is to seek solutions to reduce the impact of buildings on climate change and to promote the use of local bio-sourced or geo-sourced materials for sustainable construction. Different samples of raw earth from 3 sites were taken in the commune of Mlomp. Geotechnical tests showed that the raw earth samples from sites 2 and 3 have more clay fraction while site 1 contains more sand. The fact of integrating fibers from crushed palm leaves (Borassus aethiopum) (2%, 4% and 6%) into the 3 raw earth samples reduced the mechanical resistance to compression and traction of the 3 raw earths. The experimental results of thermal tests on samples of earth mixtures with crushed Palma leaf fibers show a decrease in thermal conductivity as well as thermal effusivity as the percentages increase (2%, 4% and 6%) of fibers in raw earth for the 3 sites. This shows that this renewable composite material can help improve the thermal insulation of building envelopes.

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.

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.

Effect of thermo-mechanical treatment process on microstructure and mechanical properties of 2A97 Al-Li alloy

2A97 Al-Li alloy was processed by thermo-mechanical treatment at different pre-stretch deformations of 0, 3% and 6%. The microstrucatre observation results reveal that some δ＇ and T1 precipitates are found in a（Al） matrix of 2A97 alloy processed by the heat treatment with no pre-stretch deformation. When the pre-stretch deformation is 3% and 6%, respectively, amounts of tiny T1 and a few of S＇ precipitates precipitates are observed in the microstructures of 2A97 alloy. The tensile test results show that the tensile properties of 2A97 alloys are improved via thermo-mechanical treatment. When the pre-stretch deformation is from 0, 3% to 6%, the ultimate tensile strength values of the 2A97 alloys increase gradually from 447.7, 516.5 to 534.3 MPa, and the elongations decrease from 17.6%, 12.8% to 10.2%, respectively. Moreover, with increasing pre-stretch deformation amount from 0 to 6%, the in-plane anisotropy value of 2A97 alloys becomes more obvious.

Effects of T9I6 thermo-mechanical process on microstructure, mechanical properties and ballistic resistance of 2519A aluminum alloy

The effects of T916 thermo-mechanical process on microstructures, mechanical properties and ballistic resistance of 2519A aluminum alloy were investigated by optical microscopy （OM）, transmission electron microscopy （TEM）, tensile tests and ballistic resistance test. After T916 treatment, the yield strength, tensile strength and elongation rate of 2519A aluminum alloy reach 501 MPa, 540 MPa and 14%, respectively. And the ballistic limit velocity of 2519A-T916 alloy （30 mm in thickness） is 715 rn/s. The microstructure varies near the sidewalls of crater. The interrupted ageing contributes to these excellent properties of the alloy. During T916 process, the precipitation of Guinier Preston （GP） zone is finer and denser during the interrupted ageing, thus resulting in well precipitated strengthening phase.

Mechanical properties of Mg-6Gd-1Y-0.5Zr alloy processed by low temperature thermo-mechanical treatment

An as-solution treated Mg-6Gd-1Y-0.4Zr alloy was processed by low temperature thermo-mechanical treatments （LT-TMT）, including cold tension with various strains followed by aging at 200 °C to peak hardness. The results show that the precipitation kinetics of the alloy experienced LT-TMT is greatly accelerated and the aging time to peak hardness is greatly decreased with increasing tensile strain. The tensile yield strength, ultimate tensile strength and elongation at room temperature of the alloy after cold tension with strain of 10% and peak aging at 200 °C are 251 MPa, 296 MPa and 8%, respectively, which are superior to the commercial heat-resistant WE54 alloy, although the latter has a higher rare earth element content.

Thermo-mechanical coupled particle model for rock

A thermo-mechanical coupled particle model for simulation of thermally-induced rock damage based on the particle simulation method was proposed.The simulation results of three verification examples,for which the analytical solutions are available,demonstrate the correctness and usefulness of the thermo-mechanical coupled particle model.This model is applied to simulating an application example with two cases：one is temperature-independent elastic modulus and strength,while the other is temperature-dependent elastic modulus and strength.The related simulation results demonstrate that microscopic crack initiation and propagation process with consideration of temperature-independent and temperature-dependent elastic modulus and strength are different and therefore,the corresponding macroscopic failure patterns of rock are also different.On the contrary,considering the temperature-dependent elastic modulus and strength has no or little effect on the heating conduction behavior.Numerical results,which are obtained by using the proposed model with temperature-dependent elastic modulus and strength,agree well with the experimental results.This also reveals that the rock subjected to heating experiences much more cracking than the rock subjected to cooling.

IMPROVING THE MECHANICAL PROPERTIES OF COPPER ALLOYS BY THERMO-MECHANICAL PROCESSING

Systematic physical simulation of thermo-mechanical processing routes has been ap-plied on a Gleeble 1500 simulator to four copper alloys (mass %) Cu-0.57Co-0.32Si,Cu-0.55Cr-0.065P, Cu-0.22Zr-0.035Si and Cu-1.01Ni-0.43Si aimed at clarifying theinfluences of processing conditions on their final properties, strength and electricalconductivity. Flow curves were determined over wide temperature and strain rateranges. Hardness was used as a measure of the strength level achieved. High hard-ness was obtained as using equal amounts (strains 0.5) of cold deformation beforeand after the precipitation annealing stage. The maximum values achieved for theCu-Co-Si, Cu-Cr-P, Cu-Zr-Si and Cu-Ni-Si alloys were 190, 165, 178 and 193 HV5,respectively. A thermo-mechanical schedule involving the hot deformation-ageing-colddeformation stages showed even better results for the Cu-Zr-Si alloy. Consequently,the processing routes were designed based on simulation test results and wires of 5 and2mm in diameters have been successfully processed in the industrial scale.

Development of multi-physics numerical simulation model to investigate thermo-mechanical fatigue crack propagation in an autofrettaged gun barrel

In this research,a detailed multi-physics study has been carried out by numerically simulating a solid fractured gun barrel for 20 thermo-mechanical cycles.The numerical model is based on thermal effects,mechanical stress fields and fatigue crack mechanics.Elastic-plastic material data of modified AISI 4340 at temperatures ranging from 25 to 1200℃and at strain rates of 4,16,32 and 48 s^(-1) was acquired from high-temperature compression tests.This was used as material property data in the simulation model.The boundary conditions applied are kept similar to the working gun barrel during continuous firing.A methodology has been provided to define thermo-mechanically active surface-to-surface type interface between the crack faces for a better approximation of stresses at the crack tip.Comparison of results from non-autofrettaged and autofrettaged simulation models provide useful information about the evolution of strains and stresses in the barrel at different points under combined thermo-mechanical loading cycles in both cases.The effect of thermal fatigue under already induced compressive yield due to autofrettage and the progressive degradation of the accumulated stresses due to thermo-mechanical cyclic loads on the internal surface of the gun barrel(mimicking the continuous firing scenario)has been analyzed.Comparison between energy release rate at tips of varying crack lengths due to cyclic thermo-mechanical loading in the non-autofrettaged and autofrettaged gun has been carried out.

NUMERICAL SIMULATION OF THE THERMO-MECHANICAL PROCESS FOR BEAM BLANK CONTINUOUS CASTING

The aim of this study was to simulate the solidification process of beam blank continuous casting, and then find the reasons for the typical defects of the beam blank. A two-dimensional transient coupled finite element model has been developed to compute the temperature and stress profile in beam blank continuous casting. The enthalpy method was used in the heat conduction equation. The thermo-mechanical property in the mushy zone was taken into consideration in this calculation. It is shown that at the mold exit the thickness of the shell had its maximum value at the flange tip and its minimum value at the fillet. The temperature had a great fluctuation on the surface of the beam blank in the secondary cooling zone. At the unbending point, the surface temperature of the web was in the brittleness temperature range under the present condition. To ensure the quality, it is necessary to weaken the intensity of secondary cooling. At the mold exit the equivalent stress and strain have higher values at the flange tip and at the web. From the spray 1 to the unbending point, the maximum values of stress and strain gradually moved to the internal section of the flange tip and the web. However, whenever, there were bigger stress and strain values near the flange tip and the web than in the other parts, it must be very easy to generate cracks at those positions. Now, online verification of this simulation has been developed, which has proved to be very useful and efficient to instruct the practical production of beam blank continuous casting.

Magneto-thermo-mechanical characterization of giant magnetostrictive materials

The variations of magnetization and magneto- striction with temperature and stress were investigated through the analysis of the effective field, induced by temperature and stress. A nonlinear magnetostrictive model of giant magnetostrictive materials was proposed. The proposed model can be used to calculate the magnetostrictive characterization of giant magnetostrictive materi- als in different temperatures and under different stresses. The coupling effects of axial stress, magnetic field, and temperature on the magnetostriction of a Terfenol-D rod were numerically simulated as well as experimentally tested. Comparison between the calculating and experimental results shows that the proposed model can better describe the magneto-thermo-mechanical characteristics of Terfenol-D rod under different temperatures and compressive stress. Therefore, the proposed model possesses an important significance for the design of magnetostrictive devices.

Multi-objective Topology Optimization of Thermo-mechanical Compliant Mechanisms

The material characteristics of a structure will change with temperature variation,and will induce stress within the structure.Currently,the optimal design for the topology of compliant mechanisms is mainly performed in single physical field.However,when compliant mechanisms work in high temperature environments,their displacement outputs are generated not only by mechanical load,but also by the temperature variation which may become the prominent factor.Therefore,the influence of temperature must be considered in the design.In this paper,a novel optimization method for multi-objective topology of thermo-mechanical compliant mechanisms is presented.First,the thermal field is analyzed with finite-element method,where the thermal strain is taken into account in the constitutive relation,and the equivalent nodal thermal load is derived with the principle of virtual work.Then the thermal load is converted into physical loads in elastic field,and the control equation of the thermo-mechanical compliant mechanism is obtained.Second,the mathematical model of the multi-objective topology optimization is built by incorporating both the flexibility and stiffness.Meanwhile,the coupling sensitivity function and the sensitivity analysis equations of thermal steady-state response are derived.Finally,optimality criteria algorithm is employed to obtain numerical solution of the multi-objective topology optimization.Numerical examples show that the compliant mechanisms have better performance and are more applicable if the temperature effect is taken into account in the design process.The presented modeling and analysis methods provide a new idea and an effective approach to topology optimization of compliant mechanisms in electrothermic coupling field and multiphysics fields.

Study on inhomogeneous cooling behavior of extruded profile with unequal and large thicknesses during quenching using thermo-mechanical coupling model

The interfacial heat transfer coefficient between hot profile surface and cooling water was determined by using inverse heat conduction model combined with end quenching experiment. Then, a Deform-3 D thermo-mechanical coupling model for simulating the on-line water quenching of extruded profile with unequal and large thicknesses was developed. The temperature field, residual stress field and distortion of profile during quenching were investigated systematically. The results show that heat transfer coefficient increases as water flow rate increases. The peak heat transfer coefficient with higher water flow rates appears at lower interface temperatures. The temperature distribution across the cross-section of profile during quenching is severe nonuniform and the maximum temperature difference is 300 ℃ at quenching time of 3.49 s. The temperature difference through the thickness of different parts of profile first increases sharply to a maximum value, and then gradually decreases. The temperature gradient increases obviously with the increase of thickness of parts. After quenching, there exist large residual stresses on the inner side of joints of profile and the two ends of part with thickness of 10 mm. The profile presents a twisting-type distortion across the cross-section under non-uniform cooling and the maximum twisting angle during quenching is 2.78°.

Effect of thermo-mechanical processing on microstructure and electrochemical behavior of Ti-Nb-Zr-V new metastable β titanium biomedical alloy

The influence of thermo-mechanical processing (TMP) on the microstructure and the electrochemical behavior of new metastableβ alloy Ti?20.6Nb?13.6Zr?0.5V (TNZV) was investigated. The TMP included hot working in belowβ transus, solution heat treatments at the same temperature and different cooling rates in addition to aging. Depending upon the TMP conditions, a wide range of microstructures with varying spatial distributions and morphologies of equiaxed/elongatedα andβ phases were attained, allowing for a wide range of electrochemical properties to be achieved. The corrosion behavior of the studied alloy was evaluated in a Ringer’s solution at 37 °C via open circuit potential?time and potentiodynamic polarization measurements.