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.

Transcriptomic and genetic approaches reveal that low-light-induced disease susceptibility is related to cellular oxidative stress in tomato

The impact of low light intensities on plant disease outbreaks represents a major challenge for global crop security,as it frequently results in significant yield losses.However,the underlying mechanisms of the effect of low light on plant defense are still poorly understood.Here,using an RNA-seq approach,we found that the susceptibility of tomato to Pseudomonas syringae pv.tomato DC3000(Pst DC3000)under low light was associated with the oxidation-reduction process.Low light conditions exacerbated Pst DC3000-induced reactive oxygen species(ROS)accumulation and protein oxidation.Analysis of gene expression and enzyme activity of ascorbate peroxidase 2(APX2)and other antioxidant enzymes revealed that these defense responses were significantly induced by Pst DC3000 inoculation under normal light,whereas these genes and their associated enzyme activities were not responsive to pathogen inocula-tion under low light.Additionally,the reduced ascorbate to dehydroascorbate(AsA/DHA)ratio was lower under low light compared with normal light conditions upon Pst DC3000 inoculation.Furthermore,the apx2 mutants generated by a CRISPR-Cas9 gene-editing approach were more susceptible to Pst DC3000 under low light conditions.Notably,this increased susceptibility could be significantly reduced by exogenous AsA treatment.Collectively,our findings suggest that low-light-induced disease susceptibility is associated with increased cellular oxidative stress in tomato plants.This study sheds light on the intricate relationship between light conditions,oxidative stress,and plant defense responses,and may pave the way for improved crop protection strategies in low light environments.

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

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

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

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

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

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

Effect of pre-deformation on the stress corrosion cracking susceptibility of aluminum alloy 2519

The effects of pre-deformation and strain rate on the stress corrosion cracking （SCC） behavior of aluminum alloy 2519 in air and in 3.5% NaCI water solution were investigated by means of slow strain rate tension （SSRT）, scanning electron microscopy （SEM）, and transmission electron microscopy （TEM）. The results indicate that the alloy is susceptible to SCC in 3.5% NaCI water solution and not in air. At the same pre-deformation, the alloy is more susceptible to SCC at 1.33 × 10^-5 s^-1 than at 6.66 × 10^-5 s^-1. Moreover, it is more susceptible to SCC at free pre-deformation than at 10% pre-deformation at the same strain rate. The number of 0 precipitated along the grain boundaries is reduced and distributed discontinuously, at the same time, the precipitate-free zones （PFZ） become narrow and the susceptibility to stress corrosion cracking is reduced after 10% pre-deformation.

Correspondence between Susceptibility to SCC of 7050 Aluminum Alloy and Passive Film-induced Stress at Various pH Values

The passive film-induced stress and the susceptibility to SCC of 7050 aluminum alloy in 3.5%sodium chloride solution at various pH values were investigated by slow strain rate testing（SSRT） and flowing stress differential method.The results showed that the passive film-induced stress and the susceptibility to SCC decreased with increasing pH values when pH≤7,while they increased with increasing pH values when pH7.However,the corrosion type was interpreted as exfoliation corrosion when pH=l and 14,and there was no film formed on the surface of the specimens.The whole variation plots of film-induced stress and the SCC susceptibility with pH values were both presented as a valley shape.The symbol and amount of the film-induced stress were related to the compositions of the passive film,which were analyzed using X-ray photoelectron spectroscopy（XPS）.

Proteomic Profiling and Protein-Protein Interaction Network Reveal the Molecular Mechanisms of Susceptibility to Drought Stress in Canola(Brassica napus L.)

Drought stress is one of the most important abiotic stresses that plants face frequently in nature.Under drought conditions,many morphological,physiological,and molecular aspects of plants are changed and as a result plants experience a remarkable reduction in growth,yield,and reproduction.To expand our understanding of the molecular basis of the plant response to drought stress,the proteomic profile and protein-protein network of canola(Brassica napus L.)were studied.The focus was to show molecular mechanisms related to canola susceptibility to drought stress.The experiment used a completely randomized design,implemented in a hydroponic system under greenhouse conditions.To impose drought stress,plants were exposed to Hoagland’s solution supplemented with polyethylene glycol(PEG)6000 for 7 days.The drought stress resulted in 161reproducible protein spots in twodimensional electrophoresis of canola leaves.The t-student test showed 21 differentially abundant proteins(DAP),of which 2 and 19 were up and down accumulated,respectively.Two spots identified as 1-aminocyclopropane-1-carboxylate oxidase and D-2-hydroxyglutarate dehydrogenase showed an increased abundance of 2.11 and 1.77,respectively.The extended protein-protein interaction of differentially abundant proteins and KEGG analysis showed 47 pathways directly and indirectly associated with canola response to drought stress.DAPs with increased abundance were associated with amino acid and signaling processes,whereas DAPs with decreased abundance were mostly connected with pathways responsible for energy production.The results of the study will help to elucidate further the molecular events associated with the susceptibility to drought stress in canola.

A new anti-influenza animal model for Traditional Chinese Medicine, restraint stress induces influenza susceptibility by regulating mitochondrial antiviral signaling pathway

There are many kinds of Chinese patent medicine used to fight against influenza efficiently in clinical practice. However, little experimental data confirmed the anti-influenza the activities since non-suitable animal model and in vitro antiviral experiments. This paradox can be explained by host factors are important in the patho- genesis and outcome of influenza infection. Accordingly, we set up a mouse model by using restraint stress plus vi- ral infection, which is more conducive to simulate the clinical features of susceptible population and evaluate the activities of Chinese herbal medicine. Our results demonstrated that stress-induced corticosterone （CORT） , a stres- sor sensor, increased the morbidity and the mortality of virus infected mice loaded with restraint stress. CORT also increased expression of Mfn2, and accordingly decreased mitochondrial antiviral signaling （MAVS） aggregates in the host cells. Mfn2 overexpression increased NP and decreased IFN-β and IFITM3 protein expressions in influenza virus infected A549 cells. These findings suggested that the mechanism of restraint stress increased the susceptibili- ty due to CORT induces activation of Mfn2 mediated MAVS pathway.

Effects of Y on hot tearing susceptibility of Mg-Zn-Y-Zr alloys

The hot tearing susceptibility of MgZn2.5YxZr0.5 （x=0.5, 1, 2, 4, 6） alloys was evaluated by thermodynamic calculations based on Clyne-Davies model. The microstructure and morphology of hot tearing regions of the alloys were observed by X-ray diffraction and scanning electron microscopy. The solidification temperature and shrinkage stress during the solidification of MgZn2.5YxZr0.5 alloys in the“T”type hot tearing permanent-mold were acquired with the attached computer. The effect factors of hot tearing susceptibility of MgZn2.5YxZr0.5 alloys, such as the solidification temperature interval, the variation of solid fraction in vulnerable region, the residual liquid fraction in the final stage, the type of the second phase of the alloys were discussed based on the above calculation and observation. The results demonstrated that the hot tearing susceptibility in the investigated alloys was found as follows：MgZn2.5Y2Zr0.5＆gt;MgZn2.5Y0.5Zr0.5＆gt;MgZn2.5Y4Zr0.5＆gt;MgZn2.5Y6Zr0.5＆gt;MgZn2.5Y1Zr0.5. The highest hot tearing susceptibility of MgZn2.5Y2Zr0.5 alloy related to the following reasons： the largest freezing range, the biggest changing of the variation of solid fraction in vulnerable region, the least liquid film in the final stage of solidification, the formation of the second phase which worsens the liquid flow and interdendritic feeding after dendrite coherency.

LncRNA cancer susceptibility 20 regulates the metastasis of human gastric cancer cells via the miR-143-5p/MEMO1 molecular axis

BACKGROUND Gastric cancer(GC)is considered as one of the most widespread malignancies.Emerging evidence has shown that lncRNAs can function as important oncogenes or tumor suppressors during GC progression.AIM To investigate the effect and mechanism of lncRNA cancer susceptibility 20(CASC20)in the proliferation and metastasis of GC cells.METHODS Data mining and clinical samples were used to evaluate the expression of CASC20 in GC and adjacent tissues.CASC20 was down-regulated in GC cells by shortinterfering RNA.Cell proliferation was evaluated by CCK-8 assay,and cell migration and invasion were detected by wound healing and Transwell assays.The expressions of proteins related to epithelial-mesenchymal transition were detected by western blot assay.RESULTS The expression of CASC20 was increased in GC tumor tissues and various GC cell lines.High CASC20 expression was correlated with a high risk of lymphatic metastasis and poor prognosis in GC patients.In vitro assays showed that silencing CASC20 reduced cell proliferation,migration,and invasion in GC cells.Mechanistic studies revealed that CASC20 exhibits oncogenic functions by regulating MEMO1 expression through competitive endogenous binding to miR-143-5p,leading to induction of epithelial-mesenchymal transition.CONCLUSION Our findings indicate that CASC20 serves as a tumor promoter by regulating metastasis in GC via the miR-143-5p/MEMO1 axis.CASC20 may be a potential therapeutic target for GC.

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

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

Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming

The world is projected to experience an approximate doubling of atmospheric CO_2 concentration in the next decades. Rise in atmospheric CO_2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 ℃-5.8 ℃ by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO_2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species(ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress(OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O_2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to longevity of animals will become very crucial challenge to biologists of the present millennium.

Shiqi herbal tea reduces the susceptibility to H1N1 influenza virus in stressed mice

Objective:It is well known that stress plays a critical role in immune response and susceptibility to diseases.Among many stressors,restraint stress has been shown to suppress immune function and increase susceptibility to infections.In this study,we employed a restraint-mouse model to investigate the effect and preliminary mechanism of ShiQi herbal tea(SQHT),a traditional Chinese medicine,on H1N1 virus infection.Methods:Mice were exposed to restraint stress and infected with H1N1 influenza virus by intranasal inoculation.SQHT(936 and 1872 mg/kg/d)was orally administrated to mice for 7 days from the first day of restraint stress.The survival rate of mice in each group was monitored daily for 21 days.Histopathological changes,inflammatory cells infiltration,and virus titer in lungs were examined.For the study of mechanisms,we investigated whether SQHT could promote interferon-β(IFN-β)generation and interferon stimulated genes(ISG)expression.Results:Our results suggested that SQHT(936 mg/kg/d)significantly reduced H1N1-induced mortality,the level of complement C5a and lung tissue inflammation,and viral replication in restraint-stressed mice.Further results revealed that in restraint-stressed mice model,SQHT(936 mg/kg/d)administration markedly improved IFN-βgeneration,and increased MX1 and IFITM3 gene expression.Conclusion:Our study demonstrates that SQHT reduces restraint stress-induced susceptibility to H1N1 infection via improving IFN-βantiviral pathway,which provides a certain basis for the clinical use of SQHT to treat H1N1 infection.

Stress corrosion cracking susceptibility of 7A52 aluminum alloy

The stress corrosion sensitivity of 7A52 aluminum alloy was investigated in the artificial sea water through slow stain rate test(SSRT). The stress corrosion cracking(SCC) susceptibility was estimated with the loss of elongation and stress corrosion sensitivity index. The results show that the susceptibility of 7A52 aluminum alloy is always high when the strain rate is in the range of 10-5-10-7s-1.It reaches the maximum at the strain rate of 8.7×10-7s-1,and the sensitivity index reaches 0.346. The characteristics of stress corrosion can be observed clearly on the fracture of tensile specimen. The process of SCC is depicted according to the fracture morphology. The SCC initiates at the edge of the specimen. Then the SCC grows rapidly because of the anode dissolving and stress concentration. When the area of specimen cannot support the tensile stress, it ruptures suddenly. The secondary cracks and quasi-cleavage surface can be found on the fracture morphology.

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

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

Residual stress distribution in different depths of TiNi/Ti_2Ni-based laser clad coating prepared at different environmental temperatures

This study aimed to effectively reduce the cracking susceptibility of the laser clad coating by enhancing the environmental temperature during laser cladding,and reveal the residual stress distribution in different depths of the coating.The TiNi/Ti2Ni-based coatings were prepared on Ti6Al4V by laser cladding at different environmental temperatures of25,400,600and800°C.The changes in residual stress along the depth of the coatings were investigated in detail by the nanoindentation method.Results showed that the average residual stress of2.90GPa in the coating prepared at25°C was largest.With the increase in environmental temperature,the average residual stress was reduced to1.34GPa(400°C),0.70GPa(600°C)and0GPa(800°C).For all the coatings,the residual stress was increased with increasing the distance from the coating surface.Enhancing the environmental temperature can effectively reduce the cracking susceptibility of the coatings.

Effect of Hydrogen on Dezincification Layer-Induced Stress

The effect of hydrogen on the dezincification layer-induced stress and the susceptibility to SCC was investigated. Experimental results showed that the dezincification layer-induced stress increased with increasing hydrogen concentration, and 3x10-6 hydrogen could increase the susceptibility to SCC of brass in ammonia solution by 10%.

Susceptibility to Hot Cracking and Weldment Heat Treatment of Haynes 230 Superalloy

This study investigates the susceptibility of hot cracking and weldment heat treatment of Haynes 230 superalloy. The Varestriant test was conducted to evaluate this susceptibility. Welding was performed by gas tungsten arc welding （GTAW） and plasma arc welding （PAW） with stress relief heat treatment and solid solution heat treatment. A tensile test is then performed to measure the changes in the mechanical properties of the heattreated material. The results indicate that the number of thermal cycles does not affect the susceptibility of Haynes 230 superalloy to hot cracking. However, it does increase the strain. In weldment of heat treatment, stress relief annealing increases the yield strength and tensile strength of the welded parts. The section of the tensile specimens shows fibrous fractures on the welded parts, regardless of whether they are heat-treated.

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

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