Genome-Wide Exploration of the Grape GLR Gene Family and Differential Responses of VvGLR3.1 and VvGLR3.2 to Low Temperature and Salt Stress

Grapes,one of the oldest tree species globally,are rich in vitamins.However,environmental conditions such as low temperature and soil salinization significantly affect grape yield and quality.The glutamate receptor(GLR)family,comprising highly conserved ligand-gated ion channels,regulates plant growth and development in response to stress.In this study,11 members of the VvGLR gene family in grapes were identified using whole-genome sequence analysis.Bioinformatic methods were employed to analyze the basic physical and chemical properties,phylogenetic trees,conserved domains,motifs,expression patterns,and evolutionary relationships.Phylogenetic and collinear analyses revealed that the VvGLRs were divided into three subgroups,showing the high conservation of the grape GLR family.These members exhibited 2 glutamate receptor binding regions(GABAb and GluR)and 3-4 transmembrane regions(M1,M2,M3,and M4).Real-time quantitative PCR analysis demonstrated the sensitivity of all VvGLRs to low temperature and salt stress.Subsequent localization studies in Nicotiana tabacum verified that VvGLR3.1 and VvGLR3.2 proteins were located on the cell membrane and cell nucleus.Additionally,yeast transformation experiments confirmed the functionality of VvGLR3.1 and VvGLR3.2 in response to low temperature and salt stress.Thesefindings highlight the significant role of the GLR family,a highly conserved group of ion channels,in enhancing grape stress resistance.This study offers new insights into the grape GLR gene family,providing fundamental knowledge for further functional analysis and breeding of stress-resistant grapevines.

Proliferating cell nuclear antigen of Ulva prolifera is involved in the response to temperature stress

Ulva prolifera is the most common specie causative to green tide,and its growth is sensitive to temperature stress.However,the mechanisms of U.prolifera response to temperature stress remain elusive.In this study,high temperature(36℃)stimulus promoted the death of unformed cell wall protoplasts and delayed the division of formed cell wall protoplasts,while low-temperature(4℃)stimulus did not,suggesting that the mechanisms of the response of U.prolifera to high and low temperature stresses are different.Transcriptome results show that proliferation-related genes were differentially expressed under high and low-temperature stresses,especially the proliferating cell nuclear antigen(PCNA)and cyclins(CYCs).Subsequently,the interaction between PCNA and Cyclin A was confirmed by Co-immunoprecipitation,yeast two-hybrid,and so on.Furthermore,high-and low temperature stresses induced the expression of PCNA and Cyclin A in varying of degrees,and activated extracellular signal-regulated kinase(ERK)signal pathway.These results suggest,PCNA,Cyclin A,and ERK signal pathway played important roles in the resistance of U.prolifera to temperature stress.Interestingly,high-temperature stress induced an increase of miR-2916 in abundance,and exhibiting reverse expression of PCNA;and PCNA was target gene of miR-2916,suggesting that miR-2916 protected U.prolifera from high-temperature stress via post-transcriptionally regulation of PCNA.This study laid a foundation for understanding the function of PCNA and Cyclin A,moreover,it has a guiding significance to explore the mechanisms of the response to temperature stress from proliferation-related genes regulatory networks in U.prolifera.

Resistance index and browning mechanism of apple peel under high temperature stress

Apples are one of the most important economic crops worldwide.Because of global warming and an aggravation of environmental,abnormally high temperatures occur frequently in fruit-growing season and seriously affect normal fruit growth and reduce fruit quality and yield.We took five-year-old Ruixue’(Qinfu 1×Pink Lady;CNA20151469.1) fruits as test materials,and the ambient temperature during fruit development was monitored.The results showed that during the fruit-growing season,especially during the rapid growth stage (July to August),the maximum daily temperature exceeded 30℃ and lasted for more than 40 days.To determine the effects of high temperature stress on the apple fruit resistance,we treated expanding,veraison,and maturity-period fruits at different temperatures.It was found that the fruits of the expanding period showed strong resistance to high temperature stress,whereas during veraison and maturity,fruit resistance to high temperature stress decreased,and the fruit peel browning phenotype appeared.Meanwhile,the content of malonaldehyde (MDA),hydrogen peroxide (H_(2)O_(2)),and superoxide anion (O._(2)^(-)) in the peel gradually increased with increasing temperature.The content of total phenols,flavanol,and flavonoids in the peel decreased substantially at 45℃.Moreover,it was found that polyphenol oxidase gene (MdPPO1) was most sensitive to high temperature stress in apple.Furthermore,transient and stable MdPPO1 overexpression significantly promoted peel browning.The transgenic materials were more sensitive to high temperatures,and browning was more severe compared to non-genetically modified organism (WT).Stable MdPPO1 knockout calli obtained via clustered regularly interspersed short palindromic repeats (CRISPR/Cas9) gene knockout technology reduced the browning phenotype,and the resultant fruits were not sensitive to the effects of high temperature stress.Thus,MdPPO1 expression may be a key factor of high temperature-related changes observed in the browning phenotype that provides a scientific theoretical basis for the selection of high temperature-resistant varieties and apple cultivation and management in the future.

Advances in Molecular Regulatory Mechanisms of Fruit Trees under Low Temperature Stress

The most recent research findings on the tolerance of fruit trees to cold stress are reviewed from a molecular perspective,including the perception and transduction of low temperature calcium signaling,CBF-dependent molecular regulatory mechanisms,non-CBF-dependent molecular regulatory mechanisms,and so forth.The objective is to provide a reference basis for further improving the cold resistance of fruit trees and cultivating new varieties of hardy plants.

Effects of Low Temperature Stress on Germination and Physiological Characteristics of Different Sweet Maize Varieties

[Objectives]The paper was to explore the effects of low temperature stress on germination and physiological characteristics of different sweet maize varieties.[Methods]Taking Taitian 264,Zhexuetian 1 and Chaotian 4 as the research objects,the changes in germination potential,germination index,plant height,biomass,and antioxidant enzyme activity of maize seeds were studied under optimal temperature conditions(25℃)and low temperature stress conditions(10℃).[Results]Under 10℃stress,the germination rate and germination index of Taitian 264 were higher than that of Zhexuetian 1 and Chaotian 4.Under low temperature stress,Taitian 264 exhibited the least reduction in height and biomass,while Zhexuetian 1 had the most reduction.Additionally,the SOD and POD activities of Taitian 264 were higher than that of Zhexuetian 1 and Chaotian 4 under both temperature conditions,while the MDA content of Taitian 264 was lower.Taitian 264 showed strong germination ability against low temperature stress.[Conclusions]This study provides a basis for timely sowing practices of sweet maize in agricultural production.

Dietary fat supplementation relieves cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis in pigs

Background Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase(AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation.Results Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver;dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation.Conclusions Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we high-light the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.

Calculation of Mass Concrete Temperature and Creep Stress under the Influence of Local Air Heat Transfer

Temperature-induced cracking during the construction of mass concrete is a significant concern.Numerical simulations of concrete temperature have primarily assumed that the concrete is placed in an open environment.The problem of heat transfer between the air and concrete has been simplified to the concrete’s heat dissipation boundary.However,in the case of tubular concrete structures,where air inlet and outlet are relatively limited,the internal air temperature does not dissipate promptly to the external environment as it rises.To accurately simulate the temperature and creep stress in tubular concrete structures with enclosed air spaces during construction,we establish an air–concrete coupled heat transfer model according to the principles of conjugate heat transfer,and the accuracy of the model is verified through experiments.Furthermore,we conduct a case study to analyze the impact of airflow within the ship lock corridor on concrete temperature and creep stress.The results demonstrate that enhancing airflow within the corridor can significantly reduce the maximum concrete temperature.Compared with cases in which airflow within the corridor is neglected,the maximum concrete temperature and maximum tensile stress can be reduced by 12.5℃ and 0.7 MPa,respectively,under a wind speed of 4 m/s.The results of the traditional calculation method are relatively close to those obtained at a wind speed of 1 m/s.However,the temperature reduction process in the traditional method is faster,and the method yields greater tensile stress values for the corridor location.

The influences of canopy temperature measuring on the derived crop water stress index

Crop water stress index(CWSI)is widely used for efficient irrigation management.Precise canopy temperature(T_(c))measurement is necessary to derive a reliable CWSI.The objective of this research was to investigate the influences of atmospheric conditions,settled height,view angle of infrared thermography,and investigating time of temperature measuring on the performance of the CWSI.Three irrigation treatments were used to create different soil water conditions during the 2020-2021 and 2021-2022 winter wheat-growing seasons.The CWSI was calculated using the CWSI-E(an empirical approach)and CWSI-T(a theoretical approach)based on the T_(c).Weather conditions were recorded continuously throughout the experimental period.The results showed that atmospheric conditions influenced the estimation of the CWSI;when the vapor pressure deficit(VPD)was>2000 Pa,the estimated CWSI was related to soil water conditions.The height of the installed infrared thermograph influenced the T_(c)values,and the differences among the T_(c)values measured at height of 3,5,and 10 m was smaller in the afternoon than in the morning.However,the lens of the thermometer facing south recorded a higher T_(c)than those facing east or north,especially at a low height,indicating that the direction of the thermometer had a significant influence on T_(c).There was a large variation in CWSI derived at different times of the day,and the midday measurements(12:00-15:00)were the most reliable for estimating CWSI.Negative linear relationships were found between the transpiration rate and CWSI-E(R^(2)of 0.3646-0.5725)and CWSI-T(R^(2)of 0.5407-0.7213).The relations between fraction of available soil water(FASW)with CWSI-T was higher than that with CWSI-E,indicating CWSI-T was more accurate for predicting crop water status.In addition,The R^(2)between CWSI-T and FASW at 14:00 was higher than that at other times,indicating that 14:00 was the optimal time for using the CWSI for crop water status monitoring.Relative higher yield of winter wheat was obtained with average seasonal values of CWSI-E and CWSI-T around 0.23 and 0.25-0.26,respectively.The CWSI-E values were more easily influenced by meteorological factors and the timing of the measurements,and using the theoretical approach to derive the CWSI was recommended for precise irrigation water management.

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.

Extraction of the key infrared radiation temperature features concerning stress and crack evolution of loaded rocks

The infrared radiation temperature(IRT)variation concerning stress and crack evolution of rocks is a critical focus in rock mechanics domain and engineering disaster warning.In this paper,a methodology to extract the key IRT features related to stress and crack evolution of loaded rocks is proposed.Specifically,the wavelet denoising and reconstruction in thermal image sequence(WDRTIS)method is employed to eliminate temporal noise in thermal image sequences.Subsequently,the adaptive partition temperature drift correction(APTDC)method is introduced to alleviate temperature drift.On this basis,the spatial noise correction method based on threshold segmentation and adaptive median filtering(OTSU-AMF)is proposed to extract the key IRT features associated with microcracks of loaded rocks.Following temperature drift correction,IRT provides an estimation of the thermoelastic factor in rocks,typically around 5.29×10^(-5) MPa^(-1) for sandstones.Results reveal that the high-temperature concentrated region in cumulative thermal images of crack evolution(TICE)can elucidate the spatiotemporal evolution of localized damage.Additionally,heat dissipation of crack evolution(HDCE)acquired from TICE quantifies the progressive failure process of rocks.The proposed methodology enhances the reliability of IRT monitoring results and provides an innovative approach for conducting research in rock mechanics and monitoring engineering disasters.

Trehalose:A sugar molecule involved in temperature stress management in plants

Trehalose(Tre)is a non-reducing disaccharide found in many species,including bacteria,fungi,invertebrates,yeast,and even plants,where it acts as an osmoprotectant,energy source,or protein/membrane protector.Despite relatively small amounts in plants,Tre concentrations increase following exposure to abiotic stressors.Trehalose-6-phosphate,a precursor of Tre,has regulatory functions in sugar metabolism,crop production,and stress tolerance.Among the various abiotic stresses,temperature extremes(heat or cold stress)are anticipated to impact crop production worldwide due to ongoing climate changes.Applying small amounts of Tre can mitigate negative physiological,metabolic,and molecular responses triggered by temperature stress.Trehalose also interacts with other sugars,osmoprotectants,amino acids,and phytohormones to regulate metabolic reprogramming that underpins temperature stress adaptation.Transformed plants expressing Tre-synthesis genes accumulate Tre and show improved stress tolerance.Genome-wide studies of Tre-encoding genes suggest roles in plant growth,development,and stress tolerance.This review discusses the functions of Tre in mitigating temperature stress—highlighting genetic engineering approaches to modify Tre metabolism,crosstalk,and interactions with other molecules—and in-silico approaches for identifying novel Tre-encoding genes in diverse plant species.We consider how this knowledge can be used to develop temperature-resilient crops essential for sustainable agriculture.

Influence of temperature, stress, and grain size on behavior of nano-polycrystalline niobium

Atomic simulations are executed to investigate the creep responses of nano-polycrystalline(NC) niobium established by using the Voronoi algorithm. The effects of varying temperature, applied stress, and grain size(GS) on creep properties and mechanisms are investigated. Notably, the occurrence of tertiary creep is exclusively observed under conditions where the applied stress exceeds 4.5 GPa and the temperature is higher than 1100 K. This phenomenon can be attributed to the significant acceleration of grain boundary and lattice diffusion, driven by the elevated temperature and stress levels. It is found that the strain rate increases with both temperature and stress increasing. However, an interesting trend is observed in which the strain rate decreases as the grain size increases. The stress and temperature are crucial parameters governing the creep behavior. As these factors intensify, the creep mechanism undergoes a sequential transformation: initially from lattice diffusion under low stress and temperature conditions to a mixed mode combining grain boundaries(GBs) and lattice diffusion at moderate stress and mid temperature levels, and ultimately leading to the failure of power-law controlled creep behavior, inclusive of grain boundary recrystallization under high stress and temperature conditions. This comprehensive analysis provides in more detail an understanding of the intricate creep behavior of nano-polycrystalline niobium and its dependence on various physical parameters.

Anisotropic strength,deformation and failure of gneiss granite under high stress and temperature coupled true triaxial compression

The anisotropic mechanical behavior of rocks under high-stress and high-temperature coupled conditions is crucial for analyzing the stability of surrounding rocks in deep underground engineering.This paper is devoted to studying the anisotropic strength,deformation and failure behavior of gneiss granite from the deep boreholes of a railway tunnel that suffers from high tectonic stress and ground temperature in the eastern tectonic knot in the Tibet Plateau.High-temperature true triaxial compression tests are performed on the samples using a self-developed testing device with five different loading directions and three temperature values that are representative of the geological conditions of the deep underground tunnels in the region.Effect of temperature and loading direction on the strength,elastic modulus,Poisson’s ratio,and failure mode are analyzed.The method for quantitative identification of anisotropic failure is also proposed.The anisotropic mechanical behaviors of the gneiss granite are very sensitive to the changes in loading direction and temperature under true triaxial compression,and the high temperature seems to weaken the inherent anisotropy and stress-induced deformation anisotropy.The strength and deformation show obvious thermal degradation at 200℃due to the weakening of friction between failure surfaces and the transition of the failure pattern in rock grains.In the range of 25℃ 200℃,the failure is mainly governed by the loading direction due to the inherent anisotropy.This study is helpful to the in-depth understanding of the thermal-mechanical behavior of anisotropic rocks in deep underground projects.

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.

Effects of the extrusion parameters on microstructure,texture and room temperature mechanical properties of extruded Mg-2.49Nd-1.82Gd-0.2Zn-0.2Zr alloy

Microstructure,texture,and mechanical properties of the extruded Mg-2.49Nd-1.82Gd-0.2Zn-0.2Zr alloy were investigated at different extrusion temperatures(260 and 320℃),extrusion ratios(10:1,15:1,and 30:1),and extrusion speeds(3 and 6 mm/s).The experimental results exhibited that the grain sizes after extrusion were much finer than that of the homogenized alloy,and the second phase showed streamline distribution along the extrusion direction(ED).With extrusion temperature increased from 260 to 320℃,the microstructure,texture,and mechanical properties of alloys changed slightly.The dynamic recrystallization(DRX)degree and grain sizes enhanced as the extrusion ratio increased from 10:1 to 30:1,and the strength gradually decreased but elongation(EL)increased.With the extrusion speed increased from 3 to 6 mm/s,the grain sizes and DRX degree increased significantly,and the samples presented the typical<2111>-<1123>rare-earth(RE)textures.The alloy extruded at 260℃ with extrusion ratio of 10:1 and extrusion speed of 3 mm/s showed the tensile yield strength(TYS)of 213 MPa and EL of 30.6%.After quantitatively analyzing the contribution of strengthening mechanisms,it was found that the grain boundary strengthening and dislocation strengthening played major roles among strengthening contributions.These results provide some guidelines for enlarging the industrial application of extruded Mg-RE alloy.

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.