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 ...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.展开更多
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 stre...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.展开更多
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...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.展开更多
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,ototox...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.展开更多
BACKGROUND Revisiting the epidemiology of posttraumatic stress symptoms(PTSSs)among university students during the coronavirus disease 2019(COVID-19)pandemic as well as understanding the mental health help-seeking beh...BACKGROUND Revisiting the epidemiology of posttraumatic stress symptoms(PTSSs)among university students during the coronavirus disease 2019(COVID-19)pandemic as well as understanding the mental health help-seeking behavior of individuals with PTSSs has critical implications for public mental health strategies in future medical pandemics.AIM To investigate the prevalence and correlates of PTSSs among university students during the first wave of the COVID-19 pandemic in China and to examine mental health help-seeking behaviors among these students.METHODS A total of 2507 Chinese university students were recruited via snowball sampling.The students completed the Seven-item Screening Scale for Post-traumatic Stress Disorder during the first wave of the COVID-19 pandemic in China.Sociodemo-graphic characteristics,pandemic-related characteristics,and mental health help-seeking behaviors of students with PTSSs were also collected.RESULTS The prevalence of PTSSs among the participants was 28.0%.Seven significant correlates of PTSSs were identified(odds ratio=1.23-3.65,P≤0.024):Female sex,being 19 years old or older,living with others or alone,a low level of family economic status,fair or poor interpersonal relationships,severe or very severe local pandemic,and having family members diagnosed with COVID-19.However,only 3.28%of the students with PTSSs reported seeking help from mental health specialists.Among the 23 students who sought help from mental health specialists,13 opted for online or telephone-based psychological consultation.CONCLUSION Our data suggest that there was a high risk of PTSSs among university students and a high level of unmet mental health needs during the COVID-19 pandemic.The delivery of mental health services online or via telephone is a promising approach to address these unmet needs.展开更多
BACKGROUND Emotional reactions,such as anxiety,irritability,and aggressive behavior,have attracted clinical attention as behavioral and emotional problems in preschool-age children.AIM To investigate the current statu...BACKGROUND Emotional reactions,such as anxiety,irritability,and aggressive behavior,have attracted clinical attention as behavioral and emotional problems in preschool-age children.AIM To investigate the current status of family rearing,parental stress,and behavioral and emotional problems of preschool children and to analyze the mediating effect of the current status of family rearing on parental stress and behavioral/emo-tional problems.METHODS We use convenience sampling to select 258 preschool children in the physical examination center of our hospital from October 2021 to September 2023.The children and their parents were evaluated using a questionnaire survey.Pearson's correlation was used to analyze the correlation between child behavioral and emotional problems and parental stress and family rearing,and the structural equation model was constructed to test the mediating effect.RESULTS The score for behavioral/emotional problems of 258 preschool children was(27.54±3.63),the score for parental stress was(87.64±11.34),and the score for parental family rearing was(31.54±5.24).There was a positive correlation between the behavioral and emotional problems of the children and the“hostile/mandatory”parenting style;meanwhile,showed a negative correlation with the“support/participation”parenting style(all P<0.05).The intermediary effect value between the family upbringing of parents in parental stress and children's behavior problems was 29.89%.CONCLUSION Parental family upbringing has a mediating effect between parental stress and behavioral and emotional problems of children.Despite paying attention to the behavioral and emotional problems of preschool-age children,clinical medical staff should provide correct and reasonable parenting advice to their parents to promote the mental health of preschool-age children.展开更多
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 cereb...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.展开更多
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...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.展开更多
Understanding the stress distribution derived from monitoring the principal stress(PS)in slopes is of great importance.In this study,a miniature sensor for quantifying the two-dimensional(2D)PS in landslide model test...Understanding the stress distribution derived from monitoring the principal stress(PS)in slopes is of great importance.In this study,a miniature sensor for quantifying the two-dimensional(2D)PS in landslide model tests is proposed.The fundamental principle and design of the sensor are demonstrated.The sensor comprises three earth pressure gages and one gyroscope,with the utilization of three-dimensional(3D)printing technology.The difficulties of installation location during model preparation and sensor rotation during testing can be effectively overcome using this sensor.Two different arrangements of the sensors are tested in verification tests.Additionally,the application of the sensor in an excavated-induced slope model is tested.The results demonstrate that the sensor exhibits commendable performance and achieves a desirable level of accuracy,with a principal stress angle error of±5°in the verification tests.The stress transformation of the slope model,generated by excavation,is demonstrated in the application test by monitoring the two miniature principal stress(MPS)sensors.The sensor has a significant potential for measuring primary stress in landslide model tests and other geotechnical model experiments.展开更多
Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challe...Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challenge in accurately shaping aluminum alloy panels.In this study,the SRA behavior of 2195-T4 Al-Cu-Li alloys were thoroughly studied under initial loading stresses within the elastic(210/250 MPa)and plastic(380/420 MPa)ranges at 180℃by stress relaxation and tensile tests as well as microstructure characterization.The findings reveal that compared with those under elastic loadings,in-plane anisotropy(IPA)values of the stress relaxation amount,yield strength and fracture elongation under plastic loadings are reduced by 60%–80%,70%–90% and 72%–89%,respectively.Similarly,IPA values of precipitate size in grains and PrecipitationFree Zones(PFZ)width at grain boundaries under plastic loading decrease by 31.4%and 94.4%respectively.These results indicate plastic loading significantly weakens the anisotropic SRA behavior,owing to numerous uniformly distributed fine T1phases and small IPA values of both T1precipitates size and PFZ width in various loading directions.Compared with those of elastic loadingaged alloys,yield strength of plastic loading-aged alloys shows high strength-ductility because of the combined effect of closely dispersed fine T1precipitates,narrowed PFZ and numerous sheared and rotated T1phases at different locations during tensile process.The uniformly distributed larger Kernel Average Misorientation(KAM)and Schmidt factor values of the plastic loading-aged alloy,as well as the cross-slip generated,also help to enhance the strength and ductility of the alloy.展开更多
Objective:There is conflicting evidence suggesting an association between Ramadan and mental health.Aim:This study aims to assess changes in depression,anxiety,and stress levels during Ramadan among university student...Objective:There is conflicting evidence suggesting an association between Ramadan and mental health.Aim:This study aims to assess changes in depression,anxiety,and stress levels during Ramadan among university students from Saudi Arabia and to measure the magnitude of change in these levels according to gender.Methods:This study is a prospective cohort study.Data was collected using a structured questionnaire that measured demographic data of the students,and levels of depression,anxiety,and stress utilizing the short form of the Depression Anxiety Stress Scales questionnaire(DASS 21).The assessments were performed starting from the month of Shaban(the month that precedes Ramadan),and the second wave of data collection was initiated beginning the second week of Ramadan until the end of the month.Differences in the proportion of students who are categorized as normal or having abnormal degrees of depression and anxiety between Shaban and Ramadan were tested using either the Chi-square test or Fisher’s exact test.Results:A total of 321 students completed the assessment during Shaban and Ramadan.More than half of the students were male(54.2%),with a mean age of 22.A statistically significant di7fference in levels of anxiety,depression,and stress between the assessment periods was detected(p<0.001).The proportion of students classified as normal increased during Ramadan across all measured conditions in comparison to during Shaban.The reduction in the number of students classified as having anxiety,depression,and stress between the assessment periods remained statistically significant across both genders.Nonetheless,degrees of change appear to be higher among male students than among female students.Conclusion:This study identified a reduction in levels of depression,anxiety,and stress among students during the month of Ramadan,as well as gender variation concerning levels of change.The results support the significance of considering social,religious,and spiritual aspects when designing interventions to address individuals’mental health.展开更多
Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals an...Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.展开更多
Evaluation of hydromechanical shear behavior of unsaturated soils is still a challenging issue. The time and cost needed for conducting precise experimental investigation on shear behavior of unsaturated soils have en...Evaluation of hydromechanical shear behavior of unsaturated soils is still a challenging issue. The time and cost needed for conducting precise experimental investigation on shear behavior of unsaturated soils have encouraged several investigators to develop analytical, empirical, or semi-empirical models for predicting the shear behavior of unsaturated soils. However, most of the previously proposed models are for specimens subjected to the isotropic state of stress, without considering the effect of initial shear stress. In this study, a hydromechanical constitutive model is proposed for unsaturated collapsible soils during shearing, with consideration of the effect of the initial shear stress. The model implements an effective stress-based disturbed state concept (DSC) to predict the stress-strain behavior of the soil. Accordingly, material/state variables were defined for both the start of the shearing stage and the critical state of the soil. A series of laboratory tests was performed using a fully automated unsaturated triaxial device to verify the proposed model. The experimental program included 23 suction-controlled unsaturated triaxial shear tests on reconstituted specimens of Gorgan clayey loess wetted to different levels of suctions under both isotropic and anisotropic stress states. The results show excellent agreement between the prediction by the proposed model and the experimental results.展开更多
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 an...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.展开更多
Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to ...Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.展开更多
Nickel(Ni)toxicity significantly impairs plant growth,photosynthesis,and metabolism by inducing oxidative stress.This study evaluates the potential of exogenous Alpha-Ketoglutarate(AKG)in mitigating Ni-induced stress ...Nickel(Ni)toxicity significantly impairs plant growth,photosynthesis,and metabolism by inducing oxidative stress.This study evaluates the potential of exogenous Alpha-Ketoglutarate(AKG)in mitigating Ni-induced stress in Peganum harmala L.Seedlings were exposed to 0,200,500,and 750μM NiCl2,with or without AKG supplementation.Under 750μM Ni stress,dry weight(DW)decreased by 33.7%,tissue water content(TWC)by 39.9%,and chlorophyll a and total chlorophyll levels were reduced by 17%and 15%,respectively.Ni exposure also significantly increased secondary metabolite production,with leaf anthocyanin content rising by 131%,and superoxide dismutase(SOD)and catalase(CAT)activities increasing by 228%and 53%,respectively,in roots at 500μM Ni.AKG treatment alleviated Ni toxicity by enhancing TWC by 39%and promoting root and shoot growth.Additionally,AKG treatment boosted the synthesis of phenolic compounds and flavonoids,contributing to improved tolerance against Ni stress.These findings demonstrate the potential of AKG in enhancing Ni tolerance in P.harmala,suggesting its promising role in bioremediation of metal-contaminated soils.This is the first study to report the beneficial effects of exogenous AKG in alleviating nickel toxicity in P.harmala L.,offering a new approach for improving plant resilience to heavy metal stress.展开更多
The leucine-rich repeat(LRR)protein family is involved in a variety of fundamental metabolic and signaling processes in plants,including growth and defense responses.LRR proteins can be divided into two categories:tho...The leucine-rich repeat(LRR)protein family is involved in a variety of fundamental metabolic and signaling processes in plants,including growth and defense responses.LRR proteins can be divided into two categories:those containing LRR domains along with other structural elements,which are further subdivided into five groups,LRR receptor-like kinases,LRR receptor-like proteins,nucleotide-binding site LRR proteins,LRR-extensin proteins,and polygalacturonase-inhibiting proteins,and those containing only LRR domains.Functionally,various LRR proteins are primarily involved in plant development and responses to environmental stress.Notably,the LRR protein family plays a central role in signal transduction pathways related to stress adaptation.In this review,we classify and analyze the functions of LRR proteins in plants.While extensive research has been conducted on the roles of LRR proteins in disease resistance signaling,these proteins also play important roles in abiotic stress responses.This review highlights recent advances in understanding how LRR proteins mediate responses to biotic and abiotic stresses.Building upon these insights,further exploration of the roles of LRR proteins in abiotic stress resistance may aid efforts to develop rice varieties with enhanced stress and disease tolerance.展开更多
To investigate the performance of utilizing the shape memory effect of SMA(Shape Memory Alloy)wire to generate recovery stress,this paper performed single heating recovery stress tests and reciprocating heating-coolin...To investigate the performance of utilizing the shape memory effect of SMA(Shape Memory Alloy)wire to generate recovery stress,this paper performed single heating recovery stress tests and reciprocating heating-cooling recovery stress tests on SMA wire under varying initial strain conditions.The effects of various strains and different energized heating methods on the recovery stress of SMA wires were explored in the single heating tests.The SMA wire was strained from 2%to 8%initially,and two distinct heating approaches were employed:one using a large current interval for rapid heating and one using a small current interval for slower heating.The experimental outcomes reveal that during a single heating cycle,the temperature-recovery stress relationship of SMA wire exhibits three distinct stages:the martensite phase stage,the transition stage from martensite to austenite phase,and the austenite phase stage.Notably,the choice of heating method does not influence the maximum recovery stress value,and the correlation between initial strain and maximum recovery stress is predominantly linear.Moreover,conducting the reciprocating temperature rise and fall performance test is important to better simulate the scenario in practical engineering where multiple recovery stress in SMA wires for structural repair.In this test,two temperature cycling methods were studied:interval rise and fall,as well as direct rise and fall.In the case of utilizing the interval temperature rise and fall method,it was observed that the recovery stress associated with cooling was significantly higher than that corresponding to heating at the same temperature.Furthermore,the recovery stress was lower upon subsequent heating than that measured during the previous heating cycle.Based on the experimental results,a prediction model for the temperature-recovery stress relationship has been proposed to simplify numerical calculations.It is hoped that an approximate temperaturerecovery stress curve can be obtained from the parameters of the SMA wire.The calculated values derived from this model show good alignment with the measured values,indicating its reliability.展开更多
Complex bridge structures designed and constructed by humans often necessitate extensive on-site execution,which carries inherent risks.Consequently,a variety of engineering practices are employed to monitor bridge co...Complex bridge structures designed and constructed by humans often necessitate extensive on-site execution,which carries inherent risks.Consequently,a variety of engineering practices are employed to monitor bridge construction.This paper presents a case study of a large-span prestressed concrete(PC)variable-section continuous girder bridge in China,proposing a feedback system for construction monitoring and establishing a finite element(FE)analysis model for the entire bridge.The alignment of the completed bridge adheres to the initial design expectations,with maximum displacement and pre-arch differences from the ideal state measuring 6.39 and 17.7 mm,respectively,which were less than the 20 mm limit required by the specification.Additionally,the stress monitoring showed that the maximum compressive stress was 10.44 MPa,which was 7.5%different from the finite element results,and better predicted the most unfavorable possible location.These results demonstrate that a scientifically rigorous construction monitoring and feedback system can ensure the safety of bridge construction and meet the expected construction standards.The findings presented in this paper provide valuable insights for bridge construction monitoring practices.展开更多
Objective High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory.Nogo-A is an important axonal growth inhibitory factor.However,its function in high-altitude hypoxia and its mechanism o...Objective High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory.Nogo-A is an important axonal growth inhibitory factor.However,its function in high-altitude hypoxia and its mechanism of action remain unclear.Methods In an in vivo study,a low-pressure oxygen chamber was used to simulate high-altitude hypoxia,and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway.Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats,and synaptic damage in the hippocampus and changes in oxidative stress levels were observed.In vitro,SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion(OGD/R)models.Results Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats,triggered oxidative stress in the hippocampal tissue,and reduced the dendritic spine density of hippocampal neurons.Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress,synaptic damage,and the learning and memory impairment induced by high-altitude exposure.Conclusion Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure.展开更多
基金supported financially by the National Natural Science Foundation of China,No.82071272(to YZ).
文摘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.
基金financially supported by the National Natural Science Foundation of China(No.52204084)the Open Research Fund of the State Key Laboratory of Coal Resources and safe Mining,CUMT,China(No.SKLCRSM 23KF004)+3 种基金the Interdisciplinary Research Project for Young Teachers of USTB(Fundamental Research Funds for the Central Universities),China(No.FRF-IDRY-GD22-002)the Fundamental Research Funds for the Central Universities and the Youth Teacher International Exchange and Growth Program,China(No.QNXM20220009)the National Key R&D Program of China(Nos.2022YFC2905600 and 2022 YFC3004601)the Science,Technology&Innovation Project of Xiongan New Area,China(No.2023XAGG0061)。
文摘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.
基金supported by the STI 2030—Major Projects 2021ZD0204000,No.2021ZD0204003 (to XZ)the National Natural Science Foundation of China,Nos.32170973 (to XZ),32071018 (to ZH)。
文摘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.
文摘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.
文摘BACKGROUND Revisiting the epidemiology of posttraumatic stress symptoms(PTSSs)among university students during the coronavirus disease 2019(COVID-19)pandemic as well as understanding the mental health help-seeking behavior of individuals with PTSSs has critical implications for public mental health strategies in future medical pandemics.AIM To investigate the prevalence and correlates of PTSSs among university students during the first wave of the COVID-19 pandemic in China and to examine mental health help-seeking behaviors among these students.METHODS A total of 2507 Chinese university students were recruited via snowball sampling.The students completed the Seven-item Screening Scale for Post-traumatic Stress Disorder during the first wave of the COVID-19 pandemic in China.Sociodemo-graphic characteristics,pandemic-related characteristics,and mental health help-seeking behaviors of students with PTSSs were also collected.RESULTS The prevalence of PTSSs among the participants was 28.0%.Seven significant correlates of PTSSs were identified(odds ratio=1.23-3.65,P≤0.024):Female sex,being 19 years old or older,living with others or alone,a low level of family economic status,fair or poor interpersonal relationships,severe or very severe local pandemic,and having family members diagnosed with COVID-19.However,only 3.28%of the students with PTSSs reported seeking help from mental health specialists.Among the 23 students who sought help from mental health specialists,13 opted for online or telephone-based psychological consultation.CONCLUSION Our data suggest that there was a high risk of PTSSs among university students and a high level of unmet mental health needs during the COVID-19 pandemic.The delivery of mental health services online or via telephone is a promising approach to address these unmet needs.
基金Supported by the Shijiazhuang Science and Technology Research and Development Program,No.221460383.
文摘BACKGROUND Emotional reactions,such as anxiety,irritability,and aggressive behavior,have attracted clinical attention as behavioral and emotional problems in preschool-age children.AIM To investigate the current status of family rearing,parental stress,and behavioral and emotional problems of preschool children and to analyze the mediating effect of the current status of family rearing on parental stress and behavioral/emo-tional problems.METHODS We use convenience sampling to select 258 preschool children in the physical examination center of our hospital from October 2021 to September 2023.The children and their parents were evaluated using a questionnaire survey.Pearson's correlation was used to analyze the correlation between child behavioral and emotional problems and parental stress and family rearing,and the structural equation model was constructed to test the mediating effect.RESULTS The score for behavioral/emotional problems of 258 preschool children was(27.54±3.63),the score for parental stress was(87.64±11.34),and the score for parental family rearing was(31.54±5.24).There was a positive correlation between the behavioral and emotional problems of the children and the“hostile/mandatory”parenting style;meanwhile,showed a negative correlation with the“support/participation”parenting style(all P<0.05).The intermediary effect value between the family upbringing of parents in parental stress and children's behavior problems was 29.89%.CONCLUSION Parental family upbringing has a mediating effect between parental stress and behavioral and emotional problems of children.Despite paying attention to the behavioral and emotional problems of preschool-age children,clinical medical staff should provide correct and reasonable parenting advice to their parents to promote the mental health of preschool-age children.
基金supported by the National Natural Science Foundation of China,Nos.82260245(to YX),81660207(to YX),81960253(to YL),82160268(to YL),U1812403(to ZG)Science and Technology Projects of Guizhou Province,Nos.[2019]1440(to YX),[2020]1Z067(to WH)+1 种基金Cultivation Foundation of Guizhou Medical University,No.[20NSP069](to YX)Excellent Young Talents Plan of Guizhou Medical University,No.(2022)101(to WH)。
文摘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.
文摘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.
基金supported by the National Nature Science Foundation of China(Grant No.42207216)the Major Program of the National Natural Science Foundation of China(Grant No.42090055)the National Nature Science Foundation of China(Grant No.42377182).
文摘Understanding the stress distribution derived from monitoring the principal stress(PS)in slopes is of great importance.In this study,a miniature sensor for quantifying the two-dimensional(2D)PS in landslide model tests is proposed.The fundamental principle and design of the sensor are demonstrated.The sensor comprises three earth pressure gages and one gyroscope,with the utilization of three-dimensional(3D)printing technology.The difficulties of installation location during model preparation and sensor rotation during testing can be effectively overcome using this sensor.Two different arrangements of the sensors are tested in verification tests.Additionally,the application of the sensor in an excavated-induced slope model is tested.The results demonstrate that the sensor exhibits commendable performance and achieves a desirable level of accuracy,with a principal stress angle error of±5°in the verification tests.The stress transformation of the slope model,generated by excavation,is demonstrated in the application test by monitoring the two miniature principal stress(MPS)sensors.The sensor has a significant potential for measuring primary stress in landslide model tests and other geotechnical model experiments.
基金support from the Key Program of the National Natural Science Foundation of China(No.51235010)。
文摘Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challenge in accurately shaping aluminum alloy panels.In this study,the SRA behavior of 2195-T4 Al-Cu-Li alloys were thoroughly studied under initial loading stresses within the elastic(210/250 MPa)and plastic(380/420 MPa)ranges at 180℃by stress relaxation and tensile tests as well as microstructure characterization.The findings reveal that compared with those under elastic loadings,in-plane anisotropy(IPA)values of the stress relaxation amount,yield strength and fracture elongation under plastic loadings are reduced by 60%–80%,70%–90% and 72%–89%,respectively.Similarly,IPA values of precipitate size in grains and PrecipitationFree Zones(PFZ)width at grain boundaries under plastic loading decrease by 31.4%and 94.4%respectively.These results indicate plastic loading significantly weakens the anisotropic SRA behavior,owing to numerous uniformly distributed fine T1phases and small IPA values of both T1precipitates size and PFZ width in various loading directions.Compared with those of elastic loadingaged alloys,yield strength of plastic loading-aged alloys shows high strength-ductility because of the combined effect of closely dispersed fine T1precipitates,narrowed PFZ and numerous sheared and rotated T1phases at different locations during tensile process.The uniformly distributed larger Kernel Average Misorientation(KAM)and Schmidt factor values of the plastic loading-aged alloy,as well as the cross-slip generated,also help to enhance the strength and ductility of the alloy.
文摘Objective:There is conflicting evidence suggesting an association between Ramadan and mental health.Aim:This study aims to assess changes in depression,anxiety,and stress levels during Ramadan among university students from Saudi Arabia and to measure the magnitude of change in these levels according to gender.Methods:This study is a prospective cohort study.Data was collected using a structured questionnaire that measured demographic data of the students,and levels of depression,anxiety,and stress utilizing the short form of the Depression Anxiety Stress Scales questionnaire(DASS 21).The assessments were performed starting from the month of Shaban(the month that precedes Ramadan),and the second wave of data collection was initiated beginning the second week of Ramadan until the end of the month.Differences in the proportion of students who are categorized as normal or having abnormal degrees of depression and anxiety between Shaban and Ramadan were tested using either the Chi-square test or Fisher’s exact test.Results:A total of 321 students completed the assessment during Shaban and Ramadan.More than half of the students were male(54.2%),with a mean age of 22.A statistically significant di7fference in levels of anxiety,depression,and stress between the assessment periods was detected(p<0.001).The proportion of students classified as normal increased during Ramadan across all measured conditions in comparison to during Shaban.The reduction in the number of students classified as having anxiety,depression,and stress between the assessment periods remained statistically significant across both genders.Nonetheless,degrees of change appear to be higher among male students than among female students.Conclusion:This study identified a reduction in levels of depression,anxiety,and stress among students during the month of Ramadan,as well as gender variation concerning levels of change.The results support the significance of considering social,religious,and spiritual aspects when designing interventions to address individuals’mental health.
基金Supported by American Diabetes AssociationAmerican Heart Association+3 种基金NIH NIEHSNIH NIANIH NINDSand NIH ARRA.
文摘Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.
文摘Evaluation of hydromechanical shear behavior of unsaturated soils is still a challenging issue. The time and cost needed for conducting precise experimental investigation on shear behavior of unsaturated soils have encouraged several investigators to develop analytical, empirical, or semi-empirical models for predicting the shear behavior of unsaturated soils. However, most of the previously proposed models are for specimens subjected to the isotropic state of stress, without considering the effect of initial shear stress. In this study, a hydromechanical constitutive model is proposed for unsaturated collapsible soils during shearing, with consideration of the effect of the initial shear stress. The model implements an effective stress-based disturbed state concept (DSC) to predict the stress-strain behavior of the soil. Accordingly, material/state variables were defined for both the start of the shearing stage and the critical state of the soil. A series of laboratory tests was performed using a fully automated unsaturated triaxial device to verify the proposed model. The experimental program included 23 suction-controlled unsaturated triaxial shear tests on reconstituted specimens of Gorgan clayey loess wetted to different levels of suctions under both isotropic and anisotropic stress states. The results show excellent agreement between the prediction by the proposed model and the experimental results.
基金supported by the National Natural Science Foundation of China,Nos.82271327 (to ZW),82072535 (to ZW),81873768 (to ZW),and 82001253 (to TL)。
文摘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.
文摘Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.
基金Researchers Supporting Project No.(RSP2025R390),King Saud University,Riyadh,Saudi Arabia.
文摘Nickel(Ni)toxicity significantly impairs plant growth,photosynthesis,and metabolism by inducing oxidative stress.This study evaluates the potential of exogenous Alpha-Ketoglutarate(AKG)in mitigating Ni-induced stress in Peganum harmala L.Seedlings were exposed to 0,200,500,and 750μM NiCl2,with or without AKG supplementation.Under 750μM Ni stress,dry weight(DW)decreased by 33.7%,tissue water content(TWC)by 39.9%,and chlorophyll a and total chlorophyll levels were reduced by 17%and 15%,respectively.Ni exposure also significantly increased secondary metabolite production,with leaf anthocyanin content rising by 131%,and superoxide dismutase(SOD)and catalase(CAT)activities increasing by 228%and 53%,respectively,in roots at 500μM Ni.AKG treatment alleviated Ni toxicity by enhancing TWC by 39%and promoting root and shoot growth.Additionally,AKG treatment boosted the synthesis of phenolic compounds and flavonoids,contributing to improved tolerance against Ni stress.These findings demonstrate the potential of AKG in enhancing Ni tolerance in P.harmala,suggesting its promising role in bioremediation of metal-contaminated soils.This is the first study to report the beneficial effects of exogenous AKG in alleviating nickel toxicity in P.harmala L.,offering a new approach for improving plant resilience to heavy metal stress.
基金supported by the National Natural Science Foundation of China(Grant Nos.32072048 and U2004204)National Key Research and Development Program of China(Grant No.2023YFF1001200)+2 种基金China Rice Research Institute Basal Research Fund(Grant No.CPSIBRF-CNRRI-202404)Academician Workstation of National Nanfan Research Institute(Sanya),Chinese Agricultural Academic Science(CAAS),(Grant Nos.YBXM2422 and YBXM2423)Agricultural Science and Technology Innovation Program of CAAS,China.
文摘The leucine-rich repeat(LRR)protein family is involved in a variety of fundamental metabolic and signaling processes in plants,including growth and defense responses.LRR proteins can be divided into two categories:those containing LRR domains along with other structural elements,which are further subdivided into five groups,LRR receptor-like kinases,LRR receptor-like proteins,nucleotide-binding site LRR proteins,LRR-extensin proteins,and polygalacturonase-inhibiting proteins,and those containing only LRR domains.Functionally,various LRR proteins are primarily involved in plant development and responses to environmental stress.Notably,the LRR protein family plays a central role in signal transduction pathways related to stress adaptation.In this review,we classify and analyze the functions of LRR proteins in plants.While extensive research has been conducted on the roles of LRR proteins in disease resistance signaling,these proteins also play important roles in abiotic stress responses.This review highlights recent advances in understanding how LRR proteins mediate responses to biotic and abiotic stresses.Building upon these insights,further exploration of the roles of LRR proteins in abiotic stress resistance may aid efforts to develop rice varieties with enhanced stress and disease tolerance.
基金financially supported by National Natural Science Foundation of China(Project No.51878156).
文摘To investigate the performance of utilizing the shape memory effect of SMA(Shape Memory Alloy)wire to generate recovery stress,this paper performed single heating recovery stress tests and reciprocating heating-cooling recovery stress tests on SMA wire under varying initial strain conditions.The effects of various strains and different energized heating methods on the recovery stress of SMA wires were explored in the single heating tests.The SMA wire was strained from 2%to 8%initially,and two distinct heating approaches were employed:one using a large current interval for rapid heating and one using a small current interval for slower heating.The experimental outcomes reveal that during a single heating cycle,the temperature-recovery stress relationship of SMA wire exhibits three distinct stages:the martensite phase stage,the transition stage from martensite to austenite phase,and the austenite phase stage.Notably,the choice of heating method does not influence the maximum recovery stress value,and the correlation between initial strain and maximum recovery stress is predominantly linear.Moreover,conducting the reciprocating temperature rise and fall performance test is important to better simulate the scenario in practical engineering where multiple recovery stress in SMA wires for structural repair.In this test,two temperature cycling methods were studied:interval rise and fall,as well as direct rise and fall.In the case of utilizing the interval temperature rise and fall method,it was observed that the recovery stress associated with cooling was significantly higher than that corresponding to heating at the same temperature.Furthermore,the recovery stress was lower upon subsequent heating than that measured during the previous heating cycle.Based on the experimental results,a prediction model for the temperature-recovery stress relationship has been proposed to simplify numerical calculations.It is hoped that an approximate temperaturerecovery stress curve can be obtained from the parameters of the SMA wire.The calculated values derived from this model show good alignment with the measured values,indicating its reliability.
基金The Guangdong Basic and Applied Basic Research Foundation(Grant#2023A1515010535).
文摘Complex bridge structures designed and constructed by humans often necessitate extensive on-site execution,which carries inherent risks.Consequently,a variety of engineering practices are employed to monitor bridge construction.This paper presents a case study of a large-span prestressed concrete(PC)variable-section continuous girder bridge in China,proposing a feedback system for construction monitoring and establishing a finite element(FE)analysis model for the entire bridge.The alignment of the completed bridge adheres to the initial design expectations,with maximum displacement and pre-arch differences from the ideal state measuring 6.39 and 17.7 mm,respectively,which were less than the 20 mm limit required by the specification.Additionally,the stress monitoring showed that the maximum compressive stress was 10.44 MPa,which was 7.5%different from the finite element results,and better predicted the most unfavorable possible location.These results demonstrate that a scientifically rigorous construction monitoring and feedback system can ensure the safety of bridge construction and meet the expected construction standards.The findings presented in this paper provide valuable insights for bridge construction monitoring practices.
基金supported by Beijing Natural Science Foundation(No.7232090)the National Natural Science Foundation of China(82101306)the Scientific and Technological Innovation 2030(2021ZD0201100).
文摘Objective High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory.Nogo-A is an important axonal growth inhibitory factor.However,its function in high-altitude hypoxia and its mechanism of action remain unclear.Methods In an in vivo study,a low-pressure oxygen chamber was used to simulate high-altitude hypoxia,and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway.Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats,and synaptic damage in the hippocampus and changes in oxidative stress levels were observed.In vitro,SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion(OGD/R)models.Results Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats,triggered oxidative stress in the hippocampal tissue,and reduced the dendritic spine density of hippocampal neurons.Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress,synaptic damage,and the learning and memory impairment induced by high-altitude exposure.Conclusion Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure.