The unfolded protein response is a cellular pathway activated to maintain proteostasis and prevent cell death when the endoplasmic reticulum is overwhelmed by unfolded proteins.However,if the unfolded protein response...The unfolded protein response is a cellular pathway activated to maintain proteostasis and prevent cell death when the endoplasmic reticulum is overwhelmed by unfolded proteins.However,if the unfolded protein response fails to restore endoplasmic reticulum homeostasis,it can trigger proinflammatory and pro-death signals,which are implicated in various malignancies and are currently being investigated for their role in retinal degenerative diseases.This paper reviews the role of the unfolded protein responsein addressing endoplasmic reticulumstress in retinal degenerative diseases.The accumulation of ubiquitylated misfolded proteins can lead to rapid destabilization of the proteome and cellular demise.Targeting endoplasmic reticulum stress to alleviate retinal pathologies involves multiple strategies,including the use of chemical chaperones such as 4-phenylbutyric acid and tauroursodeoxycholic acid,which enhance protein folding and reduce endoplasmic reticulum stress.Small molecule modulators that influence endoplasmic reticulum stress sensors,including those that increase the expression of the endoplasmic reticulum stress regulator X-box binding protein 1,are also potential therapeutic agents.Additionally,inhibitors of the RNAse activity of inositol-requiring transmembrane kinase/endoribonuclease 1,a key endoplasmic reticulum stress sensor,represent another class of drugs that could prevent the formation of toxic aggregates.The activation of nuclear receptors,such as PPAR and FXR,may also help mitigate ER stress.Furthermore,enhancing proteolysis through the induction of autophagy or the inhibition of deubiquitinating enzymes can assist in clearing misfolded proteins.Combination treatments that involve endoplasmicreticulum-stress-targeting drugs and gene therapies are also being explored.Despite these potential therapeutic strategies,significant challenges remain in targeting endoplasmic reticulum stress for the treatment of retinal degeneration,and further research is essential to elucidate the mechanisms underlying human retinal diseases and to develop effective,well-tolerated drugs.The use of existing drugs that target inositol-requiring transmembrane kinase/endoribonuclease 1 and X-box binding protein 1 has been associated with adverse side effects,which have hindered their clinical translation.Moreover,signaling pathways downstream of endoplasmic reticulum stress sensors can contribute to therapy resistance.Addressing these limitations is crucial for developing drugs that can be effectively used in treating retinal dystrophies.In conclusion,while the unfolded protein response is a promising therapeutic target in retinal degenerative diseases,additional research and development efforts are imperative to overcome the current limitations and improve patient outcomes.展开更多
Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules form...Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.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:Weight-related self-stigma(WRSS)is prevalent among individuals with different types of weight status and is associated with a range of negative health outcomes.Social support and coping models explain how i...Background:Weight-related self-stigma(WRSS)is prevalent among individuals with different types of weight status and is associated with a range of negative health outcomes.Social support and coping models explain how individuals may use different coping methods to deal with their mental health needs.Psychological distress(e.g.,depression and stress)could lead to overuse of social media and smartphones.When using social media or smartphones,individuals are likely to be exposed to negative comments regarding weight/shape/size posted on the social media.Consequently,individuals who experience problematic social media use(PSMU)or problematic smartphone use(PSPU)may develop WRSS.Therefore,the present study examined the roles of PSMU and PSPU as mediators in the relationship between psychological distress and WRSS.Methods:Using convenience sampling via an online survey,622 participants with a mean age of 23.70 years(SD=4.33)completed questions assessing sociodemographic variables,psychological distress,PSMU,PSPU,WRSS,and self-reported weight and height.Results:The hierarchical regression models showed that sex(β=0.08,p=0.01),BMI(β=0.39,p<0.001),depression(β=0.21,p=0.001),stress(β=0.18,p=0.01),PSMU(β=0.09,p=0.045),and PSPU(β=0.14,p=0.001)were significant factors for WRSS.Conclusion:The mediation models showed that both PSMU and PSPU were significant mediators in the relationships between depression and stress with WRSS.The present findings provide some evidence for understanding WRSS and has important implications for developing interventions to reduce its negative impact on individuals’health and well-being.展开更多
This study investigates the effect of high current density electropulsing on the material in a rapid stress relaxation process.An AISI 1020 steel was shot-peened to induce surface compressive residual stresses in a co...This study investigates the effect of high current density electropulsing on the material in a rapid stress relaxation process.An AISI 1020 steel was shot-peened to induce surface compressive residual stresses in a controlled manner and subsequently electropulsed to investigate the changes in microstructure and defect configuration.AISI 1020 steel was chosen as it has a simple microstructure(plain ferritic)and composition with low alloying conditions.It is an appropriate material to study the effect of trans-mitting electric pulses on the microstructural defect evolution.A combination of electron-backscattered diffraction and transmission electron microscopy proved to be an effective tool in characterizing the post-electropulsing effects critically.By application of electropulsing,a reduction in the surface residual stress layer was noticed.Also,reductions in misorientation and dislocation density together with the disentan-glement of dislocations within the cold-worked layer were observed after electropulsing.Additionally,the annihilation of shot-peening-induced deformation bands beyond the residual layer depth was observed.These effects have been rationalised by taking into account the various possibilities of athermal effects of electropulsing.展开更多
The formation of root system architecture(RSA)plays a crucial role in plant growth.OsDRO1 is known to have a function in controlling RSA in rice,however,the role of potato StDRO2,a homolog of rice OsDRO1,in root growt...The formation of root system architecture(RSA)plays a crucial role in plant growth.OsDRO1 is known to have a function in controlling RSA in rice,however,the role of potato StDRO2,a homolog of rice OsDRO1,in root growth remains unclear.In this study,we obtained potato dro2 mutant lines by Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated 9(CRISPR/Cas9)-mediated genome editing system.The mutant lines were generated from a splicing defect of the StDRO2 intron 1,which causes a nonsense mutation in StDRO2.Furthermore,the secondary structure of StDRO2 mRNA analyzed with RNAfold Web Server was altered in the dro2 mutant.Mutation of StDRO2 conveys potato adaptation through changing the RSA via alteration of auxin transport under drought stress.The potato dro2 lines showed higher plant height,longer root length,smaller root growth angle and increased tuber weight than the wild-type.The alteration of RSA was associated with a disturbance of IAA distribution in the dro2 mutant,and the levels of StPIN7 and StPIN10 detected by using real-time PCR were up-regulated in the roots of potato dro2 lines grown under drought stress.Moreover,the microRNAs(miRNAs)PmiREN024536 and PmiREN024486 targeted the StDRO2 gene,and auxin positively and negatively regulated the expression of StDRO2 and the miRNAs PmiREN024536 and PmiREN024486,respectively,in the potato roots.Our data shows that a regulatory network involving auxin,StDRO2,PmiREN024536 and PmiREN024486 can control RSA to convey potato fitness under drought stress.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
Dopamine β-monooxygenase N-terminal(DOMON)domain-containing genes are present across all taxa and are critical in cell signaling and redox transport.Despite their significance,these genes remain understudied in plant...Dopamine β-monooxygenase N-terminal(DOMON)domain-containing genes are present across all taxa and are critical in cell signaling and redox transport.Despite their significance,these genes remain understudied in plant species.In this study,we identified 15 DOMON genes in rice and analyzed their phylogenetic relationships,conserved motifs,and cis-regulatory elements.Phylogenetic analysis revealed distinct clustering of OsDOMON genes in rice and other monocots,compared with Arabidopsis thaliana.Promoter analysis showed a higher abundance of stress-related regulatory elements in Tetep,a well-known blast and abiotic stress-tolerant cultivar,compared with Nipponbare and HP2216.OsDOMON genes displayed differential expression under biotic stress(Magnaporthe oryzae infection)and abiotic stresses(drought,heat,and salinity)in contrasting cultivars.Tetep exhibited significantly higher expression levels of specific OsDOMON genes during early blast infection stages,particularly OsDOMON6.1 and OsDOMON9.2,suggesting their roles in cell wall fortification and reactive oxygen species signaling.Under abiotic stress,genes like OsDOMON3.3,OsDOMON8.1,and OsDOMON9.2 showed higher expression in Tetep,indicating their involvement in stress tolerance mechanisms.This study provides a foundation for future functional studies of OsDOMON genes,paving the way for developing rice cultivars resistant to biotic and abiotic stresses.展开更多
Acute stress disorder(ASD)is a transient psychiatric disorder that may arise subsequent to abrupt,extreme trauma exposure,and serves as a reliable indicator for the subsequent development of posttraumatic stress disor...Acute stress disorder(ASD)is a transient psychiatric disorder that may arise subsequent to abrupt,extreme trauma exposure,and serves as a reliable indicator for the subsequent development of posttraumatic stress disorder(PTSD)(Bryant,2011;Battle,2013).It exhibits rapid progression in the aftermath of trauma and persists for a duration of days or weeks(not exceeding one month),manifesting symptoms of dissociation,re-experiencing,avoidance,and hyperarousal(Bielas et al.,2018).In the absence of efficacious and prompt intervention,ASD is linked to substantial morbidity and functional impairment(McLean et al.,2022).展开更多
Dear Editor,Stress granules(SGs)are dynamic membraneless RNAprotein aggregates or organelles that are formed in response to various cellular stresses and disassemble rapidly with the decay of stresses[1].Under stressf...Dear Editor,Stress granules(SGs)are dynamic membraneless RNAprotein aggregates or organelles that are formed in response to various cellular stresses and disassemble rapidly with the decay of stresses[1].Under stressful conditions,protein translation is often inhibited suddenly.The resulting untranslated messenger ribonucleoproteins interact with the so-called"nucleator proteins"(such as G3BP1/2 and TIA1)to form the core structure of SGs,which then grow or merge into mature SGs by sequestering untranslated mRNAs and misfolded proteins[2,3].展开更多
Objective:To investigate the effect of cerebrolysin(CBL)on motor impairment,neuroinflammation,oxidative stress,and neurotransmitter profile in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s di...Objective:To investigate the effect of cerebrolysin(CBL)on motor impairment,neuroinflammation,oxidative stress,and neurotransmitter profile in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease(PD)in zebrafish.Methods:In the current study,zebrafish were treated with CBL at doses of 1.25,2.5,and 5 mL/kg body weight for 7 consecutive days.MPTP(20 mg/kg body weight)was administered on alternative days-1st,3rd,5th,and 7th.On day 7,zebrafish were sacrificed,and their brains were isolated for biochemical,neurochemical,histopathological,IHC,and neurotransmitter analysis.Results:The treatment with CBL significantly increased total distance traveled and the number of entries in the top zone,which was impaired by MPTP.CBL treatment significantly restored the level of glutathione,superoxide dismutase,and catalase while reducing malondialdehyde level.It also reduced the level of pro-inflammatory mediators interleukin-1β,interleukin-6,and tumor necrosis factor-αin the MPTP-induced PD in the zebrafish model.In histopathological evaluation,pyknotic cells and signs of inflammation were significantly reduced in CBL-treated groups.A significant dose-dependent reduction in glutamate,along with elevations in dopamine,gamma-aminobutyric acid,serotonin,and noradrenaline,was observed in zebrafish treated with CBL.An immunohistochemistry analysis demonstrated that Akt was phosphorylated promptly by CBL,which was downregulated in MPTP-induced PD in zebrafish.Conclusions:These findings suggest that CBL exerts a neuroprotective effect through activation of Akt and may hold therapeutic potential for the treatment of this devastating neurological condition.展开更多
Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response an...Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response and exacerbating glycolysis in multiple tissues.However,the redox induction mechanism of lactate in mammary gland has not been understood yet.Herein,we describe a lactate-responsive HIF1α/circadian control mechanism in oxidative stress in the mammary glands of dairy cows.Results The in vivo study showed that dairy cows with high lactate concentrations are associated with reduced milk yield and more ROS accumulation in mammary gland.Western blot results in MAC-T cells showed positive correlation between lactate concentrations,expression of HIF1αand oxidative stress indicators,but not circadian core components.To test how lactate-mediated HIF1αdysfunction leads to cell protection process,we investigated altered expression of circadian core related genes following HIF1αstabilization.We found that stabilized HIF1αby lactate inhibited stimulated expression of circadian core components due to the similarity of HRE and E-box transcription elements.Furthermore,we found that lactate treatment strengthened the binding of HIF1αwith BMAL1,HMOX1 and FOXO3 in MAC-T cells.Moreover,HIF1αknockdown altered expression of circadian rhythm related genes and reduced oxidative stress state.Conclusion In summary,our study highlights the central role of competitive transcriptional element occupancy in lactate-mediated oxidative stress of mammary gland,which is caused by HIF1αstabilization and circadian rhythm dysfunction.Our findings introduce a novel nutritional strategy with potential applications in dairy farming for optimizing milk production and maintaining mammary gland health.展开更多
BACKGROUND Patients with multiple injuries endure not just physical trauma and suffering but are also at risk of psychological conditions such as posttraumatic stress disorder(PTSD),anxiety,and depression.The co-occur...BACKGROUND Patients with multiple injuries endure not just physical trauma and suffering but are also at risk of psychological conditions such as posttraumatic stress disorder(PTSD),anxiety,and depression.The co-occurrence of PTSD in these patients may cause prolonged physical and mental health complications,thereby further increasing their healthcare expenses.AIM To determine the association between the high-risk factors of PTSD and anxiety as well as depression among patients with multiple injuries.METHODS This study selected 110 patients with multiple injuries who were admitted to our hospital from November 2022 to November 2024.The number and percentage of patients developing PTSD were tallied.Univariate and multivariate analyses were conducted to investigate the high-risk factors of PTSD in these patients.Subse-quently,the associations between these factors and the anxiety and depression levels of patients were analyzed.RESULTS Of the 110 patients,33 suffered from PTSD,representing an incidence rate of 30.0%.The univariate analysis identified age,personality,Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),economic status,negative life events,and smoking history to be significantly associated with PTSD in patients with multiple injuries.Further,the multivariate analysis revealed age,HAMA,HAMD,monthly income,and negative life events as prominent high-risk factors for PTSD in such patients.Regarding the relationships between these factors and HAMA and HAMD,age exhibited a significant positive correlation(r=0.398,P<0.001;r=0.387,P<0.001),monthly income showed a significant negative correlation(r=-0.437,P<0.001;r=-0.319,P<0.001),and negative life events demonstrated a significant positive correlation(r=0.505,P<0.001;r=0.365,P<0.001).CONCLUSION These results indicate age,HAMA,HAMD,monthly income,negative life events,etc.as high-risk factors for PTSD in patients with multiple injuries,among which age,monthly income,and negative life events are closely associated with anxiety and depression.展开更多
With the accelerated pace of population aging in China,the number of patients suffering from myocardial infarction(MI)is increasing annually.During disease progression,patients are at significantly higher risk of deve...With the accelerated pace of population aging in China,the number of patients suffering from myocardial infarction(MI)is increasing annually.During disease progression,patients are at significantly higher risk of developing severe negative emotions,and emerging evidence suggests that post-traumatic stress disorder(PTSD)is significantly associated with cardiovascular disease,which seriously affects patients’quality of life.Objective:The aim of this study was to comprehensively assess the prevalence and influencing factors of PTSD in MI patients through systematic review and Meta-analysis.Methods:A computerized search of PubMed,the Cochrane Library,Embase,Web of Science,PsycINFO,China Knowledge Network(CNKI),WanFang Data,VIP,and China Biomedical Literature Database(CBM)was conducted to collect longitudinal studies,case-control studies,and cross-sectional studies related to PTSD prevalence rates and influencing factors in MI patients published up to August 1,2024.Literature screening,data extraction and quality assessment were done independently by two researchers and Meta-analysis was done using Stata 16.0 software.This study has been registered on the PROSPERO platform,registration number:CRD42024577243.Results:A total of 16 papers were included,with a total sample size of 3,768 cases involving 8 influencing factors.The results of the Meta-analysis showed that the prevalence of PTSD in patients with MI was 20.4%(95%CI=15.0–26.5%).Female(OR=3.12,95%CI=1.97–4.97,P<0.001),high neuroticism score(OR=2.21,95%CI=1.20–4.07,P=0.011),and high intrusive rumination score(OR=2.95,95%CI=1.50–5.83,P=0.002)were the risk factors for PTSD in MI patients.While age(OR=1.01,95%CI=0.98–1.04,P=0.440),education level(OR=0.55,95%CI=0.07–4.48,P=0.574),social support rating scale(OR=0.81,95%CI=0.52–1.26,P=0.346),Killip cardiac function classification(OR=2.29,95%CI=0.91–5.80,P=0.080)and creatine kinase isoenzyme(OR=1.03,95%CI=0.99–1.05,P=0.124)were not associated with the development of PTSD in MI patients.Conclusion:The prevalence of PTSD was higher in patients with MI.The prevalence varied by evaluation tool and study area.Risk factors were multifactorial,including general factors(female)and overall assessment(high neuroticism score,high invasive rumination score).Therefore,early intervention and proper de-escalation of PTSD symptoms in patients with MI by medical staff are needed in clinical practice to reduce the risk of PTSD.展开更多
Three sandstone specimens common in rock engineering were selected to study the differences in the mechanical properties of rocks with different lithologies.The development and expansion of the internal cracks in the ...Three sandstone specimens common in rock engineering were selected to study the differences in the mechanical properties of rocks with different lithologies.The development and expansion of the internal cracks in the specimens were observed by combining the simulation system with the acoustic emission system.Through the combination of dynamic and static stresses,the deformation and damage of rocks under deep rock excavation and blasting were simulated.As the results show,the acoustic emission events of specimens with different lithologies under combined static and dynamic cyclic loading can be roughly divided into three phases:weakening,stabilizing,and surging periods.In addition,the acoustic emission characteristics of specimens with different lithologies show general consistency in different compression phases.The degree of fragmentation of specimens increases with the applied stress level;therefore,the stress level is one of the important factors influencing the damage pattern of specimens.The acoustic emission system was used to simulate the deformation and damage of rocks subjected to deep rock body excavation and engineering blasting.Cyclic dynamic perturbations under sinusoidal waves with a frequency of 5 Hz,a loading rate of 0.1 mm/min,a cyclic amplitude of 5 MPa,and a loading rate of 0.1 mm/min were applied to the three rock samples during the experiments.Among them,the fine-grained sandstones are the most sensitive to the sinusoidal cyclic perturbation,followed by the muddy siltstone and the medium-grained sandstones.On this basis,the acoustic emission energy release characteristics were analyzed,and the waveform characteristics in the damage evolution of the specimen under dynamic perturbation were studied by extracting the key points and searching for the main frequency eigenvalues.展开更多
Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods...Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods:The PTSD mouse model was subjected to single prolonged stress and shock(SPS&S),and the animals received 15 min sessions of EA at Shenmen acupoint(HT7).Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear.Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex(PFC).Additionally,the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.Results:Mice subjected to SPS&S presented increased anxiety-and fear-like behaviors.Lcn2 expression in the PFC was significantly upregulated following SPS&S,leading to increased expression of the proinflammatory cytokines tumor necrosis factor-a and interleukin-6 and suppression of PFC neuronal activity.However,EA at HT7 inhibited Lcn2 release,reducing neuroinflammation and hypoexcitability in the PFC.Lcn2 overexpression mitigated the effects of EA at HT7,resulting in anxiety-and fear-like behaviors.Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear,and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC.展开更多
In the process of deep engineering excavation,the mechanical properties of rock are significantly influenced by the coupled effects of water and high stress,which greatly increase construction difficulty.To more accur...In the process of deep engineering excavation,the mechanical properties of rock are significantly influenced by the coupled effects of water and high stress,which greatly increase construction difficulty.To more accurately investigate the impact of water disturbance on the failure process of dry rock under high stress and the failure mechanisms of saturated rock in underwater environments,a water environment test chamber and a prefabricated borehole specimen through-water device were designed.A series of experiments were conducted,including uniaxial tests,water-disturbed granite cylinder tests,and through-water disturbance tests on prefabricated hole square specimens.The results showed that the acoustic emission(AE)hits and accumulated energy after the through-water disturbance at the same time were 8.77 and 12.08 times higher than before the disturbance,respectively.And water disturbance increased the proportion of tensile failure and reduced the proportion of shear failure.A key observation was that AE events were mainly generated in the permeation areas near the borehole.The main reason was that under high stress,the weakening effect of water led to the failure of the local mineral structure of the rock,promoting crack extension and triggering overall instability.Notably,failure of the saturated specimens underwater was only observed when the applied load approached the saturation strength of the prefabricated hole square specimens.The study results provide an important theoretical basis for understanding the damage mechanism of water-disturbed rocks in deep engineering,and have significant implications for the design and construction of engineering.展开更多
Neurodegenerative diseases(NDs)such as Alzheimer’s disease(AD),Parkinson’s disease(PD),Huntington’s disease(HD),and amyotrophic lateral sclerosis(ALS)are characterized by progressive neuronal loss,which is closely ...Neurodegenerative diseases(NDs)such as Alzheimer’s disease(AD),Parkinson’s disease(PD),Huntington’s disease(HD),and amyotrophic lateral sclerosis(ALS)are characterized by progressive neuronal loss,which is closely linked to mitochondrial dysfunction.These pathologies involve a complex interplay of genetics,protein misfolding,and cellular stress,culminating in impaired energy metabolism,an increase in reactive oxygen species(ROS),and defective mitochondrial quality control.The accumulation of damaged mitochondria and dysregulation of pathways such as the Integrated Stress Response(ISR)are central to the pathogenesis of these conditions.This review explores the critical relationship between mitochondrial stress and neurodegeneration,highlighting the molecular mechanisms and biomarkers involved.It delves into the multifaceted role of melatonin as a potent neuroprotective agent.Melatonin,a lipophilic indoleamine,is produced both in the pineal gland and locally within mitochondria,where it exerts powerful antioxidant,anti-inflammatory,and anti-apoptotic effects.Its unique ability to neutralize multiple free radicals and its cascade-based antioxidant action make it superior to conventional antioxidants.Its mechanisms of action are discussed,including signaling pathway modulation and enhancement of the brain’s clearance system(the glymphatic system).Despite its potential,melatonin’s low bioavailability and rapid metabolism limit its therapeutic efficacy.In this context,nanopharmacology emerges as a promising strategy.Nanoparticles such as liposomes,polymers,and solid lipids can encapsulate melatonin and protect it from degradation,facilitating its transport across the blood-brain barrier.Preclinical evidence has shown that melatonin-loaded nanoparticles significantly improve cognitive function,reduce oxidative stress,and restore mitochondrial homeostasis in models of AD,PD,and ALS.In conclusion,the synergistic combination of melatonin and nanopharmacology offers a multimodal and highly targeted approach formitigatingmitochondrial dysfunction in NDs.While challenges remain in optimizing the formulation and safety of these nanocarriers,this combination represents a crucial frontier for developing more effective and specific treatments in the future.展开更多
The orientation effect of θʹ precipitates in stress-aged Al-Cu alloys has ambiguous interpretations. One view is that θʹ precipitates prefer to grow on the habit planes perpendicular to the applied compressive stres...The orientation effect of θʹ precipitates in stress-aged Al-Cu alloys has ambiguous interpretations. One view is that θʹ precipitates prefer to grow on the habit planes perpendicular to the applied compressive stress, while the other view suggests growth on habit planes parallel to the applied stress. In this study, stress-aged Al-4 wt.%Cu single crystal was sampled from three different <100>Al zone axes to observe the distribution of θʹ precipitates. A hybrid Monte-Carlo/ molecular dynamics simulations were used to investigate the orientation effect of θʹ precipitates. The simulation results are consistent with experimental observations and indicate that θʹ precipitates prefer to grow on the habit planes that are parallel to the direction of the applied compressive stress, not along the planes perpendicular to it. It is also found that 1/2<110> perfect dislocations are generated as θʹ precipitates plates grow thicker, and the reaction of 1/2<110> perfect dislocations decomposing into 1/6<112> Shockley dislocations lead to an increase in the length of θʹ precipitates. The former does not enhance the orientation effect, whereas the latter leads to a more significant orientation effect. Additionally, the degree of the orientation effect of θʹ precipitates is determined by the reduction of 1/2<110> dislocations with a positive correlation between them.展开更多
With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis...With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis of MASLD is complex,characterized by oxidative stress,impaired mitochondrial function and lipid metabolism,and cellular inflammation.Mitochondrial biology and function are central to the physiology of the liver.It has been suggested that mitochondrial oxidative stress plays a crucial role in MASLD progression.Excessive oxidative stress response is an important trigger for the occurrence and development of MASLD.In this review,we aim to focus on the recent advances in understanding mitochondrial oxidative stress-related mechanisms in the progression of MASLD.The in-depth elaboration of its related mechanisms is hoped to help find effective methods for treating MASLD.展开更多
基金supported by the Natural Science Foundation of Shaanxi Province(Key Program),No.2021JZ-60(to HZ)。
文摘The unfolded protein response is a cellular pathway activated to maintain proteostasis and prevent cell death when the endoplasmic reticulum is overwhelmed by unfolded proteins.However,if the unfolded protein response fails to restore endoplasmic reticulum homeostasis,it can trigger proinflammatory and pro-death signals,which are implicated in various malignancies and are currently being investigated for their role in retinal degenerative diseases.This paper reviews the role of the unfolded protein responsein addressing endoplasmic reticulumstress in retinal degenerative diseases.The accumulation of ubiquitylated misfolded proteins can lead to rapid destabilization of the proteome and cellular demise.Targeting endoplasmic reticulum stress to alleviate retinal pathologies involves multiple strategies,including the use of chemical chaperones such as 4-phenylbutyric acid and tauroursodeoxycholic acid,which enhance protein folding and reduce endoplasmic reticulum stress.Small molecule modulators that influence endoplasmic reticulum stress sensors,including those that increase the expression of the endoplasmic reticulum stress regulator X-box binding protein 1,are also potential therapeutic agents.Additionally,inhibitors of the RNAse activity of inositol-requiring transmembrane kinase/endoribonuclease 1,a key endoplasmic reticulum stress sensor,represent another class of drugs that could prevent the formation of toxic aggregates.The activation of nuclear receptors,such as PPAR and FXR,may also help mitigate ER stress.Furthermore,enhancing proteolysis through the induction of autophagy or the inhibition of deubiquitinating enzymes can assist in clearing misfolded proteins.Combination treatments that involve endoplasmicreticulum-stress-targeting drugs and gene therapies are also being explored.Despite these potential therapeutic strategies,significant challenges remain in targeting endoplasmic reticulum stress for the treatment of retinal degeneration,and further research is essential to elucidate the mechanisms underlying human retinal diseases and to develop effective,well-tolerated drugs.The use of existing drugs that target inositol-requiring transmembrane kinase/endoribonuclease 1 and X-box binding protein 1 has been associated with adverse side effects,which have hindered their clinical translation.Moreover,signaling pathways downstream of endoplasmic reticulum stress sensors can contribute to therapy resistance.Addressing these limitations is crucial for developing drugs that can be effectively used in treating retinal dystrophies.In conclusion,while the unfolded protein response is a promising therapeutic target in retinal degenerative diseases,additional research and development efforts are imperative to overcome the current limitations and improve patient outcomes.
基金supported by a grant from the Merkin Peripheral Neuropathy and Nerve Regeneration Center(to PKS)the Rutgers University Startup Fund(to PKS).
文摘Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.
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.
基金supported in part by(received funding from)the Ministry of Science and Technology,Taiwan(MOST 110-2410-H-006-115,MOST 111-2410-H-006-100)the National Science and Technology Council,Taiwan(NSTC 112-2410-H-006-089-SS2)+1 种基金the Higher Education Sprout Project,the Ministry of Education at the Headquarters of University Advancement at the National Cheng Kung University(NCKU)the 2021 Southeast and South Asia and Taiwan Universities Joint Research Scheme(NCKU 31).
文摘Background:Weight-related self-stigma(WRSS)is prevalent among individuals with different types of weight status and is associated with a range of negative health outcomes.Social support and coping models explain how individuals may use different coping methods to deal with their mental health needs.Psychological distress(e.g.,depression and stress)could lead to overuse of social media and smartphones.When using social media or smartphones,individuals are likely to be exposed to negative comments regarding weight/shape/size posted on the social media.Consequently,individuals who experience problematic social media use(PSMU)or problematic smartphone use(PSPU)may develop WRSS.Therefore,the present study examined the roles of PSMU and PSPU as mediators in the relationship between psychological distress and WRSS.Methods:Using convenience sampling via an online survey,622 participants with a mean age of 23.70 years(SD=4.33)completed questions assessing sociodemographic variables,psychological distress,PSMU,PSPU,WRSS,and self-reported weight and height.Results:The hierarchical regression models showed that sex(β=0.08,p=0.01),BMI(β=0.39,p<0.001),depression(β=0.21,p=0.001),stress(β=0.18,p=0.01),PSMU(β=0.09,p=0.045),and PSPU(β=0.14,p=0.001)were significant factors for WRSS.Conclusion:The mediation models showed that both PSMU and PSPU were significant mediators in the relationships between depression and stress with WRSS.The present findings provide some evidence for understanding WRSS and has important implications for developing interventions to reduce its negative impact on individuals’health and well-being.
基金supported by the National Research Foundation of Singapore,Rolls-Royce Singapore Pte.Ltd.,and Nanyang Technological University through grants#002123-00009 and #002124-00009.
文摘This study investigates the effect of high current density electropulsing on the material in a rapid stress relaxation process.An AISI 1020 steel was shot-peened to induce surface compressive residual stresses in a controlled manner and subsequently electropulsed to investigate the changes in microstructure and defect configuration.AISI 1020 steel was chosen as it has a simple microstructure(plain ferritic)and composition with low alloying conditions.It is an appropriate material to study the effect of trans-mitting electric pulses on the microstructural defect evolution.A combination of electron-backscattered diffraction and transmission electron microscopy proved to be an effective tool in characterizing the post-electropulsing effects critically.By application of electropulsing,a reduction in the surface residual stress layer was noticed.Also,reductions in misorientation and dislocation density together with the disentan-glement of dislocations within the cold-worked layer were observed after electropulsing.Additionally,the annihilation of shot-peening-induced deformation bands beyond the residual layer depth was observed.These effects have been rationalised by taking into account the various possibilities of athermal effects of electropulsing.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.32260085,31860064,31660501,31970609,32260718 and 31901870)the Key Projects of the Applied Basic Research Plan of Yunnan Province(Grant No.202301AS070082)+3 种基金the Start-up fund from Xishuangbanna Tropical Botanical Garden,the‘Top Talents Program in Science and Technology’from Yunnan Province,the Major Science and Technology Project in Yunnan Province(Grant Nos.202102AE090042 and 202202AE090036)the Young and Middle-Aged Academic and Technical Leaders Reserve Talent Program in Yunnan Province(Grant No.202205AC160076)China Postdoctoral Science Foundation(Grant No.2019M653849XB)the High-level Talents Introduction Plan of Yunnan Province-Young Talents Special Project。
文摘The formation of root system architecture(RSA)plays a crucial role in plant growth.OsDRO1 is known to have a function in controlling RSA in rice,however,the role of potato StDRO2,a homolog of rice OsDRO1,in root growth remains unclear.In this study,we obtained potato dro2 mutant lines by Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated 9(CRISPR/Cas9)-mediated genome editing system.The mutant lines were generated from a splicing defect of the StDRO2 intron 1,which causes a nonsense mutation in StDRO2.Furthermore,the secondary structure of StDRO2 mRNA analyzed with RNAfold Web Server was altered in the dro2 mutant.Mutation of StDRO2 conveys potato adaptation through changing the RSA via alteration of auxin transport under drought stress.The potato dro2 lines showed higher plant height,longer root length,smaller root growth angle and increased tuber weight than the wild-type.The alteration of RSA was associated with a disturbance of IAA distribution in the dro2 mutant,and the levels of StPIN7 and StPIN10 detected by using real-time PCR were up-regulated in the roots of potato dro2 lines grown under drought stress.Moreover,the microRNAs(miRNAs)PmiREN024536 and PmiREN024486 targeted the StDRO2 gene,and auxin positively and negatively regulated the expression of StDRO2 and the miRNAs PmiREN024536 and PmiREN024486,respectively,in the potato roots.Our data shows that a regulatory network involving auxin,StDRO2,PmiREN024536 and PmiREN024486 can control RSA to convey potato fitness under drought stress.
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 Indian Council of Agricultural Research(ICAR)-Senior Research Fellowship from ICAR,India(Grant No.EDN/1/25/2015-Exam cell)ICAR-Centre for Agricultural Bioinformatics and National Institute for Plant Biotechnology,India(Grant No.1006456).
文摘Dopamine β-monooxygenase N-terminal(DOMON)domain-containing genes are present across all taxa and are critical in cell signaling and redox transport.Despite their significance,these genes remain understudied in plant species.In this study,we identified 15 DOMON genes in rice and analyzed their phylogenetic relationships,conserved motifs,and cis-regulatory elements.Phylogenetic analysis revealed distinct clustering of OsDOMON genes in rice and other monocots,compared with Arabidopsis thaliana.Promoter analysis showed a higher abundance of stress-related regulatory elements in Tetep,a well-known blast and abiotic stress-tolerant cultivar,compared with Nipponbare and HP2216.OsDOMON genes displayed differential expression under biotic stress(Magnaporthe oryzae infection)and abiotic stresses(drought,heat,and salinity)in contrasting cultivars.Tetep exhibited significantly higher expression levels of specific OsDOMON genes during early blast infection stages,particularly OsDOMON6.1 and OsDOMON9.2,suggesting their roles in cell wall fortification and reactive oxygen species signaling.Under abiotic stress,genes like OsDOMON3.3,OsDOMON8.1,and OsDOMON9.2 showed higher expression in Tetep,indicating their involvement in stress tolerance mechanisms.This study provides a foundation for future functional studies of OsDOMON genes,paving the way for developing rice cultivars resistant to biotic and abiotic stresses.
基金supported by the National Natural Science Foundation of China(No.82271562)the Key Research and Development Program of Zhejiang Province of China(No.2023C03077).
文摘Acute stress disorder(ASD)is a transient psychiatric disorder that may arise subsequent to abrupt,extreme trauma exposure,and serves as a reliable indicator for the subsequent development of posttraumatic stress disorder(PTSD)(Bryant,2011;Battle,2013).It exhibits rapid progression in the aftermath of trauma and persists for a duration of days or weeks(not exceeding one month),manifesting symptoms of dissociation,re-experiencing,avoidance,and hyperarousal(Bielas et al.,2018).In the absence of efficacious and prompt intervention,ASD is linked to substantial morbidity and functional impairment(McLean et al.,2022).
基金supported by the National Natural Science Foundation of China(32394032 and 82371402)Postdoctoral Fellowship Program of China(GZC20242295)+1 种基金the Natural Science Foundation of Shaanxi Province(2025SF-YBXM-393)the Military Medical Promoting Project of FMMU(2021JSTS27).
文摘Dear Editor,Stress granules(SGs)are dynamic membraneless RNAprotein aggregates or organelles that are formed in response to various cellular stresses and disassemble rapidly with the decay of stresses[1].Under stressful conditions,protein translation is often inhibited suddenly.The resulting untranslated messenger ribonucleoproteins interact with the so-called"nucleator proteins"(such as G3BP1/2 and TIA1)to form the core structure of SGs,which then grow or merge into mature SGs by sequestering untranslated mRNAs and misfolded proteins[2,3].
基金funded by ICMR,New Delhi(Grant No.45/29/2022-PHA/BMS).
文摘Objective:To investigate the effect of cerebrolysin(CBL)on motor impairment,neuroinflammation,oxidative stress,and neurotransmitter profile in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease(PD)in zebrafish.Methods:In the current study,zebrafish were treated with CBL at doses of 1.25,2.5,and 5 mL/kg body weight for 7 consecutive days.MPTP(20 mg/kg body weight)was administered on alternative days-1st,3rd,5th,and 7th.On day 7,zebrafish were sacrificed,and their brains were isolated for biochemical,neurochemical,histopathological,IHC,and neurotransmitter analysis.Results:The treatment with CBL significantly increased total distance traveled and the number of entries in the top zone,which was impaired by MPTP.CBL treatment significantly restored the level of glutathione,superoxide dismutase,and catalase while reducing malondialdehyde level.It also reduced the level of pro-inflammatory mediators interleukin-1β,interleukin-6,and tumor necrosis factor-αin the MPTP-induced PD in the zebrafish model.In histopathological evaluation,pyknotic cells and signs of inflammation were significantly reduced in CBL-treated groups.A significant dose-dependent reduction in glutamate,along with elevations in dopamine,gamma-aminobutyric acid,serotonin,and noradrenaline,was observed in zebrafish treated with CBL.An immunohistochemistry analysis demonstrated that Akt was phosphorylated promptly by CBL,which was downregulated in MPTP-induced PD in zebrafish.Conclusions:These findings suggest that CBL exerts a neuroprotective effect through activation of Akt and may hold therapeutic potential for the treatment of this devastating neurological condition.
基金supported by National Nature Science Foundation of China(32102552 and 32172741).
文摘Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response and exacerbating glycolysis in multiple tissues.However,the redox induction mechanism of lactate in mammary gland has not been understood yet.Herein,we describe a lactate-responsive HIF1α/circadian control mechanism in oxidative stress in the mammary glands of dairy cows.Results The in vivo study showed that dairy cows with high lactate concentrations are associated with reduced milk yield and more ROS accumulation in mammary gland.Western blot results in MAC-T cells showed positive correlation between lactate concentrations,expression of HIF1αand oxidative stress indicators,but not circadian core components.To test how lactate-mediated HIF1αdysfunction leads to cell protection process,we investigated altered expression of circadian core related genes following HIF1αstabilization.We found that stabilized HIF1αby lactate inhibited stimulated expression of circadian core components due to the similarity of HRE and E-box transcription elements.Furthermore,we found that lactate treatment strengthened the binding of HIF1αwith BMAL1,HMOX1 and FOXO3 in MAC-T cells.Moreover,HIF1αknockdown altered expression of circadian rhythm related genes and reduced oxidative stress state.Conclusion In summary,our study highlights the central role of competitive transcriptional element occupancy in lactate-mediated oxidative stress of mammary gland,which is caused by HIF1αstabilization and circadian rhythm dysfunction.Our findings introduce a novel nutritional strategy with potential applications in dairy farming for optimizing milk production and maintaining mammary gland health.
基金Supported by Nanjing Municipal Special Fund for Health Science and Technology Development Support Project,No.GBX21333.
文摘BACKGROUND Patients with multiple injuries endure not just physical trauma and suffering but are also at risk of psychological conditions such as posttraumatic stress disorder(PTSD),anxiety,and depression.The co-occurrence of PTSD in these patients may cause prolonged physical and mental health complications,thereby further increasing their healthcare expenses.AIM To determine the association between the high-risk factors of PTSD and anxiety as well as depression among patients with multiple injuries.METHODS This study selected 110 patients with multiple injuries who were admitted to our hospital from November 2022 to November 2024.The number and percentage of patients developing PTSD were tallied.Univariate and multivariate analyses were conducted to investigate the high-risk factors of PTSD in these patients.Subse-quently,the associations between these factors and the anxiety and depression levels of patients were analyzed.RESULTS Of the 110 patients,33 suffered from PTSD,representing an incidence rate of 30.0%.The univariate analysis identified age,personality,Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),economic status,negative life events,and smoking history to be significantly associated with PTSD in patients with multiple injuries.Further,the multivariate analysis revealed age,HAMA,HAMD,monthly income,and negative life events as prominent high-risk factors for PTSD in such patients.Regarding the relationships between these factors and HAMA and HAMD,age exhibited a significant positive correlation(r=0.398,P<0.001;r=0.387,P<0.001),monthly income showed a significant negative correlation(r=-0.437,P<0.001;r=-0.319,P<0.001),and negative life events demonstrated a significant positive correlation(r=0.505,P<0.001;r=0.365,P<0.001).CONCLUSION These results indicate age,HAMA,HAMD,monthly income,negative life events,etc.as high-risk factors for PTSD in patients with multiple injuries,among which age,monthly income,and negative life events are closely associated with anxiety and depression.
文摘With the accelerated pace of population aging in China,the number of patients suffering from myocardial infarction(MI)is increasing annually.During disease progression,patients are at significantly higher risk of developing severe negative emotions,and emerging evidence suggests that post-traumatic stress disorder(PTSD)is significantly associated with cardiovascular disease,which seriously affects patients’quality of life.Objective:The aim of this study was to comprehensively assess the prevalence and influencing factors of PTSD in MI patients through systematic review and Meta-analysis.Methods:A computerized search of PubMed,the Cochrane Library,Embase,Web of Science,PsycINFO,China Knowledge Network(CNKI),WanFang Data,VIP,and China Biomedical Literature Database(CBM)was conducted to collect longitudinal studies,case-control studies,and cross-sectional studies related to PTSD prevalence rates and influencing factors in MI patients published up to August 1,2024.Literature screening,data extraction and quality assessment were done independently by two researchers and Meta-analysis was done using Stata 16.0 software.This study has been registered on the PROSPERO platform,registration number:CRD42024577243.Results:A total of 16 papers were included,with a total sample size of 3,768 cases involving 8 influencing factors.The results of the Meta-analysis showed that the prevalence of PTSD in patients with MI was 20.4%(95%CI=15.0–26.5%).Female(OR=3.12,95%CI=1.97–4.97,P<0.001),high neuroticism score(OR=2.21,95%CI=1.20–4.07,P=0.011),and high intrusive rumination score(OR=2.95,95%CI=1.50–5.83,P=0.002)were the risk factors for PTSD in MI patients.While age(OR=1.01,95%CI=0.98–1.04,P=0.440),education level(OR=0.55,95%CI=0.07–4.48,P=0.574),social support rating scale(OR=0.81,95%CI=0.52–1.26,P=0.346),Killip cardiac function classification(OR=2.29,95%CI=0.91–5.80,P=0.080)and creatine kinase isoenzyme(OR=1.03,95%CI=0.99–1.05,P=0.124)were not associated with the development of PTSD in MI patients.Conclusion:The prevalence of PTSD was higher in patients with MI.The prevalence varied by evaluation tool and study area.Risk factors were multifactorial,including general factors(female)and overall assessment(high neuroticism score,high invasive rumination score).Therefore,early intervention and proper de-escalation of PTSD symptoms in patients with MI by medical staff are needed in clinical practice to reduce the risk of PTSD.
基金Open Project of State Key Laboratory for Geomechanics and Deep Underground Engineering in CUMTB,Grant/Award Number:SKLGDUEK2023National Natural Science Foundation of China,Grant/Award Number:52204101Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2022QE137。
文摘Three sandstone specimens common in rock engineering were selected to study the differences in the mechanical properties of rocks with different lithologies.The development and expansion of the internal cracks in the specimens were observed by combining the simulation system with the acoustic emission system.Through the combination of dynamic and static stresses,the deformation and damage of rocks under deep rock excavation and blasting were simulated.As the results show,the acoustic emission events of specimens with different lithologies under combined static and dynamic cyclic loading can be roughly divided into three phases:weakening,stabilizing,and surging periods.In addition,the acoustic emission characteristics of specimens with different lithologies show general consistency in different compression phases.The degree of fragmentation of specimens increases with the applied stress level;therefore,the stress level is one of the important factors influencing the damage pattern of specimens.The acoustic emission system was used to simulate the deformation and damage of rocks subjected to deep rock body excavation and engineering blasting.Cyclic dynamic perturbations under sinusoidal waves with a frequency of 5 Hz,a loading rate of 0.1 mm/min,a cyclic amplitude of 5 MPa,and a loading rate of 0.1 mm/min were applied to the three rock samples during the experiments.Among them,the fine-grained sandstones are the most sensitive to the sinusoidal cyclic perturbation,followed by the muddy siltstone and the medium-grained sandstones.On this basis,the acoustic emission energy release characteristics were analyzed,and the waveform characteristics in the damage evolution of the specimen under dynamic perturbation were studied by extracting the key points and searching for the main frequency eigenvalues.
基金supported by the Anhui Provincial Department of Education Outstanding Young Teachers Cultivation Key Project(No.YQZD2023046)the Anhui University of Traditional Chinese Medicine School Talent Support Program Project(Nos.DT2400000222 and DT2100000545)。
文摘Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods:The PTSD mouse model was subjected to single prolonged stress and shock(SPS&S),and the animals received 15 min sessions of EA at Shenmen acupoint(HT7).Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear.Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex(PFC).Additionally,the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.Results:Mice subjected to SPS&S presented increased anxiety-and fear-like behaviors.Lcn2 expression in the PFC was significantly upregulated following SPS&S,leading to increased expression of the proinflammatory cytokines tumor necrosis factor-a and interleukin-6 and suppression of PFC neuronal activity.However,EA at HT7 inhibited Lcn2 release,reducing neuroinflammation and hypoexcitability in the PFC.Lcn2 overexpression mitigated the effects of EA at HT7,resulting in anxiety-and fear-like behaviors.Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear,and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC.
基金supported by the National Natural Science Foundation of China(Nos.52374080 and 52404201)。
文摘In the process of deep engineering excavation,the mechanical properties of rock are significantly influenced by the coupled effects of water and high stress,which greatly increase construction difficulty.To more accurately investigate the impact of water disturbance on the failure process of dry rock under high stress and the failure mechanisms of saturated rock in underwater environments,a water environment test chamber and a prefabricated borehole specimen through-water device were designed.A series of experiments were conducted,including uniaxial tests,water-disturbed granite cylinder tests,and through-water disturbance tests on prefabricated hole square specimens.The results showed that the acoustic emission(AE)hits and accumulated energy after the through-water disturbance at the same time were 8.77 and 12.08 times higher than before the disturbance,respectively.And water disturbance increased the proportion of tensile failure and reduced the proportion of shear failure.A key observation was that AE events were mainly generated in the permeation areas near the borehole.The main reason was that under high stress,the weakening effect of water led to the failure of the local mineral structure of the rock,promoting crack extension and triggering overall instability.Notably,failure of the saturated specimens underwater was only observed when the applied load approached the saturation strength of the prefabricated hole square specimens.The study results provide an important theoretical basis for understanding the damage mechanism of water-disturbed rocks in deep engineering,and have significant implications for the design and construction of engineering.
文摘Neurodegenerative diseases(NDs)such as Alzheimer’s disease(AD),Parkinson’s disease(PD),Huntington’s disease(HD),and amyotrophic lateral sclerosis(ALS)are characterized by progressive neuronal loss,which is closely linked to mitochondrial dysfunction.These pathologies involve a complex interplay of genetics,protein misfolding,and cellular stress,culminating in impaired energy metabolism,an increase in reactive oxygen species(ROS),and defective mitochondrial quality control.The accumulation of damaged mitochondria and dysregulation of pathways such as the Integrated Stress Response(ISR)are central to the pathogenesis of these conditions.This review explores the critical relationship between mitochondrial stress and neurodegeneration,highlighting the molecular mechanisms and biomarkers involved.It delves into the multifaceted role of melatonin as a potent neuroprotective agent.Melatonin,a lipophilic indoleamine,is produced both in the pineal gland and locally within mitochondria,where it exerts powerful antioxidant,anti-inflammatory,and anti-apoptotic effects.Its unique ability to neutralize multiple free radicals and its cascade-based antioxidant action make it superior to conventional antioxidants.Its mechanisms of action are discussed,including signaling pathway modulation and enhancement of the brain’s clearance system(the glymphatic system).Despite its potential,melatonin’s low bioavailability and rapid metabolism limit its therapeutic efficacy.In this context,nanopharmacology emerges as a promising strategy.Nanoparticles such as liposomes,polymers,and solid lipids can encapsulate melatonin and protect it from degradation,facilitating its transport across the blood-brain barrier.Preclinical evidence has shown that melatonin-loaded nanoparticles significantly improve cognitive function,reduce oxidative stress,and restore mitochondrial homeostasis in models of AD,PD,and ALS.In conclusion,the synergistic combination of melatonin and nanopharmacology offers a multimodal and highly targeted approach formitigatingmitochondrial dysfunction in NDs.While challenges remain in optimizing the formulation and safety of these nanocarriers,this combination represents a crucial frontier for developing more effective and specific treatments in the future.
基金Project(2023YFB3710503) supported by the National Key R&D Program of ChinaProject(52305439) supported by the National Natural Science Foundation of China。
文摘The orientation effect of θʹ precipitates in stress-aged Al-Cu alloys has ambiguous interpretations. One view is that θʹ precipitates prefer to grow on the habit planes perpendicular to the applied compressive stress, while the other view suggests growth on habit planes parallel to the applied stress. In this study, stress-aged Al-4 wt.%Cu single crystal was sampled from three different <100>Al zone axes to observe the distribution of θʹ precipitates. A hybrid Monte-Carlo/ molecular dynamics simulations were used to investigate the orientation effect of θʹ precipitates. The simulation results are consistent with experimental observations and indicate that θʹ precipitates prefer to grow on the habit planes that are parallel to the direction of the applied compressive stress, not along the planes perpendicular to it. It is also found that 1/2<110> perfect dislocations are generated as θʹ precipitates plates grow thicker, and the reaction of 1/2<110> perfect dislocations decomposing into 1/6<112> Shockley dislocations lead to an increase in the length of θʹ precipitates. The former does not enhance the orientation effect, whereas the latter leads to a more significant orientation effect. Additionally, the degree of the orientation effect of θʹ precipitates is determined by the reduction of 1/2<110> dislocations with a positive correlation between them.
基金supported by grants from the Top Medical Expert Team of Wuxi Taihu Talent Plan(Grant Nos.DJTD202106,GDTD202105 and YXTD202101)Medical Key Discipline Program of Wuxi Health Commission(Grant Nos.ZDXK2021007 and CXTD2021005)+1 种基金Top Talent Support Program for Young and MiddleAged People of Wuxi Health Committee(Grant No.BJ2023090)Scientific Research Program of Wuxi Health Commission(Grant Nos.Z20210 and M202208).
文摘With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis of MASLD is complex,characterized by oxidative stress,impaired mitochondrial function and lipid metabolism,and cellular inflammation.Mitochondrial biology and function are central to the physiology of the liver.It has been suggested that mitochondrial oxidative stress plays a crucial role in MASLD progression.Excessive oxidative stress response is an important trigger for the occurrence and development of MASLD.In this review,we aim to focus on the recent advances in understanding mitochondrial oxidative stress-related mechanisms in the progression of MASLD.The in-depth elaboration of its related mechanisms is hoped to help find effective methods for treating MASLD.
