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
To examine stress redistribution phenomena in bridges subjected to varying operational conditions,this study conducts a comprehensive analysis of three years of monitoring data from a 153-m double-deck road–rail stee...To examine stress redistribution phenomena in bridges subjected to varying operational conditions,this study conducts a comprehensive analysis of three years of monitoring data from a 153-m double-deck road–rail steel arch bridge.An initial statistical comparison of sensor data distributions reveals clear temporal variations in stress redistribution patterns.XGBoost(eXtreme Gradient Boosting),a gradient-boosting machine learning(ML)algorithm,was employed not only for predictive modeling but also to uncover the underlying mechanisms of stress evolution.Unlike traditional numerical models that rely on extensive assumptions and idealizations,XGBoost effectively captures nonlinear and time-varying relationships between stress states and operational/environmental factors,such as temperature,traffic load,and structural geometry.This approach allows for the identification of critical periods and conditions under which stress redistribution becomes significant.Results indicate a clear shift of stress concentrations frombeamends toward mid-span regions following the commencement of metro operations,reflecting both structural adaptation and localized overstress near arch ribs.Furthermore,the model generates robust predictions of stress evolution,demonstrating potential applications in early warning systems and fatigue risk assessment.This work represents the first application of interpretable gradient-boosting techniques to stress redistribution modeling in double-deck bridges.In addition,a Stress Redistribution Index(SRI)is proposed,derived from this monitoring study and finite-element-based transverse load distributions,to quantify temporal stress shifts between midspan and edge beams.The results provide both theoretical contributions and practical guidance for the design,inspection,and maintenance of complex bridge structures.展开更多
This study investigated the effects of parental involvement,parenting stress,and social support on the social skills of school-aged children(6-18 years old)with intellectual disabilities(ID).Data were collected from 2...This study investigated the effects of parental involvement,parenting stress,and social support on the social skills of school-aged children(6-18 years old)with intellectual disabilities(ID).Data were collected from 280 Chinese parents(mothers=70.0%,fathers=30.0%)of children with ID through purposive sampling and analyzed using partial least squares structural equation modeling(PLS-SEM).The results indicated that parental involvement not only directly enhanced children’s social skills but also indirectly improved them by alleviating parenting stress,which acted as a partial mediator.Contrary to the stress-buffering hypothesis,social support did not moderate the negative impact of parenting stress on social skills.Theoretically,this study contributes by validating ecological systems theory through a shift in focus from individual deficits to family systems,while also challenging the conventional view of stress-buffering theory.Accordingly,parent-support programs should integrate practical involvement training with systematic stress reduction and provide tailored assistance such as behavior-management training and respite care.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
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
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
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
To investigate the residual stress distribution and its influence on machining deformation in 6061-T651 aluminum alloy plates,this paper uses the crack compliance method to study the residual stress characteristics of...To investigate the residual stress distribution and its influence on machining deformation in 6061-T651 aluminum alloy plates,this paper uses the crack compliance method to study the residual stress characteristics of 6061-T651 aluminum alloy plates with a thickness of 75 mm produced by two domestic manufacturers in China.The results indicate that both types of plates exhibit highly consistent and symmetrical M-shaped residual stress profile along the thickness direction,manifested as surface layer compression and core tension.The strain energy density across all specimens ranges from 1.27 kJ/m^(3)to 1.43 kJ/m^(3).Machining deformation simulations of an aerospace component incorporating these measured stresses showed minimal final deformation difference between the material sources,with a maximum deviation of only 0.009 mm across specimens.These findings provide critical data for material selection and deformation control in aerospace manufacturing.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
In light of the pressing global challenges of climate change,declining crop resilience,and hidden hunger,it is imperative to overcome the limitations of conventional crop breeding to enhance both the nutritional quali...In light of the pressing global challenges of climate change,declining crop resilience,and hidden hunger,it is imperative to overcome the limitations of conventional crop breeding to enhance both the nutritional quality and stress tolerance of crops.Synthetic metabolic engineering presents innovative strategies for the precision modification and de novo design of metabolic pathways.This approach generally encompasses three essential steps:identifying key metabolites through metabolomics,integrating multi-omics technologies to investigate the synthesis and regulation of these metabolites,and utilizing gene editing or de novo design to modify crop metabolic pathways associated with desirable agronomic traits.This review underscores the vital role of plant metabolite diversity in enhancing crop nutritional quality and stress resilience.Integrated multi-omics analyses facilitate the metabolic engineering by identifying key genes,transporters,and transcription factors that regulate metabolite biosynthesis.Precision modification strategies employ genome editing tools to reprogram endogenous metabolic networks,while de novo design reconstructs metabolic pathways through the introduction of exogenous biological elements—thereby both approaches enable the targeted enhancement of desired traits.These strategies have been effectively implemented in major food crops.However,simultaneously enhancing nutritional quality and stress resilience remains challenging due to inherent trade-offs and resource competition in distinct metabolic pathways within plants.Future research should integrate AI-driven predictive models with multi-omics datasets to decipher dynamic metabolic homeostasis and engineer climate-smart crops that maximize yield while preserving quality and environmental adaptability.展开更多
T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue ...T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.展开更多
Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and e...Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and exerting substantial economic burdens as well.Astaxanthin(AST),a member of the xanthophylls and recognized for its robust abilities to combat inflammation and oxidation,is a common dietary sup-plement.Nonetheless,the precise molecular pathways through which AST influences DED are still poorly understood.Methods:Therapeutic targets for AST were identified using data from the GeneCards,PharmMapper,and Swiss Target Prediction databases,and STITCH datasets.Similarly,targets for dry eye disease(DED)were delineated leveraging resources such as the Therapeutic Target Database(TTD),DisGeNET,GeneCards,and OMIM databases,and DrugBank datasets.Interactions among shared targets were charted and dis-played using CytoScape 3.9.0.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to elucidate the functions of pivotal tar-gets within the protein-protein interaction network.Molecular interactions between AST and key targets were confirmed through molecular docking using AutoDock and PyMOL.Molecular dynamics simulations were performed using GROMACS 2022.3.Viability of human corneal epithelial cells(hCEC)was assessed across varying concen-trations of AST.A mouse model of experimental DED was developed using 0.1%ben-zalkonium chloride(BAC),and the animals were administered 100 mg/kg/day of AST orally for 7 days.The efficacy of the treatments was assessed through a series of di-agnostic tests to evaluate the condition of the ocular surface after the interventions.The levels of inflammation and oxidative stress were quantitatively assessed using methods such as reverse transcription-polymerase chain reaction(RT-PCR),Western blot,and immunofluorescence staining.Results:Network pharmacology suggests that AST may alleviate DED by influenc-ing oxidation-reduction signaling pathways and reducing oxidative stress provoked by BAC.In vivo experiments demonstrated an improved overall condition in AST-administered mice in contrast to the control group.Immunofluorescence staining analyses indicated a decrease in Keap1 protein in the corneal tissues of AST-treated mice and a significant increase in Nrf2 and HO-1 protein.In vitro studies demon-strated that AST significantly enhanced cell viability and suppressed reactive oxy-gen species expression under hyperosmotic(HS)conditions,thereby protecting the human corneal epithelium.Conclusion:AST is capable of shielding mice from BAC-induced DED,decelerating the progression of DED,and mitigating oxidative stress damage under HS conditions in hCEC cells.The protective impact of AST on DED may operate through stimulating the Keap1-Nrf2/HO-1 signaling pathway.Our research findings indicate that AST may be a promising treatment for DED,offering new insights into DED treatment.展开更多
OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was establishe...OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3(Smad3), Notch1, jagged, hairy and enhancer of split 1(Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3(MEG3) and mi R-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of mi R-145 to MEG3. RESULTS:BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lnc RNA MEG3/mi R-145 axis. CONCLUSION:BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lnc RNA MEG3/mi R-145 axis, effectively delaying the progression of DKD.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
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 the Key Technologies Research and Development Program under Grant 2021YFB1600300.
文摘To examine stress redistribution phenomena in bridges subjected to varying operational conditions,this study conducts a comprehensive analysis of three years of monitoring data from a 153-m double-deck road–rail steel arch bridge.An initial statistical comparison of sensor data distributions reveals clear temporal variations in stress redistribution patterns.XGBoost(eXtreme Gradient Boosting),a gradient-boosting machine learning(ML)algorithm,was employed not only for predictive modeling but also to uncover the underlying mechanisms of stress evolution.Unlike traditional numerical models that rely on extensive assumptions and idealizations,XGBoost effectively captures nonlinear and time-varying relationships between stress states and operational/environmental factors,such as temperature,traffic load,and structural geometry.This approach allows for the identification of critical periods and conditions under which stress redistribution becomes significant.Results indicate a clear shift of stress concentrations frombeamends toward mid-span regions following the commencement of metro operations,reflecting both structural adaptation and localized overstress near arch ribs.Furthermore,the model generates robust predictions of stress evolution,demonstrating potential applications in early warning systems and fatigue risk assessment.This work represents the first application of interpretable gradient-boosting techniques to stress redistribution modeling in double-deck bridges.In addition,a Stress Redistribution Index(SRI)is proposed,derived from this monitoring study and finite-element-based transverse load distributions,to quantify temporal stress shifts between midspan and edge beams.The results provide both theoretical contributions and practical guidance for the design,inspection,and maintenance of complex bridge structures.
文摘This study investigated the effects of parental involvement,parenting stress,and social support on the social skills of school-aged children(6-18 years old)with intellectual disabilities(ID).Data were collected from 280 Chinese parents(mothers=70.0%,fathers=30.0%)of children with ID through purposive sampling and analyzed using partial least squares structural equation modeling(PLS-SEM).The results indicated that parental involvement not only directly enhanced children’s social skills but also indirectly improved them by alleviating parenting stress,which acted as a partial mediator.Contrary to the stress-buffering hypothesis,social support did not moderate the negative impact of parenting stress on social skills.Theoretically,this study contributes by validating ecological systems theory through a shift in focus from individual deficits to family systems,while also challenging the conventional view of stress-buffering theory.Accordingly,parent-support programs should integrate practical involvement training with systematic stress reduction and provide tailored assistance such as behavior-management training and respite care.
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.
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 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 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.
基金supported in part by the National Natural Science Foundation of China(Nos.61201048,61107063)the National Science and Technology Major Project(No.2017-VI-001-0094).
文摘To investigate the residual stress distribution and its influence on machining deformation in 6061-T651 aluminum alloy plates,this paper uses the crack compliance method to study the residual stress characteristics of 6061-T651 aluminum alloy plates with a thickness of 75 mm produced by two domestic manufacturers in China.The results indicate that both types of plates exhibit highly consistent and symmetrical M-shaped residual stress profile along the thickness direction,manifested as surface layer compression and core tension.The strain energy density across all specimens ranges from 1.27 kJ/m^(3)to 1.43 kJ/m^(3).Machining deformation simulations of an aerospace component incorporating these measured stresses showed minimal final deformation difference between the material sources,with a maximum deviation of only 0.009 mm across specimens.These findings provide critical data for material selection and deformation control in aerospace manufacturing.
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.
基金supported by the Project of Sanya Yazhou Bay Science and Technology City (SKJC-JYRC-2024-26)the National Natural Science Foundation of China (32460072)+4 种基金Hainan Provincial Natural Science Foundation of China (323RC421)the Hainan Province Science and Technology Special Fund (ZDYF2022XDNY144)the Hainan Provincial Academician Innovation Platform Project (HDYSZX-202004)the Collaborative Innovation Center of Nanfan and High-Efficiency Tropical Agriculture, Hainan University (XTCX2022NYB06)Hainan Postdoctoral Research Grant Project
文摘In light of the pressing global challenges of climate change,declining crop resilience,and hidden hunger,it is imperative to overcome the limitations of conventional crop breeding to enhance both the nutritional quality and stress tolerance of crops.Synthetic metabolic engineering presents innovative strategies for the precision modification and de novo design of metabolic pathways.This approach generally encompasses three essential steps:identifying key metabolites through metabolomics,integrating multi-omics technologies to investigate the synthesis and regulation of these metabolites,and utilizing gene editing or de novo design to modify crop metabolic pathways associated with desirable agronomic traits.This review underscores the vital role of plant metabolite diversity in enhancing crop nutritional quality and stress resilience.Integrated multi-omics analyses facilitate the metabolic engineering by identifying key genes,transporters,and transcription factors that regulate metabolite biosynthesis.Precision modification strategies employ genome editing tools to reprogram endogenous metabolic networks,while de novo design reconstructs metabolic pathways through the introduction of exogenous biological elements—thereby both approaches enable the targeted enhancement of desired traits.These strategies have been effectively implemented in major food crops.However,simultaneously enhancing nutritional quality and stress resilience remains challenging due to inherent trade-offs and resource competition in distinct metabolic pathways within plants.Future research should integrate AI-driven predictive models with multi-omics datasets to decipher dynamic metabolic homeostasis and engineer climate-smart crops that maximize yield while preserving quality and environmental adaptability.
基金supported by the National Natural Science Foundation of China(No.81872567).
文摘T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.
基金supported by grants from the Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(PWD&RPP-MRI,JYY2023-6)the R&D Program of Beijing Municipal Education Commission(KZ20231002543).
文摘Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and exerting substantial economic burdens as well.Astaxanthin(AST),a member of the xanthophylls and recognized for its robust abilities to combat inflammation and oxidation,is a common dietary sup-plement.Nonetheless,the precise molecular pathways through which AST influences DED are still poorly understood.Methods:Therapeutic targets for AST were identified using data from the GeneCards,PharmMapper,and Swiss Target Prediction databases,and STITCH datasets.Similarly,targets for dry eye disease(DED)were delineated leveraging resources such as the Therapeutic Target Database(TTD),DisGeNET,GeneCards,and OMIM databases,and DrugBank datasets.Interactions among shared targets were charted and dis-played using CytoScape 3.9.0.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to elucidate the functions of pivotal tar-gets within the protein-protein interaction network.Molecular interactions between AST and key targets were confirmed through molecular docking using AutoDock and PyMOL.Molecular dynamics simulations were performed using GROMACS 2022.3.Viability of human corneal epithelial cells(hCEC)was assessed across varying concen-trations of AST.A mouse model of experimental DED was developed using 0.1%ben-zalkonium chloride(BAC),and the animals were administered 100 mg/kg/day of AST orally for 7 days.The efficacy of the treatments was assessed through a series of di-agnostic tests to evaluate the condition of the ocular surface after the interventions.The levels of inflammation and oxidative stress were quantitatively assessed using methods such as reverse transcription-polymerase chain reaction(RT-PCR),Western blot,and immunofluorescence staining.Results:Network pharmacology suggests that AST may alleviate DED by influenc-ing oxidation-reduction signaling pathways and reducing oxidative stress provoked by BAC.In vivo experiments demonstrated an improved overall condition in AST-administered mice in contrast to the control group.Immunofluorescence staining analyses indicated a decrease in Keap1 protein in the corneal tissues of AST-treated mice and a significant increase in Nrf2 and HO-1 protein.In vitro studies demon-strated that AST significantly enhanced cell viability and suppressed reactive oxy-gen species expression under hyperosmotic(HS)conditions,thereby protecting the human corneal epithelium.Conclusion:AST is capable of shielding mice from BAC-induced DED,decelerating the progression of DED,and mitigating oxidative stress damage under HS conditions in hCEC cells.The protective impact of AST on DED may operate through stimulating the Keap1-Nrf2/HO-1 signaling pathway.Our research findings indicate that AST may be a promising treatment for DED,offering new insights into DED treatment.
文摘OBJECTIVES:To investigate the effect of Bushen Tongluo recipe(BSTLR, 补肾通络方) on rats with diabetic kidney disease(DKD) and to explore the underlying mechanism of action. METHODS:The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3(Smad3), Notch1, jagged, hairy and enhancer of split 1(Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3(MEG3) and mi R-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of mi R-145 to MEG3. RESULTS:BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lnc RNA MEG3/mi R-145 axis. CONCLUSION:BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lnc RNA MEG3/mi R-145 axis, effectively delaying the progression of DKD.
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.
