Axial chain rockbursts(ACRs)repeatedly occur in deep tunnels during drilling and blasting methodology(D&B)within locked-in stress zones,severely hindering construction progress.In extremely cases,ACRs can persist ...Axial chain rockbursts(ACRs)repeatedly occur in deep tunnels during drilling and blasting methodology(D&B)within locked-in stress zones,severely hindering construction progress.In extremely cases,ACRs can persist for 7−10 d and affect areas exceeding 20 m along tunnel axis.Through integrated geological investigations and microseismic(MS)monitoring,the geological characteristics,MS activity patterns,and formation mechanisms of ACRs were analyzed.In tectonically active regions,locked-in stress zones arise from interactions between multiple structural planes.Blasting dynamic disturbances during tunnel excavation in these zones trigger early slippage along structural planes and fractures in the surrounding rock,with MS events developing ahead of the working face.High-energy MS events dominate during the development and occurrence stages of ACRs,extending 20−30 m(3−4 tunnel diameters)ahead of the working face.Following the ACRs,low-energy MS events primarily occur behind the working face.Tensile fracturing is the predominant failure mode during ACRs.Shear and mixed fractures primarily occur within the ACRs zone during the intra-ACR phase.Monitoring MS event locations ahead of the working face provides a reliable approach for prewarning potential ACR-prone zones.展开更多
Rocks are composed of mineral particles and micropores between mineral which has a great influence on the mechanical properties of rocks. In this paper, based on the theory of locked-in stress developed by academician...Rocks are composed of mineral particles and micropores between mineral which has a great influence on the mechanical properties of rocks. In this paper, based on the theory of locked-in stress developed by academician Chen Zongji, the locked-in stress problem in underground rock is simulated by the thermal expansion of hard rubber particles. The pore inclusion in rock is assumed to be uniformly distributed spherical cavities. Using the thermal stress theory, the stress of rock with a spherical pore inclusion is equivalent to the thermal stress generated by the spherical hard rubber inclusion. The elastic theory formula of the temperature increment and the equivalent pore pressure of the spherical hard rubber inclusion is derived. The numerical simulation of the rock mass model with a spherical hard rubber inclusion is carried out and compared to the theoretical calculation results<span lang="EN-US" style="font-family:;" minion="" pro="" capt",serif;font-size:10pt;mso-fareast-font-family:宋体;mso-bidi-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:zh-cn;mso-bidi-language:ar-sa;mso-bidi-font-weight:bold;"="">;</span><span lang="EN-US" style="font-family:;" minion="" pro="" capt",serif;font-size:10pt;mso-fareast-font-family:宋体;mso-bidi-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa;mso-bidi-font-weight:bold;"=""> the results show that they are consistent. The method proposed by this paper for simulating stress distribution in rock by thermal stress is reasonable and feasible</span><span lang="EN-US" style="font-family:;" minion="" pro="" capt",serif;font-size:10pt;mso-fareast-font-family:宋体;mso-bidi-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:zh-cn;mso-bidi-language:ar-sa;mso-bidi-font-weight:bold;"="">;</span><span lang="EN-US" style="font-family:;" minion="" pro="" capt",serif;font-size:10pt;mso-fareast-font-family:宋体;mso-bidi-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa;mso-bidi-font-weight:bold;"=""> it has a positive meaning for further study of mechanic phenomenon of rock with micropore inclusion.</span>展开更多
Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et a...Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et al.,2022).This molecular event is believed to lead to activation of stress pathways ultimately resulting in cellular dysfunction(Eldeeb et al.,2022).Accordingly,many lines of research investigations focused on dampening the formation of protein aggregates or augmenting the clearance of protein aggregates as a potential therapeutic strategy to counteract the progression of neurodegenerative diseases,albeit with little success(Costa-Mattioli and Walter,2020).Cell stress cues such as the accumulation of protein aggregates lead to the activation of stress response pathways that aid cells in responding to the damage.Despite the notion that the transient activation of these pathways helps cells cope with stressors,persistent activation can induce unwanted apoptosis of cells and reduce overall tissue strength as well as lead to an accumulation of aggregation-prone proteins(Hetz and Papa,2018).Mutations in proteins involved in stress signaling termination can cause conditions like ataxia and early-onset dementia(Conroy et al.,2014).Therefore,it is crucial for stress response signaling to be turned off once conditions have improved.Nevertheless,the mechanisms by which cells silence these signals are still elusive.展开更多
Drought stress is a serious natural challenge for tea plants that significantly affects tea yield and quality.miR171s play critical roles in plant stress responses,however,their role in drought stress tolerance in tea...Drought stress is a serious natural challenge for tea plants that significantly affects tea yield and quality.miR171s play critical roles in plant stress responses,however,their role in drought stress tolerance in tea plants(Camellia sinensis)is poorly understood.This study experimentally verified the expression patterns of csn-miR171b-3p_2 and its target,scarecrow-like(SCL).We found that csn-miR171b-3p_2 could target and regulate CsSCL6-4 to play an important role in the defense against drought stress in tea plants.CsSCL6-4 is located in the nucleus and is selfactivated in vivo.In addition,we obtained 819 putative binding regions of CsSCL6-4 using DNA affinity purification sequencing analysis,which were assigned to 786 different genes,four of which were drought-resistant genes(CsPrx,CsSDR,CsFAD7,and CsCER1).Yeast one-hybrid and dual-luciferase reporter assays revealed that CsSCL6-4 directly promoted the expression of these four drought resistance genes by binding motifs 1/2/3 in their promoter regions.Both overexpression and suppression of CsSCL6-4 proved that CsSCL6-4 participated in the defense against drought stress in tea plants by regulating the expression of CsPrx,CsSDR,CsFAD7,and CsCER1.In addition,suppression of csn-miR171b-3p_2 expression significantly increased the expression of CsSCL6-4 and activated CsSCL6-4-bound gene transcription under drought stress.Therefore,the csn-miR171b-3p_2-CsSCL6-4 module participates in tea plant resistance to drought stress by promoting the expression of drought resistance genes.Our results revealed the function of csn-miR171b-3p_2 in tea plants and provided new insights into the mechanism of tea plant resistance to drought stress.展开更多
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
N6-methyladenosine(m^(6)A)modification,the most abundant internal modification in messenger RNA(mRNA)and long non-coding RNA(lncRNA),has emerged as a critical epitranscriptomic regulatory mechanism in eukaryotes.While...N6-methyladenosine(m^(6)A)modification,the most abundant internal modification in messenger RNA(mRNA)and long non-coding RNA(lncRNA),has emerged as a critical epitranscriptomic regulatory mechanism in eukaryotes.While the importance of m^(6)A modification in various biological processes has been recognized,a comprehensive understanding of its diverse roles in plant biology and agricultural applications remains fragmented.This review analyzes recent advances inm^(6)A modification's biological functions in plants.m^(6)A modification plays crucial roles in multiple aspects of plant life,including seed germination,organ development,and reproductive structure formation.Furthermore,m^(6)A has been found to significantly influence plant responses to environmental stresses,including salt,drought,temperature,and heavy metal exposure.We also uncover m^(6)A involvement in important agricultural traits.This review provides insights into the mechanistic understanding of m^(6)A modification in plants and highlights its applications in agricultural improvement,offering a foundation for future research in crop enhancement and stress resistance.展开更多
Heavy metal(HM)contamination severely impacts global agricultural production.HMs toxicity effectively damaged the physiological functions such as imbalanced redox homeostasis,altered antioxidant enzyme activity,damage...Heavy metal(HM)contamination severely impacts global agricultural production.HMs toxicity effectively damaged the physiological functions such as imbalanced redox homeostasis,altered antioxidant enzyme activity,damage root system architecture,hindered photosynthetic apparatus,cellular toxicity,restricted mineral accumulation,and changed the metabolite production.Using phytohormones may be a successful strategy for enhancing and stimulating plant tolerance to HMs toxicity without affecting the environment.Melatonin(MT),a novel plant growth regulator,and powerful antioxidant molecule,enhances plant resilience to HMs stress by enhancing seedling growth,protecting the photosynthetic system,increasing nutritional status,balanced redox homeostasis,and restricting HMs accumulation from root to shoot.In addition,MT enhances the activity of antioxidant enzymes and triggers the ascorbate-glutathione(AsA-GSH)cycle,which helps remove excessive ROS.MT improves RuBisCO activity to improve photosynthesis and reduce the breakdown of chlorophyll.To identify future research needs,it is crucial to understand the comprehensive and intricate regulatory mechanisms of exogenous and endogenous MT-mediated reduction of heavy metal toxicity in plants.Melatonin has several functions,and this review sheds light on those functions and the molecular processes by which it alleviates HMs toxicity.More research is needed to fully understand how melatonin affects plant tolerance to heavy metals stress.展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
Based on the split hopkinson pressure bar(SHPB)tests results,the cubic specimens have been numerically modeled in this paper to investigate the impact of key factors,such as the rise time,duration,and incident pulse s...Based on the split hopkinson pressure bar(SHPB)tests results,the cubic specimens have been numerically modeled in this paper to investigate the impact of key factors,such as the rise time,duration,and incident pulse shape,on achieving stress uniformity.After analysis,the paper provides actionable methods aimed at optimizing the conditions for stress uniformity within the cubic specimen.Finally,the lateral inertia effect of cubic specimen has been scrutinized to address the existing gap in this academic area.展开更多
Background:Myocardial infarction(MI)remains a major global public health challenge.Although advances in reperfusion therapy have reduced acute mortality,post-infarction cardiac remodeling continues to pose a substanti...Background:Myocardial infarction(MI)remains a major global public health challenge.Although advances in reperfusion therapy have reduced acute mortality,post-infarction cardiac remodeling continues to pose a substantial threat to long-term cardiovascular health.Oxidative stress and the ensuing inflammatory response are key drivers of this pathological process,leading to cardiomyocyte death,myocardial fibrosis,and functional impairment.Among the regulatory pathways involved,the kelch-like ECH-associated protein 1(Keap1)/nuclear factor erythroid 2-related factor 2(Nrf2)axis has emerged as a critical therapeutic target for mitigating post-MI cardiac injury.Methods:A murine MI model was established by permanent ligation of the left anterior descending coronary artery.Mice received oral Tongxinbi formula(TXB)at low,medium,or high doses(9/18/36 g/kg)once daily for 28 days.Cardiac function was assessed by echocardiography;myocardial fibrosis by Masson’s trichrome;and endothelial integrity by CD31 immunofluorescence.Plasma markers of endothelial function and inflammation were quantified.In vitro,oxidative stress was induced by H2O2 in vascular endothelial cells and cardiomyocytes,followed by treatment with TXB drug-containing serum.Western blot and RT-qPCR were used to measure components of the Keap1/Nrf2 pathway;ELISA quantified oxidative stress and inflammatory indices.Conditioned-medium experiments evaluated endothelial cell–mediated paracrine protection of cardiomyocytes.Results:TXB significantly improved cardiac function and reduced myocardial fibrosis after MI,in association with preservation of microvascular structure and systemic attenuation of oxidative stress and inflammation.In vitro,TXB activated the endothelial Keap1/Nrf2 pathway,enhanced cellular antioxidant defenses,increased VEGF secretion,and,via endothelial cell-mediated paracrine signaling,alleviated cardiomyocyte injury under oxidative stress.Conclusion:TXB exerts anti-fibrotic and cardioprotective effects by activating Nrf2 signaling and engaging endothelial-mediated paracrine mechanisms,collectively mitigating oxidative stress and inflammation in the post-MI setting.展开更多
Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mo...Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable.展开更多
Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a na...Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a natural inhibitor of recombinant tissue plasminogen activator,neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia.However,the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear.In this study,we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models,respectively.The models were used to investigate the neuroprotective effects of neuroserpin.Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia,initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis,which was followed by a later apoptotic response.Notably,ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons.Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules,the reduction in protein synthesis,and the upregulation of apoptotic transcription factors.This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion,as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion.However,the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin.Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.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
Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily...Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.展开更多
Salinization of agricultural land is becoming increasingly severe worldwide,posing a significant threat to food security.The exogenous application of bioactive substances has been widely used to enhance plant resistan...Salinization of agricultural land is becoming increasingly severe worldwide,posing a significant threat to food security.The exogenous application of bioactive substances has been widely used to enhance plant resistance to salt stress.In this study,we used corn steep liquor(CSL),myo-inositol(MI),and their combination to improve salt tolerance in Chinese cabbage(Brassica rapa L.ssp.pekinensis)under salt stress conditions.All three treatments significantly increased plant biomass and nutrient uptake,and improved soil physicochemical properties,while alleviating oxidative damage and ion toxicity.展开更多
Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice ...Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.展开更多
Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cereb...Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.展开更多
Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challe...Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challenge in accurately shaping aluminum alloy panels.In this study,the SRA behavior of 2195-T4 Al-Cu-Li alloys were thoroughly studied under initial loading stresses within the elastic(210/250 MPa)and plastic(380/420 MPa)ranges at 180℃by stress relaxation and tensile tests as well as microstructure characterization.The findings reveal that compared with those under elastic loadings,in-plane anisotropy(IPA)values of the stress relaxation amount,yield strength and fracture elongation under plastic loadings are reduced by 60%–80%,70%–90% and 72%–89%,respectively.Similarly,IPA values of precipitate size in grains and PrecipitationFree Zones(PFZ)width at grain boundaries under plastic loading decrease by 31.4%and 94.4%respectively.These results indicate plastic loading significantly weakens the anisotropic SRA behavior,owing to numerous uniformly distributed fine T1phases and small IPA values of both T1precipitates size and PFZ width in various loading directions.Compared with those of elastic loadingaged alloys,yield strength of plastic loading-aged alloys shows high strength-ductility because of the combined effect of closely dispersed fine T1precipitates,narrowed PFZ and numerous sheared and rotated T1phases at different locations during tensile process.The uniformly distributed larger Kernel Average Misorientation(KAM)and Schmidt factor values of the plastic loading-aged alloy,as well as the cross-slip generated,also help to enhance the strength and ductility of the alloy.展开更多
A steady rise in the overall population is creating an overburden on crops due to their global demand.On the other hand,given the current climate change and population growth,agricultural practices established during ...A steady rise in the overall population is creating an overburden on crops due to their global demand.On the other hand,given the current climate change and population growth,agricultural practices established during the Green Revolution are no longer viable.Consequently,innovative practices are the prerequisite of the time struggle with the rising global food demand.The potential of nanotechnology to reduce the phytotoxic effects of these ecological restrictions has shown significant promise.Nanoparticles(NPs)typically enhance plant resilience to stressors by fortifying the physical barrier,optimizing photosynthesis,stimulating enzymatic activity for defense,elevating the concentration of stress-resistant compounds,and activating the expression of genes associated with defense mechanisms.In this review,we thoroughly cover the uptake and translocations of NPs crops and their potential valuable functions in enhancing plant growth and development at different growth stages.Additionally,we addressed how NPs improve plant resistance to biotic and abiotic stress.Generally,this review presents a thorough understanding of the significance of NPs in plants and their prospective value for plant antioxidant and crop development.展开更多
Global warming impacts plant growth and development,which in turn threatens food security.Plants can clearly respond to warm-temperature(such as by thermomorphogenesis)and high-temperature stresses.At the molecular le...Global warming impacts plant growth and development,which in turn threatens food security.Plants can clearly respond to warm-temperature(such as by thermomorphogenesis)and high-temperature stresses.At the molecular level,many small molecules play crucial roles in balancing growth and defense,and stable high yields can be achieved by fine-tuning the responses to external stimuli.Therefore,it is essential to understand the molecular mechanisms underlying plant growth in response to heat stress and how plants can adjust their biological processes to survive heat stress conditions.In this review,we summarize the heat-responsive genetic networks in plants and crop plants based on recent studies.We focus on how plants sense the elevated temperatures and initiate the cellular and metabolic responses that allow them to adapt to the adverse growing conditions.We also describe the trade-off between plant growth and responses to heat stress.Specifically,we address the regulatory network of plant responses to heat stress,which will facilitate the discovery of novel thermotolerance genes and provide new opportunities for agricultural applications.展开更多
基金Projects(52222810,52178383)supported by the National Natural Science Foundation of China。
文摘Axial chain rockbursts(ACRs)repeatedly occur in deep tunnels during drilling and blasting methodology(D&B)within locked-in stress zones,severely hindering construction progress.In extremely cases,ACRs can persist for 7−10 d and affect areas exceeding 20 m along tunnel axis.Through integrated geological investigations and microseismic(MS)monitoring,the geological characteristics,MS activity patterns,and formation mechanisms of ACRs were analyzed.In tectonically active regions,locked-in stress zones arise from interactions between multiple structural planes.Blasting dynamic disturbances during tunnel excavation in these zones trigger early slippage along structural planes and fractures in the surrounding rock,with MS events developing ahead of the working face.High-energy MS events dominate during the development and occurrence stages of ACRs,extending 20−30 m(3−4 tunnel diameters)ahead of the working face.Following the ACRs,low-energy MS events primarily occur behind the working face.Tensile fracturing is the predominant failure mode during ACRs.Shear and mixed fractures primarily occur within the ACRs zone during the intra-ACR phase.Monitoring MS event locations ahead of the working face provides a reliable approach for prewarning potential ACR-prone zones.
文摘Rocks are composed of mineral particles and micropores between mineral which has a great influence on the mechanical properties of rocks. In this paper, based on the theory of locked-in stress developed by academician Chen Zongji, the locked-in stress problem in underground rock is simulated by the thermal expansion of hard rubber particles. The pore inclusion in rock is assumed to be uniformly distributed spherical cavities. Using the thermal stress theory, the stress of rock with a spherical pore inclusion is equivalent to the thermal stress generated by the spherical hard rubber inclusion. The elastic theory formula of the temperature increment and the equivalent pore pressure of the spherical hard rubber inclusion is derived. The numerical simulation of the rock mass model with a spherical hard rubber inclusion is carried out and compared to the theoretical calculation results<span lang="EN-US" style="font-family:;" minion="" pro="" capt",serif;font-size:10pt;mso-fareast-font-family:宋体;mso-bidi-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:zh-cn;mso-bidi-language:ar-sa;mso-bidi-font-weight:bold;"="">;</span><span lang="EN-US" style="font-family:;" minion="" pro="" capt",serif;font-size:10pt;mso-fareast-font-family:宋体;mso-bidi-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa;mso-bidi-font-weight:bold;"=""> the results show that they are consistent. The method proposed by this paper for simulating stress distribution in rock by thermal stress is reasonable and feasible</span><span lang="EN-US" style="font-family:;" minion="" pro="" capt",serif;font-size:10pt;mso-fareast-font-family:宋体;mso-bidi-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:zh-cn;mso-bidi-language:ar-sa;mso-bidi-font-weight:bold;"="">;</span><span lang="EN-US" style="font-family:;" minion="" pro="" capt",serif;font-size:10pt;mso-fareast-font-family:宋体;mso-bidi-font-family:"times="" new="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa;mso-bidi-font-weight:bold;"=""> it has a positive meaning for further study of mechanic phenomenon of rock with micropore inclusion.</span>
文摘Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et al.,2022).This molecular event is believed to lead to activation of stress pathways ultimately resulting in cellular dysfunction(Eldeeb et al.,2022).Accordingly,many lines of research investigations focused on dampening the formation of protein aggregates or augmenting the clearance of protein aggregates as a potential therapeutic strategy to counteract the progression of neurodegenerative diseases,albeit with little success(Costa-Mattioli and Walter,2020).Cell stress cues such as the accumulation of protein aggregates lead to the activation of stress response pathways that aid cells in responding to the damage.Despite the notion that the transient activation of these pathways helps cells cope with stressors,persistent activation can induce unwanted apoptosis of cells and reduce overall tissue strength as well as lead to an accumulation of aggregation-prone proteins(Hetz and Papa,2018).Mutations in proteins involved in stress signaling termination can cause conditions like ataxia and early-onset dementia(Conroy et al.,2014).Therefore,it is crucial for stress response signaling to be turned off once conditions have improved.Nevertheless,the mechanisms by which cells silence these signals are still elusive.
基金supported by the Rural Revitalization Tea Industry Technical Service Project of Fujian Agriculture and Forestry University(Grant No.11899170145)the“Double firstclass”scientific and technological innovation capacity and enhancement cultivation plan of Fujian Agriculture and Forestry University(Grant No.KSYLP004)+4 种基金6.18 Tea Industry Technology Branch of Collaborative Innovation Institute(Grant No.K1520001A)Fujian Agriculture and Forestry University Construction Project for Technological Innovation and Service System of Tea Industry Chain(Grant No.K1520005A01)Tea Industry Branch of Collaborative Innovation Institute of Fujian Agriculture and Forestry University(Grant No.K1521015A)Science and Technology Innovation Special Fund Project of Fujian Agriculture and Forestry University(Grant No.KFb22020XA)the Special Fund for Science and Technology Innovation of Fujian Zhang Tianfu Tea Development Foundation(Grant No.FJZTF01).
文摘Drought stress is a serious natural challenge for tea plants that significantly affects tea yield and quality.miR171s play critical roles in plant stress responses,however,their role in drought stress tolerance in tea plants(Camellia sinensis)is poorly understood.This study experimentally verified the expression patterns of csn-miR171b-3p_2 and its target,scarecrow-like(SCL).We found that csn-miR171b-3p_2 could target and regulate CsSCL6-4 to play an important role in the defense against drought stress in tea plants.CsSCL6-4 is located in the nucleus and is selfactivated in vivo.In addition,we obtained 819 putative binding regions of CsSCL6-4 using DNA affinity purification sequencing analysis,which were assigned to 786 different genes,four of which were drought-resistant genes(CsPrx,CsSDR,CsFAD7,and CsCER1).Yeast one-hybrid and dual-luciferase reporter assays revealed that CsSCL6-4 directly promoted the expression of these four drought resistance genes by binding motifs 1/2/3 in their promoter regions.Both overexpression and suppression of CsSCL6-4 proved that CsSCL6-4 participated in the defense against drought stress in tea plants by regulating the expression of CsPrx,CsSDR,CsFAD7,and CsCER1.In addition,suppression of csn-miR171b-3p_2 expression significantly increased the expression of CsSCL6-4 and activated CsSCL6-4-bound gene transcription under drought stress.Therefore,the csn-miR171b-3p_2-CsSCL6-4 module participates in tea plant resistance to drought stress by promoting the expression of drought resistance genes.Our results revealed the function of csn-miR171b-3p_2 in tea plants and provided new insights into the mechanism of tea plant resistance to drought stress.
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 National Nature Science Foundation of China(Grant No.31660568)Guangxi Science and Technology major project(Grant No.GuikeAA22068088)+2 种基金start-up funding for introduced talents in Guangxi University,the Guangxi Colleges and Universities Young and Middle-aged Teachers'Basic Scientific Research Ability Improvement Project(Grant No.2024KY0010)Guangxi Graduate Education Innovation Program(Grant No.YCSW2024093)the Guangxi University Student Innovation and Entrepreneurship Training Program Funding Project(Grant Nos.202310593704,202310593714,202410953044S).
文摘N6-methyladenosine(m^(6)A)modification,the most abundant internal modification in messenger RNA(mRNA)and long non-coding RNA(lncRNA),has emerged as a critical epitranscriptomic regulatory mechanism in eukaryotes.While the importance of m^(6)A modification in various biological processes has been recognized,a comprehensive understanding of its diverse roles in plant biology and agricultural applications remains fragmented.This review analyzes recent advances inm^(6)A modification's biological functions in plants.m^(6)A modification plays crucial roles in multiple aspects of plant life,including seed germination,organ development,and reproductive structure formation.Furthermore,m^(6)A has been found to significantly influence plant responses to environmental stresses,including salt,drought,temperature,and heavy metal exposure.We also uncover m^(6)A involvement in important agricultural traits.This review provides insights into the mechanistic understanding of m^(6)A modification in plants and highlights its applications in agricultural improvement,offering a foundation for future research in crop enhancement and stress resistance.
文摘Heavy metal(HM)contamination severely impacts global agricultural production.HMs toxicity effectively damaged the physiological functions such as imbalanced redox homeostasis,altered antioxidant enzyme activity,damage root system architecture,hindered photosynthetic apparatus,cellular toxicity,restricted mineral accumulation,and changed the metabolite production.Using phytohormones may be a successful strategy for enhancing and stimulating plant tolerance to HMs toxicity without affecting the environment.Melatonin(MT),a novel plant growth regulator,and powerful antioxidant molecule,enhances plant resilience to HMs stress by enhancing seedling growth,protecting the photosynthetic system,increasing nutritional status,balanced redox homeostasis,and restricting HMs accumulation from root to shoot.In addition,MT enhances the activity of antioxidant enzymes and triggers the ascorbate-glutathione(AsA-GSH)cycle,which helps remove excessive ROS.MT improves RuBisCO activity to improve photosynthesis and reduce the breakdown of chlorophyll.To identify future research needs,it is crucial to understand the comprehensive and intricate regulatory mechanisms of exogenous and endogenous MT-mediated reduction of heavy metal toxicity in plants.Melatonin has several functions,and this review sheds light on those functions and the molecular processes by which it alleviates HMs toxicity.More research is needed to fully understand how melatonin affects plant tolerance to heavy metals stress.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
基金Funded by the National Natural Science Foundation of China(Nos.52278518 and 51938011)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.24KJB560021)。
文摘Based on the split hopkinson pressure bar(SHPB)tests results,the cubic specimens have been numerically modeled in this paper to investigate the impact of key factors,such as the rise time,duration,and incident pulse shape,on achieving stress uniformity.After analysis,the paper provides actionable methods aimed at optimizing the conditions for stress uniformity within the cubic specimen.Finally,the lateral inertia effect of cubic specimen has been scrutinized to address the existing gap in this academic area.
基金the Major Special Project of Jiangsu Administration of Traditional Chinese Medicine(Project No.ZT202116)the Key R&D Project of Jiangsu Province(Project No.BE2020727)+2 种基金the Yangzhou Science and Technology Program(Project No.YZ2021062,YZ2024143 and YZ2024194)the Third Batch of Academic Mentorship Program for Senior TCM Experts in Jiangsu Province(Project No.2019028)the 2023 Jiangsu Pharmaceutical Association–Aosaikang Hospital Pharmacy Research Project(Project No.A202333).
文摘Background:Myocardial infarction(MI)remains a major global public health challenge.Although advances in reperfusion therapy have reduced acute mortality,post-infarction cardiac remodeling continues to pose a substantial threat to long-term cardiovascular health.Oxidative stress and the ensuing inflammatory response are key drivers of this pathological process,leading to cardiomyocyte death,myocardial fibrosis,and functional impairment.Among the regulatory pathways involved,the kelch-like ECH-associated protein 1(Keap1)/nuclear factor erythroid 2-related factor 2(Nrf2)axis has emerged as a critical therapeutic target for mitigating post-MI cardiac injury.Methods:A murine MI model was established by permanent ligation of the left anterior descending coronary artery.Mice received oral Tongxinbi formula(TXB)at low,medium,or high doses(9/18/36 g/kg)once daily for 28 days.Cardiac function was assessed by echocardiography;myocardial fibrosis by Masson’s trichrome;and endothelial integrity by CD31 immunofluorescence.Plasma markers of endothelial function and inflammation were quantified.In vitro,oxidative stress was induced by H2O2 in vascular endothelial cells and cardiomyocytes,followed by treatment with TXB drug-containing serum.Western blot and RT-qPCR were used to measure components of the Keap1/Nrf2 pathway;ELISA quantified oxidative stress and inflammatory indices.Conditioned-medium experiments evaluated endothelial cell–mediated paracrine protection of cardiomyocytes.Results:TXB significantly improved cardiac function and reduced myocardial fibrosis after MI,in association with preservation of microvascular structure and systemic attenuation of oxidative stress and inflammation.In vitro,TXB activated the endothelial Keap1/Nrf2 pathway,enhanced cellular antioxidant defenses,increased VEGF secretion,and,via endothelial cell-mediated paracrine signaling,alleviated cardiomyocyte injury under oxidative stress.Conclusion:TXB exerts anti-fibrotic and cardioprotective effects by activating Nrf2 signaling and engaging endothelial-mediated paracrine mechanisms,collectively mitigating oxidative stress and inflammation in the post-MI setting.
文摘Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable.
基金supported in part by the National Key Research&Development Program of China,No.2022YFA1104900(to LS)the National Natural Science Foundation of China,Nos.82371175,82071535(both to LS),82101614(to YP)+5 种基金the International Science and Technology Cooperation Projects of Guangdong Province,No.2023A0505050121(to LS)Guangdong Basic and Applied Basic Research Foundation,Nos.2022B1515130007(to LS),2023A1515030012(to SZ),2022A1515010666(to WL)the Science and Technology Program of Guangzhou,Nos.202102070001(to LS),202201010041(to YP)Shenzhen Basic Research Grant,Nos.JCYJ20200109140414636,JCYJ20230807145103007(both to WL)awarded a Royal Society Newton Advanced Fellowship,No.AOMS-NAF0051003in collaboration with Zoltán Molnár,Department of Physiology,Anatomy and Genetics,University of Oxford(2017–2021)。
文摘Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a natural inhibitor of recombinant tissue plasminogen activator,neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia.However,the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear.In this study,we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models,respectively.The models were used to investigate the neuroprotective effects of neuroserpin.Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia,initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis,which was followed by a later apoptotic response.Notably,ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons.Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules,the reduction in protein synthesis,and the upregulation of apoptotic transcription factors.This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion,as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion.However,the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin.Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.
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.82304990(to NY),81973748(to JC),82174278(to JC)the National Key R&D Program of China,No.2023YFE0209500(to JC)+4 种基金China Postdoctoral Science Foundation,No.2023M732380(to NY)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,No.202102010014(to JC)Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University,No.201911(to JC)National Innovation and Entrepreneurship Training Program for Undergraduates in China,No.202310559128(to NY and QM)Innovation and Entrepreneurship Training Program for Undergraduates at Jinan University,Nos.CX24380,CX24381(both to NY and QM)。
文摘Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.
基金supported by the sub-project“Research and Application of In-Situ Value-Added Water-Soluble Fertilizer Application Technology”(Grant No.2023YFD1700204-3)under the 14th Five-Year National Key R&D Program Project“Development and Industrialization of Novel Green Value-Added Fertilizers”.
文摘Salinization of agricultural land is becoming increasingly severe worldwide,posing a significant threat to food security.The exogenous application of bioactive substances has been widely used to enhance plant resistance to salt stress.In this study,we used corn steep liquor(CSL),myo-inositol(MI),and their combination to improve salt tolerance in Chinese cabbage(Brassica rapa L.ssp.pekinensis)under salt stress conditions.All three treatments significantly increased plant biomass and nutrient uptake,and improved soil physicochemical properties,while alleviating oxidative damage and ion toxicity.
基金supported financially by the National Natural Science Foundation of China,No.82071272(to YZ).
文摘Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.
基金supported by the National Natural Science Foundation of China,Nos.82260245(to YX),81660207(to YX),81960253(to YL),82160268(to YL),U1812403(to ZG)Science and Technology Projects of Guizhou Province,Nos.[2019]1440(to YX),[2020]1Z067(to WH)+1 种基金Cultivation Foundation of Guizhou Medical University,No.[20NSP069](to YX)Excellent Young Talents Plan of Guizhou Medical University,No.(2022)101(to WH)。
文摘Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.
基金support from the Key Program of the National Natural Science Foundation of China(No.51235010)。
文摘Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challenge in accurately shaping aluminum alloy panels.In this study,the SRA behavior of 2195-T4 Al-Cu-Li alloys were thoroughly studied under initial loading stresses within the elastic(210/250 MPa)and plastic(380/420 MPa)ranges at 180℃by stress relaxation and tensile tests as well as microstructure characterization.The findings reveal that compared with those under elastic loadings,in-plane anisotropy(IPA)values of the stress relaxation amount,yield strength and fracture elongation under plastic loadings are reduced by 60%–80%,70%–90% and 72%–89%,respectively.Similarly,IPA values of precipitate size in grains and PrecipitationFree Zones(PFZ)width at grain boundaries under plastic loading decrease by 31.4%and 94.4%respectively.These results indicate plastic loading significantly weakens the anisotropic SRA behavior,owing to numerous uniformly distributed fine T1phases and small IPA values of both T1precipitates size and PFZ width in various loading directions.Compared with those of elastic loadingaged alloys,yield strength of plastic loading-aged alloys shows high strength-ductility because of the combined effect of closely dispersed fine T1precipitates,narrowed PFZ and numerous sheared and rotated T1phases at different locations during tensile process.The uniformly distributed larger Kernel Average Misorientation(KAM)and Schmidt factor values of the plastic loading-aged alloy,as well as the cross-slip generated,also help to enhance the strength and ductility of the alloy.
基金The authors extend their gratitude to the Deanship of Scientific Research(DSR),King Faisal University,Saudi Arabia,for funding the publication of this work(Project number:KFU250560).
文摘A steady rise in the overall population is creating an overburden on crops due to their global demand.On the other hand,given the current climate change and population growth,agricultural practices established during the Green Revolution are no longer viable.Consequently,innovative practices are the prerequisite of the time struggle with the rising global food demand.The potential of nanotechnology to reduce the phytotoxic effects of these ecological restrictions has shown significant promise.Nanoparticles(NPs)typically enhance plant resilience to stressors by fortifying the physical barrier,optimizing photosynthesis,stimulating enzymatic activity for defense,elevating the concentration of stress-resistant compounds,and activating the expression of genes associated with defense mechanisms.In this review,we thoroughly cover the uptake and translocations of NPs crops and their potential valuable functions in enhancing plant growth and development at different growth stages.Additionally,we addressed how NPs improve plant resistance to biotic and abiotic stress.Generally,this review presents a thorough understanding of the significance of NPs in plants and their prospective value for plant antioxidant and crop development.
基金supported by the National Natural Science Foundation of China(32171945,32301760)the Program for Innovative Research Team(in Science and Technology)in University of Henan Province,China(22IRTSTHN023)+2 种基金the Scientific and Technological Research Project of Henan Province,China(242102111116)the National Science Foundation for Postdoctoral Scientists of China(2023M731003)the Postdoctoral Research Subsidize Fund of Henan Province,China(HN2022139)。
文摘Global warming impacts plant growth and development,which in turn threatens food security.Plants can clearly respond to warm-temperature(such as by thermomorphogenesis)and high-temperature stresses.At the molecular level,many small molecules play crucial roles in balancing growth and defense,and stable high yields can be achieved by fine-tuning the responses to external stimuli.Therefore,it is essential to understand the molecular mechanisms underlying plant growth in response to heat stress and how plants can adjust their biological processes to survive heat stress conditions.In this review,we summarize the heat-responsive genetic networks in plants and crop plants based on recent studies.We focus on how plants sense the elevated temperatures and initiate the cellular and metabolic responses that allow them to adapt to the adverse growing conditions.We also describe the trade-off between plant growth and responses to heat stress.Specifically,we address the regulatory network of plant responses to heat stress,which will facilitate the discovery of novel thermotolerance genes and provide new opportunities for agricultural applications.
