Hyperpolarization of nuclear spins is crucial for advancing nuclear magnetic resonance and quantum information technologies,as nuclear spins typically exhibit extremely low polarization at room temperature due to thei...Hyperpolarization of nuclear spins is crucial for advancing nuclear magnetic resonance and quantum information technologies,as nuclear spins typically exhibit extremely low polarization at room temperature due to their small gyromagnetic ratios.A promising approach to achieving high nuclear spin polarization is transferring the polarization of electrons to nuclear spins.The nitrogen-vacancy(NV)center in diamond has emerged as a highly effective medium for this purpose,and various hyperpolarization protocols have been developed.Among these,the pulsed polarization(PulsePol)method has been extensively studied due to its robustness against static energy shifts of the electron spin.In this work,we present a novel polarization protocol and uncover a family of magic sequences for hyperpolarizing nuclear spins,with PulsePol emerging as a special case of our general approach.Notably,we demonstrate that some of these magic sequences exhibit significantly greater robustness compared to the PulsePol protocol in the presence of finite half𝜋pulse duration of the protocol,Rabi and detuning errors.This enhanced robustness positions our protocol as a more suitable candidate for hyper-polarizing nuclear spins species with large gyromagnetic ratios and also ensures better compatibility with high-efficiency readout techniques at high magnetic fields.Additionally,the generality of our protocol allows for its direct application to other solid-state quantum systems beyond the NV center.展开更多
Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
Fine-grained nuclear graphite is a key material in high-temperature gas-cooled reactors(HTGRs).During air ingress accidents,core graphite components undergo severe oxidation,threatening structural integrity.Therefore,...Fine-grained nuclear graphite is a key material in high-temperature gas-cooled reactors(HTGRs).During air ingress accidents,core graphite components undergo severe oxidation,threatening structural integrity.Therefore,understanding the oxidation behavior of nuclear graphite is essential for reactor safety.The influence of oxidation involves multiple factors,including temperature,sample size,oxidant,impurities,filler type and size,etc.The size of the filler particles plays a crucial role in this study.Five ultrafine-and superfine-grained nuclear graphite samples(5.9-34.4μm)are manufactured using identical raw materials and manufacturing processes.Isothermal oxidation tests conducted at 650℃-750℃ are used to study the oxidation behavior.Additionally,comprehensive characterization is performed to analyze the crystal structure,surface morphology,and nanoscale to microscale pore structure of the samples.Results indicate that oxidation behavior cannot be predicted solely based on filler grain size.Reactive site concentration,characterized by active surface area,dominates the chemical reaction kinetics,whereas pore tortuosity,quantified by the structural parameterΨ,plays a key role in regulating oxidant diffusion.These findings clarify the dual role of microstructure in oxidation mechanisms and establish a theoretical and experimental basis for the design of high-performance nuclear graphite capable of long-term service in high-temperature gas-cooled reactors.展开更多
When discussing atomic nuclei,deformation is one of the most common topics.However,when we connect the concept of shape with high-precision experimental measurements,sometimes the explanation may not be as simple as w...When discussing atomic nuclei,deformation is one of the most common topics.However,when we connect the concept of shape with high-precision experimental measurements,sometimes the explanation may not be as simple as we think.A recent measurement of nuclear charge radii(Phys.Rev.Lett.134,182501(2025))challenges current nuclear ab initio models.展开更多
In a series of three papers published in 2024[1-3],physicists in Austria,Germany,and the United States reported the first direct observations with table-top lasers of a new nuclear process,in which the nucleus of a th...In a series of three papers published in 2024[1-3],physicists in Austria,Germany,and the United States reported the first direct observations with table-top lasers of a new nuclear process,in which the nucleus of a thorium atom absorbs a photon and goes into an excited state,then re-emits the photon and returns to its ground state.This“thorescence”phenomenon“is exactly the same process as fluorescence,but it takes place inside the nucleus,”said Ekkehard Peik,professor and head of the department of time and frequency at the Physikalisch-Technische Bundesanstalt(the German national metrology institute)in Braunschweig,Germany.展开更多
Additive manufacturing(AM)is an innovative technique that enables the flexible design and construction of three-dimensional objects.In the nuclear industry,AM enables the use of advanced materials and high-performance...Additive manufacturing(AM)is an innovative technique that enables the flexible design and construction of three-dimensional objects.In the nuclear industry,AM enables the use of advanced materials and high-performance components.Although AM processing has been extensively investigated,the corresponding mechanical properties and structural integrity issues of AM parts have received less attention.This study reviews the mechanical behavior and key challenges of typical AM materials,fuel components,compact heat exchangers with complex geometries,and additive repair of damaged reactor components.The findings of this review will guide the efficient and reliable implementation of AM techniques in nuclear reactors.展开更多
Amborella trichopoda(Amborellaceae;hereafter simply Amborella)(Fig.1A)is a shrub endemic to New Caledonia in the Southwest Pacific that represents the sole sister species of all other extant angiosperms(Qiu et al.,199...Amborella trichopoda(Amborellaceae;hereafter simply Amborella)(Fig.1A)is a shrub endemic to New Caledonia in the Southwest Pacific that represents the sole sister species of all other extant angiosperms(Qiu et al.,1999;One Thousand Plant Transcriptomes Initiative,2019).Due to its unique phylogenetic status,it holds tremendous interest for botanists.The nuclear and mitochondrial genomes of Amborella were first published in 2013,providing valuable resources for studies on genome and gene family evolution,phylogenomics,and flower development,despite the fact that the assembly is heavily fragmented(Amborella Genome Project,2013;Rice et al.,2013).In 2024,a haplotype-resolved Amborella genome assembly was published,showing significant improvement in quality and completeness(Carey et al.,2024).展开更多
Nuclear magnetic resonance(NMR)spectroscopy is a powerful and broadly used spectroscopic technique for characterizing molecular structures and dynamics.Yet the power of NMR is restricted by its inherently low sensitiv...Nuclear magnetic resonance(NMR)spectroscopy is a powerful and broadly used spectroscopic technique for characterizing molecular structures and dynamics.Yet the power of NMR is restricted by its inherently low sensitivity due to the weak polarization of nuclear spins under conventional experiment conditions.Dynamic nuclear polarization(DNP)and chemically induced dynamic nuclear polarization(CIDNP)have been emerging as powerful in-situ hyperpolarization methods to boost NMR sensitivity.This review provides a brief overview of DNP mechanisms in the context of both solid-state and liquidstate.We delve into the molecular features of different polarizing agents and their impacts on DNP applications,which are now steadily progressing towards modern NMR magnetic field strengths and ambient temperatures.Furthermore,the progress of CIDNP,particularly photo-CIDNP as a potential alternative hyperpolarization technique of DNP,in studying protein dynamics and chemical reaction mechanisms,will be covered.This review also highlights the chemical diversity and experimental strategies crucial for these hyperpolarization techniques,showcasing their transformative role in NMR spectroscopy.展开更多
The^(229)Th nuclear optical clocks,operating via the 8.4 eV nuclear transition,hold great promise for attaining unprecedented accuracy in frequency standards and fundamental physics tests.In this study,we propose an a...The^(229)Th nuclear optical clocks,operating via the 8.4 eV nuclear transition,hold great promise for attaining unprecedented accuracy in frequency standards and fundamental physics tests.In this study,we propose an approach that utilizes highly charged^(229)Th^(6+)ions as the platform for nuclear clock,which exhibits simple electronic energy structures and enhanced nucleus–electron coupling compared to low-charge Th ions.The^(3)P_(2)↔^(3)P_(0)ionic clock transition in^(229)Th^(6+)ions has the potential to serve as a probe for nuclear structure.Moreover,we predict the existence of two excited electronic states near and slightly above the nuclear clock state,which can serve as the intermediate states in the optical repumping process.We estimate the Rabi frequencies of the electronic bridge transitions from the nuclear clock state to these intermediate states and further analyze the population dynamics of the optical repumping process,which can be completed on the millisecond timescale.Our results demonstrate the advantages of using^(229)Th^(6+)ions as the promising platform for nuclear clock.展开更多
We investigated the correlations between the net baryon number and electric charge up to the sixth order related to the interactions of nuclear matter at low temperature and explored their relationship with the nuclea...We investigated the correlations between the net baryon number and electric charge up to the sixth order related to the interactions of nuclear matter at low temperature and explored their relationship with the nuclear liquid-gas phase transition(LGPT)within the framework of the nonlinear Walecka model.The calculations showed that strong correlations between the baryon number and electric charge existed near the LGPT,and higher-order correlations were more sensitive than the lower-order correlations near the phase transition.However,in the high-temperature region away from the LGPT,the rescaled lower-order correlations were relatively larger than most of the higher-order correlations.In addition,some of the fifth-and sixth-order correlations possibly changed sign from negative to positive along the chemical freeze-out line with decreasing temperature.In combination with future experimental projects at lower collision energies,the derived results can be used to study the phase structure of strongly interacting matter and analyze the related experimental signals.展开更多
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well ...Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease. However, due to the its subtle nature and concurring events PDAC cure remains elusive. Nuclear receptors (NR) are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism, to growth and development. Given the nature of their ligands, NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases. There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages; nonetheless many aspects of their role are not fully understood. The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors, retinoic acid receptors, retinoid X receptor, androgen receptor, estrogen receptors and the orphan NR Nur, chicken ovalbumin upstream promoter transcription factor II and the liver receptor homologue-1 receptor to PDAC development, connections that could lead to the identification of novel therapies for this disease.展开更多
A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to ...A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.展开更多
This paper analyzes the role of nuclear power of China's energy structure and industry system. Comparing with other renewable energy the nuclear power chain has very low greenhouse gas emission, so it will play mo...This paper analyzes the role of nuclear power of China's energy structure and industry system. Comparing with other renewable energy the nuclear power chain has very low greenhouse gas emission, so it will play more important role in China's low-carbon economy. The paper also discussed the necessity of nuclear power development to achieve emission reduction, energy structure adjustment, nuclear power safety,environmental protection, enhancement of nuclear power technology, nuclear waste treatment, and disposal, as well as nuclear power plant decommissioning. Based on the safety record and situation of the existing power plants in China, the current status of the development of world nuclear power technology, and the features of the independently designed advanced power plants in China, this paper aims to demonstrate the safety of nuclear power. A nuclear power plant will not cause harm either to the environment and nor to the public according to the real data of radioactivity release, which are obtained from an operational nuclear plant. The development of nuclear power technology can enhance the safety of nuclear power. Further, this paper discusses issues related to the nuclear fuel cycle, the treatment, and disposal strategies of nuclear waste, and the decommissioning of a nuclear power plant, all of which are issues of public concern.展开更多
The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,...The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.展开更多
The Monte Carlo(MC)method offers significant advantages in handling complex geometries and physical processes in particle transport problems and has become a widely used approach in reactor physics analysis,radiation ...The Monte Carlo(MC)method offers significant advantages in handling complex geometries and physical processes in particle transport problems and has become a widely used approach in reactor physics analysis,radiation shielding design,and medical physics.However,with the rapid advancement of new nuclear energy systems,the Monte Carlo method faces challenges in efficiency,accuracy,and adaptability,limiting its effectiveness in meeting modern design requirements.Overcoming technical obstacles related to high-fidelity coupling,high-resolution computation,and intelligent design is essential for using the Monte Carlo method as a reliable tool in numerical analysis for these new nuclear energy systems.To address these challenges,the Nuclear Energy and Application Laboratory(NEAL)team at the University of South China developed a multifunctional and generalized intelligent code platform called MagicMC,based on the Monte Carlo particle transport method.MagicMC is a developing tool dedicated to nuclear applications,incorporating intelligent methodologies.It consists of two primary components:a basic unit and a functional unit.The basic unit,which functions similarly to a standard Monte Carlo particle transport code,includes seven modules:geometry,source,transport,database,tally,output,and auxiliary.The functional unit builds on the basic unit by adding functional modules to address complex and diverse applications in nuclear analysis.MagicMC introduces a dynamic Monte Carlo particle transport algorithm to address time-space particle transport problems within emerging nuclear energy systems and incorporates a CPU-GPU heterogeneous parallel framework to enable high-efficiency,high-resolution simulations for large-scale computational problems.Anticipating future trends in intelligent design,MagicMC integrates several advanced features,including CAD-based geometry modeling,global variance reduction methods,multi-objective shielding optimization,high-resolution activation analysis,multi-physics coupling,and radiation therapy.In this paper,various numerical benchmarks-spanning reactor transient simulations,material activation analysis,radiation shielding optimization,and medical dosimetry analysis-are presented to validate MagicMC.The numerical results demonstrate MagicMC's efficiency,accuracy,and reliability in these preliminary applications,underscoring its potential to support technological advancements in developing high-fidelity,high-resolution,and high-intelligence MC-based tools for advanced nuclear applications.展开更多
BACKGROUND Rosmarinic acid(RA)is a natural polyphenol carboxylic acid known for its role in chemoprevention.Given its widespread use as a food additive,we are interested in whether RA affects the development of colore...BACKGROUND Rosmarinic acid(RA)is a natural polyphenol carboxylic acid known for its role in chemoprevention.Given its widespread use as a food additive,we are interested in whether RA affects the development of colorectal cancer(CRC).AIM To examine the anti-tumor effects of RA on various CRC cell lines,and to further investigate the possible mechanisms.METHODS Cell Counting Kit-8 assay and optical microscopy imaging were used to evaluate the viability of CRC cell lines.Western blot,quantitative real-time polymerase chain reaction,and flow cytometry analyses were performed to assess cell viability and activation of nuclear factor-kappa B(NF-κB)signaling.Molecular modeling was used to assess the interaction between RA and inhibitory kappa B kinase beta.Luciferase assay was used to examine the activity of NF-κB-driven transcription.The combinations of RA with 5-fluorouracil or oxaliplatin were utilized to evaluate the potential synergistic action of RA with the chemotherapeutics.RESULTS RA exerted potent cytotoxic actions on all six CRC cell lines examined.RA was docked nicely into the binding pocket of inhibitory kappa B kinase beta by molecular modeling.The activity of NF-κB-driven luciferase and the phosphorylation of NF-κB p65 were decreased after exposure to the compound.Lipopolysaccharide-induced NF-κB activation was effectively inhibited by RA,too.Further,RA downregulated the expression of cell proliferationrelated cyclin D1 and MYC,which are target genes of NF-κB.Of note,the cytotoxic actions of 5-fluorouracil and oxaliplatin were markedly enhanced by RA in those CRC cells.CONCLUSION Our results indicate that RA inhibits NF-κB signaling and induces apoptosis in CRC cells.It enhances the cytotoxic actions of chemotherapeutics and might help to improve the chemotherapy of CRC.展开更多
Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and enhancers.Over the last 30 y...Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and enhancers.Over the last 30 years,research has revealed that the nuclear factor Y complex controls many aspects of brain development,including differentiation,axon guidance,homeostasis,disease,and most recently regeneration.However,a complete understanding of transcriptional regulatory networks,including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains elusive.In this review,we explore the nuclear factor Y complex’s role and mode of action during brain development,as well as how genomic technologies may expand understanding of this key regulator of gene expression.展开更多
Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein ...Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.展开更多
Pulpitis is a common infective oral disease in clinical situations.The regulatory mechanisms of immune defense in pulpitis are still being investigated.Osteomodulin(OMD)is a small leucine-rich proteoglycan family memb...Pulpitis is a common infective oral disease in clinical situations.The regulatory mechanisms of immune defense in pulpitis are still being investigated.Osteomodulin(OMD)is a small leucine-rich proteoglycan family member distributed in bones and teeth.It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells(hDPSCs).In this study,the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated.The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining.Intriguingly,the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens.The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide(LPS)-induced inflammation.A conditional Omd knockout mouse model with pulpal inflammation was established.LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice,whereas OMD administration exhibited a protective effect against pulpitis.Mechanistically,the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB(NF-κB)signaling pathway.Interleukin-1 receptor 1(IL1R1),a vital membrane receptor activating the NF-κB pathway,was significantly downregulated in OMD-overexpressing hDPSCs.Additionally,the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking.In vivo,excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist.Overall,OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway.OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.展开更多
The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing ...The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos.12475012,62461160263 for P.W.,and 62276171 for H.L.)Quantum Science and Technology-National Science and Technology Major Project of China (Project No.2023ZD0300600 for P.W.)+3 种基金Guangdong Provincial Quantum Science Strategic Initiative (Grant Nos.GDZX240-3009 and GDZX2303005 for P.W.)Guangdong Basic and Applied Basic Research Foundation (Grant No.2024-A1515011938 for H.L.)Shenzhen Fundamental ResearchGeneral Project (Grant No.JCYJ20240813141503005 for H.L.)the Talents Introduction Foundation of Beijing Normal University (Grant No.310432106 for P.W.)。
文摘Hyperpolarization of nuclear spins is crucial for advancing nuclear magnetic resonance and quantum information technologies,as nuclear spins typically exhibit extremely low polarization at room temperature due to their small gyromagnetic ratios.A promising approach to achieving high nuclear spin polarization is transferring the polarization of electrons to nuclear spins.The nitrogen-vacancy(NV)center in diamond has emerged as a highly effective medium for this purpose,and various hyperpolarization protocols have been developed.Among these,the pulsed polarization(PulsePol)method has been extensively studied due to its robustness against static energy shifts of the electron spin.In this work,we present a novel polarization protocol and uncover a family of magic sequences for hyperpolarizing nuclear spins,with PulsePol emerging as a special case of our general approach.Notably,we demonstrate that some of these magic sequences exhibit significantly greater robustness compared to the PulsePol protocol in the presence of finite half𝜋pulse duration of the protocol,Rabi and detuning errors.This enhanced robustness positions our protocol as a more suitable candidate for hyper-polarizing nuclear spins species with large gyromagnetic ratios and also ensures better compatibility with high-efficiency readout techniques at high magnetic fields.Additionally,the generality of our protocol allows for its direct application to other solid-state quantum systems beyond the NV center.
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
基金supported by the National Key Research and Development Program of China(2024YFA1612900)the National Natural Science Foundation of China(Grant No.52103365 and No.12375270)the Guangdong Innovative and Entrepreneurial Research Team Program,China(Grant No.2021ZT09L227).
文摘Fine-grained nuclear graphite is a key material in high-temperature gas-cooled reactors(HTGRs).During air ingress accidents,core graphite components undergo severe oxidation,threatening structural integrity.Therefore,understanding the oxidation behavior of nuclear graphite is essential for reactor safety.The influence of oxidation involves multiple factors,including temperature,sample size,oxidant,impurities,filler type and size,etc.The size of the filler particles plays a crucial role in this study.Five ultrafine-and superfine-grained nuclear graphite samples(5.9-34.4μm)are manufactured using identical raw materials and manufacturing processes.Isothermal oxidation tests conducted at 650℃-750℃ are used to study the oxidation behavior.Additionally,comprehensive characterization is performed to analyze the crystal structure,surface morphology,and nanoscale to microscale pore structure of the samples.Results indicate that oxidation behavior cannot be predicted solely based on filler grain size.Reactive site concentration,characterized by active surface area,dominates the chemical reaction kinetics,whereas pore tortuosity,quantified by the structural parameterΨ,plays a key role in regulating oxidant diffusion.These findings clarify the dual role of microstructure in oxidation mechanisms and establish a theoretical and experimental basis for the design of high-performance nuclear graphite capable of long-term service in high-temperature gas-cooled reactors.
基金supported by the National Natural Science Foundation of China(No.12235003).
文摘When discussing atomic nuclei,deformation is one of the most common topics.However,when we connect the concept of shape with high-precision experimental measurements,sometimes the explanation may not be as simple as we think.A recent measurement of nuclear charge radii(Phys.Rev.Lett.134,182501(2025))challenges current nuclear ab initio models.
文摘In a series of three papers published in 2024[1-3],physicists in Austria,Germany,and the United States reported the first direct observations with table-top lasers of a new nuclear process,in which the nucleus of a thorium atom absorbs a photon and goes into an excited state,then re-emits the photon and returns to its ground state.This“thorescence”phenomenon“is exactly the same process as fluorescence,but it takes place inside the nucleus,”said Ekkehard Peik,professor and head of the department of time and frequency at the Physikalisch-Technische Bundesanstalt(the German national metrology institute)in Braunschweig,Germany.
基金supported by Stable Support Initiative of the State Key Laboratory of Advanced Nuclear Energy Technology(Grant No.YNSW-0124-0101-03)the author Cheng Zhang would like to thank the support by Stable Support Program for Scientific Research of China(Grant No.WDZC-2023-02-02-05).
文摘Additive manufacturing(AM)is an innovative technique that enables the flexible design and construction of three-dimensional objects.In the nuclear industry,AM enables the use of advanced materials and high-performance components.Although AM processing has been extensively investigated,the corresponding mechanical properties and structural integrity issues of AM parts have received less attention.This study reviews the mechanical behavior and key challenges of typical AM materials,fuel components,compact heat exchangers with complex geometries,and additive repair of damaged reactor components.The findings of this review will guide the efficient and reliable implementation of AM techniques in nuclear reactors.
基金supported by the National Natural Science Foundation of China(32270217,31970205,31770211)Metasequoia funding of Nanjing Forestry University to YY。
文摘Amborella trichopoda(Amborellaceae;hereafter simply Amborella)(Fig.1A)is a shrub endemic to New Caledonia in the Southwest Pacific that represents the sole sister species of all other extant angiosperms(Qiu et al.,1999;One Thousand Plant Transcriptomes Initiative,2019).Due to its unique phylogenetic status,it holds tremendous interest for botanists.The nuclear and mitochondrial genomes of Amborella were first published in 2013,providing valuable resources for studies on genome and gene family evolution,phylogenomics,and flower development,despite the fact that the assembly is heavily fragmented(Amborella Genome Project,2013;Rice et al.,2013).In 2024,a haplotype-resolved Amborella genome assembly was published,showing significant improvement in quality and completeness(Carey et al.,2024).
基金supported by the National Natural Science Foundation of China(Grant No.22403029)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(Grant No.GZC20240475,2024M760922)+5 种基金supported by National Natural Science Foundation of China(Grant No.22174099)supported by the National Natural Science Foundation of China(Grant No.22273023)the National Key R&D Program of China(Grant No.2019YFA0905200)Shanghai Municipal Natural Science Foundation(Grant No.23ZR1418200)Natural Science Foundation of Chongqing,China(Grant No.CSTB2023NSCQ-MSX0616)Shanghai Frontiers Science Center of Molecule Intelligent Syntheses,and the Fundamental Research Funds for the Central Universities.
文摘Nuclear magnetic resonance(NMR)spectroscopy is a powerful and broadly used spectroscopic technique for characterizing molecular structures and dynamics.Yet the power of NMR is restricted by its inherently low sensitivity due to the weak polarization of nuclear spins under conventional experiment conditions.Dynamic nuclear polarization(DNP)and chemically induced dynamic nuclear polarization(CIDNP)have been emerging as powerful in-situ hyperpolarization methods to boost NMR sensitivity.This review provides a brief overview of DNP mechanisms in the context of both solid-state and liquidstate.We delve into the molecular features of different polarizing agents and their impacts on DNP applications,which are now steadily progressing towards modern NMR magnetic field strengths and ambient temperatures.Furthermore,the progress of CIDNP,particularly photo-CIDNP as a potential alternative hyperpolarization technique of DNP,in studying protein dynamics and chemical reaction mechanisms,will be covered.This review also highlights the chemical diversity and experimental strategies crucial for these hyperpolarization techniques,showcasing their transformative role in NMR spectroscopy.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB0920000)the National Key Research and Development Program of China(Grant No.2022YFB3904002)the National Natural Science Foundation of China(Grant No.12341401)。
文摘The^(229)Th nuclear optical clocks,operating via the 8.4 eV nuclear transition,hold great promise for attaining unprecedented accuracy in frequency standards and fundamental physics tests.In this study,we propose an approach that utilizes highly charged^(229)Th^(6+)ions as the platform for nuclear clock,which exhibits simple electronic energy structures and enhanced nucleus–electron coupling compared to low-charge Th ions.The^(3)P_(2)↔^(3)P_(0)ionic clock transition in^(229)Th^(6+)ions has the potential to serve as a probe for nuclear structure.Moreover,we predict the existence of two excited electronic states near and slightly above the nuclear clock state,which can serve as the intermediate states in the optical repumping process.We estimate the Rabi frequencies of the electronic bridge transitions from the nuclear clock state to these intermediate states and further analyze the population dynamics of the optical repumping process,which can be completed on the millisecond timescale.Our results demonstrate the advantages of using^(229)Th^(6+)ions as the promising platform for nuclear clock.
基金supported by the National Natural Science Foundation of China(Nos.12475145,11875213)the Natural Science Basic Research Plan in Shaanxi Province of China(No.2024JC-YBMS-018).
文摘We investigated the correlations between the net baryon number and electric charge up to the sixth order related to the interactions of nuclear matter at low temperature and explored their relationship with the nuclear liquid-gas phase transition(LGPT)within the framework of the nonlinear Walecka model.The calculations showed that strong correlations between the baryon number and electric charge existed near the LGPT,and higher-order correlations were more sensitive than the lower-order correlations near the phase transition.However,in the high-temperature region away from the LGPT,the rescaled lower-order correlations were relatively larger than most of the higher-order correlations.In addition,some of the fifth-and sixth-order correlations possibly changed sign from negative to positive along the chemical freeze-out line with decreasing temperature.In combination with future experimental projects at lower collision energies,the derived results can be used to study the phase structure of strongly interacting matter and analyze the related experimental signals.
基金Supported by Fondo per gli Investimenti della Ricerca di Base(FIRB)(RBAP10MY35_002)by Ente Cassa di Risparmio di Firenzeby FiorGen ONLUS to Galli A
文摘Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease. However, due to the its subtle nature and concurring events PDAC cure remains elusive. Nuclear receptors (NR) are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism, to growth and development. Given the nature of their ligands, NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases. There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages; nonetheless many aspects of their role are not fully understood. The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors, retinoic acid receptors, retinoid X receptor, androgen receptor, estrogen receptors and the orphan NR Nur, chicken ovalbumin upstream promoter transcription factor II and the liver receptor homologue-1 receptor to PDAC development, connections that could lead to the identification of novel therapies for this disease.
基金supported by the Army Laboratory Animal Foundation of China,No.SYDW[2020]22(to TC)the Shaanxi Provincial Key R&D Plan General Project of China,No.2022SF-236(to YM)the National Natural Science Foundation of China,No.82202070(to TC)。
文摘A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.
文摘This paper analyzes the role of nuclear power of China's energy structure and industry system. Comparing with other renewable energy the nuclear power chain has very low greenhouse gas emission, so it will play more important role in China's low-carbon economy. The paper also discussed the necessity of nuclear power development to achieve emission reduction, energy structure adjustment, nuclear power safety,environmental protection, enhancement of nuclear power technology, nuclear waste treatment, and disposal, as well as nuclear power plant decommissioning. Based on the safety record and situation of the existing power plants in China, the current status of the development of world nuclear power technology, and the features of the independently designed advanced power plants in China, this paper aims to demonstrate the safety of nuclear power. A nuclear power plant will not cause harm either to the environment and nor to the public according to the real data of radioactivity release, which are obtained from an operational nuclear plant. The development of nuclear power technology can enhance the safety of nuclear power. Further, this paper discusses issues related to the nuclear fuel cycle, the treatment, and disposal strategies of nuclear waste, and the decommissioning of a nuclear power plant, all of which are issues of public concern.
基金supported by National Natural Science Foundation of China(grant numbers 82072523 to Zhiyong Hou)Postdoctoral program of Clinical medicine of Hebei Medical University(grant numbers PD2023012 to Sujuan Xu)+2 种基金Excellent postdoctoral research funding project of Hebei Province(grant numbers B2023005011 to Sujuan Xu)The 16th special grant of China Postdoctoral Science Foundation(grant numbers 2023T160182 to Sujuan Xu)Natural Science Foundation of Hebei Province,China(grant numbers H2023206230 to Yingchao Yin,H2024206186 to Sujuan Xu).
文摘The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.
基金supported by the National Natural Science Foundation of China(Nos.12475174 and U2267207)YueLuShan Center Industrial Innovation(No.2024YCII0108)+2 种基金Natural Science Foundation of Hunan Province(No.2022JJ40345)Science and Technology Innovation Project of Hengyang(No.202250045336)the Project of State Key Laboratory of Radiation Medicine and Protection,Soochow University(No.GZK12023031)。
文摘The Monte Carlo(MC)method offers significant advantages in handling complex geometries and physical processes in particle transport problems and has become a widely used approach in reactor physics analysis,radiation shielding design,and medical physics.However,with the rapid advancement of new nuclear energy systems,the Monte Carlo method faces challenges in efficiency,accuracy,and adaptability,limiting its effectiveness in meeting modern design requirements.Overcoming technical obstacles related to high-fidelity coupling,high-resolution computation,and intelligent design is essential for using the Monte Carlo method as a reliable tool in numerical analysis for these new nuclear energy systems.To address these challenges,the Nuclear Energy and Application Laboratory(NEAL)team at the University of South China developed a multifunctional and generalized intelligent code platform called MagicMC,based on the Monte Carlo particle transport method.MagicMC is a developing tool dedicated to nuclear applications,incorporating intelligent methodologies.It consists of two primary components:a basic unit and a functional unit.The basic unit,which functions similarly to a standard Monte Carlo particle transport code,includes seven modules:geometry,source,transport,database,tally,output,and auxiliary.The functional unit builds on the basic unit by adding functional modules to address complex and diverse applications in nuclear analysis.MagicMC introduces a dynamic Monte Carlo particle transport algorithm to address time-space particle transport problems within emerging nuclear energy systems and incorporates a CPU-GPU heterogeneous parallel framework to enable high-efficiency,high-resolution simulations for large-scale computational problems.Anticipating future trends in intelligent design,MagicMC integrates several advanced features,including CAD-based geometry modeling,global variance reduction methods,multi-objective shielding optimization,high-resolution activation analysis,multi-physics coupling,and radiation therapy.In this paper,various numerical benchmarks-spanning reactor transient simulations,material activation analysis,radiation shielding optimization,and medical dosimetry analysis-are presented to validate MagicMC.The numerical results demonstrate MagicMC's efficiency,accuracy,and reliability in these preliminary applications,underscoring its potential to support technological advancements in developing high-fidelity,high-resolution,and high-intelligence MC-based tools for advanced nuclear applications.
基金Supported by Natural Science Foundation of Heilongjiang Province of China Under Grant,No.PL2024H020High-Quality Innovation Platform of Science and Education Innovation Zone in Suzhou Industrial Park-Key Platform Project,No.YZCXPT2023104.
文摘BACKGROUND Rosmarinic acid(RA)is a natural polyphenol carboxylic acid known for its role in chemoprevention.Given its widespread use as a food additive,we are interested in whether RA affects the development of colorectal cancer(CRC).AIM To examine the anti-tumor effects of RA on various CRC cell lines,and to further investigate the possible mechanisms.METHODS Cell Counting Kit-8 assay and optical microscopy imaging were used to evaluate the viability of CRC cell lines.Western blot,quantitative real-time polymerase chain reaction,and flow cytometry analyses were performed to assess cell viability and activation of nuclear factor-kappa B(NF-κB)signaling.Molecular modeling was used to assess the interaction between RA and inhibitory kappa B kinase beta.Luciferase assay was used to examine the activity of NF-κB-driven transcription.The combinations of RA with 5-fluorouracil or oxaliplatin were utilized to evaluate the potential synergistic action of RA with the chemotherapeutics.RESULTS RA exerted potent cytotoxic actions on all six CRC cell lines examined.RA was docked nicely into the binding pocket of inhibitory kappa B kinase beta by molecular modeling.The activity of NF-κB-driven luciferase and the phosphorylation of NF-κB p65 were decreased after exposure to the compound.Lipopolysaccharide-induced NF-κB activation was effectively inhibited by RA,too.Further,RA downregulated the expression of cell proliferationrelated cyclin D1 and MYC,which are target genes of NF-κB.Of note,the cytotoxic actions of 5-fluorouracil and oxaliplatin were markedly enhanced by RA in those CRC cells.CONCLUSION Our results indicate that RA inhibits NF-κB signaling and induces apoptosis in CRC cells.It enhances the cytotoxic actions of chemotherapeutics and might help to improve the chemotherapy of CRC.
基金supported by National Health and Medical Research Council GNT1105374,GNT1137645,GNT2000766 and veski Innovation Fellowship(VIF23)to RP.
文摘Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and enhancers.Over the last 30 years,research has revealed that the nuclear factor Y complex controls many aspects of brain development,including differentiation,axon guidance,homeostasis,disease,and most recently regeneration.However,a complete understanding of transcriptional regulatory networks,including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains elusive.In this review,we explore the nuclear factor Y complex’s role and mode of action during brain development,as well as how genomic technologies may expand understanding of this key regulator of gene expression.
基金supported by the National Natural Science Foundation of China,Nos.82001178(to LW),81901129(to LH),82001175(to FX)Shanghai Sailing Program,No.20YF1439200(to LW)+1 种基金the Natural Science Foundation of Shanghai,China,No.23ZR1450800(to LH)and the Fundamental Research Funds for the Central Universities,No.YG2023LC15(to ZX)。
文摘Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.
基金supported by grants from the National Natural Science Foundation of China (82071104)Science and Technology Commission of Shanghai Municipality (23XD1434200/22Y21901000)+9 种基金Shanghai Hospital Development Center(SHDC12022120)National Clinical Research Center for Oral Diseases (NCRCO2021-omics-07)Shanghai Clinical Research Center for Oral Diseases (19MC1910600)Major and Key Cultivation Projects of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYZP006)Shanghai’s Top Priority Research Center (2022ZZ01017)CAMS Innovation Fund for Medical Sciences (2019-I2M-5-037)Fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine(JYZZ237)Eastern Talent Plan Leading Project (BJZH2024001)partly supported by the Shanghai Ninth People’s Hospital affiliated with Shanghai Jiao Tong University,School of Medicine(JYJC202223)Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases (14DZ2260300)
文摘Pulpitis is a common infective oral disease in clinical situations.The regulatory mechanisms of immune defense in pulpitis are still being investigated.Osteomodulin(OMD)is a small leucine-rich proteoglycan family member distributed in bones and teeth.It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells(hDPSCs).In this study,the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated.The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining.Intriguingly,the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens.The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide(LPS)-induced inflammation.A conditional Omd knockout mouse model with pulpal inflammation was established.LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice,whereas OMD administration exhibited a protective effect against pulpitis.Mechanistically,the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB(NF-κB)signaling pathway.Interleukin-1 receptor 1(IL1R1),a vital membrane receptor activating the NF-κB pathway,was significantly downregulated in OMD-overexpressing hDPSCs.Additionally,the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking.In vivo,excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist.Overall,OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway.OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
基金supported by the Science&Technology Department of Sichuan Province(No.2019YFS0040)the Improvement Plan of“Xinglin Scholar”Scientific Research Talent,Chengdu University of Traditional Chinese Medicine(No.XKTD2022002)。
文摘The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
