AIM： To detect the DNA binding activity of nuclear factor-kappaB （NF-KB） in rat hepatocyte and to investigate the effects of NF-KB on rat hepatocyte regeneration and apoptosis after 70% portal branch Iigation. METH...AIM： To detect the DNA binding activity of nuclear factor-kappaB （NF-KB） in rat hepatocyte and to investigate the effects of NF-KB on rat hepatocyte regeneration and apoptosis after 70% portal branch Iigation. METHODS： Sixty Wistar rats were randomly divided into control group and portal branch ligation group. The animals were killed 12 h, 1, 2, 3, 7, and 14 d after surgery to determine the contents of plasma ALT. Hepatocytes were isolated and nuclear protein was extracted. DNA binding activity of NF-KB was measured by ENSA. Hepatocyte regeneration and apoptosis were observed under microscope by TUNEL staining. The ultrastructural changes of liver were observed under electron microscope. RESULTS： Seventy percent portal branch ligation produced atrophy of the ligated lobes and the perfused lobes underwent compensatory regeneration, the total liver weight and plasma ALT levels were maintained at the level of sham-operated animals throughout the experiment. After 2 d of portal branch ligation, DNA binding activity of NF-KB in hepatocyte increased and reached its peak, the number of apoptotic hepatocyte in the ligated lobes and the number of mitotic hepatocyte in the perfused lobes also reached their peak. Typical apoptotic changes and evident fibrotic changes in the ligated lobes were observed under electron microscope. CONCLUSION： After 70% portal branch ligation, DNA binding activity of NF-KB in hepatocyte is significantly increased and NF-KB plays an important role in hepatocyte regeneration and apoptosis.展开更多
BACKGROUND： It has been demonstrated that edaravone has a a neuroprotective role, inhibits free radical increase, and reduces celt apoptosis. The Notch pathway is a key factor in neurogenesis and cellular apoptosis T...BACKGROUND： It has been demonstrated that edaravone has a a neuroprotective role, inhibits free radical increase, and reduces celt apoptosis. The Notch pathway is a key factor in neurogenesis and cellular apoptosis The proinflammatory transcription factor nuclear factor-kappaB （NF-κB） plays an important role in inflammation and oxidation. OBJECTIVE： To observe the influence of edaravone on Notchl and NF-κB mRNA and protein expression in rats with focal cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： This randomized controlled neural and molecular biology experiment was performed at the Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, and the Chongqing Key Laboratory of Neurology between July 2007 and May 2008. MATERIALS： Thirty female Wistar rats were used. Edaravone was purchased from Jiangsu Xiansheng Pharmaceutical Limited Company, China. METHODS： Wistar rats were randomly divided into five groups （n = 6）. Thread was inserted into the internal carotid artery of the sham operation group but the middle cerebral artery was not ligated. A focal cerebral ischemia/reperfusion model was established by inserting thread into the right middle cerebral artery. The model rats in the edaravone groups were given tail vein injections of edaravone at 3 mg/kg body weight after ischemia for 2 hours and reperfusion for 12 or 24 hours. Ischemia/reperfusion groups （model group） received intravenous infusion of normal saline at the same volume as the edaravone groups after ischemia for 2 hours and reperfusion for 12 or 24 hours. MAIN OUTCOME MEASURES： The volume of the ischemic region was measured by 2,3,5-triphenyltetrazolium chloride staining. Notchl and NF-κB protein and mRNA expression were measured by immunohistochemistry and RT-PCR. Protein expression was represented by the absorbance value. RESULTS： Edaravone greatly reduced the focal infarct volume. Notchl and NF-κB protein and mRNA expression were rapidly upregulated following cerebral ischemia/reperfusion injury in model and edaravone groups compared with the sham operation group （P 〈 0.01 ）. In addition, edaravone treatment significantly upregulated Notchl expression but down-regulated NF-κB expression compared with model groups （P 〈 0.01）. CONCLUSION： Edaravone possibly protects brain tissue from ischemia/reperfusion injury by upregulating Notchl expression and regulating NF-κB expression.展开更多
AIM： To investigate the potential role of nuclear factor kappa-B （NF-κB） activation on the reactive oxygen species in rat acute necrotizing pancreatitis （ANP） and to assess the effect of pyrrolidine dithiocarbam...AIM： To investigate the potential role of nuclear factor kappa-B （NF-κB） activation on the reactive oxygen species in rat acute necrotizing pancreatitis （ANP） and to assess the effect of pyrrolidine dithiocarbamate （PDTC, an inhibitor of NF-κB）.METHODS： Rat ANP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. Rats were randomly assigned to three groups （10 rats each）： Control group, ANP group and PDTC group. At the 6^th of the model, the changes of the serum amylase,nitric oxide （NO）, malondialdehyde （MDA）, superoxide dismutase （SOD） and pancreatic morphological damage were observed. The expressions of inducible nitric oxide （iNOS） were observed by SP immunohistochemistry. And bhe expressions of NF-κB p65 subunit mRNA were observed by hybridization in situ.RESULTS： Serum amylase and NO level decreased significantly in ANP group as compared with PDTC administrated group [（7 170.40＋1 308.63） U/L vs（4 074.10＋1 719.78） U/L,P〈0.05], [（76.95±9.04） μmol/L vs （65.18±9.02） μmol/L,P〈0.05] respectively. MDA in both ANP and PDTC group rose significantly over that in control group [（9.88＋1.52）nmol/L, （8.60±1.41） nmol/L, vs （6.04：hl.78） nmol/L,P〈0.05], while there was no significant difference between them. SOD levels in both ANP and PDTC group underwent a significant decrease as compared with that in control[（3 214.59±297.74） NU/mL, （3 260.62±229.44） NU/mL,vs（3 977.80＋309.09） NU/mL, P〈0.05], but there was no significant difference between them. Though they were still higher bhan those in Control group, pancreas destruction was slighter in PDTC group, iNOS expression and NF-κB p65 subunit mRNA expression were lower in PDTC group as compared with ANP group.CONCLUSION： We conclude that correlation among NF-κB activation, serum amylase, reactive oxygen species level and tissue damage suggests a key role of NF-κB in the pathogenesis of ANP. Inhibition of NF-κB activation may reverse the pancreatic damage of rat ANP and the production of reactive oxygen species.展开更多
Objective： To explore the combination effects of all-trans retinoic acid （ATRA） with interferon-gamma （IFN-γ） on human hepatocarcinoma cell line SMMC-7721 and the mechanism of action. Methods： SMMC-7721 cells w...Objective： To explore the combination effects of all-trans retinoic acid （ATRA） with interferon-gamma （IFN-γ） on human hepatocarcinoma cell line SMMC-7721 and the mechanism of action. Methods： SMMC-7721 cells were divided into treated group and control group. The cells were treated with ATRA or ATRA＋ IFN-γ in the former and added with PBS in the latter. The inhibition rate of SMMC-7721 cell proliferation was detected by MTT, the cell change in morphology was observed by electron microscope. The apoptosis was detected by flow cytometry and the expression changes of nuclear factor-kappaB （NF-κB） was analyzed by Western blotting when the SMMC-7721 cells were treated with ATRA and IFN-γ. Results： The SMMC-7721 cell proliferation was suppressed and apoptosis was induced after the cells were treated with ATRA treatment, and these effects were enhanced when ATRA was combined with IFN-γ. The expression of NF-κB was reduced after SMMC-7721 cell was treated with ATRA, and reduced significantly when the cells were treated with the combination of ATRA and IFN-γ. Conclusion： IFN-γ can enhance the inhibiting effects of ATRA on cell proliferation and inducing apoptosis on SMMC-7721 cell and these effects might be mediated by inhibiting the expression of NF-κB.展开更多
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
Background Increased levels of plasma lipopolysaccharide （LPS） have been found in obesity and diabetes patients. This study was to investigate the effect of LPS on pancreatic beta-cell viability and the involvement ...Background Increased levels of plasma lipopolysaccharide （LPS） have been found in obesity and diabetes patients. This study was to investigate the effect of LPS on pancreatic beta-cell viability and the involvement of caspase 3 in NIT-1 cell line. Methods Mouse insulinoma NIT-1 cells were treated with LPS for the indicated time and dose. Cell viability was measured by cell counting kit-8 reagent. Toll-like receptor 4 （TLR4）, caspase 3 and cleaved caspase 3 were detected by Western blotting. Insulin was determined by radioimmunoassay （RIA）. Results LPS promoted NIT-1 cell proliferation at 1 μg/ml, peaked at 72 hours of incubation. A reduction in cleavage of caspase 3 was observed upon LPS treatment. Bay11-7082, a specific inhibitor of nuclear factor （NF）-κB, blunted LPS-induced inhibition of caspase 3 cleavage. Reduction in chronic insulin secretion was observed after treatment with LPS at 1 μg/ml for 48 and 72 hours, not for 24 hours. TLR4 protein was upregulated when NIT-1 cells were treated with LPS at 1 μg/ml for 24 hours. Conclusions LPS promotes early NIT-1 cell proliferation in association with NF-KB-mediated inhibition of caspase 3 cleavage. LPS exerts a time-dependent inhibitory effect on chronic insulin secretion from NIT-1 cells.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
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
G-quadruplexes,which are unique nucleic acid secondary structures formed by the folding of guaninerich DNA or RNA,are closely related to essential biological activities.They exhibit extensive application prospects owi...G-quadruplexes,which are unique nucleic acid secondary structures formed by the folding of guaninerich DNA or RNA,are closely related to essential biological activities.They exhibit extensive application prospects owing to their abundant binding sites and distinct physicochemical properties.Therefore,G-quadruplexes have attracted widespread attention in recent decades.Nuclear magnetic resonance(NMR)technology is an ideal tool for characterizing molecular structures and plays a crucial role in exploring the self-assembly process of G-quadruplexes.In this article,we introduce the basic concepts of NMR,followed by reviewing the applications of NMR in G-quadruplexes.Finally,challenges and prospects of NMR technology in the field of G-quadruplex research are discussed.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
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
In complex systems,there is a kind of parameters having only a minor impact on the outputs in most cases,but their accurate values are still critical for the operation of systems.In this paper,the authors focus on the...In complex systems,there is a kind of parameters having only a minor impact on the outputs in most cases,but their accurate values are still critical for the operation of systems.In this paper,the authors focus on the identification of these weak influence parameters in the complex systems and propose a identification model based on the parameter recursion.As an application,three parameters of the steam generator are identified,that is,the valve opening,the valve CV value,and the reference water level,in which the valve opening and the reference water level are weak influence parameters under most operating conditions.Numerical simulation results show that,in comparison with the multi-layer perceptron(MLP),the identification error rate is decreased.Actually,the average identification error rate for the valve opening decreases by 0.96%,for the valve CV decreases by 0.002%,and for the reference water level decreases by 12%after one recursion.After two recursions,the average identification error rate for the valve opening decreases by 11.07%,for the valve CV decreases by 2.601%,and for the reference water level decreases by 95.79%.This method can help to improve the control of the steam generator.展开更多
This study investigates the establishment of scientific links between the People's Republic of China(PRC)and the United Kingdom(UK)in the mid-2Oth century,focusing on the early development of China's nuclear i...This study investigates the establishment of scientific links between the People's Republic of China(PRC)and the United Kingdom(UK)in the mid-2Oth century,focusing on the early development of China's nuclear industry.Sino-British scientific interactions took place across multiple dimensions,involving various institutions and individuals.Around 1949,UK-trained Chinese nuclear scientists returned to China,bringing advanced technological knowledge and extensive practical experience.The PRC regarded the UK as a crucial gateway to overcoming the technological blockade imposed by the United States(and later the Soviet Union)and sought to establish scientific relations with the UK through semi-official and unofficial channels.Specifically,these connections manifested in the interactions between the Chinese Academy of Sciences(CAS)and the Royal Society of London,the guiding role of the Chinese Charge d'Affaires Office in London in facilitating scientific and technological exchanges,and the technology investigations led by the Ministry of Foreign Trade in the name of trade.Additionally,the Sino-British scientific network extended to the international arena,allowing China to engage in nuclear-related global organizations and events.This study highlights the significant British influence on the early development of China's nuclear industry,revealing the extent of its British influence.It argues that China's urgent need for nuclear science and industrial advancement was a key driver of its scientific engagement withthe UK.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
Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and...Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.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
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
文摘AIM： To detect the DNA binding activity of nuclear factor-kappaB （NF-KB） in rat hepatocyte and to investigate the effects of NF-KB on rat hepatocyte regeneration and apoptosis after 70% portal branch Iigation. METHODS： Sixty Wistar rats were randomly divided into control group and portal branch ligation group. The animals were killed 12 h, 1, 2, 3, 7, and 14 d after surgery to determine the contents of plasma ALT. Hepatocytes were isolated and nuclear protein was extracted. DNA binding activity of NF-KB was measured by ENSA. Hepatocyte regeneration and apoptosis were observed under microscope by TUNEL staining. The ultrastructural changes of liver were observed under electron microscope. RESULTS： Seventy percent portal branch ligation produced atrophy of the ligated lobes and the perfused lobes underwent compensatory regeneration, the total liver weight and plasma ALT levels were maintained at the level of sham-operated animals throughout the experiment. After 2 d of portal branch ligation, DNA binding activity of NF-KB in hepatocyte increased and reached its peak, the number of apoptotic hepatocyte in the ligated lobes and the number of mitotic hepatocyte in the perfused lobes also reached their peak. Typical apoptotic changes and evident fibrotic changes in the ligated lobes were observed under electron microscope. CONCLUSION： After 70% portal branch ligation, DNA binding activity of NF-KB in hepatocyte is significantly increased and NF-KB plays an important role in hepatocyte regeneration and apoptosis.
文摘BACKGROUND： It has been demonstrated that edaravone has a a neuroprotective role, inhibits free radical increase, and reduces celt apoptosis. The Notch pathway is a key factor in neurogenesis and cellular apoptosis The proinflammatory transcription factor nuclear factor-kappaB （NF-κB） plays an important role in inflammation and oxidation. OBJECTIVE： To observe the influence of edaravone on Notchl and NF-κB mRNA and protein expression in rats with focal cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： This randomized controlled neural and molecular biology experiment was performed at the Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, and the Chongqing Key Laboratory of Neurology between July 2007 and May 2008. MATERIALS： Thirty female Wistar rats were used. Edaravone was purchased from Jiangsu Xiansheng Pharmaceutical Limited Company, China. METHODS： Wistar rats were randomly divided into five groups （n = 6）. Thread was inserted into the internal carotid artery of the sham operation group but the middle cerebral artery was not ligated. A focal cerebral ischemia/reperfusion model was established by inserting thread into the right middle cerebral artery. The model rats in the edaravone groups were given tail vein injections of edaravone at 3 mg/kg body weight after ischemia for 2 hours and reperfusion for 12 or 24 hours. Ischemia/reperfusion groups （model group） received intravenous infusion of normal saline at the same volume as the edaravone groups after ischemia for 2 hours and reperfusion for 12 or 24 hours. MAIN OUTCOME MEASURES： The volume of the ischemic region was measured by 2,3,5-triphenyltetrazolium chloride staining. Notchl and NF-κB protein and mRNA expression were measured by immunohistochemistry and RT-PCR. Protein expression was represented by the absorbance value. RESULTS： Edaravone greatly reduced the focal infarct volume. Notchl and NF-κB protein and mRNA expression were rapidly upregulated following cerebral ischemia/reperfusion injury in model and edaravone groups compared with the sham operation group （P 〈 0.01 ）. In addition, edaravone treatment significantly upregulated Notchl expression but down-regulated NF-κB expression compared with model groups （P 〈 0.01）. CONCLUSION： Edaravone possibly protects brain tissue from ischemia/reperfusion injury by upregulating Notchl expression and regulating NF-κB expression.
文摘AIM： To investigate the potential role of nuclear factor kappa-B （NF-κB） activation on the reactive oxygen species in rat acute necrotizing pancreatitis （ANP） and to assess the effect of pyrrolidine dithiocarbamate （PDTC, an inhibitor of NF-κB）.METHODS： Rat ANP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. Rats were randomly assigned to three groups （10 rats each）： Control group, ANP group and PDTC group. At the 6^th of the model, the changes of the serum amylase,nitric oxide （NO）, malondialdehyde （MDA）, superoxide dismutase （SOD） and pancreatic morphological damage were observed. The expressions of inducible nitric oxide （iNOS） were observed by SP immunohistochemistry. And bhe expressions of NF-κB p65 subunit mRNA were observed by hybridization in situ.RESULTS： Serum amylase and NO level decreased significantly in ANP group as compared with PDTC administrated group [（7 170.40＋1 308.63） U/L vs（4 074.10＋1 719.78） U/L,P〈0.05], [（76.95±9.04） μmol/L vs （65.18±9.02） μmol/L,P〈0.05] respectively. MDA in both ANP and PDTC group rose significantly over that in control group [（9.88＋1.52）nmol/L, （8.60±1.41） nmol/L, vs （6.04：hl.78） nmol/L,P〈0.05], while there was no significant difference between them. SOD levels in both ANP and PDTC group underwent a significant decrease as compared with that in control[（3 214.59±297.74） NU/mL, （3 260.62±229.44） NU/mL,vs（3 977.80＋309.09） NU/mL, P〈0.05], but there was no significant difference between them. Though they were still higher bhan those in Control group, pancreas destruction was slighter in PDTC group, iNOS expression and NF-κB p65 subunit mRNA expression were lower in PDTC group as compared with ANP group.CONCLUSION： We conclude that correlation among NF-κB activation, serum amylase, reactive oxygen species level and tissue damage suggests a key role of NF-κB in the pathogenesis of ANP. Inhibition of NF-κB activation may reverse the pancreatic damage of rat ANP and the production of reactive oxygen species.
文摘Objective： To explore the combination effects of all-trans retinoic acid （ATRA） with interferon-gamma （IFN-γ） on human hepatocarcinoma cell line SMMC-7721 and the mechanism of action. Methods： SMMC-7721 cells were divided into treated group and control group. The cells were treated with ATRA or ATRA＋ IFN-γ in the former and added with PBS in the latter. The inhibition rate of SMMC-7721 cell proliferation was detected by MTT, the cell change in morphology was observed by electron microscope. The apoptosis was detected by flow cytometry and the expression changes of nuclear factor-kappaB （NF-κB） was analyzed by Western blotting when the SMMC-7721 cells were treated with ATRA and IFN-γ. Results： The SMMC-7721 cell proliferation was suppressed and apoptosis was induced after the cells were treated with ATRA treatment, and these effects were enhanced when ATRA was combined with IFN-γ. The expression of NF-κB was reduced after SMMC-7721 cell was treated with ATRA, and reduced significantly when the cells were treated with the combination of ATRA and IFN-γ. Conclusion： IFN-γ can enhance the inhibiting effects of ATRA on cell proliferation and inducing apoptosis on SMMC-7721 cell and these effects might be mediated by inhibiting the expression of NF-κB.
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This work was supported by grants from the National Natural Science Foundation of China （No. 30671974 and 81070598）. The authors declare no conflict of interest.
文摘Background Increased levels of plasma lipopolysaccharide （LPS） have been found in obesity and diabetes patients. This study was to investigate the effect of LPS on pancreatic beta-cell viability and the involvement of caspase 3 in NIT-1 cell line. Methods Mouse insulinoma NIT-1 cells were treated with LPS for the indicated time and dose. Cell viability was measured by cell counting kit-8 reagent. Toll-like receptor 4 （TLR4）, caspase 3 and cleaved caspase 3 were detected by Western blotting. Insulin was determined by radioimmunoassay （RIA）. Results LPS promoted NIT-1 cell proliferation at 1 μg/ml, peaked at 72 hours of incubation. A reduction in cleavage of caspase 3 was observed upon LPS treatment. Bay11-7082, a specific inhibitor of nuclear factor （NF）-κB, blunted LPS-induced inhibition of caspase 3 cleavage. Reduction in chronic insulin secretion was observed after treatment with LPS at 1 μg/ml for 48 and 72 hours, not for 24 hours. TLR4 protein was upregulated when NIT-1 cells were treated with LPS at 1 μg/ml for 24 hours. Conclusions LPS promotes early NIT-1 cell proliferation in association with NF-KB-mediated inhibition of caspase 3 cleavage. LPS exerts a time-dependent inhibitory effect on chronic insulin secretion from NIT-1 cells.
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.
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.
文摘G-quadruplexes,which are unique nucleic acid secondary structures formed by the folding of guaninerich DNA or RNA,are closely related to essential biological activities.They exhibit extensive application prospects owing to their abundant binding sites and distinct physicochemical properties.Therefore,G-quadruplexes have attracted widespread attention in recent decades.Nuclear magnetic resonance(NMR)technology is an ideal tool for characterizing molecular structures and plays a crucial role in exploring the self-assembly process of G-quadruplexes.In this article,we introduce the basic concepts of NMR,followed by reviewing the applications of NMR in G-quadruplexes.Finally,challenges and prospects of NMR technology in the field of G-quadruplex research are discussed.
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.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.
文摘In complex systems,there is a kind of parameters having only a minor impact on the outputs in most cases,but their accurate values are still critical for the operation of systems.In this paper,the authors focus on the identification of these weak influence parameters in the complex systems and propose a identification model based on the parameter recursion.As an application,three parameters of the steam generator are identified,that is,the valve opening,the valve CV value,and the reference water level,in which the valve opening and the reference water level are weak influence parameters under most operating conditions.Numerical simulation results show that,in comparison with the multi-layer perceptron(MLP),the identification error rate is decreased.Actually,the average identification error rate for the valve opening decreases by 0.96%,for the valve CV decreases by 0.002%,and for the reference water level decreases by 12%after one recursion.After two recursions,the average identification error rate for the valve opening decreases by 11.07%,for the valve CV decreases by 2.601%,and for the reference water level decreases by 95.79%.This method can help to improve the control of the steam generator.
文摘This study investigates the establishment of scientific links between the People's Republic of China(PRC)and the United Kingdom(UK)in the mid-2Oth century,focusing on the early development of China's nuclear industry.Sino-British scientific interactions took place across multiple dimensions,involving various institutions and individuals.Around 1949,UK-trained Chinese nuclear scientists returned to China,bringing advanced technological knowledge and extensive practical experience.The PRC regarded the UK as a crucial gateway to overcoming the technological blockade imposed by the United States(and later the Soviet Union)and sought to establish scientific relations with the UK through semi-official and unofficial channels.Specifically,these connections manifested in the interactions between the Chinese Academy of Sciences(CAS)and the Royal Society of London,the guiding role of the Chinese Charge d'Affaires Office in London in facilitating scientific and technological exchanges,and the technology investigations led by the Ministry of Foreign Trade in the name of trade.Additionally,the Sino-British scientific network extended to the international arena,allowing China to engage in nuclear-related global organizations and events.This study highlights the significant British influence on the early development of China's nuclear industry,revealing the extent of its British influence.It argues that China's urgent need for nuclear science and industrial advancement was a key driver of its scientific engagement withthe UK.
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.
文摘Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.
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 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.
