AIM:To assess the prognostic significance of nuclear factor-kB (NF-kB) and its target genes in gastric cancer. METHODS:The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using m...AIM:To assess the prognostic significance of nuclear factor-kB (NF-kB) and its target genes in gastric cancer. METHODS:The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-kB RelA. Preoperative serum levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured via immunotrubidimetry. RESULTS:Positive rate of NF-kB RelA was 42.6%. NF-kB RelA expression in tumor tissues was also related to serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL-6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated that immunostaining of NF-kB RelA, levels of IL-6, VEGF, SAA were significantly related with both disease free survival and over-all survival (OS). Multivariate analysis verified that NF-kB RelA [hazard ratio (HR): 3.40, P = 0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS. CONCLUSION: Increased expression of NF-kB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients.展开更多
AIM In this study we investigated the relationship of the X protein of HBV and nuclear factor-κB(NF-κB)and the expression of NF-κB in human hepatocellular carcinoma tissues. METHODS Immunohistochemistry SP method w...AIM In this study we investigated the relationship of the X protein of HBV and nuclear factor-κB(NF-κB)and the expression of NF-κB in human hepatocellular carcinoma tissues. METHODS Immunohistochemistry SP method was used to detect the expression of NF-κB and the X protein of HBV in human hepatocellular carcinoma tissues of 52 cases.Gene transfection mediated by lipofectamine was used to transfect the eukaryotic expression vector pCDNA3.1-HBX of HBV x gene into human hepatocellular carcinoma cell line HCC-9204 and NF-κB was detected. RESULTS NF-κB was widely expressed in human hepatocellular carcinoma tissues in a total of 52 cases and its expression was related to the X protein of HBV.NF-κB was localized both in the cytoplasm and the nuclei of hepatocellular carcinoma cells in 11 cases which were positive for the X protein of HBV while in 41 cases negative for the X protein of HBV,NF-κB was only localized in the cytoplasm of hepatocellular carcinoma cells but translocated to the nuclei of hepatocellular carcinoma cells after the eukaryotic expression vector pCDNA3.1-HBX was transfected into HCC-9204 cells. CONCLUSION This study strongly suggests that the nuclear factor NF-κB is widely expressed in hepatocellular carcinoma tissues in different styles according to the expression of the X protein of HBV.NF-κB is abnormally activated in hepatocellular carcinoma,which is probably rélated to the X protein of HBV.The X protein of HBV can activate NF-κB to translocate into nuclei of hepatocellular carcinoma cells.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
When the operating temperature of a solid oxide electrolysis cell(SOEC)is lower than the outlet temperature of a nuclear reactor,the reactor can be directly coupled with the SOEC as a high-temperature heat source.Howe...When the operating temperature of a solid oxide electrolysis cell(SOEC)is lower than the outlet temperature of a nuclear reactor,the reactor can be directly coupled with the SOEC as a high-temperature heat source.However,the key to the efficiency and return on investment of this hybrid energy system lies in the expected lifetime of the SOEC.This study assessed Ni-YSZ|YSZ|GDC|LSC fuel electrode support cells’long-term stability during electrolysis at 650℃with a current density of−0.5Acm^(−2)over 1818 h.The average voltage degradation rate of 2.63%kh^(−1)unfolded in two phases:an initial rapid decay(90 to 1120 h at 3.58%kh^(−1))and a stable decay(1120 to 1818 h at 2.14%kh^(−1)),emphasizing SOECs’probability coupling with nuclear reactors at 650℃.Post-1818-hour electrolysis revealed nickel particle formation associated with Ni(OH)_(x)diffusion and re-deposition,alongside a strontium-containing layer causing interface cracking.Despite minimal strontium segregation in the EDS,XPS data indicated surface segregation of Sr.This study provides crucial insights into prolonged SOEC operation,highlighting both its potential and challenges.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
The process of nuclear fusion in the presence of a laser field was theoretically analyzed.The analysis is applicable to most fusion reactions and different types of currently available intense lasers,from X-ray free-e...The process of nuclear fusion in the presence of a laser field was theoretically analyzed.The analysis is applicable to most fusion reactions and different types of currently available intense lasers,from X-ray free-electron lasers to solid-state near-infrared lasers.Laser fields were shown to enhance the fusion yields,and the mechanism of this enhancement was explained.Low-frequency lasers are more efficient in enhancing fusion than high-frequency lasers.The calculation results show enhancements of fusion yields by orders of magnitude with currently available intense low-frequency laser fields.The temperature requirement for controlled nuclear fusion may be reduced with the aid of intense laser fields.展开更多
Nuclear heating plays an important aspect in design and deployment of both fission and fusion reactors and experimental devices in terms of cooling requirements. Two experimental campaigns in the framework of a collab...Nuclear heating plays an important aspect in design and deployment of both fission and fusion reactors and experimental devices in terms of cooling requirements. Two experimental campaigns in the framework of a collaboration project between the French Atomic and Alternative Energy Commission(CEA) and Jožef Stefan Institute(JSI), Slovenia, have been performed at the JSI TRIGA reactor for the experimental assessment of nuclear heating in fission and fusion-relevant materials by the differential calorimetry technique, based on the CALMOS and CARMEN differential calorimeters, previously developed at CEA. The results of the first campaign performed at reactor powers between 100 and 250 kW have already been reported, highlighting some measurement difficulties. Therefore, the second campaign was performed at a lower reactor power of 30 kW to overcome these issues. Moreover, a computational analysis of the experiments was performed using the JSIR2S code package to calculate the nuclear heating levels. Both experiments and their reproduction by simulations are described in detail. We present a comparison of the previously reported measured nuclear heating values of the first campaign with the computational results, with consistent underestimation by simulations by 8–35%. We report the experimental and computational results for the second experimental campaign performed at a reactor power of 30 kW. The simulated heating values were in agreement with the measurements within the measured heating uncertainty, with simulated heating 2.7–11.3% lower than the experimental values.展开更多
To clarify fluid flow mechanisms and establish effective development conditions in continental shale oil reservoirs,a high-temperature,high-pressure steady-state flow system integrated with nuclear magnetic resonance(...To clarify fluid flow mechanisms and establish effective development conditions in continental shale oil reservoirs,a high-temperature,high-pressure steady-state flow system integrated with nuclear magnetic resonance(NMR)technology has been developed.The apparatus combines sample evacuation,rapid pressurization and saturation,and controlled displacement,enabling systematic investigation of single-phase shale oil flow under representative reservoir conditions.Related experiments allow proper quantification of the activation thresholds and relative contributions of different pore types to flow.A movable fluid index(MFI),defined using dual T_(2) cutoff values,is introduced accordingly and linked to key flow parameters.The results reveal distinct multi-scale characteristics of single-phase shale oil transport,namely micro-scale graded displacement and macro-scale segmented nonlinear behavior.As the injection-production pressure difference increases,flow pathways are activated progressively,beginning with fractures,followed by large and then smaller macropores,leading to a pronounced enhancement in apparent permeability.Although mesopores and micropores contribute little to direct flow,their indirect influence becomes increasingly important,and apparent permeability gradually approaches a stable limit at higher pressure difference.It is also shown that the MFI exhibits a strong negative correlation with the starting pressure gradient and a positive correlation with apparent permeability,providing a rapid and reliable indicator of shale oil flow capacity.Samples containing through-going fractures display consistently higher MFI values and superior flowability compared with those dominated by laminated fractures,highlighting the pivotal role of well-connected fracture networks generated by large-scale hydraulic fracturing in improving shale oil production.展开更多
Recent advances in atomic optical clocks based on electronic transitions have achieved frequency uncertainties at the10^(-19)level,enabling wide applications in testing variations of physical constants,exploring dark ...Recent advances in atomic optical clocks based on electronic transitions have achieved frequency uncertainties at the10^(-19)level,enabling wide applications in testing variations of physical constants,exploring dark matter signatures,and enhancing precision metrology for position,navigation,and timing systems.To pursue higher-precision optical clocks,the development of nuclear optical clocks has emerged,with the^(229)Th system distinguished by its unique low-lying isomeric state at~8.4 eV and a natural linewidth of approximately 100μHz,promising uncertainties below 10^(-19).The intrinsic insensitivity of nuclear transitions to external perturbations and their subatomic-scale spatial confinement provide significant advantages over electronic transitions in mitigating environmental shifts.Recent experimental breakthroughs include the excitation of the nuclear clock transition in solid-state^(229)Th-doped crystals with spectral resolution at the k Hz level.However,critical challenges persist,particularly in implementing effective laser excitation schemes(e.g.,via the electronic bridge mechanism)and closed-loop quantum control in trapped ion systems.Addressing these requires comprehensive understanding of complex many-body interactions in^(229)Th,encompassing electronic structure,nuclear deformation,hyperfine and field shift,and solid-state environmental coupling.This review synthesizes recent advancements in(i)the characterization of nuclear and atomic structures of the^(229)Th nuclear clock,and(ii)precise evaluation and mitigation of external perturbations affecting the clock transitions.The analysis provides a solid theoretical and experimental foundation for optimizing^(229)Th-based nuclear clock performance.展开更多
The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The mai...The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The main distribution area of the C. angulata is located in Fujian, South China. In total, 420 C. angulata were collected from 14 natural habitats(populations) along the Fujian coast, and their genetic diversity and structure were analyzed in the mitochondrial COI and nuclear gene ITS2 sequences. Results reveal that all the 14 populations of C. angulata exhibited high levels of genetic diversity, with a total of 57(haplotype diversity: 0.811±0.016) and 124(haplotype diversity: 0.912±0.007) haplotypes revealed by COI and ITS2, respectively. Notably, significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ) population(FS T by COI: 0.035–0.142, P<0.05;FS T by ITS2: 0.078–0.123, P<0.05) with other populations were observed for the first time, which is also supported by the results of molecular variance analysis(FC T by COI: 0.105, P<0.05;FC T by ITS2: 0.086, P<0.05) and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree. Furthermore, the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations. In addition, the population dynamics analysis suggests that the C. angulata may have undergone expansion during the third ice age of the Pleistocene. These results provide a reference for the preservation and further genetic improvement of C. angulata.展开更多
Owing to the presence of a low-energy,long-lived nuclear isomeric state,^(229)Th is an ideal candidate for developing the next generation clock—the nuclear clock—holding great promise for both applied and fundamenta...Owing to the presence of a low-energy,long-lived nuclear isomeric state,^(229)Th is an ideal candidate for developing the next generation clock—the nuclear clock—holding great promise for both applied and fundamental physics.The^(229)Th ionic nuclear optical clock has garnered considerable attention,attributed to its high precision with a relative uncertainty of≤1.5×10^(-19)and the potential for common-mode noise cancellation via self-comparison between the nuclear transition and the electronic transition of thorium ions.In this article,we focus on Th^(n+)ions(n=1,2,3)and present a comprehensive review of the current progress in the development of ionic nuclear clocks,covering essential steps such as ion generation,trapping,and cooling.Furthermore,we discuss the realization of a closed-loop clock cycle,addressing key aspects including stable isomer excitation and efficient isomer deexcitation.展开更多
Background: Osteoporosis is a common complication of chronic obstructive pulmonary disease (COPD). Recent clinical and biological researches have increasingly delineated the biomolecular pathways of bone metabolism re...Background: Osteoporosis is a common complication of chronic obstructive pulmonary disease (COPD). Recent clinical and biological researches have increasingly delineated the biomolecular pathways of bone metabolism regulation in COPD. We extended this work by examining the specific association and potential contribution of the osteoprotegerin (OPG)/receptor activator of nuclear factor-riB ligand (RANKL) axis to the pathogenesis of osteoporosis in advanced COPD. The aim of this study was to assess the relationships of serum OPG, RANKL, and tumor necrosis factor-alpha (TNF-a) with bone turnover in men with very severe COPD. Methods: Pulmonary function, T-score at the lumbar spine (LS) and femoral neck (FN), serum OPG, RANKL, soluble receptor of tumor necrosis factor-alpha-1 and 11 (sTNFR-I, sTNFR-II), osteocalcin (OC), and β-CrossLaps (βCL) levels were measured in 45 men with very severe stage COPD and 36 male non-COPD volunteers. COPD patients and healthy controls were compared using all independent t-test and Mann-Whitney U-test. The Pearson coefficient was used to assess the relationships between variables. Results: OPG and OC were lower in male COPD patients than in control subjects whereas RANKL, serum ~CL, TN F-o~, and its receptors were higher. OPG directly correlated with forced expiratory volume in I s (FEVI) % predicted (r = 0.46, P 〈 0.005), OC (r= 0.34, P 〈 0.05), LS (I.= 0.56, P 〈 0.001 ), and FN T-score (r= 0.47, P 〈 0.01 ). In contrast, serum RANKL inversely associated with LS and FN T-score (r = -0.62, P 〈 0.001 and r = -0.48, P 〈 0.001 ) but directly correlated with [3CL (r = 0.48, P 〈 0.001 ). In addition, OPG was inversely correlated with RANKL (r = -0.39, P 〈 0.01 ), TNF-a (r = -0.56, P 〈 0.001 ), and sTNFR-I (r = -0.40, P 〈 0.01 ). Conelusion: Our results suggest that serum OPG and RANKL levels are inversely associated with bone loss in men with advanced stage COPD.展开更多
Background A20, also known as tumor necrosis factor α induced protein 3 （TNFaip3）, is a cytoplasmic zinc finger protein that inhibits nuclear factor kappa-B （NF-κB） activity and prevents tumor necrosis factor （...Background A20, also known as tumor necrosis factor α induced protein 3 （TNFaip3）, is a cytoplasmic zinc finger protein that inhibits nuclear factor kappa-B （NF-κB） activity and prevents tumor necrosis factor （TNF）-mediated programmed cell death. NF-κB is a transcription factor that regulates expression of genes involved in cell proliferation, cell survival and anti-apoptosis. Several studies have implicated that the NF-κB signal pathway is associated with angiogenesis and clinico-pathological process of adenoid cystic carcinoma （ACC） of the salivary glands.Methods The ability of overexpression of A2.0 to influence the biological behavior and invasion of ACC cells was examined. The cells were stably transfected with full-length A20 cDNA. Stable gene transfer was verified by realtime-polymerase chain reaction （PCR） and Western blot analysis. The change of cell biological behavior was examined by methyl thiazolyl tetrazolium （MTT） and NF-κB luciferase reporter assay and the invasion of the cells was examined by a Matrigel invasion chamber.Results pEGPFN3-A2.0 gene was stably transferred into ACC-2 cells and overexpressed. When cells were treated with TNFα, the NF-κB activity of ACC-2-A20 cells could be down-regulated about 46.32% in contrast to ACC-2-GFP cells （P〈0.05）. A20 potently inhibited growth of A20 transfectant ACC-2-A20 compared with control vector transfected groups and the ACC-2 empty control group （P〈0.05）. The ACC-2-A20 cells showed significantly reduced ability to invade through Matdgei-coated filters compared to ACC-2-GFP and ACC-2 cells. The inhibition rate was up to 71.05% （P〈0.05）. Conclusions A2.0 gene transfer is associated with decreased tumor invasion, in part via the down-regulation of NF-κB expression, providing evidence for a potential application of A20 in designing a treatment modality for salivary gland cancers such as ACC.展开更多
Background： In addition to neurons, all components of the neurovascular unit （NVU）, such as glial, endothelial, and basal membranes, are destroyed during traumatic brain injury （TBI）. Previous studies have shown ...Background： In addition to neurons, all components of the neurovascular unit （NVU）, such as glial, endothelial, and basal membranes, are destroyed during traumatic brain injury （TBI）. Previous studies have shown that excessive stimulation ofcalpain is crucial for cerebral injury after traumatic insult. The objective of this study was to investigate whether calpain activation participated in NVU disruption and edema formation in a mouse model of controlled cortical impact （CCI）. Methods： One hundred and eight mice were divided into three groups： the sham group, the control group, and the MDL28170 group. MDL28170 （20 mg/kg）, an efficient calpain inhibitor, was administered intraperitoneally at 5 rain, 3 h, and 6 h after experimental CCI. We then measured neurobehavioral deficits, calpain activity, inflammatory mediator levels, blood-brain barrier （BBB） disruption, and NVU deficits using electron microscopy and histopathological analysis at 6 h and 24 h after CCI. Results： The MDL28170 treatment significantly reduced the extent of both cerebral contusion （MDL28170 vs. vehicle group, 16.90 ± 1.01 mm3 and 17.20±1.17 mm3 vs. 9.30 ± 1.05 mm^3 and 9.90 ± 1.17 mm3, both P 〈 0.001 ） and edema （M DL28170 vs. vehicle group, 80.76 ± 1.25% and 82.00 ± 1.84% vs. 82.55 ± 1.32% and 83.64 ± 1.25%, both P 〈 0.05）, improved neurological scores （MDL28170 vs. vehicle group, 7.50 ±0.45 and 6.33 ±0.38 vs. 12.33 ± 0.48 and 11.67±0.48, both P 〈 0.001）, and attenuated NVU damage resulting （including tight junction （TJ）, basement membrane, BBB, and neuron） from CCI at 6 h and 24 h. Moreover, MDL28170 markedly downregulated nuclear factor-κB-related inflammation （tumor necrosis factor-α [TNF-α]： MDL28170 vs. vehicle group, 1.15 ± 0.07 and 1.62± 0.08 vs. 1.59±0.10 and 2.18± 0.10, both P 〈 0.001 ： inducible nitric oxide synthase： M DL28170 vs. vehicle group, 4.51± 0.23 vs. 6.23± 0.12, P 〈 0.001 at 24 h; intracellular adhesion molecule- I ： MDL28170 vs. vehicle group, 1.45± 0.13 vs. 1.70 ± 0.12, P 〈 0.01 at 24 h） and lessened both myeloperoxidase activity （MDL28170 vs. vehicle group, 0.016± 0.001 and 0.016± 0.001 vs. 0.024± 0.001 and 0.023 ± 0.001, P 〈 0.001 and 0.01, respectively） and matrix metalloproteinase-9 （MMP-9） levels （MDL28170 vs. vehicle group, 0.87±0.13 and 1.10 ± 0.10 vs. 1.17 ± 0.13 and 1.25 ± 0.12, P 〈 0.001 and 0±05, respectively） at 6 h and 24 h after CCI. Conclusions： These findings demonstrate that MDL28170 can protect the structure of the NVU by inhibiting the inflammatory cascade, reducing the expression of MMP-9, and supporting the integrity of TJ during acute TBI.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
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
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
基金Supported by The Dong-A University Research Fund
文摘AIM:To assess the prognostic significance of nuclear factor-kB (NF-kB) and its target genes in gastric cancer. METHODS:The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-kB RelA. Preoperative serum levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured via immunotrubidimetry. RESULTS:Positive rate of NF-kB RelA was 42.6%. NF-kB RelA expression in tumor tissues was also related to serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL-6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated that immunostaining of NF-kB RelA, levels of IL-6, VEGF, SAA were significantly related with both disease free survival and over-all survival (OS). Multivariate analysis verified that NF-kB RelA [hazard ratio (HR): 3.40, P = 0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS. CONCLUSION: Increased expression of NF-kB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients.
文摘AIM In this study we investigated the relationship of the X protein of HBV and nuclear factor-κB(NF-κB)and the expression of NF-κB in human hepatocellular carcinoma tissues. METHODS Immunohistochemistry SP method was used to detect the expression of NF-κB and the X protein of HBV in human hepatocellular carcinoma tissues of 52 cases.Gene transfection mediated by lipofectamine was used to transfect the eukaryotic expression vector pCDNA3.1-HBX of HBV x gene into human hepatocellular carcinoma cell line HCC-9204 and NF-κB was detected. RESULTS NF-κB was widely expressed in human hepatocellular carcinoma tissues in a total of 52 cases and its expression was related to the X protein of HBV.NF-κB was localized both in the cytoplasm and the nuclei of hepatocellular carcinoma cells in 11 cases which were positive for the X protein of HBV while in 41 cases negative for the X protein of HBV,NF-κB was only localized in the cytoplasm of hepatocellular carcinoma cells but translocated to the nuclei of hepatocellular carcinoma cells after the eukaryotic expression vector pCDNA3.1-HBX was transfected into HCC-9204 cells. CONCLUSION This study strongly suggests that the nuclear factor NF-κB is widely expressed in hepatocellular carcinoma tissues in different styles according to the expression of the X protein of HBV.NF-κB is abnormally activated in hepatocellular carcinoma,which is probably rélated to the X protein of HBV.The X protein of HBV can activate NF-κB to translocate into nuclei of hepatocellular carcinoma cells.
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 Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA0400000),the Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.2021253)+1 种基金the Major Science and Technology Projects of China National Offshore Oil Corporation Limited during the 14th Five Year Plan(No.KJGG-2022-12-CCUS-030500)the Photon Science Center for Carbon Neutrality of Chinese Academy of Science.
文摘When the operating temperature of a solid oxide electrolysis cell(SOEC)is lower than the outlet temperature of a nuclear reactor,the reactor can be directly coupled with the SOEC as a high-temperature heat source.However,the key to the efficiency and return on investment of this hybrid energy system lies in the expected lifetime of the SOEC.This study assessed Ni-YSZ|YSZ|GDC|LSC fuel electrode support cells’long-term stability during electrolysis at 650℃with a current density of−0.5Acm^(−2)over 1818 h.The average voltage degradation rate of 2.63%kh^(−1)unfolded in two phases:an initial rapid decay(90 to 1120 h at 3.58%kh^(−1))and a stable decay(1120 to 1818 h at 2.14%kh^(−1)),emphasizing SOECs’probability coupling with nuclear reactors at 650℃.Post-1818-hour electrolysis revealed nickel particle formation associated with Ni(OH)_(x)diffusion and re-deposition,alongside a strontium-containing layer causing interface cracking.Despite minimal strontium segregation in the EDS,XPS data indicated surface segregation of Sr.This study provides crucial insights into prolonged SOEC operation,highlighting both its potential and challenges.
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(Nos.12405288,12374241,12474484,U2330401,12088101)the Natural Science Foundation of Top Talent of SZTU(No.GDRC202526)。
文摘The process of nuclear fusion in the presence of a laser field was theoretically analyzed.The analysis is applicable to most fusion reactions and different types of currently available intense lasers,from X-ray free-electron lasers to solid-state near-infrared lasers.Laser fields were shown to enhance the fusion yields,and the mechanism of this enhancement was explained.Low-frequency lasers are more efficient in enhancing fusion than high-frequency lasers.The calculation results show enhancements of fusion yields by orders of magnitude with currently available intense low-frequency laser fields.The temperature requirement for controlled nuclear fusion may be reduced with the aid of intense laser fields.
基金supported by the Slovenian Research Agency(research project NC-0001-Analysis of nuclear heating in a reactor,research core funding Reactor physics No.P2-0073,infrastructure program I0-0005)。
文摘Nuclear heating plays an important aspect in design and deployment of both fission and fusion reactors and experimental devices in terms of cooling requirements. Two experimental campaigns in the framework of a collaboration project between the French Atomic and Alternative Energy Commission(CEA) and Jožef Stefan Institute(JSI), Slovenia, have been performed at the JSI TRIGA reactor for the experimental assessment of nuclear heating in fission and fusion-relevant materials by the differential calorimetry technique, based on the CALMOS and CARMEN differential calorimeters, previously developed at CEA. The results of the first campaign performed at reactor powers between 100 and 250 kW have already been reported, highlighting some measurement difficulties. Therefore, the second campaign was performed at a lower reactor power of 30 kW to overcome these issues. Moreover, a computational analysis of the experiments was performed using the JSIR2S code package to calculate the nuclear heating levels. Both experiments and their reproduction by simulations are described in detail. We present a comparison of the previously reported measured nuclear heating values of the first campaign with the computational results, with consistent underestimation by simulations by 8–35%. We report the experimental and computational results for the second experimental campaign performed at a reactor power of 30 kW. The simulated heating values were in agreement with the measurements within the measured heating uncertainty, with simulated heating 2.7–11.3% lower than the experimental values.
基金supported by the National Science and Technology Major Project of China(Grant No.2024ZD 1004302)the Key Scientific and Technological Research project of SINOPEC(Grant No.P25186).
文摘To clarify fluid flow mechanisms and establish effective development conditions in continental shale oil reservoirs,a high-temperature,high-pressure steady-state flow system integrated with nuclear magnetic resonance(NMR)technology has been developed.The apparatus combines sample evacuation,rapid pressurization and saturation,and controlled displacement,enabling systematic investigation of single-phase shale oil flow under representative reservoir conditions.Related experiments allow proper quantification of the activation thresholds and relative contributions of different pore types to flow.A movable fluid index(MFI),defined using dual T_(2) cutoff values,is introduced accordingly and linked to key flow parameters.The results reveal distinct multi-scale characteristics of single-phase shale oil transport,namely micro-scale graded displacement and macro-scale segmented nonlinear behavior.As the injection-production pressure difference increases,flow pathways are activated progressively,beginning with fractures,followed by large and then smaller macropores,leading to a pronounced enhancement in apparent permeability.Although mesopores and micropores contribute little to direct flow,their indirect influence becomes increasingly important,and apparent permeability gradually approaches a stable limit at higher pressure difference.It is also shown that the MFI exhibits a strong negative correlation with the starting pressure gradient and a positive correlation with apparent permeability,providing a rapid and reliable indicator of shale oil flow capacity.Samples containing through-going fractures display consistently higher MFI values and superior flowability compared with those dominated by laminated fractures,highlighting the pivotal role of well-connected fracture networks generated by large-scale hydraulic fracturing in improving shale oil production.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant Nos.XDB0920100 and XDB0920101)the National Natural Science Foundation of China(Grant Nos.12174402,12393821,12274417)the Chinese Academy of Sciences Project for Young Scientists in Basic Research(Grant No.YSBR-055)。
文摘Recent advances in atomic optical clocks based on electronic transitions have achieved frequency uncertainties at the10^(-19)level,enabling wide applications in testing variations of physical constants,exploring dark matter signatures,and enhancing precision metrology for position,navigation,and timing systems.To pursue higher-precision optical clocks,the development of nuclear optical clocks has emerged,with the^(229)Th system distinguished by its unique low-lying isomeric state at~8.4 eV and a natural linewidth of approximately 100μHz,promising uncertainties below 10^(-19).The intrinsic insensitivity of nuclear transitions to external perturbations and their subatomic-scale spatial confinement provide significant advantages over electronic transitions in mitigating environmental shifts.Recent experimental breakthroughs include the excitation of the nuclear clock transition in solid-state^(229)Th-doped crystals with spectral resolution at the k Hz level.However,critical challenges persist,particularly in implementing effective laser excitation schemes(e.g.,via the electronic bridge mechanism)and closed-loop quantum control in trapped ion systems.Addressing these requires comprehensive understanding of complex many-body interactions in^(229)Th,encompassing electronic structure,nuclear deformation,hyperfine and field shift,and solid-state environmental coupling.This review synthesizes recent advancements in(i)the characterization of nuclear and atomic structures of the^(229)Th nuclear clock,and(ii)precise evaluation and mitigation of external perturbations affecting the clock transitions.The analysis provides a solid theoretical and experimental foundation for optimizing^(229)Th-based nuclear clock performance.
基金Supported by the National Natural Science Foundation of China(No.32172979)the Natural Science Foundation of Fujian Province(No.2021J05159)the 2023 Special Program for Promoting High-Quality Development of Marine and Fishery Industry in Fujian Province(No.PJHYF-L-2023-2)。
文摘The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The main distribution area of the C. angulata is located in Fujian, South China. In total, 420 C. angulata were collected from 14 natural habitats(populations) along the Fujian coast, and their genetic diversity and structure were analyzed in the mitochondrial COI and nuclear gene ITS2 sequences. Results reveal that all the 14 populations of C. angulata exhibited high levels of genetic diversity, with a total of 57(haplotype diversity: 0.811±0.016) and 124(haplotype diversity: 0.912±0.007) haplotypes revealed by COI and ITS2, respectively. Notably, significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ) population(FS T by COI: 0.035–0.142, P<0.05;FS T by ITS2: 0.078–0.123, P<0.05) with other populations were observed for the first time, which is also supported by the results of molecular variance analysis(FC T by COI: 0.105, P<0.05;FC T by ITS2: 0.086, P<0.05) and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree. Furthermore, the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations. In addition, the population dynamics analysis suggests that the C. angulata may have undergone expansion during the third ice age of the Pleistocene. These results provide a reference for the preservation and further genetic improvement of C. angulata.
基金Project supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB0920000)the National Natural Science Foundation of China(Grant No.12341401)。
文摘Owing to the presence of a low-energy,long-lived nuclear isomeric state,^(229)Th is an ideal candidate for developing the next generation clock—the nuclear clock—holding great promise for both applied and fundamental physics.The^(229)Th ionic nuclear optical clock has garnered considerable attention,attributed to its high precision with a relative uncertainty of≤1.5×10^(-19)and the potential for common-mode noise cancellation via self-comparison between the nuclear transition and the electronic transition of thorium ions.In this article,we focus on Th^(n+)ions(n=1,2,3)and present a comprehensive review of the current progress in the development of ionic nuclear clocks,covering essential steps such as ion generation,trapping,and cooling.Furthermore,we discuss the realization of a closed-loop clock cycle,addressing key aspects including stable isomer excitation and efficient isomer deexcitation.
基金This study was supported by the grant from the Russian Science Foundation (No. 14-33-00009).
文摘Background: Osteoporosis is a common complication of chronic obstructive pulmonary disease (COPD). Recent clinical and biological researches have increasingly delineated the biomolecular pathways of bone metabolism regulation in COPD. We extended this work by examining the specific association and potential contribution of the osteoprotegerin (OPG)/receptor activator of nuclear factor-riB ligand (RANKL) axis to the pathogenesis of osteoporosis in advanced COPD. The aim of this study was to assess the relationships of serum OPG, RANKL, and tumor necrosis factor-alpha (TNF-a) with bone turnover in men with very severe COPD. Methods: Pulmonary function, T-score at the lumbar spine (LS) and femoral neck (FN), serum OPG, RANKL, soluble receptor of tumor necrosis factor-alpha-1 and 11 (sTNFR-I, sTNFR-II), osteocalcin (OC), and β-CrossLaps (βCL) levels were measured in 45 men with very severe stage COPD and 36 male non-COPD volunteers. COPD patients and healthy controls were compared using all independent t-test and Mann-Whitney U-test. The Pearson coefficient was used to assess the relationships between variables. Results: OPG and OC were lower in male COPD patients than in control subjects whereas RANKL, serum ~CL, TN F-o~, and its receptors were higher. OPG directly correlated with forced expiratory volume in I s (FEVI) % predicted (r = 0.46, P 〈 0.005), OC (r= 0.34, P 〈 0.05), LS (I.= 0.56, P 〈 0.001 ), and FN T-score (r= 0.47, P 〈 0.01 ). In contrast, serum RANKL inversely associated with LS and FN T-score (r = -0.62, P 〈 0.001 and r = -0.48, P 〈 0.001 ) but directly correlated with [3CL (r = 0.48, P 〈 0.001 ). In addition, OPG was inversely correlated with RANKL (r = -0.39, P 〈 0.01 ), TNF-a (r = -0.56, P 〈 0.001 ), and sTNFR-I (r = -0.40, P 〈 0.01 ). Conelusion: Our results suggest that serum OPG and RANKL levels are inversely associated with bone loss in men with advanced stage COPD.
基金Chinese National Natural and Scientific Committee(No.30330580)
文摘Background A20, also known as tumor necrosis factor α induced protein 3 （TNFaip3）, is a cytoplasmic zinc finger protein that inhibits nuclear factor kappa-B （NF-κB） activity and prevents tumor necrosis factor （TNF）-mediated programmed cell death. NF-κB is a transcription factor that regulates expression of genes involved in cell proliferation, cell survival and anti-apoptosis. Several studies have implicated that the NF-κB signal pathway is associated with angiogenesis and clinico-pathological process of adenoid cystic carcinoma （ACC） of the salivary glands.Methods The ability of overexpression of A2.0 to influence the biological behavior and invasion of ACC cells was examined. The cells were stably transfected with full-length A20 cDNA. Stable gene transfer was verified by realtime-polymerase chain reaction （PCR） and Western blot analysis. The change of cell biological behavior was examined by methyl thiazolyl tetrazolium （MTT） and NF-κB luciferase reporter assay and the invasion of the cells was examined by a Matrigel invasion chamber.Results pEGPFN3-A2.0 gene was stably transferred into ACC-2 cells and overexpressed. When cells were treated with TNFα, the NF-κB activity of ACC-2-A20 cells could be down-regulated about 46.32% in contrast to ACC-2-GFP cells （P〈0.05）. A20 potently inhibited growth of A20 transfectant ACC-2-A20 compared with control vector transfected groups and the ACC-2 empty control group （P〈0.05）. The ACC-2-A20 cells showed significantly reduced ability to invade through Matdgei-coated filters compared to ACC-2-GFP and ACC-2 cells. The inhibition rate was up to 71.05% （P〈0.05）. Conclusions A2.0 gene transfer is associated with decreased tumor invasion, in part via the down-regulation of NF-κB expression, providing evidence for a potential application of A20 in designing a treatment modality for salivary gland cancers such as ACC.
文摘Background： In addition to neurons, all components of the neurovascular unit （NVU）, such as glial, endothelial, and basal membranes, are destroyed during traumatic brain injury （TBI）. Previous studies have shown that excessive stimulation ofcalpain is crucial for cerebral injury after traumatic insult. The objective of this study was to investigate whether calpain activation participated in NVU disruption and edema formation in a mouse model of controlled cortical impact （CCI）. Methods： One hundred and eight mice were divided into three groups： the sham group, the control group, and the MDL28170 group. MDL28170 （20 mg/kg）, an efficient calpain inhibitor, was administered intraperitoneally at 5 rain, 3 h, and 6 h after experimental CCI. We then measured neurobehavioral deficits, calpain activity, inflammatory mediator levels, blood-brain barrier （BBB） disruption, and NVU deficits using electron microscopy and histopathological analysis at 6 h and 24 h after CCI. Results： The MDL28170 treatment significantly reduced the extent of both cerebral contusion （MDL28170 vs. vehicle group, 16.90 ± 1.01 mm3 and 17.20±1.17 mm3 vs. 9.30 ± 1.05 mm^3 and 9.90 ± 1.17 mm3, both P 〈 0.001 ） and edema （M DL28170 vs. vehicle group, 80.76 ± 1.25% and 82.00 ± 1.84% vs. 82.55 ± 1.32% and 83.64 ± 1.25%, both P 〈 0.05）, improved neurological scores （MDL28170 vs. vehicle group, 7.50 ±0.45 and 6.33 ±0.38 vs. 12.33 ± 0.48 and 11.67±0.48, both P 〈 0.001）, and attenuated NVU damage resulting （including tight junction （TJ）, basement membrane, BBB, and neuron） from CCI at 6 h and 24 h. Moreover, MDL28170 markedly downregulated nuclear factor-κB-related inflammation （tumor necrosis factor-α [TNF-α]： MDL28170 vs. vehicle group, 1.15 ± 0.07 and 1.62± 0.08 vs. 1.59±0.10 and 2.18± 0.10, both P 〈 0.001 ： inducible nitric oxide synthase： M DL28170 vs. vehicle group, 4.51± 0.23 vs. 6.23± 0.12, P 〈 0.001 at 24 h; intracellular adhesion molecule- I ： MDL28170 vs. vehicle group, 1.45± 0.13 vs. 1.70 ± 0.12, P 〈 0.01 at 24 h） and lessened both myeloperoxidase activity （MDL28170 vs. vehicle group, 0.016± 0.001 and 0.016± 0.001 vs. 0.024± 0.001 and 0.023 ± 0.001, P 〈 0.001 and 0.01, respectively） and matrix metalloproteinase-9 （MMP-9） levels （MDL28170 vs. vehicle group, 0.87±0.13 and 1.10 ± 0.10 vs. 1.17 ± 0.13 and 1.25 ± 0.12, P 〈 0.001 and 0±05, respectively） at 6 h and 24 h after CCI. Conclusions： These findings demonstrate that MDL28170 can protect the structure of the NVU by inhibiting the inflammatory cascade, reducing the expression of MMP-9, and supporting the integrity of TJ during acute TBI.
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.
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.
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.
