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Astragaloside IV suppresses post-ischemic natural killer cell infiltration and activation in the brain: involvement of histone deacetylase inhibition

Baokai Dou, Shichun Li, Luyao Wei, Lixin Wang, Shiguo Zhu, Zhengtao Wang, Zunji Ke, Kaixian Chen, Zhifei Wang

《医学前沿（英文）》 2021年第15卷第1期页码 79-90 doi: 10.1007/s11684-020-0783-8

摘要： Natural killer (NK) cells, a type of cytotoxic lymphocytes, can infiltrate into ischemic brain and exacerbate neuronal cell death. Astragaloside IV (ASIV) is the major bioactive ingredient of , a Chinese herbal medicine, and possesses potent immunomodulatory and neuroprotective properties. This study investigated the effects of ASIV on post-ischemic brain infiltration and activation of NK cells. ASIV reduced brain infarction and alleviated functional deficits in MCAO rats, and these beneficial effects persisted for at least 7 days. Abundant NK cells infiltrated into the ischemic hemisphere on day 1 after brain ischemia, and this infiltration was suppressed by ASIV. Strikingly, ASIV reversed NK cell deficiency in the spleen and blood after brain ischemia. ASIV inhibited astrocyte-derived CCL2 upregulation and reduced CCR2 NK cell levels in the ischemic brain. Meanwhile, ASIV attenuated NK cell activating receptor NKG2D levels and reduced interferon-γ production. ASIV restored acetylation of histone H3 and the p65 subunit of nuclear factor-κB in the ischemic brain, suggesting inhibition of histone deacetylase (HDAC). Simultaneously, ASIV prevented p65 nuclear translocation. The effects of ASIV on reducing CCL2 production, restoring acetylated p65 levels and preventing p65 nuclear translocation were mimicked by valproate, an HDAC inhibitor, in astrocytes subjected to oxygen-glucose deprivation. Our findings suggest that ASIV inhibits post-ischemic NK cell brain infiltration and activation and reverses NK cell deficiency in the periphery, which together contribute to the beneficial effects of ASIV against brain ischemia. Furthermore, ASIV’s effects on suppressing NK cell brain infiltration and activation may involve HDAC inhibition.

关键词： astragaloside IV brain ischemia natural killer cells histone deacetylase nuclear factor-κB

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Expression of integrin in hepatic fibrosis and intervention of resveratrol

Jianye WU, Chuanyong GUO, Jun LIU, Xuanfu XUAN

《医学前沿（英文）》 2009年第3卷第1期页码 100-107 doi: 10.1007/s11684-009-0013-x

摘要： The aim of this study was to explore the expression of integrin-β1 in different stages of hepatic fibrosis and intervention of resveratrol as well as the way by which integrin-β1 promoted hepatic fibrosis. Hepatic fibrosis models of male Sprague Dawley (SD) rats were created and intragastric administration of resveratrol was given in low (40 mg/kg), middle (120 mg/kg) and high (200 mg/kg) dose groups. The expression of integrin-β1, tumor growth factor-β (TGF-β) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in different stages of hepatic fibrosis was detected by using RT-PCR. The expression of hexadecenoic acid (HA) and precollagen III (pc III) was assayed by radioimmunoassay. The expression of integrin-β1, TGF-β and TIMP-1 was determined in each group. Liver function and pathological sections of each group in different stages of hepatic fibrosis was tested to judge the therapeutic efficacy of resveratrol at different doses. The expression of integrin-β1 in normal control group was low and steady and was not increased as the development of hepatic fibrosis, but it is increased in other groups. The expression levels of integrin-β1 in the model control group (0.878±0.03, <0.01) and low dose group (0.855±0.04, <0.01) were higher than other groups, but there was no difference between model control group and low dose group ( >0.05). The expression levels of integrin-β1 and TGF-β in middle dose group and high dose group were higher than other groups ( <0.01). The expression levels of integrin-β1 and TGF-β in model control group and low dose group were lower than the normal control group ( <0.01). The expression levels of TIMP-1 in the model control and low dose groups were higher than the other groups ( <0.01). The expression levels of TIMP-1 in the middle dose group and the high dose group were lower than the normal control group ( <0.01). The expression of integrin-β1 existed in all stages of hepatic fibrosis of SD rats, and it was increased as the development of hepatic fibrosis. The expression of TGF-β and TIMP-1 was consistent with that of integrin-β1 in different stages of hepatic fibrosis. Resveratrol could improve the degree of hepatic fibrosis of SD rats and decrease the expression of integrin-β1 markedly at a dose of 120 mg/kg.

关键词： liver fibrosis integrin-β1 resveratrol tumor growth factor-β tissue inhibitor of metalloproteinase-1

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Early and marked up-regulation of TNF-α in acute respiratory distress syndrome after cardiopulmonary bypass

null

《医学前沿（英文）》 2012年第6卷第3期页码 296-301 doi: 10.1007/s11684-012-0219-1

摘要：

Despite the technique of cardiopulmonary bypass (CPB) improved the development of modern cardiac surgery, many factors during CPB have been reported to induce acute respiratory distress syndrome (ARDS). The present study was to investigate which pro-inflammatory factors involved in the early phase of ARDS. Ten patients underwent valve replacement surgery with or without ARDS were enrolled for analysis of pulmonary function and inflammatory factors release including white blood cell (WBC), neutrophils, CD11b, CD18, interleukin (IL)-8 and tumor necrosis factor-α (TNF-α). The results demonstrated that the ratio of arterial oxygen tension/fraction of inspire oxygen (PaO₂/FiO₂) was greatly reduced in ARDS patients, but only the release of TNF-α was significantly increased, which was reversely correlated to the values of PaO₂/FiO₂. Also, the count of neutrophils adhesive to pulmonary endothelial cells was significantly increased in ARDS patients. Therefore, we concluded that TNF-α was quickly up-regulated and involved in the pathogenesis of CPB-induced ARDS via guiding primed neutrophils to pulmonary interstitium.

关键词： tumor necrosis factor-α cardiopulmonary bypass inflammation acute respiratory distress syndrome

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Metabonomic study of the biochemical profiles of heterozygous myostatin knockout swine

Jianxiang XU,Dengke PAN,Jie ZHAO,Jianwu WANG,Xiaohong HE,Yuehui MA,Ning LI

《农业科学与工程前沿（英文）》 2015年第2卷第1期页码 90-99 doi: 10.15302/J-FASE-2015045

摘要： Myostatin is a transforming growth factor-β family member that normally acts to limit skeletal muscle growth. Myostatin gene ( ) knockout (KO) mice show possible effects for the prevention or treatment of metabolic disorders such as obesity and type 2 diabetes. We applied chromatography and mass spectrometry based metabonomics to assess system-wide metabolic response of heterozygous KO ( ) swine. Most of the metabolic data for swine were similar to the data for wild type (WT) control swine. There were, however, metabolic changes related to fatty acid metabolism, glucose utilization, lipid metabolism, as well as BCAA catabolism caused by monoallelic depletion.The statistical analyses suggested that: (1) most metabolic changes were not significant in swine compared to WT swine; (2) only a few metabolic properties were significantly different between KO and WT swine, especially for lipid metabolism. Significantly, these minor changes were most evident in female KO swine and suggested differences in gender sensitivity to myostatin.

关键词： myostatin transforming growth factor-β family skeletal muscle metabolic disorders chromatography mass spectrometry metabonomics

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转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化 Article

Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš

《工程（英文）》 2024年第32卷第1期页码 58-69 doi: 10.1016/j.eng.2023.09.019

摘要：

Hepatocyte nuclear factor 1 alpha (HNF1A), hepatocyte nuclear factor 4 alpha (HNF4A), and forkhead box protein A2 (FOXA2) are key transcription factors that regulate a complex gene network in the liver, creating a regulatory transcriptional loop. The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes. Our in silico analysis of HNF1A, HNF4A, and FOXA2 binding to the 10 candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the liver. Our previous studies identified HNF1A as a master regulator of fucosylation, glycan branching, and galactosylation of plasma glycoproteins. Here, we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype. We used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) molecular tool for the downregulation of the HNF1A, HNF4A, and FOXA2 genes in HepG2 cells—a human liver cancer cell line. The results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many glyco-genes, although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures. The effect is better seen as an overall change in the total HepG2 N-glycome, primarily due to the extension of biantennary glycans. We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure. We also propose a model showing feedback loops with the mutual activation of HNF1A–FOXA2 and HNF4A–FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.

关键词： Clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) Epigenetics Hepatocyte nuclear factor 1 alpha (HNF1A) Hepatocyte nuclear factor 4 alpha (HNF4A) Forkhead box protein A2 (FOXA2) N-glycosylation HepG2 cells

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Special issue: innovative nuclear energy technology

《能源前沿（英文）》 2021年第15卷第4期页码 791-792 doi: 10.1007/s11708-021-0794-4

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An old issue and a new challenge for nuclear reactor safety

F. D’AURIA

《能源前沿（英文）》 2021年第15卷第4期页码 854-859 doi: 10.1007/s11708-021-0729-0

摘要： Nuclear reactor safety (NRS) and the branch accident analysis (AA) constitute proven technologies: these are based on, among the other things, long lasting research and operational experience in the area of water cooled nuclear reactors (WCNR). Large break loss of coolant accident (LBLOCA) has been, so far, the orienting scenario within AA and a basis for the design of reactors. An incomplete vision for those technologies during the last few years is as follows: Progress in fundamentals was stagnant, namely in those countries where the WCNR were designed. Weaknesses became evident, noticeably in relation to nuclear fuel under high burn-up. Best estimate plus uncertainty (BEPU) techniques were perfected and available for application. Electronic and informatics systems were in extensive use and their impact in case of accident becomes more and more un-checked (however, quite irrelevant in case of LBLOCA). The time delay between technological discoveries and applications was becoming longer. The present paper deals with the LBLOCA that is inserted into the above context. Key conclusion is that regulations need suitable modification, rather than lowering the importance and the role of LBLOCA. Moreover, strengths of emergency core cooling system (ECCS) and containment need a tight link.

关键词： large break loss of coolant accident (LBLOCA) nuclear reactor safety (NRS) licensing perspectives basis for design of water cooled nuclear reactors (WCNR)

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Inhibition of NF-kappa B can enhance Fas-mediated apoptosis in leukemia cell line HL-60

Li WANG, Shi ZHAO, Hong-Xiang WANG, Ping ZOU

《医学前沿（英文）》 2010年第4卷第3期页码 323-328 doi: 10.1007/s11684-010-0026-5

摘要： This study explored the effects of nuclear factor-kappa B (NF-κB) inhibitor Bay 11-7082 on Fas/FasL system and Fas-mediated apoptosis in cell line HL-60 cells. The mRNA and protein levels of Fas, FasL, and X-linked inhibitor of apoptosis protein (XIAP) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FCM); the level of sFasL was evaluated by enzyme-linked immunosorbent assay (ELISA); and apoptosis was determined by FCM. After treatment with Bay 11-7082, the mRNA and protein levels of FasL and XIAP in HL-60 cells were significantly lower than in the controls ( <0.05), but the mRNA and protein levels of Fas and sFasL did not change significantly ( >0.05). Apoptotic rate of HL-60 cells treated with Bay 11-7082 was significantly higher than in the controls ( <0.05). Therefore, we conclude that Bay 11-7082 can enhance Fas-mediated apoptosis in HL-60 cells by downregulating FasL and XIAP levels.

关键词： nuclear factor-kappa B Fas/FasL system HL-60 Bay 11-7082

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让核技术为国家可持续发展再创辉煌

杜祥琬

《中国工程科学》 2008年第10卷第1期页码 9-11

摘要：

概述了对核科学技术发展及应用方向的认识，包括核技术与能源、核技术与医疗卫生、核分析技术、核辐射技术、宇航与航海核动力等5个方面，讨论了它们对国家可持续发展的意义。概括了核科学技术发展的三部曲及发展前景。

关键词：核科学核技术核工程可持续发展

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Reliability prediction and its validation for nuclear power units in service

Jinyuan SHI,Yong WANG

《能源前沿（英文）》 2016年第10卷第4期页码 479-488 doi: 10.1007/s11708-016-0425-7

摘要： In this paper a novel method for reliability prediction and validation of nuclear power units in service is proposed. The equivalent availability factor is used to measure the reliability, and the equivalent availability factor deducting planed outage hours from period hours and maintenance factor are used for the measurement of inherent reliability. By statistical analysis of historical reliability data, the statistical maintenance factor and the undetermined parameter in its numerical model can be determined. The numerical model based on the maintenance factor predicts the equivalent availability factor deducting planed outage hours from period hours, and the planed outage factor can be obtained by using the planned maintenance days. Using these factors, the equivalent availability factor of nuclear power units in the following 3 years can be obtained. Besides, the equivalent availability factor can be predicted by using the historical statistics of planed outage factor and the predicted equivalent availability factor deducting planed outage hours from period hours. The accuracy of the reliability prediction can be evaluated according to the comparison between the predicted and statistical equivalent availability factors. Furthermore, the reliability prediction method is validated using the nuclear power units in North American Electric Reliability Council (NERC) and China. It is found that the relative errors of the predicted equivalent availability factors for nuclear power units of NERC and China are in the range of –2.16% to 5.23% and –2.15% to 3.71%, respectively. The method proposed can effectively predict the reliability index in the following 3 years, thus providing effective reliability management and maintenance optimization methods for nuclear power units.

关键词： nuclear power units in service reliability reliability prediction equivalent availability factors

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中法关于核能与环境的联合研究 Feature Article

赵宪庚, 叶其蓁, Sébastien Candel, Dominique Vignon, Robert Guillaumont

《工程（英文）》 2023年第26卷第7期页码 159-172 doi: 10.1016/j.eng.2023.04.011

摘要：

本文聚焦核能的环境影响问题，将解决如下核能发电相关的主要环境问题：①控制正常运行条件下核设施的放射性排放，评估其非放射性环境影响（取水与非放射性水的排放）；②乏燃料与放射性废物的长期管理，主要是通过地质处置库处理的乏燃料或放射性废物；③防止和缓解严重核事故以及核事故的放射性释放；④改善核安全水平，以限制核能的环境影响，提升公众的核能接受度。核能的温室气体排放水平非常低，可以根据需求供应大规模、可调度电力，在此方面核能具有独特的优势。在正常运行工况下，核电站每年释放到周围公众的有效辐射剂量可以忽略不计。国际社会已经开展了大量的努力，以确定可持续管理地质处置条件下高放长寿命放射性废物的方法。过去几次严重核事故中获得的经验为核能生产相关的安全问题提供了经验，也促成了重要的安全改进，其中包括反应堆的设计和运行管理方面的改善以及事故管理指导方针的制定等。事实证明，这些经验是非常宝贵的。严重事故的环境风险已经被大幅降低，相关的规约也已经建立起来，以最大限度地减少严重核事故条件下放射性物质的释放，并避免大规模的人员疏散。还需要继续采取措施，改善反应堆的安全性，提升核工业与核监管机构的透明度，以进一步降低核能的环境影响。

关键词：核能环境影响放射性废物管理严重核事故核安全

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中国核电的可持续发展

赵仁恺

《中国工程科学》 2000年第2卷第10期页码 33-41

摘要：

文章阐述了核能是可持续发展的能源，是我国未来国民经济发展的重要支柱的论点，分析了国际核电发展现状，我国核电发展的方针政策、技术路线、现状以及共同关心的几个问题：铀资源问题、核安全问题、核废料问题和核电国产化问题，展望了我国核电发展的前景，并提出了建议：我国核电站应以现有压水堆核电站为基础，实现国产化、标准化、系列化；快中子增殖堆在我国核电建设中占有十分重要的地位，应大力支持、促进；尽快开始乏燃料后处理厂及其配套设施的建设。

关键词：核能铀资源核安全核废料国产化

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Oocyte-associated transcription factors in reprogramming after somatic cell nuclear transfer: a review

Fengxia YIN,Hui LIU,Shorgan BOU,Guangpeng LI

《农业科学与工程前沿（英文）》 2014年第1卷第2期页码 104-113 doi: 10.15302/J-FASE-2014003

摘要： Oocytes are unique cells with the inherent capability to reprogram nuclei. The reprogramming of the somatic nucleus from its original cellular state to a totipotent state is essential for term development after somatic cell nuclear transfer. The nuclear-associated factors contained within oocytes are critical for normal fertilization by sperm or for somatic cell nuclear reprogramming. The chromatin of somatic nuclei can be reprogrammed by factors in the egg cytoplasm whose natural function is to reprogram sperm chromatin. The oocyte first obtains its reprogramming capability in the early fetal follicle, and then its capacity is enriched in the late growth phase and reaches its highest capability for reprogramming as fully-grown germinal vesicle oocytes. The cytoplasmic milieu most likely contains all of the specific transcription and/or reprogramming factors necessary for cellular reprogramming. Certain transcription factors in the cytoplast may be critical as has been demonstrated for induced pluripotent stem cells. The maternal pronucleus exerts a predominant, transcription-dependent effect on embryo cytofragmentation, with a lesser effect imposed by the ooplasm and the paternal pronucleus. With deep analysis of transcriptomics in oocytes and early developmental stage embryos more maternal transcription factors inducing cellular reprogramming will be identified.

关键词： nuclear reprogramming somatic cell transcription factors transcriptomics

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Development and application of a random walk model of atmospheric diffusion in the emergency response of nuclear

CHI Bing, LI Hong, FANG Dong

《能源前沿（英文）》 2007年第1卷第2期页码 195-201 doi: 10.1007/s11708-007-0025-7

摘要： Plume concentration prediction is one of the main contents of radioactive consequence assessment for early emergency response to nuclear accidents. Random characteristics of atmospheric diffusion itself was described, a random walk model of atmospheric diffusion (Random Walk) was introduced and compared with the Lagrangian puff model (RIMPUFF) in the nuclear emergency decision support system (RODOS) developed by the European Community for verification. The results show the concentrations calculated by the two models are quite close except that the plume area calculated by Random Walk is a little smaller than that by RIMPUFF. The random walk model for atmospheric diffusion can simulate the atmospheric diffusion in case of nuclear accidents, and provide more actual information for early emergency and consequence assessment as one of the atmospheric diffusion module of the nuclear emergency decision support system.

关键词： RODOS concentration prediction information nuclear RIMPUFF

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我国核安全技术发展战略研究

彭述明,夏佳文,王毅韧,彭现科,黄洪文,郑春,丁文杰

《中国工程科学》 2021年第23卷第3期页码 113-119 doi: 10.15302/J-SSCAE-2021.03.017

摘要：

核安全是国家安全体系的重要组成部分，是发展核事业的前提、基础和生命线。先进可靠的核安全技术是保持并提高本质安全的基石，开展核安全技术战略研究对于建设核科技强国意义重大。本文采用“总 – 分 – 凝 – 综”的思路，通过院士访谈、实地调研、会议研讨、资料调研等多种途径，对我国核安全技术体系展开深入研究。结果表明：在总体国家安全观和核安全观的指引下，近年来我国核安全技术进展明显，核安全业绩良好；但也面临核安全标准体系建设有待深化、核安全软件研发统筹不足、核安全高精尖装备受制于人等瓶颈问题。为持续推进核安全治理体系与治理能力现代化，实现核大国向核强国的历史性跨越，建议进一步完善核安全标准体系；统筹资源、集中攻关，推进自主化核安全软件高质量发展；强化“政、产、学、研、用”结合，解决高端核安全装备“卡脖子”问题。

关键词：核安全技术标准体系核安全软件核安全装备