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Epigenetic combined with transcriptomic analysis of the m6A methylome after spared nerve injury-induced neuropathic pain in mice

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Neural Regeneration Research 2023年第11期18卷 2545-2552页

作者： Fanning Zeng Jun Cao zexuan hong Yitian Lu Zaisheng Qin Tao Tao Department of Anesthesiology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Anesthesiology Central People’s Hospital of ZhanjiangZhanjiangGuangdong ProvinceChina Department of Anesthesiology Shenzhen Maternity&Child Healthcare HospitalSouthern Medical UniversityShenzhenGuangdong ProvinceChina

Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuro pathic pain.N6-methyladenosine(m6A)is one of the most abundant internal RNA modifications and plays an essential function in gene regulation in many diseases.However,the global m6A modification status of mRNA in the spinal cord at different stages after neuropathic pain is unknown.In this study,we established a neuropathic pain model in mice by preserving the complete sural nerve and only damaging the common peroneal nerve.High-throughput methylated RNA immunoprecipitation sequencing res ults showed that after spared nerve injury,there were 55 m6A methylated and diffe rentially expressed genes in the spinal cord.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway results showed that m6A modification triggered inflammatory responses and apoptotic processes in the early stages after spared nerve injury.Over time,the diffe rential gene function at postoperative day 7 was enriched in "positive regulation of neurogenesis" and "positive regulation of neural precursor cell prolife ration." These functions suggested that altered synaptic morphological plasticity was a turning point in neuropathic pain formation and maintenance.Results at postoperative day 14 suggested that the persistence of neuropathic pain might be from lipid metabolic processes,such as "very-low-density lipoprotein particle clearance," "negative regulation of choleste rol transport" and "membrane lipid catabolic process." We detected the expression of m6A enzymes and found elevated mRNA expression of Ythdf2 and Ythdf3 after spared nerve injury modeling.We speculate that m6A reader enzymes also have an important role in neuropathic pain.These results provide a global landscape of mRNA m6A modifications in the spinal cord in the spared nerve injury model at diffe rent stages after injury.

关键词： epigenetic m6A reader m6A MeRIP-Seq Nlrp1b neuropathic pain RNA methylation spared nerve injury Ythdf2

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Celastrol targeting Nedd4 reduces Nrf2-mediated oxidative stress in astrocytes after ischemic stroke

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Journal of Pharmaceutical Analysis 2023年第2期13卷 156-169页

作者： zexuan hong Jun Cao Dandan Liu Maozhu Liu Mengyuan Chen Fanning Zeng Zaisheng Qin Jigang Wang Tao Tao Department of Anesthesiology Nanfang HospitalSouthern Medical UniversityGuangzhou510515China Department of Anesthesiology Central People's Hospital of ZhanjiangZhanjiangGuangdong524045China Artemisinin Research Center Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China Department of Pharmacy West China HospitalSichuan UniversityChengdu610000China Department of Pharmacy Xi'an Daxing HospitalXi'an710000China

Stroke is the second leading cause of death worldwide,and oxidative stress plays a crucial role.Celastrol exhibits strong antioxidant properties in several diseases;however,whether it can affect oxidation in cerebral ischemic-reperfusion injury(CIRI)remains unclear.This study aimed to determine whether celastrol could reduce oxidative damage during CIRI and to elucidate the underlying mechanisms.Here,we found that celastrol attenuated oxidative injury in CIRI by upregulating nuclear factor E2-related factor 2(Nrf2).Using alkynyl-tagged celastrol and liquid chromatography-tandem mass spectrometry,we showed that celastrol directly bound to neuronally expressed developmentally downregulated 4(Nedd4)and then released Nrf2 from Nedd4 in astrocytes.Nedd4 promoted the degradation of Nrf2 through K48-linked ubiquitination and thus contributed to astrocytic reactive oxygen species production in CIRI,which was significantly blocked by celastrol.Furthermore,by inhibiting oxidative stress and astrocyte activation,celastrol effectively rescued neurons from axon damage and apoptosis.Our study uncovered Nedd4 as a direct target of celastrol,and that celastrol exerts an antioxidative effect on astrocytes by inhibiting the interaction between Nedd4 and Nrf2 and reducing Nrf2 degradation in CIRI.

关键词： Celastrol Cerebral ischemia Reperfusion injury Oxidative stress Nedd4 Nrf2 Ubiquitylation

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ZYX promotes invasion and metastasis of gastric cancer cells via WNK1/SNAI1axis

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Genes & Diseases 2024年第2期11卷 564-567页

作者： Yi Jiang Dongfang Xiang Xianmei Wen Mingmin He Yan Qin Xiaoxue Yao zexuan Yan Xiuli Geng Yong Ren Xiongwei Cai Youhong Cui Yan Wang Institute of Pathology and Southwest Cancer Center Southwest HospitalArmy Medical University (Third Military Medical University)Chongqing 400038China Department of Pathology General Hospital of Central Theater Command of PLAWuhanHubei 430070China Department of Obstetrics and Gynecology Southwest HospitalArmy Medical University (Third Military Medical University)Chongqing 400038China Department of Pharmacy The Hospital of 83rd Group of PLAXinxiangHenan 453000China Department of Gynecology Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical UniversityChongqing 400013China

Gastric cancer(GC)is the third most common cause of cancer death globally and a large portion of patients are diagnosed at advanced stages with cancer invasion and metastasis1,2.However,the mechanisms underlying the invasion and metastasis of GC remain to be delineated.ZYX plays critical roles in cell mobility via cytoskeleton regulation in various cell types.3 In this study,we further reported that ZYX promoted migration,invasion,and metastasis of GC cells.Mechanistically,ZYX promoted WNK1 activation and SNAl1 up-regulation,inducing epithelial-mesenchymal transition(EMT)to enhance the mobility of GC cells.Inhibition of WNK1 impaired the mobility of GC cells.Therefore,ZYX/WNK1 could be potential therapeutic targets for GC treatment.

关键词： WNK1 invasion metastasis

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A Novel Poly(3-hexylthiophene) Engineered Interface for Electrochemical Monitoring of Ascorbic Acid During the Occurrence of Glutamate-Induced Brain Cytotoxic Edemas

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Research 2024年第1期2023卷 301-313页

作者： zexuan Meng Yuchan Zhang Lu Yang Shuang Zhao Qiang Zhou Jiajia Chen Jiuxi Sui Jian Wang Lizhong Guo Luyue Chang Jialing He Guixue Wang Guangchao Zang Institute of Life Science and Laboratory of Tissue and Cell BiologyLab Teaching and Management CenterChongqing Medical UniversityChongqing 400016China Key Laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing 400030China Jinfeng Laboratory Chongqing 401329China Department of Pathophysiology Chongqing Medical UniversityChongqingChina

Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research,its application is limited by substantial interference in complex brain environments while ensuring biosafety requirements.In this study,we introduced poly(3-hexylthiophene)(P3HT)and nitrogen-doped multiwalled carbon nanotubes(N-MWCNTs)to construct a composite membrane-modified carbon fiber microelectrode(CFME/P3HT-N-MWCNTs)for ascorbic acid(AA)detection.The microelectrode presented good linearity,selectivity,stability,antifouling,and biocompatibility and exhibited great performance for application in neuroelectrochemical sensing.Subsequently,we applied CFME/P3HT-N-MWCNTs to monitor AA release from in vitro nerve cells,ex vivo brain slices,and in vivo living rat brains and determined that glutamate can induce cell edema and AA release.We also found that glutamate activated the N-methyl-d-aspartic acid receptor,which enhanced Na^(+) and Cl^(−) inflow to induce osmotic stress,resulting in cytotoxic edema and ultimately AA release.This study is the first to observe the process of glutamate-induced brain cytotoxic edema with AA release and to reveal the mechanism.Our work can benefit the application of P3HT in in vivo implant microelectrode construction to monitor neurochemicals,understand the molecular basis of nervous system diseases,and discover certain biomarkers of brain diseases.

关键词： release microelectrode Engine

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Combined effects of climate and land-use changes on the alpha and beta functional diversities of terrestrial mammals in China

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Science China Life Sciences 2024年

作者： Chao Zhang Yumei Li Wei Wang zexuan Gao Hanqing Liu Yonggang Nie Key Laboratory of Animal Ecology and Conservation Biology Institute of Zoology Chinese Academy of Sciences College of Life Sciences Hebei University University of Chinese Academy of Sciences

Climate and land-use changes are predicted to impact biodiversity,threatening ecosystem services and functions.However,their combined effects on the functional diversity of mammals at the regional scale remain unclear,especially at the beta level.Here,we use projected climate and land-use changes in China to investigate their potential effects on the alpha and beta functional diversities of terrestrial mammals under low-and high-emission scenarios.In the current projection,we showed strong positive spatial correlations between functional richness and species richness.Functional evenness (FEve),functional specialization (FSpe),and functional originality (FOri)decreased with species richness,and functional divergence (FDiv) increased first and then plateaued.Functional beta diversity was dominated by its nestedness component,in contrast to the taxonomic facet.Potential changes in species richness are more strongly influenced by land-use change under the low-emission scenario,while under the high-emission scenario,they are more strongly influenced by climate change.Changes in functional richness (FRic) were inconsistent with those in species richness,with a magnitude of decreases greater than predicted from species richness.Moreover,mammal assemblages showed potential functional differentiation (FD) across the country,and the trends exceeded those towards taxonomic differentiation (TD).Our findings help us understand the processes underlying biodiversity responses to global changes on multiple facets and provide new insight for conservation plans.

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蛋白质翻译后修饰在脑缺血再灌注中的作用

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中华脑血管病杂志（电子版） 2022年第2期16卷 125-129页

作者：洪泽璇陶涛秦再生南方医科大学南方医院麻醉科广州510515 湛江中心人民医院麻醉科广东湛江524045

蛋白质翻译后修饰是指蛋白质在翻译中或翻译后经历的共价加工的过程,能改变蛋白的结构及功能,对发挥细胞功能及维持机体稳态至关重要。在脑缺血再灌注损伤中,蛋白质翻译后修饰对物质代谢、氧化应激、凋亡、轴突生长等过程有重要的调节... 详细信息

蛋白质翻译后修饰是指蛋白质在翻译中或翻译后经历的共价加工的过程,能改变蛋白的结构及功能,对发挥细胞功能及维持机体稳态至关重要。在脑缺血再灌注损伤中,蛋白质翻译后修饰对物质代谢、氧化应激、凋亡、轴突生长等过程有重要的调节作用。本文对脑缺血再灌注损伤中3种常见的蛋白质翻译后修饰类型——磷酸化、泛素化及乙酰化进行总结,重点阐述其在疾病发展中的作用及修饰之间的相互作用,旨在为缺血性脑卒中寻找有效治疗靶点提供思路。

关键词：脑缺血翻译后修饰磷酸化泛素化乙酰化

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基于改进麻雀搜索算法优化LSTM的滚动轴承故障诊断

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工程科学与技术 2024年第2期56卷 289-298页

作者：周玉房倩裴泽宣白磊华北水利水电大学电气工程学院河南郑州450045

为了对滚动轴承的工作状态及故障类别进行准确的诊断,本文采用长短时记忆(LSTM)神经网络作为分类器对滚动轴承数据集进行分类诊断。首先,从滚动轴承原始运行振动信号中提取时域和频域特征参数,组成具有高维特征参数的数据集;使用核主成... 详细信息

为了对滚动轴承的工作状态及故障类别进行准确的诊断,本文采用长短时记忆(LSTM)神经网络作为分类器对滚动轴承数据集进行分类诊断。首先,从滚动轴承原始运行振动信号中提取时域和频域特征参数,组成具有高维特征参数的数据集;使用核主成分分析(KPCA)方法对高维特征集进行降维处理,选取重要性程度高的特征构成输入特征向量。然后,针对LSTM神经网络在滚动轴承故障诊断中存在的超参数难以确定的问题,提出一种基于自适应t分布策略的麻雀搜索算法优化LSTM神经网络的故障诊断方法(tSSA–LSTM)。最后,使用凯斯西储大学滚动轴承数据中心的数据进行故障诊断精度测试、泛化性能测试及噪声环境下故障诊断性能测试等多个仿真实验,并将本文提出的诊断模型与麻雀搜索算法优化长短时记忆神经网络(SSA–LSTM)、遗传算法优化长短时记忆神经网络(GA–LSTM)、粒子群算法优化长短时记忆神经网络(PSO–LSTM)及传统LSTM诊断模型进行对比。结果表明:tSSA可以更有效地对LSTM的隐含层神经元数量、周期次数、学习率等超参数进行合理优化;所提方法的平均诊断准确率达到98.86%,交叉验证平均诊断结果为98.57%;所提方法在噪声干扰下的故障诊断准确率也优于对比方法。因此,本文提出的tSSA–LSTM模型不仅可以更精准地诊断滚动轴承故障状态,而且具有更强的泛化能力及抗干扰能力,有效地提高了滚动轴承故障诊断的性能。

关键词：麻雀搜索算法故障诊断长短时记忆神经网络特征提取滚动轴承

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引入相量算子和流向算子的天鹰优化算法

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浙江大学学报（工学版） 2024年第2期58卷 304-316页

作者：周玉裴泽宣王培崇陈博华北水利水电大学电气工程学院河南郑州450045 河北地质大学信息工程学院河北石家庄050031

针对天鹰优化算法搜索效率不足,容易陷入局部最优的缺点,提出多策略改进天鹰优化算法(MIAO).引入广义正态分布优化算法(GNDO),将该算法得出的结果与天鹰优化算法第1阶段得出的结果进行比较,筛选出这2种优化算法下的最优值.该操作扩大了... 详细信息

针对天鹰优化算法搜索效率不足,容易陷入局部最优的缺点,提出多策略改进天鹰优化算法(MIAO).引入广义正态分布优化算法(GNDO),将该算法得出的结果与天鹰优化算法第1阶段得出的结果进行比较,筛选出这2种优化算法下的最优值.该操作扩大了搜索空间,提高了解的质量.引入相量算子,将第2阶段变为自适应的非参数优化,提高算法的高维优化能力.针对天鹰优化算法在迭代后期存在种群多样性降低、局部开发能力不足的问题,在天鹰算法的第3阶段引入流向算子,使信息可以在每个个体间相互传递,提高种群信息的利用率,增强天鹰优化算法的开发性能.通过对16个测试函数寻优对比分析以及Wilcoxon秩和检验可知,MIAO的寻优能力和收敛速度都有较大的提升.为了验证MIAO算法的实用性和可行性,采用所提算法求解减速器设计问题,通过实际工程优化问题的实验对比分析可知,MIAO算法在处理现实优化问题上具有一定的优越性.

关键词：天鹰优化算法广义正态分布优化算法相量算子流向算子测试函数 Wilcoxon秩和检验

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熊胆粉对DEN + PBO诱发大鼠肝癌早期阶段的影响研究

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中国实验动物学报 2023年第9期31卷 1148-1155页

作者：董锐张梅洪泽宣唐倩邹昕羽贾贵阳倪元萍涉谷淳金美兰西南大学动物医学院重庆400715 东京农工大学农学研究科动物生命科学部兽医病理学研究室东京183-8509 西南大学实验动物中心重庆400715

目的为了解明熊胆粉在肝癌早期阶段的抑制作用,利用大鼠短期致癌模型进行了熊胆粉(bear bile powder, BBP)的抗癌药效实验。方法 40只5周龄雄性SD大鼠分成4组:DEN单独组(DEN-alone),模型组(DEN+PBO),低剂量组(DEN+PBO+BBP-L)(200 mg/k... 详细信息

目的为了解明熊胆粉在肝癌早期阶段的抑制作用,利用大鼠短期致癌模型进行了熊胆粉(bear bile powder, BBP)的抗癌药效实验。方法 40只5周龄雄性SD大鼠分成4组:DEN单独组(DEN-alone),模型组(DEN+PBO),低剂量组(DEN+PBO+BBP-L)(200 mg/kg),高剂量组(DEN+PBO+BBP-H)(400 mg/kg)。实验开始时,大鼠腹腔注射200 mg/kg二乙基亚硝胺(diethylnitrosamine, DEN),模型组、低剂量组及高剂量组动物饲喂了0.5%胡椒基丁醚(piperonyl butoxide, PBO)粉末饲料。低剂量组和高剂量组动物同时灌胃200或400 mg/kg BBP 8周。结果饲喂PBO粉末饲料的动物绝对及相对肝重量显著大于DEN单独组。但是,DEN+PBO+BBP-L组的GST-P阳性病灶的数量和面积与DEN+PBO组相比显著减少。同时,因DEN和PBO处理显著增加的Ki-67阳性细胞率在BBP处理组显著减少。但是,细胞周期相关的Ccne1、Cdkn1b和细胞凋亡相关的Caspase 8、Caspase 9仅在DEN+PBO+BBP-H组中显著增加,在DEN+PBO+BBP-L组中没有变化。结论 BBP在肝癌形成早期阶段通过抑制癌前病灶发挥抑制作用,且它的抗癌机制中包含着抑制细胞增殖活性和诱导细胞凋亡作用。同时,高剂量的BBP可能影响其抗癌前病灶作用。

关键词：熊胆粉肝癌早期阶段癌前病灶抑制作用

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机场飞行区多层异质链序风险传播模型研究

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北京航空航天大学学报 2024年第7期50卷 2225-2236页

作者：吴维吴泽萱王兴隆中国民航大学空中交通管理学院天津300300 北京交通大学交通运输学院北京100044

为探究机场飞行区风险发生机制及风险传播特性,增强机场飞行区安全管控能力,采用复杂网络理论,依据风险致因间的因果链序关系,构建多层异质网络风险传播模型。采用多层次因果图(AcciMap)理论分析机场飞行区运行风险传播的致因链;基于风... 详细信息

为探究机场飞行区风险发生机制及风险传播特性,增强机场飞行区安全管控能力,采用复杂网络理论,依据风险致因间的因果链序关系,构建多层异质网络风险传播模型。采用多层次因果图(AcciMap)理论分析机场飞行区运行风险传播的致因链;基于风险致因特征构建3层异质风险传播网络并根据网络特征设计概率-触发传播模型、容量-阻抗传播模型、容量-负荷传播模型;利用复杂网络理论设计风险传播评价指标,对风险网络传播特征进行分析。结果表明:多层风险网络中节点风险传播能力与节点度弱相关,节点风险灵敏指数可提升风险节点排序准确性;对风险灵敏度指数排序前15%的节点进行风险控制,可有效降低风险扩散近32%;网络风险传播结构存在高连通和松散状态,对风险扩散指数排序前15%的节点进行控制,可以有效降低网络结构鲁棒性指数使风险网络结构由高连通进入到松散状态;所建模型可有效识别风险扩散过程并进行精准控制,以提升机场飞行区风险控制水平。

关键词：航空运输机场运行复杂网络风险传播控制策略

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