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EYA4 inhibits hepatocellular carcinoma growth and invasion by suppressing NF-κB-dependent RAP1 transactivation

Cancer Communications 2018年第1期38卷 105-119页

作者： shi-jing mo Xun Hou Xiao-Yi Hao Jian-Peng Cai Xin Liu Wei Chen Dong Chen Xiao-Yu Yin Department of Pancreatobiliary Surgery The First Affiliated HospitalSun Yat-sen UniversityNo.58Zhongshan Er RoadGuangzhou 510080GuangdongP.R.China

Background:Our previous studies demonstrated that eyes absent homolog 4(EYA4),a member of the eye devel-opment-related EYA family in Drosophila,is frequently methylated and silenced in hepatocellular carcinoma(HCC)specimens and associated with shorter *** current work aimed to explore the mechanisms through which EYA4 functions as a tumor suppressor in ***:Stable EYA4-expressing plasmid(pEYA4)transfectants of the human HCC cell lines Huh-7 and PLC/PRF/5(PLC)were *** tumors were established via subcutaneous injection of the stable transfectants into BALB/c nude *** samples were obtained from 75 pathologically diagnosed HCC *** real-time polymerase chain reaction,Western blotting and immunohistochemistry were performed to determine the expression of EYA4 in cell lines,xenografts and clinical *** cell proliferation,colony formation,invasiveness and tumor formation of stable transfectants were studied.A gene expression microarray was utilized to screen genes regulated by EYA4 *** effect of EYA4 on nuclear factor-κB(NF-κB)/RAS-related protein 1(RAP1)signaling was demonstrated through the co-transfection of pEYA4 and Flag-tagged RAS-related protein 1A gene-expressing plasmid(Flag-RAP1A),functional studies,chromatin immunoprecipitation,immunofluorescence staining and cellular ubiquitination ***:The restoration of EYA4 expression in HCC cell lines suppressed cell proliferation,inhibited clonogenic outgrowth,reduced cell invasion and restrained xenograft tumor growth,and Flag-RAP1A reversed the suppressive effects of pEYA4 in *** of NF-κB with tumor necrosis factor-α(TNF-α)increased the binding of p65 to the RAP1A gene promoter and up-regulated RAP1 protein *** inhibition of NF-κB with BAY 11-7085 and p65 siRNA successfully blocked TNF-α-induced RAP1 ***4 antagonized the TNF-α-induced phosphoryla-tion and ubiquitination of inhibitor of NF-κBα(IκB

关键词： Eyes absent homolog 4(EYA4) RAS-related protein 1(RAP1) Nuclear factor-κB(NF-κB) Transactivation Hepatocellular carcinoma

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A Genetic Algorithm on Multiple Sequences Alignment Problems in Biology

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Wuhan University Journal of Natural Sciences 2002年第2期7卷 139-144页

作者： shi Feng, Huang jing, mo Zhong-xi, Zheng Hui-rao School of Mathematics and Statistics, Wuhan University, Wuhan 430072, Hubei, China School of Mathematics and Statistics Wuhan University Wuhan Hubei China

The study and comparison of sequences of characters from a finite alphabet is relevant to various areas of science, notably molecular biology. The measurement of sequence similarity involves the consideration of the possible sequence alignments in order to find an optimal one for which the “distance” between sequences is minimum. In biology informatics area, it is a more important and difficult problem due to the long length (100 at least) of sequence, this cause the compute complexity and large memory require. By associating a path in a lattice to each alignment, a geometric insight can be brought into the problem of finding an optimal alignment, this give an obvious encoding of each path. This problem can be solved by applying genetic algorithm, which is more efficient than dynamic programming and hidden Markov model using commomly now.

关键词： Key words sequence comparison biological sequences genetic algorithm

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Direct Photolithography of WO_(x)Nanoparticles for High‑Resolution Non‑Emissive Displays

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Nano-Micro Letters 2025年第3期17卷 297-309页

作者： Chang Gu Guojian Yang Wenxuan Wang Aiyan shi Wenjuan Fang Lei Qian Xiaofei Hu Ting Zhang Chaoyu Xiang Yu‑mo Zhang Laboratory of Optoelectronic Information Technology and Devices Ningbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201People’s Republic of China Hangzhou Bay Laboratory of Advanced Nano‑Optoelectronic Materials and Devices Qianwan Institute of CNITECHNingbo 315336People’s Republic of China Smart Materials for Architecture Research Lab Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314100People’s Republic of China University of Science and Technology of China Hefei 230026People’s Republic of China State Key Lab of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchun 130012People’s Republic of China

High-resolution non-emissive displays based on electrochromic tungsten oxides(WOx)are crucial for future near-eye virtual/augmented reality interactions,given their impressive attributes such as high environmental stability,ideal outdoor readability,and low energy ***,the limited intrinsic structure of inorganic materials has presented a significant challenge in achieving precise patterning/pixelation at the micron ***,we successfully developed the direct photolithography for WOx nanoparticles based on in situ photo-induced ligand *** strategy enabled us to achieve ultra-high resolution efficiently(line widthmodulation(55.9%),and durability(>3600 cycles),as well as promising applications in electronic logos,pixelated displays,flexible electronics,*** success and advancements presented here are expected to inspire and accelerate research and development(R&D)in high-resolution non-emissive displays and other ultra-fine micro-electronics.

关键词： Electrochromic Direct photolithography WOx nanoparticles In situ photo-induced ligand exchange High-resolution displays

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The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

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Neural Regeneration Research 2025年第1期20卷 209-223页

作者： shi-Yan Sun Lingyun Nie jing Zhang Xue Fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang Hefei National Research Center for Physical Sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS Center for Excellence in molecular Cell Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Brain Research Center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and ***-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains *** this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative ***,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic *** of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and *** down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive *** together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

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EYA4通过抑制NF-κB依赖的RAP1反式激活抑制肝细胞癌的生长和侵袭

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癌症 2019年第2期38卷 76-90页

作者： shi-jing mo Xun Hou Xiao-Yi Hao Jian-Peng Cai Xin Liu Wei Chen Dong Chen Xiao-Yu Yin胆胰外科中山大学附属第一医院

背景与目的我们之前研究表明,眼缺失蛋白同源物4(eyes absent homolog 4,EYA4)是果蝇眼部发育相关的眼缺乏蛋白家族成员之一,在肝细胞癌(hepatocellular carcinoma,HCC)标本中常发生甲基化和沉默,并与患者生存期短密切相关。本研究旨在... 详细信息

背景与目的我们之前研究表明,眼缺失蛋白同源物4(eyes absent homolog 4,EYA4)是果蝇眼部发育相关的眼缺乏蛋白家族成员之一,在肝细胞癌(hepatocellular carcinoma,HCC)标本中常发生甲基化和沉默,并与患者生存期短密切相关。本研究旨在探讨EYA4在HCC中作为肿瘤抑制因子的作用机制。方法转染EYA4表达质粒(pEYA4)构建稳定表达EYA4的人HCC细胞系Huh-7和PLC/PRF/5(PLC)。通过BALB/c裸鼠皮下注射稳定转染细胞建立异种移植肿瘤。组织标本来自75例病理诊断为HCC的患者。采用实时定量聚合酶链式反应(real-time polymerase chain reaction,real-time PCR)、蛋白质免疫印迹和免疫组织化学的方法检测EYA4在细胞系、异种移植物和临床标本中的表达;研究了稳定转染细胞系的细胞增殖、克隆形成、侵袭性和肿瘤形成。利用基因表达芯片筛选EYA4调节的基因。通过共转染EYA4和带Flag标签的RAS相关蛋白1A(RAS-related protein 1A,RAP1A)基因的表达质粒(pEYA4和Flag-RAP1A)、功能研究、染色质免疫共沉淀、免疫荧光染色和细胞泛素化分析等方法,研究了EYA4对核因子-κB(nuclear factor-κB,NF-κB)/RAS相关蛋白1(RAS-related protein 1,RAP1)信号通路的影响。结果恢复HCC细胞系中EYA4的表达可抑制细胞的增殖、抑制克隆形成、降低细胞的侵袭性和抑制异种移植肿瘤生长,在体外实验中Flag-RAP1A可逆转pEYA4的抑制作用。用肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)激活NF-κB通路可增加p65与RAP1A基因启动子的结合并上调RAP1蛋白的表达。用BAY 11-7085和p65 siRNA抑制NF-κB通路,成功阻断了TNF-α诱导的RAP1上调。EYA4拮抗了TNF-α诱导的NF-κB抑制因子α(inhibitor of NF-κBα,IκBα)的磷酸化和泛素化以及p65的核易位和反式激活,进而抑制了NF-κB的活性和RAP1的表达。用calyculin A阻断EYA4的丝氨酸/苏氨酸磷酸酶活性可显著消除其对NF-κB活性的抑制作用。此外,EYA4的表达与HCC临床标本中IκBα/RAP1活性呈负相关。结论我们的研究结果为明确EYA4是真正的肿瘤抑制因子提供了功能和机制的理论基础,该肿瘤抑制因子可抑制NF-κB/RAP1信号通路的异常激活,从而抑制HCC生长和侵袭。

关键词：眼缺失蛋白同源物4(eyes absent homolog 4,EYA4) RAS相关蛋白1(RAS-related protein 1,RAP1) 核因子-κB(nuclear factor-κB,NF-κB) 反式激活肝细胞癌

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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research Centre for molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

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miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

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Neural Regeneration Research 2025年第1期20卷 277-290页

作者： Meng Cong jing-jing Hu Yan Yu Xiao-Li Li Xiao-Ting Sun Li-Ting Wang Xia Wu Ling-Jie Zhu Xiao-Jia Yang Qian-Ru He Fei Ding Hai-Yan shi School of Medicine Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education and Coinnovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Physiology Jiangsu Health Vocational CollegeNanjingJiangsu ProvinceChina Department of Pathology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve ***-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular ***,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain *** investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose *** mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest *** performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest ***,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded ***,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously *** findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in ***-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell *** helps to explain the mechanism of action of the secretome and e

关键词： axotomy cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors

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Highly conductive and stable iodine doped argyrodite electrolyte for all-solid-state lithium batteries

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Journal of Energy Chemistry 2025年第1期100卷 50-58页

作者： Gaozhan Liu jing Zhang jing Yang jinghui Chen Xingyue Xiao Xiayin Yao Ningbo Institute of Materials Technology and Engineering Chinese Academy of Sciences Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences

Lithium argyrodites with high ionic conductivity and low cost are considered as one of the most prospective solid electrolytes for all-solid-state lithium ***,the poor chemical stability and compatibility with lithium metal limit their ***,Li5.4PS4.4Cl1.4I0.2solid electrolyte with high ionic conductivity of 11.49 m S cm-1and improved chemical stability is synthesized by iodine *** ultra-thin Li5.4PS4.4Cl1.4I0.2membrane with thickness of 10μm can be obtained by wet coating process,exhibiting a high ionic conductivity of 2.09 mS cm-1and low areal resistance of 1.17Ω***,iodine doping could in-situ form LiI at the lithium/electrolyte interface and improve the critical current density of Li5.4PS4.4Cl1.6from 0.8 to 1.35 mA *** resultant LiCoO2/Li5.4PS4.4Cl1.4I0.2/Li battery shows excellent cycling stability at 1 C,with a reversible specific capacity of 110.1 mA h g-1and a retention of 80.5% after 1000 *** addition,the assembled LiCoO2/Li5.4PS4.4Cl1.4I0.2membrane/Li pouch cell delivers an initial discharge capacity of 110.4 mA h g-1and 80.5% capacity retention after 100 cycles.

关键词： Solid-State Batteries

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3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration

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Nano-Micro Letters 2025年第2期17卷 18-45页

作者： Ke Yao Gaoying Hong Ximin Yuan Weicheng Kong Pengcheng Xia Yuanrong Li Yuewei Chen Nian Liu jing He Jue shi Zihe Hu Yanyan Zhou Zhijian Xie Yong He State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical EngineeringZhejiang UniversityHangzhou 310027People’s Republic of China Liangzhu Laboratory Zhejiang UniversityHangzhou 310027People’s Republic of China Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province College of Mechanical EngineeringZhejiang UniversityHangzhou 310027People’s Republic of China Stomatology Hospital School of StomatologyZhejiang University School of MedicineHangzhou 310027People’s Republic of China State Key Laboratory of Advanced Welding and Joining Harbin Institute of TechnologyHarbin 150001People’s Republic of China Institute of Digital Medicine Nanjing First HospitalNanjing Medical UniversityNanjing 210006People’s Republic of China

Hydrogel scaffolds have numerous potential applications in the tissue engineering ***,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical *** by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this ***,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent ***,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell ***,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT *** experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.

关键词： 3D printing Tough hydrogel scaffold Functional surface structure Tissue regeneration Biomaterials

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改良甲颏高度预测困难喉镜显露的准确性

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中华麻醉学杂志 2018年第4期38卷 466-469页

作者：杨扬陈觅史静莫怀忠吴宇明邹小华贵州医科大学附属医院麻醉科贵阳市550004

目的评价改良甲颏高度预测患者困难喉镜显露的准确性.方法择期气管插管全麻患者263例,年龄＞17岁,BMI＜ 33 kg/m^2,性别不限,ASA分级Ⅰ或Ⅱ级.入室后分别进行改良Mallampati评分（MMT）、甲颏高度（TMH）、改良甲颏高度（“嗅物位”... 详细信息

目的评价改良甲颏高度预测患者困难喉镜显露的准确性.方法择期气管插管全麻患者263例,年龄＞17岁,BMI＜ 33 kg/m^2,性别不限,ASA分级Ⅰ或Ⅱ级.入室后分别进行改良Mallampati评分（MMT）、甲颏高度（TMH）、改良甲颏高度（“嗅物位”甲颏高度,MTMH）测定.设定MMTⅢ或Ⅳ级为阳性预测指标.麻醉诱导后常规喉镜下显露声门,使用喉外压迫技术后Cormack-Lehane分级仍然为Ⅲ或Ⅳ级确定为困难喉镜显露.采用受试者工作特征曲线下面积（AUC）评价MMT、TMH和MTMH预测困难喉镜显露的准确性.结果困难喉镜显露患者24例,非困难喉镜显露患者239例,困难喉镜显露发生率10.0％,无气管插管失败患者.MTMH预测困难喉镜显露的AUC及其95％可信区间为0.966（0.936～0.984）,最佳临界点为46.83 mm,Youden指数为0.845 ***预测困难喉镜显露的灵敏度为91.67％、特异度为92.89％,OR值为143.647.与MMT和TMH比较,MTMH预测患者困难气道的AUC增大（P＜0.05）.结论改良甲颏高度可准确预测患者困难喉镜显露,最佳临界点为46.83 mm.

关键词：甲状软骨颏插管法气管内

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