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HLA-B-associated transcript 3 (Bat3) stabilizes and activates p53 in a HAUSP-dependent manner

Journal of Molecular Cell Biology 2020年第2期12卷 99-112页

作者： Rui Zhang Di Cui TengXue Yue Lang yunfan Zhang lianjie li Haili Sun Yu Kuang Gebin li Jun Tang Department of Basic Veterinary College of Veterinary MedicineChina Agricultural UniversityBeijing 100193China State Key Laboratory of Agrobiotechnology China Agricultural UniversityBeijing 100193China Department of Clinical Veterinary College of Veterinary MedicineChina Agricultural UniversityBeijing 100193China Clinical Research Institute Zhejiang Provincial People's HospitalPeople's Hospital of Hangzhou Medical CollegeHangzhou 310014China

The p53 pathway is a highly complex signaling network including several key *** is a critical component of the p53 pathway acting as a deubiquitinase for both p53 and its key repressor ***,we identified a novel HAUSP-interacting protein,HLA-B-associated transcript 3(Bat3)and found it to be capable of inducing p53 stabilization and activation via a HAUSP-dependent mechanism,resulting in cell growth ***,the deubiquitylating enzymatic activity of HAUSP was not required for this ***-immunoprecipitation showed that p53 coexisted in a complex with Bat3 and HAUSP in vivo,and HAUSP may serve as a binding mediator to enhance the interaction between p53 and *** studies revealed that formation of this three-protein complex interfered with the binding of p53 to its proteasome receptor S5a and promoted the accumulation of p53 in ***,Mdm2 protein abundance is also regulated by Bat3 in the presence of *** of Bat3 and HAUSP increases Mdm2 protein levels without influencing the p53–Mdm2 interaction and Mdm2-mediated p53 ubiquitination,indicating that Bat3–HAUSP-mediated protein stabilization is not specific to p53 and different mechanisms may be involved in Bat3-mediated regulation of p53–Mdm2 ***,our study unravels a novel mechanism by which p53 is stabilized and activated by HAUSP-mediated interaction with Bat3 and implies that Bat3 might function as a tumor suppressor through the stabilization of p53.

关键词： Bat3 p53 stabilization HAUSP S5a proteasome recognition

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基于三维数字化的腹横筋膜平面精准阻滞麻醉在剖宫产手术的临床研究

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中国医药科学 2020年第10期10卷 75-77页

作者：李运繁杨伟才吴丹丹龙家棋黄锋谟何志妥广东省廉江市人民医院麻醉科广东廉江524400

目的探讨研究基于三维数字化的腹横筋膜平面(TAP)精准阻滞麻醉在剖宫产手术的临床效果.方法选取2019年6~11月来我院进行剖宫产手术孕妇96例作为研究对象,按照随机数字表法分为对照组(n=48)和观察组(n=48).两组均采用超声引导TAP阻滞... 详细信息

目的探讨研究基于三维数字化的腹横筋膜平面(TAP)精准阻滞麻醉在剖宫产手术的临床效果.方法选取2019年6~11月来我院进行剖宫产手术孕妇96例作为研究对象,按照随机数字表法分为对照组(n=48)和观察组(n=48).两组均采用超声引导TAP阻滞方法用于剖宫产术后的镇痛,其中观察组采用腹壁结构的三维数字化重建,导航下行TAP阻滞麻醉,对照组采用超声引导常规给药行阻滞麻醉,治疗后对患者治疗效果进行评估,比较两组镇痛效果术后首次下床、苏醒时间以及不良反应.结果观察组术后VAS评分低于对照组(P<0.05);观察组术后首次下床时间和苏醒时间早于对照组(P<0.05);两组术后24h VAS评分均最高,之后随时间疼痛逐渐减轻(P<0.05).观察组不良反应发生率明显低于对照组(P<0.05).结论将三维数字化的TAP精准阻滞麻醉应用于剖宫产手术,极大地改善了患者预后,效果显著,对剖宫产孕妇术后起到有效的镇痛作用,减少了产妇术后的恢复时间,减少麻醉药物不良反应的发生,提高了用药安全性,值得推广应用.

关键词：剖宫产手术 TAP阻滞麻醉三维数字化重建快速康复外科镇痛

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CPT: a pre-trained unbalanced transformer for both Chinese language understanding and generation

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Science China(Information Sciences) 2024年第5期67卷 43-55页

作者： yunfan SHAO Zhichao GENG Yitao liU Junqi DAI Hang YAN Fei YANG Zhe li Hujun BAO Xipeng QIU School of Computer Science Fudan University Shanghai Key Laboratory of Intelligent Information Processing Fudan University Zhejiang Lab

In this paper, we take the advantage of previous pre-trained models(PTMs) and propose a novel Chinese pre-trained unbalanced transformer(CPT). Different from previous Chinese PTMs, CPT is designed to utilize the shared knowledge between natural language understanding(NLU) and natural language generation(NLG) to boost the performance. CPT consists of three parts: a shared encoder, an understanding decoder, and a generation decoder. Two specific decoders with a shared encoder are pretrained with masked language modeling(MLM) and denoising auto-encoding(DAE) tasks, *** the partially shared architecture and multi-task pre-training, CPT can(1) learn specific knowledge of both NLU or NLG tasks with two decoders and(2) be fine-tuned flexibly that fully exploits the potential of the model. Moreover, the unbalanced transformer saves the computational and storage cost, which makes CPT competitive and greatly accelerates the inference of text generation. Experimental results on a wide range of Chinese NLU and NLG tasks show the effectiveness of CPT.

关键词： pre-trained model transformer language model generation unified model

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Cysteine mutations impair the structural stability of phosphomannomutase 2(PMM2)in glycosylation-associated metabolic disorders

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Genes & Diseases 2023年第5期10卷 1743-1746页

作者： yunfan Pan li lin Fan Yu Jingmiao Sun Guannan Bai Xinyu He Jianhua Mao lidan Hu The Children’s Hospital Zhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Beijing Advanced Innovation Center for Structural Biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China Department of Nephrology The Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthNational Children's Regional Medical CenterHangzhouZhejiang 310052China

Glycosylation is a ubiquitous molecular modification in the process of cellular metabolism regulation,which plays a vital role in maintaining and regulating cellular *** in glycosylation enzymes may jeopardize the glycosylation process and eventually lead to the metabolic disease,manifesting with either a neurologic or multisystem phenotype,which is also known as congenital disorder of glycosylation(CDG).1 It could be classified into type I CDG and type II CDG,and the latter was referred to as the abnormal formation of nascent *** 2 CDG(PMM2-CDG),the most prevalent CDG with an incidence rate of 1 in 20,000 individuals,is mainly due to the metabolic disorder of phosphomannomutase 2(PMM2).2 PMM2 participates in the conversion of mannose-6-phosphate to *** cysteine residues,as one of the least abundant amino acids,have unique attributes to maintain the stability of protein structure,especially for catalytic activity and protein folding.3 Therefore,cysteine mutations have been identified in various diseases including *** by the crystal structure of PMM2(PDB ID:7O5Z),4 four cysteine mutations in the hPMM2,C9Y,C103F,C192G,and C241S,have been found in *** bioinformatic analysis by PROVEAN,the four cysteine mutations were predicted with“Deleterious”,ranking with the best two were C103F and C192G(C9Y:−5.493,C103F:−6.339,C192G:−11.176,C241S:−2.986).However,the underlying pathological mechanism is still *** them,C103F and C192G have only been reported in clinical study without a detailed explanation,so they were selected for our *** mutants were located near the linker region 1 and 2;C103F was located on the No.4αhelix and C192G was located on the No.7αhelix(Fig.S1A).The purpose of this study was to explore the structure and function roles of PMM2 clinical mutation and investigate the role of cysteine in PMM2 which might provide new insights into preventive and therape

关键词： stability eventually latter

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The tumor suppressor CYLD controls epithelial morphogenesis and homeostasis by regulating mitotic spindle behavior and adherens junction assembly

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Journal of Genetics and Genomics 2017年第7期44卷 343-353页

作者： Wei Xie yunfan Yang Siqi Gao Ting Song Yuhan Wu Dengwen li Min liu Jun Zhou Key Laboratory ofAnimal Resistance Biology ofShandong Province Institute of Biomedical SciencesCollege ofLife Sciences.Shandong Normal University Jinun 250014China State Key Laboratory ofMedicinal Chemical Biology College of life SciencesNankai UniversityTianjin 300071China

Epithelial morphogenesis and homeostasis are essential for animal development and tissue regeneration, and epithelial disorganization is associated with developmental disorders and tumorigenesis. However, the molecular mechanisms that contribute to the morphogenesis and homeostasis of the epithelium remain elusive. Herein, we report a novel role for the cylindromatosis （CYLD） tumor suppressor in these events. Our results show that CYLD depletion disrupts epithelial organization in both Drosophila egg chambers and mouse skin and intestinal epithelia. Microscopic analysis of proliferating cells in mouse epithelial tissues and cultured organoids reveals that loss of CYLD synergizes with tumor-promoting agents to cause the misorientation of the mitotic spindle. Mechanistic studies show that CYLD accu- mulates at the cell cortex in epithelial tissues and cultured ceils, where it promotes the formation of epithelial adherens junctions through the modulation of microtuhule dynamics. These data suggest that CYLD controls epithelial morphogenesis and homeostasis by modulating the assembly of adherens junctions and ensuring proper orientation of the mitotic spindle. Our findings thus provide novel insight into the role of CYLD in development, tissue homeostasis, and tumorigenesis.

关键词： Epithelium CYLD Mitotic spindle Cell cortex Adherens junction

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胶质瘤条件培养基促进巨噬细胞糖酵解及表型转化

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基础医学与临床 2024年第5期44卷 599-605页

作者：张迪雅李云帆郭泓江仇佳星王钰铖鞠瑞郭磊中国医学科学院基础医学研究所、北京协和医学院基础学院药理系北京100005

目的初步探索胶质瘤条件培养基诱导巨噬细胞糖酵解代谢与促癌介质表达的作用与机制。方法以经过缺氧与小鼠胶质瘤细胞系GL261条件培养基(GCM)诱导后的骨髓来源巨噬细胞(BMDM)(GCM-BMDM)为体外胶质瘤相关巨噬细胞(GAMs)模型,通过qPCR检测... 详细信息

目的初步探索胶质瘤条件培养基诱导巨噬细胞糖酵解代谢与促癌介质表达的作用与机制。方法以经过缺氧与小鼠胶质瘤细胞系GL261条件培养基(GCM)诱导后的骨髓来源巨噬细胞(BMDM)(GCM-BMDM)为体外胶质瘤相关巨噬细胞(GAMs)模型,通过qPCR检测GCM-BMDM中M1与M2促癌介质、缺氧诱导因子-1α(HIF-1α)与糖酵解相关代谢酶基因mRNA水平;采用Seahorse细胞能量测定方法检测GCM-BMDM细胞外酸化速率(ECAR);通过Western blot检测信号传导与转录激活因子6(STAT6)、信号传导与转录激活因子3(STAT3)及其磷酸化形式p-STAT6、p-STAT3蛋白水平。结果GCM刺激BMDM Hif-1α与多种M1、M2促癌介质mRNA表达(P<0.01);GCM上调BMDM多种糖酵解基因mRNA表达(P<0.01),升高糖酵解水平(P<0.001),加入乳酸脱氢酶抑制剂stiripentol(STP)处理后糖酵解水平降低(P<0.05);STP下调GCM-BMDM Hif-1α与促癌介质Il-1β、Il-6、Ido与Cd163 mRNA水平(P<0.01);STP下调GCM-BMDM p-STAT3/STAT3与p-STAT6/STAT6比值(P<0.05)。结论GCM增加糖酵解代谢,促进HIF-1α、STAT3与STAT6介导的转录调控机制以诱导GAMs的促癌表型。STP能有效抑制GAMs糖酵解并降低GAMs促癌介质的转录表达水平。

关键词：胶质瘤相关巨噬细胞糖酵解乳酸脱氢酶抑制剂

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Neuronal-like differentiation of single versus multiple treatments with human amnion-derived mesenchymal stem cells induced by basic fibroblast growth factor

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Neural Regeneration Research 2009年第9期4卷 694-698页

作者： Hongliang Jiao Fangxia Guan Xiang Hu Jianbin li Hong Shan Wei li Jun li Ying Du Bo Yang yunfan Zhou Department of Neurosurgery First Hospital of Zhengzhou University Zhengzhou 450052 Henan Province China Department of Bioengineering Zhengzhou University Zhengzhou 450001 Henan Province China Shenzhen Beike Cell Engineering Institute Shenzhen 518057 Guangdong Province China Henan Province Red Cross Blood Center Zhengzhou 450012 Henan Province China Jiangsu Public Technology Service Platform of Stem Cells and Biotherapy Taizhou 225300 Jiangsu Province China Department of Microbiology and Immunology Medical School of Zhengzhou University Zhengzhou 450001 Henan Province China

BACKGROUND： Cultures from multiple portions of umbilical cord blood mesenchymal stem cells have been shown to undergo more rapid proliferation and attachment than single portions. OBJECTIVE： To observe growth of basic fibroblast growth factor （bFGF）-induced cultures of human amnion-derived mesenchymal stem cells （AMSCs） and differentiation into neuronal-like cells. DESIGN, TIME AND SETTING： Comparative observation. The study was performed at the Laboratory of Microbiology and Immunology, Basic Medical School of Zhengzhou University from January to May 2008. METHODS： Amnia from full-term, uterine-incision delivery were donated by 12 healthy women. AMSCs were obtained by cell separation and culture techniques, and were passaged and induced by bFGF. From the third passage, a total of 1 mLAMSCs, at a density of 1.0 × 10^4/mL, was separately harvested from six samples, which served as group A. A total of 1 mL AMSCs, at a density of 1.0 × 10^4/mL, was harvested separately from the remaining six samples, which served a group B. A total of 0.5 mL from the six samples of group A and 0.5 mL from the six samples of grot, B were combined to form group C. MAIN OUTCOME MEASURES： Differences in cell quantity among the three groups were compare by cell quantification and 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） analysis. Expression of a glial cell marker, neuron-specific enolase, and nestin was detected in the three groups by immunocytochemistry. RESULTS： Cell quantification and MTT analysis of live cells, as well as AMSC absorbance, were significantly greater in group C compared with groups A and B at 18 days of culture （P 〈 0.05）, anc no significant difference was observed between groups A and B. Glial fibrillary acidic protein, neuron-specific enolase, and nestin were expressed in all groups following bFGF induction. CONCLUSION： Mixed AMSC cultures promoted proliferation, and bFGF-induced AMSCs differentiated into neuronal-like cells.

关键词： amnion mesenchymal stem cells induction mixed culture

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蠕形螨睑缘炎中西医诊治进展

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中医眼耳鼻喉杂志 2020年第4期10卷 226-229页

作者：李运帆李翔杜薇万婧雯易文华韩明江吴美玲高瑞雪何茜成都中医药大学四川成都610075 成都中医药大学附属医院四川成都610072

睑缘炎是睑缘表面、睫毛毛囊及其腺体组织的亚急性或慢性炎症。其病因复杂,一般与细菌感染、理化刺激、屈光不正、慢性结膜炎、溢泪、隐斜、不良卫生习惯和机体抵抗力下降有关,为临床常见眼病。根据临床不同特点,可分为三类:鳞屑性睑缘... 详细信息

睑缘炎是睑缘表面、睫毛毛囊及其腺体组织的亚急性或慢性炎症。其病因复杂,一般与细菌感染、理化刺激、屈光不正、慢性结膜炎、溢泪、隐斜、不良卫生习惯和机体抵抗力下降有关,为临床常见眼病。根据临床不同特点,可分为三类:鳞屑性睑缘炎、溃疡性睑缘炎、眦部睑缘炎。轻者导致患者眼部刺激症状,严重者可累及睑板腺和角膜而影响视力。近年来越来越多研究发现蠕形螨感染可能是睑缘炎的重要病因之一,但该病的诊治仍存在局限性。本文综述近年来蠕形螨睑缘炎中西医诊治进展,以供参考。

关键词：蠕形螨睑缘炎中西医诊治

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Preparation of Cerium Doped Cu/MIL-53(A1) Catalyst and Its Catalytic Activity in CO Oxidation Reaction

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Journal of Wuhan University of Technology(Materials Science) 2017年第1期32卷 23-28页

作者：谭海燕 ZHOU Yin YAN yunfan 胡卫兵 SHI Xinyu TAN Zhidou TIAN li ZHENG Yin School of Chemistry and Environmental Engineering Hubei University for Nationalities Sustainable Energy Laboratory Faculty of Material Science and Chemistry China University of Geosciences

Metal-organic framework（MOF） material MIL-53（A1） with high thermal stability was prepared by a solvothermal method,serving as a support material of cerium doped copper catalyst（Ce-Cu）/MIL-53（A1） material for CO oxidation with high catalytic *** catalytic performance between the（CuCe）/MIL-53（A1） and the Cu/MIL-53（A1） catalytic material was compared to understand the catalytic behavior of the *** catalysts were characterized by thermogravimetric-differential scanning calorimetry（TGDSC）,N2 adsorption- desorption,X-ray diffraction（XRD）,and transmission electron microscopy（TEM）.The characterization results showed that MIL-53（A1） had good stability and high surface areas,the（Ce-Cu）nanoparticles on the MIL-53（A1） support was ***,the heterogeneous catalytic composite materials（Ce-Cu）/MIL-53（A1） catalyst exhibited much higher activity than that of the Cu/MIL- 53（A1） catalyst in CO oxidation test,with 100%conversion at 80 ℃.The results reveal that（Cu-Ce）/MIL-53（A1） is the suitable candidate for achieving low temperature and higher activity CO oxidation catalyst of MOFs.

关键词： metal-organic framework solvothermal synthesis MIL-53(Al) cerium doped copper catalyst CO catalytic oxidation

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机器人辅助腹腔镜膀胱癌根治性切除术后回肠膀胱术和输尿管皮肤造口术在老龄患者中的单中心围术期效果及并发症分析

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临床泌尿外科杂志 2024年第9期39卷 760-764页

作者：韩坤何靖珂蒋林岑李云帆罗雨苏帅张金栋王德林重庆医科大学附属第一医院泌尿外科重庆400016

目的探究在接受机器人辅助腹腔镜膀胱癌根治性切除术(robot-assisted radical cystectomy,RARC)的老龄患者中,回肠膀胱术(ileal conduit,IC)和输尿管皮肤造口术(cutaneous ureterostomy,CU)对其短期内疗效的分析。方法回顾性分析2016年... 详细信息

目的探究在接受机器人辅助腹腔镜膀胱癌根治性切除术(robot-assisted radical cystectomy,RARC)的老龄患者中,回肠膀胱术(ileal conduit,IC)和输尿管皮肤造口术(cutaneous ureterostomy,CU)对其短期内疗效的分析。方法回顾性分析2016年6月—2024年2月于重庆医科大学附属第一医院泌尿外科行RARC的83例年龄≥65岁患者的临床资料,其中46例行IC,37例行CU。对于纳入患者的基线资料使用倾向性评分匹配(propensity score matching,PSM)调整患者特征后,比较PSM前后2组患者的围手术期和术后30 d预后的结果。结果PSM前相较于IC组,CU组的年龄较大(P<0.01),年龄校正查尔森合并症指数(age-adjusted Charlson comorbidity index,aCCI)的值较大(P<0.01),手术时间更短(P=0.002),PSM后2组患者在年龄、aCCI值上差异无统计学意义。在PSM前后,相较于IC组,CU组患者的术后住院时间更短(P=0.002,P=0.022)、术中失血量更少(P<0.001,P=0.005)、术后30 d并发症总发生率更低(P=0.008,P=0.016)、发生漏尿(P=0.013,P=0.028)和肠梗阻(P=0.037,P=0.028)的概率更低。结论对于合并多种全身疾病、一般情况较差的老龄肌层浸润性膀胱癌的患者,这类人群接受RARC联合CU手术在短期内的疗效可能更佳。

关键词：机器人辅助手术膀胱癌老龄回肠膀胱术输尿管皮肤造口术

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