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Palmitoylation of gnaQ/11 is critical for tumor cell proliferation and survival in gnaQ/11-mutant uveal melanoma

Frontiers of Medicine 2022年第5期16卷 784-798页

作者： Yan Zhang Baoyuan Zhang Yongyun li Yuting Dai Jiaoyang li donghe li Zhizhou Xia Jianming Zhang Ping liu Ming Chen Bo Jiao Ruibao Ren Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiCollaborative Innovation Center of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Ophthalmology Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Orbital Diseases and Ocular OncologyShanghai 200001China Department of Biology Brandeis UniversityWalthamMA 02454USA

More than 85%of patients with uveal melanoma(UM)carry a gnaQ or gna11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).gnaQ/11 relies on palmitoylation for membrane association and signal *** the palmitoylation of gnaQ/11 was discovered long before,its implication in UM remains ***,results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of gnaQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM *** inhibition through the mutation of palmitoylation sites suppressed gnaQ/11^(Q209L)-induced malignant transformation in NIH3T3 ***,the palmitoylation-deficient oncogenic gnaQ/11 failed to rescue the cell death initiated by the knock down of endogenous gnaQ/11 oncogenes in UM cells,which are much more dependent on Gα_(q/11) signaling for cell survival and proliferation than other melanoma cells without gnaQ/11 ***,the palmitoylation inhibitor,2-bromopalmitate,also specifically disrupted Gα_(q/11) downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in gnaQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor,ABT-199,in *** findings validate that gnaQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for gnaQ/11-driven UM.

关键词： uveal melanoma mutant gnaQ/11 palmitoylation BCL2 combination target therapy

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学科参考咨询循证的子宫颈癌筛查路径选择

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中国实用医药 2012年第15期7卷 52-53页

作者：张蒙纳李立宏金愉长春市群英社区卫生服务中心吉林大学中日联谊医院

目的探讨子宫颈癌普查性早期筛查的优选路径。方法从临床证据和文献证据两个方面,剖析各种筛查方法的不同适用性。结果人乳头瘤病毒(HPV)检测方法,阴性预测率高于99%,甚至达到100%。液基薄层细胞学检查(TCT),诊断符合率90%。结论大规模... 详细信息

目的探讨子宫颈癌普查性早期筛查的优选路径。方法从临床证据和文献证据两个方面,剖析各种筛查方法的不同适用性。结果人乳头瘤病毒(HPV)检测方法,阴性预测率高于99%,甚至达到100%。液基薄层细胞学检查(TCT),诊断符合率90%。结论大规模子宫颈癌筛查的路径应以HPV检测为初筛起点,筛查的路径是:HPV检测(阳性)→TCT(阳性)→阴道镜多点取材→组织病理检查。

关键词：子宫颈癌人乳头瘤病毒检测液基薄层细胞学检查

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TaNRT2.1-6B is a dual-affinity nitrate transporter contributing to nitrogen uptake in bread wheat under both nitrogen deficiency and sufficiency

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The Crop Journal 2022年第4期10卷 993-1005页

作者： Mengjiao li Tian Wang Hui Zhang Shuo liu Wenhu li Salah F.Abou Elwafa Hui Tian Key Laboratory of Plant Nutrition and Agri-environment in Northwest China Ministry of Agriculture and Rural AffairsCollege of Natural Resources and EnvironmentNorthwest A&F UniversityYangling 712100ShaanxiChina Agronomy Department Faculty of AgricultureAssiut UniversityAssiut 71526Egypt

Multiple nitrate transporter(NRT)genes exist in the genome of bread wheat,and it is of great importance to identify the elite NRT genes for N-efficient wheat cultivar breeding.A candidate gene association study(CGAS)of six N use efficiency(NUE)related traits(grain N concentration(GNC),straw N concentration(SNC),grain yield(GY),grain N accumulation(gna),shoot total N accumulation(STN)and N harvest index(NHI))was performed based on SNPs in 46 NRT2 genes using a panel composed of 286 wheat *** identified TaNRT2.1-6B as an elite NRT gene that is significantly associated with four(NHI,SNC,gna and GY)of the six NUE-related traits ***2.1-6B is located on the plasma membrane and acts as a dual-affinity *** overexpression of TaNRT2.1-6B increased the N influx and root growth of wheat,whereas gene silence lines resulted in the opposite *** overexpression of TaNRT2.1-6B also improved GY and N accumulation of wheat under either limited or sufficient N *** data provide the TaNRT2.1-6B gene and the two associated SNP markers as promising powerful tools for breeding wheat cultivars with high N uptake ability and NUE.

关键词： Candidate gene association study Wheat TaNRT2.1-6B Dual-affinity transporter Nitrogen use efficiency

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河北产淡豆豉黄酮类成分HPLC指纹图谱研究

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大豆科学 2009年第2期28卷 329-331页

作者：牛丽颖刘敏彦王玉峰杜红娜王鑫国河北医科大学中医学院河北石家庄050091 河北医科大学医药研究院河北石家庄050035

建立河北产淡豆豉黄酮类成分HPLC指纹图谱,控制淡豆豉的质量。采用3%冰乙酸-乙腈,梯度洗脱的方法进行色谱分离,对各色谱峰进行数据处理,得出淡豆豉的指纹图谱。标定了淡豆豉13个共有峰,且共有峰重现性良好。采用HPLC方法制定的淡豆豉的... 详细信息

建立河北产淡豆豉黄酮类成分HPLC指纹图谱,控制淡豆豉的质量。采用3%冰乙酸-乙腈,梯度洗脱的方法进行色谱分离,对各色谱峰进行数据处理,得出淡豆豉的指纹图谱。标定了淡豆豉13个共有峰,且共有峰重现性良好。采用HPLC方法制定的淡豆豉的指纹图谱,可用于淡豆豉的质量评价。

关键词：淡豆豉黄酮类成分 HPLC 指纹图谱

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Transgenic plants expressing the AalT/gna fusion protein show increased resistance and toxicity to both chewing and sucking pests

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Insect Science 2016年第2期23卷 265-276页

作者： Shu-Min liu Jie li Jin-Qi Zhu Xiao-Wei Wang Cheng-Shu Wang Shu-Sheng liu Xue-Xin Chen Sheng li Key Laboratory of Insect Developmental and Evolutionary Biology Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai State Key Laboratory of Rice Biology and Ministry of Agriculture Key Laboratory of Agricultural Entomology Institute of Insect Sciences Zhejiang University Hangzhou China

The adoption of pest-resistant transgenic plants to reduce yield losses and de- crease pesticide use has been successful. To achieve the goal of controlling both chewing and sucking pests in a given transgenic plant, we generated transgenic tobacco, Arabidopsis, and rice plants expressing the fusion protein, AalT/gna, in which an insecticidal scor- pion venom neurotoxin （Androctonus australis toxin, AalT） is fused to snowdrop lectin （Galanthus nivalis agglutinin, gna）. Compared with transgenic tobacco and Arabidop- sis plants expressing AaIT or gna, transgenic plants expressing AalT/gna exhibited increased resistance and toxicity to one chewing pest, the cotton bollworm, Helicoverpa armigera. Transgenic tobacco and rice plants expressing AalT/gna showed increased resistance and toxicity to two sucking pests, the whitefly, Bemisia tabaci, and the rice brown planthopper, Nilaparvata lugens, respectively. Moreover, in the field, transgenic rice plants expressing AalT/gna exhibited a significant improvement in grain yield when infested with N. lugens. This study shows that expressing the AalT/gna fusion protein in transgenic plants can be a useful approach for controlling pests, particularly sucking pests which are not susceptible to the toxin in Bt crops.

关键词： AalT AalT/gna chewing pest gna fusion protein pest control resistance sucking pest toxicity transgenic plant

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Microstructures and Properties of 550 MPa Grade High Strength Thin-walled H-beam Steel

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Journal of Wuhan University of Technology(Materials Science) 2013年第6期28卷 1217-1222页

作者： CHEN Jiping KANG Yonglin QIAN Jianqing li Shengzhi QIAN Haifan School of Materials Science and Engineering Key Lab of Metals and Processing of Anhui ProvinceAnhui University of Technology School of Materials Science and Engineering State Key Laboratory for Advanced Metals and MaterialsUniversity of Science and Technology Beijing Ma'anshan Iron and Steel Co. Ltd

The microstructures and mechanical properties of 550 MPa grade lightweight high strength thin-walled H-beam steel were experimentally studied. The experimental results show that the microstructure of the air-cooled H-beam steel sample is consisted of ferrite, pearlite and a small amount of granular bainites as well as fine and dispersive V（C,N） precipitates. The microstructure of the water-cooled steel sample is consisted of ferrite and bainite as well as a small amount of fine pearlites. The microstructure of the water-cooled sample is finer than that of the air-cooled sample with the average intercept size of the surface grains reaching to 3.5 gna. The finish rolling temperature of the thin-walled high strength H-beam steel is in the range of 750 ~C-850 ~C. The lower the finish rolling temperature and the faster the cooling rate, the finer the ferrite grains, the volume fraction of bainite is increased through water cooling process. Grain refinement strengthening and precipitation strengthening are used as major strengthening means to develop 550 MPa grade lightweight high strength thin- walled H-beam steel. Vanadium partially soluted in the matrix and contributes to the solution strengthening. The 550 MPa grade high-strength thin-walled H-beam steel could be developed by direct air cooling after hot rolling to fully meet the requirements of the target properties.

关键词： H-beam steel high strength thin-walled vanadium-nitrogen microalloying microstructure and mechanical property strengthening mechanism

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Simplified algorithm for genetic subtyping in diffuse large B-cell lymphoma

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2304-2314页

作者： Rong Shen Di Fu Lei dong Mu-Chen Zhang Qing Shi Zi-Yang Shi Shu Cheng li Wang Peng-Peng Xu Wei-li Zhao Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Pathology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Pôle de Recherches Sino-Français en Science du Vivant et Génomique Laboratory of Molecular PathologyShanghaiChina

Genetic classification helps to disclose molecular heterogeneity and therapeutic implications in diffuse large B-cell lymphoma(DLBCL).Using whole exome/genome sequencing,RNA-sequencing,and fluorescence in situ hybridization in 337 newly diagnosed DLBCL patients,we established a simplified 38-gene algorithm(termed‘LymphPlex’)based on the information on mutations of 35 genes and rearrangements of three genes(BCL2,BCL6,and MYC),identifying seven distinct genetic subtypes:TP53Mut(TP53 mutations),MCD-like(MYD88,CD79B,PIM1,MPEG1,BTG1,TBL1XR1,PRDM1,IRF4 mutations),BN2-like(BCL6 fusion,NOTCH2,CD70,DTX1,BTG2,TNFAIP3,CCND3 mutations),N1-like(NOTCH1 mutations),EZB-like(BCL2 fusion,EZH2,TNFRSF14,KMT2D,B2M,FAS,CREBBP,ARID1A,EP300,CIITA,STAT6,gna13 mutations,with or without MYC rearrangement),and ST2-like(SGK1,TET2,SOCS1,DDX3X,ZFP36L1,DUSP2,STAT3,IRF8 mutations).Extended validation of 1001 DLBCL patients revealed clinical relevance and biological signature of each genetic ***53Mut subtype showed poor prognosis,characterized by p53 signaling dysregulation,immune deficiency,and PI3K ***-like subtype was associated with poor prognosis,activated B-cell(ABC)origin,BCL2/MYC double-expression,and NF-κB ***2-like subtype showed favorable outcome within ABC-DLBCL and featured with NF-κB activation.N1-like and EZB-like subtypes were predominated by ABC-DLBCL and germinal center B-cell(GCB)-DLBCL,***-like-MYC+subtype was characterized by an immunosuppressive tumor microenvironment,while EZB-like-MYC-subtype by NOTCH ***2-like subtype showed favorable outcome within GCB-DLBCL and featured with stromal-1 *** subtype-guided targeted agents achieved encouraging clinical response when combined with ***,LymphPlex provided high efficacy and feasibility,representing a step forward to the mechanism-based targeted therapy in DLBCL.

关键词： lymphoma algorithm representing

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肺静脉血流频谱对胎儿心脏发育异常的诊断价值

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中华医学超声杂志（电子版） 2005年第2期2卷 80-82页

作者：隗冬梅吴雅峰王丽吴江张萍娜姜维 100020 首都医科大学附属北京朝阳医院超声医学科

目的探讨胎儿肺静脉血流参数改变对胎儿心脏发育异常的诊断价值.方法对126例胎龄22～38周的胎儿行心脏多普勒超声检查,检测肺静脉血流参数,根据胎儿心内结构是否正常分为:胎儿心内结构正常者为Ⅰ组(114例),又将Ⅰ组分为血流正常者为Ⅰ-1... 详细信息

目的探讨胎儿肺静脉血流参数改变对胎儿心脏发育异常的诊断价值.方法对126例胎龄22～38周的胎儿行心脏多普勒超声检查,检测肺静脉血流参数,根据胎儿心内结构是否正常分为:胎儿心内结构正常者为Ⅰ组(114例),又将Ⅰ组分为血流正常者为Ⅰ-1组(101例),存在轻度瓣膜反流者为Ⅰ-2组(13例);胎儿心内结构异常者为Ⅱ组(12例).测量胎儿肺静脉血流参数:收缩期峰值流速(S)、舒张期峰值流速(D)、心房收缩期波谷流速(A),并计算S/D、S/A、(S-A)/D,分析以上参数与分组、胎龄的直线相关关系.结果 2组间(S-A)/D值差异有统计学意义(P＜0.05),(S-A)/D与分组的相关系数为r=0.208,P=0.019,与胎龄的相关系数为r=-0.023,P=0.8,其余各参数与分组、胎龄无明显相关性.Ⅰ组内血流异常与血流正常者各参数相比无显著性差异(P>0.05).结论肺静脉血流参数可作为评价胎儿心内结构是否异常的一项指标.

关键词：胎儿心脏肺静脉血流速度彩色多普勒超声检查先天性心脏缺损肺静脉血流频谱发育异常诊断价值收缩期峰值流速多普勒超声检查

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Metabolic engineering of Corynebacterium glutamicum S9114 based on whole-genome sequencing for efficient N-acetylglucosamine synthesis

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Synthetic and Systems Biotechnology 2019年第3期4卷 120-129页

作者： Chen Deng Xueqin Lv Yanfeng liu Jianghua li Wei Lu Guocheng Du Long liu Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationJiangnan UniversityWuxi214122China Key Laboratory of Industrial Biotechnology Ministry of EducationJiangnan UniversityWuxi214122China Shandong Runde Biotechnology CO. LTDTaian271200China

Glucosamine(GlcN)and its acetylated derivative N-acetylglucosamine(GlcNAc)are widely used in the pharmaceutical ***,we attempted to achieve efficient production of GlcNAc via genomic engineering of Corynebacterium ***,we ligated the gna1 gene,which converts GlcN-6-phosphate to GlcNAc-6-phosphate by transferring the acetyl group in Acetyl-CoA to the amino group of GlcN-6-phosphate,into the plasmid pJYW4 and then transformed this recombinant vector into the *** ATCC 13032,ATCC 13869,ATCC 14067,and S9114 strains,and we assessed the GlcNAc titers at 0.5 g/L,1.2 g/L,0.8 g/L,and 3.1 g/L from each strain,*** suggested that there were likely to be significant differences among the key genes in the glutamate and GlcNAc synthesis pathways of these *** ***,we performed whole genome sequencing of the S9114 strain,which has not been previously published,and found that there are many differences among the genes in the glutamate and GlcNAc synthesis pathways among the four strains ***,nagA(encoding GlcNAc-6-phosphate deacetylase)and gamA(encoding GlcN-6-phosphate deaminase)were deleted in *** S9114 to block the catabolism of intracellular GlcNAc,leading to a 54.8%increase in GlcNAc production(from 3.1 to 4.8 g/L)when grown in a shaker *** addition,lactate synthesis was blocked by knockout of ldh(encoding lactate dehydrogenase);thus,further increasing the GlcNAc titer to 5.4 g/***,we added a key gene of the GlcN synthetic pathway,glmS,from different sources into the expression vector pJYW-4-ceN,and the resulting recombinant strain CGGN2-gna1-CgglmS produced the GlcNAc titer of 6.9 g/*** is the first report concerning the metabolic engineering of ***,and the results of this study provide a good starting point for further metabolic engineering to achieve industrial-scale production of GlcNAc.

关键词： C.glutamicum Complete genome N-acetylglucosamine Metabolic engineering

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Gambogenic acid induces apoptosis via upregulation of Noxa in oral squamous cell carcinoma

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Chinese Journal of Natural Medicines 2024年第7期22卷 632-642页

作者： CHENG Xinran FENG Mengyuan ZHANG Anjie GUO Jian GONG Yunlai HU Xiaohui HAN Quanbin li Shengbao YU Xianjun Department of Gastroenterology Taihe HospitalHubei University of MedicineShiyan 442000China Laboratory of Inflammation and Molecular Pharmacology School of Basic Medical Sciences&Biomedical Research InstituteHubei Key Laboratory of Wudang Local Chinese Medicine ResearchSchool of PharmacyHubei University of MedicineShiyan 442000China Inflammation-Cancer Transformation and Wudang Chinese Medicine Research Hubei Talent Introduction and Innovation Demonstration BaseHubei University of MedicineShiyan 442000China School of Chinese Medicine Hong Kong Baptist UniversityHong Kong 999077China

Gambogenic acid(gna),a bioactive compound derived from the resin of Garcinia hanburyi,has demonstrated significant antitumor ***,its mechanisms of action in oral squamous cell carcinoma(OSCC)remain largely *** study aimed to elucidate the apoptotic effects of gna on OSCC cell lines CAL-27 and *** results indicated that gna induced apoptosis by upregulating the pro-apoptotic protein *** investigations revealed that gna treatment led to the generation of reactive oxygen species(ROS),which activated endoplasmic reticulum(ER)stress,culminating in cell *** of ROS production and ER stress pathways significantly mitigated gna-induced Noxa upregulation and subsequent ***,in vivo studies using a murine xenograft model demonstrated that gna administration effectively inhibited the growth of CAL-27 ***,these findings underscore gna’s potential as a therapeutic agent for the treatment of OSCC.

关键词： Oral squamous cell carcinoma Gambogenic acid Apoptosis Noxa ROS/ER stress

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