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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis
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作者 Ruiqi Qiu Mingzhu Yang +5 位作者 Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng Han Bo Lei 《Neural Regeneration Research》 SCIE CAS 2025年第8期2408-2419,共12页
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso... Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa. 展开更多
关键词 APOPTOSIS AAV2-PDE6B ERK1/2 gene therapy PHOTOTRANSDUCTION PROTEOMICS rd10 retinitis pigmentosa
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抗条锈优质温光型不育系MTS-1利用价值分析 被引量:4
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作者 陶军 李生荣 +4 位作者 周强 雷加容 欧俊梅 杜小英 庞启华 《西南农业学报》 CSCD 2007年第4期854-856,共3页
对抗条锈温光型不育系MTS-1的不育特性,抗性及配制的组合杂种优势,品质特性进行了研究。结果表明:MTS-1不育性稳定,制种纯度高;MTS-1对条锈免疫且抗性遗传力强,其所配组合对条锈有较好的抗性;杂种一代优势较强;品质特性优良,粗蛋白含量... 对抗条锈温光型不育系MTS-1的不育特性,抗性及配制的组合杂种优势,品质特性进行了研究。结果表明:MTS-1不育性稳定,制种纯度高;MTS-1对条锈免疫且抗性遗传力强,其所配组合对条锈有较好的抗性;杂种一代优势较强;品质特性优良,粗蛋白含量达16.849%(干基),湿面筋含量达49.3%(14%),形成时间达4.8 min,稳定时间达7.0 min。 展开更多
关键词 mts-1 温光敏 不育系 抗条锈 优质
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介孔MTS-1催化剂的合成及其光催化活性研究 被引量:1
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作者 田进军 赵晓洋 刘玉民 《信阳师范学院学报(自然科学版)》 CAS 北大核心 2014年第4期547-550,共4页
以水热合成的微孔TS-1分子筛为基体,通过有机碱改性处理制备了介孔MTS-1催化剂.利用X-射线衍射、N2吸脱附等温线、紫外-可见光谱和透射电镜等方法对催化剂的形貌及表面特性进行了系统表征.数据表明,改性处理能明显提高材料的比表面积和... 以水热合成的微孔TS-1分子筛为基体,通过有机碱改性处理制备了介孔MTS-1催化剂.利用X-射线衍射、N2吸脱附等温线、紫外-可见光谱和透射电镜等方法对催化剂的形貌及表面特性进行了系统表征.数据表明,改性处理能明显提高材料的比表面积和孔体积.在紫外光照射下,以罗丹明B(RhB)作为光催化降解探针分子,探讨了MTS-1催化剂的光催化活性.TS-1及M-TS-1催化剂对RhB的光催化降解反应遵循一级反应动力学.TS-1和MTS-1在反应初期表现出相近的催化活性,随着反应时间的延长,MTS-1的光催化活性明显优于TS-1. 展开更多
关键词 TS-1分子筛 改性 mts-1 光催化降解
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绵羊ADAMTS-1基因遗传变异及其与产羔性状关联的分析 被引量:7
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作者 鲍建军 王晶 +5 位作者 高雯 于嘉瑞 王利宏 吕晓阳 王庆增 孙伟 《黑龙江畜牧兽医》 CAS 北大核心 2016年第5期48-52,57,282,共7页
为了研究ADAMTS-1基因的重要功能区与湖羊繁殖性状的关联性,试验采用湖羊作为研究对象,以我国固有品种小尾寒羊、洼地绵羊、阿勒泰羊作为参照群体,拟以ADAMTS-1去解链金属蛋白酶基因作为繁殖性状的候选基因,根据NCBI发表的ADAMTS-1基因... 为了研究ADAMTS-1基因的重要功能区与湖羊繁殖性状的关联性,试验采用湖羊作为研究对象,以我国固有品种小尾寒羊、洼地绵羊、阿勒泰羊作为参照群体,拟以ADAMTS-1去解链金属蛋白酶基因作为繁殖性状的候选基因,根据NCBI发表的ADAMTS-1基因序列设计引物,利用PCRSSCP方法检测4种绵羊ADAMTS-1基因第7,8外显子的多态性,分析绵羊ADAMTS-1基因部分重要功能区单核苷酸多态性及遗传变异水平。结果表明:ADAMTS-1第7外显子发现了1处A→G的碱基突变,除小尾寒羊外,其他3种羊的基因型分布均符合Hardy-Weinberg平衡,各基因型频率分布在4种绵羊间的差异均不显著;第8外显子发现了1处T→C的碱基突变,除湖羊外,其他3种绵羊的基因型分布全部符合Hardy-Weinberg平衡;第7外显子的GG基因型在产羔数上比GH基因型高0.094 7;第8外显子的IJ基因型在产羔数上比II基因型高0.053 3,说明GG和IJ基因型对湖羊的产羔性状有一定的影响,但是两个位点的不同基因型在产羔数上差异均未达显著水平(P>0.05)。说明各基因型与产羔性状关联性表现为差异不显著,初步认为ADAMTS-1基因不能作为湖羊高繁殖力的候选基因。 展开更多
关键词 绵羊 ADAmts-1基因 遗传变异 产羔性状 候选基因
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ADAMTS-1基因多态性与母猪产仔数的关系 被引量:6
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作者 向春和 贺小东 +2 位作者 赵志超 孙敬礼 黄涛 《安徽农业科学》 CAS 北大核心 2011年第1期275-276,共2页
用PCR-RFLP方法对118头大长杂交母猪的ADAMTS-1基因进行分型,并分析了ADAMTS-1不同基因型母猪的产仔数差异。结果表明,在所检测的大长杂交猪群体中,基因A为0.56,基因B为0.44;不同基因型间产仔数表现出AB>BB>AA的趋势,AA型与BB型以... 用PCR-RFLP方法对118头大长杂交母猪的ADAMTS-1基因进行分型,并分析了ADAMTS-1不同基因型母猪的产仔数差异。结果表明,在所检测的大长杂交猪群体中,基因A为0.56,基因B为0.44;不同基因型间产仔数表现出AB>BB>AA的趋势,AA型与BB型以及AB对猪的产仔数和产仔活数差异不显著。 展开更多
关键词 ADAmts-1基因 产仔数 多态性
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抑癌基因MTS1真核表达载体的构建及其在卵巢癌细胞系HO-8910中的表达 被引量:4
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作者 刘淑娟 辛晓燕 +3 位作者 胡大海 肖华胜 许汉鹏 韩军涛 《第四军医大学学报》 1999年第4期348-350,353,共4页
目的:构建多肿瘤抑制基因1(MTS1)的真核表达载体,将其转入人源性卵巢癌细胞株HO-8910中,并得到稳定表达,为进一步研究其对卵巢癌细胞的影响奠定实验基础.方法:利用BamHⅠ与EcoRⅠ从pUC19-p16质粒... 目的:构建多肿瘤抑制基因1(MTS1)的真核表达载体,将其转入人源性卵巢癌细胞株HO-8910中,并得到稳定表达,为进一步研究其对卵巢癌细胞的影响奠定实验基础.方法:利用BamHⅠ与EcoRⅠ从pUC19-p16质粒上切下MTS1cDNA片段并克隆到真核表达载体pcDNA3上,构建成MTS1真核表达载体pcDNA3-p16;利用脂质体(Fu-GENETM6)介导的基因导入法将pcDNA3-p16导入人源性卵巢癌细胞株HO-8910中;采用ABC法对转染后的不同代数细胞进行免疫细胞化学检测,观察p16蛋白的表达.结果:成功构建了MTS1真核表达载体pcDNA3-p16,并进行酶切鉴定;转染后经G418筛选2wk出现阳性克隆8910-p16,并检测到其中有p16蛋白的稳定表达.结论:成功构建MTS1真核表达载体pcDNA3-p16,并可在人源性卵巢癌细胞株HO-8910中得到稳定表达. 展开更多
关键词 多肿瘤抑制基因 卵巢癌 基因治疗
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Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用
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作者 高娜 梁平 +3 位作者 单彬 高亚乾 尹金妥 冯锐 《中国药业》 2024年第3期128-128,I0001-I0004,共5页
目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GP... 目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。 展开更多
关键词 Wilm′s tumor gene1肽疫苗 Galinpepimut-S 免疫治疗 新生抗原 肿瘤疫苗
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Knockdown of the atypical protein kinase genes GhABC1K2-A05 and GhABC1K12-A07 make cotton more sensitive to salt and PEG stress 被引量:1
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作者 Caixiang Wang Meili Li +3 位作者 Dingguo Zhang Xueli Zhang Juanjuan Liu Junji Su 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2024年第10期3370-3386,共17页
Activity of bc1 complex kinase(ABC1K)is an atypical protein kinase(aPK)that plays a crucial role in plant mitochondrial and plastid stress responses,but little is known about the responses of ABC1Ks to stress in cotto... Activity of bc1 complex kinase(ABC1K)is an atypical protein kinase(aPK)that plays a crucial role in plant mitochondrial and plastid stress responses,but little is known about the responses of ABC1Ks to stress in cotton(Gossypium spp.).Here,we identified 40 ABC1Ks in upland cotton(Gossypium hirsutum L.)and found that the Gh ABC1Ks were unevenly distributed across 17 chromosomes.The GhABC1K family members included 35 paralogous gene pairs and were expanded by segmental duplication.The GhABC1K promoter sequences contained diverse cis-acting regulatory elements relevant to hormone or stress responses.The qRT-PCR results revealed that most Gh ABC1Ks were upregulated by exposure to different stresses.Gh ABC1K2-A05 and Gh ABC1K12-A07 expression levels were upregulated by at least three stress treatments.These genes were further functionally characterized by virus-induced gene silencing(VIGS).Compared with the controls,the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced cotton lines exhibited higher malondialdehyde(MDA)contents,lower catalase(CAT),peroxidase(POD)and superoxide dismutase(SOD)activities and reduced chlorophyll and soluble sugar contents under NaCl and PEG stress.In addition,the expression levels of six stress marker genes(Gh DREB2A,Gh SOS1,Gh CIPK6,Gh SOS2,Gh WRKY33,and Gh RD29A)were significantly downregulated after stress in the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced lines.The results indicate that knockdown of Gh ABC1K2-A05 and Gh ABC1K12-A07 make cotton more sensitive to salt and PEG stress.These findings can provide valuable information for intensive studies of Gh ABC1Ks in the responses and resistance of cotton to abiotic stresses. 展开更多
关键词 COTTON ABC1K abiotic stress responses expression patterns virus-induced gene silencing(VIGS)
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AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration
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作者 Yu Yangyi Song Zhuoyue +2 位作者 Lian Qiang Ding Kang Li Guangheng 《中国组织工程研究》 CAS 北大核心 2025年第17期3537-3547,共11页
BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene ma... BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair. 展开更多
关键词 OSTEOARTHRITIS adeno-associated virus bone morphogenetic protein 4 p65-short hairpin RNA gene therapy short hairpin RNA transforming growth factor-β1 extracellular matrix articular cartilage chondrocytes.
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The role of tazarotene-induced gene 1 in carcinogenesis:is it a tumor suppressor gene or an oncogene?
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作者 CHUN-HUA WANG LU-KAI WANG +1 位作者 RONG-YAUN SHYU FU-MING TSAI 《BIOCELL》 SCIE 2024年第9期1285-1297,共13页
Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet... Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development. 展开更多
关键词 Tazarotene-induced gene 1 Retinoic acid receptor responder protein 1 Tumor suppressor gene ONCOgene
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Multi-genome evolutionary study of the ABC1 gene family and identification of the pleiotropic effects of OsABC1-13 in rice development
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作者 Fuying Ma Mingyu Liu +11 位作者 Peiwen Yan Shicong He Jian Hu Xinwei Zhang Fuan Niu Jinhao Cui Xinyu Yuan Xiaoyun Xin Liming Cao Jinshui Yang Ying Wang Xiaojin Luo 《The Crop Journal》 SCIE CSCD 2024年第4期1022-1030,共9页
In four rice genomes,85 ABC1-family genes were identified by comparative genomics,evolution,genetics,and physiology.One,OsABC1-13,was shown by knockdown and knockout experiments to affect plant height,grain size,and p... In four rice genomes,85 ABC1-family genes were identified by comparative genomics,evolution,genetics,and physiology.One,OsABC1-13,was shown by knockdown and knockout experiments to affect plant height,grain size,and photosynthetic capability. 展开更多
关键词 Multi-genome analysis Activity of bc1 complex gene PHOTOSYNTHESIS BIOMASS Osabc1-13 HAPLOTYPE
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Molecular Evolution of Rice Blast Resistance Gene bsr-d1
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作者 LI Wei ZHANG Mengchen +3 位作者 YANG Yaolong WENG Lin HU Peisong WEI Xinghua 《Rice science》 SCIE CSCD 2024年第6期700-711,共12页
Rice blast,caused by the fungus Magnaporthe oryzae,reduces rice yields by 10%to 35%.Incorporating blast resistance genes into breeding programs is an effective strategy to combat this disease.Understanding the genetic... Rice blast,caused by the fungus Magnaporthe oryzae,reduces rice yields by 10%to 35%.Incorporating blast resistance genes into breeding programs is an effective strategy to combat this disease.Understanding the genetic variants that confer resistance is crucial to this strategy.The gene Bsr-d1 encodes a C2H2-like transcription factor,and its recessive allele confers broad-spectrum resistance against infections by various strains of M.oryzae.In this study,we investigated the molecular evolution of the rice blast resistance gene bsr-d1 in a representative population consisting of 827 cultivated and wild rice accessions.Our results revealed that wild rice exhibited significantly higher nucleotide diversity,with polymorphic regions primarily concentrated in the promoter region,in contrast to indica and japonica rice varieties.The Bsr-d1 gene displayed significant differentiation between indica and japonica rice varieties,with the bsr-d1 resistance allele being unique to indica rice.Haplotype network and phylogenetic analyses suggested that the bsr-d1 resistance allele most likely originated from Oryza nivara in the region adjacent to the Indian Peninsula and the Indochina Peninsula.Moreover,we explored the utilization of bsr-d1 resistance alleles in China and designed a pair of DNA primers based on the polymorphic sites for the detection of the bsr-d1 resistance gene.In summary,our study uncovering the origin and evolution of bsr-d1 will enhance our understanding of resistance gene variation and expedite the resistance breeding process. 展开更多
关键词 broad-spectrum resistance bsr-d1 gene evolution Magnaporthe oryzae resistance breeding
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Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing
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作者 Jia-xun LI Ling-rui MENG +6 位作者 Bao-ke HOU Xiao-lu HAO Da-jiang WANG Ling-hui QU Zhao-hui LI Lei ZHANG Xin JIN 《Current Medical Science》 SCIE CAS 2024年第2期419-425,共7页
Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on ... Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population. 展开更多
关键词 autosomal recessive bestrophinopathy BEST1 gene third-generation sequencing MUTATION
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Heat-inducible SlWRKY3 confers thermotolerance by activating the SlGRXS1 gene cluster in tomato
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作者 Ying Wang Wenxian Gai +9 位作者 Liangdan Yuan Lele Shang Fangman Li Zhao Gong Pingfei Ge Yaru Wang Jinbao Tao Xingyu Zhang Haiqiang Dong Yuyang Zhang 《Horticultural Plant Journal》 SCIE CAS CSCD 2024年第2期515-531,共17页
High temperature stress is one of the major environmental factors that affect the growth and development of plants. Although WRKY transcription factors play a critical role in stress responses, there are few studies o... High temperature stress is one of the major environmental factors that affect the growth and development of plants. Although WRKY transcription factors play a critical role in stress responses, there are few studies on the regulation of heat stress by WRKY transcription factors,especially in tomato. Here, we identified a group I WRKY transcription factor, SlWRKY3, involved in thermotolerance in tomato. First, SlWRKY3 was induced and upregulated under heat stress. Accordingly, overexpression of SlWRKY3 led to an increase, whereas knock-out of SlWRKY3 resulted in decreased tolerance to heat stress. Overexpression of SlWRKY3 accumulated less reactive oxygen species(ROS), whereas knock-out of SlWRKY3 accumulated more ROS under heat stress. This indicated that SlWRKY3 positively regulates heat stress in tomato. In addition,SlWRKY3 activated the expression of a range of abiotic stress-responsive genes involved in ROS scavenging, such as a SlGRXS1 gene cluster.Further analysis showed that SlWRKY3 can bind to the promoters of the SlGRXS1 gene cluster and activate their expression. Collectively, these results imply that SlWRKY3 is a positive regulator of thermotolerance through direct binding to the promoters of the SlGRXS1 gene cluster and activating their expression and ROS scavenging. 展开更多
关键词 TOMATO WRKY transcription factor SlWRKY3 THERMOTOLERANCE SlGRXS1 gene cluster Abiotic stress
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Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy
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作者 Bismark Gatica-Garcia Michael J.Bannon +14 位作者 Irma Alicia Martínez-Dávila Luis O.Soto-Rojas David Reyes-Corona Lourdes Escobedo Minerva Maldonado-Berny ME Gutierrez-Castillo Armando J.Espadas-Alvarez Manuel A.Fernandez-Parrilla Juan U.Mascotte-Cruz CP Rodríguez-Oviedo Irais E.Valenzuela-Arzeta Claudia Luna-Herrera Francisco E.Lopez-Salas Jaime Santoyo-Salazar Daniel Martinez-Fong 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第9期2057-2067,共11页
Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,... Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease. 展开更多
关键词 A1 astrocytes A2 astrocytes gene therapy microglia motor deficits nanoparticles NEURODEgeneRATION neuroinflammation senescence α-synuclein aggregates
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Studies on the temporal,structural,and interacting features of the clubroot resistance gene Rcr1 using CRISPR/Cas9-based systems
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作者 Hao Hu Fengqun Yu 《Horticultural Plant Journal》 SCIE CAS CSCD 2024年第4期1035-1048,共14页
Clubroot disease is a severe threat to Brassica crops globally,particularly in western Canada.Genetic resistance,achieved through pyramiding clubroot resistance(CR)genes with different modes of action,is the most impo... Clubroot disease is a severe threat to Brassica crops globally,particularly in western Canada.Genetic resistance,achieved through pyramiding clubroot resistance(CR)genes with different modes of action,is the most important strategy for managing the disease.However,studies on the CR gene functions are quite limited.In this study,we have conducted investigations into the temporal,structural,and interacting features of a newly cloned CR gene,Rcr1,using CRISPR/Cas9 technology.For temporal functionality,we developed a novel CRISPR/Cas9-based binary vector,pHHIGR-Hsp18.2,to deliver Rcr1 into a susceptible canola line(DH12075)and observed that early expression of Rcr1 is critical for conferring resistance.For structural functionality,several independent mutations in specific domains of Rcr1 resulted in loss-offunction,highlighting their importance for CR phenotype.In the study of the interacting features of Rcr1,a cysteine protease gene and its homologous allele in canola were successfully disrupted via CRISPR/Cas9 as an interacting component with Rcr1 protein,resulting in the conversion from clubroot resistant to susceptible in plants carrying intact Rcr1.These results indicated an indispensable role of these two cysteine proteases in Rcr1-mediated resistance response.This study,the first of its kind,provides valuable insights into the functionality of Rcr1.Further,the new vector p HHIGR-Hsp18.2 demonstrated an inducible feature on the removal of add-on traits,which should be useful for functional genomics and other similar research in brassica crops. 展开更多
关键词 Clubroot resistance Brassica crops CANOLA Rcr1 CRISPR/Cas9 system gene knock-out Timing control Non-synonymous mutation Protein-protein interaction
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Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder:A meta-analysis
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作者 Huai-Neng Wu Shuang-Yue Zhu +2 位作者 Li-Na Zhang Bian-Hong Shen Lian-Lian Xu 《World Journal of Psychiatry》 SCIE 2024年第10期1573-1582,共10页
BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify th... BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes.METHODS Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search across PubMed,EMBASE,Web of Science,and the Cochrane Library was conducted without date restrictions,utilizing key terms related to MDD,serotonin 1A receptor polymorphism(5-HTR1A),C-1019G polymorphism,and antidepressant response.Studies meeting inclusion criteria were thoroughly screened,and quality assessed using the Newcastle-Ottawa Scale.Statistical analyses,includingχ2 and I²values,were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly.RESULTS The initial search yielded 1216 articles,with 11 studies meeting criteria for inclusion.Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy.The heterogeneity was low to moderate,and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests.CONCLUSION This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD.The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics. 展开更多
关键词 Major depressive disorder Antidepressant efficacy 5-HTR1A gene C-1019G polymorphism META-ANALYSIS
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EFFECT OF INTERLEUKIN-1β ON GROWTH HORMONE GENE EXPRESSION AND ITS POSSIBLE MOLECULAR MECHANISM IN RAT MtT/S SOMATOTROPH CELLS 被引量:3
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作者 Feng-ying Gong Jie-ying Deng Yi-fan Shi 《Chinese Medical Sciences Journal》 CAS CSCD 2008年第4期193-201,共9页
Objective To elucidate the effect of interleukin-1β (IL- 1β) on human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly es... Objective To elucidate the effect of interleukin-1β (IL- 1β) on human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly established by transfecting 484-Lucl plasmid which contained hGH gene promoter --484 to +30 bp and luciferase reporter gene. The effect of IL-1β on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. Results The 10^3 U/mL IL-1β stimulated secretion and synthesis of GH, and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 μmol/L) and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 μmol/L) completely blocked the stimulatory effect of IL-1μ, and phosphatidylinositol-3-kinase (PI3-K) inhibitor LY294002 partly abolished the effect of IL-1μ. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit- 1 nor inhibition of Pit- 1 expression affected induction of hGH promoter activity by IL-1μ. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1β, and results showed that the stimulatory effect of IL-1β was abolished following deletion of the --196 to -- 132 bp fragment. Conclusions IL-1β promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1β on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein. 展开更多
关键词 INTERLEUKIN-1Β growth hormone gene promoter mtT/S cells Pit-1 protein mitogen-activated protein kinase
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MTHFR和PAI-1基因多态性与2型糖尿病患者下肢深静脉血栓发生风险的相关性研究
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作者 张建军 靳志雄 +1 位作者 胡常晖 黄秀萍 《临床误诊误治》 CAS 2024年第18期59-63,75,共6页
目的探讨亚甲基四氢叶酸还原酶(MTHFR)C677T突变和纤溶酶原激活物抑制物-1(PAI-1)4G/5G基因多态性与2型糖尿病患者下肢深静脉血栓(DVT)发生风险的相关性。方法对2022年5月至2023年4月收治的240例2型糖尿病患者的MTHFR和PAI-1基因型进行... 目的探讨亚甲基四氢叶酸还原酶(MTHFR)C677T突变和纤溶酶原激活物抑制物-1(PAI-1)4G/5G基因多态性与2型糖尿病患者下肢深静脉血栓(DVT)发生风险的相关性。方法对2022年5月至2023年4月收治的240例2型糖尿病患者的MTHFR和PAI-1基因型进行分析。依据是否发生DVT分为非DVT组57例和DVT组183例。利用PCR-RFLP检测这2种基因的多态性,收集2组患者的临床资料,比较2组MTHFR C677T和PAI-14G/5G基因多态性、不同MTHFR C677T基因型同型半胱氨酸水平,分析下肢DVT发生的风险因素。结果DVT组中吸烟患者比例高于非DVT组,D-二聚体升高患者占比高于非DVT组(P<0.01)。DVT组MTHFR C677T TT基因型频率与非DVT组比较差异无统计学意义(P>0.05)。DVT组中PAI-14G4G基因型频率显著高于非DVT组(P<0.01)。携带MTHFR C677T TT基因型的患者同型半胱氨酸水平显著高于非携带者(P<0.05),DVT组中TT基因型同型半胱氨酸水平高于非DVT组(P<0.05)。携带MTHFR C677T TT和PAI-14G4G基因型的2型糖尿病患者发生下肢DVT的风险显著增加,OR值为7.33,排除环境因素影响后,OR'值为12.65。结论PAI-14G4G基因型是2型糖尿病患者发生下肢DVT的独立风险因素;MTHFR C677T TT和PAI-14G4G基因型同时存在时,2型糖尿病患者发生下肢DVT的风险提高。 展开更多
关键词 糖尿病 亚甲基四氢叶酸还原酶 纤溶酶原激活物抑制物-1 深静脉血栓 基因多态性 TT基因型 4G4G基因型
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MTS-1、MTS-2、MTS-3对苯甲醚羟化反应催化性能的研究
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作者 张秀华 《化学工程师》 CAS 2003年第1期60-61,共2页
愈创木酚在医药、香料工业应用很广泛,主要由木馏油进行分馏或由邻甲氧基苯胺经重氮化和水解而制得,我们选用成本低廉的新型的杂原子沸石分子筛MTS-1、MTS-2、MTS-3为催化剂,进行了苯甲醚羟化制邻甲氧基苯酚(愈创木酚)的研究,首次把杂... 愈创木酚在医药、香料工业应用很广泛,主要由木馏油进行分馏或由邻甲氧基苯胺经重氮化和水解而制得,我们选用成本低廉的新型的杂原子沸石分子筛MTS-1、MTS-2、MTS-3为催化剂,进行了苯甲醚羟化制邻甲氧基苯酚(愈创木酚)的研究,首次把杂原子沸石分子筛催化剂拓展应用到苯甲醚羟化制愈创木酚的反应中,取得了较好的效果,为苯甲醚再利用生成愈创木酚的应用开拓了广阔的前景。 展开更多
关键词 mts-1 mts-2 mts-3 催化性能 研究 沸石分子筛 催化剂 苯甲醚 羟化反应 愈创木酚
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