检索结果-南通市图书馆

Molecular mechanism of mureidomycin biosynthesis activated by introduction of an exogenous regulatory gene ssa A into Streptomyces roseosporus

引用

Science China(Life Sciences) 2021年第11期64卷 1949-1963页

作者： Ning Liu Hanye Guan Guoqing Niu lingjuan jiang Yue Li Jihui Zhang Jine Li Huarong Tan State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Biotechnology Research Center Southwest UniversityChongqing 400715China Department of Medical Research Center Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Mureidomycins(MRDs), a group of unique uridyl-peptide antibiotics, exhibit antibacterial activity against the highly refractory pathogen Pseudomonas aeruginosa. Our previous study showed that the cryptic MRD biosynthetic gene cluster(BGC) mrd in Streptomyces roseosporus NRRL 15998 could not be activated by its endogenous regulator 02995 but activated by an exogenous activator Ssa A from sansanmycin’s BGC ssa of Streptomyces sp. strain SS. Here we report the molecular mechanism for this inexplicable regulation. EMSAs and footprinting experiments revealed that Ssa A could directly bind to a 14-nt palindrome sequence of 5′-CTGRCNNNNGTCAG-3′ within six promoter regions of mrd. Disruption of three representative target genes(SSGG-02981, SSGG-02987 and SSGG-02994) showed that the target genes directly controlled by Ssa Awere essential for MRD production. The regulatory function was further investigated by replacing six regions of SSGG-02995 with those of ssa ***, only the replacement of 343–450 nt fragment encoding the 115–150 amino acids(AA) of Ssa A could activate MRD biosynthesis. Further bioinformatics analysis showed that the 115–150 AA situated between two conserved domains of Ssa *** findings significantly demonstrate that constitutive expression of a homologous exogenous regulatory gene is an effective strategy to awaken cryptic biosynthetic pathways in Streptomyces.

关键词： mureidomycin transcriptional activation exogenous regulator—SsaA cryptic gene cluster Streptomyces roseosporus Pseudomonas aeruginosa antibiotics

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

A high-fiber diet synergizes with Prevotella copri and exacerbates rheumatoid arthritis

引用

Cellular & Molecular Immunology 2022年第12期19卷 1414-1424页

作者： lingjuan jiang Mengmeng Shang Shengnan Yu Yudong Liu Hui Zhang Yangzhong Zhou Min Wang Tingting Wang Hui Li Zhihua Liu Xuan Zhang Department of Medical Research Center National Science and Technology Key Infrastructure on Translational MedicinePeking Union Medical College HospitalDepartment of RheumatologyBeijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China Department of Rheumatology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineClinical Immunology CenterChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China Department of Pathology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China Department of Internal Medicine Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China Key Laboratory of Infection and Immunity Institute of BiophysicsChinese Academy of SciencesBeijing100101China Institute for Immunology School of MedicineTsinghua UniversityBeijing100084China Tsinghua-Peking Center for Life Sciences Beijing100084China

Both preclinical and established rheumatoid arthritis(RA)patients display alterations in the gut *** *** preferentially enriched in a subset of RA ***,we isolated a Prevotella strain,*** RA,from the feces of RA patients and showed that colonization of *** RA exacerbated arthritis in a collagen-induced arthritis(CIA)*** the presence of *** RA colonization,a high-fiber diet exacerbated arthritis via microbial alterations and intestinal *** of *** together with a high-fiber diet enabled the digestion of complex fiber,which led to the overproduction of organic acids,including fumarate,succinate and short-chain fatty *** promoted proinflammatory responses in macrophages,and supplementation with succinate exacerbated arthritis in the CIA *** findings highlight the importance of dysbiosis when evaluating the effects of dietary interventions on RA pathogenesis and provide new insight into dietary interventions or microbiome modifications to improve RA management.

关键词： Rheumatoid arthritis Dysbiosis Prevotella copri High-fber diet Microbiota-derived metabolites

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Helicobacter pylori may participate in the development of inflammatory bowel disease by modulating the intestinal microbiota

引用

Chinese Medical Journal 2022年第6期135卷 634-638页

作者： Xiaoyin Bai lingjuan jiang Gechong Ruan Tingting Liu Hong Yang Department of Gastroenterology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Medical Research Center Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Inflammatory bowel disease(IBD)is a non-specific inflammatory disease of the gastrointestinal(GI)tract that is generally accepted to be closely related to intestinal dysbiosis in the *** infections contribute a key role in the pathogenesis of IBD;however,although the results of recent clinical studies have revealed an inverse correlation between Helicobacter pylori(***)infection and IBD,the exact mechanism underlying the development of IBD remains ***,as a star microorganism,has been a focus for decades,and recent preclinical and real-world studies have demonstrated that *** not only affects the changes in the gastric microbiota and microenvironment but also influences the intestinal microbiota,indicating a potential correlation with *** analysis revealed that *** infection increased the diversity of the intestinal microbiota,reduced the abundance of Bacteroidetes,augmented the abundance of Firmicutes,and produced short-chain fatty acid-producing bacteria such as *** these factors may decrease vulnerability to *** studies investigating the ***-intestinal microbiota metabolite axis should be performed to understand the mechanism underlying the development of IBD.

关键词： H.pylori Helicobacter inflammatory

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

溃疡性结肠炎患者肠道脂肪酸氧化和肉碱代谢相关基因表达变化

引用

中华医学杂志 2024年第36期104卷 3422-3429页

作者：江玲娟国明月杨红中国医学科学院北京协和医学院北京协和医院临床医学研究所北京100730 中国医学科学院北京协和医学院北京协和医院消化内科北京100730

目的分析溃疡性结肠炎(UC)患者肠道脂肪酸氧化和肉碱代谢相关基因表达变化。方法回顾性纳入2018年1月1日至2023年12月31日北京协和医院就诊的UC患者(UC组)和定期行结肠镜检查排除息肉的非UC对照者(对照组),收集2组结肠组织样本并提取RNA... 详细信息

目的分析溃疡性结肠炎(UC)患者肠道脂肪酸氧化和肉碱代谢相关基因表达变化。方法回顾性纳入2018年1月1日至2023年12月31日北京协和医院就诊的UC患者(UC组)和定期行结肠镜检查排除息肉的非UC对照者(对照组),收集2组结肠组织样本并提取RNA,采用实时荧光定量聚合酶链反应技术检测脂肪酸氧化和肉碱代谢相关基因的mRNA表达水平,并分析其与炎症基因表达的相关性。利用高通量基因表达数据库(GEO)中UC患者和对照者结肠黏膜转录组数据,分析脂肪酸氧化和肉碱代谢相关基因的表达情况。免疫组化检测2组肠道组织中肉碱转运蛋白SLC6A14的表达水平。选择8周龄雄性C57BL/6小鼠,分为饮水组(饮用日常水)及葡聚糖硫酸钠(DSS)组(饮用2.5%DSS溶液),每组各4只,利用DSS诱导小鼠急性结肠炎模型,检测2组小鼠肠道组织中的SLC6A14和白细胞介素-6(IL-6)的mRNA表达水平的差异。结果UC组共纳入22例患者,男12例,女10例,年龄16~64(40±12)岁;对照组10名,男3名,女7名,年龄43~72(64±8)岁。UC组肠道中与脂肪酸氧化及转运有关的基因mRNA表达水平低于对照组,如CD36[0.40(0.27,0.55)比0.93(0.39,2.93)]、CPT1A[0.39(0.07,0.54)比0.93(0.41,1.71)]、CPT1B(0.37±0.36比1.37±0.89)、CPT2[0.36(0.30,0.43)比1.14(0.68,1.34)]、CRAT[0.31(0.25,0.41)比1.06(0.64,1.73)]、CROT[0.14(0.10,0.21)比0.95(0.77,1.27)](均P<0.05);UC组肠道中与肉碱转运相关基因mRNA表达水平低于对照组,如OCTN1[0.18(0.10,0.41)比0.83(0.41,1.47)]、OCTN2[0.01(0.00,0.01)比0.47(0.35,2.15)](均P<0.05)。UC患者肠道中肉碱转运蛋白编码基因SLC6A14的mRNA表达水平高于对照组[11.31(5.34,23.50)比0.78(0.07,3.70),P<0.001],且与炎症基因IL-6表达呈正相关(r=0.425,95%CI:0.076~0.681,P=0.019)。GEO数据库分析发现,UC组与脂肪酸氧化、转运有关基因CD36、CPT1A、CPT2、CRAT、CROT的表达水平低于对照组(均P<0.05),而SLC6A14表达水平高于对照组(P<0.05)。UC组结肠组织中SLC6A14蛋白表达水平高于对照组(0.45±0.07比0.30±0.01,P=0.019)。DSS组小鼠肠道中基因SLC6A14的mRNA表达水平高于饮水组(1.83±0.90比0.60±0.10,P=0.035)。结论UC患者肠道中与脂肪酸氧化和肉碱代谢相关的基因CD36、CPT1A、CPT1B、CPT2、CRAT、CROT、OCTN1和OCTN2的表达水平降低,且同时转运氨基酸和肉碱的基因SLC6A14的表达水平升高。

关键词：结肠炎,溃疡性脂肪酸转运脂肪酸氧化肉碱代谢白细胞介素6

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity

引用

Signal Transduction and Targeted Therapy 2023年第2期8卷 795-812页

作者： Bo Zhang Jiaqi Sun Yeshuang Yuan Dezhong Ji Yeting Sun Yudong Liu Shengjie Li Xingxing Zhu Xunyao Wu Jin Hu Qiu Xie Ling Wu Lulu Liu Boyang Cheng Yuanjie Zhang lingjuan jiang Lidan Zhao Fei Yu Wei Song Min Wang Yue Xu Shiliang Ma Yunyun Fei Lihe Zhang Demin Zhou Xuan Zhang State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College HospitalDepartment of RheumatologyBeijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Rheumatology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineClinical Immunology CenterGraduate School of Peking Union Medical CollegeChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Rheumatology and Clinical Immunology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeThe Ministry of Education Key LaboratoryBeijing 100730China

Interleukin-2(IL-2)is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells(Tregs)and effector cells,leading to paradoxical ***,we report a strategy that exploited genetic code expansion-guided incorporation of the latent bioreactive artificial amino acid fluorosulfate-L-tyrosine(FSY)into IL-2 for proximity-enabled covalent binding to IL-2Rαto selectively promote Treg *** found that FSY-bearing IL-2 variants,such as L72-FSY,covalently bound to IL-2Rαvia sulfur-fluoride exchange when in proximity,resulting in persistent recycling of IL-2 and selectively promoting the expansion of Tregs but not effector *** assessment of L72-FSY-expanded Tregs demonstrated that L72-FSY maintained Tregs in a central memory phenotype without driving terminal differentiation,as demonstrated by simultaneously attenuated expression of lymphocyte activation gene-3(LAG-3)and enhanced expression of programmed cell death protein-1(PD-1).Subcutaneous administration of L72-FSY in murine models of pristane-induced lupus and graft-versus-host disease(GvHD)resulted in enhanced and sustained therapeutic efficacy compared with wild-type IL-2 *** efficacy of L72-FSY was further improved by N-terminal PEGylation,which increased its circulatory retention for preferential and sustained *** proximity-enabled covalent binding strategy may accelerate the development of pleiotropic cytokines as a new class of immunomodulatory therapies.

关键词： sustained proximity consequences

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

我国学前融合教育研究综述

引用

科教导刊 2016年第10期 37-38页

作者：蒋玲娟陇南师范高等专科学校甘肃陇南742500

近几年来,学前教育越来越受到国家的重视,无论是需要特殊对待的幼儿,还是正常的幼儿,都应该接受科学合理的学前教育。如今学前融合教育不断发展起来,成为学前教育的一种新模式。融合教育具有很多优势,它不仅可以促进正常幼儿的健康发展... 详细信息

近几年来,学前教育越来越受到国家的重视,无论是需要特殊对待的幼儿,还是正常的幼儿,都应该接受科学合理的学前教育。如今学前融合教育不断发展起来,成为学前教育的一种新模式。融合教育具有很多优势,它不仅可以促进正常幼儿的健康发展,还能够提高特殊幼儿的认知水平。本文对学前融合教育的相关研究、存在的问题进行了分析,并对学前融合教育未来的发展提出了相关建议。

关键词：学前融合教育特殊教育师资力量

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Toward understanding the role of genomic repeat elements in neurodegenerative diseases

引用

Neural Regeneration Research 2025年第3期20卷 646-659页

作者： Zhengyu An Aidi jiang Jingqi Chen Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan UniversityShanghaiChina Zhangjiang Fudan International Innovation Center ShanghaiChina

Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

关键词： Alzheimer's disease ataxia deep learning long-read sequencing neurodegeneration neurodegenerative diseases Parkinson's disease repeat element structural variant

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

谷氏菌素生物合成基因gouC和gouD的功能研究

引用

微生物学报 2016年第3期56卷 406-417页

作者：韦俊宏张集慧江玲娟谭华荣牛国清西南大学家蚕基因组生物学国家重点实验室重庆400715 中国科学院微生物研究所微生物资源前期开发国家重点实验室北京100101

【目的】由于谷氏菌素产生菌禾粟链霉菌的遗传操作效率较低,本研究在谷氏菌素生物合成基因簇成功异源表达的基础上,通过在异源宿主天蓝色链霉菌M1146中阻断谷氏菌素生物合成基因gouC和gouD,研究其在谷氏菌素生物合成中的作用,为谷氏菌... 详细信息

【目的】由于谷氏菌素产生菌禾粟链霉菌的遗传操作效率较低,本研究在谷氏菌素生物合成基因簇成功异源表达的基础上,通过在异源宿主天蓝色链霉菌M1146中阻断谷氏菌素生物合成基因gouC和gouD,研究其在谷氏菌素生物合成中的作用,为谷氏菌素生物合成途径的阐明奠定基础。【方法】以含有谷氏菌素生物合成基因簇的黏粒D6-4H为基础,通过PCR-targeting的方法分别将gouC和gouD敲除得到重组质粒p GOUe-ΔC和p GOUe-ΔD。通过接合转移将这两个重组质粒分别导入天蓝色链霉菌M1146中,获得gouC和gouD的缺失突变株M1146-GOUe-ΔC和M1146-GOUe-ΔD,通过HPLC分析突变株的谷氏菌素中间产物积累情况,分离纯化后对其进行结构鉴定和生物活性检测。【结果】gouC和gouD的缺失均导致谷氏菌素不能合成,突变株发酵液中积累了不同的中间产物,生物活性分析发现这些中间产物均失去了对肿瘤细胞的抑制活性。【结论】gouC和gouD是谷氏菌素生物合成的重要基因,与谷氏菌素肽基部分的肌氨酸残基合成相关。本研究为阐明谷氏菌素的生物合成机制提供了更多的依据。

关键词：禾粟链霉菌谷氏菌素生物合成基因簇功能研究产物鉴定

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

壳聚糖的两亲性衍生物制备及在药物载体方面的应用

引用

天水师范学院学报 2011年第5期31卷 27-31页

作者：姜凌娟周惠云河南科技大学化工与制药学院河南洛阳471003

壳聚糖由于生物适应性强、生物可降解、原材料丰富等优点被公认为最具发展潜力的生物材料.其两亲性衍生物具有疏水性内核和亲水性外壳的胶束结构,主要用于难溶性药物、抗癌药物的缓控释和靶向载体.综述了近年来壳聚糖两亲性衍生物的制... 详细信息

壳聚糖由于生物适应性强、生物可降解、原材料丰富等优点被公认为最具发展潜力的生物材料.其两亲性衍生物具有疏水性内核和亲水性外壳的胶束结构,主要用于难溶性药物、抗癌药物的缓控释和靶向载体.综述了近年来壳聚糖两亲性衍生物的制备和在药物载体方面的应用,并对其发展趋势和应用前景作了简单评述.

关键词：壳聚糖两亲性药物载体

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Miyaoka-type inequalities for terminal threefolds with nef anti-canonical divisors

引用

Science China Mathematics 2025年第1期68卷 1-18页

作者： Masataka Iwai Chen jiang Haidong Liu Department of Mathematics Graduate School of ScienceOsaka University Shanghai Center for Mathematical Sciences & School of Mathematical Sciences Fudan University Department of mathematics Sun Yat-sen University

In this paper,we study Miyaoka-type inequalities on Chern classes of terminal projective 3-folds with nef anti-canonical *** X be a terminal projective 3-fold such that-KXis *** show that if c1（X） · c2（X）≠0,then c1（X） · c2（X） ≥ 1/252;if further X is not rationally connected,then c1（X） · c2（X） ≥ 4/5 and this inequality is *** order to prove this,we give a partial classification of such varieties along with many *** also study the nonvanishing of c1（X）dim X-2· c2（X） for terminal weak Fano varieties and prove a Miyaoka-Kawamata-type inequality.

关键词： terminal threefolds Miyaoka-type inequality boundedness

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：