检索结果-南通市图书馆

Carbonic anhydrase-like enzymes in the formation of Lycopodium alkaloid

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of Natural Medicines 2024年第3期22卷 193-194页

作者： DONG Huiwen GE Huiming state key laboratory of pharmaceutical biotechnology Institute of Functional BiomoleculesSchool of Life SciencesNanjing UniversityNanjing 210023China

Plant alkaloids,renowned for their structural diversity and bioactivity,are prominent in both modern and traditional medicine[1].Unraveling the intricacies of plant alkaloid biosynthesis could pave the way for the discovery of new natural products and *** may also shed light on the roles of existing pathways in host biology and provide valuable tools for metabolic engineering in plants and microbes[2].Unlike other major classes of plant natural products,such as terpenoids and polyketides,the formation of alkaloid scaffolds does not conform to a uniform chemical theme or depend on a singular enzyme class[3].A case in point is the Lycopodium alkaloids in the Lycopodiaceae family,where the enzymes responsible for their core scaffold construction remain unidentified[4].

关键词： Lycopodium alkaloid Carbonic anhydrase-like enzymes Biosynthesis

Comprehensive integration of single-cell transcriptomic data illuminates the regulatory network architecture of plant cell fate specification

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Plant Diversity 2024年第3期46卷 372-385页

作者： Shanni Cao Xue Zhao Zhuojin Li Ranran Yu Yuqi Li Xinkai Zhou Wenhao Yan Dijun Chen Chao He state key laboratory of pharmaceutical biotechnology School of Life SciencesNanjing UniversityNanjing 210023China National key laboratory of Crop Genetic Improvement Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China

Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific *** we introduced a comprehensive single-cell transcriptomic atlas of Arabidopsis *** atlas is the result of meticulous integration of 63 previously published scRNA-seq datasets,addressing batch effects and conserving biological *** integration spans a broad spectrum of tissues,including both below-and above-ground *** a rigorous approach for cell type annotation,we identified 47 distinct cell types or states,largely expanding our current view of plant cell *** systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordinated manner to control cell-type specific gene *** together,our study not only offers extensive plant cell atlas exploration that serves as a valuable resource,but also provides molecular insights into gene-regulatory programs that varies from different cell types.

关键词： Arabidopsis Single cell transcriptome Gene regulatory network Data integration Plant cell atlas

Disulfide bridge-targeted metabolome mining unravels an antiparkinsonian peptide

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第2期14卷 881-892页

作者： Zhiwu Tong Xiahong Xie Huiming Ge Ruihua Jiao Tingting Wang Xincun Wang Wenying Zhuang Gang Hu Renxiang Tan state key laboratory of pharmaceutical biotechnology Institute of Functional BiomoleculesSchool of Life SciencesNanjing UniversityNanjing 210023China state key laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese MedicineNanjing 210023China Institute of Microbiology Chinese Academy of SciencesBeijing 100101China

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics,thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical ***,the success rate is decreasing,presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely‘overlooked’during the characterization ***,we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP(ribosomally synthesized and post-translationally modified peptide),named acalitide,by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug *** is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease(AcaB)-catalyzed lactamization of AcaA,an unprecedented precursor *** a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation *** together,the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson’s disease that is globally prevailing in an alarming manner.

关键词： Fungal RiPPs Biosynthesis Macrocyclic peptide Acalitide Antiparkinsonian

Dynamic shielding of bacterial outer membrane vesicles for safe and efficient chemo-immunotherapy against tumors

在线全文

学校读者我要写书评

暂无评论

Nano Research 2024年第2期17卷 836-847页

作者： Shuping Li Xin Li Jiaqi Meng Weier Bao Shuang Wang Peng Ye Xiao-Dong Gao Wei Wei key laboratory of Carbohydrate Chemistry and biotechnology Ministry of Education School of BiotechnologyJiangnan UniversityWuxi 214122China state key laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China school of Chemical Engineering University of Chinese Academy of SciencesBeijing 100049China

Bacterial outer membrane vesicles(OMVs)are potent immunostimulants of regulating the tumor microenvironment(TME)for immunotherapy,and can be used to deliver ***,the severe systemic inflammatory response triggered by OMVs upon intravenous(i.v.)injection has limited their ***,we developed a safe and effective strategy by conjugating doxorubicin-loaded serum albumin(SA-DOX,AD)onto the surface of OMVs using a matrix metalloproteinase(MMP)-cleavable peptide linker(cL).This approach enabled the dynamic shielding of OMVs to reduce the systemic side effects while simultaneously enhancing the anti-tumor effects through ***,the resulting OMV-cL-AD formulation exhibited significantly enhanced accumulation at the tumor site after ***,facilitated by the SA decoration on the OMVs ***,the shield on the OMV-cL-AD was cleaved by the over-expressed MMP in the TME,leading to the release of both OMVs and *** process provided OMV-induced immunotherapy and DOX-induced chemotherapy,resulting in synergistic tumor *** conclusion,our work demonstrated the potential of OMV-cL-AD as an effective immunochemotherapy strategy that can prolong the survival time of mice without inducing side effects.

关键词： outer membrane vesicles doxorubicin tumor microenvironment immunotherapy chemotherapy

Widespread and active piezotolerant microorganisms mediate phenolic compound degradation under high hydrostatic pressure in hadal trenches

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Marine life Science & Technology 2024年第2期6卷 331-348页

作者： Hao Ling Yongxin Lv Yu Zhang Ning‑Yi Zhou Ying Xu state key laboratory of Microbial Metabolism Joint International Research Laboratory of Metabolic and Developmental Sciences and School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China school of Oceanography Shanghai Jiao Tong UniversityShanghai 200240China state key of laboratory of Ocean Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Phenolic compounds,as well as other aromatic compounds,have been reported to be abundant in hadal *** high-throughput sequencing studies have hinted at the potential of hadal microbes to degrade these compounds,direct microbiological,genetic and biochemical evidence under in situ pressures remain ***,a microbial consortium and a pure culture of Pseudomonas,newly isolated from Mariana Trench sediments,efficiently degraded phenol under pressures up to 70 and 60 MPa,respectively,with concomitant increase in *** analyzing a high-pressure(70 MPa)culture metatranscriptome,not only was the entire range of metabolic processes under high pressure generated,but also genes encod-ing complete phenol degradation via ortho-and meta-cleavage pathways were *** isolate of Pseudomonas also contained genes encoding the complete degradation *** transcribed genes(dmpKLMNOP_(sed))were functionally identified to encode a multicomponent hydroxylase catalyzing the hydroxylation of phenol and its methylated derivatives by heterogeneous *** addition,key catabolic genes identified in the metatranscriptome of the high-pressure cultures and genomes of bacterial isolates were found to be all widely distributed in 22 published hadal microbial *** microbiological,genetic,bioinformatics,and biochemical levels,this study found that microorganisms widely found in hadal trenches were able to effectively drive phenolic compound degradation under high hydrostatic *** information will bridge a knowledge gap concerning the microbial aromatics degradation within hadal trenches.

关键词： Hadal trench High hydrostatic pressure Phenolic compounds degradation Piezotolerant microorganisms Widespread distribution

Strategies that regulate LSD1 for novel therapeutics

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第4期14卷 1494-1507页

作者： Meng Li Mengge Dai Bing Cheng Shaotong Li Enhui Guo Junwei Fu Ting Ma Bin Yu school of pharmaceutical sciences&key laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China College of Chemistry Zhengzhou UniversityZhengzhou 450001China Tianjian laboratory of Advanced Biomedical sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China Pingyuan laboratory State Key Laboratory of Antiviral DrugsHenan Normal UniversityXinxiang 453007China state key laboratory of pharmaceutical biotechnology Nanjing UniversityNanjing 210023China

Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic ***-specific demethylase 1(LSD1),the first identified histone de-methylase,is universally overexpressed in various ***1 dysregulation is closely associated with cancer,viral infections,and neurodegenerative diseases,etc.,making it a promising therapeutic *** LSD1 inhibitors and two small-molecule degraders(UM171 and BEA-17)have entered the clinical ***1 can remove methyl groups from histone 3 at lysine 4 or lysine 9(H3K4 or H3K9),resulting in either transcription repression or *** the roles of LSD1 in transcrip-tional regulation are well-established,studies have revealed that LSDl can also be dynamically regulated by other *** example,the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with ***,some post-transcriptional modifica-tions and cellular metabolites can also regulate LSD1 expression or its demethylase ***,in this review,we will systematically summarize how proteins involved in the transcriptional corepressor complex,various post-translational modifications,and metabolites act as regulatory factors for LSD1 ac-tivity.

关键词： LSD1 regulation Transcription repression Transcription activation the Corepressor complex Post-transcriptional modifications Metabolites

Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Zoological Research 2024年第1期45卷 13-24页

作者： Wei Liang Kang Li Haiyou Gao Kunming Li Jiansong Zhang Qian Zhang Xinying Jiao Jialong Yang Xiumei Wei state key laboratory of Estuarine and Coastal Research School of Life SciencesEast China Normal UniversityShanghai 200241China laboratory for Marine Biology and biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdaoShandong 266237China

Mammalian T-cell responses require synergism between the first signal and co-stimulatory ***,whether and how dual signaling regulates the T-cell response in early vertebrates remains *** the present study,we discovered that the Nile tilapia(Oreochromis niloticus)encodes key components of the LAT signalosome,namely,LAT,ITK,GRB2,VAV1,SLP-76,GADS,and PLC-γ*** components are evolutionarily conserved,and CD3εmAb-induced T-cell activation markedly increased their ***,at least ITK,GRB2,and VAV1 were found to interact with LAT for signalosome *** of the first signal,the NF-κB,MAPK/ERK,and PI3K-AKT pathways were activated upon CD3εmAb ***,treatment of lymphocytes with CD28 mAbs triggered the AKT-mTORC1 pathway downstream of the co-stimulatory *** CD3εand CD28 mAb stimulation enhanced ERK1/2 and S6 phosphorylation and elevated NFAT1,c-Fos,IL-2,CD122,and CD44 expression,thereby signifying T-cell ***,rather than relying on the first or co-stimulatory signal alone,both signals were required for T-cell *** T-cell activation was accompanied by marked apoptosis and cytotoxic *** findings suggest that tilapia relies on dual signaling to maintain an optimal T-cell response,providing a novel perspective for understanding the evolution of the adaptive immune system.

关键词： Oreochromis niloticus CD3 CD28 T cells Adaptive immunity Evolution

Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

在线全文

学校读者我要写书评

暂无评论

National Science Review 2024年第2期11卷 124-134页

作者： Jingyu Li Weibo Hou Qi Zhao Wei Han Hongdi Cui Songling Xiao Ling Zhu Jiadan Qu Xiaoyu Liu Weitao Cong Jingling Shen Yuzheng Zhao Shaorong Gao Guoning Huang Qingran Kong Chongqing key laboratory of Human Embryo Engineering Center for Reproductive Medicine Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical University Oujiang laboratory Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life Sciences Wenzhou Medical University Frontier Science Center for Stem Cell Research School of Life Sciences and Technology Tongji University school of pharmaceutical Science Wenzhou Medical University Institute of life sciences College of Life and Environmental Sciences Wenzhou University Optogenetics&Synthetic Biology Interdisciplinary Research Center State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation(ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-Co A and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

关键词： mammalian preimplantation development lactate epigenetic remodeling histone lactylation zygotic genome activation

STING signaling in islet macrophages impairs insulin secretion in obesity

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Science China(life sciences) 2024年第2期67卷 345-359页

作者： Ze Hong Saihua Chen Jing Sun Dan Cheng Hanli Guo Jiahao Mei Xiang Zhang Munire Maimaiti Haiping Hao Peng Cao Haiyang Hu Chen Wang school of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China state key laboratory of Natural Medicines Department of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 211198China school of life sciences Westlake UniversityHangzhou 310012China

The innate immune regulator stimulator of interferon genes(STING)mediates self-DNA sensing and leads to the induction of type I interferons and inflammatory cytokines,which promotes the progression of various inflammatory and autoimmune *** immune system plays a critical role in regulating obesity-induced islet dysfunction,whereas the potential effect of STING signaling is not fully ***,we demonstrate that STING is mainly expressed and activated in islet macrophages upon high-fat diet(HFD)***^(-/-)alleviates HFD-induced islet inflammation by inhibiting the expression of pro-inflammatory cytokines and the infiltration of ***,palmitic acid incubation promotes mitochondrial DNA leakage into the cytosol and subsequently activates STING pathway in ***,STING activation in macrophages impairs glucose-stimulated insulin secretion by mediating the engulfment ofβcell insulin secretory *** inhibiting STING activation enhances insulin secretion to control ***,our results reveal a regulatory mechanism in controlling the islet inflammation and insulin secretion in dietinduced obesity and suggest that selective blocking of the STING activation may be a promising strategy for treating type 2 diabetes.

关键词： STING obesity type 2 diabetes insulin macrophages islet