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Genetic association analysis-based networks and classification of human UCP1 polymorphisms

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Genes & Diseases 2024年第3期11卷 63-65页

作者： Donghai Li State key laboratory of pharmaceutical biotechnology School of Life SciencesNanjing UniversityJiangsu 210023China

Uncoupling protein 1(UCP1,also known as thermogenin or SLC25A7)plays an important role in the uncoupling of oxidative phosphorylation and adaptive non-shivering thermogenesis(NST).The genomic location for UCP1 is chromosome 4 q31.1:140,555,770--140,568,961(GRCh38/hg38)and its size is 13,192 bases split into 6 *** dbSNP,3650 short genetic variations of human UCP1 are *** this study,UCP1 serves as an example to construct polymorphism-trait networks and enable a func-tional classification.

关键词： classification. UCP1 networks

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

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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

Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H:quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase

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Chinese Journal of Natural Medicines 2024年第1期22卷 75-88页

作者： SONG Jiangzhou ZOU Guiqing ZHAO Zhou ZHU Ya XUE Jiayu AO Lanjia SUN Huiyong HAO Haiping ZHANG Bo XU Xiaowei State key laboratory of Natural Medicines Key Lab of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China State key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

NAD(P)H:quinone oxidoreductase 1(NQO1)is a flavin protease highly expressed in various cancer ***1 catalyzes a futile redox cycle in substrates,leading to substantial reactive oxygen species(ROS)*** ROS generation results in extensive DNA damage and elevated poly(ADP-ribose)polymerase 1(PARP1)-mediated consumption of nicotinamide adenine dinucleotide(NAD^(+)),ultimately causing cell *** phosphoribosyltransferase(NAMPT),the rate-limiting enzyme in the NAD^(+)salvage synthesis pathway,emerges as a critical target in cancer *** concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+*** this study,we designed,synthesized,and assessed a novel series of proqodine A derivatives targeting both NQO1 and *** these,compound T8 demonstrated potent antitumor ***,T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and *** discovery offers a promising new molecular entity for advancing anticancer research.

关键词： NQO1 ROS NAMPT NAD^(+) T8

A growth-regulating factor 7(GRF7)-mediated gene regulatory network promotes leaf growth and expansion in sugarcane

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The Crop Journal 2024年第2期12卷 422-431页

作者： Qiaoyu Wang Yihan Li Dadong Lin Xiaoxi Feng Yongjun Wang Tianyou Wang Hongyan Ding Jisen Zhang State key lab for Conservation and Utilization of Subtropical AgroBiological Resources and Guangxi key lab for Saccharum Biology Guangxi UniversityNanning 530005GuangxiChina Center for Genomics and biotechnology/Fujian Provincial key laboratory of Haixia Applied Plant Systems Biology/key laboratory of Saccharum Biology and Genetic Breeding/national Engineering Research Center for Saccharum Fujian Agriculture and Forestry UniversityFuzhou 350002FujianChina

Knowledge of the function of growth-regulating factors(GRFs)in sugarcane(Saccharum officinarum and ***)growth and development could assist breeders in selecting desirable plant ***,limited information about GRFs is available in Saccharum due to their *** this study,22 GRFs were identified in the two species and their conserved domains,gene structures,chromosome location,and synteny were ***7 expression varied among tissues and responded to diurnal ***7-YFP was localized preferentially in the nucleus and appears to act as a transcriptional ***7 positively regulated the size and length of rice leaves,possibly by regulating cell size and plant *** seven potential transcription factors binding to the SsGRF7 promoter in ***,four showed positive expression patterns,and two showed negative expression patterns relative to SsGRF7.

关键词： Expression analysis Growth-regulating factor Leaf development Sugarcane Transcription factors

Two H3K36 methyltransferases differentially associate with transcriptional activity and enrichment of facultative heterochromatin in rice blast fungus

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aBIOTECH 2024年第1期5卷 1-16页

作者： Mengting Xu Ziyue Sun Huanbin Shi Jiangnan Yue Xiaohui Xiong Zhongling Wu Yanjun Kou Zeng Tao Ministry of Agriculture key laboratory of Molecular Biology of Crop Pathogens and Insects Institute of BiotechnologyZhejiang UniversityHangzhou 310058China State key lab of Rice Biology and Breeding China National Rice Research InstituteHangzhou 310021China

Di-and tri-methylation of lysine 36 on histone H3(H3K36me2/3)is catalysed by histone methyltransferase Set2,which plays an essential role in transcriptional *** there is a single H3K36 methyltransferase in yeast and higher eukaryotes,two H3K36 methyltransferases,Ash1 and Set2,were present in many filamentous ***,their roles in H3K36 methylation and transcriptional regulation remained *** with methods of RNA-seq and ChIP-seq,we revealed that both Ash1 and Set2 are redundantly required for the full H3K36me2/3 activity in Magnaporthe oryzae,which causes the devastating worldwide rice blast ***1 and Set2 distinguish genomic H3K36me2/3-marked regions and are differentially associated with repressed and activated transcription,***,Ash1-catalysed H3K36me2 was co-localized with H3K27me3 at the chromatin,and Ash1 was required for the enrichment and transcriptional silencing of H3K27me3-occupied *** the different roles of Ash1 and Set2,in H3K36me2/3 enrichment and transcriptional regulation on the stress-responsive genes,they differentially respond to various stresses in ***,we reveal a novel mechanism by which two H3K36 methyltransferases catalyze H3K36me2/3 that differentially associate with transcriptional activities and contribute to enrichment of facultative heterochromatin in eukaryotes.

关键词： Ash1 Facultative heterochromatin H3K36me2/3 Magnaporthe oryzae Set2 Transcriptional regulation

Gut liver brain axis in diseases:the implications for therapeutic interventions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 79-104页

作者： Mengyao Yan Shuli Man Benyue Sun Long Ma Lanping Guo Luqi Huang Wenyuan Gao State key laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&Technology300457 TianjinChina national Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina Tianjin key laboratory for Modern Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityWeijin Road300072 TianjinChina

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract,liver,and nervous *** the past few decades,breakthrough progress has been made in the gut liver brain axis,mainly through understanding its formation mechanism and increasing treatment *** this review,we discuss various complex networks including barrier permeability,gut hormones,gut microbial metabolites,vagus nerve,neurotransmitters,immunity,brain toxic metabolites,β-amyloid(Aβ)metabolism,and epigenetic regulation in the gut-liver-brain *** therapies containing antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation(FMT),polyphenols,low FODMAP diet and nanotechnology application regulate the gut liver brain ***,some special treatments targeting gut-liver axis include farnesoid X receptor(FXR)agonists,takeda G protein-coupled receptor 5(TGR5)agonists,glucagon-like peptide-1(GLP-1)receptor antagonists and fibroblast growth factor 19(FGF19)*** gut-brain axis embraces cognitive behavioral therapy(CBT),antidepressants and tryptophan metabolism-related *** liver-brain axis contains epigenetic regulation and Aβmetabolism-related *** the future,a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

关键词： metabolism therapeutic immunity

Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR–Stat3/Akt pathway

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Journal of Molecular Cell Biology 2024年第1期16卷 29-42页

作者： Qiyao Liu Manyun Li Minli Sun Ruyue Xin Yushu Wang Qin Chen Xiang Gao Zhaoyu Lin MOE key laboratory of Model Animals for Disease Study State Key Laboratory of Pharmaceutical BiotechnologyJiangsu Key Laboratory of Molecular MedicineModel Animal Research CenterNational Resource Center for Mutant Mice of ChinaNanjing Drum Tower HospitalSchool of MedicineNanjing UniversityNanjing 210061China Department of Oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200240China

Homeostasis of the skin barrier is essential for maintaining normal skin *** A(GSDMA)is highly expressed in the skin and associated with many skin diseases,such as melanoma and *** mice,GSDMA is encoded by three gene homologues,namely Gsdma1,Gsdma2,and *** Gsdma3 gain-of-function mutations cause hair loss and skin inflammation,Gsdma3-deficient mice do not show any visible phenotypes in skin and hair *** explore the physiological function of GSDMA,we generated conventional Gsdma1/2/3 knockout(KO)*** mice showed significantly alleviated epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate(PMA).Furthermore,the alleviation of epidermal hyperplasia depended on the expression of Gsdma1/2/3 specifically in ***,Gsdma1/2/3 depletion downregulated epidermal growth factor receptor(EGFR)ligands,leading to the decreased EGFR–Stat3/Akt *** results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR–Stat3/Akt pathway.

关键词： GSDMA epidermal hyperplasia PMA Hb-egf EGFR Stat3 Akt

Piperazine-derived ionizable lipids for enhanced mRNA delivery and cancer immunotherapy

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Nano Research 2024年第8期17卷 7357-7364页

作者： Kai Xu Yujia Xu Jin Sun Xinwei Cheng Chenxi Lu Wenzhong Chen Bingfang He Tianyue Jiang School of pharmaceutical Sciences Nanjing Tech UniversityNanjing 211816China Department of Nano Formulation Nanjing GeneLeap BiotechnologyNanjing 210061China

Messenger ribonucleic acid(mRNA)-based therapeutics hold great prospects in disease treatment and lipid nanoparticles(LNPs)are the most extensively applied non-viral platform for RNA delivery in *** the clinical success of LNPs as vehicles have been achieved,developing LNPs with enhanced mRNA transmembrane delivery and transfection efficiency in a non-toxic manner is highly desirable and *** this study,we designed a series of new ionizable amino lipids with piperazinederived headgroups and constructed a group of LNPs to promote the transfection activity of mRNA *** them,LNP formulated with lipid 10(L10-LNP)can efficiently package mRNA and perform superior transfection efficiency both in vitro and in vivo,which is mainly attributed to the improved intracellular uptake and effective endosomal *** verified that a single administration of L10-LNP packaging interleukin(IL)-12 mRNA induced tumor shrink and even regression by robust activation of immune effector CD8^(+)T cells and stimulating the generation of IFN-γwithout causing systemic toxicity,which provides a promising platform for clinical cancer immunotherapy.

关键词： ionizable lipid lipid nanoparticle piperazine-derived lipid mRNA therapeutics cancer immunotherapy

Acatulides A-G,neuroprotective macrolides from Acaulium album H-JQSF

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Chinese Chemical Letters 2024年第3期35卷 379-383页

作者： Zhi-Wu Tong Ting-Ting Wang Pei Yang Jia-Lin Sun Chen-Peng Zhang Salman Khan Xin-Cun Wang Rui-Hua Jiao Hui-Ming Ge Wen-Ying Zhuang Gang Hu Ren Xiang Tan State key laboratory of pharmaceutical biotechnology Institute of Functional BiomoleculesNanjing UniversityNanjing 210023China State key laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese MedicineNanjing 210023China Insitute of Microbiology Chinese Academy of SciencesBeijing 100101China

Fungal symbionts co-evolve with hosts and microbial co-inhabitants to acquire an unpredictable potential for producing novel bioactive metabolites,but the knowledge about the topic remains patchy and *** we present the chemical characterization of acatulides A-G(1-7)as architecturally unprecedented macrolides from the solid-state culture of Acaulium album H-JQSF,an arthropod-associated *** acatulide structures were elucidated by spectroscopic analysis,modified Mosher's method and single-crystal X-ray *** plausible biosynthetic pathways for compounds 1-4 are ***,acatulides B-D(2-4)and G(7)were demonstrated to be neuroprotective against the 1-methyl-4-phenylpyridinium(MPP+)-induced damage to SH-SY5Y cells and nematode Caenorhabditis elegans(***).

关键词： Acaulium album Macrolides Acatulides A–G Mosher’s method Neuroprotective