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Discovery of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis

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Chinese Journal of Natural Medicines 2024年第9期22卷 842-853页

作者： WANG Sibei LIU Yuhui LIANG Yue XI Yaru ZHAI Yupeng LEE Dongho XU Jing GUO Yuanqiang state {1. laboratory of Medicinal Chemical Biology College of Pharmacyand Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300350China state {1. laboratory of Functions and Applications of Medicinal Plants Guizhou Medical UniversityGuiyang 550014China Department of Plant biotechnology College of Life Sciences and BiotechnologyKorea UniversitySeoul 02841South Korea

Eight novel clerodane diterpenoids(1.8)were isolated from the twigs of Casearia *** structures were elucidated through comprehensive nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass spectrometry(HRESI-MS),and electronic circular dichroism(ECD)*** addition to structural determination,surface plasmon resonance(SPR)assays were conducted to investigate molecular interactions,revealing that compound 8 exhibited high affinity for vascular endothelial growth factor receptor 2(VEGFR2),a key regulator of tumor *** in vivo experiments demonstrated that compound 8 effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft *** findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.

关键词： Clerodane diterpenoids Casearia graveolens Surface plasmon resonance Vascular endothelial growth factor receptor 2 Antitumor activity Zebrafish

Nickel-catalyzed enantioselective reductive amination of benzylic ketones in alcohols

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Science China Chemistry 2024年第8期67卷 2566-2570页

作者： Xiuhua Wang Jianrong Steve Zhou state {1. laboratory of Chemical Oncogenomics School of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhen 518055China

Asymmetric reductive amination directly converts ketones and amines to alkylamines, which are important motifs in *** report that cationic nickel complexes of chiral diphosphines promote enantioselective reductive amination of benzylic ketones with both arylamines and benzhydrazide. Isopropanol was used as a safe and cheap source of hydrogen instead of formic acid. The reaction can be readily applied to a concise synthesis of diarylethylamines, a class of neuroactive substances.

关键词： transfer hydrogenation nickel catalysis chiral alkylamine reductive amination synthetic method

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 {1. laboratory of Pharmaceutical biotechnology School of Life SciencesNanjing UniversityNanjing 210023China National key {1. 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 {1. 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

Carbene-catalyzed enantioselective seleno-Michael addition as access to antimicrobial active Se-containing heterocycles

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Science China Chemistry 2024年第7期67卷 2199-2205页

作者： Hongyan Long Sha Zhao Chunyan Jian Xiuli Wu Fengfei Lu Minghong Liao Fengrui Che Xingxing Wu Yonggui Robin Chi state {1. laboratory of Green Pesticide Key Laboratory of Green Pesticide and Agricultural BioengineeringMinistry of EducationGuizhou UniversityGuiyang 550025China School of Chemistry Chemical Engineeringand BiotechnologyNanyang Technological UniversitySingapore 637371Singapore

Organoseleniums exhibit a diverse set of biological activities that are pivotal for drug discovery and are widely explored in synthetic chemistry and material *** many transformations have been developed for non-enantioselective C–Se bond formations,the catalyst-controlled stereoselective preparation of chiral organoseleniums continues to be of considerable *** particular,there are limited studies on the enantioselective seleno-Michael addition reactions to access chiral selenium functional ***,we disclose a carbene-catalyzed highly enantioselective nucleophilic C–Se bond construction through formal[3+3]annulations between selenocarboxamides and bromoenals,affording seleno-thiazinone products with good yields and excellent *** choice of a weak inorganic base was pivotal to suppressing the unproductive racemization and decomposition of the selenium ***,the catalytically generated chiral selenium-containing heterocyclic products feature remarkable antimicrobial activities that could serve as promising lead scaffolds for further agrochemical development.

关键词： seleno-Michael addition organocatalysis N-heterocyclic carbene seleno-heterocycles antimicrobial activity

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

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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 {1. of Carbohydrate Chemistry and biotechnology Ministry of Education School of BiotechnologyJiangnan UniversityWuxi 214122China state {1. 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

m^(6)A modification of plant virus enables host recognition by NMD factors in plants

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Science China(Life Sciences) 2024年第1期67卷 161-174页

作者： Hao He Linhao Ge Yalin Chen Siwen Zhao Zhaolei Li Xueping Zhou Fangfang Li state {1. laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China state {1. laboratory of Rice Biology Institute of BiotechnologyZhejiang UniversityHangzhou 310029China

N^(6)-methyladenosine(m^(6)A)is the most abundant eukaryotic mRNA modification and is involved in various biological *** evidence has implicated that m^(6)Amodification is an important anti-viral defense mechanism in mammals and plants,but it is largely unknown how m^(6)Aregulates viral infection in *** we report the dynamic changes and functional anatomy of m^(6)Ain Nicotiana benthamiana and Solanum lycopersicum during Pepino mosaic virus(PepMV)infection.m^(6)Amodification in the PepMV RNA genome is conserved in these two *** of the m^(6)Awriters,mRNA adenosine methylase A(MTA),and HAKAI inhibit the PepMV RNA accumulation accompanied by increased viral m^(6)Amodifications,whereas deficiency of these writers decreases the viral RNA m^(6)Alevels but enhances virus *** study reveals that the cytoplasmic YTH-domain family protein NbECT2A/2B/2C as m^(6)Areaders are involved in anti-viral ***-protein interactions indicate that NbECT2A/2B/2C interact with nonsense-mediated mRNA decay(NMD)-related proteins,including NbUPF3 and NbSMG7,but not with NbUPF1.m^(6)Amodification-mediated restriction to PepMV infection is dependent on NMD-related *** findings provide new insights into the functionality of m^(6)Aanti-viral activity and reveal a distinct immune response that NMD factors recognize the m^(6)Areaders-viral m^(6)ARNA complex for viral RNA degradation to limit virus infection in plants.

关键词： m^(6)A Pepino mosaic virus plant defense m^(6)A readers NMD factors

Carbonic anhydrase-like enzymes in the formation of Lycopodium alkaloid

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

作者： DONG Huiwen GE Huiming state {1. 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

A pair of nuclear factor Y transcription factors act as positive regulators in jasmonate signaling and disease resistance in Arabidopsis

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Journal of Integrative Plant Biology 2024年第9期66卷 2042-2057页

作者： Chuyu Lin Chenghao Lan Xiaoxiao Li Wei Xie Fucheng Lin Yan Liang Zeng Tao Ministry of Agriculture key {1. of Molecular Biology of Crop Pathogens and Insects Institute of BiotechnologyZhejiang UniversityHangzhou 310058China state {1. laboratory for Managing Biotic and Chemical Treats to the Quality and Safety of Agro‐products Institute of BiotechnologyZhejiang UniversityHangzhou 311400China

The plant hormone jasmonate(JA)regulates plant growth and immunity by orchestrating a genome-wide transcriptional *** the resting stage,JASMONATE-ZIM DOMAIN(JAZ)proteins act as main repressors to regulate the expression of JA-responsive genes in the JA signaling ***,the mechanisms underlying de-repression of JA-responsive genes in response to JA treatment remain ***,we report two nuclear factor Y transcription factors NF-YB2 and NF-YB3(thereafter YB2 and YB3)play key roles in such de-repression in ***2 and YB3 function redundantly and positively regulate plant resistance against the necrotrophic pathogen Botrytis cinerea,which are specially required for transcriptional activation of a set of JA-responsive genes following ***,YB2 and YB3 modulated their expression through direct occupancy and interaction with histone demethylase Ref6 to remove repressive histone ***,YB2 and YB3 physically interacted with JAZ repressors and negatively modulated their abundance,which in turn attenuated the inhibition of JAZ proteins on the transcription of JA-responsive genes,thereby activating JA response and promoting disease ***,our study reveals the positive regulators of YB2 and YB3 in JA signaling by positively regulating transcription of JA-responsive genes and negatively modulating the abundance of JAZ proteins.

关键词： histone demethylase jasmonate response JAZ repressor necrotrophic resistance nuclear factor

Lime pretreatment of maize stover and solubilization of pretreated solids by enzymatic hydrolysis and Clostridium thermocellum fermentation

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International Journal of Agricultural and Biological Engineering 2024年第4期17卷 288-296页

作者： Guanying Wang Gang Zhang Xiongjun Shao state {1. laboratory of Biocatalysis and Enzyme Engineering/Hubei {1. laboratory of Industrial biotechnology School of Life SciencesHubei UniversityWuhan 430062China

Lime pretreatment on maize stover was conducted with various pretreatment conditions selected by central composite *** and lignin contents in pretreated maize stover were relatively *** of glucose monomer and oligomers decreased while concentration of xylooligomers increased in the pretreatment hydrolysate with increasing pretreatment *** overall carbohydrate recovery was at least 85%for the conditions *** removal during pretreatment was found to have a linear correlation with lignin *** had a higher effect in enhancing carbohydrate solubilization for enzymatic hydrolysis than that for *** *** all the pretreated solids,Clostridium thermocellum fermentation was found to result in much higher carbohydrate solubilization than enzymatic hydrolysis with a cellulase loading of 8 mg/g solids and a xylanase loading of 2 mg/g *** solubilization was found to have a linear correlation with lignin removal during lime pretreatment for both enzymatic hydrolysis and *** *** the current challenges,this research provides a new idea for the industrial application of lignocellulosic biorefinery.

关键词： central composite design lime pretreatment enzymatic hydrolysis clostridium thermocellum carbohydrate solubilization