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Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed–1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2567-2580页

作者： Hongying Li Jianrui Li Jiayu Li Hu Li Xuekai Wang Jing Jiang Lei Lei Han Sun Mei Tang Biao Dong Weiqing He Shuyi Si Bin Hong Yinghong Li Danqing Song Zonggen Peng Yongsheng Che Jian-Dong Jiang CAMS Key laboratory of Antiviral Drug Research Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Beijing Key laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Key laboratory of biotechnology of Antibiotics the National Health and Family Planning Commission(NHFPC)Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral ***,we show that carrimycin,a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials,decreases the efficiency of programmed–1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum *** binds directly to the coronaviral frameshift-stimulatory element(FSE)RNA pseudoknot,interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription *** carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on *** the FSE mechanism is essential in all coronaviruses,carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE *** finding may open a new direction in antiviral drug discovery for coronavirus variants.

关键词： Carrimycin Coronavirus Broad-spectrum antiviral activity Programmed-1 ribosomal frameshifting RNA pseudoknot Antiviral agent RNA target Synergistic inhibitory effect

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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 laboratory of Molecular Biology of Crop Pathogens and Insects Institute of BiotechnologyZhejiang UniversityHangzhou 310058China State Key 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

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Rational management of the plant microbiome for the Second Green Revolution

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Plant Communications 2024年第4期5卷 1-15页

作者： Xiaofang Li Xin Zheng Nikita Yadav Shouvik Saha El-Sayed Salama Xiangkai Li Likun Wang Byong-Hun Jeon Center for Agricultural resources Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuang 050021China Department of Earth resources and Environmental Engineering Hanyang UniversitySeoul 04763South Korea natural resources Research Institute University of Minnesota DuluthHermantownMN 55811USA Department of biotechnology Brainware UniversityBarasatKolkata 700125West BengalIndia Department of Occupational and Environmental Health School of Public HealthLanzhou UniversityLanzhouGansu 730000China Ministry of Education Key laboratory of Cell Activities and Stress Adaptations School of Life ScienceLanzhou UniversityLanzhouGansu 730000China

The Green Revolution of the mid-20th century transformed agriculture worldwide and has resulted in envi-ronmental challenges.A new approach,the Second Green Revolution,seeks to enhance agricultural pro-ductivity while minimizing negative environmental *** microbiomes play critical roles in plant growth and stress responses,and understanding plant–microbiome interactions is essential for developing sustainable agricultural practices that meet food security and safety challenges,which are among the United Nations Sustainable Development *** review provides a comprehensive exploration of key deterministic processes crucial for developing microbiome management strategies,including the host effect,the facilitator effect,and microbe–microbe interactions.A hierarchical framework for plant mi-crobiome modulation is proposed to bridge the gap between basic research and agricultural *** framework emphasizes three levels of modulation:single-strain,synthetic community,and in situ mi-crobiome ***,rational management of plant microbiomes has wide-ranging applications in agriculture and can potentially be a core technology for the Second Green Revolution.

关键词： Second Green Revolution plant microbiome rational management host effect microbiome heritability

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A sustainable process to 100%bio-based nylons integrated chemical and biological conversion of lignocellulose

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Green Energy & Environment 2024年第2期9卷 390-402页

作者： Ruijia Hu Ming Li Tao Shen Xin Wang Zhuohua Sun Xinning Bao Kequan Chen Kai Guo Lei Ji Hanjie Ying Pingkai Ouyang Chenjie Zhu College of biotechnology and Pharmaceutical Engineering Nanjing Tech UniversityNanjingChina National Engineering Research Center for biotechnology Nanjing Tech UniversityNanjingChina Beijing Key laboratory of Lignocellulosic Chemistry Beijing Forestry UniversityBeijingChina

Considerable progress has been made in recent years to the development of sustainable polymers from bio-based *** this study,100%bio-based nylons were prepared via an integrated chemical and biological process from *** novel nylons were obtained by the melt polymerization of 3-propyladipic acid derived from lignin and 1,5-pentenediamine/1,4-butanediamine derived from carbohydrate *** to the concept is a three-step noble metal free catalytic chemical funnelling sequence(Raney Ni mediated reductive catalytic fractionation-reductive funnelling-oxidative funnelling),which allowed for obtaining a single component 3-propyladipic acid from lignin with high *** structural and thermodynamic properties of the obtained nylons have been systematically investigated,and thus obtained transparent bio-based nylons exhibited higher Mw(>32,000)and excellent thermal stability(Td5%>265℃).Considering their moderate Tg and good melt strength,these transparent bio-based nylons could serve as promising functional additives or temperature-responsive materials.

关键词： Lignocellulose Lignin Reductive catalytic fractionation Bio-based nylon

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Establishment of a transformation system in close relatives of wheat under the assistance of TaWOX5

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Journal of Integrative Agriculture 2024年第6期23卷 1839-1849页

作者： Yanan Chang Junxian Liu Chang Liu Huiyun Liu Huali Tang Yuliang Qiu Zhishan Lin Ke Wang Yueming Yan Xingguo Ye Institute of Crop Sciences Chinese Academy of Agricultural SciencesBeijing 100081China Beijing Key laboratory of Plant Gene resources and biotechnology for Carbon Reduction and Environment Improvement/College of Life Science Capital Normal UniversityBeijing 100048China College of Agronomy and biotechnology China Agricultural UniversityBeijing 100193China State Key laboratory of Plant Cell and Chromosome Engineering/Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100101China

Species closely related to wheat are important genetic resources for agricultural production,functional genomics studies and wheat *** this study,a wheat gene related to regeneration,TaWOX5,was applied to establish the Agrobacterium-mediated transformation systems of Triticum monococcum,hexaploid triticale,and rye(Secale cereale L.)using their immature *** plants were efficiently *** the transformation process,the Agrobacterium infection efficiency was assessed by histochemical staining forβ-glucuronidase(GUS).Finally,the transgenic nature of regenerated plants was verified by polymerase chain reaction(PCR)-based genotyping for the presence of the GUS and bialaphos resistance(bar)genes,histochemical staining for GUS protein,and the QuickStix strip assay for bar *** transformation efficiency of *** genotype PI428182 was 94.4%;the efficiencies of four hexaploid triticale genotypes Lin456,ZS3297,ZS1257,and ZS3224 were 52.1,41.2,19.4,and 16.0%,respectively;and the transformation efficiency of rye cultivar Lanzhou Heimai was 7.8%.Fluorescence in situ hybridization(FISH)and genomic in situ hybridization(GISH)analyses indicated that the GUS transgenes were integrated into the distal or near centromere(proximal)regions of the chromosomes in transgenic *** and hexaploid triticale *** the transgenic hexaploid triticale plants,the foreign DNA fragment was randomly integrated into the AABB and RR ***,the transgene was almost stably inherited in the next generation by Mendel’s *** findings in this study will promote the genetic improvement of the three plant species for grain or forage production and the improvement of cereal species including wheat for functional genomics studies.

关键词： Triticum monococcum hexaploid triticale rye TaWOX5 Agrobacterium transformation efficiency

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A NAC transcription factor MNAC3-centered regulatory network negatively modulates rice immunity against blast disease

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Journal of Integrative Plant Biology 2024年第9期66卷 2017-2041页

作者： Hui Wang Yan Bi Yuqing Yan Xi Yuan Yizhou Gao Muhammad Noman Dayong Li Fengming Song National Key laboratory for Rice Biology and Breeding Institute of BiotechnologyZhejiang UniversityHangzhou 310058China Ministry of Agriculture Key laboratory of Molecular Biology of Crop Pathogens and Insect Pests Institute of BiotechnologyZhejiang UniversityHangzhou 310058China Key laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province Institute of BiotechnologyZhejiang UniversityHangzhou 310058China College of Chemistry and Life Sciences Zhejiang Normal UniversityJinhua 321004China

NAC transcription factors(TFs)are pivotal in plant immunity against diverse ***,we report the functional and regulatory network of MNAC3,a novel NAC TF,in rice ***3,a transcriptional activator,negatively modulates rice immunity against blast and bacterial leaf blight diseases and pathogen-associated molecular pattern(PAMP)-triggered immune ***3 binds to a CACG cis-element and activates the transcription of immune-negative target genes OsINO80,OsJAZ10,and *** negative function of MNAC3 in rice immunity depends on its transcription of downstream genes such as OsINO80 and ***3 interacts with immunity-related OsPP2C41(a protein phosphatase),ONAC066(a NAC TF),and OsDjA6(a DnaJ chaperone).ONAC066 and OsPP2C41 attenuate MNAC3 transcriptional activity,while OsDjA6 promotes *** of MNAC3 at S163 is critical for its negative functions in rice ***2C41,which plays positive roles in rice blast resistance and chitin-triggered immune responses,dephosphorylates MNAC3,suppressing its transcriptional activity on the target genes OsINO80,OsJAZ10,and OsJAZ11 and promoting the translocation of MNAC3 from nucleus to *** results establish a MNAC3-centered regulatory network in which OsPP2C41 dephosphorylates MNAC3,attenuating its transcriptional activity on downstream immune-negative target genes in ***,these findings deepen our understanding of molecular mechanisms in rice immunity and offer a novel strategy for genetic improvement of rice disease resistance.

关键词： NAC transcription factor MNAC3 OsINO80 OsJAZ10 OsJAZ11 protein phosphatase OsPP2C41 rice immunity

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Selectively T cell phosphorylation activation of azvudine in the thymus tissue with immune protection effect

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3140-3154页

作者： Ning Sheng Rui Li Yang Li Zhe Wang Lulu Wang Yuhuan Li Jinlan Zhang Jiandong Jiang State Key laboratory of Bioactive Substance and Function of natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Institute of Medicinal biotechnology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Thymus is the important immune organ,responsible for T cell development and *** lower circulating T counts have been observed in patients who died from COVID-19 compared with ***,also known as FNC,is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 *** this study,single-cell transcriptome,proteomics,and parallel reaction monitoring(PRM)were applied to insight into the activation process of FNC in rat and SARS-CoV-2 rhesus monkey *** results indicated that thymic immune cells possess a robust metabolic capacity for cytidine-analogue drugs such as *** enzymes involved in the FNC phosphorylation process,such as Dck,Cmpk1,and Nme2,were highly expressed in CD4+ T cells,CD8+ T cells,and DP(CD4+ CD8+)***,FNC could upregulate multiple phosphorylated kinases in various cell types while downregulating the phosphatases,phosphoribosyl transferases,and deaminases,*** robust phosphorylation capacity of the thymus for cytidine analogue drug FNC,and the activation effect of FNC on the NAs metabolism system potentially contribute to its enrichment in the thymus and immune protection *** suggests that it is crucial to consider the expression level of phosphorylation kinases when evaluating NA drug properties,as an important factor during antiviral drug design.

关键词： Azvudine T cell Thymus Phosphorylation activation Nucleoside analogue

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Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species

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Chinese Journal of natural Medicines 2024年第4期22卷 375-384页

作者： ZENG Zhen ZHANG Chen HU Jiadong WANG Feiyan WU Ziding WANG Jing ZHANG Jun YANG Shuda CHEN Junfeng LI Mingming TONG Qi QIU Shi CHEN Wansheng The SATCM Key laboratory for New resources&Quality Evaluation of Chinese Medicine Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Department of Pharmacy Second Affiliated Hospital of Navy Medical UniversityShanghai 200003China Kunming Plant Classification biotechnology Co. Ltd.Kunming 650500China School of Pharmaceutical Sciences and Yunnan Key laboratory of Pharmacology for natural Products Kunming Medical UniversityKunming 650500China State Key laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Beijing100700China

The aerial parts of Mosla chinensis *** Mosla chinensis cv.'Jiangxiangru'(MCJ)are widely utilized in traditional Chinese medicine(TCM),known collectively as ***,due to clinical effectiveness concerns and frequent misidentification,the original plants have increasingly been substituted by various species within the genera Elsholtzia and *** challenge in distinguishing between these genera arises from their similar morphological and metabolic *** address this issue,our study introduced a rapid method for metabolic characterization,employing high-resolution mass spectrometry-based *** detailed biosynthetic and chemometric analyses,we pinpointed five phenolic compounds—salviaflaside,cynaroside,scutellarein-7-O-D-glucoside,rutin,and vicenin-2—among 203 identified compounds,as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia *** methodology holds promise for broad application in the analysis of plant aerial parts,especially in verifying the authenticity of aromatic traditional medicinal *** findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.

关键词： Genus Elsholtzia Genus Mosla Traditional Chinese medicine Xiang-ru Non-volatile phenolic compounds Liquid chromatography-mass spectrometry

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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 Key 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

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Methanolic extract of Ephedra alata inhibits breast cancer cells in vitro and in vivo

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Asian Pacific Journal of Tropical Biomedicine 2024年第4期14卷 154-161页

作者： Fairouz Sioud Aida Lahmer Mouna Selmi Fadwa Chaabane Leila Chekir-Ghedira Research Unit Bioactive natural Products and biotechnology UR17ES49 Faculty of Dental Medicine of MonastirUniversity of MonastirAvicenne Street5000 MonastirTunisia laboratory of Pharmacognosy Faculty of PharmacyUniversity of MonastirAvicenne Street5000 MonastirTunisia

Objective:To determine the anticancer potential of the methanolic extract from Ephedra alata against breast cancer both in vitro and in ***:The effects of the methanolic extract of Ephedra alata on the viability,migration as well as apoptosis of breast cancer 4T1 cells were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,Transwell assay,and annexin V-FITC staining assay,*** examination was also carried ***,a murine breast cancer model was established to evaluate the inhibitory effect of the *** parameters including hepatic and non-hepatic enzymes,malondialdehyde,and glutathione were ***:The methanolic extract of Ephedra alata showed a strong anti-proliferative and anti-migratory activity against 4T1 cells in a dose-dependent *** also induced apoptosis in 4T1 *** an in vivo mouse model,the extract markedly inhibited tumor growth,reduced malondialdehyde,and hepatic and non-hepatic enzymes as well as increased glutathione ***:The methanolic extract of Ephedra alata inhibits breast cancer in vitro and in vivo,which may be a promising anticancer agent.

关键词： Ephedra Breast cancer Apoptosis Antioxidant Migration

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