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Identification of a natural PLA2 inhibitor from the marine fungus Aspergillus sp.c1 for MAFLD treatment that suppressed lipotoxicity by inhibiting the IRE-1a/XBP-1s axis and JNK signaling

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Acta Pharmaceutica Sinica B 2024年第1期14卷 304-318页

作者： Yong Rao Rui Su Chenyan Wu Xingxing Chai Jinjian Li Guanyu Yang Junjie Wu Tingting Fu Zhongping Jiang Zhikai Guo Congjun Xu Ling Huang Key Laboratory of tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikou 570200China Hainan Key Laboratory of tropical Microbe Resources Institute of Tropical Bioscience and BiotechnologyChinese Academy of Tropical Agricultural Sciences&Key Laboratory for Biology and Genetic Resources of Tropical Crops of Hainan ProvinceHainan Institute for Tropical Agricultural ResourcesHaikou 571101China School of Pharmaceutical Sciences Guangdong Provincial Key Laboratory of New Drug Design and EvaluationSun Yat-sen UniversityGuangzhou 510275China Laboratory Animal Center of Guangdong Medical University Dongguan 523808China

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease(MAFLD).However,there are few reported lipotoxicity ***,we identified a natural anti-lipotoxicity candidate,HN-001,from the marine fungus Aspergillus ***-001 dose-and time-dependently reversed palmitic acid(PA)-induced hepatocyte *** protection was associated with IRE-1a-mediated XBP-1 splicing inhibition,which resulted in suppression of XBP-1s nuclear translocation and transcriptional *** of XBP-1s attenuated lipotoxicity,but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown ***,the ER stress and lipotoxicity amelioration was associated with *** HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity,reduced lysophosphatidylcholine(LPC)level,subsequently ameliorated *** contrast,overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of ***,HN-001 treatment suppressed the downstream pro-apoptotic JNK *** vivo,chronic administration of HN-001(i.p.)in mice alleviated all manifestations of MAFLD,including hepatic steatosis,liver injury,inflammation,and *** effects were correlated with PLA2/IRE-1a/XBP-1s axis and JNK signaling *** data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity,and provide a natural structural basis for developing anti-MAFLD candidates.

关键词： Lipotoxicity MAFLD ER stress IRE-1a XBP-1s JNK PLA2

The Clausena lansium genome provides new insights into alkaloid diversity and the evolution of the methyltransferase family

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Journal of Integrative Agriculture 2024年第10期23卷 3537-3553页

作者： Yongzan Wei Yi Wang Fuchu Hu Wei Wang Changbin Wei Bingqiang Xu Liqin Liu Huayang Li Can Wang Hongna Zhang Zhenchang Liang Jianghui Xie State Key Laboratory of Biological Breeding of tropical Crops Institute of Tropical Bioscience and BiotechnologyChineseAcademy of Tropical Agricultural SciencesHaikou 571101China Key Laboratory of Genetic Resources Evaluation and Utilization of tropical Fruits and Vegetables(Co-construction by Ministryand Province) Ministry of Agriculture and Rural Affairs/Institute of Tropical Fruit TreesHainan Academy of Agricultural SciencesHaikou 571100China Beijing Key Laboratory of Grape Sciences and Enology CAS Key Laboratory of Plant ResourcesInstitute of BotanyChineseAcademy of SciencesBeijing 100093China Key Laboratory of tropical Fruit Biology(Ministry of Agriculture and Rural Affairs) South Subtropical Crops Research InstituteChinese Academy of Tropical Agricultural SciencesZhanjiang 524091China Haikou Experimental Station Chinese Academy of Tropical Agricultural SciencesHaikou 571101China Sanya institute of Breeding and Multiplication/School of tropical Agriculture and Forestry Hainan UniversityHaikou 570228China Sanya Research Academy Chinese Academy of Tropical Agricultural SciencesSanya 572019China

Wampee(Clausena lansium)is an important evergreen fruit tree native to southern China that has a long history of use for medicinal ***,a chromosome-level genome of *** was constructed with a genome size of 282.9 Mb and scaffold N50 of 30.75 *** assembled genome contains 48.70%repetitive elements and 24,381 protein-coding *** genomic analysis showed that *** diverged from Aurantioideae 15.91-24.95 million years ***,some expansive and specific gene families related to methyltransferase activity and S-adenosylmethionine-dependent methyltransferase activity were also *** analysis indicated that N-methyltransferase(NMT)is mainly involved in alkaloid biosynthesis and O-methyltransferase(OMT)participates in the regulation of coumarin accumulation in *** suggested that wampee's richness in alkaloids and coumarins might be due to the gene expansions of NMT and *** tandem repeat event was one of the major reasons for the NMT ***,the reference genome of *** will facilitate the identification of some useful medicinal compounds from wampee resources and reveal their biosynthetic pathways.

关键词： Clausena lansium genome evolution methyltransferase activity alkaloid biosynthesis coumarin accumulation

Pathogenic Surveillance of Foodborne Illness-Related Diarrhea—Beijing Municipality,China,2013-2023

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China CDC weekly 2024年第24期6卷 568-573页

作者： Chao Wang Tongyu Wang Yanlin Niu Yangbo Wu Jinru Jiang Xiaochen Ma institute for Nutrition and Food hygiene Beijing Center for Disease Prevention and ControlBeijingChina

What is already known about this topic?Foodborne diseases present a significant public health concern,particularly in China,where they represent a significant food safety ***,there is a need for a thorough and systematic analysis of the extended epidemiological patterns of foodborne diseases in Beijing *** is added by this report?Monitoring results show that Norovirus and diarrheagenic Escherichia coli(DEC)are the most commonly identified foodborne diarrheal *** aged 19–30 are at a higher risk of foodborne diarrhea in Beijing,with Salmonella infection being associated with fever *** are the implications for public health practice?This study analyzes 11 years of consecutive monitoring data to enhance understanding of the epidemiological and clinical features of foodborne diarrhea in *** aims to identify high-risk populations,assist in clinical pathogen identification and treatment,and support the development of tailored preventive strategies.

关键词： Beijing safety borne

R2R3-type Lo MYB21 affects jasmonate-regulated development and dehiscence of anthers in lily(Lilium oriental hybrids)

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Horticultural Plant Journal 2024年第1期10卷 239-251页

作者： Zheng Tong Tingting Dong Qiuhua Li Rui Wang Junna He Bo Hong institute of tropical Bioscience and Biotechnology Chinese Academy of Tropical Agricultural Sciences&Hainan Institute for Tropical Agricultural ResourcesHaikouHainan 571101China Beijing Key Laboratory of Development and Quality Control of Ornamental Crops Department of Ornamental HorticultureChina Agricultural UniversityBeijing 100193China Beijing Garden Expo Management Center Beijing 100072China

Lilies are widely cultivated for cut flowers,but their large anthers carry a considerable amount of colored pollen that is dispersed *** the molecular mechanism of anther development and dehiscence could help solve this ***21,encoding a putative R2R3v-myb avian myeloblastosis viral oncogene homolog(MYB)transcription factor,was identified from oriental lilies(Lilium‘Siberia’).Real-time quantitative PCR analysis showed that LoMYB21 was mainly expressed in the anther,filament and stigma and had high expression during the late stages of lily anther ***21 had transactivation activity and was located in the nucleus through yeast one-hybrid assays and transient expression in Nicotiana *** of LoMYB21 by virus-induced gene silencing(VIGS)in Lilium‘Siberia’led to anther indehiscence and reduced the expression of genes related to Jasmonate acid(JA)biosynthesis and signal *** of LoMYB21 in DEX::LoMYB21 transgenic Arabidopsis caused procumbent inflorescences that became infertile,accompanied by higher expression of JA biosynthetic and signaling *** results demonstrated that JA content and signaling were abnormal in silenced lily and transgenic LoMYB21 Arabidopsis,which affected anther *** study indicated that LoMYB21 could regulate lily anther dehiscence through JA biosynthesis and signaling during the late stages of anther development.

关键词： Lilium LoMYB21 Anther dehiscence Jasmonate acid

Predictors of Global Disparities in COVID-19 Vaccination Coverage — 219 Countries and Territories, December 2020–July 2022

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China CDC weekly 2024年第15期6卷 318-323,I0006,I0007页

作者： Ying Zhang Shujie Zang Xu Zhang Zhiqiang Qu Xinyu Zhou Leesa Lin Zhiyuan Hou School of Public Health and Global Health InstituteFudan UniversityShanghaiChina Department of Infectious Disease Epidemiology London School of Hygiene&Tropical MedicineLondonUnited Kingdom Laboratory of Data Discovery for Health(D24H) Hong Kong Science ParkHong Kong Special Administrative RegionChina

What is already known about this topic?The significant disparities in global coronavirus disease 2019(COVID-19)vaccine coverage hamper the pace of epidemic *** is a need to better understand the factors contributing to disparities in COVID-19 vaccination rates across *** is added by this report?This report revealed significant associations between vaccination coverage and various country-level *** pandemic preparedness,higher levels of trust,and a lower proportion of young population aged 0–14 were strongly correlated with higher COVID-19 vaccination *** are the implications for public health practices?Our findings emphasize the need for enhanced pandemic preparedness and governance,coupled with building trust in government and healthcare *** also needs to address the hesitancy of vaccinating children and adolescents aged 0–14 as the vaccination campaign progresses.

关键词： vaccination vaccine COV

Bioactive chemical constituents from the marine-derived fungus Cladosporium ***-5

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Journal of Oceanology and Limnology 2024年第3期42卷 905-914页

作者： Luting DAI Qingyi XIE Jiaocen GUO Qingyun MA Li YANG Jingzhe YUAN Haofu DAI Zhifang YU Youxing ZHAO College of Food Science and Technology Nanjing Agricultural UniversityNanjing 210095China Key Laboratory of Research and Development of Natural Product from Li Folk Medicine of Hainan Province Institute of Tropical Bioscience and BiotechnologyChinese Academy of Tropical Agricultural Sciences&Hainan Academy of Tropical Agricultural ResourceHaikou 571101China

A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium *** and HRESIMS spectra elucidation determined the planar structure of *** electronic circular dichroism(ECD)experiment assigned the absolute configuration of *** 1,2,4–6,and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells *** compounds(1,3–5,and 13)emerged resistance to protein tyrosine phosphatase 1B(PTP1B),further kinetic analysis and molecular docking study indicated that the most potent compound 13(IC50value of 10.74±0.61μmol/L)was found as a noncompetitive inhibitor for *** plasmon resonance(SPR)and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1(NPC1L1),which has been identified as significant therapeutic target for *** addition,compounds 3,6,and 14 showed attractive inhibitory activity against the phytopathogenic fungi:Colletotrichum ***,library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.

关键词： Cladosporium sp. marine-derived fungus neuroprotective effects protein tyrosine phosphatase 1B(PTP1B) Niemann-Pick C1 Like 1(NPC1L1) antifungal activity

Revealing the role of CCoAOMT1: fine-tuning bHLH transcription factors for optimal anther development

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Science China(Life Sciences) 2024年第3期67卷 565-578页

作者： Zesen Lai Jianzheng Wang Ying Fu Menghan Wang Hong Ma Shiqing Peng Fang Chang State Key Laboratory of Genetic Engineering Ministry of Education Key Laboratory of Biodiversity Sciences and Ecological Engineering and Institute of Biodiversity SciencesInstitute of Plant BiologySchool of Life SciencesFudan UniversityShanghai 200438China School of tropical Agriculture and Forestry Agriculture-Rural Affairs and Rural RevitalizationHainan UniversityHaikou 570228China Key Laboratory of Biology and Genetic Resources of tropical Crops Ministry of AgricultureInstitute of Tropical Bioscience and BiotechnologyChinese Academy of Tropical Agricultural SciencesHaikou 571101China Department of Biology Huck Institutes of the Life SciencesPennsylvania State UniversityUniversity ParkPA 16802USA

The tapetum,a crucial innermost layer encompassing male reproductive cells within the anther wall,plays a pivotal role in normal pollen *** transcription factors (TFs) bHLH010/089/091 redundantly facilitate the rapid nuclear accumulation of DYSFUNCTIONAL TAPETUM 1,a gatekeeper TF in the ***,the regulatory mechanisms governing the activity of bHLH010/089/091 remain *** this study,we reveal that caffeoyl coenzyme A O-methyltransferase 1 (CCoAOMT1) is a negative regulator affecting the nuclear localization and function of bHLH010 and bHLH089,probably through their K259 *** findings underscore that CCoAOMT1 promotes the nuclear export and degradation of bHLH010 and ***,elevated CCoAOMT1 expression resulted in defective pollen development,mirroring the phenotype observed in bhlh010 bhlh089 ***,our investigation revealed that the K259A mutation in the bHLH089 protein disrupted its translocation from the nucleus to the cytosol and impeded its degradation induced by ***,transgenic plants with the probHLH089::bHLH089^(K259A)construct failed to rescue proper pollen development or gene expression in bhlh010 bhlh089 ***,these findings emphasize the need to maintain balanced TF homeostasis for male *** firmly establish CCoAOMT1 as a pivotal regulator that is instrumental in achieving equilibrium between the induction of the tapetum transcriptional network and ensuring appropriate anther development.

关键词： anther development nuclear localization bHLH O-methyltransferase transcription factor homeostasis

Comparative analyses of mitogenomes in the social bees with insights into evolution of long inverted repeats in the Meliponini

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Zoological Research 2024年第1期45卷 160-175页

作者： Yu-Ran Li Zheng-Wei Wang Richard T.Corlett Wen-Bin Yu Yunnan Key Laboratory for the Conservation of tropical Rainforests and Asian Elephants&Center for Integrative Conservation Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesMenglaYunnan 666303China CAS Key Laboratory of tropical Forest Ecology Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesMenglaYunnan 666303China Southeast Asia Biodiversity Research institute Chinese Academy of SciencesMenglaYunnan 666303China University of Chinese Academy of Sciences Shijingshan DistrictBeijing 100049China

The insect mitogenome is typically a compact circular molecule with highly conserved gene ***,mitogenome structural variations have been reported in specific taxa,and gene rearrangements,usually the tRNAs,occur in different *** synapomorphies of mitogenome organizations can provide information for phylogenetic inferences,comparative analyses of mitogenomes have been given increasing ***,most studies use a very few species to represent the whole genus,tribe,family,or even order,overlooking potential variations at lower taxonomic levels,which might lead to some incorrect *** provide new insights into mitogenome organizations and their implications for phylogenetic inference,this study conducted comparative analyses for mitogenomes of three social bee tribes(Meliponini,Bombini,and Apini)based on the phylogenetic framework with denser taxonomic sampling at the species and population *** analyses revealed that mitogenomes of Apini and Bombini are the typical type,while those of Meliponini show diverse variations in mitogenome sizes and *** inverted repeats(IRs)cause significant gene rearrangements of protein coding genes(PCGs)and rRNAs in Indo-Malay/Australian stingless bee *** evolution analyses showed that the lineage with IRs have lower dN/dS ratios for PCGs than lineages without IRs,indicating potential effects of IRs on the evolution of mitochondrial *** finding of IRs and different patterns of gene rearrangements suggested that Meliponini is a hotspot in mitogenome *** conserved PCGs and rRNAs whose rearrangements were found only in the mentioned lineages within Meliponini,tRNA rearrangements are common across all three tribes of social bees,and are significant even at the species level,indicating that comprehensive sampling is needed to fully understand the patterns of tRNA rearrangements,and their implications for phylogenetic inference.

关键词： Social bees Phylogeny Mitogenome structure Gene rearrangement Inverted repeats

Two gene clusters and their positive regulator SlMYB13 that have undergone domestication-associated negative selection control phenolamide accumulation and drought tolerance in tomato

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Molecular Plant 2024年第4期17卷 579-597页

作者： Peng Cao Jun Yang Linghao Xia Zhonghui Zhang Zeyong Wu Yingchen Hao Penghui Liu Chao Wang Chun Li Jie Yang Jun Lai Xianggui Li Meng Deng Shouchuang Wang School of Breeding and Multiplication(Sanya institute of Breeding and Multiplication) Hainan UniversitySanya 572025China College of tropical Agriculture and Forestry Hainan UniversityHaikou 572208China Collaborative Innovation Center of Nanfan and High-Efficiency tropical Agriculture Hainan UniversityHaikou 572208China

Among plant metabolites,phenolamides,which are conjugates of hydroxycinnamic acid derivatives and polyamines,play important roles in plant adaptation to abiotic and biotic ***,the molecular mechanisms underlying phenolamide metabolism and regulation as well as the effects of domestication and breeding on phenolamide diversity in tomato remain largely *** this study,we performed a metabolite-based genome-wide association study and identified two biosynthetic gene clusters(BGC7 and BGC11)containing 12 genes involved in phenolamide metabolism,including four biosynthesis genes(two 4CL genes,one C3H gene,and one CPA gene),seven decoration genes(five AT genes and two UGT genes),and one transport protein gene(DTX29).Using gene co-expression network analysis we further discovered that SlMYB13 positively regulates the expression of two gene clusters,thereby promoting phenolamide *** and physiological analyses showed that BGC7,BGC11 and SlMYB13 enhance drought tolerance by enhancing scavenging of reactive oxygen species and increasing abscisic acid content in *** variation analysis suggested that BGC7,BGC11 and SlMYB13 were negatively selected during tomato domestication and improvement,leading to reduced phenolamide content and drought tolerance of cultivated ***,our study discovers a key mechanism of phenolamide biosynthesis and regulation in tomato and reveals that crop domestication and improvement shapes metabolic diversity to affect plant environmental adaptation.

关键词： tomato phenolamides gene cluster drought tolerance natural variation evolution