Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation inv...Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation involve either C6-C10 cyclization(path a) or C2-C10 cyclization(path b) after the C10carbocation formation,but neither has been experimentally validated.Here,we have identified a second mangicdiene synthase Man D,which is derived from Fusarium sp.JNU-XJ070152-01 and shares high amino acid sequence identity with Fg MS.Through heterologous expression of man D in Aspergillus oryzae NSAR1,we observed production not only of mangicdiene(1) and variecoltetraene(2),previously identified by expression of Fg MS in Escherichia coli,but also two novel sesterterpene skeletons fusadiene(3)and fusatriene(4).The identification of fusadiene and fusatriene supports the occurrence of two key carbocation intermediates in path b,thus experimentally confirming that mangicdiene is built via path b for the first time,consistent with previous density functional theory(DFT) calculation results.展开更多
Terpenoids,one of the most diverse and structurally varied natural products in nature,are widely distributed in plants,microbes,and other organisms.Their structural diversity confers significant importance in medicine...Terpenoids,one of the most diverse and structurally varied natural products in nature,are widely distributed in plants,microbes,and other organisms.Their structural diversity confers significant importance in medicine,food,flavorings,and energy.However,traditional methods of plant extraction and chemical synthesis have limitations in industrial applications.Consequently,microbial cell factories have emerged as an important platform for terpenoid production.Terpene synthases(TPSs)are crucial in determining the structural and functional diversity of terpenoids.This review discussed the origin and classificationof TPSs,outlines commonly used TPS mining methods,and summarizes advances in TPS engineering.In addition,it also explores the influenceof machine learning on enzyme mining,the existing challenges and the future opportunities alongside cutting-edge technologies.展开更多
Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourc...Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourced from clove and cannabis amongst others,and d-limonene is abundant in the Citrus genera.Apart from their use in agriculture,cosmetics,and food industries,these terpenes possess a wide range of therapeutic activities,including antimicrobial,analgesic,and anticancer activities.This review discusses the anticancer effects of these two compounds against malignant tumors including breast,lung,gastrointestinal,bone,blood,endometrial,and bladder cancer.Beta-caryophyllene induces apoptosis and prevents proliferation and metastasis through the downregulation of HSP60,HTRA,survivin,XIAP,Bcl-xL,and Bcl-2 and the upregulation of caspase 3,annexin V,p21,Bad,Bak,and Bax.The anticancer activity is also mediated by G1/M arrest,ROS induction,and JAK1/STAT activation.d-Limonene exerts its anticancer effects by upregulating autophagy-linked genes,Bax,and caspase 3 and downregulating cyclin D1 and Bcl-2.These compounds also elicit synergistic effects upon co-administration with anticancer drugs and show great prospects as useful agents in the fight against cancer.展开更多
Neurodegenerative diseases are a major public health challenge,mainly affecting the elderly population and compromising their cognitive,sensory,and motor functions.Currently,available therapies focus on alleviating sy...Neurodegenerative diseases are a major public health challenge,mainly affecting the elderly population and compromising their cognitive,sensory,and motor functions.Currently,available therapies focus on alleviating symptoms and slowing the progression of these conditions,but they do not yet offer a definitive cure.In this scenario,terpenes emerge as promising natural alternatives due to their neuroprotective properties.These compounds can reduce the formation of protein aggregates,neutralize free radicals,and inhibit pro-inflammatory enzymes,which are crucial factors in the development of neurodegenerative diseases.In addition,terpenes also play an important role in the regulation and remodeling of the extracellular matrix,a key target for improving neuronal functions.Substances such as linalool,pinene,and eugenol,among others,have potential therapeutic effects by modulating inflammatory and oxidative stress processes,the main factors that contribute to the progression of these diseases.Studies suggest that these compounds act on signaling pathways that regulate the extracellular matrix,improving neuronal integrity and,consequently,cognitive and motor function.This work aims to review the potential of terpenes in the treatment of neurodegenerative disorders,with emphasis on their ability to regulate oxidative stress and inflammation,as well as to remodel the extracellular matrix.The interaction between these mechanisms points to the promising use of terpenes as an innovative and natural therapeutic approach to combat these diseases.展开更多
One new and 16 known compounds were isolated from Abies sibirica. Their structures were assigned mainly on the basis of NMR and MS spectroscopic data. In bioassay for anti-proliferative activity against four human tum...One new and 16 known compounds were isolated from Abies sibirica. Their structures were assigned mainly on the basis of NMR and MS spectroscopic data. In bioassay for anti-proliferative activity against four human tumor cells, compound 7 exhibited selective anti-proliferative activity against COLO-205 tumor cell with an IC50 value of 0.9 μg/mL.展开更多
Since the olden times,infectious diseases have largely affected human existence.The newly emerged infections are excessively caused by viruses that are largely associated with mammal reservoirs.The casualties of these...Since the olden times,infectious diseases have largely affected human existence.The newly emerged infections are excessively caused by viruses that are largely associated with mammal reservoirs.The casualties of these emergencies are significantly influenced by the way human beings interact with the reservoirs,especially the animal ones.In our review we will consider the evolutionary and the ecological scales of such infections and their consequences on the public health,with a focus on the pathogenic influenza A virus.The nutraceutical properties of fungal and plant terpene-like molecules will be linked to their ability to lessen the symptoms of viral infections and shed light on their potential use in the development of new drugs.New challenging methods in antiviral discovery will also be discussed in this review.The authors believe that pharmacognosy is the“wave of future pharmaceuticals”,as it can be continually produced and scaled up under ecofriendly requirements.Further diagnostic methods and strategies however are required to standardise those naturally occurring resources.展开更多
Terpenoids are the main components contributing to the fragrance of Lilium‘Siberia’,and LiTPS2 plays a critical role in the biosynthesis of monoterpenoids.Although the major terpene synthases in Lilium‘Siberia’hav...Terpenoids are the main components contributing to the fragrance of Lilium‘Siberia’,and LiTPS2 plays a critical role in the biosynthesis of monoterpenoids.Although the major terpene synthases in Lilium‘Siberia’have been identified,how these TPS genes are transcriptionally regulated remains elusive in this distinguished flower.This study aimed to identify transcription factors that regulate the terpene synthesis in Lilium,and disclose the related underlying transcriptional regulation mechanism.In this study,we identified three R2R3-MYB TFs—LiMYB1,LiMYB305 and LiMYB330,which were involved in regulating the biosynthesis of terpenes in Lilium‘Siberia’.Quantitative real-time PCR showed spatial and temporal expression patterns consistent with the emission patterns of terpene compounds.When LiMYB1,LiMYB305 and LiMYB330were overexpressed in flowers,the release of some main monoterpenes,such as linalool and ocimene,as well as the expression of TPS genes,especially for LiTPS2,were enhanced.A virus-induced gene silencing(VIGS)assay showed that silencing these three LiMYBs decreased the level of monoterpenes by down-regulating the expression of the TPS genes.The yeast one-hybrid and transient expression assays indicated that all three LiMYBs could bind to and activate the promoter of LiTPS2.Moreover,the yeast two-hybrid assay verified that LiMYB1 could interact with LiMYB308 and LiMYB330,indicating their synergistic roles in the regulation of floral terpene biosynthesis.In general,these results indicated that LiMYB1,LiMYB305,and LiMYB330 might play essential roles in terpene biosynthesis in Lilium and would provide a new perspective for the transcriptional regulation of volatile terpenes in flowers.展开更多
The aim of the present study was to evaluate terpenes degradation rate in the rumen fluid from adapted and non-adapted animals.Four castrated healthy animals,two rams and two bucks,were used.Animals were daily orally ...The aim of the present study was to evaluate terpenes degradation rate in the rumen fluid from adapted and non-adapted animals.Four castrated healthy animals,two rams and two bucks,were used.Animals were daily orally dosed for 2 weeks with 1 g of each of the following terpenes,α-pinene,limonene andβ-caryophyllene.At the end of each week,rumen fluid(RF)samples were assayed in vitro for their potential to degrade terpenes over time.For each animal,a 10 mL reaction medium(RM)at a ratio 1:9(v/v)was prepared and a terpenes solution at a concentration of 100μg/ml each,was added in each RM tube.Tubes were incubated at 39℃ under anaerobic conditions and their contents sampled at 0,2,4,8,21 and 24 h.RF could degrade terpenes as it was shown by the significantly(P<0.05)higher overall degradation rates.Individual terpene degradation rates,were significantly(P<0.05)higher in week 5 for limonene and marginally(P=0.083)higher also in week 5 forα-pinene.In conclusion,the findings of the present preliminary study suggest that terpenes can be degraded in the rumen fluid.展开更多
Senescence is a natural, energy-dependent, physiological, developmental and an ecological process that is controlled by the plant’s own genetic program, allowing maximum recovery of nutrients from older organs for th...Senescence is a natural, energy-dependent, physiological, developmental and an ecological process that is controlled by the plant’s own genetic program, allowing maximum recovery of nutrients from older organs for the survival of the plant, as such;it is classified as essential component of the growth and development of plants. In some cases, under one or many environmental stresses, senescence is triggered in plants. Despite many studies in the area, less consideration has been given to plant secondary metabolites, especially the role of VTCs on plant senescence. This review seeks to capture the biosynthesis and signal transduction of VTCs, the physiology of VTCs in plant development and how that is linked to some phytohormones to induce senescence. Much progress has been made in the elucidation of metabolic pathways leading to the biosynthesis of VTCs. In addition to the classical cytosolic mevalonic acid (MVA) pathway from acetyl-CoA, the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, originating from glyceraldehyde-3-phosphate (GAP) and pyruvate, leads to the biosynthesis of isoprenoid precursors, isopentenyl diphosphate and dimethyl allyl diphosphate. VTCs synthesis and emission are believed to be tightly regulated by photosynthetic carbon supply into MEP pathway. Thus, under abiotic stresses such as drought, high salinity, high and low temperature, and low CO2 that directly affect stomatal conductance and ultimately biochemical limitation to photosynthesis, there has been observed induction of VTC synthesis and emissions, reflecting the elicitation of MEP pathway. This reveals the possibility of important function(s) of VTCs in plant defense against stress by mobilizing resources from components of plants and therefore, senescence. Our current understanding of the relationship between environmental responses and senescence mostly comes from the study of senescence response to phytohormones such as abscisic acid, jasmonic acid, ethylene and salicylic acid, which are extensively involved in response to various abiotic and biotic stresses. These stresses affect synthesis and/or signaling pathways of phytohormones to eventually trigger expression of stress-responsive genes, which in turn appears to affect leaf senescence. Comparison of plant response to stresses in relation to patterns of VTCs and phytohormones biosynthesis indicates a considerable crosstalk between these metabolic processes and their signal to plant senescence.展开更多
Objective: To investigate the anti-cancer effect of frankincense derived heavy oil obtained by Soxhlet extraction method on breast cancer cells(MDA-MB-231), and to study its chemical profile using gas chromatography m...Objective: To investigate the anti-cancer effect of frankincense derived heavy oil obtained by Soxhlet extraction method on breast cancer cells(MDA-MB-231), and to study its chemical profile using gas chromatography mass spectrometry analysis.Methods: Hexane was used to extract heavy oil from frankincense resin. Chemical profiling of heavy oil was done using Perkin Elmer Clarus GC system with mass spectrometer. MDA-MB-231 cells were treated with different dilutions(1:1 000, 1:1 500,1:1 750, 1:2 000, 1:2 250, 1:2 500, 1:2 750, 1:3 000, 1:3 250) of heavy oil for 24 h. The cells were observed by using light microscopy. Cell viability was measured by MTT assay.Results: Gas chromatography mass spectrometry chemical profiling of frankincense derived heavy oil revealed the presence of terpenes such as a-pinene(61.56%), a-amyrin(20.6%), b-amyrin(8.1%), b-phellandrene(1.47%) and camphene(1.04%). Heavy terpene cocktail induced significant MDA-MB-231 cell death at each concentration tested. Noticeably, very low concentration of Soxhlet derived heavy terpenes elicits considerable cytotoxicity on MDA-MB-231 cells compared to hydro distillated essential oil derived from frankincense resin.Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Our in vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft model in vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.展开更多
Genome mining for the search and discovery of two new globin-like enzymes,TriB from Fusarium poae and TutaA from Schizophyllum commne,are involved in the synthesis of two linear terpenes tricinonoic acid(1)and 2-buten...Genome mining for the search and discovery of two new globin-like enzymes,TriB from Fusarium poae and TutaA from Schizophyllum commne,are involved in the synthesis of two linear terpenes tricinonoic acid(1)and 2-butenedioic acid(3).Both in vivo heterologous biosynthesis and in vitro biochemical assays showed that these two enzymes catalyzed the C-C double bond cleavage of a cyclic sesquiterpene precursor(-)-germacrene D(7)and a linear diterpene backbone schizostain(2),respectively.Our work presents an unusual formation mechanism of linear terpenes from fungi and expands the functional skills of globin-like enzymes in the synthesis of terpene compounds.展开更多
This study investigates the potential of cannabidiol(CBD),one major cannabinoid of the plant Cannabis sativa,alone and in combination with a terpene-enriched extract from Humulus lupulus(“Hops 1”),on the LPS-respons...This study investigates the potential of cannabidiol(CBD),one major cannabinoid of the plant Cannabis sativa,alone and in combination with a terpene-enriched extract from Humulus lupulus(“Hops 1”),on the LPS-response of RAW 264.7 macrophages as an established in vitro model of inflammation.With the present study,we could support earlier findings of the anti-inflammatory potential of CBD,which showed a dose-dependent[0-5μM]reduction in nitric oxide and tumor necrosis factor-alpha(TNF-α)released by LPS-stimulated RAW 264.7 macrophages.Moreover,we observed an additive anti-inflammatory effect after combined CBD[5μM]and hops extract[40μg/mL]treatment.The combination of CBD and Hops 1 showed effects in LPS-stimulated RAW 264.7 cells superior to the single sub-stance treatments and akin to the control hydrocortisone.Furthermore,cellular CBD uptake increased dose-depend-ently in the presence of terpenes from Hops 1 extract.The anti-inflammatory effect of CBD and its cellular uptake positively correlated with terpene concentration,as indicated by comparison with a hemp extract containing both CBD and terpenes.These findings may contribute to the postulations for the so-called“entourage effect”between cannabinoids and terpenes and support the potential of CBD combined with phytomolecules from a non-cannabi-noid source,such as hops,for the treatment of inflammatory diseases.展开更多
In this study,two new kaurane diterpenes(16,17),together with 12 lignans(1-12),a triterpene(15),and two other compounds(13,14)were isolated from the woods of Agathis dammara.The structure of the new compound was deter...In this study,two new kaurane diterpenes(16,17),together with 12 lignans(1-12),a triterpene(15),and two other compounds(13,14)were isolated from the woods of Agathis dammara.The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy,and its absolute configuration was determined by electronic circular dichroism(ECD)exciton chirality method.Compounds 5,11,14 exhibit significant hypoglycaemic activity in zebrafish,and their mechanism of action is to enhance glucose uptake in zebrafish.展开更多
There is no doubt that the chemical composition of plants,including norvolatile and volatile compounds,is widely affected by abiotic and biotic stress.Plants are able to biosynthesize a variety of secondary metabolite...There is no doubt that the chemical composition of plants,including norvolatile and volatile compounds,is widely affected by abiotic and biotic stress.Plants are able to biosynthesize a variety of secondary metabolites against actions of natural enemies,such as herbivores,fungus,virus and bacteria.The present study revealed that the chemical compositions of leaf essential oils from Ipomoea alba underwent quantitative and qualitative alterations both when infested with the grasshopper Elaeochlora trilineata and mechanically damaged.Grasshopper attack and mechanical wounding induced the biosynthesis of nine volatile compounds in leaves of I.alba:cumene,α-ylangene,β-panasinsene,β-gurjunene aromadendrene,β-funebrene,spirolepechinene,cubenol and sclareolide.The amount of germacrene D(33.2%to 20.4%)decreased when the leaves were mechanically damaged;but when the leaves were attacked by a grasshopper,the germacrene D increased from 33.2%to 39.4%.The results showed that I.alba leaves clearly responded to abiotic and biotic stress and contribute to an understanding of plant responses to stress conditions.展开更多
In this work, we propose an original approach to the thin-layer identification of secondary metabolites (terpenes) based on the acquisition of multicomponent images integrating terpenes to be identified. Its principle...In this work, we propose an original approach to the thin-layer identification of secondary metabolites (terpenes) based on the acquisition of multicomponent images integrating terpenes to be identified. Its principle consists initially of segmentation by region of each component of the image based on the attribute tuples or colors of each region of the digital image. Then we proceeded to the calculations of region parameters such as standard deviation, entropy, average pixel color, eccentricity from an algorithm on the matlab software. These values allowed us to build a database. Finally, we built an algorithm for identifying secondary metabolites (terpenes) on the basis of these data. The relevance of our method of identifying or recognizing terpenes has been demonstrated compared to other methods, such as the one based on the calculation of frontal ratios which cannot discriminate between two terpenes having the same frontal ratio. The robustness of our method with respect to the identification of linalool, limonene was tested.展开更多
Lanxangia tsaoko is widely utilized in human cuisine as a popular flavoring agent due to its distinctive aroma.It also has a long history of use in traditional Chinese medicine.The edible and medicinal properties of L...Lanxangia tsaoko is widely utilized in human cuisine as a popular flavoring agent due to its distinctive aroma.It also has a long history of use in traditional Chinese medicine.The edible and medicinal properties of L.tsaoko are primarily attributed to its diverse array of volatile metabolites.Previous research has mainly focused on classifying the constituents and their pharmacological activities in L.tsaoko,leaving gaps in comprehensive identification and elucidation of the biosynthetic mechanisms of these metabolites.In this study,we employed a multi-omics approach and functional characterization to investigate the biosynthesis of volatile terpenoids in L.tsaoko.The results demonstrated that terpenoids constituted the highest proportion of volatile compounds in L.tsaoko.Additionally,42 terpene synthase(TPS)coding genes were identified through genome-wide analysis.Functional characterization revealed that eight LtTPSs effectively catalyzed geranyl pyrophosphate to produce monoterpenoids,while four LtTPSs converted farnesyl pyrophosphate to generate sesquiterpenoids.Genome-wide and single-gene duplication events contributed to functional diversification among LtTPSs with high identity,promoting the diversity of terpenoids.These findings provide a foundation for understanding the biosynthesis of volatile terpenoids in L.tsaoko,enhance the current knowledge of TPS,and contribute to the broader understanding of the biochemical diversity of terpenoids in plants.展开更多
Moutan Cortex terpene glycoside is derived from the dried root bark of Paeonia suffruticosa Andr.in the Paeoniaceae family,which holds significant value as a traditional Chinese medicine.This study investigated that M...Moutan Cortex terpene glycoside is derived from the dried root bark of Paeonia suffruticosa Andr.in the Paeoniaceae family,which holds significant value as a traditional Chinese medicine.This study investigated that Moutan Cortex terpene glycoside(MCTG)improved diabetic kidney disease(DKD)by targeting sirtuin 1(SIRT1)mediated autophagy pathway.Mechanistic insights were gained using DKD model rats and human umbilical vein endothelial cells(HUVECs)to delineate how MCTG operated in the treatment of DKD.Furthermore,network pharmacology was used to identify the primary metabolic pathways affected by MCTG,with key targets being confirmed through polymerase chain reaction(PCR),Western blot,Transmission electron microscope,immunofluorescence staining and monodansylcadaverine(MDC)staining.Finally,small interfering RNA transfection testified SIRT1 in advanced glycation end-products(AGEs)-induced HUVECs injury.MCTG effectively decreased blood glucose rise in DKD rats and reduced levels of cytokines and biochemical indicators.Network pharmacology revealed that metabolism was the main pathway of Moutan Cortex,and the main targets were verified by PCR and protein experiments.Based on these results,we found that Moutan Cortex could improve DKD and SIRT1 was a potential target.Furthermore,knockdown of SIRT1 attenuated AGEs-induced the expression of Beclin 1 and microtubule-associated protein 1 light chain 3 II/I(LC3 II/I)in HUVECs.In summary,this study demonstrated that Moutan Cortex could alleviate DKD via down-regulating SIRT1-mediated autophagy pathway.展开更多
Tripterygium wilfordii and T.hypoglaucum,which belong to family Celastraceae,are perennial vine shrubs with medicinal uses in treating rheumatoid arthritis,cancer,and male contraception.Among the bioactive ingredients...Tripterygium wilfordii and T.hypoglaucum,which belong to family Celastraceae,are perennial vine shrubs with medicinal uses in treating rheumatoid arthritis,cancer,and male contraception.Among the bioactive ingredients,the macrocyclic dihydroagarofuran sesquiterpene alkaloids(DASAs),also serving as chemotaxonomic markers of Celastraceae,are well-known for cytotoxicity and insecticidal properties.Despite intensive phytochemical investigations over the last half-century,the DASAs biosynthetic pathway remains unsolved.Here,we mined multi-omics data of Tripterygium species and identified 14 sesquiterpene synthase genes.Detailed characterization revealed that a group of enzymes(TwTPS5,TwTPS16,ThTPS5)catalyzed the key step committed to the biosynthesis of DASAs in Tripterygium,as evidenced by CRISPR/Cas9 knockout of TwTPS5 in T.wilfordii.Our biochemical assay showed that these enzymes converted FPP to gamma-selinene.Homologues in other Celastraceae species(EaTPS3,CaTPS5,and CaTPS6)also produced gamma-selinene,suggesting functional conservation in this DASAs-producing lineage.Notably,knocking out TwTPS5 resulted in a reduction of DASAs and enhanced accumulation of pharmaceutically valuable compounds,generating a safer and innovative medicinal plant resource for future applications.展开更多
Aldehydes,heterocyclic aromatic amines(HAAs)and terpenes were sparsely studied for their sex-hormone disrupting effect in children and adolescents,although people are widely exposed.This study aimed to investigate the...Aldehydes,heterocyclic aromatic amines(HAAs)and terpenes were sparsely studied for their sex-hormone disrupting effect in children and adolescents,although people are widely exposed.This study aimed to investigate the individual and mixture effect of aldehydes,HAAs and terpenes on sex hormones among children and adolescents and explore the effect modification of Vitamin D(VD).Six aldehydes,three HAAs and three terpenes were collected from the National Health and Nutrition Examination Survey 2013-2014,which sampled representative U.S.population.Five sex hormone indicators[testosterone(TT),estradiol(E2),sex hormone binding globulin(SHBG),free androgen index(FAI)and ratio of TT to E2(TT/E2)]were measured.Multiple linear regression and Bayesian kernel machine regression were used to explore the individual-and joint-exposure to these chemicals with each sex hormone,respectively.We primarily found some chemicals were positively associated with SHBG and negatively associated with TT,E2,and FAI among male adolescents.In addition,when stratified by pubertal status,we mainly found certain chemicals were negatively associated with TT,E2,FAI and TT/E2 in pubertal male and prepubertal female.Joint exposure to HAAs were associated with significant decrease in TT and FAI in male adolescent.These associations present age-,sex-and development-dependent patterns.VD modified these associations with significant results more pronounced in VD≥75 nmol/L group.Our study provided novel findings for the hormonal effect of aldehydes,HAAs and terpenes in children and adolescents,and is also significant for potential avenues for public health action and intervention.展开更多
Land plants co-speciate with a diversity of continually expanding plant specialized metabolites(PSMs) and root microbial communities(microbiota).Homeostatic interactions between plants and root microbiota are essentia...Land plants co-speciate with a diversity of continually expanding plant specialized metabolites(PSMs) and root microbial communities(microbiota).Homeostatic interactions between plants and root microbiota are essential for plant survival in natural environments.A growing appreciation of microbiota for plant health is fuelling rapid advances in genetic mechanisms of controlling microbiota by host plants.PSMs have long been proposed to mediate plant and single microbe interactions.However,the effects of PSMs,especially those evolutionarily new PSMs,on root microbiota at community level remain to be elucidated.Here,we discovered sesterterpenes in Arabidopsis thaliana,produced by recently duplicated prenyltransferase-terpene synthase(PT-TPS) gene clusters,with neo-functionalization.A single-residue substitution played a critical role in the acquisition of sesterterpene synthase(sesterTPS) activity in Brassicaceae plants.Moreover,we found that the absence of two root-specific sesterterpenoids,with similar chemical structure,significantly affected root microbiota assembly in similar patterns.Our results not only demonstrate the sensitivity of plant microbiota to PSMs but also establish a complete framework of host plants to control root microbiota composition through evolutionarily dynamic PSMs.展开更多
基金financially supported by grants from the National Key Research and Development Program of China (No.2024YFE0102000)the National Natural Science Foundation of China (Nos.81925037,82321004,U22A20371,U24A20782,32170060,22177037,22207039,22307045)+6 种基金the Guangdong Major Project of Basic and Applied Basic Research (No.2023B0303000026)the Guangdong Natural Science Funds for Distinguished Young Scholars (No.2022B1515020028,China)the Guangdong International Science and Technology Cooperation Base (No.2021A0505020015,China)the Guangdong Basic and Applied Basic Research Foundation (Nos.2023B1515040016,2023A1515110388)the Innovative and Research Teams Project of Guangdong Higher Education Institution (No.2021KCXTD001,China)the Guangzhou Science and Technology Project (Nos.202206010020,2024A04J6241,2023A04J0080,China)the Fundamental Research Funds for the Central Universities (Nos.21623105,21624210)。
文摘Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation involve either C6-C10 cyclization(path a) or C2-C10 cyclization(path b) after the C10carbocation formation,but neither has been experimentally validated.Here,we have identified a second mangicdiene synthase Man D,which is derived from Fusarium sp.JNU-XJ070152-01 and shares high amino acid sequence identity with Fg MS.Through heterologous expression of man D in Aspergillus oryzae NSAR1,we observed production not only of mangicdiene(1) and variecoltetraene(2),previously identified by expression of Fg MS in Escherichia coli,but also two novel sesterterpene skeletons fusadiene(3)and fusatriene(4).The identification of fusadiene and fusatriene supports the occurrence of two key carbocation intermediates in path b,thus experimentally confirming that mangicdiene is built via path b for the first time,consistent with previous density functional theory(DFT) calculation results.
基金supported by the National Key Research and Development Program of China(2020YFA0908300)the Natural Science Foundation of China(22138006,22278240).
文摘Terpenoids,one of the most diverse and structurally varied natural products in nature,are widely distributed in plants,microbes,and other organisms.Their structural diversity confers significant importance in medicine,food,flavorings,and energy.However,traditional methods of plant extraction and chemical synthesis have limitations in industrial applications.Consequently,microbial cell factories have emerged as an important platform for terpenoid production.Terpene synthases(TPSs)are crucial in determining the structural and functional diversity of terpenoids.This review discussed the origin and classificationof TPSs,outlines commonly used TPS mining methods,and summarizes advances in TPS engineering.In addition,it also explores the influenceof machine learning on enzyme mining,the existing challenges and the future opportunities alongside cutting-edge technologies.
文摘Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourced from clove and cannabis amongst others,and d-limonene is abundant in the Citrus genera.Apart from their use in agriculture,cosmetics,and food industries,these terpenes possess a wide range of therapeutic activities,including antimicrobial,analgesic,and anticancer activities.This review discusses the anticancer effects of these two compounds against malignant tumors including breast,lung,gastrointestinal,bone,blood,endometrial,and bladder cancer.Beta-caryophyllene induces apoptosis and prevents proliferation and metastasis through the downregulation of HSP60,HTRA,survivin,XIAP,Bcl-xL,and Bcl-2 and the upregulation of caspase 3,annexin V,p21,Bad,Bak,and Bax.The anticancer activity is also mediated by G1/M arrest,ROS induction,and JAK1/STAT activation.d-Limonene exerts its anticancer effects by upregulating autophagy-linked genes,Bax,and caspase 3 and downregulating cyclin D1 and Bcl-2.These compounds also elicit synergistic effects upon co-administration with anticancer drugs and show great prospects as useful agents in the fight against cancer.
基金Anderson Nogueira Mendes(#302704/2023-0)is grateful to the public Brazilian agency“Conselho Nacional de Desenvolvimento Científico e Tecnológico”(CNPq)for their personal scholarships.
文摘Neurodegenerative diseases are a major public health challenge,mainly affecting the elderly population and compromising their cognitive,sensory,and motor functions.Currently,available therapies focus on alleviating symptoms and slowing the progression of these conditions,but they do not yet offer a definitive cure.In this scenario,terpenes emerge as promising natural alternatives due to their neuroprotective properties.These compounds can reduce the formation of protein aggregates,neutralize free radicals,and inhibit pro-inflammatory enzymes,which are crucial factors in the development of neurodegenerative diseases.In addition,terpenes also play an important role in the regulation and remodeling of the extracellular matrix,a key target for improving neuronal functions.Substances such as linalool,pinene,and eugenol,among others,have potential therapeutic effects by modulating inflammatory and oxidative stress processes,the main factors that contribute to the progression of these diseases.Studies suggest that these compounds act on signaling pathways that regulate the extracellular matrix,improving neuronal integrity and,consequently,cognitive and motor function.This work aims to review the potential of terpenes in the treatment of neurodegenerative disorders,with emphasis on their ability to regulate oxidative stress and inflammation,as well as to remodel the extracellular matrix.The interaction between these mechanisms points to the promising use of terpenes as an innovative and natural therapeutic approach to combat these diseases.
基金supported by program NCET FoundationNSFC(No.30725045)+4 种基金partially supported by Global Research Network for Medicinal Plants(GRNMP)King Saud University,Shanghai Leading Academic Discipline Project(No.B906),FP7- PEOPLE-IRSES-2008(TCMCANCER Project 230232)Key Laboratory of Drug Research for Special Environments,PLA,Shanghai Engineering Research Center for the Preparation of Bioactive Natural Products(No.10DZ2251300)the Scientific Foundation of Shanghai China(No.09DZ1975700,09DZ1971500, 10DZ1971700)the Twelfth Five-Year National Science & Technology Support Program(No.2012BAI29B06)
文摘One new and 16 known compounds were isolated from Abies sibirica. Their structures were assigned mainly on the basis of NMR and MS spectroscopic data. In bioassay for anti-proliferative activity against four human tumor cells, compound 7 exhibited selective anti-proliferative activity against COLO-205 tumor cell with an IC50 value of 0.9 μg/mL.
基金the Leverhulme Trust(ECF-2018-691)the University of Warwick through an Early Career Fellowship.
文摘Since the olden times,infectious diseases have largely affected human existence.The newly emerged infections are excessively caused by viruses that are largely associated with mammal reservoirs.The casualties of these emergencies are significantly influenced by the way human beings interact with the reservoirs,especially the animal ones.In our review we will consider the evolutionary and the ecological scales of such infections and their consequences on the public health,with a focus on the pathogenic influenza A virus.The nutraceutical properties of fungal and plant terpene-like molecules will be linked to their ability to lessen the symptoms of viral infections and shed light on their potential use in the development of new drugs.New challenging methods in antiviral discovery will also be discussed in this review.The authors believe that pharmacognosy is the“wave of future pharmaceuticals”,as it can be continually produced and scaled up under ecofriendly requirements.Further diagnostic methods and strategies however are required to standardise those naturally occurring resources.
基金supported by Beijing Natural Science Foundation,China(Grant No.6202022)National Natural Science Foundation of China,China(Grant No.31971708)National Key Research and Development Program of China(Grant No.2019YFD1001002)。
文摘Terpenoids are the main components contributing to the fragrance of Lilium‘Siberia’,and LiTPS2 plays a critical role in the biosynthesis of monoterpenoids.Although the major terpene synthases in Lilium‘Siberia’have been identified,how these TPS genes are transcriptionally regulated remains elusive in this distinguished flower.This study aimed to identify transcription factors that regulate the terpene synthesis in Lilium,and disclose the related underlying transcriptional regulation mechanism.In this study,we identified three R2R3-MYB TFs—LiMYB1,LiMYB305 and LiMYB330,which were involved in regulating the biosynthesis of terpenes in Lilium‘Siberia’.Quantitative real-time PCR showed spatial and temporal expression patterns consistent with the emission patterns of terpene compounds.When LiMYB1,LiMYB305 and LiMYB330were overexpressed in flowers,the release of some main monoterpenes,such as linalool and ocimene,as well as the expression of TPS genes,especially for LiTPS2,were enhanced.A virus-induced gene silencing(VIGS)assay showed that silencing these three LiMYBs decreased the level of monoterpenes by down-regulating the expression of the TPS genes.The yeast one-hybrid and transient expression assays indicated that all three LiMYBs could bind to and activate the promoter of LiTPS2.Moreover,the yeast two-hybrid assay verified that LiMYB1 could interact with LiMYB308 and LiMYB330,indicating their synergistic roles in the regulation of floral terpene biosynthesis.In general,these results indicated that LiMYB1,LiMYB305,and LiMYB330 might play essential roles in terpene biosynthesis in Lilium and would provide a new perspective for the transcriptional regulation of volatile terpenes in flowers.
文摘The aim of the present study was to evaluate terpenes degradation rate in the rumen fluid from adapted and non-adapted animals.Four castrated healthy animals,two rams and two bucks,were used.Animals were daily orally dosed for 2 weeks with 1 g of each of the following terpenes,α-pinene,limonene andβ-caryophyllene.At the end of each week,rumen fluid(RF)samples were assayed in vitro for their potential to degrade terpenes over time.For each animal,a 10 mL reaction medium(RM)at a ratio 1:9(v/v)was prepared and a terpenes solution at a concentration of 100μg/ml each,was added in each RM tube.Tubes were incubated at 39℃ under anaerobic conditions and their contents sampled at 0,2,4,8,21 and 24 h.RF could degrade terpenes as it was shown by the significantly(P<0.05)higher overall degradation rates.Individual terpene degradation rates,were significantly(P<0.05)higher in week 5 for limonene and marginally(P=0.083)higher also in week 5 forα-pinene.In conclusion,the findings of the present preliminary study suggest that terpenes can be degraded in the rumen fluid.
文摘Senescence is a natural, energy-dependent, physiological, developmental and an ecological process that is controlled by the plant’s own genetic program, allowing maximum recovery of nutrients from older organs for the survival of the plant, as such;it is classified as essential component of the growth and development of plants. In some cases, under one or many environmental stresses, senescence is triggered in plants. Despite many studies in the area, less consideration has been given to plant secondary metabolites, especially the role of VTCs on plant senescence. This review seeks to capture the biosynthesis and signal transduction of VTCs, the physiology of VTCs in plant development and how that is linked to some phytohormones to induce senescence. Much progress has been made in the elucidation of metabolic pathways leading to the biosynthesis of VTCs. In addition to the classical cytosolic mevalonic acid (MVA) pathway from acetyl-CoA, the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, originating from glyceraldehyde-3-phosphate (GAP) and pyruvate, leads to the biosynthesis of isoprenoid precursors, isopentenyl diphosphate and dimethyl allyl diphosphate. VTCs synthesis and emission are believed to be tightly regulated by photosynthetic carbon supply into MEP pathway. Thus, under abiotic stresses such as drought, high salinity, high and low temperature, and low CO2 that directly affect stomatal conductance and ultimately biochemical limitation to photosynthesis, there has been observed induction of VTC synthesis and emissions, reflecting the elicitation of MEP pathway. This reveals the possibility of important function(s) of VTCs in plant defense against stress by mobilizing resources from components of plants and therefore, senescence. Our current understanding of the relationship between environmental responses and senescence mostly comes from the study of senescence response to phytohormones such as abscisic acid, jasmonic acid, ethylene and salicylic acid, which are extensively involved in response to various abiotic and biotic stresses. These stresses affect synthesis and/or signaling pathways of phytohormones to eventually trigger expression of stress-responsive genes, which in turn appears to affect leaf senescence. Comparison of plant response to stresses in relation to patterns of VTCs and phytohormones biosynthesis indicates a considerable crosstalk between these metabolic processes and their signal to plant senescence.
基金Supported by A’Sharqiyah University internal grant(ASUFSFR/CAS/DBS-01/2015)
文摘Objective: To investigate the anti-cancer effect of frankincense derived heavy oil obtained by Soxhlet extraction method on breast cancer cells(MDA-MB-231), and to study its chemical profile using gas chromatography mass spectrometry analysis.Methods: Hexane was used to extract heavy oil from frankincense resin. Chemical profiling of heavy oil was done using Perkin Elmer Clarus GC system with mass spectrometer. MDA-MB-231 cells were treated with different dilutions(1:1 000, 1:1 500,1:1 750, 1:2 000, 1:2 250, 1:2 500, 1:2 750, 1:3 000, 1:3 250) of heavy oil for 24 h. The cells were observed by using light microscopy. Cell viability was measured by MTT assay.Results: Gas chromatography mass spectrometry chemical profiling of frankincense derived heavy oil revealed the presence of terpenes such as a-pinene(61.56%), a-amyrin(20.6%), b-amyrin(8.1%), b-phellandrene(1.47%) and camphene(1.04%). Heavy terpene cocktail induced significant MDA-MB-231 cell death at each concentration tested. Noticeably, very low concentration of Soxhlet derived heavy terpenes elicits considerable cytotoxicity on MDA-MB-231 cells compared to hydro distillated essential oil derived from frankincense resin.Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Our in vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft model in vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.
基金supported by the National Natural Science Foundation of China(No.31870022)Chongqing Science Funds for Distinguished Young Scientists(No.cstc2020jcyjjqX0005)。
文摘Genome mining for the search and discovery of two new globin-like enzymes,TriB from Fusarium poae and TutaA from Schizophyllum commne,are involved in the synthesis of two linear terpenes tricinonoic acid(1)and 2-butenedioic acid(3).Both in vivo heterologous biosynthesis and in vitro biochemical assays showed that these two enzymes catalyzed the C-C double bond cleavage of a cyclic sesquiterpene precursor(-)-germacrene D(7)and a linear diterpene backbone schizostain(2),respectively.Our work presents an unusual formation mechanism of linear terpenes from fungi and expands the functional skills of globin-like enzymes in the synthesis of terpene compounds.
文摘This study investigates the potential of cannabidiol(CBD),one major cannabinoid of the plant Cannabis sativa,alone and in combination with a terpene-enriched extract from Humulus lupulus(“Hops 1”),on the LPS-response of RAW 264.7 macrophages as an established in vitro model of inflammation.With the present study,we could support earlier findings of the anti-inflammatory potential of CBD,which showed a dose-dependent[0-5μM]reduction in nitric oxide and tumor necrosis factor-alpha(TNF-α)released by LPS-stimulated RAW 264.7 macrophages.Moreover,we observed an additive anti-inflammatory effect after combined CBD[5μM]and hops extract[40μg/mL]treatment.The combination of CBD and Hops 1 showed effects in LPS-stimulated RAW 264.7 cells superior to the single sub-stance treatments and akin to the control hydrocortisone.Furthermore,cellular CBD uptake increased dose-depend-ently in the presence of terpenes from Hops 1 extract.The anti-inflammatory effect of CBD and its cellular uptake positively correlated with terpene concentration,as indicated by comparison with a hemp extract containing both CBD and terpenes.These findings may contribute to the postulations for the so-called“entourage effect”between cannabinoids and terpenes and support the potential of CBD combined with phytomolecules from a non-cannabi-noid source,such as hops,for the treatment of inflammatory diseases.
基金supported by Project XWZY-2023-0303 supported by Traditional Chinese Medicine Foundation of Xiamen.
文摘In this study,two new kaurane diterpenes(16,17),together with 12 lignans(1-12),a triterpene(15),and two other compounds(13,14)were isolated from the woods of Agathis dammara.The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy,and its absolute configuration was determined by electronic circular dichroism(ECD)exciton chirality method.Compounds 5,11,14 exhibit significant hypoglycaemic activity in zebrafish,and their mechanism of action is to enhance glucose uptake in zebrafish.
文摘There is no doubt that the chemical composition of plants,including norvolatile and volatile compounds,is widely affected by abiotic and biotic stress.Plants are able to biosynthesize a variety of secondary metabolites against actions of natural enemies,such as herbivores,fungus,virus and bacteria.The present study revealed that the chemical compositions of leaf essential oils from Ipomoea alba underwent quantitative and qualitative alterations both when infested with the grasshopper Elaeochlora trilineata and mechanically damaged.Grasshopper attack and mechanical wounding induced the biosynthesis of nine volatile compounds in leaves of I.alba:cumene,α-ylangene,β-panasinsene,β-gurjunene aromadendrene,β-funebrene,spirolepechinene,cubenol and sclareolide.The amount of germacrene D(33.2%to 20.4%)decreased when the leaves were mechanically damaged;but when the leaves were attacked by a grasshopper,the germacrene D increased from 33.2%to 39.4%.The results showed that I.alba leaves clearly responded to abiotic and biotic stress and contribute to an understanding of plant responses to stress conditions.
文摘In this work, we propose an original approach to the thin-layer identification of secondary metabolites (terpenes) based on the acquisition of multicomponent images integrating terpenes to be identified. Its principle consists initially of segmentation by region of each component of the image based on the attribute tuples or colors of each region of the digital image. Then we proceeded to the calculations of region parameters such as standard deviation, entropy, average pixel color, eccentricity from an algorithm on the matlab software. These values allowed us to build a database. Finally, we built an algorithm for identifying secondary metabolites (terpenes) on the basis of these data. The relevance of our method of identifying or recognizing terpenes has been demonstrated compared to other methods, such as the one based on the calculation of frontal ratios which cannot discriminate between two terpenes having the same frontal ratio. The robustness of our method with respect to the identification of linalool, limonene was tested.
基金funded by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2023E002)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ16-YQ-047).
文摘Lanxangia tsaoko is widely utilized in human cuisine as a popular flavoring agent due to its distinctive aroma.It also has a long history of use in traditional Chinese medicine.The edible and medicinal properties of L.tsaoko are primarily attributed to its diverse array of volatile metabolites.Previous research has mainly focused on classifying the constituents and their pharmacological activities in L.tsaoko,leaving gaps in comprehensive identification and elucidation of the biosynthetic mechanisms of these metabolites.In this study,we employed a multi-omics approach and functional characterization to investigate the biosynthesis of volatile terpenoids in L.tsaoko.The results demonstrated that terpenoids constituted the highest proportion of volatile compounds in L.tsaoko.Additionally,42 terpene synthase(TPS)coding genes were identified through genome-wide analysis.Functional characterization revealed that eight LtTPSs effectively catalyzed geranyl pyrophosphate to produce monoterpenoids,while four LtTPSs converted farnesyl pyrophosphate to generate sesquiterpenoids.Genome-wide and single-gene duplication events contributed to functional diversification among LtTPSs with high identity,promoting the diversity of terpenoids.These findings provide a foundation for understanding the biosynthesis of volatile terpenoids in L.tsaoko,enhance the current knowledge of TPS,and contribute to the broader understanding of the biochemical diversity of terpenoids in plants.
基金supported by grants from the National Natural Science Foundation of China(82474093,81973536)Jiangsu Province“Blue and Green Project”(184080H10240)+2 种基金Graduate Research Innovation Program of Jiangsu(KYCX23_0871)the National Natural Science Foundation of the Youth Science Fund Project(81703775)Health Research Program of Wuxi Municipal Health Commission(Q202107).
文摘Moutan Cortex terpene glycoside is derived from the dried root bark of Paeonia suffruticosa Andr.in the Paeoniaceae family,which holds significant value as a traditional Chinese medicine.This study investigated that Moutan Cortex terpene glycoside(MCTG)improved diabetic kidney disease(DKD)by targeting sirtuin 1(SIRT1)mediated autophagy pathway.Mechanistic insights were gained using DKD model rats and human umbilical vein endothelial cells(HUVECs)to delineate how MCTG operated in the treatment of DKD.Furthermore,network pharmacology was used to identify the primary metabolic pathways affected by MCTG,with key targets being confirmed through polymerase chain reaction(PCR),Western blot,Transmission electron microscope,immunofluorescence staining and monodansylcadaverine(MDC)staining.Finally,small interfering RNA transfection testified SIRT1 in advanced glycation end-products(AGEs)-induced HUVECs injury.MCTG effectively decreased blood glucose rise in DKD rats and reduced levels of cytokines and biochemical indicators.Network pharmacology revealed that metabolism was the main pathway of Moutan Cortex,and the main targets were verified by PCR and protein experiments.Based on these results,we found that Moutan Cortex could improve DKD and SIRT1 was a potential target.Furthermore,knockdown of SIRT1 attenuated AGEs-induced the expression of Beclin 1 and microtubule-associated protein 1 light chain 3 II/I(LC3 II/I)in HUVECs.In summary,this study demonstrated that Moutan Cortex could alleviate DKD via down-regulating SIRT1-mediated autophagy pathway.
基金supported by the National Key Research and Development Program of China(2020YFA0907901)the Yunnan Revitalization Talent Support Program“Top Team”Project(202305AT350001)the National Natural Science Foundation of China(32388201).
文摘Tripterygium wilfordii and T.hypoglaucum,which belong to family Celastraceae,are perennial vine shrubs with medicinal uses in treating rheumatoid arthritis,cancer,and male contraception.Among the bioactive ingredients,the macrocyclic dihydroagarofuran sesquiterpene alkaloids(DASAs),also serving as chemotaxonomic markers of Celastraceae,are well-known for cytotoxicity and insecticidal properties.Despite intensive phytochemical investigations over the last half-century,the DASAs biosynthetic pathway remains unsolved.Here,we mined multi-omics data of Tripterygium species and identified 14 sesquiterpene synthase genes.Detailed characterization revealed that a group of enzymes(TwTPS5,TwTPS16,ThTPS5)catalyzed the key step committed to the biosynthesis of DASAs in Tripterygium,as evidenced by CRISPR/Cas9 knockout of TwTPS5 in T.wilfordii.Our biochemical assay showed that these enzymes converted FPP to gamma-selinene.Homologues in other Celastraceae species(EaTPS3,CaTPS5,and CaTPS6)also produced gamma-selinene,suggesting functional conservation in this DASAs-producing lineage.Notably,knocking out TwTPS5 resulted in a reduction of DASAs and enhanced accumulation of pharmaceutically valuable compounds,generating a safer and innovative medicinal plant resource for future applications.
基金funded by Open Project of Hebei Key Laboratory of Environment and Human Health(202301,202303)Beihang University&Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan(BHME-201901)+2 种基金China Postdoctoral Science Foundation(2023M7303172023T160066)Fundamental Research Funds for the Central Universities(3332023042).
文摘Aldehydes,heterocyclic aromatic amines(HAAs)and terpenes were sparsely studied for their sex-hormone disrupting effect in children and adolescents,although people are widely exposed.This study aimed to investigate the individual and mixture effect of aldehydes,HAAs and terpenes on sex hormones among children and adolescents and explore the effect modification of Vitamin D(VD).Six aldehydes,three HAAs and three terpenes were collected from the National Health and Nutrition Examination Survey 2013-2014,which sampled representative U.S.population.Five sex hormone indicators[testosterone(TT),estradiol(E2),sex hormone binding globulin(SHBG),free androgen index(FAI)and ratio of TT to E2(TT/E2)]were measured.Multiple linear regression and Bayesian kernel machine regression were used to explore the individual-and joint-exposure to these chemicals with each sex hormone,respectively.We primarily found some chemicals were positively associated with SHBG and negatively associated with TT,E2,and FAI among male adolescents.In addition,when stratified by pubertal status,we mainly found certain chemicals were negatively associated with TT,E2,FAI and TT/E2 in pubertal male and prepubertal female.Joint exposure to HAAs were associated with significant decrease in TT and FAI in male adolescent.These associations present age-,sex-and development-dependent patterns.VD modified these associations with significant results more pronounced in VD≥75 nmol/L group.Our study provided novel findings for the hormonal effect of aldehydes,HAAs and terpenes in children and adolescents,and is also significant for potential avenues for public health action and intervention.
基金supported by the Priority Research Program of the Chinese Academy of Sciences(ZDRW-ZS-2019-2,QYZDBSSW-SMC021)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA08000000,XDB11020700)+1 种基金the National Program on Key Basic Research Projects(2013CB127000)the State Key Laboratory of Plant Genomics of China(2016A0219-11,SKLPG2013A0125-5)
文摘Land plants co-speciate with a diversity of continually expanding plant specialized metabolites(PSMs) and root microbial communities(microbiota).Homeostatic interactions between plants and root microbiota are essential for plant survival in natural environments.A growing appreciation of microbiota for plant health is fuelling rapid advances in genetic mechanisms of controlling microbiota by host plants.PSMs have long been proposed to mediate plant and single microbe interactions.However,the effects of PSMs,especially those evolutionarily new PSMs,on root microbiota at community level remain to be elucidated.Here,we discovered sesterterpenes in Arabidopsis thaliana,produced by recently duplicated prenyltransferase-terpene synthase(PT-TPS) gene clusters,with neo-functionalization.A single-residue substitution played a critical role in the acquisition of sesterterpene synthase(sesterTPS) activity in Brassicaceae plants.Moreover,we found that the absence of two root-specific sesterterpenoids,with similar chemical structure,significantly affected root microbiota assembly in similar patterns.Our results not only demonstrate the sensitivity of plant microbiota to PSMs but also establish a complete framework of host plants to control root microbiota composition through evolutionarily dynamic PSMs.