Alzheimer’s disease(AD)is a common neurodegenerative disease,and oxidative stress induced by amyloidβ-protein(Aβ)deposition is the key cause of neuronal apoptosis in AD patient.Hydroxy-α-sanshool(HAS)is the predom...Alzheimer’s disease(AD)is a common neurodegenerative disease,and oxidative stress induced by amyloidβ-protein(Aβ)deposition is the key cause of neuronal apoptosis in AD patient.Hydroxy-α-sanshool(HAS)is the predominant flavour substances in the pericarp of Zanthoxylum bungeanum Maxim.(Rutaceae family),which is a known condiment food and herbal medicine in China.We attempt to comprehensively elucidate the pathway and related mechanisms of HAS therapy on AD through in vivo and in vitro experiments.The results showed that HAS could inhibit cell apoptosis,suppress the reactive oxygen species(ROS),and increase the antioxidative enzymes in Aβ1-42 induced HT22 cells.In vivo,HAS attenuated the learning and memory impairment in senescence-accelerated mouse prone 8(SAMP8)mice,and protected neuronal cells in hippocampus.Interestingly,the 16S rRNA gene sequencing results showed HAS could restore the richness and diversity of the intestinal microbiota,reduce the abundance of Lactobacillus,and increase the abundance of Bateroides and Parabacteroides.Moreover,the contents of 10 metabolites were significantly changed after HAS treatment,which was beneficial to treat AD.In conclusion,HAS could inhibit apoptosis in nerve cells by attenuating Aβinduced oxidative stress level,while it can also influence the metabolic pathways and affect the gut microbiota composition of AD mice.展开更多
Common bean(Phaseolus vulgaris L.)is a vital source of protein and essential nutrients for human consumption and plays a key role in sustainable agriculture due to its nitrogen-fixing ability(Nadeem et al.,2021).Kidne...Common bean(Phaseolus vulgaris L.)is a vital source of protein and essential nutrients for human consumption and plays a key role in sustainable agriculture due to its nitrogen-fixing ability(Nadeem et al.,2021).Kidney beans,a subcategory of dry common beans,are highly valued for their rich protein,dietary fiber,low fat content,and various trace elements(Garcia-Cordero et al.,2021).Despite the release of several de novo genome assemblies(Goodstein et al.,2012;Schmutz et al.,2014;Vlasova et al.,2016;Cortinovis et al.,2024),existing common bean genomes remain incomplete,particularly in complex regions such as centromeres and telomeres,limiting a comprehensive understanding of the genomic landscape.展开更多
Red-fleshed fruits are valued for their vibrant color and high anthocyanin content.Pre-harvest fruit bagging enhances fruit peel pigmentation,but its effect on flesh coloration remains poorly characterized.This study ...Red-fleshed fruits are valued for their vibrant color and high anthocyanin content.Pre-harvest fruit bagging enhances fruit peel pigmentation,but its effect on flesh coloration remains poorly characterized.This study revealed that removing bags from‘Gengcunyangtao’red-fleshed peach fruits triggers the rapid and uniform accumulation of anthocyanins in the flesh,resulting in anthocyanin levels that exceed those in unbagged fruits.The exposure to light after bag removal triggered significant increases in anthocyanin levels within 24 h.This was accompanied by the rapid upregulation of light-responsive and flavonoid biosynthetic gene expression levels within 6 h.A metabolomic analysis indicated that anthocyanin precursors,especially p-coumaric acid,accumulated before bag removal,thereby increasing substrate availability for rapid anthocyanin synthesis.On the basis of a weighted gene co-expression network analysis,MYB transcription factors,anthocyanin transporters,glutathione S-transferase,and multidrug and toxic compound extrusion(MATE)were identified as key regulators that coordinate precursor storage along with light-induced transcriptional activation.Notably,PpMYB4 binds to the promoter of PpGSTF14 and activates its expression,thereby promoting anthocyanin accumulation.The study findings elucidated the temporal coordination of metabolic priming and light-responsive transcriptional regulation driving rapid anthocyanin biosynthesis,with possible implications for improving peach fruit flesh coloration.展开更多
Objectives:This paper aims to investigate the polyphenol metabolite variation and bioactivities of different-colored hawthorn berries(Crataegus pinnatifida).Materials and Methods:Comparative metabolomics analysis betw...Objectives:This paper aims to investigate the polyphenol metabolite variation and bioactivities of different-colored hawthorn berries(Crataegus pinnatifida).Materials and Methods:Comparative metabolomics analysis between peel and flesh of yellow hawthorn'Jinruyi'(JRY)and red-skinned ones was carried out by UPLC-MS/MS.Antioxidant activities andα-glucosidase inhibition capacity were also tested among different colored hawthorn samples.Results:A total of 453 polyphenols was characterized,among which phenolic acids and flavonoids were abundant,and were closely relevant to the antioxidant capacity of hawthorn fruits.Polyphenol profile showed accession-specific accumulation in peel or flesh of different colored hawthorn.The unique yellow hawthorn was found to have few anthocyanins but showed enhanced flux to synthesize flavones and flavonols,especially flavone C-glycosides and acylated flavonol glycosides.The specific acylation decoration included acetylation,p-coumaroylation,and malonylation.In addition,yellow hawthorn showed excellentα-glucosidase inhibitory effect,which might be associated with the high concentration of 8 polyphenols including 5 phenolic acids,2 flavone C-glycosides,and an acylated flavonol glycoside,namely,quercetin-7-O-(6ʹʹ-malonyl)glucoside.Such acylated flavonol showed the strongest correlation with the inhibition effect of hawthorn fruits onα-glucosidase,and was predicted to have the lowest binding energy with the enzyme according to molecular docking analysis,indicating its great potential as a strongα-glucosidase inhibitor and an important antidiabetic ingredient in yellow hawthorn.Conclusions:The acylated flavonol glycosides and C-glycosyl flavones might be chemotaxonomic markers differentiating varieties and bioactivities of yellow hawthorn from the traditional red-skinned ones.These findings complement the existing knowledge on the metabolite composition and nutritional properties of hawthorn fruits.展开更多
The predominant causal agent of poplar leaf blight is the pathogenic fungus Alternaria alternata (Fr.) Keissl., which exhibits host specificity toward Populus species. To elucidate the molecular response mechanisms of...The predominant causal agent of poplar leaf blight is the pathogenic fungus Alternaria alternata (Fr.) Keissl., which exhibits host specificity toward Populus species. To elucidate the molecular response mechanisms of A. alternata under fludioxonil fungicide stress, the fungus was cultured at the half-maximal effective concentration (EC₅₀) of fludioxonil. Transcriptomic and metabolomic profiles were analyzed using mycelia harvested under these conditions. Comparative analysis revealed 1,001 differentially expressed genes (DEGs) in the resistant strain (RS) relative to the wild-type strain (WT), comprising 628 upregulated and 373 downregulated genes. Concurrently, 524 differentially accumulated metabolites (DAMs) were identified, with 336 upregulated and 188 downregulated metabolites. KEGG pathway enrichment demonstrated pronounced upregulation in glycerophospholipid metabolism, α-linolenic acid metabolism, nucleic acid biosynthesis, and glycosylation processes. Conversely, arachidonic acid and galactose metabolism pathways were suppressed. Significant downregulation was observed in phosphatidylinositol signaling, aflatoxin biosynthesis, and cutin/suberin/wax biosynthesis pathways. Transcriptomic profiling further indicated that upregulated DEGs were predominantly associated with amino sugar/nucleotide sugar metabolism, ABC transporters, aflatoxin biosynthesis, and purine metabolism, while downregulated DEGs were enriched in N-glycan biosynthesis, endoplasmic reticulum protein processing, steroid biosynthesis, and riboflavin metabolism. Fludioxonil exerted substantial inhibitory effects on fungal growth, pathogenicity, and metabolic activity. Mechanistically, A. alternata counteracted fungicide-induced stress through modulation of its antioxidant defense system. This integrative multi-omics study delineates the dynamic gene expression and metabolic reprogramming in A. alternata under fludioxonil exposure, providing novel insights into potential molecular targets and informing the development of next-generation fungicidal strategies for phytopathogen control.展开更多
The aim of this article is to reveal the influence of aligned/random poly(L-lactic acid)(PLLA)nanofibers on PC12 cell differentiation from the perspective of metabolic level.First,three materials-PLLA aligned nanofibe...The aim of this article is to reveal the influence of aligned/random poly(L-lactic acid)(PLLA)nanofibers on PC12 cell differentiation from the perspective of metabolic level.First,three materials-PLLA aligned nanofibers(PLLA AF),PLLA random nanofibers(PLLA RF)and PLLA films(control)-were prepared by electrospinning and spin coating.Their surface morphologies were characterized.Subsequently,the cell viability,cell morphology and neurite length of PC12 cells on the surface of the three materials were evaluated,indicating more neurites in the PLLA RF groups but the longer average neurite length in the PLLA AF groups.Next,the metabolite profiles of PC12 cells cultured on the surface of the three nanofibers after 12 h,24 h and 36 h showed that,compared with the control,51,48 and 31 types of differential metabolites were detected at the three time points among the AF groups,respectively;and 56,45 and 41 types among the RF groups,respectively.Furthermore,the bioinformatics analysis of differential metabolites identified two pathways and three metabolites critical to PC12 cell differentiation influenced by the nanofibers.In addition,the verification experiment on critical metabolites and metabolic pathways were performed.The integrative analysis combining cytology,metabolomics and bioinformatics approaches revealed that though both PLLA AF and RF were capable of stimulating the synthesis of neurotransmitters,the PLLA AF were more beneficial for PC12 cell differentiation,whereas the PLLA RF were less effective.展开更多
Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While mos...Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While most cases follow a self-limiting course,approximately 20%-30%of cases progress to severe acute pancreatitis(SAP),characterized by pancreatic necrosis and multiorgan failure,with the mortality rate increasing to 36%-50%.展开更多
Modern biotechnology, based on recombinant DNA techniques, has made it possible to introduce new traits with great potential for crop improvement. However, concerns about unintended effects of gene transformation that...Modern biotechnology, based on recombinant DNA techniques, has made it possible to introduce new traits with great potential for crop improvement. However, concerns about unintended effects of gene transformation that possibly threaten environment or consumer health have persuaded scientists to set up pre-release tests on genetically modified organisms. Assessment of ＇substantial equivalence＇ concept that established by comparison of genetically modified organism with a comparator with a history of safe use could be the first step of a comprehensive risk assessment. Metabolite level is the dchest in performance of changes which stem from genetic or environmental factors. Since assessment of all metabolites in detail is very costly and practically impossible, statistical evaluation of processed data of grain spectroscopic values could be a time and cost effective substitution for complex chemical analysis. To investigate the ability of multivariate statistical techniques in comparison of metabolomes as well as testing a method for such comparisons with available tools, a transgenic rice in combination with its traditionally bred parent were used as test material, and the discriminant analysis were applied as supervised method and principal component analysis as unsupervised classification method on the processed data which were extracted from Fourier transform infrared spectroscopy and nuclear magnetic resonance spectral data of powdered rice and rice extraction and badey grain samples, of which the latter was considered as control. The results confirmed the capability of statistics, even with initial data processing applications in metabolome studies. Meanwhile, this study confirms that the supervised method results in more distinctive results.展开更多
Variation in metabolite profiles of Haematococcus pluvialis(a type of unicellular green algal)under light stress is a key issue of study at the present.To investigate the effect of light intensity on accumulation of a...Variation in metabolite profiles of Haematococcus pluvialis(a type of unicellular green algal)under light stress is a key issue of study at the present.To investigate the effect of light intensity on accumulation of astaxanthin in H.pluvialis,a 26-day batch culture experiment of H.pluvialis under the light intensity levels at 73,127,182,236,and 291μmol/(m^(2)·s)was conducted.Therefore,the optimal light intensity and the corresponding metabolic pathways of accumulation in H.pluvialis were determined.Results show that 236μmol/(m^(2)·s)was the optimum light intensity to induce astaxanthin accumulation,at which a maximum content of 9.01 mg/L was achieved on Day 24.A total of 132 metabolites were identified and quantified,of which 38 differential metabolites were highlighted and classified,including 3 fatty acids or intermediates,5 amino acids or derivatives,5 carbohydrates or intermediates,16nucleoside derivatives,and 9 other metabolites using LC-MS/MS technique.Subsequently,16 statistically significant differential metabolic pathways were enriched and annotated based on Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis between the control and the 236μmol/(m^(2)·s)treatment group(P<0.05).In addition,the bioprocesses included cellular basal metabolism and signaling systems,such as carbohydrate metabolism,amino acid metabolism,glycerol and derivatives metabolism,nucleotide and derivative metabolism,and inositol phosphate metabolism were activated and regulated under strong light stress conditions.Moreover,4 hub metabolites containing D-glucose-6-phosphate,L-tyrosine,glycerol-3-phosphate,and L-glutamine were identified,based on which the associated metabolic network was constructed.The study provided a metabolomic view of astaxanthin accumulation in H.pluvialis under strong light stress.展开更多
Rice sheath blight(RSB)is a major destructive disease impeding rice production.Identifying key germplasm resources with increased resistance remains a challenge.However,the mechanisms underlying disease resistance are...Rice sheath blight(RSB)is a major destructive disease impeding rice production.Identifying key germplasm resources with increased resistance remains a challenge.However,the mechanisms underlying disease resistance are not yet fully understood.Cytochrome P450 monooxygenases(CYP450s)serve biosynthesis and metabolic detoxification functions in plants,but there is limited information about their role in the response induced by RSB.This study demonstrated that CYT02 belongs to the CYP73A100 subfamily and is a typical member of the CYP450s.Overexpression(OE)in rice of the cytochrome P450 monooxygenase cyt02 conferred increased resistance to RSB and increased vegetative tillering.Cyt02 may increase RSB resistance by regulating plant hormone synthesis,regulate reactive oxygen species(ROS)by coordinating the activity of antioxidant enzymes,and initiate phytoalexin synthesis in response to fungal infection.These research findings have laid a foundation for a deeper understanding of the function of cyt02 and offered a potential target gene for breeding rice varieties resistant to sheath blight.展开更多
In our previous studies,we obtained scallops with black mantles by treating fertilized eggs with EMS(ethylmethane sulfonate)in the Argopecten scallop variety“Bohai”.While scallops that are potentially rich in melani...In our previous studies,we obtained scallops with black mantles by treating fertilized eggs with EMS(ethylmethane sulfonate)in the Argopecten scallop variety“Bohai”.While scallops that are potentially rich in melanin may have higher market values,the mechanisms underlying the occurrence of these black-mantled are largely unknown.We sequenced and compared the transcriptomes and metabolomes of the mantles from the black-mantled“Bohai Red”scallops and those from the scallops with normal-colored(white)mantles.Results reveal that the pigment component in the black mantle of scallops was melanin indeed.Based on the transcriptome data,1314 differentially expressed genes were obtained and subjected to the gene ontology(GO)enrichment analysis.The upregulated genes in the black mantle were mainly enriched in transition metal ion binding,hydrolytic enzyme activity,and copper ion binding.Several candidate genes associated with black mantle formation in scallops were identified.Among them,the downregulation of monoamine oxidase(MAO)and glutathione S-transferases(GST)genes and upregulation of cytochrome P 450 family 3 subfamily A(CYP 3 A)and protein kinase A(PKA)genes may have a positive effect on the formation of black mantle in scallops.The differentially expressed metabolites were mainly enriched in metabolism-related biological pathways,suggesting that the formation of black mantle in scallops may affect physiological functions related to metabolism in scallops.This study provided new evidence for understanding the mechanisms of coloration in scallop tissues,which eventually benefit the selection of new scallop strain with high melanin content.展开更多
Tartary buckwheat(Fagopyrum tataricum)is an important pseudocereal feed crop with medicinal and nutritional value.Drought is one of the main causes of reduced growth and yield in these plants.We investigated the growt...Tartary buckwheat(Fagopyrum tataricum)is an important pseudocereal feed crop with medicinal and nutritional value.Drought is one of the main causes of reduced growth and yield in these plants.We investigated the growth,physiological,and metabolic responses of the widely promoted Tartary buckwheat variety Chuan Qiao No.1 to polyethylene glycol(PEG)-mediated drought stress.Drought significantly decreased shoot length,shoot biomass and relative water content.Root length,malondialdehyde content,electrolyte leakage,activities of superoxide dismutase,peroxidase,catalase and amylase,and contents of soluble sugar,soluble protein and proline were increased by PEG-mediated drought.Untargeted metabolomics analysis identified 32 core metabolites in seedlings subjected to PEG-mediated drought,16 of which increased—including quercetin,isovitexin,cyanidin 3-O-beta-D-glucoside,L-arginine,and glycerophosphocholine,while the other 16 decreased—including 3-methoxytyramine,2,6-diaminopimelic acid,citric acid,UDP-alpha-D-glucose,adenosine,keto-D-fructose.The 32 core metabolites were enriched in 29 metabolic pathways,including lysine biosynthesis,citrate(TCA)cycle,anthocyanin biosynthesis,and aminoacyl-tRNA biosynthesis.Among them,taurine and hypotaurine metabolism,flavor and flavor biosynthesis,indole alkaline biosynthesis,and alanine,aspartate and glutamate metabolism were the four main metabolic pathways affected by drought.Our findings provide new insights into the physiological and metabolic response mechanisms of Tartary buckwheat to drought stress.展开更多
Biological nitrification inhibitors(BNIs)are released from plant roots and inhibit the nitrification activity of microorganisms in soils,reducing NO_(3)^(‒)leaching and N2O emissions,and increasing nitrogenuse efficie...Biological nitrification inhibitors(BNIs)are released from plant roots and inhibit the nitrification activity of microorganisms in soils,reducing NO_(3)^(‒)leaching and N2O emissions,and increasing nitrogenuse efficiency(NUE).Several recent studies have focused on the identification of new BNIs,yet little is known about the genetic loci that govern their biosynthesis and secretion.We applied a combined transcriptomic and metabolomic analysis to investigate possible biosynthetic pathways and transporters involved in the biosynthesis and release of BNI 1,9-decanediol(1,9-D),which was previously identified in rice root exudates.Our results linked four fatty acids,icosapentaenoic acid,linoleate,norlinolenic acid,and polyhydroxy-α,ω-divarboxylic acid,with 1,9-D biosynthesis and three transporter families,namely the ATP-binding cassette protein family,the multidrug and toxic compound extrusion family,and the major facilitator superfamily,with 1,9-D release from roots into the soil medium.Our finding provided candidates for further work on the genes implicated in the biosynthesis and secretion of 1,9-D and pinpoint genetic loci for crop breeding to improve NUE by enhancing 1,9-D secretion,with the potential to reduce NO_(3)^(‒)leaching and N2O emissions from agricultural soils.展开更多
Cancer,like other diseases accompanied by metabolic changes,shows characteristic DNA/RNA modifications and activities of modifying enzymes,resulting in fluctuations in nucleoside levels.In this study,we undertook targ...Cancer,like other diseases accompanied by metabolic changes,shows characteristic DNA/RNA modifications and activities of modifying enzymes,resulting in fluctuations in nucleoside levels.In this study,we undertook targeted metabolomic analyses of nucleotides in different cancer cell culture models using a sensitive and reproducible ion-pair HPLC method.The experimental data were analyzed by principal component analysis(PCA)to identify potential biomarkers in cancer cells,and statistical significance was determined by one-way analysis of variance.As a result,a clear differentiation of normal and tumor cells into two clusters was shown,indicating abnormal metabolism of nucleotides in tumor cells.Six variables(AMP,UDP,CTP levels with a significance of Po0.05;ATP,UTP and GMP levels with a significance of Po0.01)were considered as potential biomarkers;the content of AMP,UTP,GMP and ATP was significantly higher in cancer cells.The receiver operating characteristic(ROC)curve analysis allowed us to discriminate normal cells from tumor cells based on area under the curve(AUC).The sequence of their AUC values were:ATP(0.979)4UTP(0.938)4CTP¼GMP(0.896)4AMP(0.812)4UDP(0.792),so we conclude that ATP and UTP are the best potential biomarkers in tumor cells.This study may provide a valuable tool for studying minute alterations of intracellular nucleotide pools induced by anticancer/antiviral drugs,diseases or environmental factors.展开更多
Nucleotide pools in mammalian cells change due to the influence of antitumor drugs,which may help in evaluating the drug effect and understanding the mechanism of drug action.In this study,an ion-pair RP-HPLC method w...Nucleotide pools in mammalian cells change due to the influence of antitumor drugs,which may help in evaluating the drug effect and understanding the mechanism of drug action.In this study,an ion-pair RP-HPLC method was used for a simple,sensitive and simultaneous determination of the levels of 12 nucleotides in mammalian cells treated with antibiotic antitumor drugs(daunorubicin,epirubicin and dactinomycin D).Through the use of this targeted metabolomics approach to find potential biomarkers,UTP and ATP were verified to be the most appropriate biomarkers.Moreover,a holistic statistical approach was put forward to develop a model which could distinguish 4 categories of drugs with different mechanisms of action.This model can be further validated by evaluating drugs with different mechanismsof action.This targeted metabolomics study may provide a novel approach to predict the mechanism of action of antitumor drugs.展开更多
Ganoderma lucidum,with a long history of medicinal use and good nutritional value,is regarded as a health food.The G.lucidum fruiting body extract has been proposed as a fermentation medium to promote the growth of pr...Ganoderma lucidum,with a long history of medicinal use and good nutritional value,is regarded as a health food.The G.lucidum fruiting body extract has been proposed as a fermentation medium to promote the growth of probiotic organisms such as Lactobacilli.However,the effects of G.lucidum on the bioactivity and fermentation metabolites of Lactobacillus rhamnosus GG(LGG)require further studies.In this study,the effects of G.lucidum aqueous extract(GLE)on the growth of LGG were evaluated.During the 48-h fermentation,lactic acid content increased from 0 to 4.64 mg/ml and the pH was reduced from 5.8 to 4.0.The effect of GLE on the key metabolites of LGG was analyzed using non-targeted metabonomics based on LC-MS/MS.Metabonomics analysis identified pyrocatechuic acid,taurocholic acid,estradiol and other differential metabolites with clear physiological functions.These metabolites were significantly enriched over 10 metabolic pathways including pyrimidine metabolism,tyrosine metabolism,alanine,aspartate and glutamate metabolism.These metabolites and metabolic pathways propose that LGG has better probiotic effect when fermented with GLE.These findings provide theoretical support for the application of G.lucidum extract to improve Lactobacilli probiotic benefits.展开更多
Background:The mechanisms underlying social dysfunction caused by repeated sevoflurane in early life remain unclear.Whether the gut microbiota-metabolite-brain axis is involved in the mechanism of sevoflurane developm...Background:The mechanisms underlying social dysfunction caused by repeated sevoflurane in early life remain unclear.Whether the gut microbiota-metabolite-brain axis is involved in the mechanism of sevoflurane developmental neurotoxicity still lacks report.Methods:Mice received 3%sevoflurane at postnatal day(PND)6,7,and 8 for 2 h per day.Metagenomic sequencing and untargeted metabolomic analysis were applied to investigate the effects of sevoflurane on gut microbiota and metabolism.The animal social behavior and the synaptic development were analyzed during PND 35.Subsequently,fecal microbiota transplantation(FMT)from the control group and bile acid administration were performed to see the expected rescuing effect on socially related behaviors that were impaired by repeated sevoflurane exposure in the mice.Results:In the 3-chamber test,sevoflurane-exposed mice spent less time with stranger mice compared with the control group.The density of both the apical and basal spine decreased in mice exposed to sevoflurane.In addition,repeated sevoflurane exposure led to a notable alteration in the gut microbiota and metabolite synthesis,particularly bile acid.FMT reduced the production of intestinal bile acid and attenuated the effect of sevoflurane exposure on social function and synaptic development.Cholestyramine treatment mimics the protective effects of FMT.Conclusions:The gut microbiota-metabolite-brain axis underlies social dysfunction caused by sevoflurane exposure in early age,and bile acid regulation may be a promising intervention to this impairment.展开更多
There has been extensive research on the biological recycling of PET waste to address the issue of plastic waste pollution,with ethylene glycol(EG)being one of the main components recovered from this process.Therefore...There has been extensive research on the biological recycling of PET waste to address the issue of plastic waste pollution,with ethylene glycol(EG)being one of the main components recovered from this process.Therefore,finding ways to convert PET monomer EG into high-value products is crucial for effective PET waste recycling.In this study,we successfully engineered Escherichia coli to utilize EG and produce glycolic acid(GA),expecting to facilitate the biological recycling of PET waste.The engineered E.coli,able to utilize 10 g/L EG to produce 1.38 g/L GA within 96 h,was initially constructed.Subsequently,strategies based on overexpression of key enzymes and knock-out of the competing pathways are employed to enhance EG utilization along with GA biosynthesis.An engineered E.coli,characterized by the highest GA production titer and substrate conversion rate,was obtained.The GA titer increased to 5.1 g/L with a yield of 0.75 g/g EG,which is the highest level in the shake flake experiments.Transcriptional level analysis and metabolomic analysis were then conducted,revealing that overexpression of key enzymes and knock-out of the competing pathways improved the metabolic flow in the EG utilization.The improved metabolic flow also leads to accelerated synthesis and metabolism of amino acids.展开更多
Background Patients with disorders of consciousness(DoC)exhibit varied revival outcomes based on different etiologies and diagnoses,the mechanisms of which remain largely unknown.The fluctuating clinical presentations...Background Patients with disorders of consciousness(DoC)exhibit varied revival outcomes based on different etiologies and diagnoses,the mechanisms of which remain largely unknown.The fluctuating clinical presentations in DoC pose challenges in accurately assessing consciousness levels and prognoses,often leading to misdiagnoses.There is an urgent need for a deeper understanding of the physiological changes in DoC and the development of objective diagnostic and prognostic biomarkers to improve treatment guidance.Methods To explore biomarkers and understand the biological processes,we conducted a comprehensive untargeted metabolomic analysis on serum samples from 48 patients with DoC.Patients were categorized based on etiology(TBI vs.non-TBI),CRS-R scores,and prognosis.Advanced analytical techniques,including PCA and OPLS-DA models,were employed to identify differential metabolites.Results Our analysis revealed a distinct separation in metabolomic profiles among the different groups.The primary differential metabolites distinguishing patients with varying etiologies were predominantly phospholipids,with a notable decrease in glycerophospholipids observed in the TBI group.Patients with higher CRS-R scores exhibited a pattern of impaired carbohydrate metabolism coupled with enhanced lipid metabolism.Notably,serum concentrations of both LysoPE and PE were reduced in patients with improved outcomes,suggesting their potential as prognostic biomarkers.Conclusions Our study underscores the critical role of phospholipid metabolism in the brain’s metabolic alterations in patients with DoC.It identifies key biomarkers for diagnosis and prognosis,offering insights that could lead to novel therapeutic targets.These findings highlight the value of metabolomic profiling in understanding and potentially treating DoC.展开更多
基金supported by Natural Science Foundation of Sichuan Province(2022NSFSC0720)State Administration of Traditional Chinese Medicine of Sichuan Province of China(2020HJZX001)Project of Sichuan Provincial Health Commission(21PJ130).
文摘Alzheimer’s disease(AD)is a common neurodegenerative disease,and oxidative stress induced by amyloidβ-protein(Aβ)deposition is the key cause of neuronal apoptosis in AD patient.Hydroxy-α-sanshool(HAS)is the predominant flavour substances in the pericarp of Zanthoxylum bungeanum Maxim.(Rutaceae family),which is a known condiment food and herbal medicine in China.We attempt to comprehensively elucidate the pathway and related mechanisms of HAS therapy on AD through in vivo and in vitro experiments.The results showed that HAS could inhibit cell apoptosis,suppress the reactive oxygen species(ROS),and increase the antioxidative enzymes in Aβ1-42 induced HT22 cells.In vivo,HAS attenuated the learning and memory impairment in senescence-accelerated mouse prone 8(SAMP8)mice,and protected neuronal cells in hippocampus.Interestingly,the 16S rRNA gene sequencing results showed HAS could restore the richness and diversity of the intestinal microbiota,reduce the abundance of Lactobacillus,and increase the abundance of Bateroides and Parabacteroides.Moreover,the contents of 10 metabolites were significantly changed after HAS treatment,which was beneficial to treat AD.In conclusion,HAS could inhibit apoptosis in nerve cells by attenuating Aβinduced oxidative stress level,while it can also influence the metabolic pathways and affect the gut microbiota composition of AD mice.
基金supported by the National Natural Science Foundation of China(32241045,32241046,32241038)the Major Special Science and Technology Projects in Shanxi Province(202101140601027)+3 种基金Shanxi Provincial Agricultural Key Technologies Breakthrough Project(NYGG01)Doctoral Research Starting Project at Shanxi Agricultural University(2024BQ77)the National Key Research and Development Program of China(2023YFD1202705/2023YFD120270503,2023YFD1202703/2023YFD1202703-4)Shanxi HouJi Laboratory Self-proposed Research Project(202304010930003/202304010930003-03).
文摘Common bean(Phaseolus vulgaris L.)is a vital source of protein and essential nutrients for human consumption and plays a key role in sustainable agriculture due to its nitrogen-fixing ability(Nadeem et al.,2021).Kidney beans,a subcategory of dry common beans,are highly valued for their rich protein,dietary fiber,low fat content,and various trace elements(Garcia-Cordero et al.,2021).Despite the release of several de novo genome assemblies(Goodstein et al.,2012;Schmutz et al.,2014;Vlasova et al.,2016;Cortinovis et al.,2024),existing common bean genomes remain incomplete,particularly in complex regions such as centromeres and telomeres,limiting a comprehensive understanding of the genomic landscape.
基金supported by the Key Scientific and Technological Grant of Zhejiang for Breeding New Agricultural Varieties(Grant No.2021C12066-4)Huzhou Agricultural Science and Technology Innovation Team Project(Grant No.2022HN01).
文摘Red-fleshed fruits are valued for their vibrant color and high anthocyanin content.Pre-harvest fruit bagging enhances fruit peel pigmentation,but its effect on flesh coloration remains poorly characterized.This study revealed that removing bags from‘Gengcunyangtao’red-fleshed peach fruits triggers the rapid and uniform accumulation of anthocyanins in the flesh,resulting in anthocyanin levels that exceed those in unbagged fruits.The exposure to light after bag removal triggered significant increases in anthocyanin levels within 24 h.This was accompanied by the rapid upregulation of light-responsive and flavonoid biosynthetic gene expression levels within 6 h.A metabolomic analysis indicated that anthocyanin precursors,especially p-coumaric acid,accumulated before bag removal,thereby increasing substrate availability for rapid anthocyanin synthesis.On the basis of a weighted gene co-expression network analysis,MYB transcription factors,anthocyanin transporters,glutathione S-transferase,and multidrug and toxic compound extrusion(MATE)were identified as key regulators that coordinate precursor storage along with light-induced transcriptional activation.Notably,PpMYB4 binds to the promoter of PpGSTF14 and activates its expression,thereby promoting anthocyanin accumulation.The study findings elucidated the temporal coordination of metabolic priming and light-responsive transcriptional regulation driving rapid anthocyanin biosynthesis,with possible implications for improving peach fruit flesh coloration.
基金supported by the Key Research and Development Program of Zhejiang Province(2021C02001)the Natural Science Foundation of Shandong Province(No.ZR2023QC228)+1 种基金the Serving Local Economic Development Project of Shandong(Linyi)Institute of Modern Agriculture,Zhejiang University(No.ZDNY-2021-FWLY01004)the Fundamental Research Funds for the Central Universities(No.226-2022-00215),China.
文摘Objectives:This paper aims to investigate the polyphenol metabolite variation and bioactivities of different-colored hawthorn berries(Crataegus pinnatifida).Materials and Methods:Comparative metabolomics analysis between peel and flesh of yellow hawthorn'Jinruyi'(JRY)and red-skinned ones was carried out by UPLC-MS/MS.Antioxidant activities andα-glucosidase inhibition capacity were also tested among different colored hawthorn samples.Results:A total of 453 polyphenols was characterized,among which phenolic acids and flavonoids were abundant,and were closely relevant to the antioxidant capacity of hawthorn fruits.Polyphenol profile showed accession-specific accumulation in peel or flesh of different colored hawthorn.The unique yellow hawthorn was found to have few anthocyanins but showed enhanced flux to synthesize flavones and flavonols,especially flavone C-glycosides and acylated flavonol glycosides.The specific acylation decoration included acetylation,p-coumaroylation,and malonylation.In addition,yellow hawthorn showed excellentα-glucosidase inhibitory effect,which might be associated with the high concentration of 8 polyphenols including 5 phenolic acids,2 flavone C-glycosides,and an acylated flavonol glycoside,namely,quercetin-7-O-(6ʹʹ-malonyl)glucoside.Such acylated flavonol showed the strongest correlation with the inhibition effect of hawthorn fruits onα-glucosidase,and was predicted to have the lowest binding energy with the enzyme according to molecular docking analysis,indicating its great potential as a strongα-glucosidase inhibitor and an important antidiabetic ingredient in yellow hawthorn.Conclusions:The acylated flavonol glycosides and C-glycosyl flavones might be chemotaxonomic markers differentiating varieties and bioactivities of yellow hawthorn from the traditional red-skinned ones.These findings complement the existing knowledge on the metabolite composition and nutritional properties of hawthorn fruits.
基金supported by the Northeast Asia Biodiversity Research Center(grant number 411147021003).
文摘The predominant causal agent of poplar leaf blight is the pathogenic fungus Alternaria alternata (Fr.) Keissl., which exhibits host specificity toward Populus species. To elucidate the molecular response mechanisms of A. alternata under fludioxonil fungicide stress, the fungus was cultured at the half-maximal effective concentration (EC₅₀) of fludioxonil. Transcriptomic and metabolomic profiles were analyzed using mycelia harvested under these conditions. Comparative analysis revealed 1,001 differentially expressed genes (DEGs) in the resistant strain (RS) relative to the wild-type strain (WT), comprising 628 upregulated and 373 downregulated genes. Concurrently, 524 differentially accumulated metabolites (DAMs) were identified, with 336 upregulated and 188 downregulated metabolites. KEGG pathway enrichment demonstrated pronounced upregulation in glycerophospholipid metabolism, α-linolenic acid metabolism, nucleic acid biosynthesis, and glycosylation processes. Conversely, arachidonic acid and galactose metabolism pathways were suppressed. Significant downregulation was observed in phosphatidylinositol signaling, aflatoxin biosynthesis, and cutin/suberin/wax biosynthesis pathways. Transcriptomic profiling further indicated that upregulated DEGs were predominantly associated with amino sugar/nucleotide sugar metabolism, ABC transporters, aflatoxin biosynthesis, and purine metabolism, while downregulated DEGs were enriched in N-glycan biosynthesis, endoplasmic reticulum protein processing, steroid biosynthesis, and riboflavin metabolism. Fludioxonil exerted substantial inhibitory effects on fungal growth, pathogenicity, and metabolic activity. Mechanistically, A. alternata counteracted fungicide-induced stress through modulation of its antioxidant defense system. This integrative multi-omics study delineates the dynamic gene expression and metabolic reprogramming in A. alternata under fludioxonil exposure, providing novel insights into potential molecular targets and informing the development of next-generation fungicidal strategies for phytopathogen control.
基金This study received the support of the National Natural Science Foundation of China(31170910,31971254 and 31271012).
文摘The aim of this article is to reveal the influence of aligned/random poly(L-lactic acid)(PLLA)nanofibers on PC12 cell differentiation from the perspective of metabolic level.First,three materials-PLLA aligned nanofibers(PLLA AF),PLLA random nanofibers(PLLA RF)and PLLA films(control)-were prepared by electrospinning and spin coating.Their surface morphologies were characterized.Subsequently,the cell viability,cell morphology and neurite length of PC12 cells on the surface of the three materials were evaluated,indicating more neurites in the PLLA RF groups but the longer average neurite length in the PLLA AF groups.Next,the metabolite profiles of PC12 cells cultured on the surface of the three nanofibers after 12 h,24 h and 36 h showed that,compared with the control,51,48 and 31 types of differential metabolites were detected at the three time points among the AF groups,respectively;and 56,45 and 41 types among the RF groups,respectively.Furthermore,the bioinformatics analysis of differential metabolites identified two pathways and three metabolites critical to PC12 cell differentiation influenced by the nanofibers.In addition,the verification experiment on critical metabolites and metabolic pathways were performed.The integrative analysis combining cytology,metabolomics and bioinformatics approaches revealed that though both PLLA AF and RF were capable of stimulating the synthesis of neurotransmitters,the PLLA AF were more beneficial for PC12 cell differentiation,whereas the PLLA RF were less effective.
基金supported by National Natural Science Foundation of China(81272737).
文摘Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While most cases follow a self-limiting course,approximately 20%-30%of cases progress to severe acute pancreatitis(SAP),characterized by pancreatic necrosis and multiorgan failure,with the mortality rate increasing to 36%-50%.
文摘Modern biotechnology, based on recombinant DNA techniques, has made it possible to introduce new traits with great potential for crop improvement. However, concerns about unintended effects of gene transformation that possibly threaten environment or consumer health have persuaded scientists to set up pre-release tests on genetically modified organisms. Assessment of ＇substantial equivalence＇ concept that established by comparison of genetically modified organism with a comparator with a history of safe use could be the first step of a comprehensive risk assessment. Metabolite level is the dchest in performance of changes which stem from genetic or environmental factors. Since assessment of all metabolites in detail is very costly and practically impossible, statistical evaluation of processed data of grain spectroscopic values could be a time and cost effective substitution for complex chemical analysis. To investigate the ability of multivariate statistical techniques in comparison of metabolomes as well as testing a method for such comparisons with available tools, a transgenic rice in combination with its traditionally bred parent were used as test material, and the discriminant analysis were applied as supervised method and principal component analysis as unsupervised classification method on the processed data which were extracted from Fourier transform infrared spectroscopy and nuclear magnetic resonance spectral data of powdered rice and rice extraction and badey grain samples, of which the latter was considered as control. The results confirmed the capability of statistics, even with initial data processing applications in metabolome studies. Meanwhile, this study confirms that the supervised method results in more distinctive results.
基金Supported by the Tianjin Excellent Science and Technology Commissioners Project (No.22ZYCGSN00010)the Open Fund of Tianjin Key Laboratory of Aquatic Ecology and Aquaculture (No.TJAE201805)+1 种基金the Open Fund of Key Laboratory of Marine Ecosystem Dynamics (No.MED202013)the Tianjin Natural Science Foundation Project (No.18JCQNJC14800)。
文摘Variation in metabolite profiles of Haematococcus pluvialis(a type of unicellular green algal)under light stress is a key issue of study at the present.To investigate the effect of light intensity on accumulation of astaxanthin in H.pluvialis,a 26-day batch culture experiment of H.pluvialis under the light intensity levels at 73,127,182,236,and 291μmol/(m^(2)·s)was conducted.Therefore,the optimal light intensity and the corresponding metabolic pathways of accumulation in H.pluvialis were determined.Results show that 236μmol/(m^(2)·s)was the optimum light intensity to induce astaxanthin accumulation,at which a maximum content of 9.01 mg/L was achieved on Day 24.A total of 132 metabolites were identified and quantified,of which 38 differential metabolites were highlighted and classified,including 3 fatty acids or intermediates,5 amino acids or derivatives,5 carbohydrates or intermediates,16nucleoside derivatives,and 9 other metabolites using LC-MS/MS technique.Subsequently,16 statistically significant differential metabolic pathways were enriched and annotated based on Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis between the control and the 236μmol/(m^(2)·s)treatment group(P<0.05).In addition,the bioprocesses included cellular basal metabolism and signaling systems,such as carbohydrate metabolism,amino acid metabolism,glycerol and derivatives metabolism,nucleotide and derivative metabolism,and inositol phosphate metabolism were activated and regulated under strong light stress conditions.Moreover,4 hub metabolites containing D-glucose-6-phosphate,L-tyrosine,glycerol-3-phosphate,and L-glutamine were identified,based on which the associated metabolic network was constructed.The study provided a metabolomic view of astaxanthin accumulation in H.pluvialis under strong light stress.
基金supported by the Sichuan Province International Science and Technology Innovation Cooperation(2024YFHZ0299)the Project of Science and Technology Department of Sichuan Province(2022YFH0031)Chengdu Science and Technology Bureau(2024-YF05-02168-SN).
文摘Rice sheath blight(RSB)is a major destructive disease impeding rice production.Identifying key germplasm resources with increased resistance remains a challenge.However,the mechanisms underlying disease resistance are not yet fully understood.Cytochrome P450 monooxygenases(CYP450s)serve biosynthesis and metabolic detoxification functions in plants,but there is limited information about their role in the response induced by RSB.This study demonstrated that CYT02 belongs to the CYP73A100 subfamily and is a typical member of the CYP450s.Overexpression(OE)in rice of the cytochrome P450 monooxygenase cyt02 conferred increased resistance to RSB and increased vegetative tillering.Cyt02 may increase RSB resistance by regulating plant hormone synthesis,regulate reactive oxygen species(ROS)by coordinating the activity of antioxidant enzymes,and initiate phytoalexin synthesis in response to fungal infection.These research findings have laid a foundation for a deeper understanding of the function of cyt02 and offered a potential target gene for breeding rice varieties resistant to sheath blight.
基金Supported by the Natural Science Foundation of Shandong Province(No.ZR 2020 MC 192)the Agricultural Industrial Technology System in Shandong Province(No.SDIT-14)+2 种基金the Fund for Agriculture Seed Improvement Project of Shandong Province(No.2020 LZGC 016)the Scientific and Technological Project of Yantai,Shandong Province(No.2022 XCZX 083)the Science and Technology Innovation Capacity Improvement Project of Shandong Province(No.2021 TSGC 1229)。
文摘In our previous studies,we obtained scallops with black mantles by treating fertilized eggs with EMS(ethylmethane sulfonate)in the Argopecten scallop variety“Bohai”.While scallops that are potentially rich in melanin may have higher market values,the mechanisms underlying the occurrence of these black-mantled are largely unknown.We sequenced and compared the transcriptomes and metabolomes of the mantles from the black-mantled“Bohai Red”scallops and those from the scallops with normal-colored(white)mantles.Results reveal that the pigment component in the black mantle of scallops was melanin indeed.Based on the transcriptome data,1314 differentially expressed genes were obtained and subjected to the gene ontology(GO)enrichment analysis.The upregulated genes in the black mantle were mainly enriched in transition metal ion binding,hydrolytic enzyme activity,and copper ion binding.Several candidate genes associated with black mantle formation in scallops were identified.Among them,the downregulation of monoamine oxidase(MAO)and glutathione S-transferases(GST)genes and upregulation of cytochrome P 450 family 3 subfamily A(CYP 3 A)and protein kinase A(PKA)genes may have a positive effect on the formation of black mantle in scallops.The differentially expressed metabolites were mainly enriched in metabolism-related biological pathways,suggesting that the formation of black mantle in scallops may affect physiological functions related to metabolism in scallops.This study provided new evidence for understanding the mechanisms of coloration in scallop tissues,which eventually benefit the selection of new scallop strain with high melanin content.
基金We acknowledge the Project of National Key Research and Development Program of China(2020YFD1001403)China Agriculture Research System(CARS-07-B-1)+3 种基金Science&Technology Department of Sichuan Province(2022YFQ0041)the National Natural Science Foundation of China(31601260,32160428)Innovative Training Program for College Students(S202111079058)Special Research Fund from Key Laboratory of Coarse Cereal Processing,Ministry of Agriculture and Rural Affairs(2020CC012)to facilitate the research.
文摘Tartary buckwheat(Fagopyrum tataricum)is an important pseudocereal feed crop with medicinal and nutritional value.Drought is one of the main causes of reduced growth and yield in these plants.We investigated the growth,physiological,and metabolic responses of the widely promoted Tartary buckwheat variety Chuan Qiao No.1 to polyethylene glycol(PEG)-mediated drought stress.Drought significantly decreased shoot length,shoot biomass and relative water content.Root length,malondialdehyde content,electrolyte leakage,activities of superoxide dismutase,peroxidase,catalase and amylase,and contents of soluble sugar,soluble protein and proline were increased by PEG-mediated drought.Untargeted metabolomics analysis identified 32 core metabolites in seedlings subjected to PEG-mediated drought,16 of which increased—including quercetin,isovitexin,cyanidin 3-O-beta-D-glucoside,L-arginine,and glycerophosphocholine,while the other 16 decreased—including 3-methoxytyramine,2,6-diaminopimelic acid,citric acid,UDP-alpha-D-glucose,adenosine,keto-D-fructose.The 32 core metabolites were enriched in 29 metabolic pathways,including lysine biosynthesis,citrate(TCA)cycle,anthocyanin biosynthesis,and aminoacyl-tRNA biosynthesis.Among them,taurine and hypotaurine metabolism,flavor and flavor biosynthesis,indole alkaline biosynthesis,and alanine,aspartate and glutamate metabolism were the four main metabolic pathways affected by drought.Our findings provide new insights into the physiological and metabolic response mechanisms of Tartary buckwheat to drought stress.
基金supported by the National Natural Science Foundation of China(Grant Nos.32030099 and 32072670)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA28020301)+1 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.2023326)the Enterprise Cooperation Projects of China(Grant No.Am20210407RD).
文摘Biological nitrification inhibitors(BNIs)are released from plant roots and inhibit the nitrification activity of microorganisms in soils,reducing NO_(3)^(‒)leaching and N2O emissions,and increasing nitrogenuse efficiency(NUE).Several recent studies have focused on the identification of new BNIs,yet little is known about the genetic loci that govern their biosynthesis and secretion.We applied a combined transcriptomic and metabolomic analysis to investigate possible biosynthetic pathways and transporters involved in the biosynthesis and release of BNI 1,9-decanediol(1,9-D),which was previously identified in rice root exudates.Our results linked four fatty acids,icosapentaenoic acid,linoleate,norlinolenic acid,and polyhydroxy-α,ω-divarboxylic acid,with 1,9-D biosynthesis and three transporter families,namely the ATP-binding cassette protein family,the multidrug and toxic compound extrusion family,and the major facilitator superfamily,with 1,9-D release from roots into the soil medium.Our finding provided candidates for further work on the genes implicated in the biosynthesis and secretion of 1,9-D and pinpoint genetic loci for crop breeding to improve NUE by enhancing 1,9-D secretion,with the potential to reduce NO_(3)^(‒)leaching and N2O emissions from agricultural soils.
基金support of Natural Science Foundation of Liaoning Province(No.201102210)Program for Liaoning Innovative Research Team in University(No.LH2012018)National Undergraduate Training Programs for Innovation and Entrepreneurship(No.201210163007).
文摘Cancer,like other diseases accompanied by metabolic changes,shows characteristic DNA/RNA modifications and activities of modifying enzymes,resulting in fluctuations in nucleoside levels.In this study,we undertook targeted metabolomic analyses of nucleotides in different cancer cell culture models using a sensitive and reproducible ion-pair HPLC method.The experimental data were analyzed by principal component analysis(PCA)to identify potential biomarkers in cancer cells,and statistical significance was determined by one-way analysis of variance.As a result,a clear differentiation of normal and tumor cells into two clusters was shown,indicating abnormal metabolism of nucleotides in tumor cells.Six variables(AMP,UDP,CTP levels with a significance of Po0.05;ATP,UTP and GMP levels with a significance of Po0.01)were considered as potential biomarkers;the content of AMP,UTP,GMP and ATP was significantly higher in cancer cells.The receiver operating characteristic(ROC)curve analysis allowed us to discriminate normal cells from tumor cells based on area under the curve(AUC).The sequence of their AUC values were:ATP(0.979)4UTP(0.938)4CTP¼GMP(0.896)4AMP(0.812)4UDP(0.792),so we conclude that ATP and UTP are the best potential biomarkers in tumor cells.This study may provide a valuable tool for studying minute alterations of intracellular nucleotide pools induced by anticancer/antiviral drugs,diseases or environmental factors.
基金supported financially by the Natural Science Foundation of Liaoning Province,China (No.201102210)the Program for Liaoning Innovative Research Team in University (No.LH2012018)
文摘Nucleotide pools in mammalian cells change due to the influence of antitumor drugs,which may help in evaluating the drug effect and understanding the mechanism of drug action.In this study,an ion-pair RP-HPLC method was used for a simple,sensitive and simultaneous determination of the levels of 12 nucleotides in mammalian cells treated with antibiotic antitumor drugs(daunorubicin,epirubicin and dactinomycin D).Through the use of this targeted metabolomics approach to find potential biomarkers,UTP and ATP were verified to be the most appropriate biomarkers.Moreover,a holistic statistical approach was put forward to develop a model which could distinguish 4 categories of drugs with different mechanisms of action.This model can be further validated by evaluating drugs with different mechanismsof action.This targeted metabolomics study may provide a novel approach to predict the mechanism of action of antitumor drugs.
基金funded by Graduate Innovation Fund of Harbin Normal University,grant number HSDBSCX2021-107.
文摘Ganoderma lucidum,with a long history of medicinal use and good nutritional value,is regarded as a health food.The G.lucidum fruiting body extract has been proposed as a fermentation medium to promote the growth of probiotic organisms such as Lactobacilli.However,the effects of G.lucidum on the bioactivity and fermentation metabolites of Lactobacillus rhamnosus GG(LGG)require further studies.In this study,the effects of G.lucidum aqueous extract(GLE)on the growth of LGG were evaluated.During the 48-h fermentation,lactic acid content increased from 0 to 4.64 mg/ml and the pH was reduced from 5.8 to 4.0.The effect of GLE on the key metabolites of LGG was analyzed using non-targeted metabonomics based on LC-MS/MS.Metabonomics analysis identified pyrocatechuic acid,taurocholic acid,estradiol and other differential metabolites with clear physiological functions.These metabolites were significantly enriched over 10 metabolic pathways including pyrimidine metabolism,tyrosine metabolism,alanine,aspartate and glutamate metabolism.These metabolites and metabolic pathways propose that LGG has better probiotic effect when fermented with GLE.These findings provide theoretical support for the application of G.lucidum extract to improve Lactobacilli probiotic benefits.
基金supported by National Natural Science Foundation of China to Y.Z.(grant no.82201414)H.Z.(grant nos.82371277 and 82171170)L.L.(grant no.82101345).
文摘Background:The mechanisms underlying social dysfunction caused by repeated sevoflurane in early life remain unclear.Whether the gut microbiota-metabolite-brain axis is involved in the mechanism of sevoflurane developmental neurotoxicity still lacks report.Methods:Mice received 3%sevoflurane at postnatal day(PND)6,7,and 8 for 2 h per day.Metagenomic sequencing and untargeted metabolomic analysis were applied to investigate the effects of sevoflurane on gut microbiota and metabolism.The animal social behavior and the synaptic development were analyzed during PND 35.Subsequently,fecal microbiota transplantation(FMT)from the control group and bile acid administration were performed to see the expected rescuing effect on socially related behaviors that were impaired by repeated sevoflurane exposure in the mice.Results:In the 3-chamber test,sevoflurane-exposed mice spent less time with stranger mice compared with the control group.The density of both the apical and basal spine decreased in mice exposed to sevoflurane.In addition,repeated sevoflurane exposure led to a notable alteration in the gut microbiota and metabolite synthesis,particularly bile acid.FMT reduced the production of intestinal bile acid and attenuated the effect of sevoflurane exposure on social function and synaptic development.Cholestyramine treatment mimics the protective effects of FMT.Conclusions:The gut microbiota-metabolite-brain axis underlies social dysfunction caused by sevoflurane exposure in early age,and bile acid regulation may be a promising intervention to this impairment.
基金supported by the National Key Research and Development Program of China(2019YFA0706900)National Natural Science Foundation of China(22278310).
文摘There has been extensive research on the biological recycling of PET waste to address the issue of plastic waste pollution,with ethylene glycol(EG)being one of the main components recovered from this process.Therefore,finding ways to convert PET monomer EG into high-value products is crucial for effective PET waste recycling.In this study,we successfully engineered Escherichia coli to utilize EG and produce glycolic acid(GA),expecting to facilitate the biological recycling of PET waste.The engineered E.coli,able to utilize 10 g/L EG to produce 1.38 g/L GA within 96 h,was initially constructed.Subsequently,strategies based on overexpression of key enzymes and knock-out of the competing pathways are employed to enhance EG utilization along with GA biosynthesis.An engineered E.coli,characterized by the highest GA production titer and substrate conversion rate,was obtained.The GA titer increased to 5.1 g/L with a yield of 0.75 g/g EG,which is the highest level in the shake flake experiments.Transcriptional level analysis and metabolomic analysis were then conducted,revealing that overexpression of key enzymes and knock-out of the competing pathways improved the metabolic flow in the EG utilization.The improved metabolic flow also leads to accelerated synthesis and metabolism of amino acids.
基金supported by the National Key Research and Development Program of China(No.2021ZD0204200)National Natural Science Foundation of China(No.82170524,31901039)+2 种基金Beijing Medical Research(No.2018-7)CAMS Innovation Fund for Medical Sciences(2021-I2M-1-016)Biologic Medicine Information Center of China,National Scientific Data Sharing Platform for Population and Health.
文摘Background Patients with disorders of consciousness(DoC)exhibit varied revival outcomes based on different etiologies and diagnoses,the mechanisms of which remain largely unknown.The fluctuating clinical presentations in DoC pose challenges in accurately assessing consciousness levels and prognoses,often leading to misdiagnoses.There is an urgent need for a deeper understanding of the physiological changes in DoC and the development of objective diagnostic and prognostic biomarkers to improve treatment guidance.Methods To explore biomarkers and understand the biological processes,we conducted a comprehensive untargeted metabolomic analysis on serum samples from 48 patients with DoC.Patients were categorized based on etiology(TBI vs.non-TBI),CRS-R scores,and prognosis.Advanced analytical techniques,including PCA and OPLS-DA models,were employed to identify differential metabolites.Results Our analysis revealed a distinct separation in metabolomic profiles among the different groups.The primary differential metabolites distinguishing patients with varying etiologies were predominantly phospholipids,with a notable decrease in glycerophospholipids observed in the TBI group.Patients with higher CRS-R scores exhibited a pattern of impaired carbohydrate metabolism coupled with enhanced lipid metabolism.Notably,serum concentrations of both LysoPE and PE were reduced in patients with improved outcomes,suggesting their potential as prognostic biomarkers.Conclusions Our study underscores the critical role of phospholipid metabolism in the brain’s metabolic alterations in patients with DoC.It identifies key biomarkers for diagnosis and prognosis,offering insights that could lead to novel therapeutic targets.These findings highlight the value of metabolomic profiling in understanding and potentially treating DoC.
