Traditional Chinese medicine(TCM),especially the plant-based,represents complex chemical system containing various primary and secondary metabolites.These botanical metabolites are structurally diversified and exhibit...Traditional Chinese medicine(TCM),especially the plant-based,represents complex chemical system containing various primary and secondary metabolites.These botanical metabolites are structurally diversified and exhibit significant difference in the acidity,alkalinity,molecular weight,polarity,and content,etc,which thus poses great challenges in assessing the quality of TCM[1].展开更多
Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However...Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.展开更多
BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a no...BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a normal weight or are not obese.They are said to have lean-type MAFLD,and few studies of such patients are available.Because MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.MAFLD and analyze metabolic pathways.UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD patients.RESULTS Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P<0.05).Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy indi-viduals(P<0.01).The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals(P<0.05)and the expression of triglycerides and fasting blood glucose were increased(P<0.01).A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P<0.05 and variable importance in projection>1.The levels of PA,OA,LA,and AA were significantly increased compared with healthy individuals.CONCLUSION The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified biomarkers.PA,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.展开更多
Intrahepatic cholestasis of pregnancy(ICP)is related to cholestatic disorder in pregnancy.Total urinary sulfated bile acids(SBAs)were found increased in ICP.We distinguished the metabolic profiling of urinary SBAs in ...Intrahepatic cholestasis of pregnancy(ICP)is related to cholestatic disorder in pregnancy.Total urinary sulfated bile acids(SBAs)were found increased in ICP.We distinguished the metabolic profiling of urinary SBAs in ICP to find potential biomarkers for the diagnosis and grading of ICP.The targeted metabolomics based on high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to analyze urinary SBAs profiling in mild and severe ICP cases,as well as healthy controls.16 kinds of urinary SBAs were determined by HPLC-MS/MS.Sulfated dihydroxy glycine bile acid(di-GBA-S),glycine cholic acid 3-sulfate(GCA-3S),sulfated dihydroxy taurine bile acid(di-TBA-S)and taurine cholic acid 3-sulfate(TCA-3S)increased significantly in ICP group compared with the control group.Seven kinds of SBAs were significantly different(p<0.05)between the ICP group and the control group,with the variable importance in the projection(VIP)value more than one by the orthogonal partial least squares discriminant analysis(OPLS-DA).GCA-3S was well-suited to be used as the biomarker for the diagnosis of ICP with the sensitivity of 100%and specificity of 95.5%.A multi-variable logistic regression containing GCA-3S and di-GBA-S-1 was constructed to distinguish severe ICP from mild ICP,with the sensitivity of 94.4%and specificity of 100%.The developed HPLC-MS/MS method is suitable for the measurement of urinary SBAs profiling.Moreover,the urinary SBAs in the metabolomic profiling have the potential to be used as non-intrusive biomarkers for the diagnosis and grading of ICP.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
Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA le...Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.展开更多
Background:Integrating metabolomics in sports science provides valuable insights into the biochemistry of bodies during physical activity.However,due to their invasiveness,traditional blood sampling methods present ch...Background:Integrating metabolomics in sports science provides valuable insights into the biochemistry of bodies during physical activity.However,due to their invasiveness,traditional blood sampling methods present challenges in sports settings.The study investigated sex-specific metabolic responses,addressing a significant gap in exercise research,where female participation remains underrepresented.Methods:To address this,we explored volumetrically accurate microsampling as a dried blood spot(DBS)technique for assessing metabolomic changes in response to acute exercise in more than 130 participants.This study employed a targeted quantitative approach using isotopically labeled internal standards to measure over 100 metabolites with DBS,providing accurate and traceable results.An accuracy assessment using standard reference material and stability testing over 90 days further evaluated the suitability of DBS for sports metabolomics.Results:Our findings confirm that DBS offers a valid approach to capture metabolic changes during exercise,with 11 compounds within the confidence interval of the reference material and 59 compounds overlapping with database values.A wide panel of metabolites showed significant changes in differences of absolute concentrations upon bout exercise,with succinate and xanthine being the most significant compounds.Metabolites from the underexplored class of pyrimidines also showed significant changes.Conclusion:While metabolic regulations upon exercise are similar in both sexes,differences in the correlation with fitness-related metadata,such as peak volitional oxygen consumption and performance,indicate a higher complexity in women and a limitation of previous knowledge to men only.The quantification approach together with the simplicity of the sampling paves the way to expand this type of research toward other fields of personalized medical services.展开更多
Two cotton research institute(CRI)near-isogenic lines,CRI-12 glanded and CRI-12 glandless,were used to pinpoint potential genes and metabolic pathways linked to gossypol biosynthesis through transcriptome sequencing.W...Two cotton research institute(CRI)near-isogenic lines,CRI-12 glanded and CRI-12 glandless,were used to pinpoint potential genes and metabolic pathways linked to gossypol biosynthesis through transcriptome sequencing.We discovered more than 235 million clean reads and 1,184 differentially expressed genes(DEGs).Consecutively,we conducted a weighted gene co-expression network analysis and found a strong correlation between white and yellow modules containing GhTPS(GH_D09G0090)and GhCYP(GH_D05G2016)hub genes with the gossypol content.Importance of the GhTPS and GhCYP genes was demonstrated using RT-qPCR,virusinduced gene silencing(VIGS),and target metabolite analysis.Silencing these genes resulted in fewer glands on both leaves and stems two weeks after the infection compared to the wild type.In addition,152 metabolites were identified through targeted metabolite profiling.Differential metabolite screening revealed 12 and 18 significantly different metabolites in TRV:GhTPS and TRV:GhCYP plants vs.the control group,respectively,showing a reduction in the accumulation of metabolites compared to the control.Content of hemigossypol,the final product of gossypol biosynthesis,was also reduced,as revealed by target metabolite analysis,suggesting the role of these genes in the gossypol biosynthetic pathway.Furthermore,a highly significant difference in gossypol content between the glanded and glandless lines was recorded.Findings of this study reveal a strong link between the gossypol content and GhTPS and GhCYP hub genes,suggesting their role in the gossypol biosynthetic pathway to reduce the accumulation of hemigossypol,which may offer new comprehension into the regulatory checkpoints of the gossypol biosynthesis pathway in cotton.展开更多
Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows pro...Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows promise in relieving DPN symptoms.Neurotransmitter dysregulation is central to DPN pathophysiology.This study aimed to investigate EA’s effects on DPN via targeted neurotransmitter metabolomics.Methods:A streptozotocin-induced mouse model of DPN was developed,and EA treatment was administered for two weeks to assess the therapeutic potential of EA.Following the collection of sciatic nerve samples,LC-MS-based targeted metabolomics analyses investigations were performed to examine alterations in DPN-associated neurotransmitter metabolism brought on by EA therapy.Multivariate statistical analyses were employed to assess metabolite expression patterns,using cluster heatmaps to display neurotransmitter expression results.KEGG pathway analyses were also used to explore the functional classifications of these neurotransmitters and associated metabolic pathways.Results:Targeted neurotransmitter-focused metabolomics analyses led to the identification of 34 putative biomarkers associated with EA treatment,of which 5 showed significant changes,such as beta-alanine(increased by 80.37%,P=0.0004)and kynurenine(decreased by 29.36%,P=0.0163).KEGG pathway analysis indicated that changes in the abundance of these metabolites were associated with the cAMP signaling pathway,neuroactive ligand-receptor interactions,the synaptic vesicle cycle,and other pathways.Conclusion:The results indicate that EA can efficiently regulate neurotransmitter metabolism and restore peripheral nerve function,suggesting a feasible non-pharmacological strategy for DPN treatment and warranting clinical translation.展开更多
Apples often exhibit bitter pits in response to metabolic disorders during ripening and storage;however, the mechanisms underlying the bitter pit(BP) development remain unclear. Here, metabolome and transcriptome anal...Apples often exhibit bitter pits in response to metabolic disorders during ripening and storage;however, the mechanisms underlying the bitter pit(BP) development remain unclear. Here, metabolome and transcriptome analyses were performed to investigate BP pulp of 'Fuji'. Two auxin-response genes, MdGH3.1 and MdSAUR36, were screened. Their expression as well as the auxin content in BP pulp were found to be higher than those in healthy pulp(P < 0.01). In the field, excess CO(NH2)2increased the incidence of BP. Moreover, the auxin content and MdGH3.1 expression increased in apples after nitrogen fertilization. On Day 30 before harvest, the two genes were transiently transferred to the fruit, and 20.69% and 23.21% of BP fruits were harvested. After 10 μmol·L-1auxin was infiltrated at low pressure into postharvest fruit, the increase in MdGH3.1 expression occurred earlier than that in MdSAUR36. MdGH3.1 increased the expression of MdSAUR36, but MdSAUR36 did not increase expression of MdGH3.1. Therefore, we suggest that MdGH3.1 acts upstream of MdSAUR36 during BP formation and that these genes induce BP formation by regulating auxin and phenylpropanoid biosynthesis.展开更多
During post-harvest storage of Cucumis sativus fruit,the application of trypsin treatment could increaseflavonoid compound levels and reduce oxidative damage.To investigate the mechanism of trypsin-inducedflavonoid bio-...During post-harvest storage of Cucumis sativus fruit,the application of trypsin treatment could increaseflavonoid compound levels and reduce oxidative damage.To investigate the mechanism of trypsin-inducedflavonoid bio-synthesis in C.sativus,we conducted a combined analysis of transcriptomics and widely targeted metabolomics.One hundred and seventy-five significantly different metabolites were obtained from metabolomics data.The kyoto encyclopedia of genes and genomes(KEGG)functional enrichment results indicated that these metabolites were mainly involved in the phenylpropanoid biosynthesis pathway.By combining the results of the weighted gene co-expression network analysis(WGCNA)with the 130 upregulated phenylpropanoid metabolites,22 significantly upregulated phenylpropanoid metabolites were identified.Trilobatin was identified as the most prominent meta-bolite through cluster analysis and variable importance in projection(VIP)analysis.High performance liquid chro-matography(HPLC)experiments confirmed that trilobatin was the key metabolite induced by trypsin.The transcriptomic results showed that 1068 genes in the brown module of WGCNA were highly positively correlated withflavonoid biosynthesis.The gene set enrichment analysis(GSEA)identified leading edges in 4 key KEGG path-ways.Finally,combined with WGCNA and GSEA analysis results,35 core genes were obtained.The co-expression network of transcriptomics and metabolomics suggested that CsWRKY28 and CsMYC2 regulated the biosynthesis of trilobatin.The quantitative real-time polymerase chain reaction(RT-qPCR)and dual luciferase experiments con-firmed the activation effect of CsWRKY28 on CsMYC2 and downstream target genes.This study revealed the key transcription factors involved in the trypsin-controlled biosynthesis of trilobatin in C.sativus and provided a new theoretical basis for elucidating the molecular mechanism of trypsin preservation.展开更多
Salt stress inhibits plant growth and affects the biosynthesis of its secondary metabolites.Flavonoids are natural compounds that possess many important biological activities,playing a significant role in the medicina...Salt stress inhibits plant growth and affects the biosynthesis of its secondary metabolites.Flavonoids are natural compounds that possess many important biological activities,playing a significant role in the medicinal activity of Eucommia ulmoides(E.ulmoides).To investigate the mechanism by which salt stress affects the biosynthesis of flavonoids in E.ulmoides,a comprehensive analysis of metabolomics and transcriptomics was conducted.The results indicated that salt stress led to the wilting and darkening of E.ulmoides leaves,accompanied by a decrease in chlorophyll levels,and significantly induced malondialdehyde(MDA)and relative electrical conductivity.During salt stress,most metabolites in the flavonoid biosynthesis pathway of E.ulmoides were upregulated,indicating that flavonoid biosynthesis is likely the main induced pathway under salt stress.Among them,secondary metabolites such as 6-Hydroxyluteolin and Quercetin are likely key metabolites induced by salt stress.The correlation analysis of transcriptomics and metabolomics revealed that EuSHT is a hub gene induced by salt stress,promoting the production of flavonoids such as 6-Hydroxyluteolin.The co-expression network showed a strong positive correlation between EuSHT and the biosynthesis of 6-Hydroxyluteolin and Quercetin,while it exhibited a negative correlation with Catechin biosynthesis.The branches leading to Luteolin and Dihydroquercetin are likely the main pathways for flavonoid compound biosynthesis in the plant stress response during salt stress.The results of this study provided a preliminary mechanism of secondary metabolites such as flavonoids in the medicinal plant E.ulmoides induced by salt stress and provided new theoretical support for discussing the mechanism of plant stress response.It also provided useful information for subsequent exploration of resistance genes in E.ulmoides.展开更多
Trypsin,a novel superoxide scavenger,significantly enhances the storage quality of Hylocereus undatus(H.undatus).To elucidate the preservation mechanism of trypsin on H.undatus,a widely targeted metabolomic analysis,a...Trypsin,a novel superoxide scavenger,significantly enhances the storage quality of Hylocereus undatus(H.undatus).To elucidate the preservation mechanism of trypsin on H.undatus,a widely targeted metabolomic analysis,and transcriptomics analysis were conducted.Firstly,a total of 453 metabolites were identified,with organic acids and their derivatives constituting the largest proportion(25%).Amino acids and their metabolites,prominent among organic acids,were further analyzed.Among them,73 metabolites were associated with amino acids,and 37 exhibited significant differences.The most enriched Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway was arginine biosynthesis(map00220),with polyamine metabolites showing the most pronounced differences,particularly spermine(FC=1.7594).Compared with the control group,4-hydroxy-2-oxoglutaric acid was significantly upregulated(FC=2.117)in the process of spermine biosynthesis.Furthermore,the results of Gene Ontology(GO)and KEGG enrichment analysis of the H.undatus transcriptome profile revealed that trypsin treatment led to 187 differentially expressed genes associated with arginine.Both GO and KEGG analyses exhibited significant enrichment in the spermine biosynthetic process(GO:0006597)(map:00220)within the arginine biosynthesis pathway.Moreover,most enzymes and metabolites within the spermine biosynthesis pathway in H.undatus were upregulated.The results of the PPI network highlighted that ADC,SPDS,and SAMDC,among others,were pivotal proteins involved in trypsin-regulated arginine metabolism and spermine synthesis.This study revealed that trypsin could significantly delay postharvest senescence of H.undatus at room temperature.This effect might be attributed to trypsin triggering the synthesis of 4-hydroxy-2-oxoglutaric acid in the fruit peel,thereby promoting the biosynthesis of spermine and other polyamines.展开更多
Background:Hypertrophic cardiomyopathy(HCM)is an underdiagnosed genetic heart disease worldwide.The management and prognosis of obstructive HCM(HOCM)and non-obstructive HCM(HNCM)are quite different,but it also remains...Background:Hypertrophic cardiomyopathy(HCM)is an underdiagnosed genetic heart disease worldwide.The management and prognosis of obstructive HCM(HOCM)and non-obstructive HCM(HNCM)are quite different,but it also remains challenging to discriminate these two subtypes.HCM is characterized by dysmetabolism,and myocardial amino acid(AA)metabolism is robustly changed.The present study aimed to delineate plasma AA and derivatives profiles,and identify potential biomarkers for HCM.Methods:Plasma samples from 166 participants,including 57 cases of HOCM,52 cases of HNCM,and 57 normal controls(NCs),who first visited the International Cooperation Center for HCM,Xijing Hospital between December 2019 and September 2020,were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics.Three separate classification algorithms,including random forest,support vector machine,and logistic regression,were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM.Results:The univariate analysis showed that the serine,glycine,proline,citrulline,glutamine,cystine,creatinine,cysteine,choline,and aminoadipic acid levels in the HCM group were significantly different from those in the NC group.Four AAs and derivatives(Panel A;proline,glycine,cysteine,and choline)were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs.The receiver operating characteristic(ROC)analysis in Panel A yielded an area under the ROC curve(AUC)of 0.83(0.75-0.91)in the training set and 0.79(0.65-0.94)in the validation set.Moreover,among 10 AAs and derivatives(arginine,phenylalanine,tyrosine,proline,alanine,asparagine,creatine,tryptophan,ornithine,and choline)with statistical significance between HOCM and HNCM,3 AAs(Panel B;arginine,proline,and ornithine)were selected to differentiate the two subgroups.The AUC values in the training and validation sets for Panel B were 0.83(0.74-0.93)and 0.82(0.66-0.98),respectively.Conclusions:The plasma AA and derivatives profiles were distinct between the HCM and NC groups.Based on the differential profiles,the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.展开更多
The synchronized absorption of amino acids and glucose in the gut is essential for amino acid utilization and protein synthesis in the body.The study aimed to investigate how the starch digestion rate and amino acid l...The synchronized absorption of amino acids and glucose in the gut is essential for amino acid utilization and protein synthesis in the body.The study aimed to investigate how the starch digestion rate and amino acid levels impact the growth and intestinal starch and amino acid digestion,transport,and metabolism in juvenile broilers.The experiment was conducted with 702 Arbor Acres Plus broilers at 1 d old,which were randomly divided into 9 treatments with 6 replicates of 13 chickens each.The treatments included 3 different starch sources(corn,waxy corn,and tapioca)with 3 different apparent ileal digestible lysine(AID Lys)levels(1.08%,1.20%,and 1.32%).A notable interaction was noted for dietary starch sources and AID Lys levels in the feed-to-gain ratio(F/G)and distal ileal starch digestibility(P<0.01).The tapioca starch and waxy corn starch diets with 1.32%of AID Lys significantly decreased F/G compared with corn starch(P<0.01).There was no significant difference in F/G of broilers among waxy corn starch diet with 1.08%AID Lys level,tapioca starch diet with 1.20%AID Lys level,and corn starch diet with 1.32%AID Lys level(P>0.05).The 1.32%AID Lys level and the waxy corn starch both improved the body weight(BW)of broilers from 0 to 3 weeks of age,intestinal starch digestibility,and intestinal villi height or the ratio of villi height to crypt depth(P<0.05).Compared with the corn starch diet,waxy corn starch and tapioca starch diets significantly elevated the AID of Met,Glu,Lys,Arg,Asp,His,Ile,Tyr,Gly,and Val levels(P<0.05).The carbon metabolomics results revealed that the waxy corn starch diet significantly reduced malic acid and cis-aconitic acid levels(P<0.05)in the tricarboxylic acid cycle compared to the corn starch diet.It was concluded that a waxy corn starch diet improves the growth performance of broilers by improving intestinal morphology,increasing the absorption and transport of amino acids,reducing the amino acid oxidation for energy supply in the intestinal mucosa,and promoting protein synthesis in muscles,which not only reduces the need for dietary AID Lys but also saves on production costs.展开更多
Most research on antibiotics in the environment disregards chiral antibiotics,such as ofloxacin(OF).In this study,tadpoles of Rana nigromaculata were exposed to 1μg/L OF and levofloxacin(LVFX,an enantiomer of OF)for ...Most research on antibiotics in the environment disregards chiral antibiotics,such as ofloxacin(OF).In this study,tadpoles of Rana nigromaculata were exposed to 1μg/L OF and levofloxacin(LVFX,an enantiomer of OF)for 75 d.Compared with dextrofloxacin,LVFX treatment had a greater effect on the inhibition of bodyweight,body length,development stage,and pathological liver damage.Therefore,OF exerts a stereoselective inhibitory effect on both growth and development,which is consistent with the results at the systemic metabolism level.Transcriptomic analysis revealed that the differentially expressed genes between OF and LVFX were mainly immune related.Targeted metabolomics showed that the stereoselective biological effect of OF on R.nigromaculata was caused by differences in contents of PE-O 16:0-22:4,PE 16:0-14:0,TAG 45:0-FA16:0,PE-P 18:0-16:0,PE 16:0-16:0,PC 16:0-22:4+AcO,PE 18:1-18:3,PC 16:1-18:1+AcO,and PC 18:1-18:3+AcO.Furthermore,two enantiomers of OF were selectively bound to enzymes related to lipid metabolism.This study provides both theoretical and practical references for the accurate evaluation and scientific control of the ecological risk of chiral antibiotics.展开更多
Background The diagnosis of central precocious puberty(CPP)relies on a gonadotropin releasing hormone stimulation test to assess the activation of the hypothalamic-pituitary-gonadal axis;this is costly and painful.Bil...Background The diagnosis of central precocious puberty(CPP)relies on a gonadotropin releasing hormone stimulation test to assess the activation of the hypothalamic-pituitary-gonadal axis;this is costly and painful.Bile acids(BAs)have emerged as pivotal signaling molecules in the reproductive system.This study aimed to identify circulating BA profile signatures and explored if they may serve as biomarkers for CPP diagnosis in girls.Methods We enrolled 431 girls,including 241 in the training cohort and 190 in the validation cohort.Participants were divided into four groups based on their body mass index Z-score and whether they were diagnosed with CPP.Ultra-performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs.Results There were 18 individual BAs that were statistically different between CPP and non-CPP counterparts.The majority of these BAs(14/18)correlated significantly with sex-related hormones(P<0.05).In girls with normal weight(NW),a logistic regression model combining chenodeoxycholic acid,tauro α-muricholic acid,and 6-ketolithocholic acid achieved an area under the receiver operating characteristic curve(AUC)of 0.885.For girls who were overweight/obese(OB),hyocholic acid and taurohyocholic acid enhanced the diagnostic efficiency of basal luteinizing and follicle stimulating hormones to an AUC value 0.914.In validation cohort,75.34%NW girls and 84.09%OB girls were accurately classified.Conclusions Serum BA profiles of CPP girls showed significant changes that were associated with serum sex-related hormone levels.BA profiles could be potential biomarkers in CPP diagnosis and screening.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
Carotenoids are the main pigments responsible for the coloration and account for the major antioxidant activity of tomato(Solanum lycopersicum L.)fruit.Significant increments in total carotenoids and lycopene levels w...Carotenoids are the main pigments responsible for the coloration and account for the major antioxidant activity of tomato(Solanum lycopersicum L.)fruit.Significant increments in total carotenoids and lycopene levels were observed in tomato fruit illuminated by red light relative to white light in previous studies,but the mechanism of carotenoid biosynthesis regulated by red light is stll unclear.In the present study,the influence of red light on carotenoid biosynthesis in postharvest tomato fruit was conducted using targeted metabolomics and transcriptomic methods.A total of 25 differentially accumulated carotenoids and 1939 differentially expressed genes were isolated and identified.The results illustrated that the contents of phytoene and lycopene were considerably higher in fruit treated with red light than those with white light at 12 h.These differentially expressed genes are mainly enriched in plant hormone signal transduction,photosynthesis,secondary metabolite biosynthesis,and plant circadian rhythm.Moreover,from the results of coexpression network analysis,15 transcription factors from red light-treated fruit were screened;among these,transcription factors of SIERF4,SlbHLH93 and SllAA29,which are involved in signal transduction of light and hormones,respectively,may also play important roles in carotenoid biosynthesis regulated by red light in tomato fruit.It is concluded that red light enhanced carotenoid biosynthesis in postharvest tomato fruit and the mechanisms of enhanced carotenoid biosynthesis were not only associated with the direct regulation by red light signalling,but also with the indirect regulation by hormonal signalling.展开更多
Aerial ammonia exposure leads to tissue damage and metabolic dysfunction.However,it is unclear how different organs are coordinated to defend against aerial ammonia exposure.Twenty-four pigs were randomly divided into...Aerial ammonia exposure leads to tissue damage and metabolic dysfunction.However,it is unclear how different organs are coordinated to defend against aerial ammonia exposure.Twenty-four pigs were randomly divided into 4 groups,exposed to 0,10,25 or 35 mg/m^(3) ammonia respectively for 25 d.After above 25 mg/m^(3) ammonia exposure,decreased aspartate(P=0.016),glutamate(P=0.030)and increased ornithine(P=0.002)were found in the ammonia-removing liver,and after high ammonia(35 mg/m^(3))exposure,glutamine synthetase(GS)expression was increased(P=0.012).An increased glutamate(P=0.004)and decreased glutaminase(GLS)expression(P=0.083)were observed in the lungs after high ammonia exposure.There was also an increasing trend of glutamine in the kidneys after high ammonia exposure(P=0.066).For branched-chain amino acid(BCAA)catabolism,high ammonia exposure increased BCAA content in both the lungs and muscle(P<0.05),whereas below 25 mg/m^(3) ammonia exposure increased BCAA only in the lungs(P<0.05).The expression of BCAA transaminase(BCAT1/2)and dehydrogenase complex(BCKDHA/B and DBT)were inhibited to a varying degree in the liver,lungs and muscle after above 25 mg/m^(3) ammonia exposure,especially high ammonia exposure.The expression of BCKDH complex and glutamate-glutamine metabolism-related genes were highly expressed in the liver,followed by the lungs and muscle(P<0.01),whereas the BCAT2 expression was highest in the lungs(P=0.002).Altogether,low ammonia exposure sufficed to evoke the urea cycle to detoxify ammonia in the liver.The process of ammonia removal in the liver and potential ability of the lungs to detoxify ammonia were enhanced with increasing ammonia.Furthermore,high ammonia exposure impaired the BCAA catabolism and decreased the transcripts of the BCAA catabolism-related enzymes,resulting in high BCAA content in extrahepatic tissues.Therefore,with aerial ammonia increasing,an increased urea cycle and glutamine synthesis were ammonia defensive strategies,and high ammonia exposure impaired the BCAA catabolism.展开更多
文摘Traditional Chinese medicine(TCM),especially the plant-based,represents complex chemical system containing various primary and secondary metabolites.These botanical metabolites are structurally diversified and exhibit significant difference in the acidity,alkalinity,molecular weight,polarity,and content,etc,which thus poses great challenges in assessing the quality of TCM[1].
基金supported by the National Natural Science Foundation of China(Grant Nos.:82104827 and 82274336)the National High Level Hospital Clinical Research Funding,China(Grant No.:2022-PUMCH-A-265)the Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(Grant No.:CACM-2022-QNRC2-B14).
文摘Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.
基金Supported by Shanghai Natural Science Foundation,No.22ZR1455900Shanghai Putuo District Health System Science and Technology Innovation Project Key Project,No.ptkwws202201Shanghai Putuo District Xinglin Excellent Youth Talent Training Program,No.ptxlyq2201.
文摘BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a normal weight or are not obese.They are said to have lean-type MAFLD,and few studies of such patients are available.Because MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.MAFLD and analyze metabolic pathways.UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD patients.RESULTS Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P<0.05).Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy indi-viduals(P<0.01).The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals(P<0.05)and the expression of triglycerides and fasting blood glucose were increased(P<0.01).A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P<0.05 and variable importance in projection>1.The levels of PA,OA,LA,and AA were significantly increased compared with healthy individuals.CONCLUSION The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified biomarkers.PA,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.
基金The present work was supported by the Chongqing Postdoctoral Science Foundation(Xm201313)National Natural Science Foundation of China(81471473)Research Fund for the Doctoral Program of Higher Education of China(20115503110013).
文摘Intrahepatic cholestasis of pregnancy(ICP)is related to cholestatic disorder in pregnancy.Total urinary sulfated bile acids(SBAs)were found increased in ICP.We distinguished the metabolic profiling of urinary SBAs in ICP to find potential biomarkers for the diagnosis and grading of ICP.The targeted metabolomics based on high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to analyze urinary SBAs profiling in mild and severe ICP cases,as well as healthy controls.16 kinds of urinary SBAs were determined by HPLC-MS/MS.Sulfated dihydroxy glycine bile acid(di-GBA-S),glycine cholic acid 3-sulfate(GCA-3S),sulfated dihydroxy taurine bile acid(di-TBA-S)and taurine cholic acid 3-sulfate(TCA-3S)increased significantly in ICP group compared with the control group.Seven kinds of SBAs were significantly different(p<0.05)between the ICP group and the control group,with the variable importance in the projection(VIP)value more than one by the orthogonal partial least squares discriminant analysis(OPLS-DA).GCA-3S was well-suited to be used as the biomarker for the diagnosis of ICP with the sensitivity of 100%and specificity of 95.5%.A multi-variable logistic regression containing GCA-3S and di-GBA-S-1 was constructed to distinguish severe ICP from mild ICP,with the sensitivity of 94.4%and specificity of 100%.The developed HPLC-MS/MS method is suitable for the measurement of urinary SBAs profiling.Moreover,the urinary SBAs in the metabolomic profiling have the potential to be used as non-intrusive biomarkers for the diagnosis and grading of ICP.
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supported by the National Key R&D Program of China(2021YFD1300404)。
文摘Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.
基金This work is supported by the University of Vienna,the Faculty of Chemistry and Centre for Sport Science and University Sports.The Vienna Business Agency,Austria funded FR.
文摘Background:Integrating metabolomics in sports science provides valuable insights into the biochemistry of bodies during physical activity.However,due to their invasiveness,traditional blood sampling methods present challenges in sports settings.The study investigated sex-specific metabolic responses,addressing a significant gap in exercise research,where female participation remains underrepresented.Methods:To address this,we explored volumetrically accurate microsampling as a dried blood spot(DBS)technique for assessing metabolomic changes in response to acute exercise in more than 130 participants.This study employed a targeted quantitative approach using isotopically labeled internal standards to measure over 100 metabolites with DBS,providing accurate and traceable results.An accuracy assessment using standard reference material and stability testing over 90 days further evaluated the suitability of DBS for sports metabolomics.Results:Our findings confirm that DBS offers a valid approach to capture metabolic changes during exercise,with 11 compounds within the confidence interval of the reference material and 59 compounds overlapping with database values.A wide panel of metabolites showed significant changes in differences of absolute concentrations upon bout exercise,with succinate and xanthine being the most significant compounds.Metabolites from the underexplored class of pyrimidines also showed significant changes.Conclusion:While metabolic regulations upon exercise are similar in both sexes,differences in the correlation with fitness-related metadata,such as peak volitional oxygen consumption and performance,indicate a higher complexity in women and a limitation of previous knowledge to men only.The quantification approach together with the simplicity of the sampling paves the way to expand this type of research toward other fields of personalized medical services.
基金financial help from the National Key R&D Program of China(2021YFE0101200)the Key Research and Development Project of Jiangsu Province,China(Modern Agriculture,BE2022364)+1 种基金the State Key Laboratory of Cotton Bio-breeding and Integrated Utilization Open Fund,China(CB2024A06)support of the Ministry of Science,Technological Development and Innovation of the Republic of Serbia(451-03-66/2024-03/200007)。
文摘Two cotton research institute(CRI)near-isogenic lines,CRI-12 glanded and CRI-12 glandless,were used to pinpoint potential genes and metabolic pathways linked to gossypol biosynthesis through transcriptome sequencing.We discovered more than 235 million clean reads and 1,184 differentially expressed genes(DEGs).Consecutively,we conducted a weighted gene co-expression network analysis and found a strong correlation between white and yellow modules containing GhTPS(GH_D09G0090)and GhCYP(GH_D05G2016)hub genes with the gossypol content.Importance of the GhTPS and GhCYP genes was demonstrated using RT-qPCR,virusinduced gene silencing(VIGS),and target metabolite analysis.Silencing these genes resulted in fewer glands on both leaves and stems two weeks after the infection compared to the wild type.In addition,152 metabolites were identified through targeted metabolite profiling.Differential metabolite screening revealed 12 and 18 significantly different metabolites in TRV:GhTPS and TRV:GhCYP plants vs.the control group,respectively,showing a reduction in the accumulation of metabolites compared to the control.Content of hemigossypol,the final product of gossypol biosynthesis,was also reduced,as revealed by target metabolite analysis,suggesting the role of these genes in the gossypol biosynthetic pathway.Furthermore,a highly significant difference in gossypol content between the glanded and glandless lines was recorded.Findings of this study reveal a strong link between the gossypol content and GhTPS and GhCYP hub genes,suggesting their role in the gossypol biosynthetic pathway to reduce the accumulation of hemigossypol,which may offer new comprehension into the regulatory checkpoints of the gossypol biosynthesis pathway in cotton.
基金supported by Pudong New Area Science and Technology Development Fund Special Research Project on the Livelihood of Institutions(No.PKJ2023-Y03)Pudong New Area Chinese Medicine Senior Teacher Training Program(No.PDZY-2023-0801)Talents Training Program of the Seventh People’s Hospital,Shanghai University of Traditional Chinese Medicine(No.JY2024-08).
文摘Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows promise in relieving DPN symptoms.Neurotransmitter dysregulation is central to DPN pathophysiology.This study aimed to investigate EA’s effects on DPN via targeted neurotransmitter metabolomics.Methods:A streptozotocin-induced mouse model of DPN was developed,and EA treatment was administered for two weeks to assess the therapeutic potential of EA.Following the collection of sciatic nerve samples,LC-MS-based targeted metabolomics analyses investigations were performed to examine alterations in DPN-associated neurotransmitter metabolism brought on by EA therapy.Multivariate statistical analyses were employed to assess metabolite expression patterns,using cluster heatmaps to display neurotransmitter expression results.KEGG pathway analyses were also used to explore the functional classifications of these neurotransmitters and associated metabolic pathways.Results:Targeted neurotransmitter-focused metabolomics analyses led to the identification of 34 putative biomarkers associated with EA treatment,of which 5 showed significant changes,such as beta-alanine(increased by 80.37%,P=0.0004)and kynurenine(decreased by 29.36%,P=0.0163).KEGG pathway analysis indicated that changes in the abundance of these metabolites were associated with the cAMP signaling pathway,neuroactive ligand-receptor interactions,the synaptic vesicle cycle,and other pathways.Conclusion:The results indicate that EA can efficiently regulate neurotransmitter metabolism and restore peripheral nerve function,suggesting a feasible non-pharmacological strategy for DPN treatment and warranting clinical translation.
基金the Agricultural Variety Improvement Project of Shandong Province(Grant No.2019LZGC007)Taishan Scholar Foundation of Shandong Province(Grant No.tstp20221134)China Agriculture Research System Foundation(Grant No.CARS-27).
文摘Apples often exhibit bitter pits in response to metabolic disorders during ripening and storage;however, the mechanisms underlying the bitter pit(BP) development remain unclear. Here, metabolome and transcriptome analyses were performed to investigate BP pulp of 'Fuji'. Two auxin-response genes, MdGH3.1 and MdSAUR36, were screened. Their expression as well as the auxin content in BP pulp were found to be higher than those in healthy pulp(P < 0.01). In the field, excess CO(NH2)2increased the incidence of BP. Moreover, the auxin content and MdGH3.1 expression increased in apples after nitrogen fertilization. On Day 30 before harvest, the two genes were transiently transferred to the fruit, and 20.69% and 23.21% of BP fruits were harvested. After 10 μmol·L-1auxin was infiltrated at low pressure into postharvest fruit, the increase in MdGH3.1 expression occurred earlier than that in MdSAUR36. MdGH3.1 increased the expression of MdSAUR36, but MdSAUR36 did not increase expression of MdGH3.1. Therefore, we suggest that MdGH3.1 acts upstream of MdSAUR36 during BP formation and that these genes induce BP formation by regulating auxin and phenylpropanoid biosynthesis.
基金This work was supported by the National Key Research and Development Program of China(2017YFC1600802)the National and Local Joint Engineering Laboratory of High Efficiency and Superior-Quality Cultivation and Fruit Deep Processing Technology of Characteristic Fruit Trees in South Xinjiang of China(No.FE202303).
文摘During post-harvest storage of Cucumis sativus fruit,the application of trypsin treatment could increaseflavonoid compound levels and reduce oxidative damage.To investigate the mechanism of trypsin-inducedflavonoid bio-synthesis in C.sativus,we conducted a combined analysis of transcriptomics and widely targeted metabolomics.One hundred and seventy-five significantly different metabolites were obtained from metabolomics data.The kyoto encyclopedia of genes and genomes(KEGG)functional enrichment results indicated that these metabolites were mainly involved in the phenylpropanoid biosynthesis pathway.By combining the results of the weighted gene co-expression network analysis(WGCNA)with the 130 upregulated phenylpropanoid metabolites,22 significantly upregulated phenylpropanoid metabolites were identified.Trilobatin was identified as the most prominent meta-bolite through cluster analysis and variable importance in projection(VIP)analysis.High performance liquid chro-matography(HPLC)experiments confirmed that trilobatin was the key metabolite induced by trypsin.The transcriptomic results showed that 1068 genes in the brown module of WGCNA were highly positively correlated withflavonoid biosynthesis.The gene set enrichment analysis(GSEA)identified leading edges in 4 key KEGG path-ways.Finally,combined with WGCNA and GSEA analysis results,35 core genes were obtained.The co-expression network of transcriptomics and metabolomics suggested that CsWRKY28 and CsMYC2 regulated the biosynthesis of trilobatin.The quantitative real-time polymerase chain reaction(RT-qPCR)and dual luciferase experiments con-firmed the activation effect of CsWRKY28 on CsMYC2 and downstream target genes.This study revealed the key transcription factors involved in the trypsin-controlled biosynthesis of trilobatin in C.sativus and provided a new theoretical basis for elucidating the molecular mechanism of trypsin preservation.
基金supported by the National Key Research and Development Program of China(2017YFC1600802)Henan Provincial Science and Technology Research Project,China(No.232102110134).
文摘Salt stress inhibits plant growth and affects the biosynthesis of its secondary metabolites.Flavonoids are natural compounds that possess many important biological activities,playing a significant role in the medicinal activity of Eucommia ulmoides(E.ulmoides).To investigate the mechanism by which salt stress affects the biosynthesis of flavonoids in E.ulmoides,a comprehensive analysis of metabolomics and transcriptomics was conducted.The results indicated that salt stress led to the wilting and darkening of E.ulmoides leaves,accompanied by a decrease in chlorophyll levels,and significantly induced malondialdehyde(MDA)and relative electrical conductivity.During salt stress,most metabolites in the flavonoid biosynthesis pathway of E.ulmoides were upregulated,indicating that flavonoid biosynthesis is likely the main induced pathway under salt stress.Among them,secondary metabolites such as 6-Hydroxyluteolin and Quercetin are likely key metabolites induced by salt stress.The correlation analysis of transcriptomics and metabolomics revealed that EuSHT is a hub gene induced by salt stress,promoting the production of flavonoids such as 6-Hydroxyluteolin.The co-expression network showed a strong positive correlation between EuSHT and the biosynthesis of 6-Hydroxyluteolin and Quercetin,while it exhibited a negative correlation with Catechin biosynthesis.The branches leading to Luteolin and Dihydroquercetin are likely the main pathways for flavonoid compound biosynthesis in the plant stress response during salt stress.The results of this study provided a preliminary mechanism of secondary metabolites such as flavonoids in the medicinal plant E.ulmoides induced by salt stress and provided new theoretical support for discussing the mechanism of plant stress response.It also provided useful information for subsequent exploration of resistance genes in E.ulmoides.
基金the National Key Research and Development Program of China(2017YFC1600802).
文摘Trypsin,a novel superoxide scavenger,significantly enhances the storage quality of Hylocereus undatus(H.undatus).To elucidate the preservation mechanism of trypsin on H.undatus,a widely targeted metabolomic analysis,and transcriptomics analysis were conducted.Firstly,a total of 453 metabolites were identified,with organic acids and their derivatives constituting the largest proportion(25%).Amino acids and their metabolites,prominent among organic acids,were further analyzed.Among them,73 metabolites were associated with amino acids,and 37 exhibited significant differences.The most enriched Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway was arginine biosynthesis(map00220),with polyamine metabolites showing the most pronounced differences,particularly spermine(FC=1.7594).Compared with the control group,4-hydroxy-2-oxoglutaric acid was significantly upregulated(FC=2.117)in the process of spermine biosynthesis.Furthermore,the results of Gene Ontology(GO)and KEGG enrichment analysis of the H.undatus transcriptome profile revealed that trypsin treatment led to 187 differentially expressed genes associated with arginine.Both GO and KEGG analyses exhibited significant enrichment in the spermine biosynthetic process(GO:0006597)(map:00220)within the arginine biosynthesis pathway.Moreover,most enzymes and metabolites within the spermine biosynthesis pathway in H.undatus were upregulated.The results of the PPI network highlighted that ADC,SPDS,and SAMDC,among others,were pivotal proteins involved in trypsin-regulated arginine metabolism and spermine synthesis.This study revealed that trypsin could significantly delay postharvest senescence of H.undatus at room temperature.This effect might be attributed to trypsin triggering the synthesis of 4-hydroxy-2-oxoglutaric acid in the fruit peel,thereby promoting the biosynthesis of spermine and other polyamines.
基金funded by the National Key Research&Development Program of China(No.2018YFA0107400)Program for Chang-Jiang Scholars and Innovative Research Team in University(No.PCSIRT-14R08).
文摘Background:Hypertrophic cardiomyopathy(HCM)is an underdiagnosed genetic heart disease worldwide.The management and prognosis of obstructive HCM(HOCM)and non-obstructive HCM(HNCM)are quite different,but it also remains challenging to discriminate these two subtypes.HCM is characterized by dysmetabolism,and myocardial amino acid(AA)metabolism is robustly changed.The present study aimed to delineate plasma AA and derivatives profiles,and identify potential biomarkers for HCM.Methods:Plasma samples from 166 participants,including 57 cases of HOCM,52 cases of HNCM,and 57 normal controls(NCs),who first visited the International Cooperation Center for HCM,Xijing Hospital between December 2019 and September 2020,were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics.Three separate classification algorithms,including random forest,support vector machine,and logistic regression,were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM.Results:The univariate analysis showed that the serine,glycine,proline,citrulline,glutamine,cystine,creatinine,cysteine,choline,and aminoadipic acid levels in the HCM group were significantly different from those in the NC group.Four AAs and derivatives(Panel A;proline,glycine,cysteine,and choline)were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs.The receiver operating characteristic(ROC)analysis in Panel A yielded an area under the ROC curve(AUC)of 0.83(0.75-0.91)in the training set and 0.79(0.65-0.94)in the validation set.Moreover,among 10 AAs and derivatives(arginine,phenylalanine,tyrosine,proline,alanine,asparagine,creatine,tryptophan,ornithine,and choline)with statistical significance between HOCM and HNCM,3 AAs(Panel B;arginine,proline,and ornithine)were selected to differentiate the two subgroups.The AUC values in the training and validation sets for Panel B were 0.83(0.74-0.93)and 0.82(0.66-0.98),respectively.Conclusions:The plasma AA and derivatives profiles were distinct between the HCM and NC groups.Based on the differential profiles,the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
基金supported by the National Key R&D Program of China(2021YFD1300404).
文摘The synchronized absorption of amino acids and glucose in the gut is essential for amino acid utilization and protein synthesis in the body.The study aimed to investigate how the starch digestion rate and amino acid levels impact the growth and intestinal starch and amino acid digestion,transport,and metabolism in juvenile broilers.The experiment was conducted with 702 Arbor Acres Plus broilers at 1 d old,which were randomly divided into 9 treatments with 6 replicates of 13 chickens each.The treatments included 3 different starch sources(corn,waxy corn,and tapioca)with 3 different apparent ileal digestible lysine(AID Lys)levels(1.08%,1.20%,and 1.32%).A notable interaction was noted for dietary starch sources and AID Lys levels in the feed-to-gain ratio(F/G)and distal ileal starch digestibility(P<0.01).The tapioca starch and waxy corn starch diets with 1.32%of AID Lys significantly decreased F/G compared with corn starch(P<0.01).There was no significant difference in F/G of broilers among waxy corn starch diet with 1.08%AID Lys level,tapioca starch diet with 1.20%AID Lys level,and corn starch diet with 1.32%AID Lys level(P>0.05).The 1.32%AID Lys level and the waxy corn starch both improved the body weight(BW)of broilers from 0 to 3 weeks of age,intestinal starch digestibility,and intestinal villi height or the ratio of villi height to crypt depth(P<0.05).Compared with the corn starch diet,waxy corn starch and tapioca starch diets significantly elevated the AID of Met,Glu,Lys,Arg,Asp,His,Ile,Tyr,Gly,and Val levels(P<0.05).The carbon metabolomics results revealed that the waxy corn starch diet significantly reduced malic acid and cis-aconitic acid levels(P<0.05)in the tricarboxylic acid cycle compared to the corn starch diet.It was concluded that a waxy corn starch diet improves the growth performance of broilers by improving intestinal morphology,increasing the absorption and transport of amino acids,reducing the amino acid oxidation for energy supply in the intestinal mucosa,and promoting protein synthesis in muscles,which not only reduces the need for dietary AID Lys but also saves on production costs.
基金supported by the National Natural Science Foundation of China(No.42207321)the Fundamental Research Funds for the Central Universities(China)(No.B230201006).
文摘Most research on antibiotics in the environment disregards chiral antibiotics,such as ofloxacin(OF).In this study,tadpoles of Rana nigromaculata were exposed to 1μg/L OF and levofloxacin(LVFX,an enantiomer of OF)for 75 d.Compared with dextrofloxacin,LVFX treatment had a greater effect on the inhibition of bodyweight,body length,development stage,and pathological liver damage.Therefore,OF exerts a stereoselective inhibitory effect on both growth and development,which is consistent with the results at the systemic metabolism level.Transcriptomic analysis revealed that the differentially expressed genes between OF and LVFX were mainly immune related.Targeted metabolomics showed that the stereoselective biological effect of OF on R.nigromaculata was caused by differences in contents of PE-O 16:0-22:4,PE 16:0-14:0,TAG 45:0-FA16:0,PE-P 18:0-16:0,PE 16:0-16:0,PC 16:0-22:4+AcO,PE 18:1-18:3,PC 16:1-18:1+AcO,and PC 18:1-18:3+AcO.Furthermore,two enantiomers of OF were selectively bound to enzymes related to lipid metabolism.This study provides both theoretical and practical references for the accurate evaluation and scientific control of the ecological risk of chiral antibiotics.
基金supported by the Key Research and Development Program of Zhejiang(No.2023C03047)the National Key Research and Development Program of China(No.2021YFC2701900)the National Natural Science Foundation of China(Nos.82170583 and 82370863).
文摘Background The diagnosis of central precocious puberty(CPP)relies on a gonadotropin releasing hormone stimulation test to assess the activation of the hypothalamic-pituitary-gonadal axis;this is costly and painful.Bile acids(BAs)have emerged as pivotal signaling molecules in the reproductive system.This study aimed to identify circulating BA profile signatures and explored if they may serve as biomarkers for CPP diagnosis in girls.Methods We enrolled 431 girls,including 241 in the training cohort and 190 in the validation cohort.Participants were divided into four groups based on their body mass index Z-score and whether they were diagnosed with CPP.Ultra-performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs.Results There were 18 individual BAs that were statistically different between CPP and non-CPP counterparts.The majority of these BAs(14/18)correlated significantly with sex-related hormones(P<0.05).In girls with normal weight(NW),a logistic regression model combining chenodeoxycholic acid,tauro α-muricholic acid,and 6-ketolithocholic acid achieved an area under the receiver operating characteristic curve(AUC)of 0.885.For girls who were overweight/obese(OB),hyocholic acid and taurohyocholic acid enhanced the diagnostic efficiency of basal luteinizing and follicle stimulating hormones to an AUC value 0.914.In validation cohort,75.34%NW girls and 84.09%OB girls were accurately classified.Conclusions Serum BA profiles of CPP girls showed significant changes that were associated with serum sex-related hormone levels.BA profiles could be potential biomarkers in CPP diagnosis and screening.
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 by the Natural Science Foundation of Shandong Province (ZR2020MC148)the China Agriculture Research System (CARS-23-C04)+1 种基金the National Key Research and Development Programme (2016YFB0302403)the Science and Tech Innovation Teamin Shandong Agriculture University-Facility Horticulture Advantages Team (SYL2017YSTD07),China。
文摘Carotenoids are the main pigments responsible for the coloration and account for the major antioxidant activity of tomato(Solanum lycopersicum L.)fruit.Significant increments in total carotenoids and lycopene levels were observed in tomato fruit illuminated by red light relative to white light in previous studies,but the mechanism of carotenoid biosynthesis regulated by red light is stll unclear.In the present study,the influence of red light on carotenoid biosynthesis in postharvest tomato fruit was conducted using targeted metabolomics and transcriptomic methods.A total of 25 differentially accumulated carotenoids and 1939 differentially expressed genes were isolated and identified.The results illustrated that the contents of phytoene and lycopene were considerably higher in fruit treated with red light than those with white light at 12 h.These differentially expressed genes are mainly enriched in plant hormone signal transduction,photosynthesis,secondary metabolite biosynthesis,and plant circadian rhythm.Moreover,from the results of coexpression network analysis,15 transcription factors from red light-treated fruit were screened;among these,transcription factors of SIERF4,SlbHLH93 and SllAA29,which are involved in signal transduction of light and hormones,respectively,may also play important roles in carotenoid biosynthesis regulated by red light in tomato fruit.It is concluded that red light enhanced carotenoid biosynthesis in postharvest tomato fruit and the mechanisms of enhanced carotenoid biosynthesis were not only associated with the direct regulation by red light signalling,but also with the indirect regulation by hormonal signalling.
基金supported by the National Key Research and Development Program of China(2016YFD0500501)Agricultural Research Outstanding Talents and Innovation Team(2016-nybrc03)the Fundamental Research Funds for the Central Institute,the Agricultural Science and Technology Innovation Program(ASTIPIAS07)。
文摘Aerial ammonia exposure leads to tissue damage and metabolic dysfunction.However,it is unclear how different organs are coordinated to defend against aerial ammonia exposure.Twenty-four pigs were randomly divided into 4 groups,exposed to 0,10,25 or 35 mg/m^(3) ammonia respectively for 25 d.After above 25 mg/m^(3) ammonia exposure,decreased aspartate(P=0.016),glutamate(P=0.030)and increased ornithine(P=0.002)were found in the ammonia-removing liver,and after high ammonia(35 mg/m^(3))exposure,glutamine synthetase(GS)expression was increased(P=0.012).An increased glutamate(P=0.004)and decreased glutaminase(GLS)expression(P=0.083)were observed in the lungs after high ammonia exposure.There was also an increasing trend of glutamine in the kidneys after high ammonia exposure(P=0.066).For branched-chain amino acid(BCAA)catabolism,high ammonia exposure increased BCAA content in both the lungs and muscle(P<0.05),whereas below 25 mg/m^(3) ammonia exposure increased BCAA only in the lungs(P<0.05).The expression of BCAA transaminase(BCAT1/2)and dehydrogenase complex(BCKDHA/B and DBT)were inhibited to a varying degree in the liver,lungs and muscle after above 25 mg/m^(3) ammonia exposure,especially high ammonia exposure.The expression of BCKDH complex and glutamate-glutamine metabolism-related genes were highly expressed in the liver,followed by the lungs and muscle(P<0.01),whereas the BCAT2 expression was highest in the lungs(P=0.002).Altogether,low ammonia exposure sufficed to evoke the urea cycle to detoxify ammonia in the liver.The process of ammonia removal in the liver and potential ability of the lungs to detoxify ammonia were enhanced with increasing ammonia.Furthermore,high ammonia exposure impaired the BCAA catabolism and decreased the transcripts of the BCAA catabolism-related enzymes,resulting in high BCAA content in extrahepatic tissues.Therefore,with aerial ammonia increasing,an increased urea cycle and glutamine synthesis were ammonia defensive strategies,and high ammonia exposure impaired the BCAA catabolism.
