Comparative Metabolomic Analysis Research Articles

Transcriptomics and metabolomics reveal the underlying mechanism of drought treatment on anthocyanin accumulation in postharvest blood orange fruit

BackgroundAnthocyanins are the most important compounds for nutritional quality and economic values of blood orange. However, there are few reports on the pre-harvest treatment accelerating the accumulation of anthocyanins in postharvest blood orange fruit. Here, we performed a comparative transcriptome and metabolomics analysis to elucidate the underlying mechanism involved in seasonal drought (SD) treatment during the fruit expansion stage on anthocyanin accumulation in postharvest ‘Tarocco’ blood orange fruit.ResultsOur results showed that SD treatment slowed down the fruit enlargement and increased the sugar accumulation during the fruit development and maturation period. Obviously, under SD treatment, the accumulation of anthocyanin in blood orange fruit during postharvest storage was significantly accelerated and markedly higher than that in CK. Meanwhile, the total flavonoids and phenols content and antioxidant activity in SD treatment fruits were also sensibly increased during postharvest storage. Based on metabolome analysis, we found that substrates required for anthocyanin biosynthesis, such as amino acids and their derivatives, and phenolic acids, had significantly accumulated and were higher in SD treated mature fruits compared with that of CK. Furthermore, according to the results of the transcriptome data and weighted gene coexpression correlation network analysis (WGCNA) analysis, phenylalanine ammonia-lyase (PAL3) was considered a key structural gene. The qRT-PCR analysis verified that the PAL3 was highly expressed in SD treated postharvest stored fruits, and was significantly positively correlated with the anthocyanin content. Moreover, we found that other structural genes in the anthocyanin biosynthesis pathway were also upregulated under SD treatment, as evidenced by transcriptome data and qRT-PCR analysis.ConclusionsThe findings suggest that SD treatment promotes the accumulation of substrates necessary for anthocyanin biosynthesis during the fruit ripening process, and activates the expression of anthocyanin biosynthesis pathway genes during the postharvest storage period. This is especially true for PAL3, which co-contributed to the rapid accumulation of anthocyanin. The present study provides a theoretical basis for the postharvest quality control and water-saving utilization of blood orange fruit.

Comparative transcriptomic and metabolomics analysis of modified atmosphere responses in Tribolium castaneum (Coleoptera: Tenebrionidae).

Modified atmosphere is effective in controlling Tribolium castaneum Herbst, but it has adaptations. Comprehending the potential mechanism of resistance to T. castaneum in a modified atmosphere will help advance related management methods. This study conducted a comparative transcriptomic and metabolomic analysis to understand the physiological mechanism of T. castaneum in adapting to CO2 stress. Results showed that there were a large number of differentially expressed genes (DEGs) in T. castaneum treated with different concentrations of CO2. Gene ontology (GO) analysis revealed significant enrichment of DEGs mainly in binding, catalytic activity, cell, membrane, membrane part, protein-containing complex, biological regulation, and cellular and metabolic process. Kyoto Encyclopedia of Genes and Genomes analysis showed that different treatments had different effects on the metabolic pathways of T. castaneum. DEGs induced by 25% CO2 were involved in arginine and proline metabolism, and 50% air + 50% CO2 treatment affected most kinds of metabolic pathways, mainly the signal transduction pathway, including PI3K-Akt signaling pathway, AMPK signaling pathway, neurotrophin signaling pathway, insulin signaling pathway, and thyroid hormone signaling. Ribosome and DNA replication were enriched under high CO2 stress (75% and 95%). The metabolomics revealed that different concentrations of CO2 treatments might inhibit the growth of T. castaneum through acidosis, or they may adapt to anoxic conditions through histamine and N-acetylhistamine. Multiple analyses have shown significant changes in histamine and N-acetylhistamine levels, as well as their associated genes, with increasing CO2 concentration. In conclusion, this study comprehensively revealed the molecular mechanism of T. castaneum responding to CO2 stress and provided the basis for an effectively modified atmosphere in the T. castaneum.

A comparative untargeted metabolomic analysis and assessment of antiplasmodial potential of nine Albizia species.

The genus Albizia is one of the richest genera in phenolics besides other classes of secondary metabolites including saponins, terpenes, and alkaloids with promising medicinal applications. In the current study, UHPLC-PDA-ESI-MS/MS-based metabolic profiling of leaves of Albizia lebbeck, Albizia julibrissin, Albizia odoratissima, Albizia procera, Albizia anthelmintica, Albizia guachapele, Albizia myriophylla, Albizia richardiana, and Albizia lucidior resulted in the tentative identification of 64 metabolites, mainly flavonoids, phenolic acids, saponins, and alkaloids. Some metabolites were identified in Albizia for the first time and could be used as species-specific chemotaxonomic markers, including: apigenin 7-O-dihydroferuloyl hexoside isomers, apigenin 7-O-pentosyl hexoside, quercetin 3-O-rutinoside 7-O-deoxyhexoside, quercetin 3,7-di-O-hexoside deoxyhexoside, quercetin 7-O-feruloyl hexoside, methyl myricetin 7-O-deoxyhexoside, kaempferol di-3-O-di-deoxyhexoside-7-O-hexoside, and kaempferol 3-O-neohesperidoside 7-O-hexoside. Comparative untargeted metabolomic analysis was undertaken to discriminate between species and provide a chemotaxonomic clue that can be used together with morphological and genetic analyses for more accurate classification within this genus. Moreover, the in vitro antiplasmodial activity was assessed and correlated to the metabolic profile of selected species. This was followed by a molecular docking study and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction of the identified budmunchiamine alkaloids, revealing promising interactions with the active site of lactate dehydrogenase of Plasmodium falciparum and good pharmacokinetics and pharmacodynamics, which could help in designing novel antimalarial drugs.

Comparative transcriptome and metabolome analysis revealed diversity in the response of resistant and susceptible rose (Rosa hybrida) varieties to Marssonina rosae.

Rose black spot disease caused by Marssonina rosae is among the most destructive diseases that affects the outdoor cultivation and production of roses; however, the molecular mechanisms underlying the defensive response of roses to M. rosae have not been clarified. To investigate the diversity of response to M. rosae in resistant and susceptible rose varieties, we performed transcriptome and metabolome analyses of resistant (KT) and susceptible (FG) rose varieties and identified differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) in response to M. rosae at different time points. In response to M. rosae, DEGs and DAMs were mainly upregulated compared to the control and transcription factors were concentrated in the WRKY and AP2/ERF families. Gene Ontology analysis showed that the DEGs of FG were mainly enriched in biological processes, such as the abscisic acid-activated signaling pathway, cell wall, and defense response, whereas the DEGs of KT were mainly enriched in Golgi-mediated vesicle transport processes. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs of both varieties were concentrated in plant-pathogen interactions, plant hormone signal transduction, and mitogen-activated protein kinase signaling pathways, with the greatest number of DEGs associated with brassinosteroid (BR) in the plant hormone signal transduction pathway. The reliability of the transcriptome results was verified by qRT-PCR. DAMs of KT were significantly enriched in the butanoate metabolism pathway, whereas DAMs of FG were significantly enriched in BR biosynthesis, glucosinolate biosynthesis, and tryptophan metabolism. Moreover, the DAMs in these pathways were significantly positively correlated with the DEGs. Disease symptoms were aggravated when FG leaves were inoculated with M. rosae after 24-epibrassinolide treatment, indicating that the response of FG to M. rosae involves the BR signaling pathway. Our results provide new insights into the molecular mechanisms underlying rose response to M. rosae and lay a theoretical foundation for formulating rose black spot prevention and control strategies and cultivating resistant varieties.

Induction of stearoyl-CoA desaturase confers cell density-dependent ferroptosis resistance in melanoma.

Ferroptosis is a form of regulated cell death that is induced by inhibiting glutathione peroxidase 4 (GPX4), which eliminates lipid peroxidation. Ferroptosis induction is influenced by the cell environment. However, the cellular states altering ferroptosis susceptibility remain largely unknown. We found that melanoma cell lines became resistant to ferroptosis as cell density increased. Comparative transcriptome and metabolome analyses revealed that cell density-dependent ferroptosis resistance was coupled with a shift toward a lipogenic phenotype accompanied by strong induction of stearoyl-CoA desaturase (SCD). Database analysis of gene dependency across hundreds of cancer cell lines uncovered a negative correlation between GPX4 and SCD dependency. Importantly, SCD inhibition, either pharmacologically or through genetic knockout, sensitized melanoma cells to GPX4 inhibition, thereby attenuating ferroptosis resistance in cells at high density. Our findings indicate that transition to an SCD-inducing, lipogenic cell state produces density-dependent resistance to ferroptosis, which may provide a therapeutic strategy against melanoma.

Integrated transcriptome and metabolome analysis provides insights into blue light response of Flammulina filiformis

Blue light promotes primordium differentiation and fruiting body formation of mushroom. However, the blue light response mechanism of mushroom remains unclear. In this study, mycelium of Flammulina filiformis was exposed to blue light, red light and dark conditions, and then the comparative metabolome and transcriptome analysis was applied to explore metabolic regulation mechanism of F. filiformis under blue light and red light conditions. The yield of the fruiting body of F. filiformis under blue light condition was much higher than that under dark and red light conditions. Metabolome analysis showed that blue light treatment reduced the concentrations of many low molecular weight carbohydrates in the pilei, but it promoted the accumulation of some low molecular weight carbohydrates in the stipes. Blue light also decreased the accumulation of organic acids in the stipes. Blue light treatment reduced the levels of tyrosine and tryptophan in the stipes, but it largely promoted the accumulation of lysine in this organ. In the stipes of F. filiformis, blue light shifted metabolite flow to synthesis of lysine and carbohydrates through inhibiting the accumulation of aromatic amino acids and organic acids, thereby enhancing its nutritional and medicinal values. The transcriptome analysis displayed that blue light enhanced accumulation of lysine in fruiting body of F. filiformis through downregulation of lysine methyltransferase gene and L-lysine 6-monooxygenase gene. Additionally, in the stipes, blue light upregulated many hydrolase genes to improve the ability of the stipe to biodegrade the medium and elevated the growth rate of the fruiting body.

Comparative antioxidant and metabolomic analysis for the identification of differential response of mussel (Mytilus coruscus) to four succinate dehydrogenase inhibitor fungicides.

Succinate dehydrogenase inhibitor fungicides (SDHIs) are frequently detected in the marine environment. However, studies on the toxicity of SDHIs to marine organisms, Mytilus coruscus (M. coruscus), are poorly reported. Therefore, the antioxidant activities and metabolomic response of four SDHIs, namely, boscalid (BC), thifluzamide (TF), fluopyram (FO), and bixafen (BIX), to (M. coruscus), were comprehensively investigated. The antioxidant activity of BC and TF was significantly increased (p<0.05), whereas those of FO and BIX were significantly decreased. Furthermore, metabolite discriminations among M. coruscus to four SDHIs were illustrated by an untargeted metabolomics approach. A total of 52, 50, 93, and 129 differential metabolites were obtained for BC, TF, FO, and BIX. KEGG of the different metabolites show that the four SDHIs had differential effects on the metabolic pathways of M. coruscus. The current study demonstrated four SDHIs triggered glucose metabolism, lipid metabolism, tricarboxylic acid cycle, and oxidative phosphorylation processes and caused the disruption of nutrient and energy conversion processes in mussels. Finally, five biomarkers were screened by analyzing common differential metabolites that emerged from the four SDHI exposures, which could be used for risk assessment of marine ecosystem exposure to SDHIs. Our results demonstrated the use of metabolomics to understand the potential mechanisms of toxicity of four SDHIs to mussels and to identify potential targets for future targeted risk assessment.

Pseudomonas aeruginosa heme metabolites biliverdin IXβ and IXδ are integral to lifestyle adaptations associated with chronic infection.

The opportunistic pathogen Pseudomonas aeruginosa causes long-term chronic infection in the airways of cystic fibrosis patients. The ability to scavenge iron and to establish chronic infection within this environment coincides with a switch to utilize heme as the primary iron source. Herein, we show the heme metabolites biliverdin beta and delta are themselves important signaling molecules integrating the switch in iron acquisition systems with cooperative behaviors such as motility and biofilm formation that are essential for long-term chronic infection. These significant findings will enhance the development of viable multi-targeted therapeutics effective against both heme utilization and cooperative behaviors essential for survival and persistence within the host.

A comparative metabolomics analysis of phytochemcials and antioxidant activity between broccoli floret and by-products (leaves and stalks)

Leaves and stalks, which account for about 45% and 25% of broccoli biomass, respectively, are usually discarded during broccoli production, leading to the waste of green resources. In this study, the phytochemical composition and antioxidant capacity of broccoli florets and their by-products (leaves and stalks) were comprehensively analyzed. The metabolomics identified several unique metabolites (e.g., scopoletin, Harpagoside, and sinalbin) in the leaves and stalks compared to florets. Notably, the leaves were found to be a rich source of flavonoids and coumarins, with superior antioxidant capacity. The random forest model and correlation analysis indicated that flavonoids, coumarin, and indole compounds were the important factors contributing to the antioxidant activity. Moreover, the stalks contained higher levels of carbohydrates and exhibited better antioxidant enzyme activity. Together, these results provided valuable data to support the comprehensive utilization of broccoli waste, the development of new products, and the expansion of the broccoli industry chain.

Neuropeptide ACP is required for fat body lipid metabolism homeostasis in locusts.

Fat body metabolism plays crucial roles in each aspect of insect life traits. Although neuropeptides have been documented to be one of the major neuroendocrinal regulators involved in fat body metabolism, the detailed regulatory mechanism is poorly explored. Here, we conducted comparative metabolome and transcriptome analyses of fat body between wide type (WT) and adipokinetic hormone/corazonin-related peptide (ACP) loss of function mutants of the migratory locust, Locusta migratoria. We found that knockout of ACP resulted in significantly reduced fat body triacylglycerol content but enhanced abundance of phospholipids, particularly phosphatidylcholine and phosphatidylethanolamine. Additionally, the expression levels of genes involved in triacylglycerol and phospholipid synthesis and degradation were significantly altered in the fat body of ACP mutants. Moreover, female ACP mutants displayed much higher fecundity compared to WT females. These findings highlight the important role of neuropeptide ACP in fat body lipid metabolism homeostasis in locusts.

Enhanced phenylpropanoid metabolism underlies resistance to Fusarium oxysporum f. sp. vasinfectum race 4 infection in the cotton cultivar Pima-S6 (Gossypium barbadense L.).

Introduction: Fusarium oxysporum f. sp. vasinfectum (FOV) race 4 (FOV4) is a highly pathogenic soil-borne fungus responsible for Fusarium wilt in cotton (Gossypium spp.) and represents a continuing threat to cotton production in the southwest states of the United States, including California, New Mexico, and Texas. Pima (G. barbadense L.) cotton, which is highly valued for its fiber quality, has been shown to be more susceptible to this pathogen than Upland (G. hirsutum L.) cotton. Still, some Pima cultivars present resistance to FOV4 infection. Methods: To gain insights into the FOV4-resistance mechanism, we performed comparative transcriptional and metabolomic analyses between FOV4-susceptible and FOV4-resistant Pima cotton entries. FOV4-resistant Pima-S6 and FOV4-susceptible Pima S-7 and Pima 3-79 cotton plants were infected with FOV4 in the greenhouse, and the roots harvested 11days post-infection for further analysis. Results: We found that an enhanced root phenylpropanoid metabolism in the resistant Pima-S6 cultivar determines FOV4-resistance. Gene-ontology enrichment of phenylpropanoid biosynthesis and metabolism categories correlated with the accumulation of secondary metabolites in Pima-S6 roots. Specifically, we found esculetin, a coumarin, an inhibitor of Fusarium's growth, accumulated in the roots of Pima-S6 even under non-infected conditions. Genes related to the phenylpropanoid biosynthesis and metabolism, including phenylalanine ammonia-lyase 2 (PAL2) and pleiotropic drug resistance 12 (PDR12) transporter, were found to be upregulated in Pima-S6 roots. Discussion: Our results highlight an essential role for the phenylpropanoid synthesis pathway in FOV4 resistance in Pima-S6 cotton. These genes represent attractive research prospects for FOV4-disease resistance and breeding approaches of other cotton cultivars of economic relevance.

Comparative physiological, metabolomic and transcriptomic analyses reveal the mechanisms of differences in pear fruit quality between distinct training systems

BackgroundCanopy architecture is critical in determining the fruit-zone microclimate and, ultimately, in determining an orchard’s success in terms of the quality and quantity of the fruit produced. However, few studies have addressed how the canopy environment leads to metabolomic and transcriptomic alterations in fruits. Designing strategies for improving the quality of pear nutritional components relies on uncovering the related regulatory mechanisms.ResultsWe performed an in-depth investigation of the impact of canopy architecture from physiological, metabolomic and transcriptomic perspectives by comparing pear fruits grown in a traditional freestanding system (SP) or a flat-type trellis system (DP). Physiological studies revealed relatively greater fruit sizes, soluble solid contents and titratable acidities in pear fruits from DP systems with open canopies. Nontargeted metabolite profiling was used to characterize fruits at the initial ripening stage. Significant differences in fruit metabolites, including carbohydrates, nucleic acids, alkaloids, glycerophospholipids, sterol lipids, and prenol lipids, were observed between the two groups. Transcriptomic analysis indicated that a series of organic substance catabolic processes (e.g., the glycerol-3-phosphate catabolic process, pectin catabolic process and glucan catabolic process) were overrepresented in fruits of the DP system. Moreover, integrative analysis of the metabolome and transcriptome at the pathway level showed that DP pear fruits may respond to the canopy microenvironment by upregulating phenylpropanoid biosynthesis pathway genes such as PpPOD. Transient assays revealed that the contents of malic acid and citric acid were lower in the pear flesh of PpPOD RNAi plants, which was associated with regulating the expression of organic acid metabolism-related genes.ConclusionsOur results provide fundamental evidence that at the physiological and molecular levels, open-canopy architecture contributes to improving pear fruit quality and is correlated with increased levels of carbohydrates and lipid-like molecules. This study may lead to the development of rational culture practices for enhancing the nutritional traits of pear fruits.

Metabolism and transcriptional regulation in chilling injury development of nectarine fruit during postharvest cold storage

Peach fruit is susceptible to chilling injury during postharvest long-term cold storage, but the understanding of metabolic and transcriptional reaction of nectarine cultivar fruit to cold storage remains incomplete. In this study, nectarine fruit was used for a low temperature treatment, which gradually leading to the deterioration of fruit quality. Comparative metabolome and transcriptome analyses were performed to comprehensively understand the metabolic and transcriptional changes occurring during cold storage in nectarine fruit. The result showed that numerous primary and secondary metabolites exhibited increased levels following the low-temperature treatment. And there were 3400 differentially expressed genes continuously regulated by cold storage, which were mostly enriched in metabolic and secondary metabolite biosynthesis pathways. The combined pathways enrichment of differential metabolites and genes were primarily centered on secondary metabolite biosynthesis. Correspondingly, a strong correlation was observed between changes in secondary metabolites and the expression of key enzymes including 4-coumarate CoA ligase (4CL), hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HCT), flavonol synthase (FLS), dihydroflavonol reductase (DFR), and UDP-glycose flavonoid glycosyltransferase (UFGT), which were involved in flavonoids biosynthesis. Additionally, several fruit quality characteristics (carotenoids, cell wall components, antioxidant enzymes) and stress related signaling genes were markedly affected by cold storage. These findings offer new insights into the networks governing metabolic and transcriptional regulation during nectarine fruit cold storage.

Comparative metabolomic analysis reveals nutritional properties and pigmentation mechanism of tea-scented rosehips.

The fruits of the genus Rosa, commonly known as rosehips, have attracted significant attention owing to their rich content of various bioactive compounds. However, their utility is generally secondary to the ornamental appeal of their flowers. This study aimed to explore the quality differences among tea-scented rosehips found in Yunnan, China, including those of Rosa odorata var. odorata (RO), Rosa odorata var. gigantea (RG), and Rosa yangii (RY). Morphological characteristics, chemical composition, and antioxidant activity of their fruits were evaluated. The study revealed significant variability in composition and biological activities based on fruit color. RO exhibited the highest levels of polyphenols, flavonoids, anthocyanins, carotenoids, and vitamin C, with the strongest antioxidant activity (10.99 μmol Trolox·g-1 ), followed by RG (7.91 μmol Trolox·g-1 ) and RY (6.52 μmol Trolox·g-1 ). This supports RO's potential as a functional food source. Untargeted metabolomics identified and quantified 502 metabolites, with flavonoids (171) and phenolic acids (147) as the main metabolites. The differential metabolites among the fruits are primarily enriched for flavonoid biosynthesis and phenylpropanoid biosynthesis pathways. Insights into color formation supported the role of anthocyanins, flavones, and flavonols in fruit color variation. Tea-scented rosehips offer vibrant colors and high nutritional value with potent biological activities. Rosa odorata var. odorata stands out as a functional food source owing to its rich bioactive compounds. These findings lay the groundwork for utilizing rosehips in functional foods, health supplements, and food additives, emphasizing the practical and beneficial applications of Rosa spp. independent of their ornamental value. © 2023 Society of Chemical Industry.

Metabolomic-based analysis reveals bile acid-mediated ovarian failure induced by low temperature in zebrafish.

As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish ( Danio rerio) ovaries exposed to a temperature gradient ranging from the thermopreferendum temperature of the species, 27°C, to lower temperatures of 22°C, 20°C, and 13°C over a period of two weeks. Comparative metabolomic (six biological replicates for each temperature) and transcriptomic (four biological replicates for each temperature) analyses were conducted under the four temperature conditions. Results indicated that lower temperatures inhibited oocyte development and differential metabolites were involved in steroid hormone production, antioxidant function, and lipid and protein catabolism. Disrupted reproductive hormones, increased proteolysis, and lipid degradation significantly impeded oocyte development and egg maturation. Notably, a significant increase in bile acid content was noted in the ovaries of the cold-treated fish, indicating that bile acids play a critical role in ovarian failure. Overall, these findings provide valuable insights into the mechanisms governing the reproductive response of fish to cold stress.

Comparative metabolomics analysis reveals secondary cell wall thickening as a barrier to resist Aspergillus flavus infection in groundnut

AbstractAflatoxin contamination caused by Aspergillus flavus significantly threatens food safety and human health. Resistance to aflatoxin is a highly complex and quantitative trait, but the underlying molecular and biochemical mechanisms are poorly understood. The present study aims to identify the resistance‐related metabolites in groundnut that influence the defense mechanism against aflatoxin. Here, metabolite profiling of resistant (55–437) and susceptible (TMV‐2) groundnut genotypes, which exhibited contrasting levels of resistance to A. flavus growth and aflatoxin accumulation under pathogen‐ or mock‐inoculated treatments, was undertaken using liquid chromatography and high‐resolution mass spectrometry (LC‐HRMS). Non‐targeted metabolomic analysis revealed key resistance‐related metabolites belonging to phenylpropanoids, flavonoids, fatty acids, alkaloids, and terpenoid biosynthetic pathways. The phenylpropanoids ‐ hydroxycinnamic acid amides (HCAAs) and lignins were among the most abundantly accumulated metabolites in the resistant genotype compared to the susceptible genotype. HCAAs and lignins are deposited as polymers and conjugated metabolites to strengthen the secondary cell wall, which acts as a barrier to pathogen entry. Further, histochemical staining confirmed the secondary cell wall thickening due to HCAAs and lignin depositions. Quantitative real‐time PCR studies revealed higher expressions of phenylalanine ammonia‐lyase (PAL), 4‐coumarate: CoA ligase (4CL), cinnamoyl CoA reductase (CCR2), cinnamoyl alcohol dehydrogenase (CAD1), agmatine hydroxycinnamoyl transferase (ACT), chalcone synthase (CHS), dihydroflavonol 4‐reductase (DFR) and flavonol synthase (FLS) in the pathogen‐inoculated resistant genotype than in the susceptible genotype. This study reveals that the resistance to aflatoxin contamination in groundnut genotypes is associated with secondary cell wall thickening due to the deposition of HCAAs and lignins.

Comparative metabolomics analysis of unique yellow hawthorn (Crataegus pinnatifida) and red-skinned cultivars reveals a different polyphenol biosynthesis flux and antioxidative and antidiabetic potential

Abstract 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 and α-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 excellent α-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 on α-glucosidase, and was predicted to have the lowest binding energy with the enzyme according to molecular docking analysis, indicating its great potential as a strong α-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.

A comparative urinary proteomic and metabolomic analysis between renal aa amyloidosis and membranous nephropathy with clinicopathologic correlations

Urinary omics has become a powerful tool for elucidating pathophysiology of glomerular diseases. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urine proteomic and metabolomic analysis between recently diagnosed renal AA amyloidosis (AA) and membranous nephropathy (MN) patients. Urine samples of 22 (8 AA, 8 MN and 6 healthy control) patients were analyzed with nLC-MS/MS and GC/MS for proteomic and metabolomic studies, respectively. Pathological specimens were scored for glomerulosclerosis and tubulointerstitial fibrosis grades. Functional enrichment analysis between AA and control groups showed enrichment in cell adhesion related sub-domains. Uromodulin (UMOD) was lower, whereas ribonuclease 1 (RNase1) and α-1-microglobulin/bikunin precursor (AMBP) were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = −0.48, p = 0.03) and AMBP-eGFR (r = −0.69, p = 0.003) variables. Metabolomic analysis showed myo-inositol and urate were higher in AA compared to MN group. A positive correlation was detected between RNase1 and urate independent of eGFR values (r = 0.63, p = 0.01). Enrichment in cell adhesion related domains suggested a possible increased urinary shear stress due to amyloid fibrils. UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be related with systemic inflammation in AA amyloidosis. SignificanceUrinary omics studies have become a standard tool for biomarker studies. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urinary omics analysis between recently diagnosed renal AA amyloidosis (AA), membranous nephropathy (MN) patients and healthy controls. Pathological specimens were scored with glomerulosclerosis (G) and tubulointerstitial fibrosis (IF) grades to consolidate the results of the omics studies and correlation analyzes. Functional enrichment analysis showed enrichment in cell adhesion related sub-domains due to downregulation of cadherins; which could be related with increased urinary shear stress due to amyloid deposition and disruption of tissue micro-architecture. In comparative proteomic analyzes UMOD was lower, whereas RNase1 and AMBP were higher in AA compared to MN group. Whereas in metabolomic analyzes; myo-inositol, urate and maltose were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = −0.48, p = 0.03), AMBP-eGFR (r = −0.69, p = 0.003) and between RNase1-Urate independent of eGFR values (r = 0.63, p = 0.01). This study is the first comprehensive urinary omics analysis focusing on renal AA Amyloidosis to the best of our knowledge. Based on physiologic roles and clinicopathologic correlations of the molecules; UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be increased with systemic inflammation and endothelial damage in AA amyloidosis.

Integrating transcriptome and metabolome to explore the growth-promoting mechanisms of GABA in blueberry plantlets.

Tissue culture technology is the main method for the commercial propagation of blueberry plants, but blueberry plantlets grow slowly and have long growth cycles under in vitro propagation, resulting in low propagation efficiency. In addition, the long culturing time can also result in reduced nutrient content in the culture medium, and the accumulation of toxic and harmful substances that can lead to weak growth for the plantlets or browning and vitrification, which ultimately can seriously reduce the quality of the plantlets. Gamma-aminobutyric acid (GABA) is a four-carbon non-protein amino acid that can improve plant resistance to various stresses and promote plant growth, but the effects of its application and mechanism in tissue culture are still unclear. In this study, the effects of GABA on the growth of in vitro blueberry plantlets were analyzed following the treatment of the plantlets with GABA. In addition, the GABA-treated plantlets were also subjected to a comparative transcriptomic and metabolomic analysis. The exogenous application of GABA significantly promoted growth and improved the quality of the blueberry plantlets. In total, 2,626 differentially expressed genes (DEGs) and 377 differentially accumulated metabolites (DAMs) were detected by comparison of the control and GABA-treated plantlets. Most of the DEGs and DAMs were involved in carbohydrate metabolism and biosynthesis of secondary metabolites. The comprehensive analysis results indicated that GABA may promote the growth of blueberry plantlets by promoting carbon metabolism and nitrogen assimilation, as well as increasing the accumulation of secondary metabolites such as flavonoids, steroids and terpenes.

Safety assessment, whole genome sequence, and metabolome analysis of Streptococcus thermophilus CICC 20372 for bone cement fermentation.

Bone is a kind of meat processing by-product with high nutritional value but low in calorie, which is a typical food in China and parts of East Asian countries. Microbial fermentation by lactic acid bacteria showed remarkable advantages to increase the absorption of nutrients from bone cement by human body. Streptococcus thermophilus CICC 20372 is proven to be a good starter for bone cement fermentation. No genes encoding virulence traits or virulence factors were found in the genome of S. thermophilus CICC 20372 by a thorough genomic analysis. Its notable absence of antibiotic resistance further solidifies the safety. Furthermore, the genomic analysis identified four types of gene clusters responsible for the synthesis of antimicrobial metabolites. A comparative metabolomic analysis was performed by cultivating the strain in bone cement at 37°C for 72h, with the culture in de Man, Rogosa, and Sharpe (MRS) medium as control. Metabolome analysis results highlighted the upregulation of pathways involved in 2-oxocarboxylic acid metabolism, ATP-binding cassette (ABC) transporters, amino acid synthesis, and nucleotide metabolism during bone cement fermentation. S. thermophilus CICC 20372 produces several metabolites with health-promoting function during bone cement fermentation, including indole-3-lactic acid, which is demonstrated ameliorative effects on intestinal inflammation, tumor growth, and gut dysbiosis. In addition, lots of nucleotide and organic acids were accumulated at higher levels, which enriched the fermented bone cement with a variety of nutrients. Collectively, these features endow S. thermophilus CICC 20372 a great potential strain for bone food processing.