Metabolomic Levels Research Articles

Pulsed Electric Field Induces Significant Changes in the Metabolome of Fusarium Species and Decreases Their Viability and Toxigenicity

Fusarium fungi are widespread pathogens of food crops, primarily associated with the formation of mycotoxins. Therefore, effective mitigation strategies for these toxicogenic microorganisms are required. In this study, the potential of pulsed electric field (PEF) as an advanced technology of increasing use in the food processing industry was investigated to minimize the viability of Fusarium pathogens and to characterize the PEF-induced changes at the metabolomic level. Spores of four Fusarium species (Fusarium culmorum, Fusarium graminearum, Fusarium poae, and Fusarium sporotrichioides) were treated with PEF and cultured on potato dextrose agar (PDA) plates. The viability of the Fusarium species was assessed by counting the colony-forming units, and changes in the mycotoxin content and metabolomic fingerprints were evaluated by using UHPLC-HRMS/MS instrumental analysis. For metabolomic data processing and compound identification, the MS-DIAL (v. 4.80)–MS-CleanR–MS-Finder (v. 3.52) software platform was used. As we found out, both fungal viability and the ability to produce mycotoxins significantly decreased after the PEF treatment for all of the species tested. The metabolomes of the treated and untreated fungi showed statistically significant differences, and PEF-associated biomarkers from the classes oxidized fatty acid derivatives, cyclic hexapeptides, macrolides, pyranocoumarins, carbazoles, and guanidines were identified.

Identification of serum biomarkers for cystic echinococcosis in sheep through untargeted metabolomic analysis using LC–MS/MS technology

Abstract Background Echinococcosis is a zoonotic disease caused by an Echinococcus tapeworm infection. While diagnostic methods for humans often rely on ultrasound imaging and immunodiagnostic techniques, diagnosis in intermediate hosts typically has no widely used diagnostic markers, hampering disease control efforts. Methods The differences in serum metabolites of sheep infected with Echinococcus granulosus and a control group were analyzed using ultrahigh-performance liquid chromatography (UHPLC) separation with tandem mass spectrometry (MS/MS) detection. This provided a basis for the early diagnosis and pathogenetic study of cystic echinococcosis (CE) in intermediate hosts at the metabolomics level. Orthogonal projections to latent structures–discriminant analysis (OPLS-DA) were used to analyze different metabolites in the serum of the two groups. The differentially abundant metabolites were entered into the MetaboAnalyst 5.0 online analysis website for processing, and the top-15-ranked metabolic pathways were set to produce bubble plots and differential abundance score plots, with a significant difference of P < 0.05 and a false discovery rate (FDR) < 0.1 as the screening conditions. Results Data analyses of serum samples from both groups identified a total of 1905 significantly different metabolites, where 841 metabolites were upregulated and 1064 metabolites were downregulated. Twelve metabolites were significantly upregulated and 21 metabolites were significantly downregulated in the experimental group. Then, the 1,7-dihydroxyxanthone, 2-methylbutyrylglycine, 3,3-dimethylglutaric acid, 5,12-dihydroxy-6,8,10,14,17-eicosapentaenoic acid, 9-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid, and trimethylamine N-oxide 6 metabolites were selected as diagnostically valuable candidate biomarkers (area under the curve [AUC] > 0.7). These differential metabolites are involved in various metabolic pathways, including amino acid metabolites (arginine, l-isoleucine, l-valine) and fatty acid metabolism (fenugreek, arachidonic acid, linolenic acid). Compared with the control group, sheep in the CE group had increased serum levels of fenugreek acid, while all other metabolites such as glycine showed significantly reduced serum levels (P < 0.01). Conclusions Through non-targeted metabolomic analysis of the serum of CE-infected sheep, differential metabolites closely related to amino acid metabolism and the fatty acid metabolism pathway were identified. These differentially abundant metabolites can serve as biomarkers for diagnosing CE infection in intermediate sheep hosts. Graphical abstract

Tailored culture strategies to promote antimicrobial secondary metabolite production in Diaporthe caliensis: a metabolomic approach

BackgroundIn the search for new antimicrobial secondary metabolites of fungi, optimizing culture conditions remains a critical challenge, as standard laboratory approaches often result in low yields. While non-selective methods, such as modifying culture media, have been effective in expanding the chemical diversity of fungal metabolites, they have not yet established a direct link to key process parameters crucial for further optimization. This study investigates the capacity of Diaporthe caliensis as a biofactory for biologically active secondary metabolites, employing tailored culture media to explore the relationship between chemical diversity and critical process variables.ResultsThe metabolomic profiles, antibacterial activities, and production yields of the extracts were analyzed to progressively adjust the culture conditions. This study was conducted in five steps, evaluating carbon and nitrogen source concentration, nitrogen source type, salt supplementation, and pH adjustment. Altering the rice starch concentration affected biomass yield per unit of oxygen consumed, while modifications to the nitrogen source concentration influenced both the bioactivity and chemical space by Diaporthe caliensis. Despite changes at the metabolome level, the extracts consistently exhibited potent antibacterial activities, influenced by the nitrogen source, added salts and pH adjustments. For instance, when using corn steep liquor and rice starch, supplemented with micronutrients, different metabolites were produced depending on whether buffer or water was used, though both conditions showed similar antibacterial activities (IC50 ≈ 0.10 mg mL− 1 against Staphylococcus aureus and ≈ 0.14 mg mL− 1 against Escherichia coli). In the treatment where buffer was used to stabilize pH change, there was an increase in the production of phomol-like compounds which are associated with known antibiotic properties. In contrast, in the treatments using water, the drop in pH stimulated the production of previously unidentified metabolites with potential antimicrobial activity.ConclusionsThis study proposes a strategic methodology for the tailored formulation of culture media aiming to promote the biosynthesis of diverse secondary metabolites. This approach revealed the critical role of nutrient limitation and pH regulation in stimulating the production of polyketide-lactone derivatives, including the antibiotic phomol. Ultimately, the systematic, custom-designed culture conditions developed in this work offer a promising strategy for expanding the chemical diversity of Diaporthe caliensis, while providing valuable insights into the key parameters needed for optimizing this fungal biofactory.Graphical

Transcriptomic and Metabolomic Analyses of the Piz-t-Mediated Resistance in Rice against Magnaporthe oryzae.

Magnaporthe oryzae causes devastating rice blast disease, significantly impacting rice production in many countries. Among the many known resistance (R) genes, Piz-t confers broad-spectrum resistance to M. oryzae isolates and encodes a nucleotide-binding site leucine-rich repeat receptor (NLR). Although Piz-t-interacting proteins and those in the signal transduction pathway have been identified over the last decade, the Piz-t-mediated resistance has not been fully understood at the transcriptomic and metabolomic levels. In this study, we performed transcriptomic and metabolomic analyses in the Piz-t plants after inoculation with M. oryzae. The transcriptomic analysis identified a total of 15,571 differentially expressed genes (DEGs) from infected Piz-t and wild-type plants, with 2791 being Piz-t-specific. K-means clustering, GO term analysis, and KEGG enrichment pathway analyses of the total DEGs identified five groups of DEGs with distinct gene expression patterns at different time points post inoculation. GO term analysis of the 2791 Piz-t-specific DEGs revealed that pathways related to DNA organization, gene expression regulation, and cell division were highly enriched in the group, especially at early infection stages. The gene expression patterns in the transcriptomic datasets were well correlated with the metabolomic profiling. Broad-spectrum "pathway-level" metabolomic analyses indicated that terpenoid, phenylpropanoid, flavonoid, fatty acid, amino acid, glycolysis/TCA, and phenylalanine pathways were altered in the Piz-t plants after M. oryzae infection. This study offers new insights into the molecular dynamics of transcripts and metabolites in R-gene-mediated resistance against M. oryzae and provides candidates for enhancing rice blast resistance through the engineering of metabolic pathways.

The dynamics of adaptive evolution in microalgae in a high-CO2 ocean.

Marine microalgae demonstrate a notable capacity to adapt to high CO2 and warming in the context of global change. However, the dynamics of their evolutionary processes under simultaneous high CO₂ and warming conditions remain poorly understood. Here, we analyze the dynamics of evolution in experimental populations of a model marine diatom Phaeodactylum tricornutum. We conducted whole-genome resequencing of populations under ambient, high-CO2, warming and high CO2 + warming at 2-yr intervals over a 4-yr adaptation period. The common genes selected between 2- and 4-yr adaptation were found to be involved in protein ubiquitination and degradation and the tricarboxylic acid (TCA) cycle, and were consistently selected regardless of the experimental conditions or adaptation duration. The unique genes selected only by 4-yr adaptation function in respiration, fatty acid, and amino acid metabolism, facilitating adaptation to prolonged high CO2 with warming conditions. Corresponding changes at the metabolomic level, with significant alterations in metabolites abundances involved in these pathways, support the genomic findings. Our study, integrating genomic and metabolomic data, demonstrates that long-term adaptation of microalgae to high CO2 and/or warming can be characterized by a complex and dynamic genetic process and may advance our understanding of microalgae adaptation to global change.

Aging and Pathological Conditions Similarity Revealed by Meta-Analysis of Metabolomics Studies Suggests the Existence of the Health and Age-Related Metapathway.

Background: The incidence of many diseases increases with age and leads to multimorbidity, characterized by the presence of multiple diseases in old age. This phenomenon is closely related to systemic metabolic changes; the most suitable way to study it is through metabolomics. The use of accumulated metabolomic data to characterize this phenomenon at the system level may provide additional insight into the nature and strength of aging-disease relationships. Methods: For this purpose, metabolic changes associated with human aging and metabolic alterations under different pathological conditions were compared. To do this, the published results of metabolomic studies on human aging were compared with data on metabolite alterations collected in the human metabolome database through metabolite set enrichment analysis (MSEA) and combinatorial analysis. Results: It was found that human aging and pathological conditions involve the set of the same metabolic pathways with a probability of 99.96%. These data show the high identity of the aging process and the development of diseases at the metabolic level and allow to identify the set of metabolic pathways reflecting age-related changes closely associated with health. Based on these pathways, a metapathway was compiled, changes in which are simultaneously associated with health and age. Conclusions: The knowledge about the strength of the convergence of aging and pathological conditions has been supplemented by the rigor evidence at the metabolome level, which also made it possible to outline the age and health-relevant place in the human metabolism.

Probing the biocompatibility of Mo2C nanosheet through an integrated metabolomics approach: Toward boosting energy metabolism.

An Mo2C nanosheet is an important two-dimensional nanomaterial with distinguished catalytic activity in biochemical applications. However, detailed information on Mo2C-induced changes in metabolic shifts, biosafety, and molecular mechanisms is insufficient. Integrated metabolomics (including aqueous metabolomics, lipidomics, and spatial metabolomics) has provided an excellent choice with massive bioinformation. In addition, the notion of "nanometabolomics" was first proposed and utilized to refer to these metabolomics studies on the biosafety, biocompatibility, and biological response of nanomaterials. Nanometabolomics innovatively combined nanoscience and metabolomics with massive bioinformation at the molecular level. For instance, in this work, nanometabolomics specialized in probing an Mo2C-induced metabolic shift of human umbilical vein endothelial cells (HUVECs) through integrated metabolomics. Furthermore, integrated metabolomics was used to examine the metabolic shift of HUVECs at the metabolome and lipidome levels, as well as the spatial distribution of different metabolites. The findings demonstrated that high doses (1 mg/ml) of an Mo2C nanosheet might produce an immediate improvement in HUVECs' energy metabolism, which was closely related to the improved morphology and function of mitochondria. The integrated metabolomics outcomes of this unique "Mo2C-cell" system increased our understanding of an Mo2C nanosheet. The proposed new word "nanometabolomics" could also be considered an excellent notion in representing nanomaterial-involved metabolomics studies.

Mutation of the K+ transporter SlHAK5 of tomato alters pistil morphology, ionome, metabolome and transcriptome in flowers.

K+ accumulation in plant tissues is a crucial factor for plant growth and development. The tomato high-affinity K+ transporter SlHAK5 is essential for root K+ acquisition from low external concentrations. It is also involved in K+ accumulation in pollen and plant fertility as slhak5 KO plants show a low rate of pollen germination, impaired pollen tube growth and parthenocarpic fruits. Here, we present a thorough analysis of slhak5 flowers, which showed relevant defects at the anatomic, ionomic, metabolomic and transcriptomic levels. First, slhak5 flowers exhibited shorter styles and enlarged ovaries that, together with a low number of seeds in fruits from slhak5 X WT crosses, indicated an effect of the slhak5 mutation on female fertility. Second, a lower accumulation of Ca2+, as well as of several metabolites such as amino acids, citric acid and sugars, was observed in mutant flowers, whereas indole-3-acetic acid content was increased when compared to the wild-type. Third, RNAseq conducted on pistils and stamens of wild-type and slhak5 plants revealed that transport and signalling pathways are significantly enriched in the gene expression analyses of stamens. Thus, it can be concluded that a functional SlHAK5 transporter is required to maintain appropriate Ca2+, metabolite and gene expression levels in flowers, and its absence leads to important reductions in both male and female fertility.

Changes in blood metabolomes as potential biomarkers for severity and prognosis in doxorubicin-induced heart failure: a study in HER2-positive and HER2-negative breast cancer patients

Abstract Background The use of doxorubicin for breast cancer treatment is often limited due to cardiotoxicity. Doxorubicin was shown to cause the alterations of cardiac metabolome levels in doxorubicin-treated rats. Interestingly, these changes were robustly associated with the development of doxorubicin-induced heart failure. Unfortunately, measurements of cardiac metabolome levels are rarely possible in humans. Hence, non-invasive biomarkers as representatives of doxorubicin-induced heart failure are required in clinical research and practice. Human epidermal growth factor receptor 2 (HER2) is a point of interest in breast cancer treatment. HER2 is associated with tumor aggressiveness. However, it was observed that HER2 protected against systemic oxidative stress and dilated cardiomyopathy. Therefore, we hypothesized that the alterations of blood metabolome levels and cardiac functions following doxorubicin treatment were different between HER2-positive and HER2-negative breast cancer patients. Purpose We determined the potential roles of changes in blood metabolomes as severity and prognostic markers of doxorubicin-induced heart failure. In addition, the changes in blood metabolomes and cardiac parameters following doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients were compared. Methods HER2-positive (n=37) and HER2-negative (n=37) breast cancer patients were enrolled. Echocardiography, heart rate variability, and blood collection were performed at baseline and 2 weeks after completion of doxorubicin treatment in all patients, as well as at 3 months after completion of doxorubicin treatment in HER2-negative breast cancer patients. Blood obtained at all 3 time points was processed for measuring cardiac injury markers. Blood obtained at baseline and 2 weeks after completion of doxorubicin treatment was also processed for measuring oxidative stress in peripheral blood mononuclear cells using flow cytometry and 85 metabolome levels in plasma using mass spectrometry-based targeted metabolomics. Results Cardiac injury and systolic dysfunction at 2 weeks after completion of doxorubicin treatment were comparable between HER2-positive and HER2-negative breast cancer patients. However, only HER2-negative breast cancer patients exhibited increased systemic oxidative stress and cardiac autonomic dysfunction at this time point. Moreover, 33 and 29 blood metabolomes were altered at 2 weeks after completion of doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients, respectively (Figure). Interestingly, the changes in most of these metabolomes were correlated with the changes in cardiac parameters, both at 2 weeks and 3 months after completion of doxorubicin treatment (Figure). Conclusions The changes in blood metabolomes following doxorubicin treatment were dependent on HER2 status, which might be served as severity and prognostic markers of doxorubicin-induced heart failure.

Streptomyces improves sugarcane drought tolerance by enhancing phenylalanine biosynthesis and optimizing the rhizosphere environment

Drought stress is a common hazard faced by sugarcane growth, and utilizing microorganisms to enhance plant tolerance to abiotic stress has become an important method for sustainable agricultural development. Several studies have demonstrated that Streptomyces chartreuses WZS021 improves sugarcane tolerance to drought stress. However, the molecular mechanisms underlying tolerance at the transcriptional and metabolomic levels remain unclear. We comprehensively evaluated the physiological and molecular mechanisms by which WZS021 enhances drought tolerance in sugarcane, by performing transcriptome sequencing and non-targeted metabolomics; and examining rhizosphere soil properties and plant tissue antioxidant capacity. WZS021 inoculation improved the rhizosphere nutritional environment (AP, ammonia, OM) of sugarcane and enhanced the antioxidant capacity of plant roots, stems, and leaves (POD, SOD, CAT). Comprehensive analyses of the transcriptome and metabolome revealed that WZS021 mainly affects plant drought tolerance through phenylalanine metabolism, plant hormone signal transduction, and flavonoid biosynthesis pathways. The drought tolerance signaling molecules mediated by WZS021 include petunidin, salicylic acid, α-Linoleic acid, auxin, geranylgeraniol and phenylalanine, as well as key genes related to plant hormone signaling transduction (YUCCA, amiE, AUX, CYPs, PAL, etc.). Interestingly, inoculation with WZS021 during regular watering induces a transcriptome-level response to biological stress in sugarcane plants. This study further elucidates a WZS021-dependent rhizosphere-mediated regulatory mechanism for improving sugarcane drought tolerance, providing a theoretical basis for increasing sugarcane production capacity.

Trace antibiotic exposure affects murine gut microbiota and metabolism

Gut microbiota is important for host metabolism regulation. Antibiotic exposure disturbs this regulation by affecting the microbiome. Trace levels of antibiotics in water have been widely reported and the impact on gut microbiota remains understudied. We provide evidence of trace antibiotic exposure affecting the host's gut microbiota using a mouse model exposed to trace amounts of azithromycin (AZI) or ciprofloxacin (CIP) in drinking water. AZI exposure in males changed the distribution of gram-positive (Firmicutes and Bacteroidetes) and gram-negative (Proteobacteria, Fusobacteria, and Verrucomicrobia) bacteria at an early age. Both AZI and CIP resulted in abnormal microbiota maturation. Additionally, the production of short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, in females is affected. Serum hormone and metabolome levels shifted after trace antibiotic exposure. AZI and CIP exposure broadly disrupted original host-microbe interaction relationships between the gut microbiota and SCFAs or serum metabolites. In this study, we demonstrated that trace antibiotic exposure was associated with extensive gut microbiota and metabolism perturbation in mice and that the potential health risks in susceptible populations should be considered.

ABA deficiency and its impact on ion and metabolite profiles in tomato roots under single and combined stress conditions

Abscisic acid (ABA) plays a crucial role in the stress response of plants. Although the impact of ABA on individual stresses has been extensively studied, there is less research on its role in plants grown under stress combination, such as salinity and high temperature. This study analyzes the response at the ionomic and metabolomic levels of tomato roots to ABA deficiency under single salinity or heat stress, as well as under the combination of both stresses, using ABA-deficient (flacca, flc) tomato plants. ABA was found to be crucial in ionic regulation, particularly for Na, K, Ca, and other ions such as Cu, Mn, Zn, Mo, and Fe. However, its influence depended on the type of stress applied, indicating the complexity of plant responses to these adverse environmental factors. In our study, phenylpropanoids, terpenoids, and nitrogenous compounds were the metabolites most affected by endogenous ABA concentration and environmental treatment. On the other hand, the application of exogenous ABA to flc mutants did not fully restore root dry weight, although it did cause significant changes at the ionomic and metabolomic levels. Salinity and heat applied in combination aggravated the vulnerability of flc mutants compared to single stresses, making the application of exogenous ABA more effective under single stresses than under the combined stresses. Finally, a correlation analysis between the ionome and metabolome revealed that the accumulation or deficiency of some ions (i.e., Na, Zn, and Fe) was correlated with the abundance of important metabolites related to amino acid biosynthesis and terpenoid metabolism, among others.

Multiomics approach discloses lipids and metabolites profiles associated to Parkinson's disease stages and applied therapies

Profiling circulating lipids and metabolites in Parkinson's disease (PD) patients could be useful not only to highlight new pathways affected in PD condition but also to identify sensitive and effective biomarkers for early disease detection and potentially effective therapeutic interventions. In this study we adopted an untargeted omics approach in three groups of patients (No L-Dopa, L-Dopa and DBS) to disclose whether long-term levodopa treatment with or without deep brain stimulation (DBS) could reflect a characteristic lipidomic and metabolomic signature at circulating level. Our findings disclosed a wide up regulation of the majority of differentially regulated lipid species that increase with disease progression and severity. We found a relevant modulation of triacylglycerols and acyl-carnitines, together with an altered profile in adiponectin and leptin, that can differentiate the DBS treated group from the others PD patients. We found a highly significant increase of exosyl ceramides (Hex2Cer) and sphingoid bases (SPB) in PD patients mainly in DBS group (p < 0.0001), which also resulted in a highly accurate diagnostic performance. At metabolomic level, we found a wide dysregulation of pathways involved in the biosynthesis and metabolism of several amino acids. The most interesting finding was the identification of a specific modulation of L-glutamic acid in the three groups of patients. L-glutamate levels increased slightly in No L-Dopa and highly in L-Dopa patients while decreased in DBS, suggesting that DBS therapy might have a beneficial effect on the glutamatergic cascade. All together, these data provide novel insights into the molecular and metabolic alterations underlying PD therapy and might be relevant for PD prediction, diagnosis and treatment.

Vitamin and zeatin treatments promote colchicine-induced haploid chromosome doubling in maize

Doubled haploid (DH) technology is an efficient method used in commercial maize breeding. Chromosome doubling is a vital step of DH technology; however, the underlying processes regulating chromosome doubling of haploid is still not well understood, which is key to optimize the technology. In this study, the immature haploid embryos of the maize inbred line Zheng58 treated with amiprophos-methyl (APM) or colchicine were used to analyze transcriptomic and metabolomic changes, 75 and 60 differential expressed metabolites (DEMs) were identified between control treatment, respectively. Most differentially expressed genes (DEGs) related to artificial chromosome doubling were down regulated; these were mainly involved in mitosis process. Both DEMs and DEGs co-expression analyses showed that, compared to controls, zeatin biosynthesis and cofactor and vitamin metabolism were significantly enriched in both APM and colchicine treatments. In a parallel experiment, exogenous vitamins including thiamine, nicotinic acid, vitamin B6, or trans-zeatin were added to colchicine treatment; there were synergistic effects between vitamins or zeatin and colchicine in haploid artificial chromosome doubling. These results provide novel insights in exploring the molecular responses to antimitotic reagents at both the transcriptomic and metabolomic levels. In addition, the application efficiency of haploid breeding will be greatly improved by the key factors for artificial chromosome doubling.

Unveiling senescence-associated ocular pathogenesis via lacrimal gland organoid magnetic bioassembly platform and HMGB1-Box A gene therapy

Dry eye disease (DED) is a multifactorial aging disorder leading to tear film insufficiency and instability. Yet, an important knowledge gap lingers in understanding senescence-associated ocular pathogenesis, due to limited in vitro translational lacrimal gland (LG) models. Consequently, this remains a major roadblock to discover effective therapies for the restoration of tear film secretion. Herein, the authors reported the magnetic bioassembly of two LG organoid platforms to recapitulate functional and aging states. Using a proof-of-concept approach, porcine primary LG cells were assembled into organoids via a magnetic 3D bioprinting (M3DB) platform. This platform could form reproducible LG organoids with epithelial hallmarks (AQP5+) and exhibit epithelial secretory functions (lysozyme activity). DNA damage-induced senescence and cell death was induced with etoposide, and LG organoid hypofunction and senescence-associated pathogenesis were observed. To confer DNA protection against aging, a novel gene therapy with Box A domain of high-mobility group box-1 (HMGB1-Box A) previously established by our group, was applied here to prevent LG cellular senescence for the first time. HMGB1-Box A transfection prevented LG organoids from senescence-associated pathogenesis at the transcriptomic, metabolomic and proteomic levels. Thus, M3DB platforms could generate functional and DNA damage-induced senescence LG organoids, and this latter damage could be prevented with HMGB1-Box A gene therapy.

Multi-omics study on the mixed culture of Trichoderma reesei and Aspergillus niger with improved lignocellulase production

The mixed culture of Trichoderma reesei and Aspergillus niger were found to improve lignocellulase production and ameliorate the composition (Fang et al., 2010; Fang et al., 2013; Zhao et al., 2018) [1-3]. However, the mechanism behind remained unclear. Here we conducted multi-omics study of the mixed culture to elucidate the mechanism comprehensively, including proteomics of the secretomes, metabolomics of the fermentation broths and transcriptomics. The mechanisms at transcriptional, proteomic and metabolomic levels were clarified. Proteomics show many proteins in the secretomes were up-regulated by the mix culture of T. reesei and A. niger, and lignocellulase production and the composition were improved, but the protein numbers and abundances of the lignocellulases were reduced. Transcriptomics demonstrate that lignocellulase gene expressions, stress responses and anti-stress were co-regulated in T. reesei, and that most lignocellulase genes in T. reesei were up-regulated and most A. niger lignocellulase genes were down-regulated. Metabolomics reveal the chemicals and the mechanism of the communication between T. reesei and A. niger in the mixed culture for improved lignocellulase production. The secondary metabolites such as p-cresol, nodularin and tolazoline could play important roles. Integrative analyses indicate that the secondary metabolites, stress-response, anti-stress, starch and sucrose metabolism and lignocellulase gene expressions were orchestrated. As a result, the roles of T. reesei and A. niger in the mixed culture were defined. The mechanism of the mixed culture for improved lignocellulase production was obtained, in short T. reesei was the major role and A. niger the minor. This work provides theory and targets as basis to obtain complete understanding of the mechanism and guide engineering of the microbial consortium of T. reesei and A. niger for further improvements.

Integrated transcriptomics and metabolomics reveal the mechanism of polystyrene nanoplastics toxicity to mice

Microplastic (MP) are an emerging environmental pollutant, which has toxic effects on organisms, and it has received extensive attention currently. Studying the transcriptomic and metabolic responses of mice to nanoplastic-contaminated water is critical for understanding molecular-level toxicity of nanoplastics (NPs), but there are few studies on this topic. To analyze the effects of different concentrations of polystyrene (PS) nanoplastic-contaminated water on mice at the transcriptome and metabolism of spleens to study the molecular toxicity. Here, testing of histopathology of spleen of female mice was performed after drinking water containing 0.1 μm PS-NPs (1 mg/mL and 50 mg/mL) at different concentrations for 49 days, respectively. The spleen tissue samples were subjected to metabolome and transcriptome sequencing. Four differentially expressed genes were randomly chosen for qRT-PCR to confirm the correctness of transcriptome sequencing. Common Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that a large number of differential genes and differential metabolites mainly focused on immune, inflammation, neurodegenerative disease, cardiovascular disease, nervous, etc. in the organism systems module; lipid, amino acid, taurine and hypotaurine metabolisms, etc. in the metabolism module; signaling translation, signaling molecules and interaction, and neuroactive ligand-receptor interaction, etc. in the environmental information processing. The results showed that pathway analysis at transcriptome and metabolome levels confirmed that the immune system of mice was affected after drinking water contaminated with polystyrene nanoplastics.

The influence of environment on invasive Carpobrotus sp. populations across genetic clusters

The study aims to explore the natural variation in the metabolome of different populations of the invasive plant Carpobrotus from different genetic clusters and geographical origins to enhance our comprehension of its involvement in the adaptation process and phenotypic diversity. The metabolomic profile of shoots was analysed in four populations from two different genetic clusters (Cluster A: Cádiz and A Lanzada; Cluster B: La Marina and Samil) and two different biogeographical regions in Spain (Atlantic: Samil and A Lanzada; Mediterranean: Cádiz and La Marina), collected in the field and subsequently grown in the greenhouse. In addition, climatic, and physiological parameters were analysed. The Mediterranean populations (Cádiz and La Marina) showed lower initial weight and length measurements in morphological parameters than the Atlantic populations. On the contrary, only root parameters showed significant differences in growth parameters among populations. The analysis of ion levels revealed a consistent pattern of higher concentrations in shoots compared to roots, with significant differences among populations, particularly in sodium (Na+) and chlorides (Cl−) levels. Regarding metabolomic analysis, clear correlations between the metabolome, genetic and climatic conditions of Carpobrotus sp.pl populations are described. Pairwise comparisons using t-tests and Principal Component Analysis (PCA) indicated that the differences in metabolomic profile between the Samil and La Marina populations, which correspond to the same genetic cluster (cluster B), were smaller than in the rest of the comparisons indicating that populations from the same genetic cluster were more similar metabolically than those from the same climatic region. The study identified key metabolites representative of each cluster, with significant differences in amino acids, organic acids, and sugars contributing to the variation among populations. Pathway analysis highlighted the impact of climatic conditions on metabolic pathways, particularly in populations from Cluster A. In conclusion, the different populations were more similar according to the genetic cluster than to the climatic region of origin when studied at the metabolomic level. Consequently, the metabolites more representative of each cluster were also identified.

Nicotinamide riboside modulates the reactive species interactome, bioenergetic status and proteomic landscape in a brain-region-specific manner

Nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), has robust cognitive benefits and alleviates neuroinflammation in Alzheimer's Disease (AD) mouse models without decreasing beta-amyloid plaque pathology. Such effects may be mediated by the reactive species interactome (RSI), at the metabolome level. In this study, we employed in vitro and in vivo models of oxidative stress, aging and AD to profile the effects of NR on neuronal survival, RSI, and the whole proteome characterization of cortex and hippocampus. RSI analysis yielded a complex modulation upon NR treatment. We constructed protein co-expression networks and correlated them to NR treatment and all measured reactive species. We observed brain-area specific effects of NR on co-expressed protein modules of oxidative phosphorylation, fatty acid oxidation, and neurotransmitter regulation pathways, which correlated with RSI components. The current study contributes to the understanding of modulation of the metabolome, specifically after NR treatment in AD and how it may play disease-modifying roles.

Molecular communication between red blood cells of different phenotypes during blood storage in mice.

The cellular and molecular changes during red blood cell (RBC) storage that affect posttransfusion recovery (PTR) remain incompletely understood. We have previously reported that RBCs of different storage biology cross-regulate each other when stored together (co-storage cross-regulation [CSCR]). However, the mechanism of CSCR is unclear. In the current study, we tested the hypothesis that CSCR involves acquisition of molecular signatures associated with PTR. The whole blood compartment of either B6 or FVB mice was biotinylated in vivo prior to blood collection and storage. Bio-B6 or Bio.FVB were stored with RBCs from B6 mice transgenic for green florescent protein (GFP) (B6.GFP). After storage, avidin-magnetic beads were used to simultaneous purify Bio-RBCs (positive selection) and B6.GFPs (negative selection). Isolated populations were analyzed by transfusion to establish PTR, and subjected to metabolomic and proteomic analysis. B6 RBCs acquired molecular signatures associated with stored FVB RBCs at both the metabolomic and proteomic level including metabolites associated with energy metabolism, oxidative stress regulation, and oxidative damage. Mitochondrial signatures were also acquired by B6 RBCs. Protein signatures acquired by B6 RBCs include proteins associated with vesiculation. The data presented herein demonstrate the appearance of multiple molecular changes from poor-storing RBCs in good-storing RBCs during co-storage. Whether this is a result of damage causing intrinsic molecular changes in B6 RBCs or if molecules of FVB RBC origin are transferred to B6 RBCs remains unclear. These studies broaden our mechanistic understanding of RBC storage (in particular) and potentially RBC biology (in general).