PubMed

J Agric Food Chem. 2024 Aug 18. doi: 10.1021/acs.jafc.4c04756. Online ahead of print.ABSTRACTNitrogen (N) is a key factor for plant growth and affects anthocyanin synthesis. This study aimed to clarify the potential mechanisms of N levels (LN, 0 kg·ha-1; MN, 150 kg·ha-1; HN, 225 kg·ha-1) in anthocyanin synthesis and grain quality of colored grain wheat. HN increased the yield component traits and grain morphology traits in colored grain wheat while decreasing the processing and nutrient quality traits. Most quality traits were significantly negatively correlated with the yield composition and morphological traits. Anthocyanin was more accumulated under LN conditions, but other related yield and morphological traits of colored grain wheat declined. The anthocyanin content was the highest in blue wheat, followed by that in purple wheat. Cyanidin-3-O-(6-O-malonyl-β-d-glucoside) and cyanidin-3-O-rutinoside were the predominant anthocyanins in blue and purple wheat. The identified anthocyanin-related metabolites were associated with flavonoid biosynthesis, anthocyanin biosynthesis, and secondary metabolite biosynthesis. Therefore, the study provided information for optimizing nitrogen fertilizer management in producing high quality colored wheat and verified the close relationship between anthocyanin and low N condition.PMID:39155472 | DOI:10.1021/acs.jafc.4c04756

Methods Enzymol. 2024;702:317-352. doi: 10.1016/bs.mie.2024.07.001. Epub 2024 Jul 20.ABSTRACTMicroorganisms, plants, and animals alike have specialized acquisition pathways for obtaining metals, with microorganisms and plants biosynthesizing and secreting small molecule natural products called siderophores and metallophores with high affinities and specificities for iron or other non-iron metals, respectively. This chapter details a novel approach to discovering metal-binding molecules, including siderophores and metallophores, from complex samples ranging from microbial supernatants to biological tissue to environmental samples. This approach, called Native Metabolomics, is a mass spectrometry method in which pH adjustment and metal infusion post-liquid chromatography are interfaced with ion identity molecular networking (IIMN). This rule-based data analysis workflow that enables the identification of metal-binding species based on defined mass (m/z) offsets with the same chromatographic profiles and retention times. Ion identity molecular networking connects compounds that are structurally similar by their fragmentation pattern and species that are ion adducts of the same compound by chromatographic shape correlations. This approach has previously revealed new insights into metal binding metabolites, including that yersiniabactin can act as a biological zincophore (in addition to its known role as a siderophore), that the recently elucidated lepotchelin natural products are cyanobacterial metallophores, and that antioxidants in traditional medicine bind iron. Native metabolomics can be conducted on any liquid chromatography-mass spectrometry system to explore the binding of any metal or multiple metals simultaneously, underscoring the potential for this method to become an essential strategy for elucidating biological metal-binding molecules.PMID:39155117 | DOI:10.1016/bs.mie.2024.07.001

Methods Enzymol. 2024;702:215-227. doi: 10.1016/bs.mie.2024.06.005. Epub 2024 Jul 16.ABSTRACTThe sequencing of microbial genomes has far outpaced their functional annotation. Stable isotopic labeling can be used to link biosynthetic genes with their natural products; however, the availability of the required isotopically substituted precursors can limit the accessibility of this approach. Here, we describe a method for using inverse stable isotopic labeling (InverSIL) to link biosynthetic genes with their natural products. With InverSIL, a microbe is grown on an isotopically substituted medium to create a fully substituted culture, and subsequently, the incorporation of precursors of natural isotopic abundance can be tracked by mass spectrometry. This eliminates issues with isotopically substituted precursor availability. We demonstrate the utility of this approach by linking a luxI-type acyl-homoserine lactone synthase gene in a bacterium that grows on methanol with its quorum sensing signal products. In the future, InverSIL can also be used to link biosynthetic gene clusters hypothesized to produce siderophores with their natural products.PMID:39155113 | DOI:10.1016/bs.mie.2024.06.005

Phytochemistry. 2024 Aug 16:114249. doi: 10.1016/j.phytochem.2024.114249. Online ahead of print.ABSTRACTShort rotation coppices (SRCs) represent an important source of biomass. Since they are grown in various mixtures, SRCs represent an excellent opportunity for assessing the effects of local plant neighbourhoods on their performance. We used a common garden experiment consisting of plots that varied in genotype diversity of SRC willows to test for the effects of chemical traits of individual plants and chemical variation in the plots where they grew on insect herbivory. We also explored whether the composition of willows planted in a plot affected their chemistry. To do this, we performed untargeted metabolomics and quantified various chemical traits related to the total set of metabolites we detected, flavonoids, and salicinoids in four willow genotypes. We measured the leaf herbivory that the plants suffered. The genotypes differed in most chemical traits, yet we found only limited effects of individual traits on herbivory damage. Instead, herbivory damage was positively correlated with structural variation in salicinoids in a plot. When analysing the effects of plot chemical variation on herbivory damage separately for each genotype, we found both positive and negative correlations between the two, suggesting both associational resistance and susceptibility. Finally, we also observed a significant effect of the interaction between genotype and plot composition on structural variation in plant chemistry. Overall, our results suggest that high chemical variation in mixed willow SRCs does not necessarily lower the herbivory damage, possibly due to spillover effects of insect herbivores among genotypes. Our results also show that different genotypes respond differently to plot composition in terms of herbivory damage and chemical composition, which may affect their suitability for growing in mixed stands.PMID:39155032 | DOI:10.1016/j.phytochem.2024.114249

Sci Total Environ. 2024 Aug 16:175592. doi: 10.1016/j.scitotenv.2024.175592. Online ahead of print.ABSTRACTN-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a widely used antioxidant in rubber products, and its corresponding ozone photolysis product N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), have raised public concerns due to their environmental toxicity. However, there is an existing knowledge gap on the toxicity of 6PPD and 6PPD-Q to aquatic plants. A model aquatic plant, Chlorella vulgaris (C. vulgaris), was subjected to 6PPD and 6PPD-Q at concentrations of 50, 100, 200, and 400 μg/L to investigate their effects on plant growth, photosynthetic, antioxidant system, and metabolic behavior. The results showed that 6PPD-Q enhanced the photosynthetic efficiency of C. vulgaris, promoting growth of C. vulgaris at low concentrations (50, 100, and 200 μg/L) while inhibiting growth at high concentration (400 μg/L). 6PPD-Q induced more oxidative stress than 6PPD, disrupting cell permeability and mitochondrial membrane potential stability. C. vulgaris responded to contaminant-induced oxidative stress by altering antioxidant enzyme activities and active substance levels. Metabolomics further identified fatty acids as the most significantly altered metabolites following exposure to both contaminants. In conclusion, this study compares the toxicity of 6PPD and 6PPD-Q to C. vulgaris, with 6PPD-Q demonstrating higher toxicity. This study provides valuable insight into the risk assessment of tire wear particles (TWPs) derived chemicals in aquatic habitats and plants.PMID:39154997 | DOI:10.1016/j.scitotenv.2024.175592

Sci Total Environ. 2024 Aug 16:175588. doi: 10.1016/j.scitotenv.2024.175588. Online ahead of print.ABSTRACTIn light of increasing concerns about microplastic pollution, it is crucial to understand the biological impacts of biodegradable PHB microplastics on marine organisms. This study included a 96-h exposure experiment to assess acute toxicity at PHB concentrations of 0 mg/L, 100 mg/L, 500 mg/L and 1000 mg/L. Additionally, a 60-day feeding trial was conducted with PHB concentrations of 0, 0.5, 1.0 and 2.0 g/kg to evaluate the long-term effects on growth, physiological health and metabolic responses of Litopenaeus vannamei. Results from the exposure experiment indicated that PHB microplastics up to 100 mg/L were non-toxic to shrimp. However, the 60-day feeding trial revealed that higher concentrations led to slight reductions in survival rates and growth performance, indicating a concentration-dependent response. Analysis of antioxidant and immune enzymes showed minimal changes across most parameters. However, increases in malondialdehyde content and lysozyme activity at higher PHB levels suggested a stress response. Microbial analysis indicated higher species richness and greater community diversity in the PHB group compared to controls, as evidenced by Chao1, ACE, Shannon and Simpson indices. Linear discriminant analysis revealed that Enterobacteriales and related taxa were more prevalent in the PHB group, while Rhodobacteraceae and associated taxa dominated the control group. Pathway analysis highlighted enhanced signal transduction, cell mobility and metabolic resource reallocation in response to PHB-induced stress. Integrated transcriptomic and metabolomic analyses revealed significant regulatory changes, especially in lipid metabolism pathways. These findings suggest that while PHB microplastics trigger adaptive metabolic responses in shrimp, they do not cause acute toxicity. Significant variations in intestinal microbiome composition reflect potential shifts in gut health dynamics due to PHB ingestion. This study enhances our understanding of the ecological impacts of microplastics and underscores the necessity for further research into the environmental safety of biodegradable alternatives.PMID:39154993 | DOI:10.1016/j.scitotenv.2024.175588

Gene. 2024 Aug 16:148826. doi: 10.1016/j.gene.2024.148826. Online ahead of print.ABSTRACTDictamnine(DIC), as the key pharmacological component of the classical Chinese herbal medicine cortex dictamni, possesses multiple pharmacological activities such as anti-microbial, anti-allergic, anti-cancer, and anti-inflammatory activities, however it is also the main toxicant of cortex dictamni induced hepatic damage, yet the underlying molecular mechanisms causing hepatic damage are still largely unknown. With the purpose of explore possibilities hepatotoxicity of dictamnine in zebrafish and to identify the key regulators and metabolites involved in the biological process, we administered zebrafish to dictamnine at a sub-lethal dose (<LC10) for 24 h and performed biochemical index tests, pathological observations, metabolomics, and transcriptomics analyses. The results showed that the liver function indexes such as ALT and AST were affected after the exposure treatment with dictamnine, and the hepatic damage, lipid droplet formation, and increased apoptosis were observed in zebrafish by HE, oil red O(ORO), and Acridine orange hydrochloride(AO)staining. Transcriptome sequencing analysis showed that dictamnine exposure could generate 5696 down-regulated and 4936 up-regulated DEGs(Differential Expressed Genes); metabolomics analysis showed that 36 potential biomarkers were disturbed by dictamnine exposure treatment in juvenile zebrafish. Integration of metabolomics data and transcriptomics data showed that Patatin like phospholipase domain containing 3 Gene Patatin Like Phospholipase Domain Containing 3(PNPLA3), Lactase Gene(LCT), and Galactosidase Beta 1(GLB1) genes were involved in the regulation of 12 key potential biomarkers related to Galactose metabolism and Glycerophospholipid metabolism, such as LysoPC(16:0/0:0) and UDP-4-dehydro-6-deoxy-D-glucose, which in turn regulated pathways of Galactose metabolism and Glycerophospholipid metabolism and consequently induced hepatotoxicity. The comprehensive evaluation of the hepatotoxicity induced by dictamnine was realized from multiple levels, perspectives and indexes by the integrated evaluation method of zebrafish modeling, which supported the applicability of zebrafish in the evaluation of hepatotoxicity of traditional Chinese medicine, and supplied the scientific basis for elucidating the molecular mechanism of the hepatotoxicity induced by dictamnine, as well as guided the development of the toxicity-reducing therapies by dictamnine in the future.PMID:39154970 | DOI:10.1016/j.gene.2024.148826

J Lipid Res. 2024 Aug 16:100622. doi: 10.1016/j.jlr.2024.100622. Online ahead of print.ABSTRACTThis prospective observational study compared the 1H NMR blood lipidomes and metabolomes of 71 community-acquired pneumonia (CAP) patients, 75 COVID-19 pneumonia patients, and 75 healthy controls (matched by age and sex) to identify potential biomarkers and pathways associated with respiratory infections. Both pneumonia groups had comparable severity indices, including mortality, invasive mechanical ventilation, and intensive care unit admission rates. COVID-19 pneumonia patients exhibited more pronounced hypolipidemia, with significantly lower levels of total cholesterol and LDL-c compared to CAP patients. Atherogenic lipoprotein subclasses (VLDL-cholesterol, IDL-cholesterol, IDL-triglyceride, and LDL-triglyceride/LDL-cholesterol) were significantly increased in severe cases of both pneumonia types, while lower HDL-c and small, dense HDL particles were associated with more severe illness. Both infected groups showed decreased esterified cholesterol and increased triglycerides, along with reduced phosphatidylcholine, lysophosphatidylcholine, PUFA, omega-3 fatty acids, and DHA. Additionally, infected patients had elevated levels of glucose, lactate, 3-hydroxybutyrate, and acetone, which are linked to inflammation, hypoxemia, and sepsis. Increased levels of branched-chain amino acids, alanine, glycine, and creatine, which are involved in energy metabolism and protein catabolism, were also observed. Neurotransmitter synthesis metabolites like histidine and glutamate were higher in infected patients, especially those with COVID-19. Notably, severe infections showed a significant decrease in glutamine, essential for lymphocyte and macrophage energy. Severity in COVID-19 pneumonia was also associated with elevated glycoprotein levels (glycoprotein A, glycoprotein B, glycoprotein F), indicating an inflammatory state. These findings suggest that metabolomic and lipidomic changes in pneumonia are connected to bioenergetic pathways regulating the immune response.PMID:39154734 | DOI:10.1016/j.jlr.2024.100622

J Mol Cell Cardiol. 2024 Aug 16:S0022-2828(24)00135-4. doi: 10.1016/j.yjmcc.2024.08.002. Online ahead of print.ABSTRACTIt is still debated whether changes in metabolic flux are cause or consequence of contractile dysfunction in non-ischemic heart disease. We have previously proposed a model of cardiac metabolism grounded in a series of six moiety-conserved, interconnected cycles. In view of a recent interest to augment oxygen availability in heart failure through iron supplementation, we integrated this intervention in terms of moiety conservation. Examining published work from both human and murine models, we argue this strategy restores a mitochondrial cycle of energy transfer by enhancing mitochondrial pyruvate carrier (MPC) expression and providing pyruvate as a substrate for carboxylation and anaplerosis. Metabolomic data from failing heart muscle reveal elevated pyruvate levels with a concomitant decrease in the levels of Krebs cycle intermediates. Additionally, MPC is downregulated in the same failing hearts, as well as under hypoxic conditions. MPC expression increases upon mechanical unloading in the failing human heart, as does contractile function. We note that MPC deficiency also alters expression of enzymes involved in pyruvate carboxylation and decarboxylation, increases intermediates of biosynthetic pathways, and eventually leads to cardiac hypertrophy and dilated cardiomyopathy. Collectively, we propose that an unbroken chain of moiety-conserved cycles facilitates energy transfer in the heart. We refer to the transport and subsequent carboxylation of pyruvate in the mitochondrial matrix as an example and a proposed target for metabolic support to reverse impaired contractile function. Since the days of bed rest, digitalis, and diuresis, the management of heart failure has tested many new ideas. Although big strides have been made to delay, or even reverse altered cardiac structure and function by mechanical and pharmacological interventions, it remains unknown whether the metabolic alterations in the failing heart are a cause or consequence of its compromised state of contraction.PMID:39154711 | DOI:10.1016/j.yjmcc.2024.08.002

Crit Rev Oncol Hematol. 2024 Aug 16:104480. doi: 10.1016/j.critrevonc.2024.104480. Online ahead of print.ABSTRACTGastrointestinal (GI) cancer continues to pose a significant global health challenge. Recent advances in our understanding of the complex relationship between the host and gut microbiota have shed light on the critical role of metabolic interactions in the pathogenesis and progression of GI cancer. In this study, we examined how microbiota interact with the host to influence signalling pathways that impact the formation of GI tumours. Additionally, we investigated the potential therapeutic approach of manipulating GI microbiota for use in clinical settings. Revealing the complex molecular exchanges between the host and gut microbiota facilitates a deeper understanding of the underlying mechanisms that drive cancer development. Metabolic interactions hold promise for the identification of microbial signatures or metabolic pathways associated with specific stages of cancer. Hence, this study provides potential strategies for the diagnosis, treatment and management of GI cancers to improve patient outcomes.PMID:39154670 | DOI:10.1016/j.critrevonc.2024.104480

J Reprod Immunol. 2024 Aug 12;165:104315. doi: 10.1016/j.jri.2024.104315. Online ahead of print.ABSTRACTReproductive diseases and illnesses pose significant challenges in cattle farming, affecting fertility, milk production, and overall herd health. In recent years, the integration of various omics approaches, including transcriptomics, proteomics, metagenomics, miRNAomics, and metabolomics, has revolutionized the study of these conditions. This systematic review summarised the findings from studies that investigated reproductive disease biomarkers in both male and female cattle. After extracting 6137 studies according to exclusion and inclusion criteria, a total of 60 studies were included in this review. All studies identified were associated with female cattle and none were related to reproductive diseases in bulls. The analysis highlights specific biomarkers, metabolic pathways, and microbial compositions associated with bovine reproductive disease conditions, providing valuable insights into the underlying molecular mechanisms of disease. Pro-inflammatory cytokines such as IL-1β, IL-8, IL-4, IL-6, TNFα and acute-phase response proteins such as SAA and HP have been identified as promising biomarkers for bovine reproductive diseases. However, further research is needed to validate these markers clinically and to explore potential strategies for improving cow reproductive health. The role of bulls as carriers of venereal diseases has been underestimated in the current literature and therefore needs more attention to understand their impact on infectious reproductive diseases of female cattle.PMID:39154625 | DOI:10.1016/j.jri.2024.104315

EBioMedicine. 2024 Aug 17;107:105279. doi: 10.1016/j.ebiom.2024.105279. Online ahead of print.ABSTRACTBACKGROUND: 1H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals.METHODS: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by 1H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors.FINDINGS: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays. Interestingly, a previously reported multi-analyte score indicating mortality risk (MetaboHealth) could also be accurately reconstructed. Sixteen of our derived surrogates, including the MetaboHealth surrogate, showed significant associations with mortality, independent of relevant covariates.INTERPRETATION: The addition of our metabolic analyte-derived surrogates to the well-established epigenetic clock GrimAge demonstrates that our surrogates potentially represent valuable mortality signal.FUNDING: BBMRI-NL, X-omics, VOILA, Medical Delta, NWO, ERC.PMID:39154540 | DOI:10.1016/j.ebiom.2024.105279

Placenta. 2024 Aug 14;155:78-87. doi: 10.1016/j.placenta.2024.08.009. Online ahead of print.ABSTRACTINTRODUCTION: An early evaluating system for autism spectrum disorder (ASD) severity is crucial. Questionnaire survey is challenging for accurately assessing the severity levels for ASD in children.METHODS: Offspring with ASD-like phenotypes were induced by treating pregnant mice with Poly (I:C) at GD12.5 and the placentae corresponding to the offspring were obtained by caesarean. The autism severity composite score (ASCS) for offspring was calculated through behavioral tests. HE staining and immunohistochemistry were used to observe the morphology of placenta. Candidate biomarkers were identified by weighted protein co-expression network analysis (WPCNA) combined with machine learning and further validated by ELISA. Sperman's was used to analyze the correlation between biomarkers and metabolome.RESULTS: The placental weight and mean vascular area of male offspring with ASD-like phenotypes were significantly decreased compared with typical mice. According to the WPCNA, four modules were identified and significantly correlated with ASCS of offspring. Two biomarkers (ASPG and DAD1) with high correlation with ASCS in offspring were identified.DISCUSSION: VEGF pathway may contribute to sexual dimorphism in placental morphology within mice with ASD-like phenotypes in term. The placental ASPG and DAD1 levels could reflect ASD-like symptom severity levels in male/female mice offspring.PMID:39154487 | DOI:10.1016/j.placenta.2024.08.009

J Hazard Mater. 2024 Aug 14;478:135537. doi: 10.1016/j.jhazmat.2024.135537. Online ahead of print.ABSTRACTFrequent cyanobacterial blooms pose a serious threat to the aquatic ecosystem and human health, so developing an efficient algae removal method is a long-term goal for bloom management. Current technologies for algal bloom control need urgent improvement in terms of algicide recovery, eco-friendliness and cost. Here we propose a contact-electro-catalytic method, using polytetrafluoroethylene (PTFE) film as a reusable catalyst. This contact-electro-catalytic approach involves the generation of reactive oxygen species (e.g., O2•-, HO•, 1O2 and H2O2) through water-PTFE contact electrification under the low-frequency ultrasonic waves, facilitating the inactivation of algae. The removal rate of the cyanobacterium Microcystis aeruginosa (M. aeruginosa) exposured to the water-PTFE contact-electro-catalytic system is almost five times greater than that of ultrasound alone after 5 h. A mechanistic investigation revealed that the contact-electro-catalytic system damaged the photosynthetic activity, antioxidant system and membrane integrity of the cells. Additionally, LC-MS metabolomic analysis indicated that this system caused substantial significant disruptions in the TCA cycle, amino acid metabolism, purine metabolism and phospholipid metabolism. Three-dimensional fluorescence spectroscopy suggested contact-electro-catalysis could further availably degrade the organic matter. We anticipate that this method can provide an eco-friendly, highly efficient and economic approach for effective control of harmful algal blooms.PMID:39154479 | DOI:10.1016/j.jhazmat.2024.135537

Food Chem. 2024 Aug 10;461:140836. doi: 10.1016/j.foodchem.2024.140836. Online ahead of print.ABSTRACTThis study aimed to establish a strategy for identifying dietary intake biomarkers using a non-targeted metabolomic approach, including metabolic pathway and network analysis. The strategy was successfully applied to identify dietary intake biomarkers in fecal samples from pigs fed two doses of a polyphenol-rich fruit and vegetable (FV) diet following the Dietary Guidelines for Americans (DGA) recommendations. Potential biomarkers were identified among dietary treatment groups using liquid chromatography-high resolution mass spectrometry (LC-HRMS) based on a non-targeted metabolomic approach with metabolic pathway and network analysis. Principal component analysis (PCA) results showed significant differences in fecal metabolite profiles between the control and two FV intervention groups, indicating a diet-induced differential fecal metabolite profile after FV intervention. Metabolites from common flavonoids, e.g., (epi)catechin and protocatechuic acid, or unique flavonoids, e.g., 5,3',4'-trihydroxy-3-methoxy-6,7-methylenedioxyflavone and 3,5,3',4'-tetrahydroxy-6,7-methylenedioxyflavone, were identified as highly discriminating factors, confirming their potential as fecal markers for the FV dietary intervention. Microbiota pathway prediction using targeted flavonoids provided valuable and reliable biomarker exploration with high confidence. A correlation network analysis between these discriminatory ion features was applied to find connections to possible dietary biomarkers, further validating these biomarkers with biochemical insights. This study demonstrates that integrating metabolic pathways and network analysis with a non-targeted metabolomic approach is highly effective for rapid and accurate identification and prediction of fecal biomarkers under controlled dietary conditions in animal studies. This approach can also be utilized to study microbial metabolisms in human clinical research.PMID:39154458 | DOI:10.1016/j.foodchem.2024.140836

Vet Res. 2024 Aug 18;55(1):103. doi: 10.1186/s13567-024-01358-y.ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV) is a severe disease with substantial economic consequences for the swine industry. The DEAD-box helicase 3 (DDX3X) is an RNA helicase that plays a crucial role in regulating RNA metabolism, immunological response, and even RNA virus infection. However, it is unclear whether it contributes to PRRSV infection. Recent studies have found that the expression of DDX3X considerably increases in Marc-145 cells when infected with live PRRSV strains Ch-1R and SD16; however, it was observed that inactivated viruses did not lead to any changes. By using the RK-33 inhibitor or DDX3X-specific siRNAs to reduce DDX3X expression, there was a significant decrease in the production of PRRSV progenies. In contrast, the overexpression of DDX3X in host cells substantially increased the proliferation of PRRSV. A combination of transcriptomics and metabolomics investigations revealed that in PRRSV-infected cells, DDX3X gene silencing severely affected biological processes such as ferroptosis, the FoxO signalling pathway, and glutathione metabolism. The subsequent transmission electron microscopy (TEM) imaging displayed the typical ferroptosis features in PRRSV-infected cells, such as mitochondrial shrinkage, reduction or disappearance of mitochondrial cristae, and cytoplasmic membrane rupture. Conversely, the mitochondrial morphology was unchanged in DDX3X-inhibited cells. Furthermore, silencing of the DDX3X gene changed the expression of ferroptosis-related genes and inhibited the virus proliferation, while the drug-induced ferroptosis inversely promoted PRRSV replication. In summary, these results present an updated perspective of how PRRSV infection uses DDX3X for self-replication, potentially leading to ferroptosis via various mechanisms that promote PRRSV replication.PMID:39155369 | DOI:10.1186/s13567-024-01358-y

Cell Rep. 2024 Aug 17;43(8):114631. doi: 10.1016/j.celrep.2024.114631. Online ahead of print.ABSTRACTEnzymatic modification of DNA nucleobases can coordinate gene expression, nuclease protection, or mutagenesis. We recently discovered a clade of phage-specific cytosine methyltransferase (MT) and 5-methylpyrimidine dioxygenase (5mYOX) enzymes that produce 5-hydroxymethylcytosine (5hmC) as a precursor for enzymatic hypermodifications on viral genomes. Here, we identify phage MT- and 5mYOX-associated glycosyltransferases (GTs) that catalyze linkage of diverse sugars to 5hmC nucleobase substrates. Metavirome mining revealed thousands of biosynthetic gene clusters containing enzymes with predicted roles in cytosine sugar hypermodification. We developed a platform for high-throughput screening of GT-containing pathways, relying on the Escherichia coli metabolome as a substrate pool. We successfully reconstituted several pathways and isolated diverse sugar modifications appended to cytosine, including mono-, di-, or tri-saccharides comprised of hexoses, N-acetylhexosamines, or heptose. These findings expand our knowledge of hypermodifications on nucleic acids and the origins of corresponding sugar-installing enzymes.PMID:39154342 | DOI:10.1016/j.celrep.2024.114631

Clin Proteomics. 2024 Aug 17;21(1):54. doi: 10.1186/s12014-024-09504-6.ABSTRACTBACKGROUND: Proteomics and metabolomics offer substantial potential for advancing kidney transplant research by providing versatile opportunities for gaining insights into the biomolecular processes occurring in donors, recipients, and grafts. To achieve this, adequate quality and numbers of biological samples are required. Whilst access to donor samples is facilitated by initiatives such as the QUOD biobank, an adequately powered biobank allowing exploration of recipient-related aspects in long-term transplant outcomes is missing. Rich, yet unverified resources of recipient material are the serum repositories present in the immunological laboratories of kidney transplant centers that prospectively collect recipient sera for immunological monitoring. However, it is yet unsure whether these samples are also suitable for -omics applications, since such clinical samples are collected and stored by individual centers using non-uniform protocols and undergo an undocumented number of freeze-thaw cycles. Whilst these handling and storage aspects may affect individual proteins and metabolites, it was reasoned that incidental handling/storage artifacts will have a limited effect on a theoretical network (pathway) analysis. To test the potential of such long-term stored clinical serum samples for pathway profiling, we submitted these samples to discovery proteomics and metabolomics.METHODS: A mass spectrometry-based shotgun discovery approach was used to obtain an overview of proteins and metabolites in clinical serum samples from the immunological laboratories of the Dutch PROCARE consortium. Parallel analyses were performed with material from the strictly protocolized QUOD biobank.RESULTS: Following metabolomics, more than 800 compounds could be identified in both sample groups, of which 163 endogenous metabolites were found in samples from both biorepositories. Proteomics yielded more than 600 proteins in both groups. Despite the higher prevalence of fragments in the clinical, non-uniformly collected samples compared to the biobanked ones (42.5% vs 26.5% of their proteomes, respectively), these fragments could still be connected to their parent proteins. Next, the proteomic and metabolomic profiles were successfully mapped onto theoretical pathways through integrated pathway analysis, which showed significant enrichment of 79 pathways.CONCLUSIONS: This feasibility study demonstrated that long-term stored serum samples from clinical biorepositories can be used for qualitative proteomic and metabolomic pathway analysis, a notion with far-reaching implications for all biomedical, long-term outcome-dependent research questions and studies focusing on rare events.PMID:39154002 | DOI:10.1186/s12014-024-09504-6

Microbiol Res. 2024 Aug 2;288:127841. doi: 10.1016/j.micres.2024.127841. Online ahead of print.ABSTRACTIn the prospect of novel potential biocontrol agents, a new strain BDI-IS1 belonging to the recently described Bacillus nakamurai was selected for its strong in vitro antimicrobial activities against a range of bacterial and fungal phytopathogens. Genome mining coupled with metabolomics revealed that BDI-IS1 produces multiple non-ribosomal secondary metabolites including surfactin, iturin A, bacillaene, bacillibactin and bacilysin, together with some some ribosomally-synthesized and post-translationally modified peptides (RiPPs) such as plantazolicin, and potentially amylocyclicin, bacinapeptin and LCI. Reverse genetics further showed the specific involvement of some of these compounds in the antagonistic activity of the strain. Comparative genomics between the five already sequenced B. nakamurai strains showed that non-ribosomal products constitute the core metabolome of the species while RiPPs are more strain-specific. Although the secondary metabolome lacks some key bioactive metabolites found in B. velezensis, greenhouse experiments show that B. nakamurai BDI-IS1 is able to protect tomato and maize plants against early blight and northern leaf blight caused by Alternaria solani and Exserohilum turcicum, respectively, at levels similar to or better than B. velezensis QST713. The reduction of these foliar diseases, following root or leaf application of the bacterial suspension demonstrates that BDI-IS1 can act by direct antibiosis and by inducing plant defence mechanisms. These findings indicate that B. nakamurai BDI-IS1 can be considered as a good candidate for biocontrol of plant diseases prevailing in tropical regions, and encourage further research into its spectrum of activity, its requirements and the conditions needed to ensure its efficacy.PMID:39153465 | DOI:10.1016/j.micres.2024.127841

Ecotoxicol Environ Saf. 2024 Aug 16;284:116891. doi: 10.1016/j.ecoenv.2024.116891. Online ahead of print.ABSTRACTShrimp are non-negligible victims of cadmium (Cd) contamination, and there is still a lack of strategies for mitigating Cd toxicity in shrimp. Bacillus cereus, with its significant heavy metal (HM) tolerance and chelating effects, is a representative beneficial bacterium to be investigated for mitigating the toxicity of Cd exposure. This study revealed the effects and potential mechanisms of B. cereus in mitigating chronic Cd toxicity in shrimp by analyzing growth performance, hepatopancreatic Cd accumulation, pathology, as well as comprehensive hepatopancreatic transcriptomics and metabolomics in Litopenaeus vannamei. The results showed that shrimp's growth inhibition, hepatopancreatic Cd accumulation and physiological structure damage in B. cereus+chronic Cd group were effectively alleviated compared with the chronic Cd treatment group. The pathways related to amino acid metabolism, glycolipid metabolism, immune response, and antioxidant stress were significantly activated in the B. cereus+chronic Cd group, including glycolysis, pentose phosphate pathway, oxidative phosphorylation, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids pathways. The key differentially expressed genes (e.g., macrophage migration inhibitory factor, glycine cleavage system H protein, glycine dehydrogenase, phosphoglucomutase-2, asparaginase, ATP synthase subunit, cytochrome c, and 4-hydroxyphenylpyruvate dioxygenase) and metabolites (e.g., L-leucine, D-ribose, gluconic acid, 6-Phosphogluconic acid, sedoheptulose 7-phosphate, 1-Kestose, glyceric acid, arachidic acid, prostaglandins, 12-Keto-tetrahydro-leukotriene B4, and gamma-glutamylcysteine) associated with the above pathways were significantly altered. This study demonstrated that B. cereus is an effective mitigator for the treatment of chronic Cd poisoning in shrimp. B. cereus may play a role in alleviating the toxicity of Cd by enhancing the antioxidant performance, immune defense ability, metabolic stability, and energy demand regulation of shrimp. The study provides reference materials for the study of B. cereus in alleviating Cd toxicity of shrimp and broadens the application of probiotics in treating HM toxicity.PMID:39153280 | DOI:10.1016/j.ecoenv.2024.116891