PubMed

BMC Genomics. 2024 Oct 29;25(1):1014. doi: 10.1186/s12864-024-10785-2.ABSTRACTBACKGROUND: Ophiocordyceps sinensis (O. sinensis) is the dominant bacterium in the asexual stage of Chinese cordyceps, and its growth usually suffers from water stress. Thus, simulating its ecological growth environment is crucial for artificial cultivation. This study aimed to reveal the mechanism underlying the water stress tolerance of Ophiocordyceps sinensis (O. sinensis) by combining metabolomic and transcriptome analyses to identify crucial pathways related to differentially expressed genes (DEGs) and metabolites (DEMs) involved in the response to water stress.RESULTS: Gene coexpression analysis revealed that many genes related to 'betalain biosynthesis', 'tyrosine metabolism', 'linoleic acid metabolism', 'fructose and mannose metabolism', and 'starch and sucrose metabolism' were highly upregulated after 20d-water stress. Metabolomic analysis revealed that many metabolites regulated by these genes in these metabolic pathways were markedly decreased. On the one hand, we surmised that carbohydrate metabolism and the β-oxidation pathway worked cooperatively to generate enough acyl-CoA and then entered the TCA cycle to provide energy when exposed to water stress. On the other hand, the betalain biosynthesis and tyrosine metabolism pathway might play crucial roles in response to water stress in O. sinensis by enhancing cell osmotic potential and producing osmoregulatory substances (betaine) and antioxidant pigments (eumelanin).CONCLUSIONS: Overall, our findings provide important information for further exploration of the mechanism underlying the water stress tolerance of O. sinensis for the industrialization of artificial cultivation of Chinese cordyceps.PMID:39472792 | DOI:10.1186/s12864-024-10785-2

BMC Plant Biol. 2024 Oct 29;24(1):1025. doi: 10.1186/s12870-024-05700-6.ABSTRACTBACKGROUND: Mango is a tropical fruit with high economic value. The selection of suitable dwarf mango varieties is an important aspect of mango breeding. However, the mechanisms that regulate mango dwarfing remain unclear.RESULTS: In this study, we compared the transcriptomes and metabolomes of mango varieties Guiqi (a dwarfed variety) and Jinhuang (an arborized variety). A total of 4,954 differentially expressed genes and 317 differentially abundant metabolites were identified between the two varieties, revealing the molecular mechanism of the gibberellin 3β-hydroxylase gene GA3ox in regulating dwarfing traits in mangoes using joint transcriptome and metabolome analyses. The results showed that differentially expressed genes were enriched in the diterpenoid biosynthesis pathway and that differentially abundant metabolites were annotated to their upstream pathway, the terpenoid backbone biosynthesis. A gene regulation network based on these two pathways was constructed, indicating the upregulation of the GA3ox gene and the accumulation of gibberellin in dwarfed mangoes. We then transferred the GA3ox gene to tobacco plants following the application of gibberellin, and the morphology and height of the transgenic tobacco plants largely recovered the phenotype.CONCLUSIONS: These results demonstrated that GA3ox plays a role in the regulation of dwarf traits. Our study provides an important theoretical basis for studying the regulatory mechanisms underlying mango dwarfism to facilitate mango breeding.PMID:39472789 | DOI:10.1186/s12870-024-05700-6

Commun Biol. 2024 Oct 29;7(1):1411. doi: 10.1038/s42003-024-07075-8.NO ABSTRACTPMID:39472761 | DOI:10.1038/s42003-024-07075-8

Cell Death Differ. 2024 Oct 29. doi: 10.1038/s41418-024-01406-2. Online ahead of print.ABSTRACTOxaliplatin-based therapeutics is a widely used treatment approach for hepatocellular carcinoma (HCC) patients; however, drug resistance poses a significant clinical challenge. Epigenetic modifications have been implicated in the development of drug resistance. In our study, employing siRNA library screening, we identified that silencing the m6A writer METTL3 significantly enhanced the sensitivity to oxaliplatin in both in vivo and in vitro HCC models. Further investigations through combined RNA-seq and non-targeted metabolomics analysis revealed that silencing METTL3 impeded the pentose phosphate pathway (PPP), leading to a reduction in NADPH and nucleotide precursors. This disruption induced DNA damage, decreased DNA synthesis, and ultimately resulted in cell cycle arrest. Mechanistically, METTL3 was found to modify E3 ligase TRIM21 near the 3'UTR with N6-methyladenosine, leading to reduced RNA stability upon recognition by YTHDF2. TRIM21, in turn, facilitated the degradation of the rate-limiting enzyme of PPP, G6PD, through the ubiquitination-proteasome pathway. Importantly, high expression of METTL3 was significantly associated with adverse prognosis and oxaliplatin resistance in HCC patients. Notably, treatment with the specific METTL3 inhibitor, STM2457, significantly improved the efficacy of oxaliplatin. These findings underscore the critical role of the METTL3/TRIM21/G6PD axis in driving oxaliplatin resistance and present a promising strategy to overcome chemoresistance in HCC.PMID:39472692 | DOI:10.1038/s41418-024-01406-2

Sci Rep. 2024 Oct 29;14(1):25948. doi: 10.1038/s41598-024-77436-0.ABSTRACTAlthough ethyl formate (EF) fumigant and low temperature applications are widely used for pest management, studies related to their mechanisms of action and subsequent metabolic changes in Drosophila suzukii models are still unclear. In this study, a comparative metabolome analysis was performed to investigate the major metabolites modified by EF and low temperature and how they are related to and affect insect physiology. Most of the identified metabolites function in metabolic pathways related to the biosynthesis of amino acids, nucleotides and cofactors. In addition, a combined treatment with EF and low temperature significantly altered the tricarboxylic acid cycle (TCA) and the levels of the purine and pyrimidine classes of metabolites. Interestingly, the levels of cytochrome P450 and glutathione metabolites involved in detoxification dramatically changed under stress conditions compared to those in the control group.PMID:39472532 | DOI:10.1038/s41598-024-77436-0

Oncogene. 2024 Oct 29. doi: 10.1038/s41388-024-03191-1. Online ahead of print.ABSTRACTSystemic levels of methylmalonic acid (MMA), a byproduct of propionate metabolism, increase with age and MMA promotes tumor progression via its direct effects in tumor cells. However, the role of MMA in modulating the tumor ecosystem remains to be investigated. The proliferation and function of CD8+ T cells, key anti-tumor immune cells, declines with age and in conditions of vitamin B12 deficiency, which are the two most well-established conditions that lead to increased systemic levels of MMA. Thus, we hypothesized that increased circulatory levels of MMA would lead to a suppression of CD8+ T cell immunity. Treatment of primary CD8+ T cells with MMA induced a dysfunctional phenotype characterized by robust immunosuppressive transcriptional reprogramming and marked increases in the expression of the exhaustion regulator, TOX. Accordingly, MMA treatment upregulated exhaustion markers in CD8+ T cells and decreased their effector functions, which drove the suppression of anti-tumor immunity in vitro and in vivo. Mechanistically, MMA-induced CD8+ T cell exhaustion was associated with a suppression of NADH-regenerating reactions in the TCA cycle and concomitant defects in mitochondrial function. Thus, MMA has immunomodulatory roles, thereby highlighting MMA as an important link between aging, immune dysfunction, and cancer.PMID:39472497 | DOI:10.1038/s41388-024-03191-1

Nat Commun. 2024 Oct 29;15(1):9330. doi: 10.1038/s41467-024-52909-y.ABSTRACTDietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data from Drosophila Genetic Reference Panel (DGRP) strains raised under AL and DR conditions, combining metabolomic, phenotypic, and genome-wide information. We employed two computational and complementary methods across species-random forest modeling within the DGRP as our primary analysis and Mendelian randomization in human cohorts as a secondary analysis. We pinpointed key traits with cross-species relevance as well as underlying heterogeneity and pleiotropy that influence lifespan and healthspan. Notably, orotate was linked to parental age at death in humans and blocked the DR lifespan extension in flies, while threonine supplementation extended lifespan, in a strain- and sex-specific manner. Thus, utilizing natural genetic variation data from flies and humans, we employed a systems biology approach to elucidate potential therapeutic pathways and metabolomic targets for diet-dependent changes in lifespan and healthspan.PMID:39472442 | DOI:10.1038/s41467-024-52909-y

Chem Biodivers. 2024 Oct 29:e202402227. doi: 10.1002/cbdv.202402227. Online ahead of print.ABSTRACTOcotea is an important genus of Lauraceae plant family that comprises over 400 species, many of which pose challenges in taxonomic differentiation due to their complex botanical characteristics. Chemosystematics, and more recently, chemophenetics, have emerged as valuable tools to address these challenges based on their natural products (NPs) composition. O. diospyrifolia (Meisn.) Mez is a poorly studied species with known pharmacological potential. Here, we applied ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS) allied to a curated in-house database with all previous isolated NPs from the Ocotea genus (OcoteaDB), gas phase fragmentations reactions, and biosynthesis. The strategy resulted in compounds annotated in confidence levels 2 (n=27), 3 (n=231), and 4 (n=21) according to the Metabolomics Standards Initiative (MSI). Additional annotations based on fragmentation proposals (n=16) were also included. The study revealed that O. diospyrifolia is a great alkaloid producer, even though different lignoids, which also comes from the shikimate pathway, were annotated. Additionally, the flavonoid profile predominantly consists of flavonol glycosides, complementing prior reports. This study provides the first comprehensive chemical profile of O. diospyrifolia leaves, which corroborates the chemotaxonomy of the species, and also contributes to further characterization studies, as the UHPLC-HRMS data is publicly available.PMID:39472301 | DOI:10.1002/cbdv.202402227

Sci Total Environ. 2024 Oct 27:177135. doi: 10.1016/j.scitotenv.2024.177135. Online ahead of print.ABSTRACTDrylands are home to over 38 % of the world's population and are among the areas most sensitive to climate change and human activity. Most xerophytes rely on arbuscular mycorrhizal fungi (AMF) for improved drought tolerance. Although research has focused on crops and economically significant plants, the response of sand-fixation shrubs to AMF under drought conditions remains underexplored. This study aims to investigate how AMF affects the drought adaptation strategies of the sand-fixation shrub Artemisia ordosica. A culture system for A. ordosica and the main symbiotic partner Funneliformis mosseae was established, and phenotypic, metabolomic, and transcriptomic analyses were conducted to assess physiological changes induced by arbuscular mycorrhizal symbiosis (AMS) under varying drought stress conditions. AMS influenced A. ordosica's metabolic pathways and its drought adaptation strategies, promoted the redistribution of sugars and flavonoids, and shaped different metabolic patterns of seedlings and adult A. ordosica. AMS had an important shaping ability in the accumulation of proline at A. ordosica seedlings, but had a significant influence on the accumulation of sugars of A. ordosica at the adult growth stage. AMS enhanced the ability of the host to adapt to extreme drought by modulating metabolites at the adult growth stage of A. ordosica. AMS also facilitated an accumulation of key metabolites under well-watered conditions but also intensified interactions with pathogens, leading to a trade-off between drought adaptation and immune capacity under extreme drought of A. ordosica during the adult growth stage. This study uses metabolome and transcriptome methods to explore AMS effects on A. ordosica's drought adaptation strategies, revealing a significant trade-off between drought adaptation and immune capacity. The findings highlight AMS's role in modifying the drought adaptation strategies of A. ordosica in desert ecosystems, and enhance our understanding of key species for sand fixation and ecological restoration, and maintain ecological security.PMID:39471960 | DOI:10.1016/j.scitotenv.2024.177135

Clin Chim Acta. 2024 Oct 27:120022. doi: 10.1016/j.cca.2024.120022. Online ahead of print.ABSTRACTBACKGROUND: Bladder cancer (BC) is a common malignant tumour of the urinary system. Currently, the gold standard for diagnosing BC is cystoscopy, but it is an invasive examination that can lead to a certain psychological burden on the patient. In this study, we aimed to identify non-invasive potential metabolic biomarkers that could improve the diagnostic accuracy of bladder cancer.METHODS: Urine from 30 healthy people and 50 BC patients, including 40 non-muscle-invasive bladder cancer (NMIBC) patients and 10 muscle-invasive bladder cancer (MIBC) patients, were analyzed by liquid chromatography coupled with mass spectrometry to identify potential diagnostic metabolites. Binary Logistic regression was used to construct biomarker panels. Correlation analysis and construction of compound-reaction-enzyme-gene network were also performed to explore the possible mechanisms of BC development.RESULTS: Twenty-six metabolites were identified for differentiating BC patients from healthy controls, and eight metabolites were identified for differentiating NMIBC patients form MIBC patients. The biomarker panel consisting of urate, 4-Androstene-3α, 17β-diol and 3-Indoxyl sulfate can distinguish well between BC patients and healthy controls, with an area under the ROC curve (AUC) value of 0.983. And the biomarker panel consisting of L-Octanoylcarnitine, γ-Glutamylleucine, and heptanoylcarnitine for distinguishing NMIBC patients from MIBC patients had an AUC value of 0.941.CONCLUSIONS: The diagnostic capability of the biomarker panels are superior to that of any single potential biomarker. This panel significantly benefits bladder cancer diagnostics and reveals insight into bladder cancer pathogenesis.PMID:39471892 | DOI:10.1016/j.cca.2024.120022

Benef Microbes. 2024 Oct 25:1-15. doi: 10.1163/18762891-bja00048. Online ahead of print.ABSTRACTCow's milk protein allergy (CMPA) in infancy is associated with intestinal microbial dysbiosis, characterised by low Bifidobacteriaceae levels. The present study aimed to investigate the impact of two human milk oligosaccharides (HMO), lactose (L), and their combination on the faecal microbiome and metabolome of infants with CMPA. Stool samples of 12 term infants with probable CMPA (mean age 4.3 months) were analysed using a validated intestinal fermentation assay (SIFR® technology). For each substrate (i.e. HMO (2'-fucosyllactose [2'-FL] and lacto-N-neotetraose [LNnT]), L and HMO + L), taxonomic microbiome characterisation and untargeted metabolite profiling were performed at multiple timepoints. At baseline, the tested faecal microbiota overall displayed low abundances of Bifidobacteriaceae. Fermentation with either HMO or lactose significantly enriched Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium pseudocatenulatum and, for HMO + L, also Bifidobacterium bifidum. The increase in HMO-utilising bifidobacteria was associated with a significant rise in levels of short-chain fatty acids, aromatic lactic acids and N-acetylated amino acids, with additive effects being observed for HMO + L. The above data suggest that the combination of 2'-FL, LNnT and lactose helps to alleviate the previously reported CMPA-associated intestinal bacterial dysbiosis and induces the production of several beneficial metabolites. The clinical significance of these findings for infants with CMPA requires further investigation.PMID:39471839 | DOI:10.1163/18762891-bja00048

Cell Metab. 2024 Oct 25:S1550-4131(24)00409-1. doi: 10.1016/j.cmet.2024.10.013. Online ahead of print.ABSTRACTHepatic de novo lipogenesis (DNL) is a fundamental physiologic process that is often pathogenically elevated in metabolic disease. Treatment is limited by incomplete understanding of the metabolic pathways supplying cytosolic acetyl-CoA, the obligate precursor to DNL, including their interactions and proportional contributions. Here, we combined extensive 13C tracing with liver-specific knockout of key mitochondrial and cytosolic proteins mediating cytosolic acetyl-CoA production. We show that the mitochondrial pyruvate carrier (MPC) and ATP-citrate lyase (ACLY) gate the major hepatic lipogenic acetyl-CoA production pathway, operating in parallel with acetyl-CoA synthetase 2 (ACSS2). Given persistent DNL after mitochondrial citrate carrier (CiC) and ACSS2 double knockout, we tested the contribution of exogenous and leucine-derived acetoacetate to acetoacetyl-CoA synthetase (AACS)-dependent DNL. CiC knockout increased acetoacetate-supplied hepatic acetyl-CoA production and DNL, indicating that ketones function as mitochondrial-citrate reciprocal DNL precursors. By delineating a mitochondrial-cytosolic DNL substrate supply network, these findings may inform strategies to therapeutically modulate DNL.PMID:39471817 | DOI:10.1016/j.cmet.2024.10.013

EBioMedicine. 2024 Oct 28;109:105427. doi: 10.1016/j.ebiom.2024.105427. Online ahead of print.ABSTRACTBACKGROUND: The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms.METHODS: We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts).FINDINGS: The ICI benefit group was enriched for propionate (P = 0.01) and butyrate/isobutyrate (P = 0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P < 0.001, butyrate/isobutyrate P = 0.002). The acetyl-CoA pathway (P = 0.02) in beneficial species mainly mediated butyrate production. Microbiota sequences from irAE patients aligned with antigenic epitopes found in autoimmune diseases. Microbiotas of responsive patients contained more lung cancer-related antigens (P = 0.07), which was validated in the Routy cohort (P = 0.02). Escherichia coli and SGB15342 of Faecalibacterium prausnitzii showed strain-level variations corresponding to clinical phenotypes. Metabolome validation reviewed more abundant acetic acid (P = 0.03), propionic acid (P = 0.09), and butyric acid (P = 0.02) in the benefit group than the resistance group, and patients with higher acetic, propionic, and butyric acid levels had a longer progression-free survival and lower risk of tumor progression after adjusting for histopathological subtype and stage (P < 0.05).INTERPRETATION: Long-term ICI survivors have coevolved a compact microbial community with high butyrate production, and molecular mimicry of autoimmune and tumor antigens by microbiota contribute to outcomes. These results not only characterize the gut microbiotas of patients who benefit long term from ICIs but pave the way for "smart" fecal microbiota transplantation. Registered in the Chinese Clinical Trial Registry (ChiCTR2000032088).FUNDING: This work was supported by Beijing Natural Science Foundation (7232110), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-072, 2023-PUMCH-C-054), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-010).PMID:39471749 | DOI:10.1016/j.ebiom.2024.105427

Mult Scler Relat Disord. 2024 Oct 15;92:105942. doi: 10.1016/j.msard.2024.105942. Online ahead of print.ABSTRACTMultiple sclerosis (MS) remains a challenging neurological condition for diagnosis and management and is often detected in late stages, delaying treatment. Artificial intelligence (AI) is emerging as a promising approach to extracting MS information when applied to different patient datasets. Given the critical role of metabolites in MS profiling, metabolomics data may be an ideal platform for the application of AI to predict disease. In the present study, a machine-learning (ML) approach was used for a detailed analysis of metabolite profiles and related pathways in patients with MS and healthy controls (HC). This approach identified unique alterations in biochemical metabolites and their correlation with disease severity parameters. To enhance the efficiency of using metabolic profiles to determine disease severity or the presence of MS, we trained an AI model on a large volume of blood-based metabolomics datasets. We constructed this model using an artificial neural network (ANN) architecture with perceptrons. Data were divided into training, validation, and testing sets to determine model accuracy. After training, accuracy reached 87 %, sensitivity was 82.5 %, specificity was 89 %, and precision was 77.3 %. Thus, the developed model seems highly robust, generalizable with a wide scope and can handle large amounts of data, which could potentially assist neurologists. However, a large multicenter cohort study is necessary for further validation of large-scale datasets to allow the integration of AI in clinical settings for accurate diagnosis and improved MS management.PMID:39471746 | DOI:10.1016/j.msard.2024.105942

Talanta. 2024 Oct 21;283:127083. doi: 10.1016/j.talanta.2024.127083. Online ahead of print.ABSTRACTEndometrial cancer (EC) is the most prevalent cancer within the female reproductive system in developed countries. Despite its high incidence, there is currently no established laboratory screening test for EC, making early detection challenging. This study introduces an innovative, minimally invasive, and cost-effective method utilizing three-dimensional fluorescence analysis combined with machine learning algorithms to enhance early EC detection. Intrinsic fluorescence of blood serum samples was measured using a luminescence spectrophotometer, which captured fluorescence spectra as synchronous excitation spectra and visualized them through wavelength contour matrices. The spectral data were processed using machine learning algorithms, including Random Forest (RF), Logistic Regression (LR), Support Vector Machine (SVM), and Stochastic Gradient Descent (SGD), along with exploratory techniques such as Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA). Fluorescence ratios R300/330 and R360/490, indicative of altered tryptophan metabolism and redox state changes, were identified as fluorescent spectral markers and represent key metabolic biomarkers. These ratios demonstrated high diagnostic efficacy with AUC values of 0.88 and 0.91, respectively. Among the ML algorithms, LR and RF exhibited high sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), showing significant promise for clinical application. After optimization, LR achieved a sensitivity of 0.94, specificity of 0.89, and an impressive AUC value of 0.94. The application of this novel approach in laboratory diagnostics has the potential to significantly enhance early detection and improve prognosis for EC patients.PMID:39471720 | DOI:10.1016/j.talanta.2024.127083

Redox Biol. 2024 Oct 18;78:103401. doi: 10.1016/j.redox.2024.103401. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is an inflammatory autoimmune disease mediated by immune cell dysfunction for which there is no universally effective prevention and treatment strategy. As primary effector cells, neutrophils are important in the inflammatory joint attack during the development of RA. Here, we used single-cell sequencing technology to thoroughly analyze the phenotypic characteristics of bone marrow-derived neutrophils in type II collagen (COL2)-induced arthritis (CIA) models, including mice primed and boosted with COL2. We identified a subpopulation of neutrophils with high expression of neutrophil cytoplasmic factor 1 (NCF1) in primed mice, accompanied by a characteristic reactive oxygen species (ROS) response, and a decrease in Ncf1 expression in boosted mice with the onset of arthritis. Furthermore, we found that after ROS reduction, arthritis occurred in primed mice but was attenuated in boosted mice. This bidirectional effect of ROS suggested a protective role of ROS during immune priming. Mechanistically, we combined functional assays and metabolomics identifying Ncf1-deficient neutrophils with enhanced migration, chemotactic receptor CXCR2 expression, inflammatory cytokine secretion, and Th1/Th17 differentiation. This alteration was mainly due to the metabolic reprogramming of Ncf1-deficient neutrophils from an energy supply pathway dominated by gluconeogenesis to an inflammatory immune pathway associated with the metabolism of histidine, glycine, serine, and threonine signaling, which in turn induced arthritis. In conclusion, we have systematically identified the functional and inflammatory phenotypic characteristics of neutrophils under ROS regulation, which provides a theoretical basis for understanding the pathogenesis of RA, to further improve prevention strategies and identify novel therapeutic targets.PMID:39471640 | DOI:10.1016/j.redox.2024.103401

J Hazard Mater. 2024 Oct 28;480:136306. doi: 10.1016/j.jhazmat.2024.136306. Online ahead of print.ABSTRACTF53B (6:2 chlorinated polyfluorinated ether sulfonate), a substitute for perfluorooctane sulfonate (PFOS), is widely used as a chromium mist inhibitor in the electroplating industry. However, significant concern has arisen owing to its biological toxicity. Several studies on F53B toxicity in mammals have focused on hepatotoxicity, immunotoxicity, developmental toxicity, and reproductive toxicity, while its neurotoxic effects, especially in relation to neurodegenerative diseases such as Parkinson's disease (PD), remain unclear. In this study, we investigated the neurotoxic effects of F53B on dopaminergic neurons and explored its potential risk associated with PD in a cellular model. Potential target prediction and validation experiments demonstrated that F53B induced apoptosis in dopaminergic neurons. We also discovered that F53B triggered oxidative stress and inflammatory responses, and stimulated nitric oxide (NO) generation in the PD cellular model. Subsequently, untargeted metabolomics and lipidomics approaches were integrated to explore the molecular mechanisms underlying the response of dopaminergic neurons to F53B exposure. The results suggested that F53B disrupted arginine and proline metabolism, energy metabolism, and caused lipid dysregulation, particularly promoting the hydrolysis of sphingomyelin (SM) into ceramide (Cer). Overall, this study provides evidence that F53B exposure could increase the potential risk of PD and offers novel insights into its neurotoxicity mechanisms.PMID:39471628 | DOI:10.1016/j.jhazmat.2024.136306

Microbiol Res. 2024 Oct 22;290:127933. doi: 10.1016/j.micres.2024.127933. Online ahead of print.ABSTRACTPseudomonads are well-known for their plant growth-promoting properties and biocontrol capabilities against microbial pathogens. Recently, their potential to protect crops from parasitic plants has garnered attention. This study investigates the potential of different Pseudomonas strains to inhibit broomrape growth and to protect host plants against weed infestation. Four Pseudomonas strains, two P. fluorescens JV391D17 and JV391D10, one P. chlororaphis JV395B and one P. ogarae F113 were cultivated using various carbon sources, including fructose, pyruvate, fumarate, and malate, to enhance the diversity of potential Orobanche growth inhibition (OGI)-specialized metabolites produced by Pseudomonas strains. Both global and targeted metabolomic approaches were utilized to identify specific OGI metabolites. Both carbon sources and Pseudomonas genetic diversity significantly influenced the production of OGI metabolites. P. chlororaphis JV395B and P. ogarae F113 produced unique OGI metabolites belonging to different chemical families, such as hydroxyphenazines and phloroglucinol compounds, respectively. Additionally, metabolomic analyses identified an unannotated potential OGI ion, M375T65. This ion was produced by all Pseudomonas strains but was found to be over-accumulated in JV395B, which likely explains its superior OGI activity. Then, greenhouse experiments were performed to evaluate the biocontrol efficacy of selected strains: they showed the efficacy of these strains, particularly JV395B, in reducing broomrape infestation in rapeseed. These findings suggest that certain Pseudomonas strains, through their metabolite production, can offer a sustainable biocontrol strategy against parasitic plants. This biocontrol activity can be optimized by environmental factors, such as carbon amendments. Ultimately, this approach presents a promising alternative to chemical herbicides.PMID:39471583 | DOI:10.1016/j.micres.2024.127933

Food Chem. 2024 Oct 21;464(Pt 2):141740. doi: 10.1016/j.foodchem.2024.141740. Online ahead of print.ABSTRACTThis study aimed to unraveling the color evolution and metabolic pathways of pelargonidin-3-O-glucoside (P3G) during lactic acid fermentation of the strawberry juice color simulation system. The results revealed that fermentation with both Lactobacillus plantarum and Lactobacillus acidophilus caused a decline in pH of the strawberry juice color simulation system and significantly accelerated the decrease in P3G content. The CIELAB space model pointed out that parameters a⁎ and b⁎ of the group treated with both lactic acid bacteria and P3G initially increased to a peak level and then gradually decreased, shifting the overall color towards orange and then gradually fading. Furthermore, untargeted metabolomics results revealed that P3G was progressively degraded and converted to pyruvate, methylparaben, 3,4-dihydroxybenzoic acid, p-anisic acid, and terephthalic acid, affecting the metabolic pathways of glycolysis, d-amino acids, benzoate degradation, aromatic compounds degradation, and aminobenzoate degradation in lactic acid bacteria.PMID:39471556 | DOI:10.1016/j.foodchem.2024.141740

Protein Cell. 2024 Oct 29:pwae063. doi: 10.1093/procel/pwae063. Online ahead of print.NO ABSTRACTPMID:39471360 | DOI:10.1093/procel/pwae063