PubMed

Theranostics. 2024 Oct 28;14(18):7219-7240. doi: 10.7150/thno.99926. eCollection 2024.ABSTRACTRationale: Sunitinib is a small-molecule tyrosine kinase inhibitor associated with the side-effect of liver injury. The impaired cell type in liver and the hepatotoxicity mechanisms is still unclear. Methods: Spatial metabolomics, transmission electron microscopy, immunofluorescence co-staining, and isolation of bile duct cells and liver sinusoidal endothelial cells (LSECs) were used to evaluate the zonated hepatotoxicity of sunitinib. Farnesoid X receptor (FXR) conditional knockout mice, metagenomics analysis, bacteria clearance, bacterial culture, Parabacteroides distasonis and 3-oxolithocholic acid supplementation were used to evaluate the hepatotoxicity mechanisms of sunitinib. Results: Phenotype analysis found that hepatic autophagy, apoptosis, and mitochondrial injury were observed in vivo or in vitro after sunitinib treatment. By using spatial metabolomics and isolation of bile duct cells and LSECs, the zonated drug toxicity was observed around the portal vein. Hepatocytes, bile duct cells, and LSECs were damaged after sunitinib treatment. FXR inhibition and gut microbiota depletion aggravated sunitinib-induced liver injury. For diurnal variation, sunitinib-induced liver injury was enhanced at night compared with that at day, and FXR and gut microbiota participated in circadian rhythmic hepatotoxicity induced by sunitinib. Conclusions: Our data suggested activation of FXR and Parabacteroides distasonis supplementation may be used to improve sunitinib-induced hepatotoxicity.PMID:39629129 | PMC:PMC11610149 | DOI:10.7150/thno.99926

Front Oncol. 2024 Nov 19;14:1504738. doi: 10.3389/fonc.2024.1504738. eCollection 2024.NO ABSTRACTPMID:39629001 | PMC:PMC11612568 | DOI:10.3389/fonc.2024.1504738

Anim Nutr. 2024 Jul 24;19:41-55. doi: 10.1016/j.aninu.2024.04.027. eCollection 2024 Dec.ABSTRACTThe rumen is an important organ that enables ruminants to digest nutrients. However, the biological mechanism by which the microbiota and its derived fatty acids regulate rumen development is still unclear. In this study, 18 female Haimen goats were selected and slaughtered at d 30, 60, and 90 of age. Multi-omics analyses (rumen microbial sequencing, host transcriptome sequencing, and rumen epithelial metabolomics) were performed to investigate host-microbe interactions from preweaning to postweaning in a goat model. With increasing age, and after the introduction of solid feed, the increased abundances of Prevotella and Roseburia showed positive correlations with volatile fatty acid (VFA) levels and morphological parameters (P < 0.05). Epithelial transcriptomic analysis showed that the expression levels of hub genes, including 3-hydroxy-3-methylglutaryl-CoA synthase isoform 2 (HMGCS2), enoyl-CoA hydratase, short chain 1 (ECHS1), and peroxisome proliferator activated receptor gamma (PPARG), were positively associated with animal phenotype (P < 0.05). These hub genes were mainly correlated to VFA metabolism, oxidative phosphorylation, and the mammalian target of rapamycin (mTOR) and peroxisome proliferator activated receptor (PPAR) signaling pathways (P < 0.05). Moreover, the primary metabolites in the epithelium changed from glucose preweaning to (R)-3-hydroxybutyric acid (BHBA) and acetoacetic acid (ACAC) postweaning (P < 0.05). Diet and butyrate were the major factors shaping epithelial metabolomics in young ruminants (P < 0.05). Multi-omics analysis showed that the rumen microbiota and VFA were mainly associated with the epithelial transcriptome, and that alterations in gene expression influenced host metabolism. The "butanoate metabolism" pathway, which transcriptomic and metabolomic analyses identified as being upregulated with age, produces ketones that regulate the "oxidative phosphorylation" pathway, which could provide energy for the development of rumen papillae. Our findings reveal the changes that occur in the rumen microbiota, host transcriptome, and metabolome with age, and validate the role of microbiota-derived VFA in manipulating host gene expression and subsequent metabolism. This study provides insight into the molecular mechanisms of host-microbe interactions in goats and supplies a theoretical basis and guidance for precise nutritional regulation during the critical time window for rumen development of young ruminants.PMID:39628645 | PMC:PMC11612656 | DOI:10.1016/j.aninu.2024.04.027

Front Plant Sci. 2024 Nov 19;15:1431004. doi: 10.3389/fpls.2024.1431004. eCollection 2024.ABSTRACTRoot exudation of N is a plant input to the soil environment and may be differentially regulated by the plant during drought. Organic N released by root systems has important implications in rhizosphere biogeochemical cycling considering the intimate coupling of C and N dynamics by microbial communities. Besides amino acids, diverse molecules exuded by root systems constitute a significant fraction of root exudate organic N but have yet to receive a metabolomic and quantitative investigation during drought. To observe root exudation of N during drought, mature cotton plants received progressive drought and recovery treatments in an aeroponic system throughout their reproductive stage and were compared to control plants receiving full irrigation. Root exudates were nondestructively sampled from the same plants at 9 timepoints over 18 days. Total organic C and N were quantified by combustion, inorganic N with spectrophotometric methods, free amino acids by high performance liquid chromatography (HPLC), and untargeted metabolomics by Fourier-transform ion cyclotron resonance-mass spectrometry (FT-ICR-MS). Results indicate that organic N molecules in root exudates were by far the greatest component of root exudate total N, which accounted for 20-30% of root exudate mass. Drought increased root exudation of organic N (62%), organic C (6%), and free amino acid-N (562%), yet free amino acids were <5% of the N balance. Drought stress significantly increased root exudation of serine, aspartic acid, asparagine, glutamic acid, tryptophan, glutamine, phenylalanine, and lysine compared to the control. There was a total of 3,985 molecules detected across root exudate samples, of which 41% contained N in their molecular formula. There were additionally 349 N-containing molecules unique to drought treatment and 172 unique to control. Drought increased the relative abundance and redistributed the molecular weights of low molecular weight N-containing molecules. Time-series analysis revealed root exudation of organic N was stimulated by drought and was sensitive to the degree of drought stress.PMID:39628529 | PMC:PMC11611595 | DOI:10.3389/fpls.2024.1431004

Front Nutr. 2024 Nov 19;11:1465499. doi: 10.3389/fnut.2024.1465499. eCollection 2024.ABSTRACTOBJECT: To clarify the clinical efficacy of washed microbiota transplantation (WMT) for metabolic syndrome (MetS), and explore the differences in the metabolic profile of bacterial outer membrane vesicles (OMVs) in donor fecal bacteria suspension received by MetS patients with good and poor outcomes, and to construct a predictive model for the efficacy of WMT for MetS using differential metabolites.METHODS: Medical data 65 MetS patients who had completed at least 2 courses of WMT from 2017.05 to 2023.07 were collected. Fecal bacteria suspension of WMT donors were collected, and the clinical data of MetS patients treated with WMT during this period were collected as well. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared. OMVs were isolated from donor fecal bacteria suspension and off-target metabolomic sequencing was performed by Liquid Chromatograph Mass Spectrometer (LC-MS).RESULTS: Compared with baseline, Body mass index (BMI), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) of MetS patients showed significant decreases after the 1st (short-term) and 2nd (medium-term) courses, and fasting blood glucose (FBG) also showed significant decreases after the 1st session. There was a significant difference between the Marked Response OMVs and the Moderate Response OMVs. It was showed that 960 metabolites were significantly up-regulated in Marked Response OMVs and 439 metabolites that were significantly down-regulated. The ROC model suggested that 9-carboxymethoxymethylguanine, AUC = 0.8127, 95% CI [0.6885, 0.9369], was the most potent metabolite predicting the most available metabolite for efficacy.CONCLUSION: WMT had significant short-term and medium-term clinical efficacy in MetS. There were differences in the structure of metabolites between Marked Response OMVs and Moderate Response OMVs. The level of 9-Carboxy methoxy methylguanine in Marked Response OMVs can be a good predictor of the efficacy of WMT in the treatment of MetS.PMID:39628464 | PMC:PMC11611574 | DOI:10.3389/fnut.2024.1465499

Front Nutr. 2024 Nov 19;11:1450386. doi: 10.3389/fnut.2024.1450386. eCollection 2024.ABSTRACTINTRODUCTION: A growing body of literature associates branched-chain amino acid (BCAA) catabolism to increased fatty acid oxidation and better metabolic health. Hence, BCAA-rich diets may improve body composition and muscle protein synthesis. However, the role of individual characteristics such as a low aerobic fitness, a well-established risk factor for cardio-metabolic diseases, has not been studied.METHODS: This study examined 64 female rats from the high-capacity runner (HCR) and low-capacity runner (LCR) rat model. Rats from each line (HCR or LCR) were divided into four groups; differing from diet (CTRL or BCAA) and from the opportunity to voluntarily run on a running wheel (NONRUNNER or RUNNER). Groups were matched for body mass and maximal running capacity within each line. We measured maximal running capacity and metabolism before and after the intervention of diet and voluntary running activity. After the end of the experiment, serum samples were collected for metabolome analysis.RESULTS: We are the first to show that BCAA supplementation has a more pronounced impact on LCRs compared to HCRs. Specifically, in LCR rats, BCAA supplementation led to reduced daily voluntary running distance and an enrichment of serine metabolism in the serum metabolome. While voluntary running increased food intake and energy expenditure, its effects on the serum metabolome were minimal in HCRs.CONCLUSION: The present research highlights the benefit achieved by combining BCAA supplementation with running activity, especially in the LCR line. Importantly, our results underscore the interconnected role of BCAAs and fatty acid metabolism in promoting overall metabolic health.PMID:39628463 | PMC:PMC11611553 | DOI:10.3389/fnut.2024.1450386

Aging Cell. 2024 Dec 4:e14434. doi: 10.1111/acel.14434. Online ahead of print.ABSTRACTThe metabolism of branched-chain amino acids by gut microbiota can improve overall health and may reverse aging. In this study, we investigated Parabacteroides merdae, a gut microbe that is known to catabolise branched-chain amino acids (BCAAs). Three metabolites of BCAAs isovalerate, 2-methylbutyrate, and isobutyrate were used to treat D-gal induced aging mice. The results showed that these treatments could delay aging in mice by providing health benefits in reducing oxidative stress and inflammation, improving muscle capacity, reversing brain acetylcholine levels, and regulating blood glucose. The mechanism was preliminarily explored by combining the gut microbiota metagenome and faecal serum metabolome. Parabacteroides merdae altered the species composition and structure of the gut microbiota in mice. Increasing the abundance of beneficial bacteria, such as Bifidobacterium pseudolongum. Three metabolites affects the gut microbiota and the body's pathways of protein and improves the overall health through a variety of signaling pathways. Overall, regulating the gut microbiota involved in branched-chain amino acid metabolism to bring health benefits may be a new way of reversing aging.PMID:39628383 | DOI:10.1111/acel.14434

Environ Sci Technol. 2024 Dec 4. doi: 10.1021/acs.est.4c09535. Online ahead of print.ABSTRACTWastewater microbial communities within conventional activated sludge (CAS) systems can perform hundreds of biotransformations whose relative importance, frequency, and temporal stability remain largely unexplored. To improve our understanding of biotransformations in CAS systems, we collected 24 h composite samples from the influent and effluent of a CAS system over 14 days, analyzed samples using high-resolution mass spectrometry (HRMS), and conducted a nontarget analysis of our HRMS acquisitions. We found that over 50% of the chemical features in the influent were completely removed, and the daily number of detected features exhibited low variability with a coefficient of variation of 0.07. Additionally, we found 352 Core chemical features present in every sample at both locations. We used chemical features to search for evidence of 19 potential biotransformations and detected 9 of these biotransformations at a frequency of over 80 times per day, where evidence for dehydrogenations, hydroxylations, and acetylations was most frequently detected. The daily number of detections for the 9 biotransformations exhibited coefficients of variation ranging from 0.13-0.20, revealing the broad temporal stability for these wastewater microbial community functions. This stability contrasts with the previously observed temporal variability for micropollutant biotransformations, suggesting that micropollutant biotransformations are linked to specialized microbial community functions.PMID:39628310 | DOI:10.1021/acs.est.4c09535

Physiol Plant. 2024 Nov-Dec;176(6):e14649. doi: 10.1111/ppl.14649.ABSTRACTIn maize (Zea mays L), the fungus Fusarium verticillioides can behave as a pathogen, but it is also able of asymptomatic colonization as an endophyte. Therefore, it would be of great value to identify metabolites and/or metabolic pathways implicated in mutualistic and pathogenic interactions. The objectives of the present study were: (i) to investigate the effect of seed colonization by F. verticillioides on maize growth in a group of inbreds with contrasting resistance to F. verticillioides; (ii) to know if maize priming by Fusarium seed infection affects maize response to other parasites and if these differences could depend on genotype resistance to Fusarium; and (iii) to determine which metabolites could be associated to beneficial/detrimental changes on maize performance. Targeted and untargeted metabolomic approaches were carried out to characterize the response of control and primed plants to the most common maize pest in the Mediterranean area, Sesamia nonagrioides Lefèbvre (Lepidoptera: Noctuidae). The study cannot assume a differential pattern of infection between resistant and susceptible inbreds, but seed inoculation with F. verticillioides upon infestation with S. nonagrioides, significantly altered defense metabolism in resistant inbreds. Meanwhile it also induced a lipid response in susceptible inbreds that could mediate their increased plant susceptibility to insect attack. Although an endophytic interaction between the fungus and specific genotypes cannot be proven, defense pathways were favorably altered by F. verticillioides colonization among resistant inbreds.PMID:39627872 | DOI:10.1111/ppl.14649

J Transl Med. 2024 Dec 3;22(1):1098. doi: 10.1186/s12967-024-05868-3.ABSTRACTBACKGROUND: It is unclear regarding the association between metabolomic state/genetic risk score(GRS) and brain volumes and how much of variance of brain volumes is attributable to metabolomic state or GRS.METHODS: Our analysis included 8635 participants (52.5% females) aged 40-70 years at baseline from the UK Biobank. Metabolomic profiles were assessed using nuclear magnetic resonance at baseline (between 2006 and 2010). Brain volumes were measured using magnetic resonance imaging between 2014 and 2019. Machine learning was used to generate metabolomic state and GRS for each of 21 brain phenotypes.RESULTS: Individuals in the top 20% of metabolomic state had 2.4-35.7% larger volumes of 21 individual brain phenotypes compared to those in the bottom 20% while the corresponding number for GRS ranged from 1.5 to 32.8%. The proportion of variance of brain volumes (R [2]) explained by the corresponding metabolomic state ranged from 2.2 to 19.4%, and the corresponding number for GRS ranged from 0.8 to 8.7%. Metabolomic state provided no or minimal additional prediction values of brain volumes to age and sex while GRS provided moderate additional prediction values (ranging from 0.8 to 8.8%). No significant interplay between metabolomic state and GRS was observed, but the association between metabolomic state and some regional brain volumes was stronger in men or younger individuals. Individual metabolomic profiles including lipids and fatty acids were strong predictors of brain volumes.CONCLUSIONS: In conclusion, metabolomic state is strongly associated with multiple brain volumes but provides minimal additional prediction value of brain volumes to age + sex. Although GRS is a weaker contributor to brain volumes than metabolomic state, it provides moderate additional prediction value of brain volumes to age + sex. Our findings suggest metabolomic state and GRS are important predictors for multiple brain phenotypes.PMID:39627804 | DOI:10.1186/s12967-024-05868-3

Sci Rep. 2024 Dec 3;14(1):30027. doi: 10.1038/s41598-024-81194-4.ABSTRACTMechanisms linking pre-pregnancy obesity to increased preterm birth risk are unclear. Here, we examined the impact of pre-pregnancy obesity on metabolites, Fms-related tyrosine kinase 3 ligand (Flt3L), and proinflammatory cytokine profiles in preterm birth. We used cytokine bead array, ELISA and Gas Chromatography-Mass Spectrometry (GC-MS) to determine cytokine and metabolite profiles in maternal and cord blood samples from 124 pregnant women in Australia, who gave birth at term (n = 86) or preterm (n = 38). Besides the expected variations in birth weight and gestational age, all demographic characteristics, including pre-pregnancy body mass index, were similar between the term and preterm birth groups. Mothers in the preterm birth group had reduced Flt3L (P = 0.002) and elevated IL-6 (P = 0.002) compared with term birthing mothers. Among mothers who gave birth preterm, those with pre-pregnancy obesity had lower Flt3L levels (P = 0.02) compared with lean mothers. Flt3L and IL-6 were similar in cord blood across both groups, but TNFα levels (P = 0.02) were reduced in preterm newborns. Metabolomic analysis revealed significant shifts in essential metabolites in women with pre-pregnancy obesity, some of which were linked to preterm births. Our findings suggest that maternal pre-pregnancy obesity alters the metabolome and reduces Flt3L expression, potentially increasing risk of preterm birth.PMID:39627409 | DOI:10.1038/s41598-024-81194-4

Sci Rep. 2024 Dec 3;14(1):30101. doi: 10.1038/s41598-024-81600-x.ABSTRACTRenal ischemia-reperfusion injury (IRI) is an important cause of acute kidney injury (AKI). However, the pathophysiological changes and mechanisms during IRI-AKI progression remain unclear. This study aims toinvestigate the potential mechanisms in the progression of IRI-AKI by integrating metabolomics and transcriptomics data, providing a reference for the subsequent identification of biomarkers and therapeutic targets. IRI-AKI rat models with 30 min of ischemia and 24-72 h of reperfusion surgery simulating the progression of AKI were established. Compared to the control group underwent sham surgery (NC group), most of the differentially expressed metabolites (DEMs) in IRI-AKI 24 h and IRI-AKI 72 h decreased, mainly including amino acids, organic acids, and carnitines. Additionally, we found that DEMs were mainly enriched in amino acid-related pathways, among which valine, leucine, and isoleucine biosynthesis were dramatically altered in all comparisons. Transcriptomics revealed that differentially expressed genes (DEGs) were primarily involved in amino acid, lipid, and fatty acid metabolism. By integrating metabolomics and transcriptomics, we found valine, leucine, and isoleucine biosynthesis play key roles in IRI-AKI development. Our findings concluded that valine, leucine, and isoleucine pathways are hubs that potentially connect transcriptomes to metabolomes, providing new insights regarding the pathogenesis of IRI-AKI and its potential biomarkers and therapeutic strategies.PMID:39627404 | DOI:10.1038/s41598-024-81600-x

Sci Rep. 2024 Dec 3;14(1):30078. doi: 10.1038/s41598-024-77871-z.ABSTRACTQuality control plays a crucial role in maintaining the reputation of agricultural organizations by ensuring that their products meet the expected standards and preventing any loss during the packaging process. A significant responsibility of quality control is conducting periodic product assessments. However, subjective interpretation during physical inspections of fruits can lead to variability in reporting. To counter this, assessing total soluble solids (Brix) and percent acidity (Acid) can provide a more objective approach. Nevertheless, it is essential to note that many fruit metabolites can impact these parameters. Nuclear magnetic resonance (NMR) spectroscopy, particularly 1H-NMR, has become a popular tool for quality control in recent years due to its precision, sample preservation, and high throughput analysis. This manuscript investigates if the standard Brix/Acid tests are directly related to the levels of metabolites during cold storage. Using citrus as the model system, a metabolomics analysis was conducted to identify patterns in the cold storage metabolite profiles of the juice, albedo, and flavedo tissues. The results show that Brix (or total dissolved solids) correlates well with sucrose, glucose, and fructose levels and moderately with choline levels. Acid (percent acidity) levels displayed a negative correlation with both fructose and choline levels. Interestingly, the formate levels were susceptible to storage time and directly related to Acid measurements. This study suggests metabolomics could be a complementary technique to quality control of fruits in cold storage, especially with cost-effective desktop NMR spectrometers.PMID:39627282 | DOI:10.1038/s41598-024-77871-z

Sci Rep. 2024 Dec 3;14(1):30046. doi: 10.1038/s41598-024-75388-z.ABSTRACTConsidering the role of dietary methyl donor (DMD) in numerous biochemical processes, we hypothesized that DMD could play an important role in metabolic syndrome such as hyperlipidemia, hypertension, insulin resistance, and appetite in obese individuals. This cross-sectional study was conducted on 335 obese people. We collected dietary data using a valid and reliable 147-question Food Frequency Questionnaire (FFQ). Multivariate multinomial logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between dietary methyl intake and cardio-metabolic risk factors. After adjusting for confounding variables, individuals at the fourth and third quartile of DMD, were more likely to have lower low-density lipoprotein cholesterol (LDL-C) (OR = 0.968, CI = 0.943-0.994, P = 0.015 and OR = 0.978, CI = 0.957-0.998, P = 0.03 respectively) versus first quartile. Also, total cholesterol (TC) showed a significant decrease in forth quartile of DMD in model III (OR = 0.974, CI = 0.951-0.997, P = 0.029). Current results suggested that, high DMDs' consumption, significantly associated with decreased risk of cardiometabolic risk factors.PMID:39627237 | DOI:10.1038/s41598-024-75388-z

Int J Food Sci Nutr. 2024 Dec 3:1-15. doi: 10.1080/09637486.2024.2435849. Online ahead of print.ABSTRACTThis study integrated analyses of gut microbiota and metabolomics to investigate the impact of ellagic acid (EA) on non-alcoholic fatty liver disease (NAFLD). Compared to the high-fructose diet (HFruD) group, the EA group exhibited reduced body weight and fat mass, alongside improvements in blood glucose and lipid metabolism. Liver metabolomics analysis revealed that EA increased the abundance of metabolites in pathways related to unsaturated fatty acids, amino acids and bile acids. Furthermore, EA induced alterations in the composition and structure of gut microbiota, notably decreasing bacterial genera enriched by HFruD while promoting beneficial bacteria such as Faecalibaculum. Correlation analysis demonstrated significant associations among NAFLD markers, gut microbiota and liver metabolites influenced by EA. This study provides new insights into the anti-NAFLD effects of EA, suggesting EA as a promising nutraceutical for improving NAFLD.PMID:39627026 | DOI:10.1080/09637486.2024.2435849

J Psychiatry Neurosci. 2024 Dec 3;49(6):E413-E426. doi: 10.1503/jpn-240038. Print 2024 Nov-Dec.ABSTRACTBACKGROUND: The intricate interplay between peripheral adaptive immune cells and the central nervous system (CNS) has garnered increasing recognition. Given that alterations in cell quantities often translate into modifications in metabolite profiles and that these metabolic changes can potentially traverse the bloodstream and enter the CNS, thereby modulating the progression of mental illnesses, we sought to explore the metabolic profiles of peripheral immune cells in a ketamine-treated mouse model of schizophrenia.METHODS: We used flow cytometry to scrutinize the alterations in peripheral adaptive immune cells in a ketamine-induced schizophrenia mouse model. Subsequently, we implemented an untargeted metabolomic approach with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to detect the metabolite profiles of peripheral abnormal lymphocytes and identify differential metabolites present in plasma. We then employed targeted metabolomics using UPLC-MS/MS to quantify the common differential metabolites detected in mouse plasma.RESULTS: Flow cytometry analysis detected a notable increase in the count of peripheral CD3+ T cells in a ketamine-induced schizophrenia mouse model. Subsequent untargeted metabolomics analysis revealed that the amino acid metabolism pathway underwent substantial alterations. A detailed quantification of 22 amino acid profiles in the peripheral plasma indicated significant elevation in the levels of glycine, alanine, asparagine, and aspartic acid.LIMITATIONS: Our ongoing research has yet to conclusively identify the precise amino acid metabolism pathway that serves as the pivotal factor in the manifestation of the schizophrenia-like phenotype induced by ketamine.CONCLUSION: The peripheral amino acid metabolism pathway is involved in the ketamine-induced schizophrenia-like phenotype. The metabolic profile of peripheral immune cells could provide accurate biomarkers for the diagnosis and treatment of psychiatric diseases.PMID:39626901 | DOI:10.1503/jpn-240038

Environ Toxicol Pharmacol. 2024 Dec 1:104598. doi: 10.1016/j.etap.2024.104598. Online ahead of print.ABSTRACTThe growing usage of glucocorticoids for a variety of diseases raises concerns since these drugs, including the anti-inflammatory dexamethasone (DEX), are frequently found in the environment. The impact of DEX was evaluated on mussels Mytilus galloprovincialis (Lamarck, 1819) by exposure to environmental concentrations (C1: 4ng/L; C2: 40ng/L; C3: 400ng/L; C4: 2000 ng/L), and sampling at 3 (T3), 6 (T6), and 12 (T12) days. A multi-biomarker approach was applied on gills, involved in gas exchange, feed filtering, and osmoregulation. A dose- and time-dependent uptake of DEX was recorded, besides haemocyte infiltration, increased neutral and acid mucopolysaccharides, and a general pro-oxidant effect witnessed by lipid peroxidation and altered antioxidant system. Metabolomics revealed rise in protein turnover and energy demand by fluctuations in free amino acids (alanine, glycine) and energy-related metabolites (succinate, ATP/ADP). It is necessary to reduce DEX dosage from the environment by recovery strategies and effective eco-pharmacovigilance programs.PMID:39626850 | DOI:10.1016/j.etap.2024.104598

Bioresour Technol. 2024 Dec 1:131923. doi: 10.1016/j.biortech.2024.131923. Online ahead of print.ABSTRACTWe developed a stepwise method to transform Chlorella sorokiniana microalgal biomass into a potent biostimulant. The method, including maceration, high-pressure homogenization, and enzymatic hydrolysis, preserves the bioactive properties of the biomass as a biostimulant while minimizing plant inhibitory effects. Fractions were characterized individually, and optimal concentrations were determined using a rapid Arabidopsis root assay. A blend of optimal concentrations of fractions was identified as the most stimulating extract, increasing the root elongation by 25%. When applied to tomato plants and monitored using high-throughput plant phenotyping, the blend displayed a 25 % reduction in mineral fertilizer use. Metabolomic analysis of the tomato plants showed significantly enhanced carbon and nitrogen metabolism in the leaves. Our findings indicate that the stepwise processing not only produces an effective biostimulant but also generates substantial residual biomass for a potential multiproduct biorefinery approach that can improve the overall techno-economic outlook.PMID:39626806 | DOI:10.1016/j.biortech.2024.131923

Curr Biol. 2024 Nov 26:S0960-9822(24)01518-5. doi: 10.1016/j.cub.2024.11.011. Online ahead of print.ABSTRACTTransitioning into and out of dormancy is a crucial survival strategy for many organisms. In unicellular cyanobacteria, surviving nitrogen-starved conditions involves tuning down their metabolism and reactivating it once nitrogen becomes available. Glucose-6-phosphate dehydrogenase (G6PDH), the enzyme that catalyzes the first step of the oxidative pentose phosphate (OPP) pathway, plays a key role in this process. G6PDH is produced at the onset of nitrogen starvation but remains inactive in dormant cells, only to be rapidly reactivated when nitrogen is restored. In this study, we investigated the mechanisms underlying this enzymatic regulation and found that G6PDH inactivation is primarily due to the accumulation of inhibitory metabolites. Moreover, our findings demonstrate that metabolite-level regulation is the driving force behind the resuscitation program. This study highlights the critical importance of metabolite-level regulation in ensuring rapid and precise enzymatic control, enabling microorganisms to swiftly adapt to environmental changes and undergo developmental transitions.PMID:39626669 | DOI:10.1016/j.cub.2024.11.011

Food Chem. 2024 Nov 26;467:142245. doi: 10.1016/j.foodchem.2024.142245. Online ahead of print.ABSTRACTWith the popularization of probiotic products, tapping high-quality probiotics is crucial. Therefore, in this study, Lacticaseibacillus rhamnosus (X9C17) was selected from a pool of 54 isolates for its remarkable ability to survive in simulated gastrointestinal fluid (Gastric juice: 81.08 %, intestinal juice: 48 %), after which its probiotic characteristics were evaluated. Strain X9C17 exhibits strong antibacterial properties, hydrophobicity, self-aggregation ability and significant antioxidant capacity, and it can produce essential amino acids, including glycine and proline. Therefore, the experimental results show that X9C17 has potential probiotic function. Metabolomics methods were used to study the changes in metabolites in X9C17 fermented milk. The hydroxycinnamic acid, L-3-phenyllactic acid, amino acids and multiple vitamins accumulated in the fermented milk, played a positive role in the probiotic function and unique flavour of the product. In summary, This study offers new insights and data supporting the physiological mechanisms of probiotics and their application in functional fermented foods.PMID:39626560 | DOI:10.1016/j.foodchem.2024.142245