PubMed

Brain Res. 2024 Dec 18:149409. doi: 10.1016/j.brainres.2024.149409. Online ahead of print.ABSTRACTDepression is underpinned by a complex pathogenesis that involves the hippocampus and dorsal raphe nucleus (DRN) of the central nervous system. Although electroacupuncture (EA) is proven to be safe and effective for alleviating depression symptoms and causes minimal side effects its underlying therapeutic mechanism remains unclear. In this study, we performed targeted metabolomics to identify metabolite alterations in the hippocampus and DRN of Wistar Kyoto (WKY) rats and elucidate the role and potential mechanism of action of EA. Our results indicated that 3 weeks of consecutive EA significantly ameliorated depression-like behavior in WKY rats. Targeted metabolomics revealed 42 differentially expressed metabolites (DEMs) in the hippocampus and 97 DEMs in the DRN between Wistar and WKY rats. In addition, we observed 19 hippocampal DEMs and 41 DRN DEMs between WKY and EA-treated rats. Subsequent pathway analyses indicated that these DEMs were primarily enriched in amino acid-related metabolic pathways. Moreover, six DEMs were found to be significantly associated with at least one depression-like behavior, indicating their involvement in the pathogenesis of depression. EA intervention modulated the levels of 1-methylhistidine, 3-methylhistidine, carnosine, and riboflavin in depressed rats. Collectively, these findings demonstrate that disturbances in cerebral metabolites, especially amino acids, may be one of the causes underlying depression in WKY rats, and the therapeutic effect of EA is potentially mediated through the modulation of the levels of these metabolites.PMID:39706240 | DOI:10.1016/j.brainres.2024.149409

Food Chem. 2024 Dec 13;468:142479. doi: 10.1016/j.foodchem.2024.142479. Online ahead of print.ABSTRACTMuscle fiber is an important factor in beef quality. Here, we compared fast-type longissimus dorsi muscle and slow-type psoas major muscle from cattle using transcriptomic, proteomic and metabolomic analyses. A total of 1717 differentially expressed genes (DEGs), 297 differentially abundant proteins (DAPs) and 193 differentially abundant metabolites (DAMs) were identified between LD and PM tissue, respectively. For verification, we selected 10 DEGs for qRT-PCR and 6 DAPs for western blotting, and showed they were consistent between the two approaches. GO and KEGG enrichment analyses revealed that some DEGs, DAPs and DAMs were enriched in muscle fiber type-associated GO terms and pathways. Many of them are involved in glycolysis, TCA and fatty acid metabolism. Integrated multi-omics analysis showed a correlation coefficient of 0.6244 between the transcriptome and proteome. This study provides a new understanding of molecular mechanisms involved in the determination of bovine muscle fiber type and meat quality.PMID:39706111 | DOI:10.1016/j.foodchem.2024.142479

J Hazard Mater. 2024 Dec 15;485:136895. doi: 10.1016/j.jhazmat.2024.136895. Online ahead of print.ABSTRACTBisphenol S (BPS) is widely used as a substitute for Bisphenol A (BPA). While perinatal BPS exposure is suspected to increase susceptibility to high-caloric diet-induced adipogenesis, how BPS affects offspring remains largely unknown. This study explored effects of prenatal BPS exposure on adiposity and insulin resistance in high-fat diet (HFD)-fed C57BL/6 offspring, revealing significant changes in body weight, glucose tolerance, insulin sensitivity, and histopathology. Employing nontargeted metabolomics and 16S rRNA sequencing, we constructed a comprehensive atlas of metabolome and microbiome shifts across heart, liver, pancreas, white adipose tissue (WAT), brown adipose tissue (BAT), and feces. Male offspring showed greater metabolic and microbial disturbances. Low-dose BPS exposure (0.05 mg/kg/d) induced changes across entire atlas comparable to high-dose (5 mg/kg/d). BAT and WAT were key target tissues with the most significant metabolic disturbances. BPS disrupted fatty acid β-oxidation in WAT by reducing carnitine carriers, causing WAT fat accumulation. A resistance mechanism to BPS exposure was indicated by both mobilization of BAT compensatory thermogenesis, characterized by increased carnitines and UCP1 expression, and an increase in beneficial commensal bacteria. Their competition and imbalance contributed to obesity and insulin resistance in offspring, highlighting the potential for early interventions targeting key metabolites and microbiota.PMID:39706018 | DOI:10.1016/j.jhazmat.2024.136895

Environ Int. 2024 Dec 16;195:109215. doi: 10.1016/j.envint.2024.109215. Online ahead of print.ABSTRACTAryl organophosphorus flame retardants (aryl-OPFRs), commonly used product additives with close ties to daily life, have been regrettably characterized by multiple well-defined toxicity risks. Triphenyl phosphate (TPHP) and tri-o-cresyl phosphate (TOCP), two structurally similar aryl-OPFRs, were observed in our previous study to exhibit contrasting immunotoxic effects on THP-1 macrophages, yet the underlying mechanisms remain unclear. This study sought to address the knowledge gap by integrating transcriptomic and metabolomic analyses to elucidate the intricate mechanisms. During individual omics analyses, we unfortunately only obtained highly similar results for both TPHP and TOCP, failing to identify the key reasons for their differences. These results revealed comparable disturbances induced by both compounds, including disruptions in nucleic acid synthesis and energy metabolism, blocking ADP to ATP conversion by reducing TCA cycle intermediates, consequently leading to ATP depletion. However, through integrative analysis, specific pathways affected by each compound were successfully identified, shedding light on their unique effects. TPHP reduced GTP levels necessary for Rap1 activation, thereby inhibiting phagocytosis and adhesion of THP-1 macrophages. Conversely, TOCP stimulated the mTOR signaling pathway, enhancing phosphorylation of downstream proteins S6K, RHOA, and PKC, consequently promoting immune responses. This study not only clarified the distinct immunotoxic mechanisms of TPHP and TOCP but also provided critical insights into how structural variations in aryl-OPFRs can lead to markedly different immune responses, thereby informing future risk assessments and regulatory strategies for these compounds.PMID:39705979 | DOI:10.1016/j.envint.2024.109215

Sci Total Environ. 2024 Dec 19;958:178068. doi: 10.1016/j.scitotenv.2024.178068. Online ahead of print.ABSTRACTGlyphosate (Gly), the world's most widely used herbicide in agriculture, can poison the red swamp crayfish, Procambarus clarkii, via spray drift and surface runoff into surface waters. However, there is a paucity of research on the mechanisms that affect crayfish tolerance to Gly at typical environmental concentrations. To address this research gap, we investigated the effects of Gly stress (0, 6, 12, 24, and 72 h) at different concentrations (0, 1.20, 3.60, 7.20, and 10.80 mg·L-1) on antioxidant enzyme activity in crayfish hepatopancreas. Furthermore, we analyzed the species' tolerance mechanism to Gly exposure at a typical environmental concentration (3.60 mg·L-1) based on integrative transcriptomics, metabolomics, and proteomics. The Gly concentration and exposure time affected the crayfish's antioxidant system, and interacted with each other (P < 0.01). Gly concentrations higher than 7.20 mg·L-1 and exposure times longer than 48 h caused oxidative stress. When the Gly concentrations were lower than 3.60 mg·L-1, crayfish tolerated Gly exposure within 72 h by self-regulating superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). A multi-omics analysis revealed that crayfish upregulated the expression of amino acid metabolites (such as glutamate, proline, and lysine) and amino acid transformation-related genes (such as GlnA and P5CS) to tolerate Gly stress by enhancing the antioxidant capacity, ammonia‑nitrogen regulation, and energy supply of the organism. Metallothionein and polyadenylate-binding proteins, which are potential markers of Gly exposure, crucially influenced crayfish tolerance to Gly by synthesizing metalloenzymes and scavenging reactive oxygen species. This study revealed the Gly tolerance mechanism in crayfish and can provide a theoretical reference for commercial eco-farming in rice-crayfish integrated aquaculture systems.PMID:39705948 | DOI:10.1016/j.scitotenv.2024.178068

Int J Med Inform. 2024 Dec 16;195:105765. doi: 10.1016/j.ijmedinf.2024.105765. Online ahead of print.ABSTRACTBACKGROUND: Gas chromatography-mass spectrometry (GC-MS) has been shown to be a potentially efficient metabolic profiling platform in urine analysis. However, the widespread use of GC-MS for inborn errors of metabolism (IEM) screening is constrained by the rarity of IEM in population, and the difficult and specialized complexity of the interpretation of GC-MS organic acid profiles.METHODS: Based on 355,197 GC-MS test cases accumulated from 2013 to 2021 in China, a random forest-based machine learning model was proposed, trained, and evaluated. Weighted undersampling or oversampling data processing and staged modeling strategies were used to handle the highly imbalanced data and improve the ability of the model to identify different types of rare IEM cases.RESULT: In the first-stage model, which only identified positive cases without discriminating the specific IEM, the screening sensitivity was 0.938 (or 0.991 if abnormal cases were also included). The average sensitivity of the second-stage models that classify 11 particular IEMs is 0.992, with an average specificity and accuracy of 0.944 and 0.969, respectively. The SHAP values visualized for each model explain the basis for the differential diagnosis made by the model.CONCLUSION: With sufficient high-quality data, machine learning models can provide high-sensitivity GC-MS interpretation and greatly improve the efficiency and quality of GC-MS based IEM screening.PMID:39705916 | DOI:10.1016/j.ijmedinf.2024.105765

J Pharm Biomed Anal. 2024 Dec 16;255:116640. doi: 10.1016/j.jpba.2024.116640. Online ahead of print.ABSTRACTIn response to the urgent need for effective treatments during the rapid spread and high mortality rate of COVID-19, existing drugs were repurposed for potential antiviral effects, including favipiravir, originally designed as an RNA-dependent RNA polymerase inhibitor for influenza. Despite limited antiviral effectiveness against COVID-19, favipiravir has been reported to cause several adverse drug events (ADEs) in the body. Recent studies have shown that favipiravir can damage various tissues in rats. However, a detailed analysis of its effects on the metabolomics profile of tissues using high-resolution spectroscopic technologies has not yet been conducted. In this study, it was aimed to analyze the metabolomic changes in rat kidney tissues induced by favipiravir, using high-resolution nuclear magnetic resonance (NMR) spectroscopy. Sixty male Wistar Albino rats were randomly divided into three groups: control, low-dose favipiravir (200 mg/kg), and high-dose favipiravir (300 mg/kg), with 20 rats per group. Each group received its respective treatment via oral gavage. After the treatment period, kidney tissue samples were collected and subjected to 1H NMR analysis. Bioinformatics analysis of the obtained 1H NMR spectra suggests that favipiravir induces dose-dependent metabolic changes in kidney tissue, with higher doses causing more profound disruptions in several pathways.PMID:39705846 | DOI:10.1016/j.jpba.2024.116640

Microbiol Res. 2024 Dec 18;292:128030. doi: 10.1016/j.micres.2024.128030. Online ahead of print.ABSTRACTThe recruitment of the phosphorus-solubilizing rhizobacteria plays an important role in response to phosphorus deficiency. Through the treatments of Arabidopsis thaliana (Col-0) and the FERONIA (FER) functional deficient mutants (fer-4 and fer-5) with the soil suspension in various phosphorus conditions, we discovered that FER could promote phosphorus-solubilizing rhizobacteria enrichment to rescue the defective plant during phosphorus deficiency. The amplicon sequencing data reflected that the phosphorus-solubilizing rhizobacterial genus Alcaligenes was significantly enriched of Col-0 than fer-4 in low phosphorus conditions. Metabolomics analysis revealed that there were more α-D-Glucose (α-D-Glc) and L-Leucine (L-Leu) in Col-0 roots than those in fer-4 roots. The alterations of α-D-Glc and L-Leu mediated by FER had high-positive correlations to the enrichment of Alcaligenes. We successfully isolated a phosphorus-solubilizing rhizobacteria strain identified as Alcaligenes faecalis PSB15. The α-D-Glc and L-Leu could promote the strain PSB15 growth on LB agar plates and assist fer-4 in recovering from phosphorus starvation in the low phosphorus (LP) liquid medium vermiculite with tricalcium phosphate (TCP). The α-D-Glc and L-Leu could be considered as promising compounds to enrich beneficial phosphorus-solubilizing rhizobacteria, such as Alcaligenes, and provide a reference for overcoming the plight of phosphorus deficiency in crops in the field of agricultural production in the future.PMID:39705833 | DOI:10.1016/j.micres.2024.128030

Microbiol Res. 2024 Dec 18;292:128031. doi: 10.1016/j.micres.2024.128031. Online ahead of print.ABSTRACTIntercropping is emerging as a sustainable strategy to manage soil-borne diseases, yet the underlying mechanisms remain largely elusive. Here, we investigated how intercropping chrysanthemum (Chrysanthemum morifolium) with ginger (Zingiber officinale) suppressed Fusarium wilt and influenced the associated rhizo-microbiome. Chrysanthemum plants in intercropping systems exhibited a marked reduction in wilt severity and greater biomass compared to those grown in monoculture. In contrast, soil sterilization intensified wilt severity and abrogated the benefits of intercropping, highlighting the critical role of soil microbiota. 16S rRNA gene amplicon analysis revealed that intercropping significantly changed the composition and structure of rhizo-bacterial communities, particularly enriching Burkholderia species, which were closely associated with plant growth and disease resistance. Further investigation demonstrated that ginger root exudates, including sinapyl alcohol and 6-gingerol, greatly promoted the proliferation and colonization of Burkholderia sp. in chrysanthemum rhizosphere, conferring the enhanced disease suppression. Metabolomic profiling revealed that ginger root exudates stimulated the release of specific metabolites by chrysanthemum roots, which promoted the growth and biofilm formation of Burkholderia sp. Our findings uncovered the mechanism by which intercropping chrysanthemum with ginger plants modulated the rhizo-microbiome and thereby resulted in the enhanced disease suppression, offering insights into optimizing plant-microbe interactions for improving crop health and productivity.PMID:39705829 | DOI:10.1016/j.micres.2024.128031

J Nat Prod. 2024 Dec 20. doi: 10.1021/acs.jnatprod.4c01140. Online ahead of print.ABSTRACTA combined strategy of 2D-NMR-metabolomics-driven substructure tracking with genome mining led to the targeted discovery of 10 nocobactin-type lipopeptides (1-10) from the Arctic-derived phychrophillic Nocardia sp. L-016, among which 1-5 are new compounds, named nocardimicins S-W. The phenoxazole moiety in 1-10, featuring unique NMR values and correlations, was used as a probe for tracking nocardimicin analogues. The structures of 1-5 were established based on extensive MS and NMR spectroscopic analyses. The biosynthesis of nocardimicins (1-10) in Nocardia sp. L-016 is proposed to be achieved by the noc biosynthetic gene cluster, which is composed of two sub-gene clusters (I and II) separated by a 228 kb region. Compounds 1-10 showed moderate inhibition against human cancer cell lines of HCT116 and HepG2 with IC50 values in the range of 3.5-10.2 μM. This work provides an effective application of paired-omics technologies in the discovery of new natural products.PMID:39705533 | DOI:10.1021/acs.jnatprod.4c01140

Medicine (Baltimore). 2024 Dec 20;103(51):e40975. doi: 10.1097/MD.0000000000040975.ABSTRACTHyperuricemic nephropathy is a metabolic disease in which renal uric acid deposition and excretion are impaired due to elevated levels of uric acid in the blood, leading to impaired renal tubule function and chronic renal disease. Hyperuricemic nephropathy is one of the important complications of hyperuricemia, which seriously affects the quality of life and prognosis of patients. The pathogenesis of hyperuricemic nephropathy involves a variety of factors, including: amino acid metabolism disorder, energy metabolism abnormality, increased nucleotide metabolism, lipid metabolism disorder and bile acid metabolism imbalance, REDOX process disorder, cell cycle and apoptosis imbalance, signal transduction and inflammatory response enhancement, and intestinal flora imbalance. In recent years, omics techniques such as metabolomics, transcriptomics and intestinal microecology have been used to reveal the metabolic, gene and microflora characteristics of hyperuricemic nephropathy from different levels, as well as their interactions and regulatory mechanisms. This paper reviews these studies, analyzes the existing problems and challenges, and puts forward future research directions and suggestions, aiming at providing new theoretical basis and practical guidance for the prevention and treatment of hyperuricemic nephropathy.PMID:39705438 | DOI:10.1097/MD.0000000000040975

Sci China Life Sci. 2024 Dec 18. doi: 10.1007/s11427-024-2779-9. Online ahead of print.ABSTRACTProlonged exposure to high-altitude environments may increase the risk of cognitive decline in young migrants. Recent studies suggest that hypobaric hypoxia-induced alterations in gut microbial composition could partly contribute to this risk. However, the absence of direct evidence from cohort studies and an unclear mechanism hinder intervention development based on this hypothesis. This study recruited 109 young male migrants living in Xizang to investigate the microbial mechanisms underlying cognitive impairment associated with high-altitude migration. Multi-omic analysis revealed distinct microbiome and metabolome features in migrants with cognitive decline, notably a reduced abundance of Clostridium species and disrupted fecal absorption of L-valine. Mechanistic studies showed that hypobaric hypoxia significantly damaged the intestinal barrier, leading to lipopolysaccharide (LPS) leakage and an influx of inflammatory factors into the peripheral blood, which activated microglia and caused neuronal injury in the hippocampus of mice. Additionally, compromised L-valine absorption due to intestinal barrier damage correlated with lower hippocampal glutamate levels and neurotrophic factors. Intervention with Clostridium sp. effectively restored the intestinal barrier and enhanced L-valine absorption, which mitigated hypobaric hypoxia-induced inflammation and hippocampal neural damage in mice. In conclusion, cognitive impairment among young migrants at high altitude may be attributed to hypobaric hypoxia-induced gut microbiota disruption and subsequent intestinal barrier dysfunction. This study may provide a promising approach for preventing and treating high-altitude-associated cognitive impairment.PMID:39704932 | DOI:10.1007/s11427-024-2779-9

J Neurooncol. 2024 Dec 20. doi: 10.1007/s11060-024-04902-0. Online ahead of print.ABSTRACTPURPOSE: To review applications of cerebral spinal fluid (CSF) biomarkers for the diagnosis, monitoring and treatment of leptomeningeal metastatic disease (LMD) among patients with metastatic solid tumors.METHODS: A narrative review identified original research related to CSF biomarkers among patients with metastatic solid tumors and LMD. Pre-clinical research (e.g. studies conducted in animal models) was not included. A descriptive analysis of literature was undertaken, with a focus on clinical applications related to the diagnosis, monitoring and treatment of LMD.RESULTS: The low cellularity of CSF in comparison to plasma is an advantage for liquid biopsy, given that circulating tumor DNA (ctDNA) is not significantly diluted by genomic DNA from non-cancer cells. This results in higher variant allelic frequencies and increased sensitivity in detecting ctDNA compared to plasma. However, the clinical significance of positive ctDNA and/or circulating tumor cells (CTCs) in the CSF, particularly in the absence of other signs of LMD (either clinical and/or radiological), remains unclear. While the use of CSF liquid biopsy to monitor treatment response is promising, this approach requires prospective validation using larger sample sizes prior to adoption in routine clinical care. Discovery efforts involving proteomics and metabolomics have potential to identify proteins involved in the regulation of energy metabolism, vasculature, and inflammation in LMD, which in turn, may offer insights into novel treatment approaches.CONCLUSION: CSF liquid biopsy should be incorporated in prospective studies for patients with LMD to validate promising diagnostic and/or predictive biomarkers of treatment response, as well as new therapeutic targets.PMID:39704899 | DOI:10.1007/s11060-024-04902-0

Plant Cell Rep. 2024 Dec 20;44(1):8. doi: 10.1007/s00299-024-03399-1.ABSTRACTN-Sulfonated IAA was discovered as a novel auxin metabolite in Urtica where it is biosynthesized de novo utilizing inorganic sulfate. It showed no auxin activity in DR5::GUS assay, implying possible inactivation/storage mechanism. A novel auxin derivative, N-sulfoindole-3-acetic acid (IAA-N-SO3H, SIAA), was discovered in stinging nettle (Urtica dioica) among 116 sulfonated metabolites putatively identified by a semi-targeted UHPLC-QqTOF-MS analysis of 23 plant/algae/fungi species. These sulfometabolites were detected based on the presence of a neutral loss of sulfur trioxide, as indicated by the m/z difference of 79.9568 Da in the MS2 spectra. The structure of newly discovered SIAA was confirmed by synthesizing its standard and comparing retention time, m/z and MS2 spectrum with those of SIAA found in Urtica. To study its natural occurrence, 73 species in total were further analyzed by UHPLC-QqTOF-MS or targeted UHPLC-MS/MS method with a limit of detection of 244 fmol/g dry weight. However, SIAA was only detected in Urtica at a concentration of 13.906 ± 9.603 nmol/g dry weight. Its concentration was > 30 times higher than that of indole-3-acetic acid (IAA), and the SIAA/IAA ratio was further increased under different light conditions, especially in continuous blue light. In addition to SIAA, structurally similar metabolites, N-sulfoindole-3-lactic acid, 4-(sulfooxy)phenyllactic acid and 4-(sulfooxy)phenylacetic acid, were detected in Urtica for the first time. SIAA was biosynthesized from inorganic sulfate in seedlings, as confirmed by the incorporation of exogenous 34S-ammonium sulfate (1 mM and 10 mM). SIAA exhibited no auxin activity, as demonstrated by both the Arabidopsis DR5::GUS assay and the Arabidopsis phenotype analysis. Sulfonation of IAA may therefore be a mechanism for IAA deactivation and/or storage in Urtica, similar to sulfonation of the jasmonates in Arabidopsis.PMID:39704813 | DOI:10.1007/s00299-024-03399-1

ACS Nano. 2024 Dec 20. doi: 10.1021/acsnano.4c11505. Online ahead of print.ABSTRACTSpatial omics methods are extensions of traditional histological methods that can illuminate important biomedical mechanisms of physiology and disease by examining the distribution of biomolecules, including nucleic acids, proteins, lipids, and metabolites, at microscale resolution within tissues or individual cells. Since, for some applications, the desired resolution for spatial omics approaches the nanometer scale, classical tools have inherent limitations when applied to spatial omics analyses, and they can measure only a limited number of targets. Nanotechnology applications have been instrumental in overcoming these bottlenecks. When nanometer-level resolution is needed for spatial omics, super resolution microscopy or detection imaging techniques, such as mass spectrometer imaging, are required to generate precise spatial images of target expression. DNA nanostructures are widely used in spatial omics for purposes such as nucleic acid detection, signal amplification, and DNA barcoding for target molecule labeling, underscoring advances in spatial omics. Other properties of nanotechnologies include advanced spatial omics methods, such as microfluidic chips and DNA barcodes. In this review, we describe how nanotechnologies have been applied to the development of spatial transcriptomics, proteomics, metabolomics, epigenomics, and multiomics approaches. We focus on how nanotechnology supports improved resolution and throughput of spatial omics, surpassing traditional techniques. We also summarize future challenges and opportunities for the application of nanotechnology to spatial omics methods.PMID:39704725 | DOI:10.1021/acsnano.4c11505

J Exp Med. 2025 Feb 3;222(2):e20240728. doi: 10.1084/jem.20240728. Epub 2024 Dec 20.ABSTRACTInvariant natural killer T (iNKT) cells are unconventional T cells recognizing lipid antigens in a CD1d-restricted manner. Among these lipid antigens, α-galactosylceramide (α-GalCer), which was originally identified in marine sponges, is the most potent antigen. Although the presence of α-anomeric hexosylceramide and microbiota-derived branched α-GalCer is reported, antigenic α-GalCer has not been identified in mammals. Here, we developed a high-resolution separation and detection system, supercritical fluid chromatography tandem mass spectrometry (SFC/MS/MS), that can discriminate hexosylceramide diastereomers (α-GalCer, α-GlcCer, β-GalCer, or β-GlcCer). The B16 melanoma tumor cell line does not activate iNKT cells; however, ectopic expression of CD1d was sufficient to activate iNKT cells without adding antigens. B16 melanoma was unlikely to generate iNKT cell antigens; instead, antigen activity was detected in cell culture serum. Activity-based purification and SFC/MS/MS identified dihydrosphingosine-based saturated α-GalCer as an antigenic component in serum, bile, and lymphoid tissues. These results show the first evidence for the presence of potent antigenic α-GalCer in mammals.PMID:39704712 | DOI:10.1084/jem.20240728

Physiol Plant. 2024 Nov-Dec;176(6):e70006. doi: 10.1111/ppl.70006.ABSTRACTMelatonin (MT) serves an indispensable function in plant development and their response to abiotic stress. Although numerous drought-tolerance genes have been ascertained in wheat, further investigation into the molecular pathways controlling drought stress tolerance remains necessary. In this investigation, it was observed that MT treatment markedly enhanced drought resistance in wheat by diminishing malondialdehyde (MDA) levels and augmenting the activity of antioxidant enzymes POD, APX, and CAT compared to untreated control plants. Transcriptomic analysis disclosed that melatonin treatment activated the tryptophan metabolism and flavonoid biosynthesis pathways. Furthermore, quantitative reverse transcription PCR (qRT-PCR) outcomes validated that the expression trends of these differentially expressed genes aligned with the transcriptomic data. Metabolomic profiling identified alterations in the abundance of several metabolites, including tryptamine, MT, formylanthranilate, 3-hydroxyanthranilate, 6-hydroxymelatonin, naringenin chalcone, astragalin, pinbanksin, and caffeoyl quinic acid. Co-expression analysis suggested that various transcription factors-encompassing AP2/ERF-ERF, WRKY, bZIP, C2H2, bHLH, NAC, and MYB-participated in controlling the differentially expressed genes across multiple pathways. Ultimately, these findings highlight that exogenous MT application bolsters wheat's drought tolerance through the modulation of tryptophan metabolism and flavonoid biosynthesis. These insights provide novel perspectives on the molecular frameworks mediating MT's effect on drought resistance and pinpointing candidate genes for potential genetic enhancement programs in wheat.PMID:39704497 | DOI:10.1111/ppl.70006

J Inherit Metab Dis. 2025 Jan;48(1):e12832. doi: 10.1002/jimd.12832.ABSTRACTX-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder resulting from pathogenic variants in the ABCD1 gene that primarily affects the nervous system and is characterized by progressive axonal degeneration in the spinal cord and peripheral nerves and leukodystrophy. Dysfunction of peroxisomal very long-chain fatty acid (VLCFA) degradation has been implicated in ALD pathology, but the impact on astrocytes, which critically support neuronal function, remains poorly understood. Fibroblasts from four ALD patients were reprogrammed to generate human-induced pluripotent stem cells (hiPSC). hiPSC-derived astrocytes were generated to study the impact of ALD on astrocytic fatty acid homeostasis. Our study reveals significant changes in the lipidome of ALD hiPSC-derived astrocytes, characterized by an enrichment of VLCFAs across multiple lipid classes, including triacylglycerols, cholesteryl esters, and phosphatidylcholines. Importantly, ALD hiPSC-derived astrocytes not only exhibit intrinsic lipid dysregulation but also affect the dendritic tree complexity of neurons in co-culture systems. These findings highlight the cell-autonomous effects of pathogenic variants in the ABCD1 protein on astrocytes and their microenvironment, shed light on potential mechanisms underlying ALD neuropathology, and underscore the critical role of astrocytes in neuronal health.PMID:39704488 | DOI:10.1002/jimd.12832

Environ Sci Technol. 2024 Dec 20. doi: 10.1021/acs.est.4c07881. Online ahead of print.ABSTRACTFoliar application of beneficial nanoparticles exhibits potential in mitigating combined stresses from heavy metals and polycyclic aromatic hydrocarbons (PAHs) in crops, necessitating a comprehensive understanding of plant-rhizosphere-microbial processes to promote sustainable nanotechnology in agriculture. Herein, we investigated the mitigating mechanisms of foliar application of zinc oxide nanoparticles (nZnO) on lettuce growth under phenanthrene (Phe) and cadmium (Cd) costress. Compared to Phe + Cd treatment, low (L-nZnO) and high (H-nZnO) concentration of nZnO increased fresh biomass (27.2% and 8.42%) and root length (20.4% and 39.6%) and decreased MDA (35.0% and 40.0%) and H2O2 (29.0% and 15.6%) levels. L-nZnO and H-nZnO decreased Cd in roots (26.8% and 41.8%) and enhanced Zn in roots (19.9% and 107%), stems (221% and 2510%), and leaves (233% and 1500%), suggesting the long-distance migration of Zn from leaves to roots and subsequently regulating the metabolic pathways and microbial communities. Metabolomics revealed that nZnO modulated leaf glycerophospholipid metabolism and amino acid pathways and promoted rhizosphere soil carbon and phosphorus metabolism. Additionally, nZnO enriched the plant-growth-promoting, extreme, and stress-resistant bacteria in roots and leaves and heavy-metal-resistant and PAH-degrading bacteria in rhizosphere soil. These findings underscore the promising nanostrategy of nZnO to benefit plant growth in soil cocontaminated with heavy metals and PAHs.PMID:39704184 | DOI:10.1021/acs.est.4c07881

Haematologica. 2024 Dec 19. doi: 10.3324/haematol.2024.285154. Online ahead of print.ABSTRACTPlasma metabolomics analysis was performed on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r/B-NHL) infused with approved CD19.CAR-T cell products at the time of pre-lymphodepletion (PLD) and at day +1, +7, and +30 after CAR-T cell infusion. At the PLD time point, a metabolic profile characterized by high lipoproteins and lactate and low glucose contributed to poor outcome prediction in association with high lactate dehydrogenase levels. At day+1, higher plasma levels of lipid metabolism products and lower glucose and glycoproteins levels were observed in tisa-cel compared to axi-cel-treated patients. At day+30, discriminant analysis found two clusters in a subgroup of patients, one with CR lasting one year after therapy, and another who relapsed within one year (relapsed>D30). This latter showed a higher content of N-GlycA, a known biomarker of systemic inflammation that is also correlated with C-reactive protein in our case setting of relapsing patients. Our data show complex metabolomic changes that track the evolution of the disease and drug activity in the first 30 days of CAR-T cell therapy. Conceivably, a pro-inflammatory drift may be linked to a forthcoming disease relapse in CAR-T patients.PMID:39704157 | DOI:10.3324/haematol.2024.285154