PubMed

Plant Physiol. 2024 Dec 11:kiae642. doi: 10.1093/plphys/kiae642. Online ahead of print.ABSTRACTThe SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex is involved in various aspects of plant development and stress responses. Here, we investigated the role of BRM (BRAHMA), a core catalytic subunit of the SWI/SNF complex, in Arabidopsis thaliana seed biology. brm-3 seeds exhibited enlarged size, reduced yield, increased longevity, and enhanced secondary dormancy, but did not show changes in primary dormancy or salt tolerance. Some of these phenotypes depended on the expression of DOG1, a key regulator of seed dormancy, as they were restored in the brm-3 dog1-4 double mutant. Transcriptomic and metabolomic analyses revealed that BRM and DOG1 synergistically modulate the expression of numerous genes. Some of the changes observed in the brm-3 mutant, including increased glutathione levels, depended on a functional DOG1. We demonstrated that the BRM-containing chromatin remodeling complex directly controls secondary dormancy through DOG1 by binding and remodeling its 3' region, where the promoter of the long non-coding RNA asDOG1 is located. Our results suggest that BRM and DOG1 cooperate to control seed physiological properties and that BRM regulates DOG1 expression through asDOG1. This study reveals chromatin remodeling at the DOG1 locus as a molecular mechanism controlling the interplay between seed viability and dormancy.PMID:39661382 | DOI:10.1093/plphys/kiae642

Anal Chem. 2024 Dec 11. doi: 10.1021/acs.analchem.4c03808. Online ahead of print.ABSTRACTVarious rounded turn designs in Structures for Lossless Ion Manipulation (SLIM) were explored via ion trajectory simulations. The optimized design was integrated into a SLIM ion mobility (IM) system coupled with a time-of-flight (TOF) mass spectrometer (MS) for further experimental investigation. The SLIM-TOF IM-MS system was assessed for IM resolution and ion transmission efficiency across a wide m/z range using various RF frequencies and buffer gas combinations. High ion transmission efficiency and high resolution ion mobility (HRIM) separation were achieved for Agilent tune mix ions through a ∼12.8 m serpentine separation path in both nitrogen and helium. In helium, ion transmission for low m/z ions was enhanced at higher RF trapping frequency, enabling the detection of ions with m/z below 50 and all 17 amino acids from a standard mixture. Lossless ion transmission was observed for glycine (m/z 76) in both passthrough and HRIM modes. HRIM resolution was benchmarked using L-isoleucine, L-leucine, and various other isobaric and isomeric metabolites with m/z values of 60-89. This work demonstrates a rounded turn SLIM design that enables HRIM measurements for small molecule analytes, with a particular focus on metabolomics, where IM offers a means to enhance the speed, robustness, and specificity of analytical workflows.PMID:39661157 | DOI:10.1021/acs.analchem.4c03808

Ann Hematol. 2024 Dec 11. doi: 10.1007/s00277-024-06089-w. Online ahead of print.ABSTRACTAcute myeloid leukemia (AML) with FLT3-ITD mutation represents a quarter of AML patients and is associated with high relapse rate and dismal prognosis. FLT3 tyrosine kinase inhibitors (TKIs) were developed in order to target this genetic alteration and among these TKIs, AC220 (quizartinib) combined with chemotherapy has already shown an increased overall survival for patients with AML with FLT3-ITD mutation. Even though this increase in overall survival was significant, it remains discrete, and relapse rate is still high, so there is an unmet medical need. All-trans retinoic acid (ATRA) is well known for its effectiveness in acute promyelocytic leukemia (APL) treatment and has already been shown to have synergistic effects combined with another TKI, sorafenib. In this study, quizartinib, a more potent FLT3-TKI, was tested in combination with ATRA in the AML FLT3-ITD positive cell lines MOLM-13 and MV4-11. ATRA has effectively improved AC220 induced cell death via caspase activation. In addition, ATRA in combination with AC220 treatment notably enhanced BECN1 cleavage compared to AC220 treatment alone. Finally, in a xenotransplantation model ATRA plus AC220 was more efficient to reduce the leukemic burden than monotherapy with ATRA or AC220. Taken together, our results are a proof of the concept that ATRA and AC220 have synergistic anti-leukemic effects.PMID:39661129 | DOI:10.1007/s00277-024-06089-w

mSystems. 2024 Dec 11:e0045724. doi: 10.1128/msystems.00457-24. Online ahead of print.ABSTRACTEmerging evidence highlights the potential impact of intratumoral microbiota on cancer. However, the microbial composition and function in glioma remains elusive. Consequently, our study aimed to investigate the microbial community composition in glioma tissues and elucidate its role in glioma development. We parallelly performed microbial profiling, transcriptome sequencing, and metabolomics detection on tumor and adjacent normal brain tissues obtained from 50 glioma patients. We employed immunohistochemistry, multicolor immunofluorescence, and fluorescence in situ hybridization (FISH) staining to observe the presence and location of bacteria. Furthermore, an animal model was employed to validate the impact of key bacteria on glioma development. Six genera were found to be significantly enriched in glioma tissues compared to adjacent normal brain tissues, including Fusobacterium, Longibaculum, Intestinimonas, Pasteurella, Limosilactobacillus, and Arthrobacter. Both bacterial RNA and lipopolysaccharides (LPS) were observed in glioma tissues. Integrated microbiomics, transcriptomics, and metabolomics revealed that genes associated with intratumoral microbes were enriched in multiple synapse-associated pathways and that metabolites associated with intratumoral microbes were (R)-N-methylsalsolinol, N-acetylaspartylglutamic acid, and N-acetyl-l-aspartic acid. Further mediation analysis suggested that the intratumoral microbiome may affect the expression of neuron-related genes through bacteria-associated metabolites. In addition, both in vivo and in vitro models of glioma show that Fusobacterium nucleatum promotes glioma proliferation and upregulates CCL2, CXCL1, and CXCL2 levels. Our findings shed light on the intricate interplay between intratumoral bacteria and glioma.IMPORTANCE: Our study adopted a multi-omics approach to unravel the impact of intratumoral microbes on neuron-related gene expression through bacteria-associated metabolites. Importantly, we found bacterial RNA and LPS signals within glioma tissues, which were traditionally considered sterile. We identified key microbiota within glioma tissues, including Fusobacterium nucleatum (Fn). Through in vivo and in vitro experiments, we identified the crucial role of Fn in promoting glioma progression, suggesting that Fn could be a potential diagnostic and therapeutic target for glioma patients. These findings offer valuable insights into the intricate interplay between intratumoral bacteria and glioma, offering novel inspiration to the realm of glioma biology.PMID:39660865 | DOI:10.1128/msystems.00457-24

Front Immunol. 2024 Nov 26;15:1464664. doi: 10.3389/fimmu.2024.1464664. eCollection 2024.ABSTRACTINTRODUCTION: Peyer's patches (PPs) are crucial antigen-inductive sites of intestinal mucosal immunity. Prior research indicated that, in contrast to other ruminants, PPs in the small intestine of Bactrian camels are found in the duodenum, jejunum, and ileum and display polymorphism. Using this information, we analyzed the microbial and metabolic characteristics in various segments of the Bactrian camel's small intestine to further elucidate how the immune system varies across different regions.METHODS: In this study, the microbiota and metabolite of 36 intestinal mucosal samples, including duodenal (D-PPs), jejunal (J-PPs), and ileal PPs (I-PPs), were profiled for six Bactrian camels using 16S rRNA gene sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS). To confirm meaningful associations, we conducted connection analyses on the significantly different objects identified in each group's results. ELISA was used to analyze the levels of IgA, IgG, and IgM in the same tissues.RESULTS: The microbiota and metabolite profiles of J-PPs and I-PPs were found to be similar, whereas those of D-PPs were more distinct. In J-PPs and I-PPs, the dominant bacterial genera included Clostridium, Turicibacter, and Shigella. In contrast, D-PPs had a significant increase in the abundance of Prevotella, Fibrobacter, and Succinobacter. Regarding the metabolomics, D-PPs exhibited high levels of polypeptides, acetylcholine, and histamine. On the other hand, J-PPs and I-PPs were characterized by an enrichment of free amino acids, such as L-arginine, L-glutamic acid, and L-serine. These metabolic differences mainly involve amino acid production and metabolic processes. Furthermore, the distribution of intestinal immunoglobulins highlighted the specificity of D-PPs. Our results indicated that proinflammatory microbes and metabolites were significantly enriched in D-PPs. In contrast, J-PPs and I-PPs contained substances that more effectively enhance immune responses, as evidenced by the differential distribution of IgA, IgG, and IgM.DISCUSSION: The intestinal microenvironment of Bactrian camels displays distinct regional disparities, which we propose are associated with variations in immunological function throughout different segments of the small intestine. This study highlights the specific traits of the intestinal microbiota and metabolites in Bactrian camels, offering a valuable reference for understanding the relationship between regional intestinal immunity and the general health and disease of the host.PMID:39660142 | PMC:PMC11628504 | DOI:10.3389/fimmu.2024.1464664

Anim Nutr. 2024 Jul 23;19:117-130. doi: 10.1016/j.aninu.2024.04.028. eCollection 2024 Dec.ABSTRACTThis study aimed to develop a compensatory growth model using growing beef cattle by changing dietary protein and to investigate the underlying mechanisms of compensatory protein deposition in muscle tissue. Twelve Charolais bulls were randomly assigned to one of two groups with two periods: 1) a control group (CON) fed a 13% crude protein (CP) diet for 6 weeks; 2) a treatment group (REC) fed a 7% CP diet for 4 weeks (restriction period) and fed a 13% CP diet in the following 2 weeks (re-alimentation period). Growth performance, digestibility, nitrogen balance, targeted metabolomics of amino acids (AA) in plasma, and transcriptional profiling in muscle tissue were analyzed. Protein restriction decreased average daily gain (ADG; P < 0.05), while protein re-alimentation increased ADG relative to the CON (P < 0.05). Compared to the CON, REC reduced retained N (P < 0.05), and protein re-alimentation increased retained N and N utilization efficiency (P < 0.05), due to reduced urinary urea, hippuric acid, and creatinine excretions (P < 0.05). Ruminal NH3-N in the REC was lower than that in the CON in the protein re-alimentation period (P < 0.05). However, there was no difference in microbial protein and plasma urea nitrogen concentrations. Dietary protein restriction decreased plasma valine and aspartic acid concentrations relative to the CON (P < 0.05), and increased proline and 3-methyl-L-histidine concentrations (P < 0.05). After dietary protein re-alimentation, REC increased plasma citrulline concentrations (P < 0.05). The transcriptional profiling revealed that REC upregulated the AA transporter SLC3A1, and protein re-alimentation downregulated SLC7A8 in the muscle cell membrane. Within the muscle cell, upregulated cytosolic arginine sensor for mTORC1 subunit 2 (CASTOR2) inhibited protein synthesis by inhibiting the mammalian target of rapamycin complex 1 phosphorylation in the protein restriction period, while DNA-damage-inducible transcript 4 (DDIT4) activated the mTOR signaling pathway and promoted protein synthesis in the protein re-alimentation period. In summary, the targeted metabolomics and transcriptomics analyses demonstrated that protein re-alimentation following restriction can promote protein synthesis and reduce muscle breakdown by regulating AA metabolism and functional transcripts related to AA transporters and the mTOR signaling pathway.PMID:39659991 | PMC:PMC11630643 | DOI:10.1016/j.aninu.2024.04.028

Neurooncol Adv. 2024 Nov 19;6(1):vdae187. doi: 10.1093/noajnl/vdae187. eCollection 2024 Jan-Dec.ABSTRACTBACKGROUND: Glioblastoma, a lethal high-grade glioma, has not seen improvements in clinical outcomes in nearly 30 years. Ion channels are increasingly associated with tumorigenesis, and there are hundreds of brain-penetrant drugs that inhibit ion channels, representing an untapped therapeutic resource. The aim of this exploratory drug study was to screen an ion channel drug library against patient-derived glioblastoma cells to identify new treatments for brain cancer.METHODS: Seventy-two ion channel inhibitors were screened in patient-derived glioblastoma cells, and cell viability was determined using the ViaLight Assay. Cell cycle and apoptosis analysis were determined with flow cytometry using PI and Annexin V staining, respectively. Protein and phosphoprotein expression was determined using mass spectrometry and analyzed using gene set enrichment analysis. Kaplan-Meier survival analyses were performed using intracranial xenograft models of GBM6 and WK1 cells.RESULTS: The voltage-gated sodium channel modulator, DPI-201-106, was revealed to reduce glioblastoma cell viability in vitro by inducing cell cycle arrest and apoptosis. Phosphoproteomics indicated that DPI-201-106 may impact DNA damage response (DDR) pathways. Combination treatment of DPI-201-106 with the CHK1 inhibitor prexasertib or the PARP inhibitor niraparib demonstrated synergistic effects in multiple patient-derived glioblastoma cells both in vitro and in intracranial xenograft mouse models, extending survival of glioblastoma-bearing mice.CONCLUSIONS: DPI-201-106 enhances the efficacy of DDR inhibitors to reduce glioblastoma growth. As these drugs have already been clinically tested in humans, repurposing DPI-201-106 in novel combinatorial approaches will allow for rapid translation into the clinic.PMID:39659830 | PMC:PMC11630809 | DOI:10.1093/noajnl/vdae187

Food Chem X. 2024 Nov 16;24:102016. doi: 10.1016/j.fochx.2024.102016. eCollection 2024 Dec 30.ABSTRACTThis study examines the microbial community composition, metabolite characteristics, and the relationship between the two during the fermentation process of Yi traditional fermented liquor. Yi traditional fermented foods have a profound historical and cultural background, with significant ethnic characteristics. As a case in point, Yi traditional fermented liquor is typically prepared using local plants or traditional Chinese herbs as fermentation substrates and undergoes a lengthy fermentation process, resulting in a fermented beverage that is reputed to have beneficial effects on human health. These foods are not only characterised by a distinctive flavor profile, but are also perceived to possess certain health benefits in the context of traditional ethnic medicine and wellness practices. The community composition of bacteria and fungi was analyzed using 16S rRNA and ITS1 sequencing technologies, which revealed that microbial diversity was higher in the early stages of fermentation but gradually decreased as fermentation progressed. A total of 130 major volatile flavor compounds and 26 key metabolites were identified at different stages of fermentation. These included acids, sugars, amino acids and flavonoids, which significantly influence the flavor and nutritional value of the fermented products. The study indicates a significant correlation between specific microbial populations (such as yeasts) and key metabolites (such as flavonoids and amino acids). These findings emphasise the significance of the interplay between microbial communities and metabolites in shaping the quality and efficacy of fermented products. They offer a scientific foundation for optimizing traditional fermented food production processes.PMID:39659683 | PMC:PMC11629247 | DOI:10.1016/j.fochx.2024.102016

Food Chem X. 2024 Nov 20;24:102021. doi: 10.1016/j.fochx.2024.102021. eCollection 2024 Dec 30.ABSTRACTAnaerobic fermentation (AF) is critical process for Yunnan De'ang pickled tea production. Therefore, widely targeted metabolomics and metagenomics were integrated to reveal the AF mechanism. Lactic acid bacteria (LAB) (e.g. Lactiplantibacillus plantarum, Lactobacillus vaccinostercus and Lactobacillus paracollinoides) and yeasts like Candida metapsilosis and Cyberlindnera fabianii dominated in the AF. Based on bacterial community succession and metabolites variation, the whole AF processes were divided into two phases, i.e., before and after four months. A total of 327 characteristic metabolites (VIP >1.0, P < 0.05, and FC > 1.50 or < 0.67) were selected from the AF. Besides amino acids increase, LAB and yeasts also promoted non-galloylated catechins, and several simple flavones/flavonols, flavanones/flavanonols and methoxy flavones/flavonols accumulations along with galloylated catechins, flavonol/flavone glycosides and anthocyanins decrease during the AF. This study would improve the understanding about AF mechanism of tea-leaves from the perspectives of flavonoids metabolism and microbial community succession.PMID:39659682 | PMC:PMC11629561 | DOI:10.1016/j.fochx.2024.102021

Bioinform Adv. 2024 Nov 14;4(1):vbae178. doi: 10.1093/bioadv/vbae178. eCollection 2024.ABSTRACTMOTIVATION: The availability of longitudinal omics data is increasing in metabolomics research. Viewing metabolomics data over time provides detailed insight into biological processes and fosters understanding of how systems react over time. However, the analysis of longitudinal metabolomics data poses various challenges, both in terms of statistical evaluation and visualization.RESULTS: To make explorative analysis of longitudinal data readily available to researchers without formal background in computer science and programming, we present MEtabolite Trajectory ExplORer (MeTEor). MeTEor is an R Shiny app providing a comprehensive set of statistical analysis methods. To demonstrate the capabilities of MeTEor, we replicated the analysis of metabolomics data from a previously published study on COVID-19 patients.AVAILABILITY AND IMPLEMENTATION: MeTEor is available as an R package and as a Docker image. Source code and instructions for setting up the app can be found on GitHub (https://github.com/scibiome/meteor). The Docker image is available at Docker Hub (https://hub.docker.com/r/gordomics/meteor). MeTEor has been tested on Microsoft Windows, Unix/Linux, and macOS.PMID:39659589 | PMC:PMC11631383 | DOI:10.1093/bioadv/vbae178

Theranostics. 2024 Nov 4;14(19):7534-7553. doi: 10.7150/thno.101229. eCollection 2024.ABSTRACTRationale: Ischemia-reperfusion-induced acute kidney injury (IR-AKI), characterized by the abrupt decline in renal function, is distinguished by the intricate interplay between oxidative stress and inflammation. In this study, a reactive oxygen species (ROS) scavenger-CF@PDA was developed to effectively target antioxidant and anti-inflammatory pathways to disrupt the oxidative stress-inflammation cycle in IR-AKI. Methods: UV-vis absorption spectra, FTIR spectra, and TEM were employed to determine the successful construction of CF@P. ABTS, TMB, and NBT analyses were performed to detect the antioxidant ability and enzyme-mimicking ability of CF@P. In vitro and in vitro, the antioxidant/anti-inflammatory effect of CF@P was detected by MTT, qPCR, fluorescence, and flow cytometry. Multi-omics revealed the mechanism of CF@P in IR-AKI therapy, and molecular docking was further used to determine the mechanism. MRI and photoacoustic imaging were employed to explore the dual-mode imaging capacity of CF@P in IR-AKI management. Results: CF@P could disrupt the oxidative stress-inflammatory cascade by scavenging ROS, reducing pro-inflammatory cytokines, and modulation of macrophage polarization. Subsequent multi-omics indicated that the renal protective effects may be attributed to the inhibition of pyruvate dehydrogenase kinase 4 (PDK4). Metabolomics demonstrated that CF@P could improve the production of antioxidant compounds and reduce nephrotoxicity. Additionally, CF@P exhibited promising capabilities in T1-MRI and photoacoustic imaging for AKI management. Conclusions: Collectively, CF@P, possessing antioxidant/anti-inflammatory properties by inhibiting PDK4, as well as imaging capabilities and superior biocompatibility, holds promise as a therapeutic strategy for IR-AKI.PMID:39659578 | PMC:PMC11626943 | DOI:10.7150/thno.101229

Theranostics. 2024 Oct 28;14(19):7292-7308. doi: 10.7150/thno.99323. eCollection 2024.ABSTRACTRationale: Metabolic dysfunction is one of the key pathological events after ischemic stroke. Disruption of cerebral blood flow impairs oxygen and energy substrate delivery, leading to mitochondrial oxidative phosphorylation dysfunction and cellular bioenergetic stress. Investigating the effects of circSCMH1, a brain repair-related circular RNA, on metabolism may identify novel therapeutic targets for stroke treatment. Methods: CircSCMH1 was encapsulated into brain-targeting extracellular vesicles (EVs) mediated by rabies virus glycoprotein (RVG). Using a mouse model of photothrombotic (PT) stroke, we employed metabolomics and transcriptomics, combined with western blotting and behavioral experiments, to identify the metabolic targets regulated in RVG-circSCMH1-EV-treated mice. Additionally, immunofluorescence staining, chromatin immunoprecipitation (ChIP), pull-down, and western blotting were utilized to elucidate the underlying mechanisms. Results: The targeted delivery of circSCMH1 via RVG-EVs was found to promote post-stroke brain repair by enhancing mitochondrial fusion and inhibiting mitophagy through suppression of kynurenine 3-monooxygenase (KMO) expression. Mechanistically, circSCMH1 exerted its inhibitory effect on KMO expression by binding to the transcription activator STAT5B, thereby impeding its nuclear translocation. Conclusions: Our study reveals a novel mechanism by which circSCMH1 downregulates KMO expression, thereby enhancing mitochondrial fusion and inhibiting mitophagy, ultimately facilitating post-stroke brain repair. These findings shed new light on the role of circSCMH1 in promoting stroke recovery and underscore its potential as a therapeutic target for the treatment of ischemic stroke.PMID:39659575 | PMC:PMC11626939 | DOI:10.7150/thno.99323

Front Microbiol. 2024 Nov 26;15:1463958. doi: 10.3389/fmicb.2024.1463958. eCollection 2024.ABSTRACTThe gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic-pituitary-adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.PMID:39659426 | PMC:PMC11628546 | DOI:10.3389/fmicb.2024.1463958

Front Plant Sci. 2024 Nov 26;15:1434462. doi: 10.3389/fpls.2024.1434462. eCollection 2024.ABSTRACTINTRODUCTION: It is desirable to rehabilitate desert ecosystems with a selection of native plant species that render ecosystem services and yield natural products for creating a high-value industry, e.g., pharmaceuticals or cosmetics. However, plant growth under arid and hyper-arid conditions, such as in the Arabian Peninsula, is constrained by heat, freshwater scarcity, and alkaline sandy soils with low nutrient and water holding capacity. Therefore, it is imperative to develop nature-based sustainable technologies to improve arid soil conditions, as well as increase irrigation and nutrient-use eficiency.METHODS: Here, we report on a study evaluating the effects of two complementary soil amendment technologies, namely Superhydrophobic sand (SHS) mulch and engineered biochar (EB) on the growth of Moringa oleifera plants. Effects of SHS (1cm-thick), EB (2% w/w), and SHS+EB treatments were tracked in greenhouse plants under normal (N, 100% field capacity) and reduced (R, 50% of N) irrigation scenarios for over 150 days, where EB treatments were pre-loaded with nutrients and remaining treatments received traditional NPK fertilizer.RESULTS: Significant benefits of the SHS, EB, and SHS+EB treatments were found in terms of increased plant height, trunk diameter, leaf area, leaf chlorophyll content index, stomatal conductance, and shoot and root biomass in comparison with the controls. Evaporation water savings due to SHS mulching significantly enhanced transpiration under N and R scenarios. Similarly, EB and SHS+EB treated plants experienced higher transpiration than in the control plants under N and R conditions (p< 0.05). In response to water stress due to excessive evaporation, metabolomics analysis showed a higher accumulation of amino acids in control plants than other treatments under both irrigation regimes. Meanwhile, a higher abundance of sugars (i.e., D-Mannose, D-Fructose, glucose) and organic acid (i.e., malic acid) was observed in SHS and EB-treatments for Variable Importance in Projection (VIP) scores >1.0 (i.e., the scores considered of significance in contributing to the differences between treatment groups).DISCUSSION: The results show the synergistic benefits of SHS and EB technologies for addressing the challenges of water scarcity and nutrient limitation in arid regions, which couldcontribute to the success and sustainability of agriculture and greening efforts in such regions.PMID:39659422 | PMC:PMC11628278 | DOI:10.3389/fpls.2024.1434462

Front Plant Sci. 2024 Nov 26;15:1475416. doi: 10.3389/fpls.2024.1475416. eCollection 2024.ABSTRACTINTRODUCTION: Inducing natural resistance against pathogen infection in postharvest tomatoes is a sustainable strategy for reducing postharvest losses. The action model underlying the resistance enhancement of tomatoes induced by bacterial volatile organic compounds (VOCs) against Botrytis cinerea, however, have not been explored.METHODS: In this study, RNA-seq, metabolomics and physiological analysis were used to evaluate global change of defense response induced by VOCs in tomatoes.RESULTS: The application of VOCs inhibited the damage to tomatoes caused by B. cinerea. VOCs treatment had remarkable beneficial effects on the activities of the main defence-related enzymes, including chitinases, glucanases, peroxidases, ascorbate peroxidases, polyphenol oxidases, and phenylalanine ammonia-lyases. The expression of response genes involved in salicylic acid and jasmonic acid biosynthesis and signalling pathways was enhanced upon VOCs treatment. Metabolomics data demonstrated that VOC treatment triggered the accumulation of phenolic acids, including substrates in phenolic acid biosynthesis pathways, hydroxycinnamic acid, hydroxybenzoic acid, and their derivatives. Transcriptomics analysis and qRT-PCR verification revealed that VOCs treatment significantly upregulates the expression of core genes related to phenolic acid biosynthesis, specifically in shikimate pathway (SlDAHPS, SlSDH, SlCS, and SlADT3) and phenylalanine metabolic pathway (SlPAL, Sl4CL, SlBAHD1, SlCYP98A2 and SlCAP84A1).DISCUSSION: Results confirmed that VOCs enhanced tomatoes postharvest resistance against B. cinerea by regulating defence enzyme activity, SA/JA signalling, and phenolic acid biosynthesis pathway. This study provides new insights into the mechanisms by which VOCs fumigation manages postharvest grey mould in tomatoes.PMID:39659409 | PMC:PMC11628293 | DOI:10.3389/fpls.2024.1475416

J Sci Food Agric. 2024 Dec 11. doi: 10.1002/jsfa.14062. Online ahead of print.ABSTRACTBACKGROUND: Ginsenosides, the primary active ingredients in Panax ginseng, are secondary metabolites. However, their content varies significantly across batches due to differences in environmental conditions and production methods. Ecological stress can increase the levels of reactive oxygen species (ROS) in plants, and ROS can enhance secondary metabolism. Nitric oxide (NO) can promote the production of O2 ·- and H2O2. This study utilized physiological and non-targeted metabolomics to investigate how NO regulates ginseng quality and how P. ginseng adapts to adversity.RESULTS: Sodium nitroprusside (SNP, an NO donor) at 0.5 mmol·L-1 significantly increased ROS levels, with O2 ·- increasing by 64.3% (P < 0.01) and H2O2 by 79.2% (P < 0.01). Nitric oxide influenced P. ginseng metabolism, with 24 metabolites showing significant differences. Rotenone, lactic acid, and gluconic acid, which are involved in ROS metabolism, increased significantly, whereas tyrosine decreased. Metabolites involved in secondary metabolic pathways, including campesterol, ginsenosides Rh1, Rb1, Rc, Rd, Rg3, phenylalanine, and tryptophan, increased markedly, whereas 2,3-oxidosqualene, glucose 1-phosphate, ferulic acid, and pyrogallol decreased. Isocitric acid, succinic acid, and 3-isopropylmalic acid, associated with respiratory metabolism, showed significant increases, but pyruvic acid decreased. Finally, 18:0 Lyso PC and 9-hydroxy-10E,12Z-octadecadienoic acid, linked to cell membrane protection, increased significantly, and mannose and raffinose decreased.CONCLUSION: Sodium nitroprusside enhances the physiological resilience of P. ginseng under stress and improves its quality. © 2024 Society of Chemical Industry.PMID:39659278 | DOI:10.1002/jsfa.14062

Proteomics. 2024 Dec 10:e202400271. doi: 10.1002/pmic.202400271. Online ahead of print.ABSTRACTAdvances in high-throughput omics technologies have enabled system-wide characterization of biological samples across multiple molecular levels, such as the genome, transcriptome, and proteome. However, as sample sizes rapidly increase in large-scale multi-omics studies, sample mix-ups have become a prevalent issue, compromising data integrity and leading to erroneous conclusions. The interconnected nature of multi-omics data presents an opportunity to identify and correct these errors. This review examines the potential sources of sample mix-ups and evaluates the methodologies and tools developed for detecting and correcting these errors, with an emphasis on approaches applicable to proteomics data. We categorize existing tools into three main groups: expression/protein quantitative trait loci-based, genotype concordance-based, and gene/protein expression correlation-based approaches. Notably, only a handful of tools currently utilize the proteogenomics approach for correcting sample mix-ups at the proteomics level. Integrating the strengths of current tools across diverse data types could enable the development of more versatile and comprehensive solutions. In conclusion, verifying sample identity is a critical first step to reduce bias and increase precision in subsequent analyses for large-scale multi-omics studies. By leveraging these tools for identifying and correcting sample mix-ups, researchers can significantly improve the reliability and reproducibility of biomedical research.PMID:39659081 | DOI:10.1002/pmic.202400271

J Agric Food Chem. 2024 Dec 10. doi: 10.1021/acs.jafc.4c06072. Online ahead of print.ABSTRACTIn this study, we investigated the ameliorative effects of selenium-enriched Lactobacillus fermentum FZU3103 (Lf@Se) and its pathway on alcoholic liver injury (ALI) in mice. The results showed that Lf@Se was superior to Lf and inorganic selenium in alleviating ALI. Oral Lf@Se effectively prevented lipid metabolism disorders, improved liver function, promoted alcohol metabolism, and alleviated liver oxidative damage in mice. 16S amplicons sequencing indicated that Lf@Se intervention modulated intestinal flora homeostasis by increasing (decreasing) the abundance of beneficial bacteria (harmful bacteria), which is associated with the improvement of liver function. Besides, Lf@Se intervention altered the liver metabolic profile, and the characteristic biomarkers were mainly involved in tyrosine metabolism, retinol metabolism, galactose metabolism, and primary bile acid biosynthesis. Additionally, Lf@Se intervention regulated liver gene expression for lipid metabolism and oxidative stress. Western blot analysis revealed increased expression levels of intestinal tight junction proteins after Lf@Se intervention, thereby ameliorating alcohol-induced intestinal barrier damage.PMID:39658842 | DOI:10.1021/acs.jafc.4c06072

Adv Sci (Weinh). 2024 Dec 10:e2412222. doi: 10.1002/advs.202412222. Online ahead of print.ABSTRACTMammalian pre-implantation development is a complex process involving sophisticated regulatory dynamics. WD repeat domain 36 (WDR36) is known to play a critical role in mouse early embryonic development, but its regulatory function in human embryogenesis is still elusive due to limited access to human embryos. The human pluripotent stem cell-derived blastocyst-like structure, termed a blastoid, offers an alternative means to study human development in a dish. In this study, after verifying that WDR36 inhibition disrupted polarization in mouse early embryos, it is further demonstrated that WDR36 interference can block human blastoid formation, dominantly hindering the trophectoderm lineage commitment. Both transcriptomics and targeted metabolomics analyses revealed that WDR36 interference downregulated glucose metabolism. WDR36 can interact with glycolytic metabolic protein lactate dehydrogenase A (LDHA), thereby positively regulating glycolysis during the late stage of human blastoid formation. Taken together, the study has established a mechanistic connection between WDR36, glucose metabolism, and cell fate determination during early embryonic lineage commitment, which may provide potential insights into novel therapeutic targets for early adverse pregnancy interventions.PMID:39656902 | DOI:10.1002/advs.202412222

Cardiovasc Res. 2024 Dec 6:cvae250. doi: 10.1093/cvr/cvae250. Online ahead of print.ABSTRACTAIMS: The transcription factor NRF2 is well recognized as a master regulator of antioxidant responses and cytoprotective genes. Previous studies showed that NRF2 enhances resistance of mouse hearts to chronic hemodynamic overload at least in part by reducing oxidative stress. Evidence from other tissues suggests that NRF2 may modulate glucose intermediary metabolism but whether NRF2 has such effects in the heart is unclear. Here, we investigate the role of NRF2 in regulating glucose intermediary metabolism and cardiac function during disease stress.METHODS AND RESULTS: Cardiomyocyte-specific Keap1 knockout (csKeap1KO) mice, deficient in the endogenous inhibitor of NRF2, were used as a novel model of constitutively active NRF2 signaling. Targeted metabolomics and isotopomer analysis were employed in studies with 13C6-glucose in csKeap1KO and wild-type (WT) mice. Pharmacological and genetic approaches were utilized in neonatal rat ventricular cardiomyocytes (NRVM) to explore molecular mechanisms. We found that cardiac-specific activation of NRF2 redirected glucose metabolism towards the pentose phosphate pathway (PPP), a branch pathway of glycolysis, and mitigated pressure overload-induced cardiomyocyte death and cardiac dysfunction. Activation of NRF2 also protected against myocardial infarction-induced DNA damage in remote myocardium and cardiac dysfunction. In vitro, knockdown of Keap1 upregulated PPP enzymes and reduced cell death in NRVM subjected to chronic neurohumoral stimulation. These pro-survival effects were abolished by pharmacological inhibition of the PPP or silencing of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of NRF2 in NRVM increased stress-induced DNA damage which was rescued by supplementing the cells with either NADPH or nucleosides, the two main products of the PPP.CONCLUSIONS: These results indicate that NRF2 regulates cardiac metabolic reprogramming by stimulating the diversion of glucose into the PPP, thereby generating NADPH and providing nucleotides to prevent stress-induced DNA damage and cardiac dysfunction.PMID:39657243 | DOI:10.1093/cvr/cvae250