PubMed

Sci Rep. 2024 Feb 13;14(1):3626. doi: 10.1038/s41598-024-53929-w.ABSTRACTMental disorders are complex disorders influenced by multiple genetic, environmental, and biological factors. Specific microbiota imbalances seem to affect mental health status. However, the mechanisms by which microbiota disturbances impact the presence of depression, stress, anxiety, and eating disorders remain poorly understood. Currently, there are no robust biomarkers identified. We proposed a novel pyramid-layer design to accurately identify microbial/metabolomic signatures underlying mental disorders in the TwinsUK registry. Monozygotic and dizygotic twins discordant for mental disorders were screened, in a pairwise manner, for differentially abundant bacterial genera and circulating metabolites. In addition, multivariate analyses were performed, accounting for individual-level confounders. Our pyramid-layer study design allowed us to overcome the limitations of cross-sectional study designs with significant confounder effects and resulted in an association of the abundance of genus Parabacteroides with the diagnosis of mental disorders. Future research should explore the potential role of Parabacteroides as a mediator of mental health status. Our results indicate the potential role of the microbiome as a modifier in mental disorders that might contribute to the development of novel methodologies to assess personal risk and intervention strategies.PMID:38351227 | PMC:PMC10864280 | DOI:10.1038/s41598-024-53929-w

Sci Rep. 2024 Feb 13;14(1):3627. doi: 10.1038/s41598-024-54144-3.ABSTRACTThe study aimed to assess the metabolomic profile of the synovial fluid (SF) of dogs affected by spontaneous osteoarthritis (OA) and compare any differences based on disease progression. Sixty client-owned dogs affected by spontaneous OA underwent clinical, radiographic, and cytologic evaluations to confirm the diagnosis. The affected joints were divided into four study groups based on the Kallgreen-Lawrence classification: OA1 (mild), OA2 (moderate), OA3 (severe), and OA4 (extremely severe/deforming). The osteoarthritic joint's SF was subjected to cytologic examination and 1H-NMR analysis. The metabolomic profiles of the study groups' SF samples were statistically compared using one-way ANOVA. Sixty osteoarthritic joints (45 stifles, 10 shoulders and 5 elbows) were included in the study. Fourteen, 28, and 18 joints were included in the OA1, OA2, and OA3 groups, respectively (0 joints in the OA4 group). Metabolomic analysis identified 48 metabolites, five of which were significantly different between study groups: Mannose and betaine were elevated in the OA1 group compared with the OA2 group, and the 2-hydroxyisobutyrate concentration decreased with OA progression; in contrast, isoleucine was less concentrated in mild vs. moderate OA, and lactate increased in severe OA. This study identified different 1H-NMR metabolomic profiles of canine SF in patients with progressive degrees of spontaneous OA, suggesting 1H-NMR metabolomic analysis as a potential alternative method for monitoring OA progression. In addition, the results suggest the therapeutic potentials of the metabolomic pathways that involve mannose, betaine, 2-hydroxyisobutyrate, isoleucine, and lactate.PMID:38351089 | PMC:PMC10864333 | DOI:10.1038/s41598-024-54144-3

BMC Bioinformatics. 2024 Feb 14;25(1):69. doi: 10.1186/s12859-024-05679-9.ABSTRACTBACKGROUND: Technological advances have enabled the generation of unique and complementary types of data or views (e.g. genomics, proteomics, metabolomics) and opened up a new era in multiview learning research with the potential to lead to new biomedical discoveries.RESULTS: We propose iDeepViewLearn (Interpretable Deep Learning Method for Multiview Learning) to learn nonlinear relationships in data from multiple views while achieving feature selection. iDeepViewLearn combines deep learning flexibility with the statistical benefits of data and knowledge-driven feature selection, giving interpretable results. Deep neural networks are used to learn view-independent low-dimensional embedding through an optimization problem that minimizes the difference between observed and reconstructed data, while imposing a regularization penalty on the reconstructed data. The normalized Laplacian of a graph is used to model bilateral relationships between variables in each view, therefore, encouraging selection of related variables. iDeepViewLearn is tested on simulated and three real-world data for classification, clustering, and reconstruction tasks. For the classification tasks, iDeepViewLearn had competitive classification results with state-of-the-art methods in various settings. For the clustering task, we detected molecular clusters that differed in their 10-year survival rates for breast cancer. For the reconstruction task, we were able to reconstruct handwritten images using a few pixels while achieving competitive classification accuracy. The results of our real data application and simulations with small to moderate sample sizes suggest that iDeepViewLearn may be a useful method for small-sample-size problems compared to other deep learning methods for multiview learning.CONCLUSION: iDeepViewLearn is an innovative deep learning model capable of capturing nonlinear relationships between data from multiple views while achieving feature selection. It is fully open source and is freely available at https://github.com/lasandrall/iDeepViewLearn .PMID:38350879 | DOI:10.1186/s12859-024-05679-9

Stat Med. 2024 Jan 10. doi: 10.1002/sim.9994. Online ahead of print.ABSTRACTThe prevalence of chronic non-communicable diseases such as obesity has noticeably increased in the last decade. The study of these diseases in early life is of paramount importance in determining their course in adult life and in supporting clinical interventions. Recently, attention has been drawn to approaches that study the alteration of metabolic pathways in obese children. In this work, we propose a novel joint modeling approach for the analysis of growth biomarkers and metabolite associations, to unveil metabolic pathways related to childhood obesity. Within a Bayesian framework, we flexibly model the temporal evolution of growth trajectories and metabolic associations through the specification of a joint nonparametric random effect distribution, with the main goal of clustering subjects, thus identifying risk sub-groups. Growth profiles as well as patterns of metabolic associations determine the clustering structure. Inclusion of risk factors is straightforward through the specification of a regression term. We demonstrate the proposed approach on data from the Growing Up in Singapore Towards healthy Outcomes cohort study, based in Singapore. Posterior inference is obtained via a tailored MCMC algorithm, involving a nonparametric prior with mixed support. Our analysis has identified potential key pathways in obese children that allow for the exploration of possible molecular mechanisms associated with childhood obesity.PMID:38197220 | DOI:10.1002/sim.9994

Proteomics Clin Appl. 2024 Jan 9:e2300035. doi: 10.1002/prca.202300035. Online ahead of print.ABSTRACTPURPOSE: This study was aimed to analyze serum amino acid metabolite profiles in frailty patients, gain a better understanding of the metabolic mechanisms in frailty, and assess the diagnostic value of metabolomics-based biomarkers of frailty.EXPERIMENTAL DESIGN: This study utilized the ultra-performance liquid chromatography tandem mass spectrometry to examine amino acids associated with frailty. Additionally, we employed multivariate statistical methods, metabolomic data analysis, receiver operating characteristic (ROC) curve analysis, and pathway enrichment analysis.RESULTS: Among the assayed amino acid metabolites, we identified biomarkers for frailty. ROC curve analysis for frailty diagnosis based on the modified Fried's frailty index showed that the areas under ROC curve of tryptophan, phenylalanine, aspartic acid, and combination were 0.775, 0.679, 0.667, and 0.807, respectively. ROC curve analysis for frailty diagnosis based on Frail Scale showed that the areas under ROC curve of cystine, phenylalanine, and combination of amino acids (cystine, L-Glutamine, citrulline, tyrosine, kynurenine, phenylalanine, glutamin acid) were 0.834, 0.708, and 0.854 respectively.CONCLUSION AND CLINICAL RELEVANCE: In this study, we explored the serum amino acid metabolite profiles in frailty patients. These present metabolic analyses may provide valuable information on the potential biomarkers and the possible pathogenic mechanisms of frailty.CLINICAL SIGNIFICANCE: Frailty is a clinical syndrome, as a consequence it is challenging to identify at early course of the disease, even based on the existing frailty scales. Early diagnosis and appropriate patient management are the key to improve the survival and limit disabilities in frailty patients. Proven by the extensive laboratory and clinical studies on frailty, comprehensive analysis of metabolic levels in frail patients, identification of biomarkers and study of pathogenic pathways of metabolites contribute to the prediction and early diagnosis of frailty. In this study, we explored the serum amino acid metabolite profiles in frailty patients. These present metabolic analyses may provide valuable information on the potential biomarkers and the possible pathogenic mechanisms of frailty.PMID:38196151 | DOI:10.1002/prca.202300035

Int Microbiol. 2024 Jan 9. doi: 10.1007/s10123-023-00475-6. Online ahead of print.ABSTRACTSun-drying is a traditional process for preparing dried shrimp in coastal area of South China, but its impacts on nutrition and the formation of flavor-contributory substances in dried shrimp remain largely unknown. This study aimed to examine the effects of the production process on the microbiota and metabolites in dried shrimp. 16S rDNA amplicon sequencing was employed to identify 170 operational taxonomic units (OTUs), with Vibrio, Photobacterium, and Shewanella emerging as the primary pathogenic bacteria in shrimp samples. Lactococcus lactis was identified as the principal potential beneficial microorganism to accrue during the dried shrimp production process and found to contribute significantly to the development of desirable shrimp flavors. LC-MS-based analyses of dried shrimp sample metabolomes revealed a notable increase in compounds associated with unsaturated fatty acid biosynthesis, arachidonic acid metabolism, amino acid biosynthesis, and flavonoid and flavanol biosynthesis throughout the drying process. Subsequent exploration of the relationship between metabolites and bacterial communities highlighted the predominant coexistence of Bifidobacterium, Clostridium, and Photobacterium contributing heterocyclic compounds and metabolites of organic acids and their derivatives. Conversely, Arthrobacter and Staphylococcus were found to inhibit each other, primarily in the presence of heterocyclic compounds. This comprehensive investigation provides valuable insights into the dynamic changes in the microbiota and metabolites of dried shrimps spanning different drying periods, which we expect to contribute to enhancing production techniques and safety measures for dried shrimp processing.PMID:38196020 | DOI:10.1007/s10123-023-00475-6

Tree Physiol. 2024 Jan 9:tpae003. doi: 10.1093/treephys/tpae003. Online ahead of print.ABSTRACTNeedle blights are serious fungal diseases affecting European natural and planted pine forests. Brown-spot needle blight disease (BSNB), caused by the fungus Lecanosticta acicola, causes canopy defoliation and severe productivity losses with consequences depending on host susceptibility. To gain new insights into BSNB plant-pathogen interactions, constitutive and pathogen-induced traits were assessed in two host species with differential disease susceptibility. Six-months-old Pinus radiata (susceptible) and Pinus pinea (more resistant) seedlings were needle inoculated with L. acicola under controlled conditions. Eighty days after inoculation, healthy-looking needles from symptomatic plants were assessed for physiological parameters and sampled for biochemical analysis. Disease progression, plant growth, leaf gas-exchanges and biochemical parameters were complemented with hormonal and untargeted primary metabolism analysis and integrated for a holistic analysis. Constitutive differences between pine species were observed. Pinus pinea presented higher stomatal conductance and transpiration rate and higher amino and organic acids, abscisic acid as well as putrescine content than P. radiata. Symptoms from BSNB disease were observed in 54.54% of P. radiata and 45.45% of P. pinea seedlings, being more pronounced and generalized in P. radiata. For both species, plant height, sub-stomatal CO2 concentration and water-use efficiency were impacted by infection. In P. radiata, total soluble sugars, starch and total flavonoids content increased after infection. No differences in hormone content after infection were observed. However, secondary metabolism was induced in P. pinea visible through total phenolics, flavonoids and putrescine accumulation. Overall, the observed results suggest that P. pinea constitutive and induced traits may function as two layers of a defence strategy which contributed for an increased BSNB resistance in comparison with P. radiata. This is the first integrative study linking plant physiological and molecular traits in Pinus-Lecanosticta acicola pathosystem, contributing to a better understanding of the underlying resistance mechanisms to BSNB disease in pines.PMID:38195942 | DOI:10.1093/treephys/tpae003

Commun Biol. 2024 Jan 9;7(1):69. doi: 10.1038/s42003-023-05759-1.ABSTRACTOur previous work has shown that D-ribose (RIB)-induced depressive-like behaviors in mice. However, the relationship between variations in RIB levels and depression as well as potential RIB participation in depressive disorder is yet unknown. Here, a reanalysis of metabonomics data from depressed patients and depression model rats is performed to clarify whether the increased RIB level is positively correlated with the severity of depression. Moreover, we characterize intestinal epithelial barrier damage, gut microbial composition and function, and microbiota-gut-brain metabolic signatures in RIB-fed mice using colonic histomorphology, 16 S rRNA gene sequencing, and untargeted metabolomics analysis. The results show that RIB caused intestinal epithelial barrier impairment and microbiota-gut-brain axis dysbiosis. These microbial and metabolic modules are consistently enriched in peripheral (fecal, colon wall, and serum) and central (hippocampus) glycerophospholipid metabolism. In addition, three differential genera (Lachnospiraceae_UCG-006, Turicibacter, and Akkermansia) and two types of glycerophospholipids (phosphatidylcholine and phosphatidylethanolamine) have greater contributions to the overall correlations between differential genera and glycerophospholipids. These findings suggest that the disturbances of gut microbiota by RIB may contribute to the onset of depressive-like behaviors via regulating glycerophospholipid metabolism, and providing new insight for understanding the function of microbiota-gut-brain axis in depression.PMID:38195757 | DOI:10.1038/s42003-023-05759-1

Nat Commun. 2024 Jan 9;15(1):393. doi: 10.1038/s41467-023-44468-5.ABSTRACTIgG secreted by B cells carry asparagine N(297)-linked glycans in the fragment crystallizable (Fc) region. Changes in Fc glycosylation are related to health or disease and are functionally relevant, as IgG without Fc glycans cannot bind to Fcɣ receptors or complement factors. However, it is currently unknown whether ɣ-heavy chain (ɣHC) glycans also influence the function of membrane-bound IgG-B-cell receptors (BCR) and thus the outcome of the B-cell immune response. Here, we show in a germinal center (GC)-derived human B-cell line that ɣHC glycans do not affect membrane expression of IgG-BCRs. Furthermore, antigen binding or other BCR-facilitated mechanisms appear unaffected, including BCR downmodulation or BCR-mediated signaling. As expected, secreted IgG lacking Fc glycosylation is unable to carry out effector functions. Together, these observations indicate that IgG-Fc glycosylation serves as a mechanism to control the effector functions of antibodies, but does not regulate the activation of IgG-switched B cells, as its absence had no apparent impact on BCR function.PMID:38195612 | DOI:10.1038/s41467-023-44468-5

Biomark Res. 2024 Jan 9;12(1):6. doi: 10.1186/s40364-023-00555-9.ABSTRACTBACKGROUND: Metabolic associated steatohepatitis (MASH) is metabolic disease that may progress to cirrhosis and hepatocellular carcinoma. Mouse models of diet-induced MASH, which is characterized by the high levels of fats, sugars, and cholesterol in diets, are commonly used in research. However, mouse models accurately reflecting the progression of MASH in humans remain to be established. Studies have explored the potential use of serological metabolites as biomarkers of MASH severity in relation to human MASH.METHODS: We performed a comparative analysis of three mouse models of diet-induced MASH in terms of phenotypic and metabolomic characteristics; MASH was induced using different diets: a high-fat diet; a Western diet; and a high-fat, high-cholesterol diet. Liver cirrhosis was diagnosed using standard clinical approaches (e.g., METAVIR score, hyaluronan level, and collagen deposition level). Mouse serum samples were subjected to nuclear magnetic resonance spectroscopy-based metabolomic profiling followed by bioinformatic analyses. Metabolomic analysis of a retrospective cohort of patients with hepatocellular carcinoma was performed; the corresponding cirrhosis scores were also evaluated.RESULTS: Using clinically relevant quantitative diagnostic methods, the severity of MASH was evaluated. Regarding metabolomics, the number of lipoprotein metabolites increased with both diet and MASH progression. Notably, the levels of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) significantly increased with fibrosis progression. During the development of diet-induced MASH in mice, the strongest upregulation of expression was noted for VLDL receptor. Metabolomic analysis of a retrospective cohort of patients with cirrhosis indicated lipoproteins (e.g., VLDL and LDL) as predominant biomarkers of cirrhosis.CONCLUSIONS: Our findings provide insight into the pathophysiology and metabolomics of experimental MASH and its relevance to human MASH. The observed upregulation of lipoprotein expression reveals a feedforward mechanism for MASH development that may be targeted for the development of noninvasive diagnosis.PMID:38195587 | DOI:10.1186/s40364-023-00555-9

Life Sci Alliance. 2024 Jan 9;7(3):e202302057. doi: 10.26508/lsa.202302057. Print 2024 Mar.ABSTRACTJuvenile neuronal ceroid lipofuscinosis (or Batten disease) is an autosomal recessive, rare neurodegenerative disorder that affects mainly children above the age of 5 yr and is most commonly caused by mutations in the highly conserved CLN3 gene. Here, we generated cln3 morphants and stable mutant lines in zebrafish. Although neither morphant nor mutant cln3 larvae showed any obvious developmental or morphological defects, behavioral phenotyping of the mutant larvae revealed hyposensitivity to abrupt light changes and hypersensitivity to pro-convulsive drugs. Importantly, in-depth metabolomics and lipidomics analyses revealed significant accumulation of several glycerophosphodiesters (GPDs) and cholesteryl esters, and a global decrease in bis(monoacylglycero)phosphate species, two of which (GPDs and bis(monoacylglycero)phosphates) were previously proposed as potential biomarkers for CLN3 disease based on independent studies in other organisms. We could also demonstrate GPD accumulation in human-induced pluripotent stem cell-derived cerebral organoids carrying a pathogenic variant for CLN3 Our models revealed that GPDs accumulate at very early stages of life in the absence of functional CLN3 and highlight glycerophosphoinositol and BMP as promising biomarker candidates for pre-symptomatic CLN3 disease.PMID:38195117 | DOI:10.26508/lsa.202302057

Toxicol Appl Pharmacol. 2024 Jan 7:116806. doi: 10.1016/j.taap.2024.116806. Online ahead of print.ABSTRACTCadmium (Cd) is a naturally occurring, toxic environmental metal found in foods. Humans do not have an efficient mechanism for Cd elimination; thus, Cd burden in humans increases with age. Cell and mouse studies show that Cd burden from low environmental levels of exposure impacts lung cell metabolism, proliferation signaling and cell growth as part of disease-promoting profibrotic responses in the lungs. Prior integrative analysis of metabolomics and transcriptomics identified the zDHHC11 transcript as a central functional hub in response to Cd dose. zDHHC11 encodes a protein S-palmitoyltransferase, but no evidence is available for effects of Cd on protein S-palmitoylation. In the present research, we studied palmitoylation changes in response to Cd and found increased protein S-palmitoylation in human lung fibroblasts that was inhibited by 2-bromopalmitate (2-BP), an irreversible palmitoyltransferase inhibitor. Mass spectrometry-based proteomics showed palmitoylation of proteins involved in divalent metal transport and in fibrotic signaling. Mechanistic studies showed that 2-BP inhibited palmitoylation of divalent metal ion transporter ZIP14 and also inhibited cellular Cd uptake. Transcription analyses showed that Cd stimulated transforming growth factor (TGF)-β1 and β3 expression within 8 h and lung fibrotic markers α-smooth muscle actin, matrix metalloproteinase-2, and collagen 1α1 gene expression and that these effects were blocked by 2-BP. Because 2-BP also blocked palmitoylation of proteins controlled by TGFβ1, these results show that palmitoylation impacts Cd-dependent fibrotic signaling both by enhancing cellular Cd accumulation and by supporting post-translational processing of TGFβ1-dependent proteins.PMID:38195004 | DOI:10.1016/j.taap.2024.116806

Cell Rep Med. 2024 Jan 8:101355. doi: 10.1016/j.xcrm.2023.101355. Online ahead of print.ABSTRACTDespite the encouraging efficacy of anti-PD-1/PD-L1 immunotherapy in microsatellite-instability-high/deficient mismatch repair (MSI-H/dMMR) advanced gastrointestinal cancer, many patients exhibit primary or acquired resistance. Using multi-omics approaches, we interrogate gut microbiome, blood metabolome, and cytokines/chemokines of patients with MSI-H/dMMR gastrointestinal cancer (N = 77) at baseline and during the treatment. We identify a number of microbes (e.g., Porphyromonadaceae) and metabolites (e.g., arginine) highly associated with primary resistance to immunotherapy. An independent validation cohort (N = 39) and mouse model are used to further confirm our findings. A predictive machine learning model for primary resistance is also built and achieves an accuracy of 0.79 on the external validation set. Furthermore, several microbes are pinpointed that gradually changed during the process of acquired resistance. In summary, our study demonstrates the essential role of gut microbiome in drug resistance, and this can be utilized as a preventative diagnosis tool and therapeutic target in the future.PMID:38194971 | DOI:10.1016/j.xcrm.2023.101355

Ecotoxicol Environ Saf. 2024 Jan 8;271:115885. doi: 10.1016/j.ecoenv.2023.115885. Online ahead of print.ABSTRACTTobacco plants (Nicotiana tabacum L.) exhibit considerable potential for phytoremediation of soil cadmium (Cd) pollutants, owing to their substantial biomass and efficient metal accumulation capabilities. The reduction of Cd accumulation in tobacco holds promise for minimizing Cd intake in individuals exposed to cigar smoking. NRAMP transporters are pivotal in the processes of Cd accumulation and resistance in plants; however, limited research has explored the functions of NRAMPs in tobacco plants. In this investigation, we focused on NtNRAMP6c, one of the three homologs of NRAMP6 in tobacco. We observed a robust induction of NtNRAMP6c expression in response to both Cd toxicity and iron (Fe) deficiency, with the highest expression levels detected in the roots. Subsequent subcellular localization and heterologous expression analyses disclosed that NtNRAMP6c functions as a plasma membrane-localized Cd transporter. Moreover, its overexpression significantly heightened the sensitivity of yeast cells to Cd toxicity. Through CRISPR-Cas9-mediated knockout of NtNRAMP6c, we achieved a reduction in Cd accumulation and an enhancement in Cd resistance in tobacco plants. Comparative transcriptomic analysis unveiled substantial alterations in the transcriptional profiles of genes associated with metal ion transport, photosynthesis, and macromolecule catabolism upon NtNRAMP6c knockout. Furthermore, our study employed plant metabolomics and rhizosphere metagenomics to demonstrate that NtNRAMP6c knockout led to changes in phytohormone homeostasis, as well as shifts in the composition and abundance of microbial communities. These findings bear significant biological implications for the utilization of tobacco in phytoremediation strategies targeting Cd pollutants in contaminated soils, and concurrently, in mitigating Cd accumulation in tobacco production destined for cigar consumption.PMID:38194857 | DOI:10.1016/j.ecoenv.2023.115885

Ecotoxicol Environ Saf. 2024 Jan 8;270:115943. doi: 10.1016/j.ecoenv.2024.115943. Online ahead of print.ABSTRACTNickel oxide nanoparticles (NiONPs) are toxic heavy metal compounds that induce liver fibrosis and metabolic disorders. Current research shows that the intestinal microbiota regulates liver metabolism through the gut-liver axis. However, it is unclear whether NiONPs affect the intestinal microbiota and the relationship between microbiota and liver metabolic disorders. Therefore, in this study, we established liver fibrosis model by administering 0.015, 0.06 and 0.24 mg/mL NiONPs through tracheal instillation twice a week for 9 weeks in rats, then we collected serum and fecal sample for whole metabolomics and metagenomic sequencing. As the result of sequencing, we screened out seven metabolites (beta-D-glucuronide, methylmalonic acid, linoleic acid, phosphotidylcholine, lysophosphatidylinositol, docosapentaenoic acid and progesterone) that related to functional alterations (p < 0.05), and obtained a decrease of probiotics abundances (p < 0.05) as well as a variation of the microbiota enzyme activity (p < 0.05), indicating that NiONPs inhibited the proliferation of probiotics. As the result of correlation analysis, we found a positive correlation between differential metabolites and probiotics, such as lysophosphatidylinositol was positively correlated with Desulfuribacillus, Jeotgallibacillus and Rummeliibacillus (p < 0.05). We also found that differential metabolites had correlations with differential proteins and enzymes of intestinal microbiota, such as glucarate dehydratase, dihydroorotate dehydrogenase and acetyl-CoA carboxylase (p < 0.05). Finally, we screened six metabolic pathways with both differential intestinal microbiota enzymes and metabolites were involved, such as pentose and glucuronate interconversions, and linoleic acid metabolism. In vitro experiments showed that NiONPs increased the transcriptional expression of Col1A1 in LX-2 cells, while reducing the mRNA expression of serine/threonine activators, acetyl coenzyme carboxylase, and lysophosphatidylinositol synthase, and short chain fatty acid sodium butyrate can alleviate these variation trends. The results proved that the intestinal microbiota enzyme systems were associated with serum metabolites, suggesting that the disturbance of intestinal microbiota and reduction of probiotics promoted the occurrence and development of NiONPs-induced liver fibrosis by affecting metabolic pathways.PMID:38194811 | DOI:10.1016/j.ecoenv.2024.115943

Plant Biotechnol J. 2024 Jan 9. doi: 10.1111/pbi.14278. Online ahead of print.ABSTRACTWolfberry is a plant with medicinal and food values. However, its bioactive ingredients and the corresponding genetic bases have not been determined. Here, we de novo generated a chromosome-level genome assembly for wolfberry, yielding a genome sequence of ~1.77 Gb with contig N50 of 50.55 Mb and 39 224 predicted gene models. A variation map, using 307 re-sequenced accessions, was called based on this genome assembly. Furthermore, the fruit metabolome of these accessions was profiled using 563 annotated metabolites, which separated Lycium barbarum L. and non-L. barbarum L. The flavonoids, coumarins, alkaloids and nicotinic acid contents were higher in the former than in the latter. A metabolite-based genome-wide association study mapped 156 164 significant single nucleotide polymorphisms corresponding to 340 metabolites. This included 19 219 unique lead single nucleotide polymorphisms in 1517 significant association loci, of which three metabolites, flavonoids, betaine and spermidine, were highlighted. Two candidate genes, LbUGT (evm.TU.chr07.2692) and LbCHS (evm.TU.chr07.2738), with non-synonymous mutations, were associated with the flavonoids content. LbCHS is a structural gene that interacts with a nearby MYB transcription factor (evm.TU.chr07.2726) both in L. barbarum and L. ruthenicum. Thus, these three genes might be involved in the biosynthesis/metabolism of flavonoids. LbSSADH (evm.TU.chr09.627) was identified as possibly participating in betaine biosynthesis/metabolism. Four lycibarbarspermidines (E-G and O) were identified, and only the lycibarbarspermidines O content was higher in L. barbarum varieties than in non-L. barbarum varieties. The evm.TU.chr07.2680 gene associated with lycibarbarspermidines O was annotated as an acetyl-CoA-benzylalcohol acetyltransferase, suggesting that it is a candidate gene for spermidine biosynthesis. These results provide novel insights into the specific metabolite profile of non-L. barbarum L. and the genetic bases of flavonoids, betaine and spermidine biosynthesis/metabolism.PMID:38194521 | DOI:10.1111/pbi.14278

J Plant Res. 2024 Jan 9. doi: 10.1007/s10265-023-01512-1. Online ahead of print.ABSTRACT'Red Meat Honey Crisp (RMHC)' has been widely cultivated by growers in recent years due to its early maturity, and red meat type characteristics. As a bud variant of 'Super Red (SR)' peach, red flesh is the most distinctive characteristic of 'Red Meat Honey Crisp (RMHC)'. However, the mechanism of red flesh formation in 'RMHC' remains unclear. In this study, 79 differentially produced metabolites were identified by metabolomics analysis. The anthocyanin content in 'RMHC' was significantly higher than that in 'SR' during the same period, such as cyanidin O-syringic acid and cyanidin 3-O-glucoside. Other flavonoids also increased during the formation of red flesh, including flavonols (6-hydroxykaempferol-7-O-glucoside, hyperin), flavanols (protocatechuic acid, (+)-gallocatechin), and flavonoids (chrysoeriol 5-O-hexoside, tricetin). In addition, transcriptomic analysis and RT-qPCR showed that the expression levels of the flavonoid synthesis pathway transcription factor MYB75 and some structural genes, such as PpDFR, PpCHS, PpC4H, and PpLDOX increased significantly in 'RMHC'. Subcellular localization analysis revealed that MYB75 was localized to the nucleus. Yeast single hybridization assays showed that MYB75 bound to the cis-acting element CCGTTG of the PpDFR promoter region. The MYB75-PpDFR regulatory network was identified to be a key pathway in the reddening of 'RMHC' flesh. Moreover, this is the first study to describe the cause for red meat reddening in 'RMHC' compared to 'SR' peaches using transcriptomics, metabolomics and molecular methods. Our study identified a key transcription factor involved in the regulation of the flavonoid synthetic pathway and contributes to peach breeding-related efforts as well as the identification of genes involved in color formation in other species.PMID:38194204 | DOI:10.1007/s10265-023-01512-1

Appl Microbiol Biotechnol. 2024 Dec;108(1):1-17. doi: 10.1007/s00253-023-12882-w. Epub 2024 Jan 9.ABSTRACTMildew poses a significant threat to tobacco production; however, there is limited information on the structure of the abundant and rare microbial subcommunities in moldy tobacco leaves. In this study, we employed high-throughput sequencing technology to discern the disparities in the composition, diversity, and co-occurrence patterns of abundant and rare fungal and bacterial subcommunities between moldy and normal tobacco leaves collected from Guizhou, Shanghai, and Jilin provinces, China. Furthermore, we explored the correlation between microorganisms and metabolites by integrating the metabolic profiles of moldy and normal tobacco leaves. The results showed that the fungi are more sensitive to mildew than bacteria, and that the fungal abundant taxa exhibit greater resistance and environmental adaptability than the rare taxa. The loss of rare taxa results in irreversible changes in the diversity, richness, and composition of the fungal community. Moreover, rare fungal taxa and abundant bacterial taxa played crucial roles in maintaining the stability and functionality of the tobacco microecosystem. In moldy tobacco, however, the disappearance of rare taxa as key nodes resulted in reduced connectivity and stability within the fungal network. In addition, metabolomic analysis showed that the contents of indoles, pyridines, polyketones, phenols, and peptides were significantly enriched in the moldy tobacco leaves, while the contents of amino acids, carbohydrates, lipids, and other compounds were significantly reduced in these leaves. Most metabolites showed negative correlations with Dothideomycetes, Alphaproteobacteria, and Gammaproteobacteria, but showed positive correlations with Eurotiales and Bacilli. This study has demonstrated that abundant fungal taxa are the predominant biological agents responsible for tobacco mildew, while bacteria may indirectly contribute to this process through the production and degradation of metabolites. KEY POINTS: • Fungi exhibited greater sensitivity to mildew of tobacco leaf compared to bacteria • Rare fungal taxa underwent significant damage during the mildew process • Mildew may damage the defense system of the tobacco leaf microecosystem.PMID:38194134 | DOI:10.1007/s00253-023-12882-w

Anim Biotechnol. 2024 Jan 9:1-14. doi: 10.1080/10495398.2023.2294785. Online ahead of print.ABSTRACTYak is an important dominant livestock species at high altitude, and the growth performance of yak has obvious differences under different feeding methods. This experiment was conducted to compare the effects of different feeding practices on growth performance and meat quality of yaks through combined transcriptomic and metabolomic analyses. In terms of yak growth performance, compared with traditional grazing, in-house feeding can significantly improve the average daily weight gain, carcass weight and net meat weight of yaks; in terms of yak meat quality, in-house feeding can effectively improve the quality of yak meat. A combined transcriptomic and metabolomic analysis revealed 31 co-enriched pathways, among which arginine metabolism, proline metabolism and glycerophospholipid metabolism may be involved in the development of the longissimus dorsi muscle of yak and the regulation of meat quality-related traits. The experimental results increased our understanding of yak meat quality and provided data materials for subsequent deep excavation of the mechanism of yak meat quality.PMID:38193799 | DOI:10.1080/10495398.2023.2294785

JCI Insight. 2024 Jan 9;9(1):e174753. doi: 10.1172/jci.insight.174753.ABSTRACTEpilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation. Recent human and animal model studies have implicated new immunotherapeutic and metabolomic approaches that may benefit patients with epilepsy. In this Review, we detail the proinflammatory immune landscape of epilepsy and contrast this with the immunosuppressive microenvironment in patients with glioma-related epilepsy. In the tumor setting, excessive neuronal activity facilitates immunosuppression, thereby contributing to subsequent glioma progression. Metabolic modulation of the IDH1-mutant pathway provides a dual pathway for reversing immune suppression and dampening seizure activity. Elucidating the relationship between neurons and immunoreactivity is an area for the prioritization and development of the next era of ASMs.PMID:38193532 | DOI:10.1172/jci.insight.174753