PubMed

Plant Cell Environ. 2024 Feb 21. doi: 10.1111/pce.14865. Online ahead of print.ABSTRACTGummy stem blight (GSB), a widespread disease causing great loss to cucurbit production, has become a major threat to melon cultivation. However, the melon-GSB interaction remains largely unknown. Here, full-length transcriptome and widely targeted metabolome were used to investigate the defence responses of resistant (PI511089) and susceptible (Payzawat) melon accessions to GSB pathogen infection at 24 h. The biosynthesis of secondary metabolites and MAPK signalling pathway were specifically enriched for differentially expressed genes in PI511890, while carbohydrate metabolism and amino acid metabolism were specifically enriched in Payzawat. More than 1000 novel genes were identified and MAPK signalling pathway was specifically enriched for them in PI511890. There were 11 793 alternative splicing events involving in the defence response to GSB. Totally, 910 metabolites were identified in Payzawat and PI511890, and flavonoids were the dominant metabolites. Integrated full-length transcriptome and metabolome analysis showed eriodictyol and oxalic acid were the potential marker metabolites for GSB resistance in melon. Moreover, posttranscription regulation was widely involved in the defence response of melon to GSB pathogen infection. These results not only improve our understanding on the interaction between melon and GSB, but also facilitate the genetic improvement of melon with GSB resistance.PMID:38379450 | DOI:10.1111/pce.14865

Toxicol Mech Methods. 2024 Feb 20:1-14. doi: 10.1080/15376516.2024.2322006. Online ahead of print.ABSTRACTThis study focuses on the comparative metabolic profiling and effects of two steroid types: natural and synthetic, specifically 17α-methyl testosterone (17α-MT) at varying concentrations (1.5, 2, and 3 mg/kg) in rainbow trout (Oncorhynchus mykiss). Over a 75-day feeding trial, growth metrics such as feed efficiency, daily specific growth, live weight gain, total weight gain, and survival rate were systematically monitored every 15 days. At the end of the feeding trial, histopathology, immunohistochemistry, and metabolome analyses were performed in the high-concentration groups (3 mg/kg natural and 3 mg/kg synthetic), in which the lowest survival rate was determined. Key findings reveal that the type of hormone significantly influences growth parameters. While some natural steroids enhanced certain growth aspects, synthetic variants often yielded better results. The metabolomic analysis highlighted significant shifts in the metabolism of tryptophan, purine, folate, primary bile acids, phosphonates, phosphinates, and xenobiotics via cytochrome P450 pathways. Histopathologically, the natural hormone groups showed similar testicular, hepatic, muscular, gill, cerebral, renal, and intestinal tissue structures to the control, with minor DNA damage and apoptosis observed through immunohistochemistry. Conversely, the synthetic hormone groups exhibited moderate DNA damage and mild degenerative and necrotic changes in histopathology.PMID:38379298 | DOI:10.1080/15376516.2024.2322006

Plant Commun. 2024 Feb 19:100847. doi: 10.1016/j.xplc.2024.100847. Online ahead of print.ABSTRACTCarotenoids in plant foods function as provitamin A for health benefits. One of the vital provitamin A carotenoids, β-cryptoxanthin, is typically plentiful in citrus fruits. However, the genetic basis underlying the accumulation of β-cryptoxanthin in citrus remains largely elusive. Here, we performed a widely targeted metabolomic analysis of 65 major carotenoids and carotenoid derivatives to characterize the carotenoid accumulation in Citrus and determined the taxonomic profile of β-cryptoxanthin. We newly sequenced 81 representative accessions and additionally collected 69 previous Citrus cultivars to uncover the genetic basis of β-cryptoxanthin accumulation using a genome-wide association study (GWAS). We identified a causal gene, CitCYP97B, which encodes a cytochrome P450 protein, but its substrate and metabolic pathways in land plants are undetermined. Therefore, we validated that CitCYP97B functions as a novel monooxygenase that specifically hydroxylates the β-ring of β-cryptoxanthin in a heterologous expression system. In planta experiments further supported that CitCYP97B negatively regulated β-cryptoxanthin content. Based on the Citrus sequencing accessions, we found that two critical structural cis-element variations contribute to the elevated expression of CitCYP97B, thereby altering the β-cryptoxanthin accumulation in fruits. Hybridization/introgression contributes to the prevalence of two cis-element variations in different Citrus types during the citrus evolution. Overall, our findings extend the regulation and diversity of carotenoid metabolism in fruit crops and provide a genetic target for generating β-cryptoxanthin biofortified products.PMID:38379285 | DOI:10.1016/j.xplc.2024.100847

J Anim Physiol Anim Nutr (Berl). 2024 Feb 20. doi: 10.1111/jpn.13943. Online ahead of print.ABSTRACTObjectives were to determine the effects of supplementing rumen-protected choline (RPC) from an established source with low (L, 28.8%) or a prototype with less lipid coating protection and high (H, 60.0%) concentrations of choline chloride on digestibility of fat and supra-mammary lymph metabolome in feed-restricted cows. Pregnant, nonlactating Holstein cows (n = 33; 11/treatment) at mean (±standard deviation) 231 ± 4.7 days of gestation were blocked by body condition (4.23 ± 0.47) and assigned to receive 0 (CON) or 25.8 g/d of choline ion from L (L25.8) or H (H25.8). Cows were adapted to the diet and then fed-restricted to 42% of the net energy of lactation required for maintenance and pregnancy for 9 days. Intake of metabolizable methionine was maintained at 19 g/d. On Day 9, cows were fed 450 g of saturated fatty acids (SFA), and feces and blood were sampled continuously for 24 h. Supra-mammary lymph was sampled 6 h after feeding SFA and metabolome was characterized. Feeding RPC increased digestibility of fat (CON = 80.4 vs. RPC = 86.0 ± 1.9%) and reduced the concentration of haptoglobin in serum (CON = 174 vs. RPC = 77 ± 14 µg/ml) independent of source of RPC fed. Feeding RPC increased the concentrations of triacylglycerol in serum (CON = 15.1 vs. RPC = 17.8 ± 1.9 mg/dl) in feed-restricted cows after feeding SFA, and the increment tended to be greater for cows fed H25.8 than L25.8. Supplementing RPC tended to increase the concentrations of triacylglycerol (CON = 11.4 vs. RPC = 15.8 ± 3.4 mg/dl) in supra-mammary lymph. Feeding RPC increased the concentration of choline and affected the concentrations of analytes involved in metabolic pathways associated with amino acid metabolism and biosynthesis of phospholipids in lymph compared with CON. Feeding RPC, independent of source used, increased fat digestibility with some changes in lymph metabolome in cows under negative nutrient balance.PMID:38379267 | DOI:10.1111/jpn.13943

Cell Biochem Funct. 2024 Mar;42(2):e3934. doi: 10.1002/cbf.3934.ABSTRACTImmunometabolism, which studies cellular metabolism and immune cell function, is a possible cancer treatment. Metabolic pathways regulate immune cell activation, differentiation, and effector functions, crucial to tumor identification and elimination. Immune evasion and tumor growth can result from tumor microenvironment metabolic dysregulation. These metabolic pathways can boost antitumor immunity. This overview discusses immune cell metabolism, including glycolysis, oxidative phosphorylation, amino acid, and lipid metabolism. Amino acid and lipid metabolic manipulations may improve immune cell activity and antitumor immunity. Combination therapy using immunometabolism-based strategies may enhance therapeutic efficacy. The complexity of the metabolic network, biomarker development, challenges, and future approaches are all covered, along with a summary of case studies demonstrating the effectiveness of immunometabolism-based therapy. Metabolomics, stable isotope tracing, single-cell analysis, and computational modeling are also reviewed for immunometabolism research. Personalized and combination treatments are considered. This review adds to immunometabolism expertise and sheds light on metabolic treatments' ability to boost cancer treatment immunological response. Also, in this review, we discussed the immune response in cancer treatment and altering metabolic pathways to increase the immune response against malignancies.PMID:38379261 | DOI:10.1002/cbf.3934

Commun Biol. 2024 Feb 20;7(1):208. doi: 10.1038/s42003-024-05823-4.ABSTRACTClear cell renal cell carcinoma (ccRCC) is the most common kidney cancer in the adult population. Late diagnosis, resistance to therapeutics and recurrence of metastatic lesions account for the highest mortality rate among kidney cancer patients. Identifying novel biomarkers for early cancer detection and elucidating the mechanisms underlying ccRCC will provide clues to treat this aggressive malignant tumor. Here, we report that the ubiquitin ligase praja2 forms a complex with-and ubiquitylates the AP2 adapter complex, contributing to receptor endocytosis and clearance. In human RCC tissues and cells, downregulation of praja2 by oncogenic miRNAs (oncomiRs) and the proteasome markedly impairs endocytosis and clearance of the epidermal growth factor receptor (EGFR), and amplifies downstream mitogenic and proliferative signaling. Restoring praja2 levels in RCC cells downregulates EGFR, rewires cancer cell metabolism and ultimately inhibits tumor cell growth and metastasis. Accordingly, genetic ablation of praja2 in mice upregulates RTKs (i.e. EGFR and VEGFR) and induces epithelial and vascular alterations in the kidney tissue.In summary, our findings identify a regulatory loop between oncomiRs and the ubiquitin proteasome system that finely controls RTKs endocytosis and clearance, positively impacting mitogenic signaling and kidney cancer growth.PMID:38379085 | DOI:10.1038/s42003-024-05823-4

Plant Cell Rep. 2024 Feb 21;43(3):74. doi: 10.1007/s00299-023-03098-3.ABSTRACTHanMYB1 was found to play positive roles in the modulation of anthocyanins metabolism based on the integrative analysis of different color cultivars and the related molecular genetic analyses. As a high value ornamental and edible crop with various colors, sunflowers (Helianthus annuus L.) provide an ideal system to understand the formation of flower color. Anthocyanins are major pigments in higher plants, which is associated with development of flower colors and ability of oxidation resistance. Here, we performed an integrative analysis of the transcriptome and flavonoid metabolome in five sunflower cultivars with different flower colors. According to differentially expressed genes and differentially accumulated flavonoids, these cultivars could be grouped into yellow and red. The results showed that more anthocyanins were accumulated in the red group flowers, especially the chrysanthemin. Some anthocyanins biosynthesis-related genes like UFGT (UDP-glycose flavonoid glycosyltransferase) also expressed more in the red group flowers. A MYB transcriptional factor, HanMYB1, was found to play vital positive roles in the modulation of anthocyanins metabolism by the integrative analysis. Overexpressed HanMYB1 in tobacco could deepen the flower color, increase the accumulation of anthocyanins and directly active the express of UFGT genes. Our findings indicated that the MYB transcriptional factors provide new insight into the dynamic regulation of the anthocyanin biosynthesis in facilitating sunflower color formation and anthocyanin accumulation.PMID:38379014 | DOI:10.1007/s00299-023-03098-3

Sci Rep. 2024 Feb 20;14(1):4185. doi: 10.1038/s41598-024-54736-z.ABSTRACTDry eye syndrome (DES) is a complex ocular condition characterized by an unstable tear film and inadequate tear production, leading to tissue damage. Despite its common occurrence, there is currently no comprehensive in vitro model that accurately reproduce the cellular characteristics of DES. Here we modified a corneal epithelium-on-a-chip (CEpOC) model to recapitulate DES by subjecting HCE-T human corneal epithelial cells to an air-liquid (AL) interface stimulus. We then assessed the effects of AL stimulation both in the presence and absence of diclofenac (DCF), non-steroidal anti-inflammatory drug. Transcriptomic analysis revealed distinct gene expression changes in response to AL and AL_DCF, affecting pathways related to development, epithelial structure, inflammation, and extracellular matrix remodeling. Both treatments upregulated PIEZO2, linked to corneal damage signaling, while downregulating OCLN, involved in cell-cell junctions. They increased the expression of inflammatory genes (e.g., IL-6) and reduced mucin production genes (e.g., MUC16), reflecting dry eye characteristics. Metabolomic analysis showed increased secretion of metabolites associated with cell damage and inflammation (e.g., methyl-2-oxovaleric acid, 3-methyl-2-oxobutanoic acid, lauroyl-carnitine) in response to AL and even more with AL_DCF, indicating a shift in cellular metabolism. This study showcases the potential use of AL stimulus within the CEpOC to induce cellular characteristics relevant to DES.PMID:38379013 | DOI:10.1038/s41598-024-54736-z

Sci Rep. 2024 Feb 20;14(1):4236. doi: 10.1038/s41598-024-54813-3.ABSTRACTBreast milk composition is influenced by maternal diet. This study aimed to evaluate if supplementation of maternal diet with a prebiotic fibre, through its potential effect on milk composition, can be a leverage to orientate the gut microbiota of infants in a way that would be beneficial for their health. Twelve sows received a diet supplemented with short chain fructo-oligosaccharides or maltodextrins during the last month of gestation and the lactation. Oligosaccharidic and lipidomic profiles of colostrum and mature milk (21 days), as well as faecal microbiota composition and metabolomic profile of 21 day-old piglets were evaluated. The total porcine milk oligosaccharide concentration tended to be lower in scFOS-supplemented sows, mainly due to the significant reduction of the neutral core oligosaccharides (in particular that of a tetrahexose). Maternal scFOS supplementation affected the concentration of 31 lipids (mainly long-chain triglycerides) in mature milk. Faecal short-chain fatty acid content and that of 16 bacterial metabolites were modified by scFOS supplementation. Interestingly, the integrative data analysis gave a novel insight into the relationships between (i) maternal milk lipids and PMOs and (ii) offspring faecal bacteria and metabolites. In conclusion, scFOS-enriched maternal diet affected the composition of mature milk, and this was associated with a change in the colonisation of the offspring intestinal microbiota.PMID:38378944 | DOI:10.1038/s41598-024-54813-3

Mol Psychiatry. 2024 Feb 20. doi: 10.1038/s41380-024-02477-w. Online ahead of print.ABSTRACTPsilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or "full spectrum" (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the effects of PME to those of PSIL on the head twitch response (HTR), neuroplasticity-related synaptic proteins and frontal cortex metabolomic profiles in male C57Bl/6j mice. HTR measurement showed similar effects of PSIL and PME over 20 min. Brain specimens (frontal cortex, hippocampus, amygdala, striatum) were assayed for the synaptic proteins, GAP43, PSD95, synaptophysin and SV2A, using western blots. These proteins may serve as indicators of synaptic plasticity. Three days after treatment, there was minimal increase in synaptic proteins. After 11 days, PSIL and PME significantly increased GAP43 in the frontal cortex (p = 0.019; p = 0.039 respectively) and hippocampus (p = 0.015; p = 0.027) and synaptophysin in the hippocampus (p = 0.041; p = 0.05) and amygdala (p = 0.035; p = 0.004). PSIL increased SV2A in the amygdala (p = 0.036) and PME did so in the hippocampus (p = 0.014). In the striatum, synaptophysin was increased by PME only (p = 0.023). There were no significant effects of PSIL or PME on PSD95 in any brain area when these were analyzed separately. Nested analysis of variance (ANOVA) showed a significant increase in each of the 4 proteins over all brain areas for PME versus vehicle control, while significant PSIL effects were observed only in the hippocampus and amygdala and were limited to PSD95 and SV2A. Metabolomic analyses of the pre-frontal cortex were performed by untargeted polar metabolomics utilizing capillary electrophoresis - Fourier transform mass spectrometry (CE-FTMS) and showed a differential metabolic separation between PME and vehicle groups. The purines guanosine, hypoxanthine and inosine, associated with oxidative stress and energy production pathways, showed a progressive decline from VEH to PSIL to PME. In conclusion, our synaptic protein findings suggest that PME has a more potent and prolonged effect on synaptic plasticity than PSIL. Our metabolomics data support a gradient of effects from inert vehicle via chemical psilocybin to PME further supporting differential effects. Further studies are needed to confirm and extend these findings and to identify the molecules that may be responsible for the enhanced effects of PME as compared to psilocybin alone.PMID:38378926 | DOI:10.1038/s41380-024-02477-w

Nat Commun. 2024 Feb 20;15(1):1537. doi: 10.1038/s41467-024-45690-5.ABSTRACTCepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three Stephania genomes (S. japonica, S. yunnanensis, and S. cepharantha), propose the cepharanthine biosynthetic pathway, and assess the antiviral potential of compounds involved in the pathway. Among the three genomes, S. japonica has a near telomere-to-telomere assembly with one remaining gap, and S. cepharantha and S. yunnanensis have chromosome-level assemblies. Following by biosynthetic gene mining and metabolomics analysis, we identify seven cepharanthine analogs that have broad-spectrum anti-coronavirus activities, including SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine acute diarrhoea syndrome coronavirus (SADS-CoV), and porcine epidemic diarrhea virus (PEDV). We also show that two other genera, Nelumbo and Thalictrum, can produce cepharanthine analogs, and thus have the potential for antiviral compound discovery. Results generated from this study could accelerate broad-spectrum anti-coronavirus drug discovery.PMID:38378731 | DOI:10.1038/s41467-024-45690-5

BMC Med. 2024 Feb 20;22(1):81. doi: 10.1186/s12916-024-03298-y.ABSTRACTBACKGROUND: Caffeine is one of the most utilized drugs in the world, yet its clinical effects are not fully understood. Circulating caffeine levels are influenced by the interplay between consumption behaviour and metabolism. This study aimed to investigate the effects of circulating caffeine levels by considering genetically predicted variation in caffeine metabolism.METHODS: Leveraging genetic variants related to caffeine metabolism that affect its circulating levels, we investigated the clinical effects of plasma caffeine in a phenome-wide association study (PheWAS). We validated novel findings using a two-sample Mendelian randomization framework and explored the potential mechanisms underlying these effects in proteome-wide and metabolome-wide Mendelian randomization.RESULTS: Higher levels of genetically predicted circulating caffeine among caffeine consumers were associated with a lower risk of obesity (odds ratio (OR) per standard deviation increase in caffeine = 0.97, 95% confidence interval (CI) CI: 0.95-0.98, p = 2.47 × 10-4), osteoarthrosis (OR = 0.97, 95% CI: 0.96-0.98, P=1.10 × 10-8) and osteoarthritis (OR: 0.97, 95% CI: 0.96 to 0.98, P = 1.09 × 10-6). Approximately one third of the protective effect of plasma caffeine on osteoarthritis risk was estimated to be mediated through lower bodyweight. Proteomic and metabolomic perturbations indicated lower chronic inflammation, improved lipid profiles, and altered protein and glycogen metabolism as potential biological mechanisms underlying these effects.CONCLUSIONS: We report novel evidence suggesting that long-term increases in circulating caffeine may reduce bodyweight and the risk of osteoarthrosis and osteoarthritis. We confirm prior genetic evidence of a protective effect of plasma caffeine on risk of overweight and obesity. Further clinical study is warranted to understand the translational relevance of these findings before clinical practice or lifestyle interventions related to caffeine consumption are introduced.PMID:38378567 | DOI:10.1186/s12916-024-03298-y

BMC Genomics. 2024 Feb 20;25(1):199. doi: 10.1186/s12864-024-10104-9.ABSTRACTBACKGROUND: Abiotic stresses in plants include all the environmental conditions that significantly reduce yields, like drought and heat. One of the most significant effects they exert at the cellular level is the accumulation of reactive oxygen species, which cause extensive damage. Plants possess two mechanisms to counter these molecules, i.e. detoxifying enzymes and non-enzymatic antioxidants, which include many classes of specialized metabolites. Sunflower, the fourth global oilseed, is considered moderately drought resistant. Abiotic stress tolerance in this crop has been studied using many approaches, but the control of specialized metabolites in this context remains poorly understood. Here, we performed the first genome-wide association study using abiotic stress-related specialized metabolites as molecular phenotypes in sunflower. After analyzing leaf specialized metabolites of 450 hybrids using liquid chromatography-mass spectrometry, we selected a subset of these compounds based on their association with previously known abiotic stress-related quantitative trait loci. Eventually, we characterized these molecules and their associated genes.RESULTS: We putatively annotated 30 compounds which co-localized with abiotic stress-related quantitative trait loci and which were associated to seven most likely candidate genes. A large proportion of these compounds were potential antioxidants, which was in agreement with the role of specialized metabolites in abiotic stresses. The seven associated most likely candidate genes, instead, mainly belonged to cytochromes P450 and glycosyltransferases, two large superfamilies which catalyze greatly diverse reactions and create a wide variety of chemical modifications. This was consistent with the high plasticity of specialized metabolism in plants.CONCLUSIONS: This is the first characterization of the genetic control of abiotic stress-related specialized metabolites in sunflower. By providing hints concerning the importance of antioxidant molecules in this biological context, and by highlighting some of the potential molecular mechanisms underlying their biosynthesis, it could pave the way for novel applications in breeding. Although further analyses will be required to better understand this topic, studying how antioxidants contribute to the tolerance to abiotic stresses in sunflower appears as a promising area of research.PMID:38378469 | DOI:10.1186/s12864-024-10104-9

Genes Immun. 2024 Feb 20. doi: 10.1038/s41435-024-00259-6. Online ahead of print.NO ABSTRACTPMID:38378863 | DOI:10.1038/s41435-024-00259-6

Clin Chim Acta. 2024 Feb 18:117831. doi: 10.1016/j.cca.2024.117831. Online ahead of print.ABSTRACTBACKGROUND: Volatile organic compounds (VOCs) have been shown as promising biomarkers for hepatocellular carcinoma (HCC) diagnosis. We aimed to investigate the performance of VOCs for diagnosing early-stage HCC in patients at-risk for HCC.METHODS: VOCs were identified in exhaled breath samples collected from 87 early-stage HCC patients, 90 cirrhotic patients, and 72 HBV-infected patients using thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry. The VOC levels were compared between the three groups. An association between VOCs and HCC was determined using logistic regression analysis. Diagnostic performance of VOCs was estimated using the AUROC and compared to serum alpha-fetoprotein (AFP).RESULTS: The levels of acetone monomer, dimethyl sulfide, 1,4-pentadiene, isopropyl alcohol, and acetone dimer were significantly different between the three groups. After adjusting for liver function test and AFP, acetone dimer was significantly associated with HCC. Acetone dimer significantly outperformed AFP with 86.2 % vs. 61.2 % sensitivity, 87.6 % vs. 66.2 % specificity, 86.9 % vs. 63.5 % for accuracy, and AUROC of 0.908 vs. 0.665, p = 0.007, <0.001, <0.001, and 0.001, respectively, for differentiating between HCC and cirrhosis.CONCLUSION: Acetone showed a better performance than AFP for diagnosing early HCC in at-risk patients. Further studies to validate the utility of VOCs as an HCC surveillance tool are needed.PMID:38378104 | DOI:10.1016/j.cca.2024.117831

Cell Rep Med. 2024 Feb 10:101429. doi: 10.1016/j.xcrm.2024.101429. Online ahead of print.ABSTRACTObesity is a risk factor for colorectal cancer (CRC), and the involvement of gut microbiota in the pathogenesis of obesity and CRC is widely recognized. However, the landscape of fecal microbiome and metabolome distinguishing patients with obesity-related CRC from obesity remains unknown. Here, we utilize metagenomic sequencing and metabolomics from 522 patients with CRC and healthy controls to identify the characteristics of obese CRC. Our integrated analysis reveals that obesity-related CRC is characterized by elevated Peptostreptococcus stomatis, dysregulated fatty acids and phospholipids, and altered Kyoto Encyclopedia of Genes and Genomes pathways involving glycerophospholipid metabolism and lipopolysaccharide synthesis. Correlation analysis unveils microbial interactions in obesity, where the probiotic Faecalibacterium prausnitzii and the tumor-promoting species P. stomatis may engage in cross-feeding, thereby promoting tumorigenesis. In vitro experiments affirm enhanced growth under cross-feeding conditions. The mutualistic microbe-microbe interaction may contribute to the association between obesity and elevated CRC risk. Additionally, diagnostic models incorporating BMI-specific microbial biomarkers display promise for precise CRC screening.PMID:38378003 | DOI:10.1016/j.xcrm.2024.101429

Mar Environ Res. 2024 Feb 6;196:106398. doi: 10.1016/j.marenvres.2024.106398. Online ahead of print.ABSTRACTNH3-N and NO2-N always co-exist in the aquatic environment, but there is not a clear opinion on their joint toxicities to the molluscs. Presently, clams Ruditapes philippinarum were challenged by environmental concentrations of NH3-N and NO2-N, singly or in combination, and analyzed by metabolomics approaches, enzyme assays and transmission electron microscope (TEM) observation. Results showed that some same KEGG pathways with different enriched-metabolites were detected in the three exposed groups within one day, and completely different profiles of metabolites were found in the rest of the exposure period. The combined exposure induced heavier and more lasting toxicities to the clams compared with their single exposure. ACP activity and the number of secondary lysosomes were significantly increased after the combined exposure. The present study shed light on the joint-toxicity mechanism of NH3-N and NO2-N, and provided fundamental data for the toxicity research on inorganic nitrogen.PMID:38377938 | DOI:10.1016/j.marenvres.2024.106398

Poult Sci. 2024 Feb 1;103(4):103524. doi: 10.1016/j.psj.2024.103524. Online ahead of print.ABSTRACTThe objective of this study was to investigate the effects of sex on meat quality and the composition of amino and fatty acids in the breast muscles of White King pigeon squabs. Untargeted metabolomics was also conducted to distinguish the metabolic composition of plasma in different sexes. Compared with male squabs, female squabs had greater intramuscular fat (IMF) deposition and lower myofiber diameter and hydroxyproline content, leading to a lower shear force. Female squabs also had higher monounsaturated fatty acid and lower n-6 and n-3 polyunsaturated fatty acid proportions in the breast muscle, and had greater lipogenesis capacity via upregulation of PPARγ, FAS and LPL gene expression. Moreover, female squabs had lower inosine 5'-monophosphate, essential, free and sweet-tasting amino acid contents. Furthermore, Spearman's correlations between the differential plasma metabolites and key meat parameters were assessed, and putrescine, N-acetylglutamic acid, phophatidylcholine (18:0/P-16:0) and trimethylamine N-oxide were found to contribute to meat quality. In summary, the breast meat of male squabs may have better nutritional value than that of females, but it may inferior in terms of sensory properties, which can be attributed to the lower IMF content and higher shear force value. Our findings enhance our understanding of sex variation in squab meat quality, providing a basis for future research on pigeon breeding.PMID:38377688 | DOI:10.1016/j.psj.2024.103524

ACS Chem Neurosci. 2024 Feb 20. doi: 10.1021/acschemneuro.3c00494. Online ahead of print.ABSTRACTGlutamate carboxypeptidase II (GCPII, also known as PSMA or FOLH1) is responsible for the cleavage of N-acetyl-aspartyl-glutamate (NAAG) to N-acetyl-aspartate and glutamate in the central nervous system and facilitates the intestinal absorption of folate by processing dietary folyl-poly-γ-glutamate in the small intestine. The physiological function of GCPII in other organs like kidneys is still not known. GCPII inhibitors are neuroprotective in various conditions (e.g., ischemic brain injury) in vivo; however, their utilization as potential drug candidates has not been investigated in regard to not yet known GCPII activities. To explore the GCPII role and possible side effects of GCPII inhibitors, we performed parallel metabolomic and lipidomic analysis of the cerebrospinal fluid (CSF), urine, plasma, and brain tissue of mice with varying degrees of GCPII deficiency (fully deficient in Folh1, -/-; one allele deficient in Folh1, +/-; and wild type, +/+). Multivariate analysis of metabolites showed no significant differences between wild-type and GCPII-deficient mice (except for NAAG), although changes were observed between the sex and age. NAAG levels were statistically significantly increased in the CSF, urine, and plasma of GCPII-deficient mice. However, no difference in NAAG concentrations was found in the whole brain lysate likely because GCPII, as an extracellular enzyme, can affect only extracellular and not intracellular NAAG concentrations. Regarding the lipidome, the most pronounced genotype-linked changes were found in the brain tissue. In brains of GCPII-deficient mice, we observed statistically significant enrichment in phosphatidylcholine-based lipids and reduction of sphingolipids and phosphatidylethanolamine plasmalogens. We hypothesize that the alteration of the NAA-NAAG axis by absent GCPII activity affected myelin composition. In summary, the absence of GCPII and thus similarly its inhibition do not have detrimental effects on metabolism, with just minor changes in the brain lipidome.PMID:38377674 | DOI:10.1021/acschemneuro.3c00494

Front Endocrinol (Lausanne). 2024 Feb 5;15:1322563. doi: 10.3389/fendo.2024.1322563. eCollection 2024.ABSTRACTBACKGROUND/PURPOSE: Metabolic-associated fatty liver disease (MAFLD) is a major cause of chronic liver disease worldwide and is generally thought to be closely related to obesity and diabetes. However, it also affects non-obese individuals, particularly in Asian cultures.METHODS: Healthy physical examination subjects and MAFLD patients were included in the endocrinology department of Jiangsu Provincial Hospital of Traditional Chinese Medicine. MAFLD was defined as fatty liver in imaging without virus infection, drug, alcohol, or other known causes of chronic liver disease. Non-obese MAFLD was defined as MAFLD in non-obese subjects (BMI<25 kg/m2).RESULTS: The final analysis comprised 1047 participants in total. Of 946 MAFLD patients, 162 (17.12%) were diagnosed with non-obese MAFLD. Non-obese MAFLD patients were older, had lower alanine aminotransferase (ALT), triglyceride, and waist circumference, but had higher high density lipoprotein cholesterol (HDL-c) than obese MAFLD patients. Compared with non-obese healthy controls, non-obese MAFLD patients had higher BMI, ALT, gamma-glutamyl transferase (GGT), uric acid (UA), triglycerides (TG), and low density lipoprotein cholesterol (LDL-c). In terms of body composition, body fat mass (BFM), waist-hip ratio (WHR), percent body fat (PBF), visceral fat area (VFA), and fat mass index (FMI) were lower in non-obese healthy controls than non-obese MAFLD patients. A binary logistic regression analysis revealed that non-obese MAFLD was linked with lower GGT and higher HDL-c.CONCLUSION: In this study cohort, non-obese MAFLD was present at a prevalence of 13.90%. In contrast to non-obese healthy controls, non-obese MAFLD patients exhibited different metabolic profiles, but they also had different body compositions.PMID:38375190 | PMC:PMC10876088 | DOI:10.3389/fendo.2024.1322563