PubMed

Compr Rev Food Sci Food Saf. 2024 Mar;23(2):e13325. doi: 10.1111/1541-4337.13325.ABSTRACTThis manuscript presents a comprehensive review of high-resolution mass spectrometry in the field of food analysis and metabolomics. We have followed the historical evolution of metabolomics, its associated techniques and technologies, and its increasing role in food science and research. The review provides a critical comparison and synthesis of tentative identification guidelines proposed for over 15 years, offering a condensed resource for researchers in the field. We have also examined a wide range of recent metabolomics studies, showcasing various methodologies and highlighting key findings as a testimony of the versatility of the field and the possibilities it offers. In doing so, we have also carefully provided a compilation of the software tools that may be employed in this type of studies. The manuscript also explores the prospects of high-resolution mass spectrometry and metabolomics in food science. By covering the history, guidelines, applications, and tools of metabolomics, this review attempts to become a comprehensive guide for researchers in a rapidly evolving field.PMID:38532695 | DOI:10.1111/1541-4337.13325

Biol Sex Differ. 2024 Mar 26;15(1):26. doi: 10.1186/s13293-024-00602-6.ABSTRACTBACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player of lipid metabolism with higher plasma levels in women throughout their life. Statin treatment affects PCSK9 levels also showing evidence of sex-differential effects. It remains unclear whether these differences can be explained by genetics.METHODS: We performed genome-wide association meta-analyses (GWAS) of PCSK9 levels stratified for sex and statin treatment in six independent studies of Europeans (8936 women/11,080 men respectively 14,825 statin-free/5191 statin-treated individuals). Loci associated in one of the strata were tested for statin- and sex-interactions considering all independent signals per locus. Independent variants at the PCSK9 gene locus were then used in a stratified Mendelian Randomization analysis (cis-MR) of PCSK9 effects on low-density lipoprotein cholesterol (LDL-C) levels to detect differences of causal effects between the subgroups.RESULTS: We identified 11 loci associated with PCSK9 in at least one stratified subgroup (p < 1.0 × 10-6), including the PCSK9 gene locus and five other lipid loci: APOB, TM6SF2, FADS1/FADS2, JMJD1C, and HP/HPR. The interaction analysis revealed eight loci with sex- and/or statin-interactions. At the PCSK9 gene locus, there were four independent signals, one with a significant sex-interaction showing stronger effects in men (rs693668). Regarding statin treatment, there were two significant interactions in PCSK9 missense mutations: rs11591147 had stronger effects in statin-free individuals, and rs11583680 had stronger effects in statin-treated individuals. Besides replicating known loci, we detected two novel genome-wide significant associations: one for statin-treated individuals at 6q11.1 (within KHDRBS2) and one for males at 12q24.22 (near KSR2/NOS1), both with significant interactions. In the MR of PCSK9 on LDL-C, we observed significant causal estimates within all subgroups, but significantly stronger causal effects in statin-free subjects compared to statin-treated individuals.CONCLUSIONS: We performed the first double-stratified GWAS of PCSK9 levels and identified multiple biologically plausible loci with genetic interaction effects. Our results indicate that the observed sexual dimorphism of PCSK9 and its statin-related interactions have a genetic basis. Significant differences in the causal relationship between PCSK9 and LDL-C suggest sex-specific dosages of PCSK9 inhibitors.PMID:38532495 | DOI:10.1186/s13293-024-00602-6

Cancer Metab. 2024 Mar 26;12(1):10. doi: 10.1186/s40170-024-00335-5.ABSTRACTBACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has been associated with the host dysmetabolism of branched-chain amino acids (BCAAs), however, the implications for the role of BCAA metabolism in PDAC development or progression are not clear. The mitochondrial catabolism of valine, leucine, and isoleucine is a multistep process leading to the production of short-chain R-CoA species. They can be subsequently exported from mitochondria as short-chain carnitines (SC-CARs), utilized in anabolic pathways, or released from the cells.METHODS: We examined the specificities of BCAA catabolism and cellular adaptation strategies to BCAA starvation in PDAC cells in vitro. We used metabolomics and lipidomics to quantify major metabolic changes in response to BCAA withdrawal. Using confocal microscopy and flow cytometry we quantified the fluorescence of BODIPY probe and the level of lipid droplets (LDs). We used BODIPY-conjugated palmitate to evaluate transport of fatty acids (FAs) into mitochondria. Also, we have developed a protocol for quantification of SC-CARs, BCAA-derived metabolites.RESULTS: Using metabolic profiling, we found that BCAA starvation leads to massive triglyceride (TG) synthesis and LD accumulation. This was associated with the suppression of activated FA transport into the mitochondrial matrix. The suppression of FA import into mitochondria was rescued with the inhibitor of the acetyl-CoA carboxylase (ACC) and the activator of AMP kinase (AMPK), which both regulate carnitine palmitoyltransferase 1A (CPT1) activation status.CONCLUSIONS: Our data suggest that BCAA catabolism is required for the import of long chain carnitines (LC-CARs) into mitochondria, whereas the disruption of this link results in the redirection of activated FAs into TG synthesis and its deposition into LDs. We propose that this mechanism protects cells against mitochondrial overload with LC-CARs and it might be part of the universal reaction to amino acid perturbations during cancer growth, regulating FA handling and storage.PMID:38532464 | DOI:10.1186/s40170-024-00335-5

BMC Plant Biol. 2024 Mar 26;24(1):219. doi: 10.1186/s12870-024-04902-2.ABSTRACTBACKGROUND: Drought is considered the main environmental factor restricting apple production and thus the development of the apple industry. Rootstocks play an important role in enhancing the drought tolerance of apple plants. Studies of the physiology have demonstrated that 'ZC9-3' is a strong drought-resistant rootstock, whereas 'Jizhen-2' is a weak drought-resistant rootstock. However, the metabolites in these two apple rootstock varieties that respond to drought stress have not yet been characterized, and the molecular mechanisms underlying their responses to drought stress remain unclear.RESULTS: In this study, the physiological and molecular mechanisms underlying differences in the drought resistance of 'Jizhen-2' (drought-sensitive) and 'ZC9-3' (drought-resistant) apple rootstocks were explored. Under drought stress, the relative water content of the leaves was maintained at higher levels in 'ZC9-3' than in 'Jizhen-2', and the photosynthetic, antioxidant, and osmoregulatory capacities of 'ZC9-3' were stronger than those of 'Jizhen-2'. Metabolome analysis revealed a total of 95 and 156 differentially accumulated metabolites in 'Jizhen-2' and 'ZC9-3' under drought stress, respectively. The up-regulated metabolites in the two cultivars were mainly amino acids and derivatives. Transcriptome analysis revealed that there were more differentially expressed genes and transcription factors in 'ZC9-3' than in 'Jizhen-2' throughout the drought treatment. Metabolomic and transcriptomic analysis revealed that amino acid biosynthesis pathways play key roles in mediating drought resistance in apple rootstocks. A total of 13 metabolites, including L-α-aminoadipate, L-homoserine, L-threonine, L-isoleucine, L-valine, L-leucine, (2S)-2-isopropylmalate, anthranilate, L-tryptophan, L-phenylalanine, L-tyrosine, L-glutamate, and L-proline, play an important role in the difference in drought resistance between 'ZC9-3' and 'Jizhen-2'. In addition, 13 genes encoding O-acetylserine-(thiol)-lyase, S-adenosylmethionine synthetase, ketol-acid isomeroreductase, dihydroxyacid dehydratase, isopropylmalate isomerase, branched-chain aminotransferase, pyruvate kinase, 3-dehydroquinate dehydratase/shikimate 5-dehydrogenase, N-acetylglutamate-5-P-reductase, and pyrroline-5-carboxylate synthetase positively regulate the response of 'ZC9-3' to drought stress.CONCLUSIONS: This study enhances our understanding of the response of apple rootstocks to drought stress at the physiological, metabolic, and transcriptional levels and provides key insights that will aid the cultivation of drought-resistant apple rootstock cultivars. Especially, it identifies key metabolites and genes underlying the drought resistance of apple rootstocks.PMID:38532379 | DOI:10.1186/s12870-024-04902-2

Comp Med. 2024 Feb 1;74(1):3-11. doi: 10.30802/AALAS-CM-23-000044.ABSTRACTL-368,899 is a selective small-molecule oxytocin receptor (OXTR) antagonist originally developed in the 1990s to prevent preterm labor. Although its utility for that purpose was limited, L-368,899 is now one of the most commonly used drugs in animal research for the selective blockade of neural OXTR after peripheral delivery. A growing number of rodent and primate studies have used L-368,899 to evaluate whether certain behaviors are oxytocin dependent. These studies have improved our understanding of oxytocin's function in the brains of rodents and monkeys, but very little work has been done in other mammals, and only a single paper in macaques has provided any evidence that L-368,899 can be detected in the CNS after peripheral delivery. The current study sought to extend those findings in a novel species: coyotes ( Canis latrans ). Coyotes are ubiquitous North American canids that form long-term monogamous pair-bonds. Although monogamy is rare in rodents and primates, all wild canid species studied to date exhibit social monogamy. Coyotes are therefore an excellent model organism for the study of oxytocin and social bonds. Our goal was to determine whether L-368,899 is a viable candidate for future use in behavioral studies in coyotes. We used captive coyotes at the USDA National Wildlife Research Center's Predator Research Facility to evaluate the pharmacokinetics of L-368,899 in blood and CSF during a 90-min time course after intramuscular injection. We then characterized the binding affinity and selectivity of L-368,899 to coyote OXTR and the structurally similar vasopressin 1a receptor. We found that L-368,899 peaked in CSF at 15 to 30 min after intramuscular injection and slowly accumulated in blood. L-368,899 was 40 times more selective for OXTR than vasopressin 1a receptors and bound to the coyote OXTR with an affinity of 12 nM. These features of L-368,899 support its utility in future studies to probe the oxytocin system of coyotes.PMID:38532262 | DOI:10.30802/AALAS-CM-23-000044

Environ Sci Pollut Res Int. 2024 Mar 27. doi: 10.1007/s11356-024-32967-x. Online ahead of print.ABSTRACTImazethapyr is a widely used imidazolinone herbicide worldwide, and its potential adverse effects on non-target plants have raised concerns. Understanding the mechanisms of imazethapyr phytotoxicity is crucial for its agro-ecological risk assessment. Here, the comprehensive molecular responses and metabolic alterations of Arabidopsis in response to imazethapyr were investigated. Our results showed that root exposure to imazethapyr inhibited shoot growth, reduced chlorophyll contents, induced photoinhibition and decreased photosynthetic activity. By non-target metabolomic analysis, we identified 75 metabolites that were significantly changed after imazethapyr exposure, and they are mainly enriched in carbohydrate, lipid and amino acid metabolism. Transcriptomic analysis confirmed that imazethapyr significantly downregulated the genes involved in photosynthetic electron transport and the carbon cycle. In detail, 48 genes in the photosynthetic lightreaction and 11 genes in Calvin cycle were downregulated. Additionally, the downregulation of genes related to electron transport in mitochondria provides strong evidence for imazethapyr inhibiting photosynthetic carbon fixation and cellular energy metabolism as one of mechanisms of toxicity. These results revealed the molecular and metabolic basis of imazethapyr toxicity on non-target plants, contributing to environmental risk assessment and mitigate negative impact of imazethapyr residues in agricultural soils.PMID:38532215 | DOI:10.1007/s11356-024-32967-x

Transl Psychiatry. 2024 Mar 26;14(1):163. doi: 10.1038/s41398-024-02886-z.ABSTRACTMajor depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are classified as major mental disorders and together account for the second-highest global disease burden, and half of these patients experience symptom onset in adolescence. Several studies have reported both similar and unique features regarding the risk factors and clinical symptoms of these three disorders. However, it is still unclear whether these disorders have similar or unique metabolic characteristics in adolescents. We conducted a metabolomics analysis of plasma samples from adolescent healthy controls (HCs) and patients with MDD, BD, and SCZ. We identified differentially expressed metabolites between patients and HCs. Based on the differentially expressed metabolites, correlation analysis, metabolic pathway analysis, and potential diagnostic biomarker identification were conducted for disorders and HCs. Our results showed significant changes in plasma metabolism between patients with these mental disorders and HCs; the most distinct changes were observed in SCZ patients. Moreover, the metabolic differences in BD patients shared features with those in both MDD and SCZ, although the BD metabolic profile was closer to that of MDD than to SCZ. Additionally, we identified the metabolites responsible for the similar and unique metabolic characteristics in multiple metabolic pathways. The similar significant differences among the three disorders were found in fatty acid, steroid-hormone, purine, nicotinate, glutamate, tryptophan, arginine, and proline metabolism. Interestingly, we found unique characteristics of significantly altered glycolysis, glycerophospholipid, and sphingolipid metabolism in SCZ; lysine, cysteine, and methionine metabolism in MDD and BD; and phenylalanine, tyrosine, and aspartate metabolism in SCZ and BD. Finally, we identified five panels of potential diagnostic biomarkers for MDD-HC, BD-HC, SCZ-HC, MDD-SCZ, and BD-SCZ comparisons. Our findings suggest that metabolic characteristics in plasma vary across psychiatric disorders and that critical metabolites provide new clues regarding molecular mechanisms in these three psychiatric disorders.PMID:38531835 | DOI:10.1038/s41398-024-02886-z

Free Radic Biol Med. 2024 Mar 24:S0891-5849(24)00141-2. doi: 10.1016/j.freeradbiomed.2024.03.016. Online ahead of print.ABSTRACTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which the death of motor neurons leads to loss of muscle function. Additionally, cognitive and circadian disruptions are common in ALS patients, contributing to disease progression and burden. Most ALS cases are sporadic, and environmental exposures contribute to their aetiology. However, animal models of these sporadic ALS cases are scarce. The small vertebrate zebrafish is a leading organism to model neurodegenerative diseases; previous studies have proposed bisphenol A (BPA) or β-methylamino-l-alanine (BMAA) exposure to model sporadic ALS in zebrafish, damaging motor neurons and altering motor responses. Here we characterise the face and predictive validity of sporadic ALS models, showing their potential for the mechanistic study of ALS drugs. We phenotypically characterise the BPA and BMAA-induced models, going beyond motor activity and motor axon morphology, to include circadian, redox, proteostasis, and metabolomic phenotypes, and assessing their predictive validity for ALS modelling. BPA or BMAA exposure induced concentration-dependent activity impairments. Also, exposure to BPA but not BMAA induced motor axonopathy and circadian alterations in zebrafish larvae. Our further study of the BPA model revealed loss of habituation to repetitive startles, increased oxidative damage, endoplasmic reticulum (ER) stress, and metabolome abnormalities. The BPA-induced model shows predictive validity, since the approved ALS drug edaravone counteracted BPA-induced motor phenotypes, ER stress, and metabolic disruptions. Overall, BPA exposure is a promising model of ALS-related redox and ER imbalances, contributing to fulfil an unmet need for validated sporadic ALS models.PMID:38531462 | DOI:10.1016/j.freeradbiomed.2024.03.016

Food Chem. 2024 Mar 18;448:139052. doi: 10.1016/j.foodchem.2024.139052. Online ahead of print.ABSTRACTThe study investigated the effect of different sodium chloride (NaCl) concentrations (10%, 15%, and 20%) on the ripening fermentation of Pixian-Douban, a traditional fermented condiment. The results showed that NaCl affected the dynamics of physicochemical parameters, volatile components, fatty acids, amino metabolites, organic acids, and microbial composition, and their dynamic modes were different. After 253 days fermentation, the 10% NaCl Pixian-Douban had significantly (p < 0.05) higher levels of total organic acids (20,308.25 mg/kg), amino metabolites (28,144.96 mg/kg), and volatiles (3.36 mg/kg) compared to 15% and 20% NaCl Pixian-Douban. Notably, the possible health risk associated with high concentration of biogenic amines in 10% NaCl Pixian-Douban is of concern. Moreover, correlation analyses indicated that the effect of NaCl on the quality of Pixian-Douban may be mainly related to bacteria. This study deepens the knowledge about the role of NaCl in ripening fermentation of Pixian-Douban and contributes to develop low-NaCl Pixian-Douban product.PMID:38531296 | DOI:10.1016/j.foodchem.2024.139052

J Agric Food Chem. 2024 Mar 26. doi: 10.1021/acs.jafc.3c07853. Online ahead of print.ABSTRACTFlammulina velutipes has two independent and functional mating type factors, HD and PR. The HD locus contains two separate subloci: HD-a and HD-b. In this study, we investigated the roles of Hd1 genes of the HD-a and HD-b subloci in the process of mating, clamp cell formation, and regulation of FvClp1 (F. velutipes clampless1 gene) gene expression in F. velutipes. To this end, we introduced Hd1 genes from mating compatible strains into F. velutipes monokaryon L11. Overexpression of Hd1 gene FvHd-a1-1 of the HD-a sublocus resulted in the formation of pseudoclamps in L11 monokaryons. L11 mutants overexpressing the Hd1 gene FvHd-b1-2 of the HD-b sublocus also similarly developed pseudoclamps in the L11 monokaryons. Moreover, these mutant L11 monokaryons produced complete clamps when crossed with monokaryotic strains that differed at the PR loci, i.e., when selective activation of the PR pathway was obtained through crossing. Thus, Hd1 genes of the two different HD subloci in F. velutipes can activate the HD mating type pathway and induce clamp cell formation. In addition, activation of the HD pathway resulted in upregulation of the FvClp1 gene. Finally, to complete clamp cell formation, activation of the PR pathway appears to be essential. Overall, these findings were beneficial for deepening our understanding of sexual reproduction and fruiting body development of edible fungi.PMID:38530934 | DOI:10.1021/acs.jafc.3c07853

Proc Natl Acad Sci U S A. 2024 Apr 2;121(14):e2317574121. doi: 10.1073/pnas.2317574121. Epub 2024 Mar 26.ABSTRACTFine particulate matter (PM2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM2.5 and the critical toxic PM2.5 components in both regions. Among the PM2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM2.5 cytotoxicities. Its supplementation effectively attenuated PM2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM2.5 components.PMID:38530899 | DOI:10.1073/pnas.2317574121

J Agric Food Chem. 2024 Mar 26. doi: 10.1021/acs.jafc.3c08498. Online ahead of print.ABSTRACTIn this study, we evaluated the effect of increasing the salinity of irrigation water on the metabolic content and profiles of two tomato cultivars ('Jaune Flamme' (JF) and 'Red Pear' (RP)) using targeted and untargeted metabolomics approaches. Irrigation of tomato plants was performed with four different salt concentrations provided by chloride (treatment 1) and sulfate (treatment 2) salts. Targeted analysis of the methanolic extract resulted in the identification of nine major polyphenols. Among them, chlorogenic acid, rutin, and naringenin were the prominent compounds in both cultivars. In addition, the quantification of 18 free amino acids from both tomato cultivars showed that different salinity treatments significantly enhanced the levels of glutamine, glutamic acid, and γ-aminobutyric acid (GABA). Using the untargeted metabolomic approach, we identified 129 putative metabolites encompassing a diverse array of phytochemicals including polyphenols, organic acids, lipids, sugars, and amino acids. Principal component analysis (PCA) of mass spectral data acquired under positive and negative ionization modes showed a clear separation between the two cultivars. However, only positive ionization showed separation among different salinity treatments. Unsupervised and supervised learning algorithms were applied to mine the generated data and to pinpoint metabolites different from the two cultivars. These findings suggest that different salinity conditions significantly influenced the accumulation of phytochemicals in tomato cultivars. This study will help tomato breeding programs to develop value-added tomato cultivars under varying environmental conditions.PMID:38530768 | DOI:10.1021/acs.jafc.3c08498

JCI Insight. 2024 Mar 26:e167578. doi: 10.1172/jci.insight.167578. Online ahead of print.ABSTRACTSkeletal muscle wasting results from numerous pathological conditions impacting both the musculoskeletal and nervous systems. A unifying feature of these pathologies is the upregulation of members of the E3 ubiquitin ligase family, resulting in increased proteolytic degradation of target proteins. Despite the critical role E3 ubiquitin ligases in regulating muscle mass, the specific proteins they target for degradation and the mechanisms by which they regulate skeletal muscle homeostasis remain ill-defined. Here, using zebrafish loss of function models combined with in vivo cell biology and proteomic approaches, we reveal a role of atrogin-1 in regulating the levels of the endoplasmic reticulum chaperone BiP. Loss of atrogin-1 results in an accumulation of BiP, leading to impaired mitochondrial dynamics and a subsequent loss in muscle fibre integrity. We further implicate a disruption in atrogin-1 mediated BiP regulation in the pathogenesis of Duchenne muscular dystrophy. We reveal that BiP is not only upregulated in Duchenne muscular dystrophy, but its inhibition using pharmacological strategies, or by upregulating atrogin-1, significantly ameliorates pathology in a zebrafish model of Duchenne muscular dystrophy. Collectively, our data implicates atrogin-1 and BiP in the pathogenesis of Duchenne muscular dystrophy, and highlights atrogin-1's essential role in maintaining muscle homeostasis.PMID:38530354 | DOI:10.1172/jci.insight.167578

Oncologist. 2024 Mar 26:oyae048. doi: 10.1093/oncolo/oyae048. Online ahead of print.ABSTRACTBACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored.METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety.RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B.CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.PMID:38530254 | DOI:10.1093/oncolo/oyae048

Acta Paediatr. 2024 Mar 26. doi: 10.1111/apa.17219. Online ahead of print.ABSTRACTAIM: Few studies investigate factors that might influence the content of expressed breastmilk. This study aims to investigate the influence of the intervals between breastmilk pumping and the time of the day on protein and fat concentration in breastmilk.METHODS: Mothers of very preterm infants in a neonatal ward who expressed more than 400 mL per day were included. Expressed breastmilk was obtained from each mother over 30 h who were pumping at strictly planned and varying intervals: 2, 3, 4 and 6 h. All samples were analysed using infrared transmission spectroscopy.RESULTS: Ten mothers participated at a median of 22 days postpartum. A total of 176 milk samples were analysed, and the average protein and fat concentrations in g/100 mL were 1.1 ± 0.23 and 4.2 ± 1.3, respectively. The time intervals between breast pumping sessions did not impact protein content, but fat content decreased by longer intervals (p < 0.01). The time of the day for milk pumping did not influence the protein or fat content.CONCLUSION: A single milk sample collected after any 2-6 h interval, at any time during the day, represents the protein content in the breastmilk, but not the fat content which decreased with longer intervals.PMID:38530084 | DOI:10.1111/apa.17219

Small. 2024 Mar 26:e2400941. doi: 10.1002/smll.202400941. Online ahead of print.ABSTRACTMultidimensional metabolic analysis has become a new trend in establishing efficient disease monitoring systems, as the constraints associated with relying solely on a single dimension in refined monitoring are increasingly pronounced. Here, coordination polymers are employed as derivative precursors to create multishell hollow hybrids, developing an integrated metabolic monitoring system. Briefly, metabolic fingerprints are extracted from hundreds of serum samples and urine samples, encompassing not only membranous nephropathy but also related diseases, using high-throughput mass spectrometry. With optimized algorithm and initial feature selection, the established combined panel demonstrates enhanced accuracy in both subtype differentiation (over 98.1%) and prognostic monitoring (over 95.6%), even during double blind test. This surpasses the serum biomarker panel (≈90.7% for subtyping, ≈89.7% for prognosis) and urine biomarker panel (≈94.4% for subtyping, ≈76.5% for prognosis). Moreover, after attempting to further refine the marker panel, the blind test maintains equal sensitivity, specificity, and accuracy, showcasing a comprehensive improvement over the single-fluid approach. This underscores the remarkable effectiveness and superiority of the integrated strategy in discriminating between MN and other groups. This work has the potential to significantly advance diagnostic medicine, leading to the establishment of more effective strategies for patient management.PMID:38529737 | DOI:10.1002/smll.202400941

Mol Ecol. 2024 Mar 26:e17321. doi: 10.1111/mec.17321. Online ahead of print.ABSTRACTFundamental to holobiont biology is recognising how variation in microbial composition and function relates to host phenotypic variation. Sponges often exhibit considerable phenotypic plasticity and also harbour dense microbial communities that function to protect and nourish hosts. One of the most prominent sponge genera on Caribbean coral reefs is Agelas. Using a comprehensive set of morphological (growth form, spicule), chemical and molecular data on 13 recognised species of Agelas in the Caribbean basin, we were able to define only five species (=clades) and found that many morphospecies designations were incongruent with phylogenomic and population genetic analyses. Microbial communities were also strongly differentiated between phylogenetic species, showing little evidence of cryptic divergence and relatively low correlation with morphospecies assignment. Metagenomic analyses also showed strong correspondence to phylogenetic species, and to a lesser extent, geographical and morphological characters. Surprisingly, the variation in secondary metabolites produced by sponge holobionts was explained by geography and morphospecies assignment, in addition to phylogenetic species, and covaried significantly with a subset of microbial symbionts. Spicule characteristics were highly plastic, under greater impact from geographical location than phylogeny. Our results suggest that while phenotypic plasticity is rampant in Agelas, morphological differences within phylogenetic species affect functionally important ecological traits, including the composition of the symbiotic microbial communities and metabolomic profiles.PMID:38529721 | DOI:10.1111/mec.17321

Anal Chem. 2024 Mar 26. doi: 10.1021/acs.analchem.3c05576. Online ahead of print.ABSTRACTPubChem serves as a comprehensive repository, housing over 100 million unique chemical structures representing the breadth of our chemical knowledge across numerous fields including metabolism, pharmaceuticals, toxicology, cosmetics, agriculture, and many more. Rapid identification of these small molecules increasingly relies on electrospray ionization (ESI) paired with tandem mass spectrometry (MS/MS), particularly by comparison to genuine standard MS/MS data sets. Despite its widespread application, achieving consistency in MS/MS data across various analytical platforms remains an unaddressed concern. This study evaluated MS/MS data derived from one hundred molecular standards utilizing instruments from five manufacturers, inclusive of quadrupole time-of-flight (QTOF) and quadrupole orbitrap "exactive" (QE) mass spectrometers by Agilent (QTOF), Bruker (QTOF), SCIEX (QTOF), Waters (QTOF), and Thermo QE. We assessed fragment ion variations at multiple collisional energies (0, 10, 20, and 40 eV) using the cosine scoring algorithm for comparisons and the number of fragments observed. A parallel visual analysis of the MS/MS spectra across instruments was conducted, consistent with a standard procedure that is used to circumvent the still prevalent issue of mischaracterizations as shown for dimethyl sphingosine and C20 sphingosine. Our analysis revealed a notable consistency in MS/MS data and identifications, with fragment ions' m/z values exhibiting the highest concordance between instrument platforms at 20 eV, the other collisional energies (0, 10, and 40 eV) were significantly lower. While moving toward a standardized ESI MS/MS protocol is required for dependable molecular characterization, our results also underscore the continued importance of corroborating MS/MS data against standards to ensure accurate identifications. Our findings suggest that ESI MS/MS manufacturers, akin to the established norms for gas chromatography mass spectrometry instruments, should standardize the collision energy at 20 eV across different instrument platforms.PMID:38529642 | DOI:10.1021/acs.analchem.3c05576

Front Cell Infect Microbiol. 2024 Mar 11;14:1283737. doi: 10.3389/fcimb.2024.1283737. eCollection 2024.ABSTRACTGallstones are crystalline deposits in the gallbladder that are traditionally classified as cholesterol, pigment, or mixed stones based on their composition. Microbiota and host metabolism variances among the different types of gallstones remain largely unclear. Here, the bile and gallstone microbial species spectra of 29 subjects with gallstone disease (GSD, 24 cholesterol and 5 pigment) were revealed by type IIB restriction site-associated DNA microbiome sequencing (2bRAD-M). Among them (21 subjects: 18 cholesterol and 3 pigment), plasma samples were subjected to liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics. The microbiome yielded 896 species comprising 882 bacteria, 13 fungi, and 1 archaeon. Microbial profiling revealed significant enrichment of Cutibacterium acnes and Microbacterium sp005774735 in gallstone and Agrobacterium pusense and Enterovirga sp013044135 in the bile of cholesterol GSD subjects. The metabolome revealed 2296 metabolites, in which malvidin 3-(6''-malonylglucoside), 2-Methylpropyl glucosinolate, and ergothioneine were markedly enriched in cholesterol GSD subjects. Metabolite set enrichment analysis (MSEA) demonstrated enriched bile acids biosynthesis in individuals with cholesterol GSD. Overall, the multi-omics analysis revealed that microbiota and host metabolism interaction perturbations differ depending on the disease type. Perturbed gallstone type-related microbiota may contribute to unbalanced bile acids metabolism in the gallbladder and host, representing a potential early diagnostic marker and therapeutic target for GSD.PMID:38529471 | PMC:PMC10962445 | DOI:10.3389/fcimb.2024.1283737

Front Immunol. 2024 Mar 11;15:1335181. doi: 10.3389/fimmu.2024.1335181. eCollection 2024.ABSTRACTINTRODUCTION: Temporomandibular joint (TMJ) osteoarthritis (OA) is a common TMJ degenerative disease with an unclear mechanism. Synovial fluid (SF), an important component of TMJ, contains various proteins and metabolites that may directly contribute to OA. The present study aimed to investigate the influence of SF in TMJOA at the metabolite level.METHODS: Untargeted and widely targeted metabolic profiling were employed to identify metabolic changes in SF of 90 patients with different TMJOA grades according to TMJ magnetic resonance imaging.RESULTS: A total 1498 metabolites were detected. Most of the metabolites were amino acids and associated metabolites, benzene and substituted derivatives, and lipids. Among patients with mild, moderate and severe TMJOA, 164 gradually increasing and 176 gradually decreasing metabolites were identified, indicating that biosynthesis of cofactors, choline metabolism, mineral absorption and selenocompound metabolism are closely related to TMJOA grade. Combined metabolomics and clinical examination revealed 37 upregulated metabolites and 16 downregulated metabolites in patients with pain, of which 19 and 26 metabolites were positively and negatively correlated, respectively, with maximum interincisal opening. A model was constructed to diagnose TMJOA grade and nine biomarkers were identified. The identified metabolites are key to exploring the mechanism of TMJOA.DISCUSSION: In the present study, a metabolic profile was constructed and assessed using a much larger number of human SF samples from patients with TMJOA, and a model was established to contribute to the diagnosis of TMJOA grade. The findings expand our knowledge of metabolites in human SF of TMJOA patients, and provide an important basis for further research on the pathogenesis and treatment of TMJOA.PMID:38529278 | PMC:PMC10961395 | DOI:10.3389/fimmu.2024.1335181