PubMed

MedComm (2020). 2024 Feb 28;5(3):e488. doi: 10.1002/mco2.488. eCollection 2024 Mar.ABSTRACTAutism spectrum disorder (ASD) presents a significant risk to human well-being and has emerged as a worldwide public health concern. Twenty-eight children with ASD and 33 healthy children (HC) were selected for the quantitative determination of their plasma metabolites using an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) platform. A total of 1997 metabolites were detected in the study cohort, from which 116 metabolites were found to be differentially expressed between the ASD and HC groups. Through analytical algorithms such as least absolute shrinkage selection operator (LASSO), support vector machine (SVM), and random forest (RF), three potential metabolic markers were identified as FAHFA (18:1(9Z)/9-O-18:0), DL-2-hydroxystearic acid, and 7(S),17(S)-dihydroxy-8(E),10(Z),13(Z),15(E),19(Z)-docosapentaenoic acid. These metabolites demonstrated superior performance in distinguishing the ASD group from the HC group, as indicated by the area under curves (AUCs) of 0.935, 0.897, and 0.963 for the three candidate biomarkers, respectively. The samples were divided into training and validation sets according to 7:3. Diagnostic models were constructed using logistic regression (LR), SVM, and RF. The constructed three-biomarker diagnostic model also exhibited strong discriminatory efficacy. These findings contribute to advancing our understanding of the underlying mechanisms involved in the occurrence of ASD and provide a valuable reference for clinical diagnosis.PMID:38420161 | PMC:PMC10901282 | DOI:10.1002/mco2.488

Front Microbiol. 2024 Feb 14;15:1275865. doi: 10.3389/fmicb.2024.1275865. eCollection 2024.ABSTRACTINTRODUCTION: The dietary protein level plays a crucial role in maintaining the equilibrium of rumen microbiota in yaks. To explore the association between dietary protein levels, rumen microbiota, and muscle metabolites, we examined the rumen microbiome and muscle metabolome characteristics in yaks subjected to varying dietary protein levels.METHODS: In this study, 36 yaks were randomly assigned to three groups (n = 12 per group): low dietary protein group (LP, 12% protein concentration), medium dietary protein group (MP, 14% protein concentration), and high dietary protein group (HP, 16% protein concentration).RESULTS: 16S rDNA sequencing revealed that the HP group exhibited the highest Chao1 and Observed_species indices, while the LP group demonstrated the lowest. Shannon and Simpson indices were significantly elevated in the MP group relative to the LP group (P < 0.05). At the genus level, the relative abundance of Christensenellaceae_R-7_group in the HP group was notably greater than that in the LP and MP groups (P < 0.05). Conversely, the relative abundance of Rikenellaceae_RC9_gut_group displayed an increasing tendency with escalating feed protein levels. Muscle metabolism analysis revealed that the content of the metabolite Uric acid was significantly higher in the LP group compared to the MP group (P < 0.05). The content of the metabolite L-(+)-Arabinose was significantly increased in the MP group compared to the HP group (P < 0.05), while the content of D-(-)-Glutamine and L-arginine was significantly reduced in the LP group (P < 0.05). The levels of metabolites 13-HPODE, Decanoylcarnitine, Lauric acid, L-(+)-Arabinose, and Uric acid were significantly elevated in the LP group relative to the HP group (P < 0.05). Furthermore, our observations disclosed correlations between rumen microbes and muscle metabolites. The relative abundance of NK4A214_group was negatively correlated with Orlistat concentration; the relative abundance of Christensenellaceae_R-7_group was positively correlated with D-(-)-Glutamine and L-arginine concentrations.DISCUSSION: Our findings offer a foundation for comprehending the rumen microbiome of yaks subjected to different dietary protein levels and the intimately associated metabolic pathways of the yak muscle metabolome. Elucidating the rumen microbiome and muscle metabolome of yaks may facilitate the determination of dietary protein levels.PMID:38419639 | PMC:PMC10899706 | DOI:10.3389/fmicb.2024.1275865

Front Microbiol. 2024 Feb 13;15:1343572. doi: 10.3389/fmicb.2024.1343572. eCollection 2024.ABSTRACTMetagenomics, Metabolomics, and Metaproteomics have significantly advanced our knowledge of microbial communities by providing culture-independent insights into their composition and functional potential. However, a critical challenge in this field is the lack of standard and comprehensive metadata associated with raw data, hindering the ability to perform robust data stratifications and consider confounding factors. In this comprehensive review, we categorize publicly available microbiome data into five types: shotgun sequencing, amplicon sequencing, metatranscriptomic, metabolomic, and metaproteomic data. We explore the importance of metadata for data reuse and address the challenges in collecting standardized metadata. We also, assess the limitations in metadata collection of existing public repositories collecting metagenomic data. This review emphasizes the vital role of metadata in interpreting and comparing datasets and highlights the need for standardized metadata protocols to fully leverage metagenomic data's potential. Furthermore, we explore future directions of implementation of Machine Learning (ML) in metadata retrieval, offering promising avenues for a deeper understanding of microbial communities and their ecological roles. Leveraging these tools will enhance our insights into microbial functional capabilities and ecological dynamics in diverse ecosystems. Finally, we emphasize the crucial metadata role in ML models development.PMID:38419630 | PMC:PMC10900530 | DOI:10.3389/fmicb.2024.1343572

J Anim Sci Biotechnol. 2024 Feb 28;15(1):34. doi: 10.1186/s40104-023-00983-5.ABSTRACTBACKGROUND: Providing high-quality roughage is crucial for improvement of ruminant production because it is an essential component of their feed. Our previous study showed that feeding bio-fermented rice straw (BF) improved the feed intake and weight gain of sheep. However, it remains unclear why feeding BF to sheep increased their feed intake and weight gain. Therefore, the purposes of this research were to investigate how the rumen microbiota and serum metabolome are dynamically changing after feeding BF, as well as how their changes influence the feed intake, digestibility, nutrient transport, meat quality and growth performances of sheep. Twelve growing Hu sheep were allocated into 3 groups: alfalfa hay fed group (AH: positive control), rice straw fed group (RS: negative control) and BF fed group (BF: treatment). Samples of rumen content, blood, rumen epithelium, muscle, feed offered and refusals were collected for the subsequent analysis.RESULTS: Feeding BF changed the microbial community and rumen fermentation, particularly increasing (P < 0.05) relative abundance of Prevotella and propionate production, and decreasing (P < 0.05) enteric methane yield. The histomorphology (height, width, area and thickness) of rumen papillae and gene expression for carbohydrate transport (MCT1), tight junction (claudin-1, claudin-4), and cell proliferation (CDK4, Cyclin A2, Cyclin E1) were improved (P < 0.05) in sheep fed BF. Additionally, serum metabolome was also dynamically changed, which led to up-regulating (P < 0.05) the primary bile acid biosynthesis and biosynthesis of unsaturated fatty acid in sheep fed BF. As a result, the higher (P < 0.05) feed intake, digestibility, growth rate, feed efficiency, meat quality and mono-unsaturated fatty acid concentration in muscle, and the lower (P < 0.05) feed cost per kg of live weight were achieved by feeding BF.CONCLUSIONS: Feeding BF improved the growth performances and meat quality of sheep and reduced their feed cost. Therefore, bio-fermentation of rice straw could be an innovative way for improving ruminant production with minimizing production costs.PMID:38419130 | DOI:10.1186/s40104-023-00983-5

Cancer Cell Int. 2024 Feb 28;24(1):87. doi: 10.1186/s12935-024-03275-8.ABSTRACTBACKGROUND: As a key enzyme in ceramide synthesis, longevity assurance homologue 2 (LASS2) has been indicated to act as a tumour suppressor in a variety of cancers. Ferroptosis is involved in a variety of tumour processes; however, the role of LASS2 in regulating ferroptosis has yet to be explored. This article explores the potential underlying mechanisms involved.METHODS: Bioinformatics tools and immunohistochemical staining were used to evaluate LASS2 expression, and the results were analysed in relation to overall survival and clinical association in multiple cancers. Coimmunoprecipitation-coupled liquid chromatography-mass spectrometry (co-IP LC-MS) was performed to identify potential LASS2-interacting proteins in thyroid, breast, and liver cancer cell lines. Transcriptomics, proteomics and metabolomics analyses of multiple cancer cell types were performed using MS or LC-MS to further explore the underlying mechanisms involved. Among these tumour cells, the common LASS2 interaction partner transferrin receptor (TFRC) was analysed by protein-protein docking and validated by coimmunoprecipitation western blot, immunofluorescence, and proximity ligation assays. Then, we performed experiments in which tumour cells were treated with Fer-1 or erastin or left untreated, with or without inducing LASS2 overexpression, and assessed the molecular biological and cellular functions by corresponding analyses.RESULTS: Low LASS2 expression is correlated with adverse clinical characteristic and poor prognosis in patients with thyroid cancer, breast cancer or HCC. Multiomics analyses revealed significant changes in the ferroptosis signalling pathway, iron ion transport and iron homeostasis. Our in vitro experiments revealed that LASS2 overexpression regulated ferroptosis status in these tumour cells by affecting iron homeostasis, which in turn inhibited tumour migration, invasion and EMT. In addition, LASS2 overexpression reversed the changes in tumour cell metastasis induced by either Fer-1 or erastin. Mechanistically, LASS2 interacts directly with TFRC to regulate iron homeostasis in these tumour cells.CONCLUSIONS: In summary, our study reveals for the first time that LASS2 can inhibit tumour cell metastasis by interacting with TFRC to regulate iron metabolism and influence ferroptosis status in thyroid, breast, and liver cancer cells, these results suggest potential universal therapeutic targets for the treatment of these cancers.PMID:38419028 | DOI:10.1186/s12935-024-03275-8

BMC Plant Biol. 2024 Feb 28;24(1):147. doi: 10.1186/s12870-024-04823-0.ABSTRACTCarbohydrates, proteins, lipids, minerals and vitamins are nutrient substances commonly seen in rice grains, but anthocyanidin, with benefit for plant growth and animal health, exists mainly in the common wild rice but hardly in the cultivated rice. To screen the rice germplasm with high intensity of anthocyanidins and identify the variations, we used metabolomics technique and detected significant different accumulation of anthocyanidins in common wild rice (Oryza rufipogon, with purple leaf sheath) and cultivated rice (Oryza sativa, with green leaf sheath). In this study, we identified and characterized a well-known MYB transcription factor, OsC1, through phenotypic (leaf sheath color) and metabolic (metabolite profiling) genome-wide association studies (pGWAS and mGWAS) in 160 common wild rice (O. rufipogon) and 151 cultivated (O. sativa) rice varieties. Transgenic experiments demonstrated that biosynthesis and accumulation of cyanidin-3-Galc, cyanidin 3-O-rutinoside and cyanidin O-syringic acid, as well as purple pigmentation in leaf sheath were regulated by OsC1. A total of 25 sequence variations of OsC1 constructed 16 functional haplotypes (higher accumulation of the three anthocyanidin types within purple leaf sheath) and 9 non-functional haplotypes (less accumulation of anthocyanidins within green leaf sheath). Three haplotypes of OsC1 were newly identified in our germplasm, which have potential values in functional genomics and molecular breeding of rice. Gene-to-metabolite analysis by mGWAS and pGWAS provides a useful and efficient tool for functional gene identification and omics-based crop genetic improvement.PMID:38418937 | DOI:10.1186/s12870-024-04823-0

Sci Rep. 2024 Feb 28;14(1):4841. doi: 10.1038/s41598-024-55356-3.ABSTRACTWe used the Exploris 240 mass spectrometer for non-targeted metabolomics on Saccharomyces cerevisiae strain BY4741 and tested AcquireX software for increasing the number of detectable compounds and Compound Discoverer 3.3 software for identifying compounds by MS2 spectral library matching. AcquireX increased the number of potentially identifiable compounds by 50% through six iterations of MS2 acquisition. On the basis of high-scoring MS2 matches made by Compound Discoverer, there were 483 compounds putatively identified from nearly 8000 candidate spectra. Comparisons to 20 amino acid standards, however, revealed instances whereby compound matches could be incorrect despite strong scores. Situations included the candidate with the top score not being the correct compound, matching the same compound at two different chromatographic peaks, assigning the highest score to a library compound much heavier than the mass for the parent ion, and grouping MS2 isomers to a single parent ion. Because the software does not calculate false positive and false discovery rates at these multiple levels where such errors can propagate, we conclude that manual examination of findings will be required post software analysis. These results will interest scientists who may use this platform for metabolomics research in diverse disciplines including medical science, environmental science, and agriculture.PMID:38418855 | DOI:10.1038/s41598-024-55356-3

Metabolomics. 2024 Feb 28;20(2):31. doi: 10.1007/s11306-024-02088-0.ABSTRACTINTRODUCTION: The chromosome 22q11.2 deletion syndrome (22q11.2DS) is characterized by a well-defined microdeletion and is associated with a wide range of brain-related phenotypes including schizophrenia spectrum disorders (SCZ), autism spectrum disorders (ASD), anxiety disorders and attention deficit disorders (ADHD). The typically deleted region in 22q11.2DS contains multiple genes which haploinsufficiency has the potential of altering the protein and the metabolic profiles.OBJECTIVES: Alteration in metabolic processes and downstream protein pathways during the early brain development may help to explain the increased prevalence of the observed neurodevelopmental phenotypes in 22q11.2DS. However, relatively little is known about the correlation of dysregulated protein/metabolite expression and neurobehavioral impairments in individuals who developed them over time.METHODS: In this study, we performed untargeted metabolic and proteomic analysis in plasma samples derived from 30 subjects including 16 participants with 22q11.2DS and 14 healthy controls (TD) enrolled in a longitudinal study, aiming to identify a metabolic and protein signature informing about the underlying mechanisms involved in disease development and progression. The metabolic and proteomic profiles were also compared between the participants with 22q11.2DS with and without various comorbidities, such as medical involvement, psychiatric conditions, and autism spectrum disorder (ASD) to detect potential changes among multiple specimens, collected overtime, with the aim to understand the basic underlying mechanisms involved in disease development and progression.RESULTS: We observed a large number of statistically significant differences in metabolites between the two groups. Among them, the levels of taurine and arachidonic acid were significantly lower in 22q11.2DS compared to the TD group. In addition, we identified 16 proteins that showed significant changes in expression levels (adjusted P < 0.05) in 22q11.2DS as compared to TD, including those involved in 70 pathways such as gene expression, the PI3K-Akt signaling pathway and the complement system. Within participants with 22q11.2DS, no significant changes in those with and without medical or psychiatric conditions were observed.CONCLUSION: To our knowledge, this is the first report on plasma metabolic and proteomic profiling and on the identification of unique biomarkers in 22q11.2DS. These findings may suggest the potential role of the identified metabolites and proteins as biomarkers for the onset of comorbid conditions in 22q11.2DS. Ultimately, the altered protein pathways in 22q11.2DS may provide insights of the biological mechanisms underlying the neurodevelopmental phenotype and may provide missing molecular outcome measures in future clinical trials to assess early-diagnosis treatment and the efficacy of response to targeted treatment.PMID:38418685 | DOI:10.1007/s11306-024-02088-0

Sci Rep. 2024 Feb 28;14(1):4933. doi: 10.1038/s41598-024-55541-4.ABSTRACTRed flesh apple (Malus pumila var. medzwetzkyana Dieck), purple leaf plum (Prunus cerasifera Ehrhar f), and purple leaf peach (Prunus persica 'Atropurpurea') are significant ornamental plants within the Rosaceae family. The coloration of their fruits and leaves is crucial in their appearance and nutritional quality. However, qualitative and quantitative studies on flavonoids in the succulent fruits and leaves of multicolored Rosaceae plants are lacking. To unveil the diversity and variety-specificity of flavonoids in these three varieties, we conducted a comparative analysis of flavonoid metabolic components using ultra-high-performance liquid phase mass spectrometry (UPLC-MS/MS). The results revealed the detection of 311 metabolites, including 47 flavonoids, 105 flavonols, 16 chalcones, 37 dihydroflavonoids, 8 dihydroflavonols, 30 anthocyanins, 14 flavonoid carbon glycosides, 23 flavanols, 8 isoflavones, 11 tannins, and 12 proanthocyanidins. Notably, although the purple plum and peach leaves exhibited distinct anthocyanin compounds, paeoniflorin and corythrin glycosides were common but displayed varying glycosylation levels. While the green purple leaf peach fruit (PEF) and red flesh apple leaf (AL) possessed the lowest anthocyanin content, they exhibited the highest total flavonoid content. Conversely, the red flesh apple fruit (AF) displayed the highest anthocyanin content and a diverse range of anthocyanin glycosylation modifications, indicating that anthocyanins predominantly influenced the fruit's color. Purple PLF, PLL, and PEL showcased varying concentrations of anthocyanins, suggesting that their colors result from the co-color interaction between specific types of anthocyanins and secondary metabolites, such as flavonols, flavonoids, and dihydroflavonoids. This study provides novel insights into the variations in tissue metabolites among Rosaceae plants with distinct fruit and leaf colors.PMID:38418625 | DOI:10.1038/s41598-024-55541-4

Nat Commun. 2024 Feb 28;15(1):1227. doi: 10.1038/s41467-024-45099-0.ABSTRACTExploring the molecular basis of disease severity in rare disease scenarios is a challenging task provided the limitations on data availability. Causative genes have been described for Congenital Myasthenic Syndromes (CMS), a group of diverse minority neuromuscular junction (NMJ) disorders; yet a molecular explanation for the phenotypic severity differences remains unclear. Here, we present a workflow to explore the functional relationships between CMS causal genes and altered genes from each patient, based on multilayer network community detection analysis of complementary biomedical information provided by relevant data sources, namely protein-protein interactions, pathways and metabolomics. Our results show that CMS severity can be ascribed to the personalized impairment of extracellular matrix components and postsynaptic modulators of acetylcholine receptor (AChR) clustering. This work showcases how coupling multilayer network analysis with personalized -omics information provides molecular explanations to the varying severity of rare diseases; paving the way for sorting out similar cases in other rare diseases.PMID:38418480 | DOI:10.1038/s41467-024-45099-0

Nat Commun. 2024 Feb 28;15(1):1845. doi: 10.1038/s41467-024-46019-y.ABSTRACTSleep-disordered breathing (SDB) is a prevalent disorder characterized by recurrent episodic upper airway obstruction. Using data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we apply principal component analysis (PCA) to seven SDB-related measures. We estimate the associations of the top two SDB PCs with serum levels of 617 metabolites, in both single-metabolite analysis, and a joint penalized regression analysis. The discovery analysis includes 3299 individuals, with validation in a separate dataset of 1522 individuals. Five metabolite associations with SDB PCs are discovered and replicated. SDB PC1, characterized by frequent respiratory events common in older and male adults, is associated with pregnanolone and progesterone-related sulfated metabolites. SDB PC2, characterized by short respiratory event length and self-reported restless sleep, enriched in young adults, is associated with sphingomyelins. Metabolite risk scores (MRSs), representing metabolite signatures associated with the two SDB PCs, are associated with 6-year incident hypertension and diabetes. These MRSs have the potential to serve as biomarkers for SDB, guiding risk stratification and treatment decisions.PMID:38418471 | DOI:10.1038/s41467-024-46019-y

Funct Plant Biol. 2024 Feb 29. doi: 10.1071/FP23193. Online ahead of print.ABSTRACTBlack-grass (Alopecurus myosuroides) is one of the most problematic agricultural weeds of Western Europe, causing significant yield losses in winter wheat (Triticum aestivum) and other crops through competition for space and resources. Previous studies link black-grass patches to water-retaining soils, yet its specific adaptations to these conditions remain unclear. We designed pot-based waterlogging experiments to compare 13 biotypes of black-grass and six cultivars of wheat. These showed that wheat roots induced aerenchyma when waterlogged whereas aerenchyma-like structures were constitutively present in black-grass. Aerial biomass of waterlogged wheat was smaller, whereas waterlogged black-grass was similar or larger. Variability in waterlogging responses within and between these species was correlated with transcriptomic and metabolomic changes in leaves of control or waterlogged plants. In wheat, transcripts associated with regulation and utilisation of phosphate compounds were upregulated and sugars and amino acids concentrations were increased. Black-grass biotypes showed limited molecular responses to waterlogging. Some black-grass amino acids were decreased and one transcript commonly upregulated was previously identified in screens for genes underpinning metabolism-based resistance to herbicides. Our findings provide insights into the different waterlogging tolerances of these species and may help to explain the previously observed patchiness of this weed's distribution in wheat fields.PMID:38417910 | DOI:10.1071/FP23193

Org Lett. 2024 Feb 28. doi: 10.1021/acs.orglett.3c04366. Online ahead of print.ABSTRACTCytochrome-P450-mediated cross-linking of ribosomally encoded peptides (RiPPs) is rapidly expanding and displays great potential for biocatalysis. Here, we demonstrate that active site engineering of the biarylitide cross-linking enzyme P450Blt enables the formation of His-X-Tyr and Tyr-X-Tyr cross-linked peptides, thus showing how such P450s can be further exploited to produce alternate cyclic tripeptides with controlled cross-linking states.PMID:38417822 | DOI:10.1021/acs.orglett.3c04366

Am J Pathol. 2024 Feb 26:S0002-9440(24)00074-9. doi: 10.1016/j.ajpath.2024.02.005. Online ahead of print.ABSTRACTGenetic polymorphisms that impair VLDL secretion are linked to hepatic steatosis, fibrosis and hepatocellular cancer (HCC). Liver-specific deletion of microsomal triglyceride transfer protein (Mttp-LKO) impairs VLDL assembly, promoting hepatic steatosis and fibrosis, which are attenuated in Mttp-LKO X Fabp1 null (Fabp1/Mttp DKO) mice. Here we examine the impact of impaired VLDL secretion in Mttp-LKO mice on HCC incidence and progression in comparison to Fabp1/Mttp DKO mice. DEN treated Mttp-LKO mice exhibited steatosis with increased tumor burden compared to flox controls, while diethylnitrosamine (DEN)- treated Fabp1/Mttp DKO mice exhibited a paradoxical increase in tumor burden and >50% mortality by 50 weeks. Serum HDL cholesterol was elevated in both Mttp-LKO and Fabp1/Mttp DKO mice, with increased intratumoral expression of apoA1 and apoE. Lipidomic surveys revealed progressive enrichment in distinct triglyceride species in livers from Mttp-LKO mice with further enrichment in Fabp1/Mttp DKO mice. RNAseq revealed mRNA changes suggesting altered monocarboxylic acid utilization and increased aerobic glycolysis, while hepatocytes from Fabp1/Mttp DKO mice exhibited increased capacity to utilize glucose and glutamine. These metabolic shifts were accompanied by reduced expression of HNF1a, which correlated with tumor burden. Taken together, these findings demonstrate that hepatic tumorigenesis is increased in mice with impaired VLDL secretion and further accelerated via pathways including altered fatty acid compartmentalization and shifts in hepatic energy utilization.PMID:38417694 | DOI:10.1016/j.ajpath.2024.02.005

Sci Total Environ. 2024 Feb 26:171278. doi: 10.1016/j.scitotenv.2024.171278. Online ahead of print.ABSTRACTBio-organic fertilizer (BOF) was effective to promote the phytoremediation efficiency of heavy metal(loid)s-contaminated saline soil (HCSS) by improving rhizosphere soil properties, especially microbiome. However, there existed unclear impacts of BOF on plant metabolome and plant-driven manipulation on rhizosphere soil microbiota in HCSS, which were pivotal contributors to stress defense of plants trapped in adverse conditions. Here, a pot experiment was conducted to explore the mechanisms of BOF in improving alfalfa (Medicago sativa)-performing phytoremediation of HCSS. BOF application significantly increased the biomass (150.87-401.58 %) to support the augments of accumulation regarding heavy metal(loid)s (87.50 %-410.54 %) and salts (38.27 %-271.04 %) in alfalfa. BOF promoted nutrients and aggregates stability but declined pH of rhizosphere soil, accompanied by the boosts of rhizomicrobiota including increased activity, reshaped community structure, enriched plant growth promoting rhizobacteria (Blastococcus, Modestobacter, Actinophytocola, Bacillus, and Streptomyces), strengthened mycorrhizal symbiosis (Leohumicola, Funneliformis, and unclassified_f_Ceratobasidiaceae), optimized co-occurrence networks, and beneficial shift of keystones. The conjoint analysis of plant metabolome and physiological indices confirmed that BOF reprogrammed the metabolic processes (synthesis, catabolism, and long-distance transport of amino acid, lipid, carbohydrate, phytohormone, stress-resistant secondary metabolites, etc) and physiological functions (energy supply, photosynthesis, plant immunity, nutrients assimilation, etc) that are associated intimately. The consortium of root metabolome, soil metabolome, and soil microbiome revealed that BOF facilitated the exudation of metabolites correlated with rhizomicrobiota (structure, biomarker, and keystone) and rhizosphere oxidative status, e.g., fatty acyls, phenols, coumarins, phenylpropanoids, highlighting the plant-driven regulation on rhizosphere soil microbes and environment. By compiling various results and omics data, it was concluded that BOF favored the adaptation and phytoremediation efficiency of alfalfa by mediating the plant-soil-rhizomicrobiota interactions. The results would deepen understanding of the mechanisms by which BOF improved phytoremediation of HCSS, and provide theoretical guidance to soil amelioration and BOF application.PMID:38417528 | DOI:10.1016/j.scitotenv.2024.171278

Cancer Sci. 2024 Feb 28. doi: 10.1111/cas.16112. Online ahead of print.ABSTRACTIdentifying novel biomarkers for early detection of lung cancer is crucial. Non-invasively available saliva is an ideal biofluid for biomarker exploration; however, the rationale underlying biomarker detection from organs distal to the oral cavity in saliva requires clarification. Therefore, we analyzed metabolomic profiles of cancer tissues compared with those of adjacent non-cancerous tissues, as well as plasma and saliva samples collected from patients with lung cancer (n = 109 pairs). Additionally, we analyzed plasma and saliva samples collected from control participants (n = 83 and 71, respectively). Capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry were performed to comprehensively quantify hydrophilic metabolites. Paired tissues were compared, revealing 53 significantly different metabolites. Plasma and saliva showed 44 and 40 significantly different metabolites, respectively, between patients and controls. Of these, 12 metabolites exhibited significant differences in all three comparisons and primarily belonged to the polyamine and amino acid pathways; N1 -acetylspermidine exhibited the highest discrimination ability. A combination of 12 salivary metabolites was evaluated using a machine learning method to differentiate patients with lung cancer from controls. Salivary data were randomly split into training and validation datasets. Areas under the receiver operating characteristic curve were 0.744 for cross-validation using training data and 0.792 for validation data. This model exhibited a higher discrimination ability for N1 -acetylspermidine than that for other metabolites. The probability of lung cancer calculated using this model was independent of most patient characteristics. These results suggest that consistently different salivary biomarkers in both plasma and lung tissues might facilitate non-invasive lung cancer screening.PMID:38417449 | DOI:10.1111/cas.16112

Poult Sci. 2024 Feb 15;103(4):103555. doi: 10.1016/j.psj.2024.103555. Online ahead of print.ABSTRACTAt the onset of sexual maturity, the increasing circulating estrogen stimulates the formation of medullary bone, which provides available calcium for eggshell formation. The bone loss of laying hens is caused by the continuous dynamic changes of structure bone leading to bone fragility and susceptibility. The degree of medullary bone mineralization in sexual maturity is positively correlated with bone quality in the late laying stage. This study aimed to explore the molecular regulation mechanism of bone metabolism pre- and postsexual maturity in hens based on the joint analysis of transcriptome and metabolome. A total of 50 Hy-line Sonia pullets with comparable body weight at 13 wk were selected. Eight pullets were killed at 15 wk (juvenile hens, JH) and 19 wk (laying hens, LH), and LHs were killed within 3 h after oviposition. Differentially expressed genes and metabolites in tibia were analyzed based on transcriptome and metabolome, and then combined to construct the relevant metabolisms and hub genes. In the LH hens, plasma levels of estrogen and tartrate-resistant acid phosphatase were significantly elevated by 1.7 and 1.3 times. In addition, the midpoint diameter, bone mineral density and bone mineral content of the tibia and femur were higher at 19 wk of age. A total of 580 differentially expressed genes were found between the JH and LH group in the tibia, including 280 up-regulated, and 300 down-regulated genes in the LH group. Gene set enrichment analysis (GSEA) showed that the intracellular biosynthesis and secretion of matrix vesicles were significantly enrichment in the LH hens. A total of 21 differential metabolites were identified between JH and LH group. Estradiol valerate positively correlated with L-theanine, tryptophan betaine, dopamine, and perindopril. Joint analysis showed that the top 20 hub genes were enriched in cholesterol biosynthesis and phospholipid metabolism, which played a key regulatory role in bone metabolism during pre- and postsexual maturity. These results provide a theoretical foundation for maintaining efficient egg production and reducing bone health problems in laying hens.PMID:38417334 | DOI:10.1016/j.psj.2024.103555

Poult Sci. 2024 Feb 15;103(4):103530. doi: 10.1016/j.psj.2024.103530. Online ahead of print.ABSTRACTIn order to explore the difference and its underlying mechanism between young and older ducks, 60-day-old (D60) and 300-day-old (D300) of young ducks and 900-day-old ducks (D900) of older ducks were selected and studied. HE staining indicated that breast muscle fibers in the D900 group were more inseparable than D60 and D300 groups and the greater redness were showed in D300 and D900 groups. Quantitative proteomic analyses were conducted to further identify differences between young and older ducks that 61 proteins overlapped in the comparative analysis of the D900 vs. D60 and D900 vs. D300 groups. Furthermore, metabolomics analysis from the D900 group showed marked differences from the results of the D60 and D300 groups in 31 unique metabolites. In particular, lower guanosine, hypoxanthine, guanine, and doxefazepam levels indicated the increased nutritional value of older ducks. Integrated proteomics and metabolomics analysis showed that purine metabolism was specifically enriched, indicating that NME3, RRM2B, AMPD1, and AMPD3 might mainly affect meat from older ducks. In conclusion, our results indicated that meat from 900-day-old ducks possessed a unique biochemical signature that could provide candidate biomarkers to distinguish young ducks from older ducks.PMID:38417328 | DOI:10.1016/j.psj.2024.103530

J Pharm Biomed Anal. 2024 Feb 22;242:116067. doi: 10.1016/j.jpba.2024.116067. Online ahead of print.ABSTRACTRadix Astragali (Huangqi in Chinese, HQ) is a commonly used Chinese herbal medicine for thousands of years. In this study, A classic prescription Huangqi Jianzhong tang (HQJZ) was selected to evaluate the important effect of HQ on rats with chronic atrophic gastritis (CAG) from the perspective of intestinal flora in cecal contents samples. Traditional pharmacological indicators, including weight change, pathological examination and biochemical indicators showed that HQ exerted favorable contribution to HQJZ against CAG, where the efficiencies of HQ and HQJZ were better than HY (HQJZ prepared without HQ). An accurate strategy was adopted to screen out the differential metabolites in the metabolomis analysis of intestinal flora in cecal contents samples based on the optimal screening factors, including VIP (importance of variables in projection), FC (fold change), AUROC (area under the receiver operating characteristic curve) and -ln(p-value), which were evaluated based on their interpreting, grouping, and predicting abilities of the performed orthogonal partial least-squares-discriminate analysis (OPLS-DA) models. Ten altered differential metabolites were obtained and associated with the intestinal flora, which HQ exerted the important metabolic contributions to HQJZ. The efficacy on the diversity of intestinal flora and their correlations with the altered metabolites further showed the important role of HQ in HQJZ composition. This work provided valuable approach for looking for potential biomarkers associated with metabolomics research with more accuracy, and provided new insights into the mechanisms to explain the efficacy of HQ contributing to HQJZ formula.PMID:38417324 | DOI:10.1016/j.jpba.2024.116067

Curr Opin Chem Biol. 2024 Feb 27;79:102438. doi: 10.1016/j.cbpa.2024.102438. Online ahead of print.ABSTRACTChemogenetic approaches have been developed to define the mechanisms whereby the intracellular oxidant hydrogen peroxide (H2O2) modulates both physiological and pathological responses. Recombinant yeast D-amino acid oxidase (DAAO) can be exploited to modulate H₂O₂ in target cells and tissues. In vitro studies using cultured cells expressing recombinant DAAO have provided critical new information on the intracellular transport and metabolism of H2O2 with great temporal and spatial resolution. In contrast, in vivo studies using chemogenetic/transgenic animal models have explored the pathological effects of chronically elevated H2O2 in tissues. Coupled with transcriptomic, proteomic, and metabolomic methods, in vivo chemogenetic approaches are providing new insights into the adaptations to oxidative stress. This review of chemogenetic applications focuses on new models of heart failure and neurodegeneration that leverage in vivo chemogenetic modulation of oxidative stress in target tissues to identify new therapeutic targets.PMID:38417321 | DOI:10.1016/j.cbpa.2024.102438