PubMed

J Sci Food Agric. 2023 Nov 28. doi: 10.1002/jsfa.13177. Online ahead of print.ABSTRACTBACKGROUND: Pile-fermentation is one of the key steps in developing the Liupao tea (LBT) quality and unique characteristics-the complex biochemical profile of Liupao tea results from microorganisms present during the pile fermentation process. However, the critical underlying microorganisms and the marker compounds still need to be determined.RESULTS: Staphylococcus, Brevibacterium, Kocuria, Aspergillus, and Blastobotrys were the common dominant microorganisms at the end of the pile-fermentation of Liupao tea. Staphylococcus, Aspergillus, Blastobotrys, and nine other genera carried by raw tea are the core microorganisms in the LBT during pile-fermentation. A total of 29 critical compounds contributed to the metabolic changes caused by the processing of Liupao tea, and gallic acid, adenine, hypoxanthine, uridine, betaine, 3,4-dihydroxybenzaldehyde, α-Linolenic acid could be characterized as potential marker compounds. Correlation analysis showed that the core microorganisms, including Sphingomonas, Staphylococcus, Kocuria, Aureobasidium, Blastobotrys, Debaryomyce, and Trichomonascus, were closely related to major chemical components and differential compounds. Besides, Staphylococcus, Kocuria, Blastobotrys, and Trichomonascus, mutually promoting, were correlated with the enrichment of marker compounds. Integrated molecular networking and metabolic pathways revealed relevant compounds and enzymes that possibly affect the enrichment of marker compounds.CONCLUSION: This study analyzed the LBT fermentation samples by omics analysis to reveal the stable microbial community structure, critical microorganisms, and markers compounds affecting the quality of Liupao tea, which contributes to a better understanding of pile-fermentation of Liupao tea and the fermentation theory of dark tea. This article is protected by copyright. All rights reserved.PMID:38017631 | DOI:10.1002/jsfa.13177

Biotechnol Biofuels Bioprod. 2023 Nov 28;16(1):184. doi: 10.1186/s13068-023-02431-y.ABSTRACTBACKGROUND: Ensiling technology holds promise for preserving and providing high-quality forage. However, the preservation of rice straw poses challenges due to its high lignocellulosic content and low water-soluble carbohydrate levels. Developing highly effective lactic acid bacteria (LAB) for rice straw silage remains a priority.RESULTS: This study evaluated the impact of three LAB strains, Lactobacillus brevis R33 (Lac33), L. buchneri R17 (Lac17), and Leuconostoc pseudomesenteroides (Leu), on the fermentation quality of rice straw silage. Rice straw silage inoculated with Lac33 alone or in combination with other strains exhibited significantly lower neutral detergent fiber (NDF) (66.5% vs. 72.3%) and acid detergent fiber (ADF) (42.1% vs. 47%) contents, along with higher lactic acid (19.4 g/kg vs. not detected) and propionic acid (2.09 g/kg vs. 1.54 g/kg) contents compared to control silage. Bacterial community analysis revealed Lactobacillus dominance (> 80%) and suppression of unwanted Enterobacter and Clostridium. Metabolomic analysis highlighted increased carbohydrates and essential amino acids, indicating improved nutrient values in Lac33-inoculated rice straw silage and a potential explanation for Lac33 dominance.CONCLUSIONS: This research identified a highly efficient LAB candidate for rice straw silage, advancing our comprehension of fermentation from integrated microbiology and metabolomic perspectives.PMID:38017535 | DOI:10.1186/s13068-023-02431-y

BMC Med. 2023 Nov 28;21(1):469. doi: 10.1186/s12916-023-03185-y.ABSTRACTBACKGROUND: Emerging metabolomics-based studies suggested links between amino acid metabolism and metabolic dysfunction-associated fatty liver disease (MAFLD) risk; however, whether there exists an aetiological role of amino acid metabolism in MAFLD development remains unknown. The aim of the present study was to assess the causal relationship between circulating levels of amino acids and MAFLD risk.METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using summary-level data from genome-wide association studies (GWAS) to evaluate the causal relationship between genetically predicted circulating levels of amino acids and the risk of MAFLD. In the discovery MR analysis, we used data from the largest MAFLD GWAS (8434 cases and 770,180 controls), while in the replication MR analysis, we used data from a GWAS on MAFLD (1483 cases and 17,781 controls) where MAFLD cases were diagnosed using liver biopsy. We used Wald ratios or inverse variance-weighted (IVW) methods in the MR main analysis and weighted median and MR-Egger regression analyses in sensitivity analyses. Furthermore, we performed a conservative MR analysis by restricting genetic instruments to those directly involved in amino acid metabolism pathways.RESULTS: We found that genetically predicted higher alanine (OR = 1.43, 95% CI 1.13-1.81) and lower glutamine (OR = 0.83, 95% CI 0.73-0.96) levels were associated with a higher risk of developing MAFLD based on the results from the MR main and conservative analysis. The results from MR sensitivity analyses and complementary analysis using liver proton density fat fraction as a continuous outcome proxying for MAFLD supported the main findings.CONCLUSIONS: Novel causal metabolites related to MAFLD development were uncovered through MR analysis, suggesting future potential for evaluating these metabolites as targets for MAFLD prevention or treatment.PMID:38017422 | DOI:10.1186/s12916-023-03185-y

BMC Genomics. 2023 Nov 28;24(1):720. doi: 10.1186/s12864-023-09825-0.ABSTRACTBACKGROUND: Numerous factors influence the growth and development of cashmere. Existing research on cashmere has predominantly emphasized a single omics level. Integrating multi-omics analyses can offer a more comprehensive understanding by encompassing the entire spectrum. This study more accurately and comprehensively identified the key factors influencing cashmere fineness using multi-omics analysis.METHODS: This study used skin tissues of coarse cashmere type (CT_LCG) and fine cashmere type Liaoning cashmere goats (FT_LCG) for the analysis. This study employed an integrated approach involving transcriptomics, translatomics, proteomics, and metabolomics to identify substances associated with cashmere fineness. The findings were validated using parallel reaction monitoring (PRM) and multiple reaction monitoring (MRM) techniques.RESULTS: The GO functional enrichment analysis identified three common terms: multicellular organismal process, immune system process, and extracellular region. Furthermore, the KEGG enrichment analysis uncovered the involvement of the arachidonic acid metabolic pathway. Protein expression trends were verified using PRM technology. The expression trends of KRT79, as confirmed by PRM, were consistent with those observed in TMT proteomics and exhibited a positive regulatory effect on cashmere fineness. Metabolite expression trends were confirmed using MRM technology. The expression trends of 9 out of 15 validated metabolites were in agreement with those identified in the non-targeted metabolomics analysis.CONCLUSIONS: This study employed multi-omics analysis to identify key regulators of cashmere fineness, including PLA2G12A, KRT79, and prostaglandin B2. The findings of this study offer valuable data and establish a theoretical foundation for conducting comprehensive investigations into the molecular regulatory mechanisms and functional aspects of cashmere fineness.PMID:38017403 | DOI:10.1186/s12864-023-09825-0

Stem Cell Res Ther. 2023 Nov 27;14(1):339. doi: 10.1186/s13287-023-03557-4.ABSTRACTBACKGROUND: The secretome of mesenchymal stromal cells isolated from the amniotic membrane (hAMSCs) has been extensively studied for its in vitro immunomodulatory activity as well as for the treatment of several preclinical models of immune-related disorders. The bioactive molecules within the hAMSCs secretome are capable of modulating the immune response and thus contribute to stimulating regenerative processes. At present, only a few studies have attempted to define the composition of the secretome, and several approaches, including multi-omics, are underway in an attempt to precisely define its composition and possibly identify key factors responsible for the therapeutic effect.METHODS: In this study, we characterized the protein composition of the hAMSCs secretome by a filter-aided sample preparation (FASP) digestion and liquid chromatography-high resolution mass spectrometry (LC-MS) approach. Data were processed for gene ontology classification and functional protein interaction analysis by bioinformatics tools.RESULTS: Proteomic analysis of the hAMSCs secretome resulted in the identification of 1521 total proteins, including 662 unique elements. A number of 157 elements, corresponding to 23.7%, were found as repeatedly characterizing the hAMSCs secretome, and those that resulted as significantly over-represented were involved in immunomodulation, hemostasis, development and remodeling of the extracellular matrix molecular pathways.CONCLUSIONS: Overall, our characterization enriches the landscape of hAMSCs with new information that could enable a better understanding of the mechanisms of action underlying the therapeutic efficacy of the hAMSCs secretome while also providing a basis for its therapeutic translation.PMID:38012707 | PMC:PMC10683150 | DOI:10.1186/s13287-023-03557-4

Metabolomics. 2023 Nov 28;20(1):1. doi: 10.1007/s11306-023-02066-y.ABSTRACTAIMS: To identify metabolite and lipid biomarkers of diabetes in the Indian subpopulation in newly diagnosed diabetic and long-term diabetic individuals. To utilize the global polar metabolomic and lipidomic profiles to predict the susceptibility of an individual to diabetes using machine learning algorithms.MATERIALS AND METHODS: 87 individuals, including healthy, newly diabetic, and long-term diabetics on medication, were included in the study. Post consent, their serum was used to isolate polar metabolome and lipidome. NMR and LCMS were used to identify the polar metabolites and lipids, respectively. Statistical analysis was done to determine significantly altered molecules. NMR and LCMS comprehensive data were utilized to generate diabetic models using machine learning algorithms. 10 more individuals (pre-diabetic) were recruited, and their polar metabolomic and lipidomic profiles were generated. Pre-diabetic metabolic profiles were then utilized to predict the diabetic status of the metabolome and lipidome beyond glucose levels.RESULTS: Mannose, Betaine, Xanthine, Triglyceride (38:1), Sphingomyelin (d63:7), and Phosphatidic acid (37:2) are some of the top key biomarkers of diabetes. The predictive model generated showed the receiver operating characteristic area under the curve (ROC-AUC) as 1 on both test and validation data indicating excellent accuracy. This model then predicted the diabetic closeness of the metabolism of pre-diabetic individuals based on probability scores.CONCLUSION: Polar metabolic and lipid profile of diabetic individuals is very different from that of healthy individuals. Lipid profile alters before the polar metabolic profile in diabetes-susceptible individuals. Without regard to glucose, the diabetic closeness of the metabolism of any individual can be determined.PMID:38017183 | DOI:10.1007/s11306-023-02066-y

Sci Rep. 2023 Nov 28;13(1):20980. doi: 10.1038/s41598-023-47976-y.ABSTRACTStreptococcus agalactiae (S. agalactiae), group B Streptococcus (GBS), a major cause of infection in a wide variety of diseases, have been compared in different human and animal sources. We aimed to compare the bacterial proteome and metabolome profiles of human and animal S. agalactiae strains to delineate biological interactions relevant to infection. With the innovative advancement in mass spectrometry, a comparative result between both strains provided a solid impression of different responses to the host. For instance, stress-related proteins (Asp23/Gls24 family envelope stress response protein and heat shock protein 70), which play a role in the survival of GBS under extreme environmental conditions or during treatment, are highly expressed in human and animal strains. One human strain contains ꞵ-lactamase (serine hydrolase) and biofilm regulatory protein (lytR), which are important virulence regulators and potential targets for the design of novel antimicrobials. Another human strain contains the aminoglycosides-resistance bifunctional AAC/APH (A0A0U2QMQ5) protein, which confers resistance to almost all clinically used aminoglycosides. Fifteen different metabolites were annotated between the two groups. L-aspartic acid, ureidopropionic acid, adenosine monophosphate, L-tryptophan, and guanosine monophosphate were annotated at higher levels in human strains. Butyric acid, fumaric acid, isoleucine, leucine, and hippuric acid have been found in both human and animal strains. Certain metabolites were uniquely expressed in animal strains, with fold changes greater than 2. For example, putrescine modulates biofilm formation. Overall, this study provides biological insights into the substantial possible bacterial response reflected in its macromolecular production, either at the proteomic or metabolomic level.PMID:38017083 | DOI:10.1038/s41598-023-47976-y

Nat Commun. 2023 Nov 28;14(1):7793. doi: 10.1038/s41467-023-43514-6.ABSTRACTNicotinamide adenine dinucleotide (NAD) replenishment therapy using nicotinamide riboside (NR) shows promise for Parkinson's disease (PD) and other neurodegenerative disorders. However, the optimal dose of NR remains unknown, and doses exceeding 2000 mg daily have not been tested in humans. To evaluate the safety of high-dose NR therapy, we conducted a single-center, randomized, placebo-controlled, double-blind, phase I trial on 20 individuals with PD, randomized 1:1 on NR 1500 mg twice daily (n = 10) or placebo (n = 10) for four weeks. The trial was conducted at the Department of Neurology, Haukeland University Hospital, Bergen, Norway. The primary outcome was safety, defined as the frequency of moderate and severe adverse events. Secondary outcomes were tolerability defined as frequency of mild adverse events, change in the whole blood and urine NAD metabolome, and change in the clinical severity of PD, measured by MDS-UPDRS. All 20 participants completed the trial. The trial met all prespecified outcomes. NR therapy was well tolerated with no moderate or severe adverse events, and no significant difference in mild adverse events. NR therapy was associated with clinical improvement of total MDS-UPDRS scores. However, this change was also associated with a shorter interval since the last levodopa dose. NR greatly augmented the blood NAD metabolome with up to 5-fold increase in blood NAD+ levels. While NR-recipients exhibited a slight initial rise in serum homocysteine levels, the integrity of the methyl donor pool remained intact. Our results support extending the dose range of NR in phase II clinical trials to 3000 mg per day, with appropriate safety monitoring. Clinicaltrials.gov identifier: NCT05344404.PMID:38016950 | DOI:10.1038/s41467-023-43514-6

Environ Pollut. 2023 Nov 26:123040. doi: 10.1016/j.envpol.2023.123040. Online ahead of print.ABSTRACTCadmium (Cd) pollution is one of the most severe toxic metals pollution in grassland. Vicia unijuga (V. unijuga) A.Br. planted nearby the grassland farming are facing the risk of high Cd contamination. Here, we investigated the beneficial effects of a highly Cd tolerant rhizosphere bacterium, Cupriavidus sp. WS2, on Cd contaminated V. unijuga. Through plot experiments, we set up four groups of treatments: the control group (without WS2 or Cd), the Cd group (with only Cd addition), the WS2 group (with only WS2 addition), and the WS2/Cd group (with WS2 and Cd addition), and analyzed the changes in physiological indicators, rhizosphere microorganisms, and stem and leaf metabolites of V. unijuga. Results of physiological indicators indicated that Cupriavidus sp. WS2 had strong absorption and accumulation capacity of Cd, exogenous addition of strain WS2 remarkably decreased the Cd concentrations, and increased the plant heights, the biomass, the total protein concentrations, the chlorophyll contents and the photosynthetic rate in stems and leaves of V. unijuga under Cd stress. Cd treatment increased the abundance of Cd tolerant bacterial genera in rhizosphere microbiome, but these genera were down-regulated in the WS2/Cd group. Pseudotargeted metabolomic results showed that six common differential metabolites associated with antioxidant stress were increased after co-culture with WS2. In addition, WS2 activated the antioxidant system including glutathione (GSH) and catalase (CAT), reduced the contents of oxidative stress markers including malondialdehyde (MDA) and hydrogen peroxide (H2O2) in V. unijuga under Cd stress. Taken together, this study revealed that Cupriavidus sp.WS2 alleviated the toxicity of V. unijuga under Cd exposure by activating the antioxidant system, increasing the antioxidant metabolites, and reducing the oxidative stress markers.PMID:38016587 | DOI:10.1016/j.envpol.2023.123040

Life Sci. 2023 Nov 26:122302. doi: 10.1016/j.lfs.2023.122302. Online ahead of print.ABSTRACTAIMS: Deoxynivalenol (DON), namely vomitoxin, is one of the most prevalent fungal toxins in cereal crops worldwide. However, the underlying toxic mechanisms of DON remain largely unknown.MAIN METHODS: DON exposure-caused changes in the murine metabolome and gut microbiome were investigated by an LC-MS/MS-based nontargeted metabolomics approach and sequencing of 16S rRNA in fecal samples, respectively. Cellular models were then used to validate the findings from the metabolomics study.KEY FINDINGS: DON exposure increased intestinal barrier permeability evidenced by its-mediated decrease in colonic Claudin 5 and E-cadherin, as well as increases in colonic Ifn-γ, Cxcl9, Cxcl10, and Cxcr3. Furthermore, DON exposure resulted in a significant increase in murine plasma levels of deoxycholic acid (DCA). Also, DON exposure led to gut microbiota dysbiosis, which was associated with DON exposure-caused increase in plasma DCA. In addition, we found not only DON but also DCA dose-dependently caused a significant increase in the levels of IFN-γ, CXCL9, CXCL10, and/or CXCR3, as well as a significant decrease in the expression levels of Claudin 5 and/or E-cadherin in the human colonic epithelial cells (NCM460).SIGNIFICANCE: DON-mediated increase in DCA contributes to DON-caused intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.PMID:38016577 | DOI:10.1016/j.lfs.2023.122302

J Biol Chem. 2023 Nov 26:105502. doi: 10.1016/j.jbc.2023.105502. Online ahead of print.ABSTRACTFatty acid handling and complex lipid synthesis are altered in the kidney cortex of diabetic patients. We recently showed that inhibition of the renin-angiotensin system without changes in glycemia can reverse diabetic kidney disease (DKD) and restore the lipid metabolic network in the kidney cortex of diabetic (db/db) mice, raising the possibility that lipid remodeling may play a central role in DKD. However, the roles of specific enzymes involved in lipid remodeling in DKD have not been elucidated. In the present study, we used this diabetic mouse model and a proximal tubule epithelial cell line (HK2) to investigate the potential relationship between long-chain acyl-CoA synthetase 1 (ACSL1) and lipid metabolism in response to fatty acid exposure and inflammatory signals. We found ACSL1 expression was significantly increased in the kidney cortex of db/db mice, and exposure to palmitate (PA) or tumor necrosis factor (TNF-α) significantly increased Acsl1 mRNA expression in HK-2 cells. In addition, PA treatment significantly increased the levels of long-chain acylcarnitines and fatty acyl CoAs in HK2 cells, and these increases were abolished in HK2 cell lines with specific deletion of Acsl1(Acsl1KO cells), suggesting a key role for ACSL1 in fatty acid β-oxidation. In contrast, TNF-α treatment significantly increased the levels short-chain acylcarnitines and long-chain fatty acyl CoAs in HK2 cells but not in Acsl1KO cells, consistent with fatty acid channeling to complex lipids. Taken together, our data demonstrate a key role for ACSL1 in regulating lipid metabolism, fatty acid partitioning, and inflammation.PMID:38016515 | DOI:10.1016/j.jbc.2023.105502

Biochim Biophys Acta Mol Basis Dis. 2023 Nov 26:166972. doi: 10.1016/j.bbadis.2023.166972. Online ahead of print.ABSTRACTThe imbalance in gut microbiota triggers an inflammatory response that spreads from the gut to the discs and is associated with lumbar disc herniation (LDH). In this study, we investigated the mechanism of palmitic acid (PA) and trans-4-hydroxy-3-methoxycinnamic acid (THMC) on microbiota, metabolic homeostasis, and autophagy after LDH. The LDH rat model was established by puncturing the exposed intervertebral disc. 16S rDNA was used to assess the gut microbiome composition. The microbial metabolites were analyzed by UPLC-MS. The mechanism of PA and THMC in LDH was explored by fecal microbiota transplantation (FMT). We found that Yaobishu, PA, THMC, and the positive control drug Celebrex attenuated intervertebral disc damage in LDH rats and downregulated TRPV1, IL-1β, and IL-18 expression. In addition, Yaobishu reduced Oscillospirales and Ruminococcaceae abundances after LDH. PA increased Bacilli's abundance while decreasing Negativicutes and Ruminococcaceae abundances. Metabolomics showed that Yaobishu increased 2-hexanone, methyl isobutyl ketone, 2-methylpentan-3-one, and nonadecanoic acid levels but decreased pantetheine and urocanate levels. PA and THMC reduced uridine and urocanate levels. Yaobishu, PA, and THMC activated autophagy and the Wnt/β-catenin pathway in LDH rats. Moreover, antibiotics abrogated these effects. FMT-PA and FMT-THMC activated autophagy and decreased IL-1β, IL-18, Wnt1, β-catenin, and TRPV1 expression. FMT-PA and FMT-THMC partially reversed the effects of 3-MA. Taken together, our data suggest that Yaobishu, PA, and THMC relieve inflammation and pain by remodeling the gut microbiota and restoring metabolic homeostasis after LDH to activate autophagy and the Wnt/β-catenin pathway, which provide a new therapeutic target for LDH in the clinic.PMID:38016505 | DOI:10.1016/j.bbadis.2023.166972

Cell Stem Cell. 2023 Nov 21:S1934-5909(23)00393-4. doi: 10.1016/j.stem.2023.11.001. Online ahead of print.ABSTRACTWe report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis. Participants were treated with hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed. All participants displayed stability of clinical and laboratory outcomes, as well as lesion load and brain activity (MRI), compared with the study entry. Longitudinal metabolomics and lipidomics of biological fluids identified time- and dose-dependent responses with increased levels of acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of AEs and the stability of functional and structural outcomes are reassuring and represent a milestone for the safe translation of stem cells into regenerative medicines.PMID:38016468 | DOI:10.1016/j.stem.2023.11.001

Immunity. 2023 Nov 15:S1074-7613(23)00458-2. doi: 10.1016/j.immuni.2023.11.001. Online ahead of print.ABSTRACTExtensive studies demonstrate the importance of the STING1 (also known as STING) protein as a signaling hub that coordinates immune and autophagic responses to ectopic DNA in the cytoplasm. Here, we report a nuclear function of STING1 in driving the activation of the transcription factor aryl hydrocarbon receptor (AHR) to control gut microbiota composition and homeostasis. This function was independent of DNA sensing and autophagy and showed competitive inhibition with cytoplasmic cyclic guanosine monophosphate (GMP)-AMP synthase (CGAS)-STING1 signaling. Structurally, the cyclic dinucleotide binding domain of STING1 interacted with the AHR N-terminal domain. Proteomic analyses revealed that STING1-mediated transcriptional activation of AHR required additional nuclear partners, including positive and negative regulatory proteins. Although AHR ligands could rescue colitis pathology and dysbiosis in wild-type mice, this protection was abrogated by mutational inactivation of STING1. These findings establish a key framework for understanding the nuclear molecular crosstalk between the microbiota and the immune system.PMID:38016467 | DOI:10.1016/j.immuni.2023.11.001

Plant Physiol Biochem. 2023 Nov 24;206:108222. doi: 10.1016/j.plaphy.2023.108222. Online ahead of print.ABSTRACTHydrogen cyanide has been extensively used worldwide for bud dormancy break in fruit trees, consequently enhancing fruit production via expedited cultivation, especially in areas with controlled environments or warmer regions. A novel and safety nanotechnology was developed since the hazard of hydrogen cyanide for the operators and environments, there is an urgent need for the development of novel and safety approaches to replace it to break bud dormancy for fruit trees. In current study, we have systematically explored the potential of iron oxide nanoparticles, specifically α-Fe2O3, to modulate bud dormancy in sweet cherry (Prunus avium). The synthesized iron oxide nanoparticles underwent meticulous characterization and assessment using various techniques, including Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and ultraviolet-visible infrared (UV-Vis) spectroscopy. Remarkably, when applied at a concentration of 10 mg L-1 alongside gibberellin (GA4+7), these iron oxide nanoparticles exhibited a substantial 57% enhancement in bud dormancy release compared to control groups, all achieved within a remarkably short time span of 4 days. Our RNA-seq analyses further unveiled that 2757 genes within the sweet cherry buds were significantly up-regulated when treated with 10 mg L-1 α-Fe2O3 nanoparticles in combination with GA, while 4748 genes related to dormancy regulation were downregulated in comparison to the control. Moreover, we discovered an array of 58 transcription factor families among the crucial differentially expressed genes (DEGs). Through hormonal quantification, we established that the increased bud burst was accompanied by a reduced concentration of abscisic acid (ABA) at 761.3 ng/g fresh weight in the iron oxide treatment group, coupled with higher levels of gibberellins (GAs) in comparison to the control. Comprehensive transcriptomic and metabolomic analyses unveiled significant alterations in hormone contents and gene expression during the bud dormancy-breaking process when α-Fe2O3 nanoparticles were combined with GA. In conclusion, our findings provide valuable insights into the intricate molecular mechanisms underlying the impact of iron oxide nanoparticles on achieving uniform bud dormancy break in sweet cherry trees.PMID:38016371 | DOI:10.1016/j.plaphy.2023.108222

Plant Physiol Biochem. 2023 Nov 19;206:108183. doi: 10.1016/j.plaphy.2023.108183. Online ahead of print.ABSTRACTThis study investigated how cold storage affects the nutraceutical diversity and physiological quality of Torreya yunnanensis seeds, using a widely targeted UPLC-MS/MS-based metabolomics analysis. The 373 identified metabolites were divided into nine categories: lipids, phenolic acids, amino acids and derivatives, organic acids, nucleotides, saccharides, vitamins and alcohols. Among them, 49 metabolites showed significant changes after 3 months of cold storage, affecting 28 metabolic pathways. The content of amino acid-related metabolites significantly increased, while the content of sugar-related metabolites decreased during storage. Notably, the content of proline acid, shikimic acid, α-linolenic acid and branched-chain amino acids showed significant changes, indicating their potential role in seed storage. This study deepens our understanding of the nutraceutical diversity and physiological quality of T. yunnanensis seeds during storage, providing insight for conservation efforts and habitat restoration.PMID:38016368 | DOI:10.1016/j.plaphy.2023.108183

J Hazard Mater. 2023 Nov 23;465:133051. doi: 10.1016/j.jhazmat.2023.133051. Online ahead of print.ABSTRACTMicroplastics (MPs) can absorb environmental pollutants from the aquatic environment to cause mixed toxicity, which has received widespread attention. However, studies on the joint effects of MPs and insecticides are limited. As one of the most widely used pyrethroids, there was a large amount of residual cypermethrin (CYP) in water due to insufficient decomposition. Here, adult female zebrafish were exposed to MPs, CYP, and their mixtures for 21 days, respectively. After exposures, the MPs and CYP caused tissue damage to the liver. Hepatic triglyceride (TG) level increased significantly after MPs + CYP exposure, and the expression of genes about glycolipids metabolism was significantly altered. Furthermore, metabolome results suggested that MPs + CYP exposure resulted in increased content of some glycerophospholipid, affecting phospholipid metabolism-related pathways. In addition, through 16 s rDNA sequencing, it was found that MPs + CYP led to significant changes in the proportion of dominant phyla. Interestingly, Cetobacterium which increased in CYP and the co-exposure group was positively correlated with most lipid metabolites. Our results suggested that co-exposure to MPs and CYP enhanced the disturbances in hepatic phospholipid metabolism by affecting the gut microbial composition, while these changes were not observed in separate treatment groups. These results emphasized the importance of studying the joint toxicity of MPs and insecticides.PMID:38016319 | DOI:10.1016/j.jhazmat.2023.133051

J Proteome Res. 2023 Nov 28. doi: 10.1021/acs.jproteome.3c00473. Online ahead of print.ABSTRACTThe foundation for integrating mass spectrometry (MS)-based proteomics into systems medicine is the development of standardized start-to-finish and fit-for-purpose workflows for clinical specimens. An essential step in this pursuit is to highlight the common ground in a diverse landscape of different sample preparation techniques and liquid chromatography-mass spectrometry (LC-MS) setups. With the aim to benchmark and improve the current best practices among the proteomics MS laboratories of the CLINSPECT-M consortium, we performed two consecutive round-robin studies with full freedom to operate in terms of sample preparation and MS measurements. The six study partners were provided with two clinically relevant sample matrices: plasma and cerebrospinal fluid (CSF). In the first round, each laboratory applied their current best practice protocol for the respective matrix. Based on the achieved results and following a transparent exchange of all lab-specific protocols within the consortium, each laboratory could advance their methods before measuring the same samples in the second acquisition round. Both time points are compared with respect to identifications (IDs), data completeness, and precision, as well as reproducibility. As a result, the individual performances of participating study centers were improved in the second measurement, emphasizing the effect and importance of the expert-driven exchange of best practices for direct practical improvements.PMID:38015820 | DOI:10.1021/acs.jproteome.3c00473

Diabetes. 2023 Nov 28:db230694. doi: 10.2337/db23-0694. Online ahead of print.ABSTRACTOptimizing energy utilization in the kidney is critical for normal kidney function. Here, we investigate the effect of hyperglycemia and sodium-glucose cotransporter-2 (SGLT2) inhibition on urinary amino acid excretion in individuals with type 1 diabetes (T1D). The open-label ATIRMA trial assessed the impact of 8 weeks of oral empagliflozin 25 mg/day in 40 normotensive, normoalbuminuric young adults with T1D. A consecutive two-day assessment of clamped euglycemia and hyperglycemia was evaluated at baseline and post-treatment visit. Principal component analysis was performed on urinary amino acids grouped into representative metabolic pathways using MetaboAnalyst. At baseline, acute hyperglycemia was associated with changes in 25 of the 33 urinary amino acids or their metabolites. The most significant amino acid metabolites affected by acute hyperglycemia were 3-hydroxykynurenine, serotonin, glycyl-histidine, and nicotinic acid. The changes in amino acid metabolites were reflected by the induction of four biosynthetic pathways - aminoacyl-tRNA, valine, leucine and isoleucine, arginine, as well as phenylalanine, tyrosine, and tryptophan. Under acute hyperglycemia, empagliflozin significantly attenuated the increases to aminoacyl-tRNA biosynthesis and valine, leucine and isoleucine biosynthesis. Our findings using amino acid metabolomics indicate that hyperglycemia stimulates biosynthetic pathways in T1D. SGLT2 inhibition may attenuate the increase in biosynthetic pathways to optimize kidney energy metabolism.PMID:38015810 | DOI:10.2337/db23-0694

J Am Nutr Assoc. 2023 Nov 28:1-13. doi: 10.1080/27697061.2023.2284997. Online ahead of print.ABSTRACTThe field of nutrition research has traditionally focused on the effects of macronutrients and micronutrients on the body. However, it has become evident that individuals have unique genetic makeups that influence their response to food. Nutritional genomics, which includes nutrigenetics and nutrigenomics, explores the interaction between an individual's genetic makeup, diet, and health outcomes. Nutrigenetics studies the impact of genetic variation on an individual's response to dietary nutrients, while nutrigenomics investigates how dietary components affect gene regulation and expression. These disciplines seek to understand the impact of diet on the genome, transcriptome, proteome, and metabolome. It provides insights into the mechanisms underlying the effect of diet on gene expression. Nutrients can cause the modification of genetic expression through epigenetic changes, such as DNA methylation and histone modifications. The aim of nutrigenomics is to create personalized diets based on the unique metabolic profile of an individual, gut microbiome, and genetic makeup to prevent diseases and promote health. Nutrigenomics has the potential to revolutionize the field of nutrition by combining the practicality of personalized nutrition with knowledge of genetic factors underlying health and disease. Thus, nutrigenomics offers a promising approach to improving health outcomes (in terms of disease prevention) through personalized nutrition strategies based on an individual's genetic and metabolic characteristics.PMID:38015713 | DOI:10.1080/27697061.2023.2284997