PubMed

Physiol Plant. 2025 Jan-Feb;177(1):e70035. doi: 10.1111/ppl.70035.ABSTRACTPlants defend against chewing herbivores by up-regulating jasmonic acid (JA) signaling, which activates downstream signaling cascades and produces numerous secondary metabolites that act as defense molecules against the herbivores. Although secondary metabolism always remains a focus of research, primary metabolism is also reported to be realigned upon herbivory. However, JA signaling-mediated modulation of primary metabolites and their metabolic pathways in plants are mostly unexplored. Here, we applied gas chromatography-mass spectrometry-based untargeted metabolomics aided with computational statistical frameworks on wild type Arabidopsis, mutants of active JA receptor (i.e., CORONATINE-INSENSITIVE 1, COI1-1) and downstream transcription factor (i.e., MYC2) to navigate the JA signaling-mediated primary metabolism alterations during herbivory. Pathway and metabolite's chemical class enrichment analysis revealed JA signaling is crucial for constitutive as well as herbivore-induced primary metabolism and topology of their interaction networks. JA signaling majorly modulated alterations of sugars, amino acids and related metabolites. Herbivory-mediated sugar depletion and induction of methionine for aliphatic glucosinolates are also dependent on JA signaling. Taken together, our results demonstrate trails of JA signaling-mediated primary metabolic alterations associated with herbivory.PMID:39775752 | DOI:10.1111/ppl.70035

New Phytol. 2025 Jan 8. doi: 10.1111/nph.20322. Online ahead of print.ABSTRACTFuranocoumarins (FCs) are plant defence compounds derived from the phenylpropanoid pathway via the coumarin umbelliferone that harbour some therapeutic benefits yet are the underlying cause of 'grapefruit-drug interactions' in humans. Most of the pathway genes have not been identified in citrus. We employed a genetic/Omics approach on citrus ancestral species and F1 populations of mandarin × grapefruit and mandarin × pummelo. Enzyme specificity was characterized by In vivo 2-oxoglutarate-dependent dioxygenase family (2OGD) activity assays. We identified a 2OGD multi-gene cluster involved in coumarin/FC/pyranocoumarin biosynthesis; Species lacking FCs in leaves/fruit were homozygous for a 655-base solo-LTR frame-disrupting insertion within one dual specificity C2'H/F6'H encoding 2OGD gene, demonstrating that integrity of this gene is fully correlated with the capacity to biosynthesize metabolites of the extended FC pathway in leaves/fruit. A second 2OGD is the prominent gene expressed in citrus roots, which contain a unique pattern of extended FC pathway metabolites, including the predominant pyranocoumarins. A third 2OGD gene encodes a single activity F6'H, which appears to be induced at the transcript level by citrus pathogens. The results provide insights into the genetic basis underlying the difference between citrus fruit FC producers (grapefruit and pummelo) and nonproducers (mandarin and orange) and provide a gene target to breed for FC-free varieties by marker-assisted breeding or genome editing.PMID:39775733 | DOI:10.1111/nph.20322

Invest Ophthalmol Vis Sci. 2025 Jan 2;66(1):10. doi: 10.1167/iovs.66.1.10.ABSTRACTPURPOSE: To investigate the aqueous proteomics and metabolomics in low-energy and high-energy femtosecond laser-assisted cataract surgery (FLACS).METHODS: In this prospective observational study, 72 patients were randomized to 3 groups: low-energy FLACS, high-energy FLACS, and conventional phacoemulsification (controls). Aqueous was collected after femtosecond laser treatment or at the beginning of surgery (controls). Proteomic analysis was conducted using a data-independent acquisition method, whereas aqueous metabolomics were analyzed with liquid chromatography-tandem mass spectrometry. Bioinformatics analyses were performed to integrate the results of proteomics and metabolomics.RESULTS: Compared with low-energy FLACS, significantly elevated aqueous hemoglobin subunit beta, G protein subunit beta, carbonic anhydrase 1, and asymmetric dimethylarginine were observed in high-energy FLACS, suggesting significantly greater oxidative stress, inflammation, immunity, metabolism, and mitochondrial fatty acids oxidation. Compared with controls, significantly increased aqueous proteins and metabolites related to immune and inflammation (beta-crystallin B1, hemoglobin subunit beta, putrescine, and spermine) and oxidative stress (heat shock proteins, peroxiredoxins, and long-chain acylcarnitines) were observed in FLACS. Joint pathway analysis revealed nicotinate/nicotinamide metabolism and riboflavin metabolism were significantly overexpressed in high-energy FLACS compared with low-energy FLACS, whereas the pentose phosphate pathway and glycolysis were the most significant pathways when comparing FLACS with controls.CONCLUSIONS: FLACS induced higher immunological and inflammatory responses, oxidative stress reactions, and mitochondrial fatty acid oxidative stress compared with controls. These differential effects were more pronounced when a higher laser energy was used.PMID:39775700 | DOI:10.1167/iovs.66.1.10

Invest Ophthalmol Vis Sci. 2025 Jan 2;66(1):11. doi: 10.1167/iovs.66.1.11.ABSTRACTPURPOSE: Eyelid infiltrative basal cell carcinoma (iBCC) is the most common malignant tumor affecting the ocular adnexa, but studies on metabolic changes within its microenvironment and heterogeneity at the tumor invasive area are limited. This study aims to analyze metabolic differences among iBCC cell types using single-cell and spatial metabolomics analysis and to examine metabolic environment at the tumor invasive area.METHODS: Single-cell transcriptomic data of human basal cell carcinoma (BCC) were clustered and visualized using Uniform Manifold Approximation and Projection. Metabolic reprogramming was analyzed with single-cell flux estimation analysis. Spatial metabolomics data were obtained with the Timstof Flex MALDI 2 system, and Bruker software was used for region selection.RESULTS: Eight cell types were identified within the iBCC microenvironment. Differences between inflammatory cancer-associated fibroblasts and myofibroblastic cancer-associated fibroblasts were analyzed. Metabolic flux analysis showed increased glycolysis, glutamine, heme, and glutathione fluxes in the iBCC microenvironment. Spatial metabolomics revealed high levels of taurine, deoxy-GMP, O-phosphoethanolamine, and pyrithione. Both tumor and invasive regions had significant upregulation of fatty acid pathways, with marked increases in oleic and arachidonic acids at the invasive area. Specific upregulation of UDP-glucuronic acid and high UDP-glucose 6-dehydrogenase (UGDH) expression in the tumor region suggest UXS1 as a potential therapeutic target for iBCC.CONCLUSIONS: This study establishes a metabolic microenvironment atlas of iBCC, revealing significant metabolic differences and the dominance of lipid and lysosome metabolism. Potential metabolic markers and characteristic substances in the invasive area offer new insights for immunotherapy and the exploration of BCC's metabolic mechanisms.PMID:39775699 | DOI:10.1167/iovs.66.1.11

Biol Reprod. 2025 Jan 7:ioaf002. doi: 10.1093/biolre/ioaf002. Online ahead of print.ABSTRACTThe bovine conceptus elongates near Day 16 of development and releases interferon-tau (IFNT), disrupting the endometrial luteolytic mechanism to sustain luteal P4 and pregnancy. Conceptus factors other than IFNT modify local endometrial activities to support pregnancy; however, the microenvironment is largely uncharacterized. We utilized a bovine conceptus-endometrial culture system to elucidate the microenvironment in the form of RNA and protein. Estrus synchronized heifers remained cyclic (13) or were inseminated (9) to produce Day 16 cyclic endometrium and elongating conceptuses, respectively. Conceptus sections and endometrium were then used to generate tissue cultures in 1 mL of medium: (1) no tissue (Control Med; n = 7), (2) mono-cultured conceptus (Conceptus; n = 9, 3) mono-cultured endometrium (Endo; n = 13), or (4) Endo-Conceptus Co-culture (n = 15). After 12 h, tissue RNA was sequenced (RNA-Seq) and media underwent proteomic analysis (LC-MS/MS). Compared to Conceptus and Endo, co-cultured conceptus and endometrial tissue contained 3400 and 4575 differentially expressed genes (DEG), respectively (P ≤ 0.01). More abundantly expressed endometrial DEG were associated with interferon signaling whereas more abundantly expressed conceptus DEG were associated with protein homeostasis and metabolism (FDR < 0.001). When Co-culture media where compared to Endo media, 288 more abundant protiens were identified (P < 0.05). Biological processes related to these proteins included antigen presentation via MHC Class Ib and keratinization (FDR < 0.001). Within the mono-cultured conceptus and endometrial media, folate receptor alpha (FOLR1) (P < 0.001) was identified as the most abundant secreted protein suggesting the reproductive tissues elicit a microenvironment supportive of conceptus growth involving folate metabolism.PMID:39775669 | DOI:10.1093/biolre/ioaf002

Sci Rep. 2025 Jan 7;15(1):1076. doi: 10.1038/s41598-025-85416-1.ABSTRACTIn arid and semi-arid climates, native plants have developed unique strategies to survive challenging conditions. These adaptations often rely on molecular pathways that shape plant architecture to enhance their resilience. Date palms (Phoenix dactylifera) and mangroves (Avicennia marina) endure extreme heat and high salinity, yet the metabolic pathways underlying this resilience remain underexplored. Here, we integrate tissue imaging with spatial metabolomics to uncover shared and distinct adaptive features in these species. We found that mangrove roots accumulate suberin and lignin in meristematic tissues, this is unlike other plant species, where only the differentiation zones contain these compounds. Our metabolomic analysis shows that date palm roots are enriched in metabolites involved in amino acid biosynthesis, whereas compounds involved in lignin and suberin production were more abundant in mangrove roots. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed tissue- and species-specific metabolite distributions in root tissues. We identified common osmoprotectants accumulating in the exodermis/epidermis of date palm and mangrove root meristems, along with a unique metabolite highly abundant in the inner cortex of date palm roots. These findings provide valuable insights into stress adaptation pathways and highlight key tissue types involved in root stress response.PMID:39775192 | DOI:10.1038/s41598-025-85416-1

Nat Chem Biol. 2025 Jan 7. doi: 10.1038/s41589-024-01805-z. Online ahead of print.ABSTRACTIntricate coupling between metabolism and protein post-translational modifications (PTMs) has emerged as a fundamental aspect of cellular regulation. Recent studies demonstrate that protein modifications can originate from diverse metabolites, and that their regulation is closely tied to the cellular metabolic state. Here we explore recently uncovered PTMs, including the concept of 'modification of a modification', as well as associated feedback and feedforward regulatory mechanisms, in which modified proteins impact not only related metabolic pathways but also other signaling cascades affecting physiology and diseases. The recently uncovered role of nucleus-localized metabolic enzymes for histone modifications additionally highlights the importance of cell-compartment-specific metabolic states. We further comment on the utility of untargeted metabolomics and proteomics for previously unrecognized PTMs and associated metabolic patterns. Together, these advances have uncovered a dynamic interplay between metabolism and PTMs, offering new perspectives for understanding metabolic regulation and developing targeted therapeutic strategies.PMID:39775169 | DOI:10.1038/s41589-024-01805-z

Biol Reprod. 2025 Jan 8:ioaf008. doi: 10.1093/biolre/ioaf008. Online ahead of print.ABSTRACTAsthenozoospermia, a prevalent contributor to male infertility, exhibits a multifaceted pathogenesis. This study identified a significant downregulation in sperm dynein heavy chain 3 (DNAH3) protein levels in individuals with asthenozoospermia. To elucidate the role of DNAH3 in asthenozoospermia, we constructed Dnah3-knockout (KO) mice, which exhibited asthenozoospermia and sterility. The sperm motility of Dnah3-KO mice significantly declined compared to wild-type mice. However, spermatozoa from Dnah3-KO mice displayed normal morphology in haematoxylin-eosin staining and transmission electron microscopy analyses. Sperm metabolomics revealed that DNAH3 deficiency disturbed sperm energy metabolism, resulting in substantial reductions of L-palmitoylcarnitine and Glycocholic acid. Notably, offspring were successfully obtained from Dnah3-KO male mice through intracytoplasmic sperm injection. Collectively, these findings indicate that DNAH3 deficiency induces disturbances in energy metabolism, rather than abnormalities in sperm flagellar morphology, culminating in asthenozoospermia development. Our investigation provides valuable insights into understanding asthenozoospermia and offers guidance for clinical consultation.PMID:39774634 | DOI:10.1093/biolre/ioaf008

PLoS One. 2025 Jan 7;20(1):e0313580. doi: 10.1371/journal.pone.0313580. eCollection 2025.ABSTRACTDrought is one of the consequences of climate change that severely affects plant growth and development. Ophiopogon japonicus (L. f.) Ker-Gawl. (Chinese name: Chuanmaidong, abbreviated as CMD) is a commonly used herbaceous plant whose growth and development are strongly affected by drought. Here, we comprehensively analyzed the transcriptomic and metabolic responses of two CMD varieties (EP and CP) to drought stress. CP utilized a small number of differentially expressed genes to regulate a greater number of differential metabolites compared to EP, suggesting that it may be more drought tolerant. In addition, integrated transcriptome and metabolome analyses revealed that transcription factors such as WRKY, TIFY, and C2H2 regulate flavonoid synthesis in CMD. These findings provide ideas for in-depth analysis of the mechanism of CMD against drought stress, and provide a theoretical basis for breeding high-quality drought-tolerant varieties.PMID:39774546 | DOI:10.1371/journal.pone.0313580

Mol Psychiatry. 2025 Jan 7. doi: 10.1038/s41380-024-02862-5. Online ahead of print.ABSTRACTA major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression. We report a sex-specific deficiency in free-carnitine levels in women with aMCI and early-AD compared to cognitively healthy controls; no change was observed in men. We also replicated the prior finding of decreased LAC levels in both women and men with AD, supporting the robustness of the study samples assayed in our new study. The magnitude of the sex-specific free-carnitine deficiency reflected the severity of cognitive dysfunction and held in two study cohorts. Furthermore, patients with the lower free-carnitine levels showed higher β-amyloid(Aβ) accumulation and t-Tau levels assayed in cerebrospinal fluid (CSF). Computational analyses showed that the mitochondrial markers assayed in plasma are at least as accurate as CSF measures to classify disease status. Together with the mechanistic platform in rodents, these translational findings lay the groundwork to create preventive individualized treatments targeting sex-specific changes in mitochondrial metabolism that may be subtle to early cognitive dysfunction of AD risk.PMID:39774493 | DOI:10.1038/s41380-024-02862-5

Sci Rep. 2025 Jan 7;15(1):1144. doi: 10.1038/s41598-025-85252-3.ABSTRACTMaternal obesity increases risk for bronchopulmonary dysplasia (BPD) by up to 42%. Identifying metabolic features that may contribute to the association between maternal pre-pregnancy body mass index (BMI) and BPD is critical in defining the molecular relationship between these conditions. We investigated the association between maternal obesity and BPD using newborn screen metabolites as an explanatory variable. We hypothesized that elevated pre-pregnancy BMI compared to a normal BMI referent group, is associated with increased circulating short and long-chain acylcarnitines and subsequent development of BPD. This was a retrospective study with linkage of maternal pre-pregnancy BMI, with newborn screen metabolites obtained from the California Newborn Screening Program and further linked with neonatal outcomes. Results demonstrated elevated levels of phenylalanine and proline associated with an increased risk for BPD (OR 5.3, 95% CI 1.2-23.8 and OR 5.4, 95% CI 1.3-22.3) in the obesity group compared to the referent group. Short- and long-chain acylcarnitines demonstrated a mildly increased risk for BPD in neonates of mothers with severe obesity compared to controls. The findings suggest that specific metabolites may influence the molecular conditioning that increases susceptibility to BPD.PMID:39774255 | DOI:10.1038/s41598-025-85252-3

Sci Rep. 2025 Jan 8;15(1):1248. doi: 10.1038/s41598-025-85354-y.ABSTRACTAcute pancreatitis (AP) is a severe gastrointestinal condition with an increasing incidence of hyperlipidemic etiology. The investigation employed a two-sample, bidirectional Mendelian randomization method to investigate potential causal relationship between lipidome profiles, inflammatory mediators, and AP. Exploration of genetic variants across the genome in a study population of 10,630 AP cases and 844,679 non-AP individuals revealed multiple lipidome entities significantly associated with AP risk. The study identified 23 lipid species with unidirectional causal effects on AP after accounting for heterogeneity, pleiotropy, and potential reverse causation. Additionally, five inflammatory factors (CD5, IL-13, MMP-1, STAMBP, TNFRSF9) showed significant potential causal relationship with AP. Further analysis elucidated the intricate interplay between specific lipid species and inflammatory mediators in influencing AP incidence. Notably, Sterol ester (27:1/20:4) and several phosphatidylcholine species, including PC (17:0_20:4), PC (18:0_20:4), PC (18:0_20:5), and PC (O-18:2_20:4), were negatively associated with AP risk. This protective effect was partially mediated through decreased levels of inflammatory markers, particularly STAMBP and MMP-1. The study found that these phosphatidylcholines and sterol esters significantly reduced the levels of these pro-inflammatory factors, thereby potentially mitigating AP risk. Conversely, Phosphatidylinositol (16:0_18:1) demonstrated a positive association with AP risk. This detrimental effect was partially mediated by increased levels of MMP-1 and STAMBP, suggesting a pro-inflammatory mechanism. The study provides evidence that this specific phosphatidylinositol species may exacerbate AP risk by promoting inflammatory pathways. These findings elucidate the complex interplay between lipid metabolites, inflammation, and AP pathogenesis, potentially informing novel therapeutic strategies. The study highlights the utility of Mendelian randomization in uncovering potential causal relationship in AP. It underscores the requirement for further study into the molecular mechanisms underlying lipid-mediated inflammation in AP, particularly the roles of phosphatidylcholines and sterol esters in modulating inflammatory responses. Further studies are warranted to confirm our observations in laboratory models and assess their translational value in developing AP preventive and therapeutic strategies.PMID:39774240 | DOI:10.1038/s41598-025-85354-y

Curr Opin HIV AIDS. 2024 Dec 17. doi: 10.1097/COH.0000000000000907. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: To summarize the heterogeneity in the elite controllers population with the aim to identify a compatible profile with a persistent HIV remission, making distinction between persistent elite controllers, people with HIV (PWHIV) who permanently maintain virological control in the absence of antiretroviral treatment (ART), and transient elite controllers, PWHIV who eventually lose virological control. For this purpose, it is important to consider the mechanisms and biomarkers that have previously been associated with the maintenance and loss of the natural virological control.RECENT FINDINGS: Transient elite controllers, before losing virological control, exhibit a distinct metabolomic, proteomic, microRNAs (miRNA), immunological and virological profile compared to persistent elite controllers. In addition to a reduced and less polyfunctional HIV-specific T-cell response, transient elite controllers show a greater proportion of intact proviruses integrated into genic regions. In contrast, persistent elite controllers display a privileged HIV-1 reservoir profile with absence of detected intact proviruses or low proportion of clonal intact proviruses preferentially integrated into genomic features associated with HIV-1 transcriptional repression.SUMMARY: According to previous studies, the comprehensive characterization of persistent elite controllers might be crucial to identify other PWHIV with this distinct profile as spontaneously cured.PMID:39773856 | DOI:10.1097/COH.0000000000000907

J Biomed Sci. 2025 Jan 8;32(1):6. doi: 10.1186/s12929-024-01098-3.ABSTRACTBACKGROUND: Obesity is becoming one of the major non-communicable diseases with increasing incidence and risks that cannot be ignored. However effective and safe clinical treatment strategies still need to be deeply explored. Increased number and volume of adipocytes lead to overweight and obesity. The aim of our work is to identify lncRNAs that have important regulatory in differentiation of human mesenchymal stem cells (MSCs) into adipocytes, and to provide effective targets for clinical prevention and treatment of obesity and related metabolic disorders.METHODS: We extracted primary MSCs from human adipose tissue, and conducted expression profile analysis of lncRNAs during adipogenic differentiation of MSCs to screen changed lncRNAs. Characteristics of lncRNA were revealed mainly by RACE and RNA FISH. Loss- and gain-of function experiments in vivo and in vitro were used to analyze effects of lncRNA. Targeted metabolomics was utilized to detect levels of free fatty acids. RNA pull-down, mRNA stability tests, etc. were employed to explore mechanisms of lncRNA.RESULTS: Human-specific lncRNA, we named it MEK6-AS1, was the most up-regulated transcript during adipogenic differentiation of MSCs. MEK6-AS1 was highly expressed in adipose tissue samples from individuals with BMI ≥ 25 and positively correlated with adipogenic marker genes in these samples. Knocking down lncRNA inhibited expression of adipogenic differentiation markers and ectopic adipogenesis, reducing contents of various free fatty acids, as well as promoting osteogenic differentiation. Overexpression of lncRNA had the opposite effects to the above processes. We also found that MEK6-AS1 was elevated during hepatic steatosis organoid generation. Mechanistically, MEK6-AS1 worked partially through stabilization of MEK6 mRNA by NAT10.CONCLUSIONS: We have identified a human-specific lncRNA (MEK6-AS1) with position information in the genomic database but has not been extensively reported. We demonstrated that MEK6-AS1 as a novel lncRNA involved in adipogenic differentiation and adipogenesis, fatty acid metabolism, and osteogenic differentiation. We found that MEK6-AS1 may exert its effect by enhancing MEK6 mRNA stability through NAT10. Our study may provide insights into implication of lncRNAs in stem cell biology and offer a new potential therapeutic target for the prevention and treatment of obesity and other related disease.PMID:39773638 | DOI:10.1186/s12929-024-01098-3

Aging (Albany NY). 2025 Jan 6;16. doi: 10.18632/aging.206187. Online ahead of print.ABSTRACTSo far, it has been proven that benign prostatic hyperplasia (BPH) is strongly associated with inflammation resulting from, i.a. the presence of infectious agent, autoimmune disease, aging process and lipid disorders associated with metabolic syndrome (MetS). We analyzed the association between serum eicosanoides (HETE, HODE, lipoxins, prostaglandin, and leucotrien) in aging man with benign prostatic hyperplasia (BPH) and healthy controls. The study involved 219 men (with BPH, n = 144; healthy controls, n = 75). We assessed the content arachidonic and linoleic acid derivatives in the serum samples of the study participants using liquid chromatography (HPLC). The levels of: RvE1 (p < 0.001); LXA4 5S,6R,15R (p = 0.001); 10S,17R-DiDHA (p < 0.001); MaR1 (p = 0.002); 9S-HODE (p < 0.05); 15S-HETE (p < 0.05); 12S-HETE (p < 0.001); 5-oxoETE (p < 0.05) and 5-HETE (p < 0.001) were significantly higher in patients with BPH than in the control group. PGE2 (p = 0.007), LTB4 (p < 0.001), and 18RS-HEPE (p < 0.001) were significantly higher in control group. We also analyzed the relationship between LXA4 5S,6R,15R serum levels of oxidative stress markers and concomitance of MetS. We noticed a relationship between levels and MetS (F1216 = 6.114965, p = 0.01). Our research results suggest that pro-inflammatory mediators and suppressors of inflammation are involved in the development of BPH, but their exact contribution has yet to be investigated.PMID:39773533 | DOI:10.18632/aging.206187

Eur J Med Res. 2025 Jan 7;30(1):10. doi: 10.1186/s40001-024-02245-0.ABSTRACTBACKGROUND: Burn-hemorrhagic shock combined injury, a severe condition causing complex stress responses and metabolic disturbances that significantly affect clinical outcomes in both military and civilian settings, was modeled in swine to investigate the associated metabolomic and proteomic changes and identify potential biomarkers for disease prognosis.METHODS: Eight clean-grade adult male Landrace pigs (4-5 months, average weight 60-70 kg) were used to model burn-hemorrhagic shock combined injury. Serum samples collected at 0 h and 2 h post-injury were analyzed using metabolomic and proteomic measurements. The metabolomic and proteomic data were processed through partial least squares-discriminant analysis (PLS-DA) and the KEGG enrichment etc. Furthermore, the integrate analysis of the metabolomic and proteomic data was generalized by canonical correlation discriminant analysis, and the correlation between metabolites and mortality of the swine model was predicted using a multiple linear regression model by Pearson analysis.RESULTS: PLS-DA revealed a global shift in each of the metabolomic and proteomic profiles following injury. The levels of 87 signature metabolites including various types of amino acids, fatty acids and acyl-carnitines of different lengths, and many metabolites in the gluconeogenesis, glycolysis, and tricarboxylic acid (TCA) cycle are generally increased (P < 0.05) after injury and can be used as biomarkers. Pathways related to amino acids metabolism and TCA cycle were significantly enriched (P < 0.01). In proteome analysis, we found dramatically altered (P < 0.05) levels of matrix and red blood cell-related proteins, such as type I collagen and hemoglobin. Most importantly, we found that the markedly elevated (P < 0.01) succinic acid, glutaric acid, and malic acid are closely associated (r = 0.863, 0.861, and 0.821, respectively) with injury severity by Pearson analysis, and can predict mortality using a multiple linear regression model.CONCLUSIONS: The study provides compelling observations that burn-shock swine model undergoes dramatic changes in the acute phase and present a valuable panel for clinical use of prognosis.PMID:39773520 | DOI:10.1186/s40001-024-02245-0

Microb Cell Fact. 2025 Jan 7;24(1):9. doi: 10.1186/s12934-024-02636-2.ABSTRACTBACKGROUND: Sporobolomyces pararoseus is a well-studied oleaginous red yeast that can synthesize a variety of high value-added bioactive compounds. Biofilm is one of the important biological barriers for microbial cells to resist environmental stresses and maintain stable fermentation process. Here, the effect of acidic conditions on the biosynthesis of biofilms in S. pararoseus NGR was investigated through the combination of morphology, biochemistry, and multi-omics approaches.RESULTS: The results showed that the acidic environment was the key factor to trigger the biofilm formation of S. pararoseus NGR. When S. pararoseus NGR was cultured under pH 4.7, the colony morphology was wrinkled, the cells were wrapped by a large amount of extracellular matrix, and the hydrophobicity and anti-oxidative stress ability were significantly improved, and the yield of intracellular carotenoids was significantly increased. Transcriptome and metabolome profiling indicated that carbohydrate metabolism, amino acid metabolism, lipid metabolism, and nucleic acid metabolism in S. pararoseus NGR cells were significantly enriched in biofilm cells under pH 4.7 culture conditions, including 56 differentially expressed genes and 341 differential metabolites.CONCLUSIONS: These differential genes and metabolites may play an important role in the formation of biofilms by S. pararoseus NGR in response to acidic stress. The results will provide strategies for the development and utilization of beneficial microbial biofilms, and provide theoretical support for the industrial fermentation production of microorganisms to improve their resistance and maintain stable growth.PMID:39773469 | DOI:10.1186/s12934-024-02636-2

BMC Plant Biol. 2025 Jan 8;25(1):28. doi: 10.1186/s12870-024-06035-y.ABSTRACTEffective Microorganism (EM) is widely employed as a growth promoter in agricultural practices. The aging of oat seeds not only directly impairs agricultural production but also exerts adverse effects on biodiversity. The mechanism through which EM influence the germination of aging seeds remains unclear. In this experiment, the EM bacterial solution underwent pretreatment, which included the original-solution treatment (OrT), supernatant treatment (SuT), and sterile treatment (StT). Aging of oat seeds was induced using the pretreated EM bacterial solution. In this study, the EM bacterial solution facilitated the enhancement of the germination rate, germination index, and vitality index of aged seeds, with SuT demonstrating the most pronounced effects. Specifically, SuT resulted in a significant increase in APX and POD activities, while significantly reducing the malondialdehyde content. In addition, metabolic profiling highlighted the significance of 5-phosphoribosylamine in the purine metabolic pathway. Particularly in the SuT, the upregulation of 5-phosphoribosylamine facilitated the synthesis of (R)-Allantoin, consequently augmenting antioxidant enzyme activity.PMID:39773191 | DOI:10.1186/s12870-024-06035-y

Physiol Genomics. 2025 Jan 7. doi: 10.1152/physiolgenomics.00106.2024. Online ahead of print.ABSTRACTPreeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy with an incidence rate of up to 8% worldwide. However, the complete pathogenesis is still unknown. Obesity increases the risk of developing PE three-fold. To better understand the relationship of maternal risk factors, the BPH/5 mouse was described as a model of superimposed PE. Previous research demonstrated that adult BPH/5 female mice have an adverse cardiometabolic phenotype characterized by hypertension, obesity with increased white adipose tissue and dyslipidemia, exaggerated by pregnancy. We hypothesize that BPH/5 mice have gut dysbiosis characterized by changes in alpha and beta diversity of bacterial community structure as well as perturbed short chain fatty acids (SCFA) compared to controls in pregnancy. Fecal samples were used for Illumina sequencing of 16S v4 rRNA amplicons. Microbial community composition of the pregnant BPH/5 compared to C57 controls was different using PERMANOVA with Bray-Curtis dissimilarity. Alpha diversity was increased in pregnant BPH/5 dams compared to controls. Alistipes and Helicobacter were increased while Bacteroides, Lactobacillus, Parasulterrella, and Parabacteroides were decreased compared to controls. Fecal SCFAs were not different between groups, but BPH/5 serum acetic and butyric acid were decreased while isobutyric and isovaleric acid were increased specifically in pregnancy. BPH/5 pregnant colons had decreased expression of free fatty acid receptor, GPR41. In conclusion, the BPH/5 maternal fecal microbiome demonstrates microbial dysbiosis characterized by community structure and diversity changes before and after the onset of pregnancy. Gut dysbiosis may be a key mechanism linking SCFA signaling and obesity to the BPH/5 PE-like phenotype.PMID:39773069 | DOI:10.1152/physiolgenomics.00106.2024

Microbiol Spectr. 2025 Jan 8:e0190124. doi: 10.1128/spectrum.01901-24. Online ahead of print.ABSTRACTLimnospira can colonize a wide variety of environments (e.g., freshwater, brackish, alkaline, or alkaline-saline water) and develop dominant and even permanent blooms that overshadow and limit the diversity of adjacent phototrophs, especially in alkaline and saline environments. Previous phylogenomic analysis of Limnospira allowed us to distinguish two major phylogenetic clades (I and II) but failed to clearly segregate strains according to their respective habitats in terms of salinity or biogeography. In the present work, we attempted to determine whether Limnospira displays metabolic signatures specific to its different habitats, particularly brackish and alkaline-saline ecosystems. The impact of accessory gene repertoires on respective chemical adaptations was also determined. In complement of our previous phylogenomic investigation of Limnospira (Roussel et al., 2023), we develop a specific analysis of the metabolomic diversity of 93 strains of Limnospira, grown under standardized lab culture conditions. Overall, this original work showed distinct chemical fingerprints that were correlated with the respective biogeographic origins of the strains. The molecules that most distinguished the different Limnospira geographic groups were sugars, lipids, peptides, photosynthetic pigments, and antioxidants. Interestingly, these molecular enrichments might represent consequent adaptations to conditions of salinity, light, and oxidative stress in their respective sampling environments. Although the genes specifically involved in the production of these components remain unknown, we hypothesized that within extreme environments, such as those colonized by Limnospira, a large set of flexible genes could support the production of peculiar metabolite sets providing remarkable adaptations to specific local environmental conditions.IMPORTANCE: Limnospira are ubiquitous cyanobacteria with remarkable adaptive strategies allowing them to colonize and dominate a wide range of alkaline-saline environments worldwide. Phylogenomic analysis of Limnospira revealed two distinct major phylogenetic clades but failed to clearly segregate strains according to their habitats in terms of salinity or biogeography. We hypothesized that the genes found within this variable portion of the genome of these clades could be involved in the adaptation of Limnospira to local environmental conditions. In the present paper, we attempted to determine whether Limnospira displayed metabolic signatures specific to its different habitats. We also sought to understand the impact of the accessory gene repertoire on respective chemical adaptations.PMID:39772964 | DOI:10.1128/spectrum.01901-24