PubMed

mSystems. 2025 Jan 14:e0113624. doi: 10.1128/msystems.01136-24. Online ahead of print.ABSTRACTPeriodontitis is closely related to renal health, but the specific influence of Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, on the development of acute kidney injury (AKI) in mice has not been fully elucidated. In our study, AKI was induced in mice through ischemia-reperfusion injury while administering oral infection with P. gingivalis. Comprehensive analyses were conducted, including 16S rRNA sequencing, liquid chromatography-mass spectrometry (LC-MS) metabolomics, and transcriptome sequencing. In vitro, the identified metabolite was used to stimulate mouse neutrophils. Subsequently, these modified neutrophils were co-cultured with mouse renal tubular epithelial cells. The results showed that oral infection with P. gingivalis significantly exacerbated AKI in mice. 16S rRNA sequencing revealed notable shifts in gut microbiota composition. LC-MS metabolomics analysis identified significant metabolic alterations, particularly the upregulation of 3-indoleacrylic acid in the serum. Transcriptome sequencing showed an increased expression of neutrophilic granule protein (Ngp), which was closely associated with 3-indoleacrylic acid, and the presence of Porphyromonas. Cellular experiments demonstrated that 3-indoleacrylic acid could activate neutrophils, leading to an elevation in NGP protein levels, a response that was associated with renal epithelial cell injury. Oral infection with P. gingivalis exacerbated AKI through the gut-kidney axis, involving gut microbiota dysbiosis, metabolic disturbances, and increased renal expression of Ngp.IMPORTANCE: This study provides novel insights into the relationship between periodontal health and renal function. Porphyromonas gingivalis oral infection disrupted the balance of gut microbiota and was an important modifier determining the severity of acute kidney injury. Under the "gut-kidney axis," P. gingivalis might cause an increase in the level of the gut microbial metabolite 3-indoleacrylic acid, interfering with kidney immunity and disrupting the maintenance of kidney epithelium.PMID:39807890 | DOI:10.1128/msystems.01136-24

J Assoc Nurses AIDS Care. 2025 Jan 14. doi: 10.1097/JNC.0000000000000521. Online ahead of print.ABSTRACTChronic diseases such as osteoporosis and low bone mineral density (BMD) are significant public health concerns for people living with HIV (PLWH), especially with the increased life expectancy because of antiretroviral therapy (ART). This study evaluated the prevalence and associated factors of low BMD among 94 PLWH in Kerman, Iran, from September 2021 to February 2022. Using dual-energy X-ray absorptiometry, BMD was measured, with low BMD defined by specific T-scores and Z-scores. Predictors were assessed through interviews, medical records, and blood tests. Bivariable and multivariable logistic regression models identified associations between low BMD and various factors. The study found a 51.1% prevalence of low BMD, with significant associations with hypogonadism (adjusted odds ratio [aOR]: 3.19), longer ART duration (aOR per month: 1.02), and lower body mass index (aOR per unit: 0.83). The findings highlight the need for regular screening and timely intervention for low BMD among PLWH, particularly with prolonged ART use.PMID:39807800 | DOI:10.1097/JNC.0000000000000521

Hum Mol Genet. 2025 Jan 14:ddae203. doi: 10.1093/hmg/ddae203. Online ahead of print.ABSTRACTType 2 diabetes (T2D) complications pose a significant global health challenge. Omics technologies have been employed to investigate these complications and identify the biological pathways involved. In this review, we focus on four major T2D complications: diabetic kidney disease, diabetic retinopathy, diabetic neuropathy, and cardiovascular complications. We discuss advancements in omics research, summarizing findings from genetic, epigenomic, transcriptomic, proteomic, and metabolomic studies across different ancestries and disease-relevant tissues. We stress the importance of integrating multi-omics techniques to elucidate the biological mechanisms underlying T2D complications and advocate for ancestrally diverse studies. Ultimately, these insights will improve risk prediction for T2D complications and inform translation strategies.PMID:39807636 | DOI:10.1093/hmg/ddae203

Genes Cells. 2025 Jan;30(1):e13195. doi: 10.1111/gtc.13195.ABSTRACTTumor development often requires cellular adaptation to a unique, high metabolic state; however, the molecular mechanisms that drive such metabolic changes in TFE3-rearranged renal cell carcinoma (TFE3-RCC) remain poorly understood. TFE3-RCC, a rare subtype of RCC, is defined by the formation of chimeric proteins involving the transcription factor TFE3. In this study, we analyzed cell lines and genetically engineered mice, demonstrating that the expression of the chimeric protein PRCC-TFE3 induced a hypoxia-related signature by transcriptionally upregulating HIF1α and HIF2α. The upregulation of HIF1α by PRCC-TFE3 led to increased cellular ATP production by enhancing glycolysis, which also supplied substrates for the TCA cycle while maintaining mitochondrial oxidative phosphorylation. We crossed TFE3-RCC mouse models with Hif1α and/or Hif2α knockout mice and found that Hif1α, rather than Hif2α, is essential for tumor development in vivo. RNA-seq and metabolomic analyses of the kidney tissues from these mice revealed that ketone body production is inversely correlated with tumor development, whereas de novo lipid synthesis is upregulated through the HIF1α/SREBP1-dependent mechanism in TFE3-RCC. Our data suggest that the coordinated metabolic shift via the PRCC-TFE3/HIF1α/SREBP1 axis is a key mechanism by which PRCC-TFE3 enhances cancer cell metabolism, promoting tumor development in TFE3-RCC.PMID:39807625 | DOI:10.1111/gtc.13195

Adv Clin Exp Med. 2025 Jan 14. doi: 10.17219/acem/193243. Online ahead of print.ABSTRACTBACKGROUND: The search for early and minimally invasive diagnostic approaches to pancreatic cancer (PC) remains an important issue. One of the most promising directions is to find a sensitive key in the metabolic changes during widespread causes of PC, i.e., chronic pancreatitis (CP) and diabetes mellitus (DM).OBJECTIVES: The main objective of this study was to analyze the peptide pools in the blood plasma and pancreas of rats with modeling of CP and/or without type 1 DM in association with pancreas histopathological grading features.MATERIAL AND METHODS: The study was conducted on white non-linear male rats, divided into 3 groups: 1st group: control, 2nd group: rats with cerulein-stimulated CP, and 3rd group: rats with CP and streptozotocin-inducible type 1 DM. Total protein and peptide content were determined in the pancreas and blood plasma. The peptide pools were fractionated using size-exclusion chromatography.RESULTS: Rats with CP showed a high degree of fibrosis in the pancreas and grade 1 ductal pancreatic intraepithelial neoplasia (PanIN), associated with decreased total peptides in the pancreas. In rats with CP and DM, 2nd and 3rd grade PanIN with pronounced acinar metaplasia was observed in association with decreasing total pancreatic protein and peptide pools. While there was a decrease in total protein and an increase in total peptide in blood serum, the changes were more pronounced in rats with CP and DM. A study revealed both qualitative and quantitative differences in the distribution of peptide pools in 2 groups with pathologies. Qualitatively, plasma samples from pathological groups exhibited an increased number of peaks. Quantitatively, there was a higher proportion of peptides with molecular weights exceeding 700 Da observed in both plasma and pancreas.CONCLUSIONS: The analysis of peptide pools obtained from plasma and PanIN development demonstrated that the peptide pool can serve as an early and complementary indicator of PC emergence.PMID:39807606 | DOI:10.17219/acem/193243

Biochemistry. 2025 Jan 14. doi: 10.1021/acs.biochem.4c00706. Online ahead of print.ABSTRACTCoral reefs are hotspots of marine biodiversity, which results in the synthesis of a wide variety of compounds with unique molecular scaffolds, and bioactivities, rendering reefs an ecosystem of interest. The chemodiversity stems from the intricate relationships between inhabitants of the reef, as the chemistry produced partakes in intra- and interspecies communication, settlement, nutrient acquisition, and defense. However, the coral reefs are declining at an unprecedented rate due to climate change, pollution, and increased incidence of pathogenic diseases. Among pathogens, Vibrio spp. bacteria are key players resulting in high mortality. Thus, alternative strategies such as application of beneficial bacteria isolated from disease-resilient species are being explored to lower the burden of pathogenic species. Here, we apply coculturing of a coral-derived pathogenic species of Vibrio and beneficial bacteria and leverage recent advancements in untargeted metabolomics to discover engineerable beneficial traits. By chasing chemical change in coculture, we report Microbulbifer spp.-mediated degradation of amphibactins, produced by Vibrio spp. bacteria to sequester iron. Additional biochemical experiments revealed that the degradation occurs in the peptide backbone and requires the enzyme fraction of Microbulbifer. A reduction in iron affinity is expected due to the loss of one Fe(III) binding moiety. Therefore, we hypothesize that this degradation shapes community behaviors as it pertains to iron acquisition, a limiting nutrient in the marine environment, and survival. Furthermore, Vibrio sp. bacteria suppressed natural product synthesis by beneficial bacteria. Understanding biochemical mechanisms behind these interactions will enable engineering probiotic bacteria capable of lowering pathogenic burdens during heat waves and incidence of disease.PMID:39807563 | DOI:10.1021/acs.biochem.4c00706

Plant Genome. 2025 Mar;18(1):e20543. doi: 10.1002/tpg2.20543.ABSTRACTThe plant Polygonum capitatum (P. capitatum) contains a variety of flavonoids that are distributed differently among different parts. Nevertheless, differentially expressed genes (DEGs) associated with this heterogeneous distribution have not been identified. In this study, combined with transcriptomic and metabonomic analysis, we identified significant DEGs related to variations in flavonoid composition among different parts of P. capitatum. Subsequently, transcriptomic and nontargeted metabolomic analyses revealed that flavonoids and phenolic acids in different parts of P. capitatum were significantly enriched in the phenylpropanoid biosynthesis, shikimic acid biosynthesis, and flavonoid biosynthesis pathways. The expression levels of genes encoding enzymes, including shikimate O-hydroxycinnamoyltransferase (HCT), chalcone synthase (CHS), flavonoid 3',5'-hydroxylase (CYP75A), flavones 3-hydroxylase (F3H), flavonol synthase (FLS), leucoanthocyanidin reductase (LAR), trans-cinnamate 4-monooxygenase (CYP73A), and shikimate kinase (SK), were found to be the lowest in the leaves of P. capitatum via quantitative PCR. Interestingly, these genes are involved in the biosynthesis of quality markers such as gallic acid, quercetin, and quercitrin in P. capitatum. Finally, the targeted metabolomic results reconfirmed that the gallic acid, quercetin, and quercitrin contents were the highest in the leaves of P. capitatum. This research provides a theoretical basis for further understanding the differential regulatory mechanism of flavonoid metabolism in different parts of P. capitatum, providing novel insights into the pharmacognostic basis of P. capitatum.PMID:39807534 | DOI:10.1002/tpg2.20543

Acta Pharm Sin B. 2024 Dec;14(12):5393-5406. doi: 10.1016/j.apsb.2024.11.004. Epub 2024 Nov 13.ABSTRACTMacrophage-mediated inflammation plays a pivotal role in cardiovascular disease pathogenesis. However, current cell-based models lack a comprehensive understanding of crosstalk between macrophages and cardiomyocytes, hindering the discovery of effective therapeutic interventions. Here, a microfluidic model has been developed to facilitate the coculture of macrophages and cardiomyocytes, allowing for mapping key signaling pathways and screening potential therapeutic agents against inflammation-induced dynamic myocardial injury. Through metabolic profiling and bioinformatic enrichment analysis, the microchip model with dynamic cell-cell crosstalk reveals robust activation of inflammatory and oxidative stress-associated metabolic pathways, closely resembling metabolic profiles of myocardial infarction in both humans and rodents. Furthermore, an integrative screening strategy has been established to screen bioactive natural products precisely, identifying ginsenoside Rb1 and protocatechualdehyde as promising cardioprotective candidates in vitro and in vivo. Taken together, the microfluidic coculture model advances mechanistic insight into macrophage-mediated cardio-immunology and may accelerate the discovery of therapeutics for myocardial injury.PMID:39807320 | PMC:PMC11725091 | DOI:10.1016/j.apsb.2024.11.004

J Tradit Complement Med. 2024 Nov 12;15(1):106. doi: 10.1016/j.jtcme.2024.11.003. eCollection 2025 Jan.ABSTRACT[This corrects the article DOI: 10.1016/j.jtcme.2024.04.004.].PMID:39807267 | PMC:PMC11725078 | DOI:10.1016/j.jtcme.2024.11.003

For Res (Fayettev). 2024 Dec 19;4:e038. doi: 10.48130/forres-0024-0035. eCollection 2024.ABSTRACTPolyphenols, as one of the primary compounds produced by plant secondary metabolism, have garnered considerable attention because of their non-toxic, environmentally friendly, and biodegradable properties, as well as their notable medicinal value. This study presents a metabolomic analysis of polyphenols from 11 woody plants, including Camellia oleifera, Quercus acutissima, and Punica granatum, investigating a total of 40 polyphenolic metabolites. A differential metabolite dynamics map highlighted the five most differentiated substances among the 11 plants, including vitexin, dihydromyricetin, genistin, resveratrol, and isorhamnetin. To evaluate the application of polyphenol-rich plants as natural dyes, dye performance tests, and color fastness evaluations were conducted, focusing on the specific role of polyphenols in dyeing cotton fabrics. The composition of polyphenols had a minor effect on the color of dyed cotton fabrics, typically imparting only black or brown tones to the fabric. However, their effect on dyeing performance is notable, with the ratio of the dye absorption coefficient (k) to the dye scattering coefficient (s) (K/S) ranging from 1 to 20, and lightness varying from 26 to 78. The addition of mordants not only improved the dye's color fastness but also expanded the color range. Furthermore, this study identified four key substances that influence the dyeing performance of plant dyes, including naringenin, epicatechin, catechin, and dihydromyricetin, and discovered a novel natural dye compound, naringenin. Importantly, six of the 11 plant dyes selected in this study are derived from plant waste, thus providing a theoretical basis for advancing environmentally friendly and sustainable dyeing technologies.PMID:39807261 | PMC:PMC11727558 | DOI:10.48130/forres-0024-0035

Adv Sci (Weinh). 2025 Jan 14:e2409105. doi: 10.1002/advs.202409105. Online ahead of print.ABSTRACTHyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β-amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose-free diet or mannose transporter antagonists. Mechanistically, single-cell RNA sequencing and metabolomics suggested that mannose-mediated N-glycosylation of BACE1 and Nicastrin enhances their protein stability, promoting Aβ production. Additionally, reduced mannose intake decreased BACE1 and Nicastrin stability, ultimately lowering Aβ production and mitigating AD pathology. this results highlight that high-dose mannose consumption may exacerbate AD pathogenesis. Restricting dietary mannose may have therapeutic benefits.PMID:39807036 | DOI:10.1002/advs.202409105

Adv Sci (Weinh). 2025 Jan 14:e2413296. doi: 10.1002/advs.202413296. Online ahead of print.ABSTRACTLarge-scale studies indicate a strong relationship between the gut microbiome, type 2 diabetes mellitus (T2DM), and atherosclerotic cardiovascular disease (ASCVD). Here, a higher abundance of the type III secretion system (T3SS) virulence factors of Enterobacteriaceae/Escherichia-Shigella in patients with T2DM-related-ASCVD, which correlates with their atherosclerotic stenosis is reported. Overexpression of T3SS via Citrobacter rodentium (CR) infection in Apoe-/- T2DM mice exacerbated atherosclerotic lesion formation and increased gut permeability. Non-targeted metabolomic and proteomic analysis of mouse serum showed that T3SS caused abnormal glycerophospholipid metabolism in mice. Proteomics, RNA sequencing, and functional analyses showed that T3SS induced ferroptosis in intestinal epithelial cells, partly due to increased expression of ferritin heavy chains (FTH1). This findings first demonstrated that T3SS increases ferroptosis in intestinal epithelial cells, via disrupting the intestinal barrier and upregulation of phosphatidylcholine, thereby exacerbating T2DM-related ASCVD.PMID:39807021 | DOI:10.1002/advs.202413296

Cancer Metab. 2025 Jan 14;13(1):1. doi: 10.1186/s40170-024-00372-0.ABSTRACTInvasiveness of pituitary adenoma is the main cause of its poor prognosis, mechanism of which remains largely unknown. In this study, the differential proteins between invasive and non-invasive pituitary tumors (IPA and NIPA) were identified by TMT labeled quantitative proteomics. The differential metabolites in venous bloods from patients with IPA and NIPA were analyzed by untargeted metabolomics. Proteomic data showed that the top five up-regulated proteins were AD021, C2orf15, PLCXD3, HIST3H2BB and POU1F1, and the top five down-regulated proteins were AIPL1, CALB2, GLUD2, SLC4A10 and GTF2I. Metabolomic data showed that phosphatidylinositol (PI) was most remarkably up-regulated and melibiose was most obviously down-regulated. Further investigation demonstrated that PI stimulation increased the expression of PITPNM1, POU1F1, C2orf15 and LDHA as well as the phosphorylation of AKT and ERK, and promoted the proliferation, migration and invasion of GH3 cells, which were blocked by PITPNM1knockdown. Inhibiting AKT phosphorylation reduced the expression of POU1F1, C2orf15 and LDHA in PI-stimulated cells while activating AKT increased their expression in PITPNM1-silencing cells, which was similar to the function of ERK. POU1F1 silence suppressed the expression of LDHA and C2orf15. Luciferase report assay and ChIP assay demonstrated that POU1F1 positively regulated the transcription of LDHA and C2orf15. In addition, PI propelled the metastasis of GH3 cells in vivo, and elevated the expression of PITPNM1, POU1F1, C2orf15 and LDHA. These results suggested that elevated serum PI might contribute to the proliferation and invasion of pituitary adenoma by regulating the expression of PITPNM1/AKT/ERK/POU1F1 axis.PMID:39806458 | DOI:10.1186/s40170-024-00372-0

Orphanet J Rare Dis. 2025 Jan 13;20(1):21. doi: 10.1186/s13023-024-03484-4.ABSTRACTBACKGROUND: Intestinal Behçet's syndrome (IBS) has high morbidity and mortality rates with serious complications. However, there are few specific biomarkers for IBS. The purposes of this study were to investigate the distinctive metabolic changes in plasma samples between IBS patients and healthy people, active IBS and inactive IBS patients, and to identify candidate metabolic biomarkers which would be useful for diagnosing and predicting IBS.METHODS: In this study, we performed a global untargeted metabolomics approach in plasma samples from 30 IBS patients and 20 healthy subjects. P value < 0.05 and variable importance projection (VIP) values > 1 were considered to be statistically significant metabolites. Univariate receiver operating characteristic (ROC) curve analysis was plotted as a measure for assessing the clinical performance of metabolites, and area under curve (AUC) were assessed.RESULTS: A total of 147 differentially abundant metabolites (DAMs) were identified between IBS patients and normal control (NC) group. The potential pathways involved in the pathogenesis of IBS include linoleic acid metabolism; GABAergic synapse; biosynthesis of unsaturated fatty acids; valine, leucine and isoleucine biosynthesis; ovarian steroidogenesis; and others. In addition, a total of 103 significant metabolites were selected to distinguish active IBS from inactive IBS patients. Tyrosine metabolism, dopaminergic synapse and neuroactive ligand-receptor interaction were found to be closely related to the disease activity of IBS. Furthermore, three potential metabolites including quinate, stearidonic acid (SDA) and capric acid (CA) could significantly differ IBS patients from NC group. On the other hand, 1-methyladenosine (m1A), genipin, methylmalonic acid (MMA) and ascorbate could significantly differentiated active IBS from inactive IBS patients.CONCLUSION: In conclusion, this study demonstrated the characteristic plasma metabolic profiles between IBS group and NC group, as well as between active and inactive IBS patients by using an untargeted LC/MS metabolomics profiling approach. In this study, quinate, SDA and CA were identified as potential diagnostic biomarkers for IBS. Additionally, m1A, genipin, MMA and ascorbate could serve as potential biomarkers for evaluating IBS activity. These findings might provide potential valuable insights for developing therapeutic strategies to manage IBS in the future.PMID:39806438 | DOI:10.1186/s13023-024-03484-4

Cardiovasc Diabetol. 2025 Jan 13;24(1):18. doi: 10.1186/s12933-025-02581-3.ABSTRACTBACKGROUND: Existing cardiovascular risk prediction models still have room for improvement in patients with type 2 diabetes who represent a high-risk population. This study evaluated whether adding metabolomic biomarkers could enhance the 10-year prediction of major adverse cardiovascular events (MACE) in these patients.METHODS: Data from 10,257 to 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation. A total of 249 metabolites were measured with nuclear magnetic resonance (NMR) spectroscopy. Sex-specific LASSO regression with bootstrapping identified significant metabolites. The enhanced model's predictive performance was evaluated using Harrell's C-index.RESULTS: Seven metabolomic biomarkers were selected by LASSO regression for enhanced MACE risk prediction (three for both sexes, three male- and one female-specific metabolite(s)). Especially albumin and the omega-3-fatty-acids-to-total-fatty-acids-percentage among males and lactate among females improved the C-index. In internal validation with 30% of the UKB, adding the selected metabolites to the SCORE2-Diabetes model increased the C-index statistically significantly (P = 0.037) from 0.660 to 0.678 in the total sample. In external validation with ESTHER, the C-index increase was higher (+ 0.043) and remained statistically significant (P = 0.011).CONCLUSIONS: Incorporating seven metabolomic biomarkers in the SCORE2-Diabetes model enhanced its ability to predict MACE in patients with type 2 diabetes. Given the latest cost reduction and standardization efforts, NMR metabolomics has the potential for translation into the clinical routine.PMID:39806417 | DOI:10.1186/s12933-025-02581-3

BMC Genomics. 2025 Jan 13;26(1):30. doi: 10.1186/s12864-025-11208-6.ABSTRACTBACKGROUND: Megalobrama amblycephala presents unsynchronized growth, which affects its productivity and profitability. The liver is essential for substance exchange and energy metabolism, significantly influencing the growth of fish.RESULTS: To investigate the differential metabolites and genes governing growth, and understand the mechanism underlying their unsynchronized growth, we conducted comprehensive transcriptomic and metabolomic analyses of liver from fast-growing (FG) and slow-growing (SG) M. amblycephala individuals. A total of 2,097 differentially expressed genes (DEGs) were identified between FG and SG, with 830 genes exhibiting significantly higher expression level in FG. KEGG and GO enrichment analysis indicated that the DEGs with higher expression level were significantly correlated with insulin signaling pathway, steroid hormone and lipid metabolism related pathway (PPAR signaling pathway and fatty acid degradation). In the metabolomic analysis, 224 differentially expressed metabolites (DEMs) were detected, of which 128 were significantly more abundant in FG. These more abundant DEMs were prominently enriched in pathways associated with cell proliferation and energy metabolism (Oxidative phosphorylation, mTOR signaling pathway and FoxO signaling pathway). In addition, DEGs and DEMs in adenosine diphosphate (ATP) hydrolysis activity and associate with fatty acid metabolism, glucose metabolism, and amino acid metabolism pathways were both found in the transcriptomic and metabolomic integrated data. These findings suggest that the large amounts of energy generated by fatty acid, glucose metabolism and other energy metabolism pathway promote the rapid growth of FG.CONCLUSIONS: This research is the first to integrate metabolomic and transcriptomic analyses of liver to identify key genes, metabolites, and pathways to uncover the molecular and metabolic mechanisms of unsynchronized growth in M. amblycephala. The identified metabolic and genes can be potential targets for selective breeding programs to improve growth performance in aquaculture.PMID:39806290 | DOI:10.1186/s12864-025-11208-6

BMC Genom Data. 2025 Jan 13;26(1):3. doi: 10.1186/s12863-024-01294-y.ABSTRACTBACKGROUND: Wheat seeds display different colors due to the types and contents of anthocyanins, which is closely related to anthocyanin metabolism. In this study, a transcriptomic and metabolomic analysis between white and purple color wheat pericarp aimed to explore some key genes and metabolites involved in anthocyanin metabolism.RESULTS: Two wheat cultivars, a white seed cultivar Shiluan02-1 and purple seed cultivar Hengzi151 were used to identify the variations in differentially expressed genes (DEGs) and differentially accumulated flavonoids (DAFs). Based on metabolomic data, 314 metabolites and 191 DAFs were identified. Chalcone, flavonol, pro-anthocyanidin and anthocyanidin were the most differentially accumulated flavonoid compounds in Hengzi151. 2610 up-regulated and 2668 down-regulated DEGs were identified according to transcriptomic data. The results showed that some structural genes in anthocyanin synthesis pathway were prominently activated in Hengzi151, such as PAL, CAD, CHS and so on. Transcription factors (TFs) of MYB, bHLH, WD40 and some other TFs probably involved in regulating anthocyanin biosynthesis were identified. Some genes from hormone synthetic and signaling pathways that may participate in regulating anthocyanin biosynthesis also have been identified.CONCLUSIONS: Our results provide valuable information on the candidate genes and metabolites involved in the anthocyanin metabolism in wheat pericarp.PMID:39806276 | DOI:10.1186/s12863-024-01294-y

Plant Cell Rep. 2025 Jan 13;44(2):30. doi: 10.1007/s00299-024-03410-9.ABSTRACTCannabis trichome development progresses in distinct phases that underpin the dynamic biosynthesis of cannabinoids and terpenes. This study investigates the molecular mechanisms underlying cannabinoid and terpenoid biosynthesis in glandular trichomes of Cannabis sativa (CsGTs) throughout their development. Female Cannabis sativa c. Hindu Kush were cultivated under controlled conditions, and trichome development was analysed from week 3 to week 8 of the flowering period. We employed light microscopy, quantitative metabolomics and proteomics to analyse morphological changes in trichome secretory cell development, and temporal changes in metabolite accumulation and protein abundance. Our findings identified three distinct developmental phases: pre-secretory (T3), secretory (T6), and post-secretory (T8), the first time the three phases of trichome development have been identified and investigated in CsGTs. The pre-secretory phase was characterized by smaller secretory cells, limited metabolite accumulation and elevated levels of proteins involved in protein biosynthesis and cellular development. The secretory phase exhibited the highest biosynthetic activity, marked by larger secretory cells, increased plastidal activity, central carbon metabolism, and significant accumulation of cannabinoids and terpenoids. The post-secretory phase showed a decrease in secretory cell size, reduced metabolic activity, and a decrease in the abundance of primary and secondary metabolism enzymes, although THCA continued to accumulate. Key enzymes showed dynamic changes correlating with the stages of trichome development. This study provides a comprehensive understanding of the molecular mechanisms regulating cannabinoid and terpenoid biosynthesis in CsGTs, offering insights for enhancing the production of these valuable compounds through targeted breeding and biotechnological approaches.PMID:39806251 | DOI:10.1007/s00299-024-03410-9

EMBO J. 2025 Jan 13. doi: 10.1038/s44318-024-00339-3. Online ahead of print.ABSTRACTPolyglucosans are glycogen molecules with overlong chains, which are hyperphosphorylated in the neurodegenerative Lafora disease (LD). Brain polyglucosan bodies (PBs) cause fatal neurodegenerative diseases including Lafora disease and adult polyglucosan body disease (ABPD), for which treatments, biomarkers, and good understanding of their pathogenesis are currently missing. Mutations in the genes for the phosphatase laforin or the E3 ubiquitin ligase malin can cause LD. By depleting PTG, an activator of the glycogen chain-elongating enzyme glycogen synthase (GYS1), in laforin- and malin-deficient LD mice, we show that abnormal glycogen chain lengths and not hyperphosphorylation underlie polyglucosan formation, and that polyglucosan bodies induce neuroinflammation. We provide evidence indicating that a small pool of overactive GYS1 contributes to glycogen insolubility in LD and APBD. In contrast to previous findings, metabolomics experiments using in situ-fixed brains reveal only modest metabolic changes in laforin-deficient mice. These changes are not replicated in malin-deficient or APBD mice, and are not normalized in rescued LD mice. Finally, we identify a pool of metabolically volatile malto-oligoglucans as a polyglucosan body- and neuroinflammation-associated brain energy source, and promising candidate biomarkers for LD and APBD, including malto-oligoglucans and the neurodegeneration marker CHI3L1/YKL40.PMID:39806098 | DOI:10.1038/s44318-024-00339-3

Sci Rep. 2025 Jan 13;15(1):1796. doi: 10.1038/s41598-025-86083-y.ABSTRACTSweet corn is highly susceptible to water deprivation, making it crucial to identify effective strategies for enhancing its tolerance to water deficit conditions. This study investigates the novel application of Spermine as a bio-stimulant to improve sweet corn (Zea mays L. var. saccharata) resilience under hydroponic water deficit conditions. Four genotypes (Dessert, Messenger, Tyson, and Royalty) were treated with Spermine (0.2 mM foliar application), polyethylene glycol 6000 (8% and 12%), and their combinations. The impacts on growth parameters, photosynthetic performance, and oxidative stress markers were evaluated. Spermine significantly enhanced biomass parameters, counteracting the severe reductions caused by PEG-induced water deprivation. In the Dessert and Tyson genotypes, total biomass increased by 145%, while it increased by 118% in Messenger and 110% in Royalty when treated with Spermine under severe water deprivation. However, Spermine treatment application did not recorded higher differences compared to control under non water deficit conditions. In the Dessert genotype, root length increased by 36.6% under combined treatment compared to 12% PEG alone. Spermine also mitigated reductions in shoot length, improved by 90.6% and specific leaf area, with a notable 272.6% increase in Tyson under severe water deficit. Photosynthetic performance, including chlorophyll and carotenoid levels, was enhanced, with a 103.1% increase in relative chlorophyll content in Dessert under severe water deprivation. Spermine also reduced oxidative damage, as indicated by a 48.7% decrease in malondialdehyde levels in Tyson, and increased peroxidase activity, enhancing antioxidant defense in Messenger under severe water deprivation. The quantum efficiency of Photosystem II, which was significantly reduced by water deficit, showed substantial improvement with Spermine treatment, with increases of 107.2% in Tyson and 99.4% in Royalty under moderate water deprivation. These results highlight the potential of Spermine as an effective strategy to improve sweet corn resilience under water-limited conditions, offering a novel approach for sustainable crop management.PMID:39806014 | DOI:10.1038/s41598-025-86083-y