PubMed

Plants (Basel). 2024 Aug 9;13(16):2212. doi: 10.3390/plants13162212.ABSTRACTCold stress affects the seed germination and early growth of winter rapeseed, leading to yield losses. We employed transmission electron microscopy, physiological analyses, metabolome profiling, and transcriptome sequencing to understand the effect of cold stress (0 °C, LW) on the cotyledons of cold-tolerant (GX74) and -sensitive (XY15) rapeseeds. The mesophyll cells in cold-treated XY15 were severely damaged compared to slightly damaged cells in GX74. The fructose, glucose, malondialdehyde, and proline contents increased after cold stress in both genotypes; however, GX74 had significantly higher content than XY15. The pyruvic acid content increased after cold stress in GX74, but decreased in XY15. Metabolome analysis detected 590 compounds, of which 32 and 74 were differentially accumulated in GX74 (CK vs. cold stress) and XY15 (CK vs. cold stressed). Arachidonic acid and magnoflorine were the most up-accumulated metabolites in GX74 subjected to cold stress compared to CK. There were 461 and 1481 differentially expressed genes (DEGs) specific to XY15 and GX74 rapeseeds, respectively. Generally, the commonly expressed genes had higher expressions in GX74 compared to XY15 in CK and cold stress conditions. The expression changes in DEGs related to photosynthesis-antenna proteins, chlorophyll biosynthesis, and sugar biosynthesis-related pathways were consistent with the fructose and glucose levels in cotyledons. Compared to XY15, GX74 showed upregulation of a higher number of genes/transcripts related to arachidonic acid, pyruvic acid, arginine and proline biosynthesis, cell wall changes, reactive oxygen species scavenging, cold-responsive pathways, and phytohormone-related pathways. Taken together, our results provide a detailed overview of the cold stress responses in rapeseed cotyledons.PMID:39204648 | PMC:PMC11360269 | DOI:10.3390/plants13162212

Plants (Basel). 2024 Aug 7;13(16):2184. doi: 10.3390/plants13162184.ABSTRACTGlobal sorghum production has been significantly reduced due to the occurrence of sorghum root rot caused by the fungus Fusarium graminearum. The utilization of biocontrol microorganisms has emerged as an effective strategy. However, the underlying mechanisms remain unclear. Therefore, the aim of this study was to investigate the effectiveness of biocontrol bacteria in inducing sorghum resistance against sorghum root rot and explore the potential induced resistance mechanisms through metabolomics analysis. The results revealed that the biocontrol bacteria Lnkb100, identified as Serratia marcescens (GenBank: PP152264), significantly enhanced the resistance of sorghum against sorghum root rot and promoted its growth, leading to increased seed weight. Targeted metabolomics analysis demonstrated that the highest concentration of the hormone IAA (indole-3-acetic acid) was detected in the metabolites of Lnkb100. Treatment with IAA enhanced the activity of disease-related enzymes such as SOD, CAT, POD and PPO in sorghum, thereby improving its resistance against sorghum root rot. Further untargeted metabolomic analysis revealed that IAA treatment resulted in higher concentrations of metabolites involved in the resistance against F. graminearum, such as geniposidic acid, 5-L-Glutamyl-taurine, formononetin 7-O-glucoside-6″-O-malonate, as well as higher concentrations of the defense-related molecules volicitin and JA. Additionally, "secondary bile acid biosynthesis" and "glycerophospholipid metabolism" pathways were found to play significant roles in the defense response of sorghum against fungal infection. These findings provide a reliable theoretical basis for utilizing biocontrol microorganisms to control sorghum root rot.PMID:39204620 | PMC:PMC11360247 | DOI:10.3390/plants13162184

Plants (Basel). 2024 Aug 6;13(16):2180. doi: 10.3390/plants13162180.ABSTRACTFusarium root rot caused by the Fusarium species complex significantly affects the yield and quality of Angelica sinensis, a valuable medicinal herb. Traditional management primarily relies on chemical fungicides, which have led to pathogen resistance, environmental hazards, and concerns regarding public health and the active components in A. sinensis. This study explores the efficacy of a novel plant-derived biopesticide Shi Chuang Zhi Feng Ning (T1; SCZFN), alongside Bacillus subtilis wettable powder (T2) and a chemical fungicide (T3), in controlling root rot and understanding their impacts on the rhizosphere microbial community and root metabolome. Results of the field experiment demonstrated that treatments T1 and T3 achieved control efficiencies of 73.17% and 75.45%, respectively, significantly outperforming T2 (39.99%) and the control. High-throughput sequencing revealed that all treatments altered the diversity and structure of microbial communities, with T1 and T2 reducing the abundance of taxa linked to root rot, such as Muribaculaceae spp., Humicola spp., Fusarium spp., and Mycochlamys spp. Treatment T1 notably enhanced beneficial bacterial taxa, including Acidobacteria spp., Nitrospira spp., and Pedosphaeraceae spp., involved in carbon cycling and plant growth promotion. Metabolomic analysis identified 39, 105, and 45 differentially expressed metabolites (DEMs) across the treatments, demonstrating T1's potential to modulate the root metabolome effectively. Further, a correlation analysis demonstrated a stronger correlation between distinct microorganisms with significant influence and DEMs of T1 treatment compared to other treatments. These findings underscore biopesticide SCZFN's role in enhancing plant health and disease suppression in A. sinensis, providing insights into its biocontrol mechanisms and supporting the development of sustainable disease management strategies in its cultivation.PMID:39204616 | PMC:PMC11360690 | DOI:10.3390/plants13162180

Pharmaceuticals (Basel). 2024 Aug 22;17(8):1101. doi: 10.3390/ph17081101.ABSTRACTPseudotrimezia juncifolia (Klatt) Lovo & A. Gil (Iridaceae) is a popularly known species with primarily ornamental economic interest. It has traditional uses as purgative, in conditions related to the menstrual cycle, for blood purification, as wound healing, and as anti-inflammatory. The anti-inflammatory and antinociceptive activities of the decoction from its aerial stems, corms, and stamens are described here with dereplication studies on LC-MS/MS supported by the GNPS platform, where phenolic compounds were annotated and correlated with its biological activity. The decoction was evaluated in chemical (formalin and capsaicin) and thermal (hot plate) induced nociception or carrageenan-induced inflammation in mice. Decoction (at 10, 30, or 100 mg/kg doses) significantly reduced formalin- or capsaicin-induced nociception. All doses also demonstrated an antinociceptive effect in the hot plate model increasing the time the animal spent in responding to thermal signal. Naloxone partially reversed the antinociceptive effect. An anti-inflammatory effect was observed since a reduction in cell migration, protein extravasation interleukin-1, and tumor necrosis factor production induced by carrageenan in the subcutaneous air pouch was quantified. Metabolomic analyses showed a predominance of phenolic substances, mainly flavonoids and chlorogenic acids. The literature showed that these two groups have significant anti-inflammatory and analgesic activity, and chemical data corroborate the pharmacological results observed.PMID:39204205 | DOI:10.3390/ph17081101

Pharmaceuticals (Basel). 2024 Aug 16;17(8):1079. doi: 10.3390/ph17081079.ABSTRACTMedicinal plants produce various bioactive molecules with potential anti-cancer properties with favorable safety profiles. We aimed to investigate the comprehensive composition of Vernonia amygdalina leaf extract and its cytotoxic effects via apoptosis in HeLa cells. The metabolomics approach using LC-MS/MS was conducted to gather the metabolite profile of the extract. Proteomics was performed to understand the comprehensive mechanistic pathways of action. The apoptosis was visualized by cellular staining and the apoptotic proteins were evaluated. V. amygdalina leaf extract exhibited dose-dependent cytotoxic effects on both HeLa and Vero cells after 24 h of exposure in the MTT assay with the IC50 values of 0.767 ± 0.0334 and 4.043 ± 0.469 µg mL-1, respectively, which demonstrated a higher concentration required for Vero cell cytotoxicity. The metabolomic profile of 112 known metabolites specified that the majority of them were alkaloids, phenolic compounds, and steroids. Among these metabolites, deacetylvindoline and licochalcone B were suggested to implicate cytotoxicity. The cytotoxic pathways involved the response to stress and cell death which was similar to doxorubicin. The upstream regulatory proteins, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and X-box binding protein 1 (XBP1), were significantly altered, supporting the regulation of apoptosis and cell death. The levels of apoptotic proteins, c-Jun N-terminal kinases (JNK), p53, and caspase-9 were significantly increased. The novel insights gained from the metabolomic profiling and proteomic pathway analysis of V. amygdalina leaf extract have identified crucial components related to apoptosis induction, highlighting its potential to develop future chemotherapy.PMID:39204184 | DOI:10.3390/ph17081079

Pharmaceuticals (Basel). 2024 Aug 15;17(8):1074. doi: 10.3390/ph17081074.ABSTRACTThe aims of this study were to explore the significant chemical changes in functional components induced by the traditional processing method and evaluate whether this method based on nine cycles of steaming and drying can effectively enhance the medicinal effects of Polygonatum cyrtonema rhizome. A global analysis on dynamic changes in secondary metabolites during nine processing cycles was performed, and the significantly differentially accumulated secondary metabolites were initially identified based on the secondary metabolome. Unsupervised principal component analysis (PCA), hierarchical clustering analysis (HCA), and orthogonal partial least squares discriminant analysis (OPLA-DA) on secondary metabolites clearly showed that processing significantly increased the global accumulation of secondary metabolites in processed P. cyrtonema rhizomes compared to unprocessed crude rhizomes. The first six processing cycles induced drastic changes in the accumulation of functional components, while the last three did not induce further changes. The accumulations of most functional components were significantly enhanced after the first three cycles and stabilized after six cycles; meanwhile, the first three cycles also led to numerous new components. However, the enhancing effects were unavoidably reversed or weakened under continued processing lasting 6-9 cycles. Furthermore, continued processing also reduced the contents of a small number of original components to undetectable levels. Processing induced some significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, among which the first three processing cycles enhanced the synthesis of various secondary metabolites and significantly affected the metabolisms of amino acids. In conclusion, this study not only reveals that processing can effectively enhance the medicinal effects, by two main mechanisms including enhancing chemical synthesis and inducing structural transformation of functional components, but also provides theoretical guidance for the optimization of the traditional processing method based on nine cycles of steaming and drying for achieving optimal effects on enhancing the medicinal effects of P. cyrtonema rhizome.PMID:39204179 | DOI:10.3390/ph17081074

Nutrients. 2024 Aug 14;16(16):2704. doi: 10.3390/nu16162704.ABSTRACTBACKGROUND: Obesity in pregnancy is linked to adverse clinical outcomes such as gestational diabetes. Recently, a risk score calculated by different ceramide concentrations was recognized as a new way to investigate cardiovascular risk. The aim was to analyze if the ceramide risk score and cardiometabolic risk vary between normal-weight, obese, and females with prior Roux-en-Y bypass surgery (RYGB) during pregnancy.METHODS: Three cohorts were investigated: first, 25 pregnant females with a history of RYGB; second, 19 with preconception BMI ≥ 35 kg/m2; and third, 19 normal-weight (preconception BMI < 25 kg/m2). Around the 24th to 28th weeks of gestation routine laboratory assessments, 3 h 75 g oral and intravenous glucose tolerance tests were carried out. The correlation of ceramide risk scores and ceramide ratios (Cer(d18:1/18:0)/Cer(d18:1/16:0)) with metabolic parameters was analyzed via Pearson correlation. The cohorts were compared via ANOVA and unpaired t-tests.RESULTS: The RYGB cohort had lower ceramide risk scores and ratios compared to obese pregnant females (7.42 vs. 9.34, p = 0.025; 0.33 vs. 0.47, p < 0.001). Ceramide risk score and ratio were found to correlate negatively with insulin sensitivity (measured with the Matsuda (r = -0.376, p = 0.031; r = -0.455, p = 0.008) and calculated sensitivity index (r = -0.358, p = 0.044; r = -0.621, p < 0.001) in females without RYGB. The ceramide risk score correlated positively with body fat in RYGB females (r = 0.650, p = 0.012).CONCLUSIONS: We found that females after RYGB have lower ceramide risk scores and ceramide ratios compared to obese pregnant females, possibly indicating lower metabolic risk.PMID:39203840 | DOI:10.3390/nu16162704

Microorganisms. 2024 Aug 22;12(8):1729. doi: 10.3390/microorganisms12081729.ABSTRACTHeat stress negatively affects lactation performance and rumen microbiota of dairy cows, with different breeds showing varying levels of heat tolerance. This study aimed to compare the lactation performance of Montbéliarde × Holstein (MH, n = 13) and Holstein (H, n = 13) cows under heat stress, and 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS) were used to determine the rumen microbiome and metabolome in experimental cows. The results indicated that during heat stress, milk yield (p = 0.101), milk fat yield, milk protein yield, milk protein, and milk lactose (p < 0.05) in Montbéliarde × Holstein cows were higher than those in Holstein cows, whereas milk yield variation and somatic cell counts (p < 0.05) were lower than those in Holstein cows. The sequencing results indicated that the rumen of Montbéliarde × Holstein cows was significantly enriched with beneficial bacteria, such as Rikenellaceae, Allobaculum, and YRC22 (p < 0.05). In addition, correlations were observed between specific ruminal bacteria and lactation performance. Ruminal metabolites related to antioxidant and anti-inflammatory properties were significantly higher (p < 0.05) in Montbéliarde × Holstein cows than in Holstein cows. Overall, Montbéliarde × Holstein cows showed higher production efficiency under heat stress, which may be related to the different rumen mechanisms of crossbred and Holstein cows in adapting to heat stress.PMID:39203571 | PMC:PMC11357101 | DOI:10.3390/microorganisms12081729

Microorganisms. 2024 Aug 12;12(8):1653. doi: 10.3390/microorganisms12081653.ABSTRACTProstate cancer (PCa) is initially sensitive to androgen deprivation therapy (ADT) but ultimately develops resistance and progresses to castration-resistant prostate cancer (CRPC) with a poor prognosis. This study indicated that some PCa patients and mice were more sensitive to ADT and entered CRPC later, which was related to the gut microbiota, especially the enrichment of Akkermansia muciniphila (AKK). Untargeted metabolomics analysis found that serum inosine level was upregulated in the treatment-sensitive group and significantly correlated with AKK. Furthermore, we revealed that intestinal permeability and serum lipopolysaccharide (LPS) levels increased in treatment-resistant mice. LPS stimulated the upregulation of p-NF-κB p65 and AR in tumors. Supplementing AKK metabolite inosine could alleviate intestinal barrier damage and reduce serum LPS level, ultimately inhibiting castration resistance via the LPS/NF-κB/AR axis. Finally, we constructed a predictive model for CRPC combining gut microbiota and clinical information (AUC = 0.729). This study revealed the potential mechanism of gut microbiota on CRPC and provided potential therapeutic targets and prognostic indicators.PMID:39203495 | PMC:PMC11356635 | DOI:10.3390/microorganisms12081653

Microorganisms. 2024 Aug 2;12(8):1576. doi: 10.3390/microorganisms12081576.ABSTRACTPseudomonas are known as higher producers of secondary metabolites with antimicrobial properties and plant growth promoters, including resistance induction. These mechanisms should be an alternative to pesticide use in crop production. Phakopsora pachyrhizi causes Asian soybean rust, representing a high loss of yield around the world. The objective of this paper was to evaluate the application of secondary metabolites produced by Pseudomonas aeruginosa LV strain from the semi-purified fraction F4A in soybean plants to induce plant resistance against P. pachyrhizi in field conditions. The experimental design was performed in randomized blocks with three replicates using two F4A doses (1 and 10 μg mL-1) combined or not with fungicides (Unizeb Gold® or Sphere Max®). The control treatment, with Uni + Sph, saponins, flavonoids, and sphingolipids, showed higher intensities in the plants. In contrast, plants treated with the F4A fraction mainly exhibited fatty acid derivatives and some non-identified compounds with nitrogen. Plants treated with Sphere Max®, with or without F4A10, showed higher intensities of glycosylated flavonoids, such as kaempferol, luteolin, narigenin, and apigenin. Plants treated with F4A showed higher intensities of genistein and fatty acid derivatives. These increases in flavonoid compound biosynthesis and antioxidant properties probably contribute to the protection against reactive oxygen species (ROS).PMID:39203418 | PMC:PMC11355946 | DOI:10.3390/microorganisms12081576

Microorganisms. 2024 Jul 26;12(8):1532. doi: 10.3390/microorganisms12081532.ABSTRACTArthrobotrys oligospora is a typical nematode-trapping (NT) fungus, which can secrete food cues to lure, capture, and digest nematodes by triggering the production of adhesive networks (traps). Based on genomic and proteomic analyses, multiple pathogenic genes and proteins involved in trap formation have been characterized; however, there are numerous uncharacterized genes that play important roles in trap formation. The functional studies of these unknown genes are helpful in systematically elucidating the complex interactions between A. oligospora and nematode hosts. In this study, we screened the gene AOL_s00004g24 (Ao4g24). This gene is similar to the SWI/SNF chromatin remodeling complex, which was found to play a potential role in trap formation in our previous transcriptome analysis. Here, we characterized the function of Ao4g24 by gene disruption, phenotypic analysis, and metabolomics. The deletion of Ao4g24 led to a remarkable decrease in conidia yield, trap formation, and secondary metabolites. Meanwhile, the absence of Ao4g24 influenced the mitochondrial membrane potential, ATP content, autophagy, ROS level, and stress response. These results indicate that Ao4g24 has crucial functions in sporulation, trap formation, and pathogenicity in NT fungi. Our study provides a reference for understanding the role of unidentified genes in mycelium growth and trap formation in NT fungi.PMID:39203374 | PMC:PMC11356499 | DOI:10.3390/microorganisms12081532

Molecules. 2024 Aug 13;29(16):3840. doi: 10.3390/molecules29163840.ABSTRACTStilbenes in the roots of Carex acuta and Carex lepidocarpa were studied. Root samples were extracted with 100% methanol and analyzed by HPLC and LC-MS. In this way, trans-resveratrol dimers (m/z 455 Da [M + H]+), trimers (m/z 681 Da [M + H]+) and tetramers (m/z 907 Da [M + H]+) were identified in the extracts. Using LC-NMR in stop-flow mode, pallidol and trans-ε-viniferin as dimers were identified. After the separation of individual peaks and their measurement by 1H NMR, cis and trans-miyabenol A as a tetramer and cis-miyabenol C as a trimer were identified. In the case of miyabenol A, it is a chromatographically inseparable mixture of cis and trans isomers in the ratio of 2:3 according to 1H NMR measurement. In the case of cis-miyabenol C, the Z-trans-trans-miyabenol C configuration was confirmed. The remaining unidentified peak with a practically identical UV-VIS spectrum to that of cis-miyabenol C is most likely another isomer of miyabenol C.PMID:39202919 | PMC:PMC11357264 | DOI:10.3390/molecules29163840

Molecules. 2024 Aug 13;29(16):3834. doi: 10.3390/molecules29163834.ABSTRACTGuatteria olivacea R.E. Fries is an Amazonian species known as 'envira-bobó' and 'envira-fofa' and is common in the states of Amazonas, Acre, and Pará. Recently, the essential oil from the leaves of this species has shown promising antitumor activity both in vitro and in vivo. The presence of isoquinoline-derived alkaloids, including aporphinoids and tetrahydroprotoberberine alkaloids, has also been previously reported. In our ongoing search for bioactive compounds from Annonaceae Amazonian plants, the bark of G. olivacea was investigated via classical chromatography techniques, which revealed nine compounds, eight isoquinoline-derived alkaloids, a rare alkaloid with a α-gem-dimethyltetradehydrocularine structure known as gouregine, seven known aporphinoid alkaloids: isopiline, O-methylisopiline, melosmine, 9-hydroxyiguattescine, dihydromelosmine, lysicamine, and guattouregidine, and one known pimaradiene diterpene: acanthoic acid. All the isolated compounds were described for the first time in the bark of G. olivacea, and their structures were elucidated by extensive analyses of their 1D and 2D NMR spectra in combination with MS data. The NMR data of the alkaloids isopiline, O-methylisopiline, melosmine, dihydromelosmine, and guattouregidine were revised due to incomplete data in the literature and some ambiguities. The in vitro cytotoxic activities of the isolated compounds were evaluated against human cancer (HepG2, KG-1a, and HCT116) and noncancerous (MRC-5) cell lines via the Alamar blue assay after 72 h of incubation. Among the compounds evaluated against human cancer cell lines, the most active was the oxoaporphine alkaloid lysicamine, which has strong activity against HCT116 cells, with an IC50 value of 6.64 µg/mL (22.79 µmol/L). Melosmine had a moderate effect on HCT116 cells, with an IC50 value of 16.77 µg/mL (49.70 µmol/L), whereas acanthoic acid had moderate effects on HepG2 and HCT116 cells, with IC50 values of 14.63 µg/mL (48.37 µmol/L) and 21.25 µg/mL (70.25 µmol/L), respectively.PMID:39202913 | PMC:PMC11357160 | DOI:10.3390/molecules29163834

Molecules. 2024 Aug 6;29(16):3718. doi: 10.3390/molecules29163718.ABSTRACTImmature citruses are an important resource for the pharmaceutical industry due to their high levels of metabolites with health benefits. In this study, we used untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics to investigate the changes associated with fruit size in immature citrus fruits in the first weeks of growth. Three orange cultivars (Citrus sinensis 'Navel', Citrus sinensis 'Valencia', and Citrus sinensis 'Valencia Late') and a mandarin (Citrus reticulata Blanco 'Fremont') were separated into eight fruit sizes, extracted, and analyzed. Statistical analyses revealed a distinct separation between the mandarin and the oranges based on 56 metabolites, with an additional separation between the 'Navel' orange and the 'Valencia' and 'Valencia Late' oranges based on 21 metabolites. Then, metabolites that evolved significantly with fruit size growth were identified, including 40 up-regulated and 31 down-regulated metabolites. This study provides new insights into the metabolite modifications of immature Citrus sinensis and Citrus reticulata in the first weeks of growth and emphasizes the significance of including early sampled fruits in citrus maturation studies.PMID:39202798 | PMC:PMC11357260 | DOI:10.3390/molecules29163718

Genome Biol. 2024 Aug 29;25(1):234. doi: 10.1186/s13059-024-03372-x.ABSTRACTBACKGROUND: UV-B, an important environmental factor, has been shown to affect the yield and quality of rice (Oryza sativa) worldwide. However, the molecular mechanisms underlying the response to UV-B stress remain elusive in rice.RESULTS: We perform comprehensive metabolic profiling of leaves from 160 diverse rice accessions under UV-B and normal light conditions using a widely targeted metabolomics approach. Our results reveal substantial differences in metabolite accumulation between the two major rice subspecies indica and japonica, especially after UV-B treatment, implying the possible role and mechanism of metabolome changes in subspecies differentiation and the stress response. We next conduct a transcriptome analysis from four representative rice varieties under UV-B stress, revealing genes from amino acid and flavonoid pathways involved in the UV-B response. We further perform a metabolite-based genome-wide association study (mGWAS), which reveals 3307 distinct loci under UV-B stress. Identification and functional validation of candidate genes show that OsMYB44 regulates tryptamine accumulation to mediate UV-B tolerance, while OsUVR8 interacts with OsMYB110 to promote flavonoid accumulation and UV-B tolerance in a coordinated manner. Additionally, haplotype analysis suggests that natural variation of OsUVR8groupA contributes to UV-B resistance in rice.CONCLUSIONS: Our study reveals the complex biochemical and genetic foundations that govern the metabolite dynamics underlying the response, tolerance, and adaptive strategies of rice to UV-B stress. These findings provide new insights into the biochemical and genetic basis of the metabolome underlying the crop response, tolerance, and adaptation to UV-B stress.PMID:39210441 | DOI:10.1186/s13059-024-03372-x

Genes Nutr. 2024 Aug 29;19(1):18. doi: 10.1186/s12263-024-00752-7.ABSTRACTThis study aimed to identify markers of postprandial dysglycemia in the blood of self-described healthy individuals using dry blood spots (DBS) as a sampling strategy. A total of 54 volunteers, including 31 women, participated in a dietary challenge. They consumed a high-fat, high-sugar mixed meal and underwent multiple blood sampling over the course of 150 min to track their postprandial responses. Blood glucose levels were monitored with a portable glucometer and individuals were classified into two groups based on the glucose area under the curve (AUC): High-AUC (H-AUC) and Low-AUC (L-AUC). DBS sampling was performed at the same time points as the assessment of glycemia using Whatman 903 Protein Saver filter paper. A gas chromatography-mass spectrometry-based metabolite profiling was conducted in the DBS samples to assess postprandial changes in blood metabolome. Higher concentrations of metabolites associated with insulin resistance were observed in individuals from the H-AUC group, including sugars and sugar-derived products such as fructose and threonic acid, as well as organic acids and fatty acids such as succinate and stearic acid. Several metabolites detected in the GC-MS analysis remained unidentified, indicating that other markers of hyperglycemia remain to be discovered in DBS. Based on these observations, we demonstrated that the use of DBS as a non-invasive and inexpensive sampling tool allows the identification of metabolites markers of dysglycemia in the postprandial period.PMID:39210266 | DOI:10.1186/s12263-024-00752-7

Nat Aging. 2024 Aug 29. doi: 10.1038/s43587-024-00695-z. Online ahead of print.ABSTRACTInhibition of S6 kinase 1 (S6K1) extends lifespan and improves healthspan in mice, but the underlying mechanisms are unclear. Cellular senescence is a stable growth arrest accompanied by an inflammatory senescence-associated secretory phenotype (SASP). Cellular senescence and SASP-mediated chronic inflammation contribute to age-related pathology, but the specific role of S6K1 has not been determined. Here we show that S6K1 deletion does not reduce senescence but ameliorates inflammation in aged mouse livers. Using human and mouse models of senescence, we demonstrate that reduced inflammation is a liver-intrinsic effect associated with S6K deletion. Specifically, we show that S6K1 deletion results in reduced IRF3 activation; impaired production of cytokines, such as IL1β; and reduced immune infiltration. Using either liver-specific or myeloid-specific S6K knockout mice, we also demonstrate that reduced immune infiltration and clearance of senescent cells is a hepatocyte-intrinsic phenomenon. Overall, deletion of S6K reduces inflammation in the liver, suggesting that suppression of the inflammatory SASP by loss of S6K could underlie the beneficial effects of inhibiting this pathway on healthspan and lifespan.PMID:39210150 | DOI:10.1038/s43587-024-00695-z

Nat Methods. 2024 Aug 29. doi: 10.1038/s41592-024-02392-6. Online ahead of print.ABSTRACTThe integration of spatial omics technologies can provide important insights into the biology of tissues. Here we combined mass spectrometry imaging-based metabolomics and imaging mass cytometry-based immunophenotyping on a single tissue section to reveal metabolic heterogeneity at single-cell resolution within tissues and its association with specific cell populations such as cancer cells or immune cells. This approach has the potential to greatly increase our understanding of tissue-level interplay between metabolic processes and their cellular components.PMID:39210066 | DOI:10.1038/s41592-024-02392-6

Nat Microbiol. 2024 Aug 29. doi: 10.1038/s41564-024-01799-3. Online ahead of print.ABSTRACTFungal fermentation of food and agricultural by-products holds promise for improving food sustainability and security. However, the molecular basis of fungal waste-to-food upcycling remains poorly understood. Here we use a multi-omics approach to characterize oncom, a fermented food traditionally produced from soymilk by-products in Java, Indonesia. Metagenomic sequencing of samples from small-scale producers in Western Java indicated that the fungus Neurospora intermedia dominates oncom. Further transcriptomic, metabolomic and phylogenomic analysis revealed that oncom-derived N. intermedia utilizes pectin and cellulose degradation during fermentation and belongs to a genetically distinct subpopulation associated with human-generated by-products. Finally, we found that N. intermedia grew on diverse by-products such as fruit and vegetable pomace and plant-based milk waste, did not encode mycotoxins, and could create foods that were positively perceived by consumers outside Indonesia. These results showcase the traditional significance and future potential of fungal fermentation for creating delicious and nutritious foods from readily available by-products.PMID:39209985 | DOI:10.1038/s41564-024-01799-3

Nat Commun. 2024 Aug 29;15(1):7511. doi: 10.1038/s41467-024-51754-3.ABSTRACTThe formation of new ribosomes is tightly coordinated with cell growth and proliferation. In eukaryotes, the correct assembly of all ribosomal proteins and RNAs follows an intricate scheme of maturation and rearrangement steps across three cellular compartments: the nucleolus, nucleoplasm, and cytoplasm. We demonstrate that usnic acid, a lichen secondary metabolite, inhibits the maturation of the large ribosomal subunit in yeast. We combine biochemical characterization of pre-ribosomal particles with a quantitative single-particle cryo-EM approach to monitor changes in nucleolar particle populations upon drug treatment. Usnic acid rapidly blocks the transition from nucleolar state B to C of Nsa1-associated pre-ribosomes, depleting key maturation factors such as Dbp10 and hindering pre-rRNA processing. This primary nucleolar block rapidly rebounds on earlier stages of the pathway which highlights the regulatory linkages between different steps. In summary, we provide an in-depth characterization of the effect of usnic acid on ribosome biogenesis, which may have implications for its reported anti-cancer activities.PMID:39209816 | DOI:10.1038/s41467-024-51754-3