Search Results (3,953)

Understanding how plants respond to water limitation is increasingly important under accelerating climate change. Lycoris aurea, a widely distributed ornamental and medicinal bulbous plant, frequently inhabits environments with fluctuating soil moisture, yet its molecular drought-response mechanisms remain largely unexplored. In this study, we investigated L. aurea growing under field-based, in situ soil moisture regimes, comparing low (~20% soil water content) and high (~40% soil water content) conditions. We combined soil property assessments with high-resolution transcriptomic and untargeted metabolomic profiling to characterize the adaptive responses of bulb tissues under contrasting soil water conditions. Although total nitrogen, phosphorus, and potassium levels were comparable across treatments, soil moisture, representing the primary contrasting field condition, and soil pH, a correlated environmental factor, were significantly associated with variation in gene expression and metabolite accumulation (p < 0.05, n = 3). Transcriptome analyses identified a total of 1034 differentially expressed genes enriched in pathways related to amino acid metabolism, cuticle formation, cell wall modification, and osmotic adjustment. Metabolomic analysis identified a total of 1867 differentially expressed metabolites belonging to carboxylic acids and prenol lipids, showing alterations involved in amino acids, lipids, phenolic acids, and alkaloids associated with osmoprotection, membrane stabilization, and structural reinforcement under low soil moisture. Pathway-based integration analysis highlighted four core pathways, including “alanine, aspartate and glutamate metabolism” (p = 0.00371) and “cutin, suberine and wax biosynthesis” (p = 0.00873), as central hubs linking transcriptional regulation with metabolic reconfiguration. Gene-metabolite-soil correlation networks further demonstrated that drought adaptation arises from tightly coordinated biochemical and structural adjustments rather than shifts in nutrient acquisition. Together, this species-specific study provides a comprehensive multi-omics framework for understanding drought tolerance in L. aurea, reveals key molecular targets associated with plant resilience, and offers potential targets and insights for the conservation of drought-resilient Lycoris cultivars. Full article

Background: The current rise in multidrug-resistant pathogens highlights the urgent need for the discovery of novel antibacterial agents with potential clinical applications. A considerable proportion of these developed resistances may be attributable to the intrinsic response of bacteria to antibiotic-induced stress conditions in the environment. Consequently, the identification and characterization of genetic alterations in physiological processes in response to antibiotics represent promising strategies for the discovery and characterization of naturally produced novel antibacterial agents. This study investigated the antimicrobial activity of an antimicrobial active isolate Actinomadura coerulea derived from a meerkat fecal sample. Methods: The production of secondary metabolites that potentially compromise bacterial cell wall integrity was confirmed by the induction of promoter activity in whole-cell biosensors in which an antibiotic-inducible promoter was fused to the luciferase cassette. During plate-based biosensor assays, we identified naturally resistant Bacillus subtilis colonies growing in the zone of inhibition around A. coerulea colonies. After these successive rounds of selection, highly resistant spontaneous B. subtilis mutants had evolved that were subjected to whole-genome sequencing. Results: Non-silent mutations were identified in pssA, which encodes a phosphatidylserine synthase; mdtR, as a gene for the repressor of multidrug resistance proteins, and yhbD, whose function is still unknown. A new cinnamycin-like molecule, coerumycin, was discovered based on the physiological role of PssA and comprehensive genomic analysis of A. coerulea. Additional experiments with cell extracts containing coerumycin as well as the cinnamycin-like compound duramycin confirmed that the interaction between coerumycin and the bacterial cell envelope is inhibited by a loss-of-function mutation in pssA. Conclusion: Our approach demonstrates that combining the exploration of niche habitats for actinomycetes with whole-cell biosensor screening and characterization of natural resistance development provides a promising strategy for identifying novel antibiotics. Full article

Gut microbial communities perform a multitude of physiological functions for their hosts; however, the drivers and distribution patterns of microbiota in wild animals remain largely underexplored. Our understanding of how these microbial communities are structured across hosts in natural environments—especially within a single host species remains limited. Here, we characterized the gut microbial communities of four species of ocean fish using 16S rRNA high-throughput sequencing to investigate the structural and functional features of these microbial communities across different fish species. By comparing the gut microbiota compositions of blue sharks (Prionace glauca), bigeye tuna (Thunnus obesus), sickle pomfret (Taractichthys steindachneri), and mackerel (Scomber japonicus), we identified several microbial taxa—including Photobacterium, Pelomonas, Ralstonia, and Rhodococcus—that were consistently detected across all samples, indicating they likely constitute a “common microbiota”. However, the relative abundances of these taxa varied significantly among species, with Photobacterium exhibiting the highest diversity. Blue sharks and bigeye tuna harbored relatively few dominant microbial species, but the abundance of these dominant bacteria was remarkably high, and inter-individual differences in microbial composition were pronounced. In contrast, mackerel and sickle pomfret contained a greater variety of dominant genera, each with low relative abundance, and inter-individual differences within the same species were minimal. Functionally, metabolic pathways, biosynthesis of secondary metabolites, and microbial metabolism represent the predominant functional categories of the intestinal microbiota in marine fish, with only minor interspecific differences observed. In contrast, biosynthesis of amino acids, ABC transporters, and two-component systems are the key functional pathways that exhibit significant variations across different fish species. Collectively, these findings reveal differences in gut microbial stability among different fish hosts. Such variations may be associated with the hosts’ energy utilization needs, and changes in the gut microbiota play a critical role in shaping the diverse survival strategies of these fish species. Full article

The species Inula helenium belongs to the genus Inula (Asteraceae) and exhibits antibacterial and anti-inflammatory properties. It is used in respiratory and skin diseases. Its bioactivity is attributed to its eudesmanolide components, mainly to alantolactone and isoalantolactone. These components were isolated in high purity from the plant’s dried roots, either via multiple column chromatography separations or via repeated recrystallization. Two more eudesmanolides structurally similar to their parent compounds were isolated, namely 11,13-dihydro-alantolactone and 11,13-dihydro-isoalantolactone. The secondary metabolites and their derivatives were characterized in detail, for the first time, via NMR spectroscopy, GC-MS, and HRMS. Synthetic modification of the natural component structure was considered necessary for structure–activity relationship studies and biological tests. Thus, each compound was converted to its nitrile and then to the corresponding acid, or to its azide derivative and then corresponding amine. Antioxidant studies were conducted on the parent compounds, their derivatives, and the methanolic and hexane plant extracts using the DPPH radical method. The study revealed a strong antioxidant capacity of the methanolic extract. Acaricidal studies of both natural products and synthetic analogs against Varroa destructor and the comparison of their activity with the parent natural product costic acid, as well as one of its synthetic congeners, indicated that the “from nature to synthesis and vice versa” approach led to active compounds as well as to meaningful conclusions regarding the “pharmacophore” groups in the structural framework of the acaricides. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovitis, in which fibroblast-like synoviocytes (FLSs) serve as the primary effector cells that drive the destruction of joints. Baicalin has previously demonstrated efficacy in significantly ameliorating joint symptoms in rats with CIA. As such, this study aims to investigate its underlying molecular mechanisms and impact on the FLSs of rats with CIA through an integrated proteomics and transcriptomics analysis. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted based on two datasets; it revealed that the retrograde endocannabinoid signaling pathway—associated with susceptibility to RA—is the only one involved in both the signaling and metabolic processes modulated by baicalin. Nineteen differentially expressed proteins (DEPs) downregulated by baicalin comprise seventeen subunits of NADH dehydrogenase and two receptors, glutamate receptor 2 (GRIA2) and γ-aminobutyric acid receptor subunit alpha-5 (GABRA5). Three differential metabolites (DMs) were also affected by baicalin: γ-aminobutyric acid (GABA) and phosphatidylcholine (PC) were upregulated and phosphatidylethanolamine (PE) was downregulated. Our findings suggest that the baicalin-mediated alleviation of joint synovitis is closely related to the upregulation of GABA and PC; downregulation of GRIA2, GABRA5, and PE; and preservation of mitochondrial homeostasis within the retrograde endocannabinoid signaling pathway in FLSs. Full article

Mass spectrometry imaging (MSI) is an innovative analytical technique that integrates chemical analysis with spatial localization, enabling label-free, in situ detection and visualization of diverse biomolecules within tissue sections. This review summarizes the recent advances in the application of MSI to neurological disorders, with a focus on Parkinson’s disease, Alzheimer’s disease, schizophrenia, and traumatic brain injury. Studies have demonstrated that MSI can delineate the spatial heterogeneity of disease-related molecules—such as neurotransmitters, lipids, and metabolites—thereby providing new perspectives for understanding the pathological mechanisms of neurodegenerative and psychiatric diseases. Platforms including MALDI-MSI and DESI-MSI have been effectively employed for visualizing drug distribution, characterizing lipid metabolic pathways, and identifying spatial biomarkers. Although challenges remain in quantitative accuracy, spatial resolution, and the detection of low-abundance molecules, advances in high-resolution mass spectrometry, single-cell-level imaging, and multi-omics integration are expected to further enhance the utility of MSI in the investigation of brain diseases. Full article

Ramaria flavobrunnescens is an ectomycorrhizal coral mushroom that is often found growing in eucalyptus forests. The mushroom has been linked to accidental ingestion-associated livestock poisonings in South America, though the toxicological agent has not yet been described. Mushroom samples identified as R. flavobrunnescens were analyzed by liquid chromatography high-resolution mass spectrometry (LC–MS/MS) to determine the potential source of the toxicity, and to provide a metabolomic profile of the species. Previously reported Ramaria secondary metabolites were detected, including ramarins, ramariolides, pistillarin and arsenic-containing compounds. A number of bacterial species were isolated from R. flavobrunnescens that produced iron-chelating cyclic peptides, which were detected in the mushroom samples. Interestingly, we detected a series of eucalyptus tree secondary metabolites in abundance from R. flavobrunnescens fruiting bodies, some of which have reported toxicities and bioactivities. To our knowledge, this is the first report of eucalyptus secondary metabolites in a mushroom. The diversity of secondary metabolites identified in the mushroom extracts provides insight into the potential complex ecological interactions between R. flavobrunnescens, its associated microbiota, and its mycorrhizal interaction with eucalyptus trees. Full article

Drought stress severely restricts plant growth and substantially reduces crop productivity. Although drought-response mechanisms have been extensively characterized within individual plant species, the conserved metabolic strategies shared across species remain insufficiently understood. To elucidate both conserved and species-specific metabolic mechanisms underlying drought adaptation, we performed an integrated transcriptomic and metabolomic analysis in rice, maize, and tomato. Profiling of 543 annotated metabolites revealed strikingly divergent baseline metabolic landscapes: tomato leaves were enriched in triglycerides and anthocyanins, whereas maize and rice accumulated higher levels of glycerophospholipids, tricin-derived flavonoids, and B vitamins. Under drought conditions, these differences were further reflected in the distinct sets of differentially accumulated metabolites (DAMs) detected in tomato (121), rice (98), and maize (94). Despite these species-specific signatures, we identified a conserved drought-responsive module consisting of five phenolamides that were consistently induced across all three species. Reconstruction of the associated regulatory network uncovered divergent enzymatic control strategies governing phenolamide biosynthesis: the drought-induced BAHD acyltransferases OsPHT4 in rice and SlPHT3 in tomato exhibited broad-spectrum catalytic activities, whereas the maize homolog ZmPHT4 fulfilled a similar biosynthetic role through constitutive, non-drought-inducible activity. Together, this study provides a comprehensive metabolic framework for plant drought response and demonstrates that extensive species-specific metabolic architectures and transcriptional regulatory divergence coexist beneath a conserved core metabolomic response, offering promising targets for the precise genetic enhancement of crop drought tolerance. Full article

Eugenia pyriformis Cambess., popularly known as uvaia, is a native Brazilian species belonging to the Myrtaceae family that has attracted pharmacological interest due to its richness in bioactive secondary metabolites. Previous studies have reported antimicrobial and antioxidant activities of the essential oil obtained from its leaves, reinforcing its therapeutic potential. In this context, the present study aimed to extract and characterize the essential oil from E. pyriformis leaves cultivated in the mountainous region of Rio de Janeiro, Brazil, and to evaluate its anti-inflammatory potential through in vitro and in vivo models. Gas chromatography mass spectrometry (GC–MS) analysis revealed a predominance of sesquiterpene hydrocarbons, mainly γ-muurolene, δ-cadinene, and β-caryophyllene. The oil exhibited significant anti-edematogenic activity in carrageenan-, prostaglandin E₂-, and bradykinin-induced paw edema models in adult female Swiss mice, suggesting modulation of inflammatory mediators, possibly through inhibition of the cyclooxygenase (COX) pathway. Conversely, no effect was observed in the compound 48/80-induced model, indicating the absence of activity on histamine- and serotonin-mediated processes. In vitro assays demonstrated that the oil reduced TNF-α and IL-1β gene expression in RAW 264.7 macrophages, confirming its ability to modulate pro-inflammatory cytokines. Taken together, these findings demonstrate that the essential oil of E. pyriformis exerts anti-inflammatory activity through multiple targets. Full article

Delayed harvesting of grapes can alter fruit quality and plays an important role in alleviating the problem of market saturation during peak seasons, as well as in regulating the supply period of grapes. In this study, by conducting a comparative analysis of fruit quality, metabolomics (aroma compounds) and transcriptome sequencing of ‘Shine Muscat’ grapes harvested at six different on-tree ripening stages after maturity, we found that: (1) delayed harvesting led to dramatic variation in berry color change (light green to yellow) with a significant increase in soluble solids (19.5 to 20.89 Brix); (2) A total of 25 volatile aroma compounds was identified in collected berry samples, while trans-2-hexenal and hexanal exhibited the highest concentrations in all samples, marking them as key volatile compounds in ‘Shine Muscat’ grapes. Notable variation in the concentrations of linalool, n-butanol, benzyl alcohol, phenylethanol, β-citronellol, and propionic anhydride were recorded in selected harvest periods. OAV analysis results show that linalool has the largest OAV among the detected compounds, and its OAV proportion increased from 53% to 95% during the six sampling periods of ‘Shine Muscat’; (3) Transcriptome sequencing of selected samples demonstrated a positive correlation between eight terpene-synthesis-related genes and linalool accumulation. Furthermore, genes within the MEP pathway (specifically VvTPS55, VvTPS59) and several transcription factors were associated with terpenoids metabolism. Based on soluble solids and OAV results, T18–T22 period (18–22 weeks post-flowering) can become good quality on-vine storge berries. The gene expression profile and developmental patterns of metabolites in MEP pathway may helpful in functional characterization of candidate genes related to terpenoid metabolism in future studies. Full article

Type 1 Diabetes (T1D) is thought to result from the interaction of genetic and environmental factors, with different studies highlighting a potential role for the gut microbiota and its metabolites in modulating immune responses and disease development. We hypothesized that patients with T1D exhibited altered levels of circulating bacterial metabolites compared with healthy controls (HC), and that these metabolite profiles were associated with key demographic, clinical, and analytical features of the disease. A total of 91 T1D patients and 58 HC were recruited. Plasma samples were collected and analyzed with gas chromatography coupled to mass spectrometry for the detection of the metabolites: short-chain fatty acids (SCFAs: acetate [AA], propionate [PA], isobutyrate [IBA], butyrate [BA], isovalerate [IVA], valerate [VA], and methyl valerate [MVA]), medium-chain fatty acids (MCFAs: hexanoate [HxA] and heptanoate [HpA]) and para-cresol (p-cresol). We also calculated the ratios between the different SCFAs with AA. T1D patients showed significantly higher circulating AA levels than HC, along with reduced PA/AA and IBA/AA ratios, indicating an altered SCFA profile. SCFA diversity was lower in T1D patients, with reduced detection of BA, and total SCFA levels were increased mainly due to elevated AA. AA levels were higher and SCFA ratios lower in women with T1D compared with healthy women, while p-cresol levels were higher in men with T1D than in healthy men. In T1D patients, AA levels positively correlated with HbA1c, whereas PA/AA, IBA/AA, and BA/AA ratios showed negative correlations, particularly in women. MV/AA and non-AA/AA ratios were inversely associated with glucose levels, again, mainly in women. p-cresol levels correlated positively with age and ferritin and were higher in T1D patients with liver dysfunction or hypertension. Therefore, we can conclude that T1D is associated with a marked alteration in circulating gut-derived metabolites, characterized by increased AA levels, particularly in women, and an imbalance in SCFA ratios that correlates with glycemic control. These findings, together with the associations observed for p-cresol and metabolic comorbidities, support a role for the gut microbiota–host metabolic axis in T1D. Full article

Lung cancer (LC) remains the leading cause of cancer-related death worldwide, largely due to late-stage diagnosis and the limited performance of current screening strategies. In this preliminary study, headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME/GC-MS) was used to comprehensively characterize the urinary volatilome of LC patients and healthy controls (HCs), with the dual aim of defining an LC-associated volatilomic signature and identifying volatile organic metabolites (VOMs) with discriminatory potential. A total of 56 VOMs spanning multiple chemical classes were identified, revealing a distinct metabolic footprint between groups. LC patients exhibited markedly increased levels of terpenoids and aldehydes, consistent with heightened oxidative stress, including lipid peroxidation, and perturbed metabolic pathways, whereas HCs showed a predominance of sulphur-containing compounds and volatile phenols, likely reflecting active sulphur amino acid metabolism and/or microbial-derived processes. Multivariate modelling using partial least squares-discriminant analysis (PLS-DA, R² = 0.961; Q² = 0.941; p < 0.001), supported by hierarchical clustering, demonstrated robust and clearly separated group stratification. Among the detected VOMs, octanal, dehydro-p-cymene, 2,6-dimethyl-7-octen-2-ol and 3,7-dimethyl-3-octanol displayed the highest discriminative power, emerging as promising candidate urinary biomarkers of LC. These findings provide proof-of-concept that HS-SPME/GC-MS-based urinary volatilomic profiling can capture disease-specific molecular signatures and may serve as a non-invasive approach to support the early detection of LC, warranting validation in independent cohorts and integration within future multi-omics diagnostic frameworks. Full article

Background: Persistent liver pathology despite a sustained virologic response (SVR) to hepatitis C virus (HCV) therapy is a major clinical concern. This is particularly relevant for people with HIV (PWH) with HCV coinfection, a population prone to accelerated liver disease progression. This study aimed to characterize the plasma miRNA profile in PWH with cirrhosis one year after successful completion of HCV therapy, and to explore their relationship with metabolite alterations. Methods: This cross-sectional study enrolled 47 PWH who achieved HCV clearance with antiviral therapy. Using plasma samples collected approximately one year after completion of HCV therapy, participants were stratified into two groups based on liver stiffness measurement (LSM): compensated cirrhosis (n = 32, LSM ≥ 12.5 kPa) and non-cirrhosis (n = 15, LSM < 12.5 kPa). Plasma miRNAs and metabolites were determined using small RNA sequencing and untargeted capillary electrophoresis-mass spectrometry (CE-MS), respectively. Significantly differentially expressed (SDE) miRNAs were identified using generalized linear models (GLM) with a negative binomial distribution, and their correlation with metabolite levels was quantified using Spearman’s correlation. Results: In the cirrhosis group (n = 32), we identified a distinct signature of 15 SDE miRNAs (9 upregulated, 6 downregulated) compared to the non-cirrhotic group (n = 15), showing hsa-miR-10401-3p, hsa-miR-548ak, hsa-miR-141-3p, and hsa-miR-3940-3p the largest expression changes. miRNA-gene interaction and pathway enrichment analysis suggested that these 15 SDE miRNAs potentially regulate multiple genes involved in immune response and amino acid metabolism. In addition, correlation analyses with our metabolomic data revealed significant associations between specific SDE miRNAs and amino acids and their derivatives. Specifically, the expression of upregulated miRNAs (e.g., hsa-miR-10401-3p and hsa-miR-16-5p) was positively correlated with plasma levels of L-methionine and its derivatives, while downregulated miRNAs (e.g., hsa-miR-625-5p) were inversely correlated with L-tryptophan. Conclusions: In cirrhotic PWH with history of HCV coinfection, a distinct plasma miRNA signature linked to dysregulated amino acid metabolism is found one year after completion of HCV therapy. This underscores that the HCV cure does not equate to complete hepatic recovery, highlighting the critical need for long-term monitoring in this high-risk population. Full article

Background: Honeybees sustain vital ecological roles through foraging behavior, which provides pollination services and is likely regulated by dopamine signaling coupled to brain energy metabolism. However, the genetic and metabolic mechanisms underlying this regulation remain unclear. Methods: We treated honeybee workers with the dopamine receptor agonist bromocriptine and employed an integrative approach, combining liquid chromatography–mass spectrometry (LC–MS) metabolomics with single-nucleus RNA sequencing (snRNA-seq). Results: Metabolomics revealed increased levels of N6-carboxymethyllysine (CML) and a coordinated shift in central carbon metabolites, including higher glucose, pyruvate, and lactate within glycolysis, and ribose-5-phosphate in the pentose phosphate pathway (PPP). Integration with transcriptomics showed heterogeneous responses: glial cells exhibited higher glycolysis pathway scores and upregulated hexokinase expression compared to neurons, whereas major PPP enzymes were upregulated in both glial and neuronal subsets. Conclusions: These findings suggest that dopamine receptor activation is associated with altered whole-brain metabolic profiles and concurrent, cell-type-specific upregulation of glycolytic and PPP enzyme genes, particularly in glia. This study characterizes these neuro-metabolic associations, offering insights into the cellular and metabolic basis of foraging behavior in worker bees. Full article

Background: Metabolic reprogramming is increasingly recognized as a hallmark of endometrial cancer, yet tissue-based metabolic signatures remain insufficiently defined. Methods: Untargeted metabolomics was performed on paired endometrial cancer (n = 10) and adjacent normal tissues (n = 10). Differential metabolites were identified through multivariate and univariate analyses. KEGG enrichment characterized altered pathways, while Random Forest and SVM were used for machine-learning-based feature prioritization. ROC analyses were conducted to evaluate the discriminative potential of selected metabolites. Results: 300 metabolites were significantly altered. Tumor tissues showed increased sphingolipid metabolism, glutathione metabolism, and arachidonic acid metabolism, alongside decreased bile acid, phenylalanine, and steroid biosynthesis. Machine learning converged on six key metabolites that demonstrate strong tissue-discriminative capacity. Conclusions: Endometrial cancer exhibits a distinct metabolic profile characterized by lipid remodeling and redox adaptation. The six metabolites identified through machine-learning-based analyses represent candidate metabolic features associated with endometrial cancer and provide a foundation for future mechanistic studies and validation in larger, independent cohorts. Full article