Search Results (5,463)

Introduction: Hepatic fibrosis represents a critical intermediate stage in the progression from chronic liver disease to cirrhosis and ultimately hepatocellular carcinoma. Spirulina platensis, a microorganism rich in bioactive compounds, contains several functional components, among which are Spirulina polysaccharides and phycocyanin. Both have been demonstrated to exhibit multiple biological activities, including antioxidant, anti-inflammatory, and immunomodulatory effects. However, the intervention effects and mechanisms of Spirulina polysaccharides and phycocyanin on CCl₄-induced hepatic fibrosis remain unclear. 16S rRNA sequencing and non-targeted metabolomics technologies are employed to analyze bacterial taxa and metabolic pathways. Methods: Hepatic fibrosis (HF) was induced in male C57BL/6J mice via intraperitoneal injection of CCl₄. After 1 week of modeling, mice were intragastrically administered SPP or PC for 4 consecutive weeks. Gut microbiota composition and fecal metabolites were analyzed using 16S rRNA gene sequencing and metabolomics. Results: SPP showed more pronounced protective effects than PC under the experimental conditions used in this study. SPP treatment significantly alleviated hepatic fibrosis in mice. Compared with the model group, SPP administration markedly increased the abundance of bacterial taxa and modulated fecal metabolic profiles, including short-chain fatty acid metabolism. Conclusions: SPP treatment mitigates CCl₄-induced hepatic fibrosis in mice. These protective effects may be associated with the modulation of gut microbiota composition and fecal metabolic pathways, including those related to short-chain fatty acid metabolism. Full article

The increasing use of bioplastics in packaging applications necessitates rigorous evaluation of their fate in real waste management systems. While bioplastics are often marketed as biodegradable, their actual behavior under mesophilic anaerobic digestion (AD) is frequently insufficiently understood and often overestimated in commercial claims. Polylactic acid (PLA), one of the most widely produced bio-based polymers, has been widely characterized under these conditions, but little is known about the metabolomic changes associated with its biodegradation under mesophilic anaerobic conditions. This study investigates the mesophilic AD (37 °C for more than 3 months) of PLA films (2.5 × 2.5 cm) co-digested with the organic fraction of municipal solid waste (OFMSW). Biogas production and energy yield evaluation were assessed for AD, along with chemical parameters and metabolomic analyses. PLA biodegradation, calculated according to ISO 15985:2014, reached values close to 100% after more than 3 months, highlighting a prolonged lag phase under mesophilic AD conditions. The biogas production yielded about 380 Nm³ per t of volatile solids. Metabolomic profiling during AD revealed that the onset of PLA biodegradation, highlighted also by biogas emission, coincides with the appearance of key metabolites associated with PLA hydrolysis. These findings demonstrate that the mesophilic anaerobic co-digestion of PLA films with OFMSW did not cause any inhibition effect on biogas production. The results demonstrate the feasibility of incorporating PLA into existing organic waste treatment systems, thereby supporting both energy recovery and sustainable waste management. Full article

Low temperature critically pressures insect pest distributions and population dynamics; however, integrated understanding of cold stress responses in invasive pests, particularly at the adult stage, remains limited. Here, we investigated the integrated physiological, biochemical, metabolomic and transcriptomic responses of Tuta absoluta (Meyrick, 1917) exposed to control (CT: 25 °C), moderate cold stress (MCS: 15 °C) and severe cold stress (SCS: 5 °C) conditions. Our results revealed that low-temperature stress impaired T. absoluta emergence, survival, fecundity and egg hatching in a stress intensity-dependent manner. Also, low temperature reduced the olfactory-mediated host-seeking behaviors of T. absoluta females. The biochemical analyses revealed depletion of triglycerides, glycogen and Na⁺/K⁺-ATPase activity alongside compensatory trehalose accumulations, while antioxidant enzyme activities (SOD, POD, CAT) were differentially modulated indicating progressive oxidative defense impairment under low temperature. Untargeted metabolomic profiling identified extensive differential metabolite accumulations, revealing systematic dysregulation of alkaloid biosynthesis, amino acid metabolism and central carbon metabolic pathways. Transcriptomic analysis identified several differentially expressed genes (DEGs) enriched in thermogenesis, oxidative phosphorylation, MAPK signaling and neurodegeneration-associated pathways. Furthermore, integrative transcriptome–metabolome analysis revealed coordinated gene–metabolite regulatory networks scaling systematically with cold stress intensity. These findings advance our mechanistic understanding of thermal stress adaptations in T. absoluta and may contribute to the development of climate-informed pest management strategies. Full article

Pleurotus pulmonarius (Fr.) Quél. is a commercially important edible mushroom recognized for its nutritional and nutraceutical value. However, the influence of alternative agricultural waste substrates on its biochemical composition remains insufficiently characterized. This study investigated the effect of four cultivation substrates, coconut waste (PpC), paddy husk (PpP100), paddy husk supplemented with sawdust (PpP20) and rubberwood sawdust as control (PpS), on the macro- and microelement profile, secondary metabolite composition, and antioxidant activity of P. pulmonarius fruiting bodies. Analytical methods included ICP-MS and FAAS for elemental analysis; GC-MS for fatty acid, carbohydrate and phenolic profiling; Kjeldahl method for total protein; FTIR spectroscopy for structural characterization; and four complementary antioxidant assays (DPPH, ABTS, CUPRAC, FRAP). Coconut waste substrate promoted the highest protein accumulation and elevated concentrations of iron, zinc, and specific phenolic acids (vanillic, protocatechuic). Paddy husk-based substrates favored carbohydrate accumulation, particularly trehalose, while sawdust supported the greatest lipid content, dominated by linoleic acid. Potassium was the predominant macroelement across all variants. Antioxidant activity was highest in PpP100 and PpC across all four assays. FTIR confirmed a mushroom-specific polysaccharide, protein, and lipid profile in all samples. The results demonstrate that agricultural waste represents sustainable, value-added alternatives to conventional sawdust, capable of maintaining or enhancing the nutritional and nutraceutical quality of oyster mushrooms to enhance agricultural production. Full article

Postpartum dairy cows fed more rapidly fermentable starch sources have depressed dry matter intake (DMI), compounding the risk of negative energy balance and hepatic lipid accumulation. Rumen-protected choline (RPC) is supplemented to periparturient dairy cows to facilitate hepatic lipid export. Our objective was to evaluate the interaction of dietary starch fermentability (DF) and RPC supplementation on postpartum DMI and performance. Prepartum supplementation of a low dose of RPC (no RPC [C−] vs. RPC [C+; 30 g/d]) began 21 d before the expected calving date for Holstein cows with at least one parity. Postpartum, cows were assigned to 1 of 4 postpartum treatments for 21 d with a 2 × 2 factorial arrangement of starch fermentability rate (low [dry-rolled corn; LFERM] vs. high [dry-rolled wheat; HFERM]) and RPC (C− vs. C+). Prepartum, C+ decreased DMI by 2.3 kg compared with C−, but there was no evidence of treatment effect on DMI postpartum. Time and DF interacted on milk yield, with HFERM increasing milk yield after d 3 compared with LFERM. Compared with LFERM, HFERM decreased milk fat content but not fat yield. For blood metabolites, C+ decreased plasma beta-hydroxybutyrate by 0.3 mmol/L and tended to increase glucose concentration compared to C−. In conclusion, supplementation with RPC at a low rate of inclusion reduced DMI in prepartum cows and decreased postpartum plasma BHB concentrations. Further work is required to elucidate potential mechanisms of action for RPC-mediated reductions in DMI. Full article

Chronic heart failure [CHF] is a progressive clinical syndrome characterized by structural and functional impairment of the myocardium, in which energy metabolic remodeling plays a central role. Increasing evidence suggests that metabolic disturbances in CHF are not only a consequence of reduced cardiac output but also active regulators of epigenetic remodeling, thereby contributing to disease progression. Key metabolites, including α-ketoglutarate, acetyl-CoA, NAD⁺, S-adenosylmethionine, succinate, and 2-hydroxyglutarate, influence the activity of DNA methyltransferases, histone-modifying enzymes, and other chromatin regulators, thereby linking metabolic status to transcriptional control. Through these mechanisms, metabolic abnormalities promote persistent activation of pathological gene programs associated with cardiomyocyte hypertrophy, fibrosis, inflammation, apoptosis, and mitochondrial dysfunction, forming a self-reinforcing metabolic–epigenetic feedback loop in CHF. Although current guideline-directed medical therapies improve symptoms and clinical outcomes, they do not directly target this metabolic–epigenetic axis. Traditional Chinese medicine (TCM), including bioactive compounds, herbal formulas, patent medicines, and injections, has demonstrated potential in preclinical studies to modulate myocardial energy metabolism, improve mitochondrial function, and influence epigenetic regulators such as SIRT1, AMPK, and TET/JmjC-dependent pathways. However, most available evidence is derived from experimental models, and causal relationships between metabolite regulation, epigenetic remodeling, and cardiac functional improvement remain insufficiently validated. This review summarizes current knowledge on metabolite-driven epigenetic regulation in CHF and evaluates emerging evidence on the role of TCM in modulating this network. We also critically discuss key limitations, including reliance on non-clinical models, incomplete pharmacokinetic understanding, and insufficient causal validation. Finally, we propose future directions based on multi-omics integration, single-cell and spatial technologies, and systems biology approaches to facilitate mechanistic clarification and translational development of metabolism-targeted strategies for CHF. Full article

The sustainable valorization of spontaneous flora biomass for the recovery of high value-added phytochemicals represents a key opportunity within the circular bioeconomy, yet it remains constrained by the environmental limitations of conventional extraction solvents and the lack of data-driven optimization frameworks. In this study, Natural Deep Eutectic Solvents (NADES) composed of betaine and 1,3-propanediol were designed and applied as bio-based extraction media for the recovery of bioactive metabolites from Artemisia annua L. spontaneous biomass in the context of green extraction and sustainable resource utilization. Two liquid–solid extraction techniques, namely vortex-assisted extraction and ultrasound-assisted extraction, were evaluated. The influence of key process parameters, including the eutectic component molar ratio, water content, solid-to-liquid (S/L) ratio, extraction temperature, and extraction time, was systematically investigated. Results demonstrated that extraction efficiency was strongly dependent on both solvent composition and process conditions, with distinct optimum parameters for different phytochemical classes. Maximum total polyphenol content (52.08 mg GAE/mL) was achieved via ultrasound-assisted extraction at 20 °C for 15 min, using a 1:3 NADES ratio with 40% water dilution and S/L = 1:5, while the highest flavonoid yield (17.34 mg QE/mL) was obtained by vortex-assisted extraction for 45 min using a 1:6 NADES ratio under the same dilution and S/L conditions. To identify extraction conditions associated with improved process efficiency, a hybrid modeling approach combining deep neural networks with the Success-History-based Adaptive Differential Evolution (SHADE) algorithm was employed, enabling high-accuracy prediction of extraction performance across a broad parameter space. The proposed framework demonstrates the feasibility of integrating green solvent design with machine learning-driven process modeling for the efficient valorization of underutilized plant biomass, contributing to the development of resource-efficient, sustainable extraction protocols, consistent with principles of process intensification and resource-efficient extraction strategies. Full article

Plant–microbe interactions can modulate the production of bioactive compounds involved in plant growth-promoting activity. This study investigates the metabolic reprogramming of the actinomycete model strain Streptomyces coelicolor M145 during co-cultivation with Citrus aurantium and Citrus limon seeds, used as defined plant-derived chemical inputs, under contrasting nutritional conditions with or without L-tryptophan (Trp) supplementation. Untargeted metabolome profiling revealed medium- and Citrus seed-dependent metabolic shifts in co-cultures compared with corresponding Citrus seed and S. coelicolor single cultures used as controls. Under R2YE production conditions, co-cultivation with C. limon resulted in 27 extracellular metabolites, compared with 11 detected in the TSB vegetative medium; similar trends were observed for C. aurantium. Multivariate analyses confirmed that growth medium, Citrus species, and Trp significantly shaped S. coelicolor extracellular metabolic profiles, mainly in quantitative terms. Production conditions, particularly with Trp supplementation, promoted metabolites associated with antimicrobial activity and iron acquisition, whereas vegetative conditions promoted primary metabolism and biotransformation of Citrus-derived compounds. Spent medium bioassays on Solanum lycopersicum showed that these metabolic differences were correlated with distinct biological responses. Overall, these findings demonstrate that defined plant-derived inputs modulate S. coelicolor specialized metabolism in a context-dependent manner, generating metabolomic signatures associated with differential plant growth responses compared to single cultures. Full article

Chronic ultraviolet B (UVB) radiation drives cutaneous photoaging—clinically manifesting as erythema, edema, scaling, deep wrinkling, loss of elasticity, and barrier disruption—through mitochondrial reactive oxygen species (mtROS) overproduction and quality-control failure. Here we identify α-ketoglutarate (AKG; also known as 2-oxoglutarate), a TCA-cycle intermediate and essential co-substrate for α-ketoglutarate-dependent dioxygenases (α-KGDDs), as a metabolic corrector of mitochondrial redox homeostasis in UVB-induced photoaging. In a 10-week chronic UVB SKH1 hairless mouse model, microneedle-assisted transdermal delivery of AKG dose-dependently attenuated macroscopic erythema, scaling, and erosive lesions, restored skin barrier function and dermal elasticity, preserved epidermal–dermal architecture, and protected collagen and elastic fiber integrity, with efficacy comparable to all-trans retinoic acid. Mechanistically, AKG reactivated α-KGDD/prolyl hydroxylase (PHD) catalytic function and promoted proteasomal clearance of aberrantly stabilized HIF-1α under normoxia; this was accompanied by restored AMPK Thr172 phosphorylation downstream of constitutive LKB1 and recovery of PGC-1α-driven mitochondrial biogenesis. AKG preferentially attenuated mitochondrial superoxide over total cellular ROS through a co-substrate-mediated mechanism distinct from direct radical scavenging, and its protective effects were largely abrogated by DMOG (an α-KGDD inhibitor) or compound C (an AMPK inhibitor). These findings position AKG, delivered via microneedle-assisted topical application, as a candidate metabolite-based intervention targeting the α-KGDD/HIF-1α/AMPK axis for photoaging. Full article

Background: A high-fat diet (HFD) contributes to cardiometabolic disease. Gut microbiota-derived metabolites may participate in this process, but their contribution to lipid regulation is not well defined. Indoxyl sulfate (IS), a microbiota-derived metabolite, has been linked to vascular and metabolic dysfunction. Its role in lipid metabolism remains unclear. Methods: In Part A, plasma and urinary concentrations of IS were measured in plasma and urine from HFD-fed rats in which dyslipidemia had developed, together with controls. In Part B, HepG2 cells were exposed to IS, and cell viability and selected cholesterol metabolism-related transcripts and proteins were assessed. In Part C, 10-week-old, male Sprague–Dawley rats maintained on a standard diet received vehicle or IS at two doses for 8 weeks. Hepatic expression of LDLR, SREBP-2, HMG-CoA reductase, and related cholesterol metabolism markers were measured by quantitative real-time PCR and Western blotting. Results: In Part A, higher plasma IS concentrations and higher daily urinary IS excretion were found in samples collected from HFD-fed rats compared to controls. In HepG2 cells, IS reduced cell viability at higher concentrations and increased LDLR mRNA and protein expression. In IS-treated rats, total cholesterol, LDL-cholesterol, and triglycerides increased in a dose-dependent manner. Hepatic SREBP-2 and HMG-CoA reductase protein levels were increased at both IS doses, whereas LDLR protein abundance was increased at the higher dose. Moreover, serum PCSK9 levels were reduced in IS-treated rats. Conclusion: IS increased in HFD-fed rats. IS altered cholesterol metabolism-related pathways in HepG2 cells and in rats. In vivo IS administration increased circulating lipids and hepatic proteins involved in cholesterol synthesis and uptake. These findings indicate that IS may contribute to disturbed lipid homeostasis, although its role in HFD-induced dyslipidemia requires further mechanistic confirmation. Full article

Production system may affect meat quality and muscle metabolic characteristics in Tibetan sheep. In this study, the biceps femoris muscles of twelve 3-year-old Tibetan sheep with similar body weights were used as experimental materials during a 6-month experimental period. The housed group (n = 6) was defined as the control group (C group), whereas the grazing group (n = 6) was defined as the L group. Meat quality measurement, nutritional composition analysis, untargeted lipidomics, and amino acid metabolomics (AAM) were integrated to investigate the effects of contrasting grazing and house-feeding production systems on meat quality and metabolic characteristics in Tibetan sheep. The results showed that cooking loss and drip loss were significantly decreased, whereas water-holding capacity (WHC) was significantly increased in the L group. However, shear force was also increased, indicating that grazing and house-feeding systems were associated with differences in muscle WHC and shear force. The L group exhibited significant alterations in lipid composition and increased concentrations of several n-3 polyunsaturated fatty acids and increased levels of omega-3 polyunsaturated fatty acids (n-3 PUFAs), including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suggesting that grazing and house-feeding systems were associated with differences in the lipid nutritional profile of muscle. Lipidomic analysis showed that the differential lipids were mainly enriched in triacylglycerols (TGs), phosphatidylethanolamines (PEs), and phosphatidylcholines (PCs), and several PUFA-containing TGs and membrane lipid molecules were closely associated with meat quality traits. AAM analysis showed that branched-chain amino acids (BCAAs), including L-leucine and L-valine, as well as N,N-dimethylglycine, were upregulated in the L group, whereas kynurenine and 1-methyl-L-histidine were downregulated. These findings suggest that BCAA metabolism and tryptophan–kynurenine metabolism were associated with metabolic differences observed between production systems in muscle metabolic adaptation. However, amino acid metabolomics analysis revealed that no amino acid metabolites remained significant after FDR correction, and thus the observed pathway-level changes (e.g., BCAA metabolism and tryptophan–kynurenine pathway) should be interpreted as nominal and exploratory findings. Overall, the results indicate that feeding systems were associated with alterations in the lipid and amino acid metabolic profiles of the biceps femoris muscle in Tibetan sheep, which were further associated with differences in muscle WHC, shear force, lipid nutritional composition, and the profile of flavor precursors. This study provides a theoretical basis for optimizing plateau meat sheep production systems and developing high-quality Tibetan sheep meat products. Full article

Ganoderma lucidum polysaccharide peptide (GLPP) is a food-derived macromolecule with immunomodulatory potential, but its gut-centered mechanisms under chemotherapy-associated immunosuppressive stress remain unclear. This study aimed to evaluate the protective effects of GLPP against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury in mice and to explore the associated microbiota–metabolite–gene interaction network using integrated foodomics. BALB/c mice were treated with CTX and then administered GLPP at 50, 100, or 200 mg/kg/day for 42 days, with levamisole as a positive control. High-dose GLPP restored spleen index from 1.592 ± 0.266 to 1.902 ± 0.212 mg/g and thymus index from 0.322 ± 0.146 to 0.656 ± 0.081 mg/g compared with the CTX group. It also enhanced lymphocyte proliferation (OD450: 1.529 ± 0.073 vs. 1.065 ± 0.051), increased carbon clearance index (3.403 ± 0.223 vs. 2.650 ± 0.164), elevated IL-2 and IgA levels, and reduced excessive IFN-γ and TNF-α responses. GLPP alleviated intestinal mucosal injury and reshaped gut microbial profiles, particularly taxa related to Bacteroidota and Bacteroides. Metabolomics revealed putatively annotated differential metabolites associated with amino acid, nicotinate–nicotinamide, and glycerophospholipid metabolism, while transcriptomics indicated modulation of PRR/MAPK-related immune signaling. Integrated correlation analysis suggested a microbiota–metabolite–gene–immune association network involving putative gamma-Glutamylleucine(γ-Glu-Leu), leukotriene D4(LTD4)-like lipid features, and hippuric acid. These findings support GLPP as a promising immune-supporting functional food ingredient, although metabolite assignments and causal mechanisms require further validation. Full article

This study evaluated the effects of dietary supplementation with 5% Zanthoxylumbungeanum leaf (ZBL) on growth performance, slaughter traits, meat quality, caecal microbiota, serum metabolome, and muscle transcriptome in rabbits. A total of 108 male New Zealand rabbits (60 days old) were randomly assigned to two groups (nine replicates/group; six rabbits/replicate) and fed either a basal diet (CON) or a diet in which 5% wheat bran was replaced with 5% ZBL for four weeks. Growth and slaughter performance did not differ (p > 0.05). ZBL reduced drip loss and cooking loss, enhanced antioxidant capacity, reduced specific saturated (C16:0), and unsaturated (C18:1 n-9 cis) fatty acids in leg muscle (p < 0.05), and the nutritional significance of these fatty acid changes remains unclear. ZBL also altered the levels of several volatile and non-volatile compounds in serum and muscle. It increased caecal abundance of norank_f_Lachnospiraceae and Anaerofilum, elevated serum metabolites (oleuropein, 3-coumaric acid), and upregulated meat quality-related genes (NR3C2, PDZRN3) in leg muscle (p < 0.05). Correlation analyses revealed that the observed changes in meat quality were closely associated with alterations in gut microbiota, serum metabolome, and muscle transcriptome. These findings suggest that dietary 5% ZBL does not compromise growth performance and is associated with changes in rabbit meat quality, which is associated with coordinated alterations in the gut microbiota, serum metabolome, and muscle transcriptome. Full article

Cyanobacterial biosynthetic gene clusters (BGCs) remain difficult to reconstruct in heterologous systems, yet the suitability of fungal hosts for expression of cyanobacterial pathways remains largely unexplored. Here, the well-characterized lyngbyatoxin A (LTXA) biosynthetic gene cluster was used as a model system to evaluate the capacity of Aspergillus oryzae to support cyanobacterial NRPS biosynthesis. The lyngbyatoxin biosynthetic genes (ltxA, ltxB, and ltxC) were individually cloned and expressed in Aspergillus oryzae NSAR1 under the control of an inducible promoter. Metabolite production was assessed by LCMS, while transcriptional analysis was performed using RT-PCR. Codon-optimized constructs and precursor feeding experiments were used to evaluate pathway functionality. No detectable production of LTXA or pathway intermediates was observed following co-expression of ltxA–C despite confirmed transcription of ltxB and ltxC. RT-PCR analysis could not reliably detect ltxA transcripts for unknown reasons. In contrast, expression of a codon-optimized ltxC enabled biotransformation of indolactam V to LTXA in A. oryzae, confirming functional expression of the prenyltransferase. Overall, this work establishes lyngbyatoxin biosynthesis as a useful model system for evaluating fungal chassis compatibility with cyanobacterial BGCs and provides insights for future engineering of fungal platforms for natural product biosynthesis. Full article

Rice storage under suboptimal conditions leads to rapid quality deterioration. In this study, effects of low-temperature (LT, 20 °C) combined with nitrogen-controlled atmospheric conditions (NCA, 95%) on physicochemical properties, nutrient, mycotoxins and metabolites of rice during 180 d storage were comprehensively evaluated, to explore a potential preservation technique for rice. The LT + NCA treatment significantly inhibited the accumulation in free fatty acid value, malondialdehyde and electrolyte leakage, while maintaining higher catalase activity, lower amylose content and better pasting properties (higher breakdown, lower final viscosity and setback). Crucially, mycotoxin accumulation remained within safe limits across all groups, with LT + NCA showing the lowest levels. Metabolomics analysis identified 653 metabolites, with LT + NCA significantly modulating pathways related to carbohydrate metabolism (e.g., promoting raffinose accumulation while inhibiting the pentose phosphate pathway) and amino acid metabolism (enhancing glutathione metabolism and suppressing arginine biosynthesis). These metabolic rearrangements reduced oxidative damage, stabilized membrane integrity, and preserved cooking quality. Therefore, LT + NCA could be a superior strategy for delaying oxidative stress, maintaining nutritional and cooking quality, and ensuring the safety of stored rice. Full article