Search Results (901)

Alzheimer’s disease (AD) is a common age-related neurodegenerative disorder with extremely low drug development success rates, making nutritional intervention a promising strategy. Cerebral energy metabolism dysfunction is a core pathological feature of AD. Odd-chain fatty acids (OCFAs) can generate propionyl-CoA via β-oxidation to replenish the impaired tricarboxylic acid (TCA) cycle. This study characterized the lipid composition of OCFAs-enriched algal oil by UPC²-Q-TOF-MS, evaluated its neuroprotective effects on Caenorhabditis elegans (C. elegans) models with AD, Parkinson’s disease (PD), and Huntington’s disease (HD), and explored the metabolic mechanism of its key component pentadecanoic acid (C15:0) using untargeted metabolomics. Results showed that triglycerides (TAGs) represented the predominant lipid class, accounting for 97.3% of the total lipid content in the algal oil. Among all the identified TAG molecular species, TAGs containing C15:0/C17:0 accounted for more than 90%. OCFAs-enriched algal oil exhibited disease-selective neuroprotection. It significantly improved locomotor function in AD nematodes, moderately ameliorated PD-related deficits, whereas showed no efficacy in HD nematodes. Metabolomics revealed that C15:0 produced propionyl-CoA to rescue TCA cycle dysfunction and energy deficits, upregulated membrane phospholipids to repair membrane integrity, and reduced abnormal metabolites to restore metabolic homeostasis. KEGG analysis confirmed that C15:0 globally regulated core metabolic pathways including amino acid, cofactor, nucleotide, and carbon metabolism. OCFAs-enriched algal oil exerted selective anti-AD effects by repairing energy metabolism, remodeling membrane phospholipids, and restoring metabolic homeostasis, providing a novel nutritional candidate for AD intervention. Full article

Osteoporosis is a systemic skeletal disorder characterized by low bone mass, microarchitectural deterioration, and an increased risk of fracture. Its pathogenesis is closely associated with disturbances in energy metabolism, particularly glucose metabolic reprogramming in bone cells. Under osteoporotic conditions, the balance between osteoblasts and osteoclasts is disrupted, accompanied by impaired oxidative phosphorylation, dysregulated glycolysis, and reduced tricarboxylic acid cycle efficiency, ultimately leading to mitochondrial dysfunction. These metabolic alterations result in an insufficient energy supply and accelerate bone loss. Accordingly, the modulation of key enzymes involved in glucose metabolism has emerged as a promising therapeutic strategy. Strategies include the use of natural compounds, traditional Chinese medicine formulas, and specific inhibitors to modulate glucose metabolism processes and related pathways, thereby restoring cellular energy homeostasis and bone remodeling balance. This review summarizes pharmacological agents regulating glucose metabolism and proposes a hierarchical framework for therapeutic prioritization: first, inhibiting pathological glycolysis in osteoclasts (particularly via LDHA and PKM2). Second, restoring oxidative phosphorylation in osteoblasts (e.g., via COX I–V or ATP synthase). And third, employing multi-target traditional Chinese medicine formulas as complementary strategies. By establishing this cell-type-specific and pathway-specific hierarchy, the review aims to provide a theoretical basis for future research on metabolic interventions in bone diseases. Full article

Background: Children with obesity-related asthma exhibit poorer symptom control and more frequent exacerbations than their normal-weight peers, but the underlying metabolic mechanisms are unclear. This study aimed to identify drivers of obesity-related asthma through untargeted plasma metabolomic and lipidomic profiling. Methods: Plasma was obtained from normal weight (NW) asthmatic (n = 95) and non-asthmatic (n = 67) and overweight/obese (OO) asthmatic (n = 99) and non-asthmatic (n = 100) children (6–17 years). We assessed metabolic and lipidomic differences between asthmatics and controls within each BMI group using orthogonal partial least squares discriminant analysis (OPLS-DA), examined overlap with the adult Qatar Biobank cohort, and mapped metabolic–clinical interactions using Gaussian Graphical Models. Results: In the fitted OPLS-DA models, separation between asthmatic and control groups was stronger in the NW group (R²Y = 0.72/0.52) than in OO (R²Y = 0.65/0.63) children. Asthma was associated with altered tricarboxylic acid (TCA) intermediates, ether-linked phosphatidylethanolamines, and sphingomyelins (SM) in NW, and with phosphatidylcholines, lysophosphatidylcholines, and phosphatidylethanolamines in OO. Integrating metabolomic, lipidomic, and clinical data revealed connections between altered SMs and interleukins, and TCA intermediates and electrolytes, all associated with elevated leptin in NW. An increased residual volume to total lung capacity ratio in OO was associated with phospholipid shifts. The overall dynamics in lipid metabolism with asthma, conditioned on BMI, was also observed in the adult Qatar Biobank cohort. Conclusions: Among NW children with asthma, we found enhanced TCA cycle activity and inflammation linked to altered SM metabolism, whereas in OO, the findings suggest oxidative stress arising from chronic obesity-related inflammation. These data reveal BMI-specific metabolic mechanisms of pediatric asthma that might inform precision approaches to disease management. Full article

The expression of two genes, Fum1 and Fum2, encoding the mitochondrial and cytosolic forms of fumarase (EC 4.2.1.2); the methylation of individual CpGs of their promoters; and fumarase activity were studied in sunflower (Helianthus annuus L.) leaves depending on irradiation and salinity. Fumarase activity was twice as high in darkness compared to irradiation by white light and red light, while far-red light applied after darkness or after red light reverted the activity to the values in darkness, which indicates the involvement of phytochrome. Using qRT-PCR, it was demonstrated that this corresponded to the pattern of expression of the Fum1 gene, while the expression of the Fum2 gene was higher upon irradiation by white and red light, and lower in darkness and under far-red light. Under the application of 150 mM NaCl for 1, 3, 6, 12, and 24 h, fumarase activity increased fivefold from the start of incubation to 6 h, and then decreased after 12 h. These changes were associated with the transcriptional regulation of the Fum1 and Fum2 genes. Changes in the methylation status of the analyzed CpGs in their gene promoters, detected via semi-quantitative methylation-specific PCR, were associated with differences in their expression. The higher methylation levels of the analyzed CpGs in the Fum1 gene promoter under different light conditions and in the Fum2 gene promoter under salinity corresponded to low levels of their transcripts in sunflower leaves. It is suggested that the mitochondrial and cytosolic forms of fumarase are regulated by light and salinity at the gene expression level, presumably through changes in the methylation status of individual CpGs in their promoters. Full article

Lodging is a major constraint on the stable production of high-quality japonica rice in the Yangtze River Delta. This study evaluated whether different concentrations of prohexadione calcium (Pro-Ca) could improve lodging resistance while maintaining grain yield in high-quality japonica rice. Field experiments were conducted in the 2024 and 2025 growing seasons, with TA 1 cultivated in 2024 and TA 1, SY 28, and HR 1212 cultivated in 2025. Pro-Ca was applied at the jointing stage at four concentrations: CK (water spray), P1 (15 mg L⁻¹), P2 (30 mg L⁻¹) and P3 (45 mg L⁻¹). Rice yield and its components, lodging parameters, culm morphological traits, and non-targeted metabolomic profiles were analyzed. Compared with CK, the P1 treatment significantly reduced the lodging index without a significant reduction in grain yield. In contrast, the P2 and P3 treatments further decreased the lodging index by 14.0–48.1% but decreased grain yield by 6.7–17.9%, mainly due to reductions in effective panicle number and spikelets per panicle. Pro-Ca treatment significantly increased internode diameter and culm wall thickness by 4.9–29.3% and 11.7–76.5%, respectively, and promoted the accumulation of lignin by 5.4–17.7% and cellulose by 3.0–8.6%, thereby enhancing the structural reinforcement of the rice stem. A metabolomic analysis showed that Pro-Ca treatment was associated with changes in carbon- and nitrogen-related metabolites, including metabolites linked to the tricarboxylic acid (TCA) cycle and amino acid biosynthesis. These changes were accompanied by increased accumulation of phenylpropanoid pathway intermediates and lignin-related precursors, including sinapyl alcohol and coniferyl aldehyde. Therefore, in our study, 15 mg L⁻¹ Pro-Ca showed the most favorable balance between lodging resistance and yield, indicating its potential for further evaluation; however, its agronomic and economic feasibility requires additional investigation before practical recommendation. Full article

Cancer progression is closely linked to the enhanced uptake of extracellular amino acids, mediated by specific transporters that support biosynthesis, metabolic activity, and energy production through the tricarboxylic acid cycle. By increasing the expression of these transporters, tumor cells secure a continuous amino acid supply that sustains the proliferation, metabolic balance, and activation of major signaling pathways. While most studies have emphasized post-translational control of amino acid transporters, such as phosphorylation, ubiquitination, glycosylation, and palmitoylation, emerging evidence highlights regulatory crosstalk between these transporters and other membrane proteins, including G protein-coupled receptors and receptor tyrosine kinases. This review summarizes the current literature on the receptor-mediated mechanisms governing amino acid uptake and explores how interactions among families of membrane proteins contribute to the regulation of transporter activity. Full article

Mitochondrial dysfunction is a relevant hallmark of Alzheimer’s disease (AD), contributing to the impaired metabolic homeostasis involved in neuronal loss and cognitive decline. In this study, we target the metabolic dysfunction occurring in AD through a novel pharmacological approach involving the modulation of glutamate dehydrogenase (GDH), which converts glutamate to α-ketoglutarate and supports the tricarboxylic acid (TCA) cycle. In our experimental models (i.e., differentiated SH-SY5Y cells and primary rat cortical neurons exposed to glyceraldehyde and amyloid-beta peptide 1-42, respectively), the allosteric GDH activator 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) increased mitochondrial ATP production, improved cellular bioenergetics, and reduced oxidative stress, ultimately promoting neuronal survival. Ionic dysfunctions in AD are linked to disrupted calcium homeostasis and organelle storing properties. In this context, GDH activation potentiated mitochondrial and endoplasmic reticulum calcium buffering capacity by enhancing store-operated calcium entry. Oxidative stress, largely driven by mitochondrial ROS overproduction, represents another major contributor to AD pathology. In our AD models BCH-mediated GDH activation reduced ROS formation and restored mitochondrial membrane potential (ΔΨ_m). Importantly, these metabolic and ionic improvements were associated with decreased accumulation of amyloid-β (Aβ_1-42) and phosphorylated tau (pTau), two key AD biomarkers. Overall, modulation of the GDH/TCA pathway represents a promising approach for restoring metabolic dysfunctions and counteracting oxidative stress and ionic dysregulation and therefore AD neurodegeneration. Full article

The ATP-dependent inhibition of cytochrome c oxidase (CytOx, complex IV of the electron transport chain) is the second mechanism of respiratory control adjusting mitochondrial respiration in order to prevent excessive electron flow and reactive oxygen species (ROS) production. Here, we investigate how tricarboxylic acid (TCA) cycle metabolites and the subsequent complex I or complex II activities influence this regulatory mechanism. Therefore, CytOx activity was assessed by the oxygen consumption rate after cytochrome c (Cyt c) titration to stimulate complex IV activity in isolated rat heart mitochondria (RHM) and permeabilized AC16 cells. Mitochondrial membrane potential (Δψm) and ROS formation were analysed by flow cytometry. Our results show that TCA cycle intermediates differed in their impact on CytOx activity and subsequent ROS formation. NADH-linked substrates such as α-ketoglutarate, glutamate and malate increased respiratory capacity, but preserved ATP-dependent control of CytOx, indicating that elevated electron supply alone does not necessarily abolish ATP sensitivity. In contrast, succinate, which feeds electrons directly into complex II, strongly increased respiration causing the loss of ATP-dependent respiratory control in both model systems. Despite this strong respiratory effect, succinate induced only modest changes in mitochondrial membrane potential in isolated mitochondria, whereas permeabilized cardiomyocytes exhibited reduced polarization accompanied by increased superoxide formation. Together, these findings demonstrate that the effectiveness of ATP-dependent CytOx inhibition is influenced by TCA cycle activity and depends on the site of electron entry into the respiratory chain. Thus, substrate-dependent modulation of respiratory control links metabolite availability to mitochondrial redox regulation in cardiac cells. Full article

Cerebrospinal fluid (CSF) oligoclonal band (OCB) analysis remains central to the diagnostic evaluation of neuroinflammatory diseases of the central nervous system (CNS), as it reflects intrathecal immunoglobulin synthesis. However, its reliance on lumbar puncture limits its applicability for screening and repeated longitudinal assessment. Serum metabolomics offers a minimally invasive strategy to explore peripheral biochemical correlates of central immune activity. Building on previous binary OCB comparisons, the present study extends serum metabolomic analysis to encompass all five classical OCB patterns, thereby capturing a broader immunological spectrum. A total of 92 adults undergoing diagnostic evaluation for suspected CNS inflammatory disorders were retrospectively stratified according to OCB type (Types 1–5). Serum samples were analysed using targeted ¹H-NMR spectroscopy on a Bruker Avance Neo 600 MHz platform and processed using Bruker’s IVDr pipeline. Group-wise differences were assessed using non-parametric statistical testing with false discovery rate (FDR) correction, complemented by effect size estimation, exploratory multivariate analyses, and Receiver Operating Characteristic (ROC) modelling. Distributional characteristics were further examined using boxplots and violin plots. Across analytical approaches, several metabolites—most prominently leucine, 2-oxoglutaric acid, histidine, threonine, and glycerol—exhibited nominal variation and moderate effect sizes across OCB patterns. Rather than discrete metabolic separation, these metabolites demonstrated graded shifts in central tendency accompanied by substantial overlap between groups. Unsupervised principal component analysis did not reveal robust clustering, while supervised multivariate models highlighted amino acid- and tricarboxylic acid cycle-related metabolites as contributors to partial differentiation. Post hoc power analysis indicated limited sensitivity to detect small-to-moderate effects under multiple-testing correction, supporting an exploratory interpretation of the findings. Taken together, this first targeted serum ¹H-NMR metabolomic evaluation spanning all classical OCB patterns suggests that peripheral metabolic profiles may reflect graded immunometabolic variation associated with intrathecal immune activity. While not intended for diagnostic classification, these findings provide a spectrum-based framework for integrating serum metabolomics with OCB phenotyping and identify candidate metabolites for future prospectively powered and clinically characterised studies. Full article

Tiankeng ecosystems are characterized by strong microenvironmental gradients that influence plant adaptation; however, the molecular mechanisms underlying plant responses to altitudinal variation remain poorly understood. In this study, transcriptome sequencing and bioinformatic analyses were conducted to investigate the environmental adaptation mechanisms of three representative plant species (Hydrangea strigosa Rehder, Pilea martini, and Pilea sinofasciata) distributed along the vertical gradient of the Hanzhong Tiankeng in Shaanxi Province, China. Differential gene expression and functional enrichment analyses were performed to explore transcriptional responses under different altitude conditions. The results showed that flower coloration in Hydrangea strigosa Rehder was associated with the activation of sugar metabolism and triterpenoid biosynthesis pathways, suggesting potential indirect roles in modulating cellular metabolism and physiological conditions linked to flower coloration, while poor growth at the tiankeng bottom was associated with enhanced cellular respiration under low-light conditions, suggesting a potential link between energy metabolism and growth performance. In contrast, Pilea martini and Pilea sinofasciata exhibited better growth in the pit-bottom environment. Pilea martini promoted growth through enhanced carbohydrate metabolism and tricarboxylic acid cycle activity, whereas Pilea sinofasciata responded to environmental stress through hormone signaling, triterpenoid biosynthesis, and light signaling pathways. These findings reveal species-specific molecular strategies for plant adaptation to altitude-related environmental gradients in tiankeng ecosystems and provide insights into plant survival mechanisms in karst habitats. Full article

Light availability is a key environmental factor regulating nitrogen assimilation, carbon metabolism, and nutritional quality in leafy vegetables grown in controlled environments. However, how practical lighting regimes used in plant factories with artificial lighting (PFALs) influence the coordination between nitrogen assimilation and central carbon metabolism across different lettuce cultivar types remains insufficiently understood. This study investigated how moderate differences in photosynthetic photon flux density (PPFD) influence nitrogen metabolism and metabolic coordination in hydroponically cultivated lettuce. Two cultivars representing contrasting morphological types, iceberg lettuce (‘Celebration’) and leaf lettuce (‘Sunny’), were grown under LED light intensities of 150 and 200 µmol·m⁻²·s⁻¹. Nitrate, nitrite, and ammonium concentrations were measured together with the activities of nitrate reductase (NRA) and nitrite reductase (NiRA), as well as ascorbic acid content. Metabolomic profiling was additionally performed to characterize broader metabolic responses. Higher light intensity enhanced nitrate reduction capacity in both cultivars, but the resulting patterns of nitrogen accumulation were strongly genotype-dependent. The leaf lettuce cultivar ‘Sunny’ exhibited increased NRA and reduced nitrate accumulation under higher light intensity, whereas the iceberg lettuce cultivar ‘Celebration’ accumulated more nitrate under the same conditions. Ammonium responses further suggested differences in downstream nitrogen assimilation processes. Elevated light intensity also increased ascorbic acid levels in both cultivars. Metabolomic analysis revealed contrasting cultivar-specific shifts in central carbon metabolism, particularly involving soluble sugars and tricarboxylic acid cycle intermediates, indicating differential coordination between carbon metabolism and nitrogen utilization. Overall, these findings demonstrate that moderate changes in light intensity within the practical PFAL cultivation range can significantly influence the integration of carbon and nitrogen metabolism in lettuce. Importantly, cultivar-specific physiological traits determine how these metabolic responses translate into nitrate accumulation and nutritional quality in controlled-environment production systems. Full article

Producing single-cell protein (SCP) from syngas-derived ethanol and acetate offers a sustainable solution to global protein shortages, yet microbial utilization mechanisms for these mixtures remain underexplored. This study establishes a systematic bioconversion strategy using Cyberlindnera jadinii TU389. To mitigate acetaldehyde accumulation during ethanol metabolism, we engineered the strain TU546 to overexpress acylating acetaldehyde dehydrogenase (ADA6). TU546 achieved a maximum biomass of 46.7 g/L and a protein yield of 21.69 g/L, representing enhancements of 28.16% and 23.02% over the wild-type, respectively. Transcriptomic analysis revealed extensive metabolic reprogramming. In the C2 assimilation pathway, upregulated aldehyde dehydrogenase and acetyl-CoA Synthetase 1 accelerated acetate conversion to acetyl-CoA, while downregulated pyruvate decarboxylase and alcohol dehydrogenase minimized carbon flux loss. The upregulation of tricarboxylic acid cycle enzymes, the glyoxylate shunt, and acyl-coA oxidase improved carbon skeleton retention. Moreover, the upregulation of transaminases and N-acetylglutamate synthase, synergized with intensified cell proliferation signaling, redirected amino acid metabolism toward a synthesis-enhanced and degradation-controlled paradigm. This synergistic regulatory network drives the high-efficiency bioconversion of ethanol and acetate into SCP, establishing a molecular mechanistic foundation for the valorization of syngas-derived C2 substrates in biological macromolecule production. Full article

Entomopathogenic nematodes (EPNs) are crucial biocontrol agents, yet optimizing the yield and quality of infective juveniles (IJs) during commercial liquid production remains challenging. This study utilized a central composite rotatable design to optimize liquid culture parameters (ascaroside, dimethyl sulfoxide, medium volume, IJ inocula) for Heterorhabditis bacteriophora H06 and Steinernema carpocapsae All. The results demonstrated that improving aeration (inferred from reduced media volume), combined with ascr#11 regulation, synergistically enhanced IJ yield and quality. Under optimized conditions, yields reached 3.35 × 10⁵ IJs/mL for H. bacteriophora H06 and 2.67 × 10⁵ IJs/mL for S. carpocapsae All. Crucially, the IJs from the high-yield flask exhibited significantly superior infectivity (24–26% single-IJ infection rate) compared to solid-culture controls (13–14%). Targeted metabolomics profiling of sugar, energy and fatty acids of H. bacteriophora H06 revealed upregulated tricarboxylic acid (TCA) cycle intermediates (citrate, pyruvate) and the significant accumulation of stress-protectant trehalose and immune-modulating polyunsaturated fatty acids (eicosapentaenoic acid, arachidonic acid). These findings establish a fermentation strategy that simultaneously enhances IJ yield and biological quality by reducing media volume (used as a proxy for improved aeration) and supplementing ascr#11. Furthermore, the distinct metabolic profile enriched in energy, stress, and immune-modulating metabolites identified in H. bacteriophora provides a plausible explanatory framework for the parallel phenotypic improvements observed across both species. Full article

Dwarf bananas are an important tropical fruit crop. They are particularly susceptible to cold stress, which often leads to quality deterioration. Although previous studies have examined the effects of cold stress on dwarf bananas, research on effective regulatory strategies and underlying mechanisms remains limited. This study investigates the mechanistic regulatory effects of chitosan (CTS) on cold stress in postharvest dwarf bananas, revealing that CTS mitigates cold-induced injury and improves fruit quality. Using an integrated approach of metabolomics, lipidomics, and enzyme activity assays, this study explored the potential mechanisms by which CTS alleviates chilling injury. Lipidomic results showed that CTS enhances cold tolerance by regulating the metabolism of glycerides, glycerophospholipids, linoleic acid, and linolenic acid. Metabolomics data further indicated that CTS increases the levels of amino acids, carbohydrates, and key substrates and intermediates of the tricarboxylic acid (TCA) cycle in cold-stressed dwarf bananas. Collectively, these effects enhance respiration, energy homeostasis, and antioxidant capacity, enabling dwarf bananas to better tolerate low-temperature stress. Full article

This study presents a comprehensive flavour profile analysis of 12 Morchella samples (5 cultivated and 7 wild species) collected from diverse regions across China. The contents of free amino acids and volatile organic compounds were determined using UHPLC-QE-HRMS and HS-SPME-GC-MS. Flavour contribution was assessed by calculating taste activity values (TAVs) and relative odor activity values (rOAVs), and the influence of environmental factors on flavour compound accumulation was further explored. The findings indicated that cultivated Morchella exhibited pronounced fruity, floral, sweet, and mushroom-like notes (e.g., 1-octen-3-one, beta-damascone, and 1-(2-aminophenyl)ethanone), rendering them suitable for fresh consumption. In contrast, wild Morchella exhibited higher levels of herbaceous and smoky aroma compounds (e.g., (E,Z)-2,6-nonadienal, benzenemethanethiol, and non-8-enal), suggesting potential for premium product development. Correlation analysis revealed metabolic associations between taste-active amino acids and key volatile organic compounds via intermediates of the lipoxygenase pathway and the tricarboxylic acid cycle. Furthermore, environmental parameters including elevation, annual precipitation, and solar radiation were found to significantly influence the accumulation of flavour-related metabolites. These findings provide insights into the chemical basis underlying the flavour diversity of Morchella and offer a theoretical foundation for species identification, flavour-directed breeding, and differentiated product development. Full article