The ACSL family: Bridging fatty acid metabolism and cell death in cancer progression.

MiR-424-3p suppresses adipogenesis via HNRNPA0 targeting and p53-mediated ferroptosis.

Enhanced glutathione production in Saccharomyces cerevisiae via transporter activation and catabolic pathway engineering.

Crosstalk and coordination of TOR, SnRK1, and ABA in plant metabolic and environmental adaptation.

Spatial transcriptomics and single-cell analysis reveal GSTO2-mediated protective networks in oral squamous cell carcinoma tumor microenvironment.

Lignin is one of the most common biopolymers on Earth. In nature, lignin is primarily deconstructed by fungi into mixtures of aromatic compounds that are then assimilated by bacteria and fungi. Industrially, lignin is primarily generated as a byproduct of pulp and paper production and burned for process heat. However, if the appropriate assimilatory pathways were identified, deconstructed lignin could be funneled into value-added products using engineered bacteria. Foundational work has described pathways for assimilation of diverse monomeric aromatic compounds such as protocatechuate, ferulate, and syringate, as well as select dimers including those with β-O-4 and 5-5 interunit linkages. Recent advances have elucidated additional pathways for dimer assimilation, including pathways for new substrates as well as parallel pathways for previously characterized substrates. Comparing these dimer assimilation pathways can illuminate the underlying biochemical logic of assimilation for lignin-associated aromatic dimers and provide opportunities for metabolic engineering to enhance lignin valorization.

The fungal symbiont of leaf-cutter ant Atta mexicana, Leucoagaricus gongylophorus LEU18496 has the capability to produce enzymes such as cellulases, hemicellulases, and ligninases for plant biomass degradation. In this study, the fungus has been cultivated in submerged culture conditions using glucose and cellulose as carbon sources to explore gene expression level and unravel the molecular mechanisms responsible of enzyme production and carbohydrate catabolism. The transcriptomic analysis of Leucoagaricus gongylophorus LEU18496 using RNA-seq data, allowed the examination of the gene expression profiles across different carbon sources and growth phases. During the exponential growth phase on glucose there is a constitutive expression of several CAZymes, including β-glucosidase, pectinase, and endo-β-1,3-glucanase. The transcriptome data showed high expression of the creA repressor gene in the presence of glucose, underscoring its regulatory role in carbohydrate degradation and suggesting a regulatory mechanism governing CAZyme production and secretion when glucose is used as a carbon source. This study offers detailed insights into the pathways of cellulose and glucose catabolism, emphasizing the expression of key components involved in carbohydrate metabolism unraveling the metabolic strategies of L. gongylophorus providing information of the CAZymes and FOLymes production as high-value product suitable for biotechnological applications.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and pancreatic steatosis (PS) are interconnected ectopic fat conditions linked to cardiometabolic dysregulation. Their combined effect on the long-term risk of cardiometabolic multimorbidity (CMM; ≥ 2 of diabetes, hypertension, coronary heart disease, and stroke) and cardiac remodelling remains unclear. We examined cross-sectional associations between PS and the severity of MASLD histology in a biopsy-proven MASLD cohort from China. Subsequently, using the UK Biobank, we assessed the long-term risk of developing both incident CMM and cardiac structural/functional alterations (via cardiac magnetic resonance [CMR]) associated with single-organ versus dual-organ steatosis. Exploratory proteomic profiling was performed to identify potential molecular pathways. In the biopsy-proven cohort (n = 482), both continuous pancreatic proton density fat fraction and PS status were associated with severe hepatic steatosis, lobular inflammation, and fibrosis (all p < 0.05). In the UK Biobank cohort (n = 16 408; median follow-up of 5.6 years), the coexistence of MASLD and PS additively increased the risk of new-onset CMM (HR = 2.013, 95% CI: 1.219-3.322, p = 0.006). Dual-organ steatosis was also associated with marked cardiac alterations, specifically increased left ventricular mass and impaired ventricular function. Proteomics revealed upregulation of lysosomal catabolic and glycosaminoglycan-degrading pathways in dual-organ steatosis compared to single-organ steatosis. Gene Ontology highlighted heparan sulphate proteoglycan catabolism as a hallmark of dual-organ involvement. PS is associated with greater severity of MASLD histology, and the concomitant involvement of both the liver and pancreas drives a higher risk of CMM and cardiac remodelling.

Starvation elicits profound metabolic adaptations in skeletal muscle, enabling survival during nutrient scarcity. While global proteomic changes underpinning muscle atrophy have been studied, the role of lysine β-hydroxybutyrylation (Kbhb), a novel metabolite-derived post-translational modification linked to ketone metabolism, remains largely unexplored. In this study, we subjected mice to 72 h of food deprivation and performed integrative quantitative proteomics and Kbhb-modified peptide profiling on gastrocnemius muscle. Starvation induced significant body weight and muscle mass loss, accompanied by increased systemic β-hydroxybutyrate levels and widespread Kbhb modification of muscle proteins. Proteomic analysis revealed extensive downregulation of ribosomal and translation-associated proteins, coupled with upregulation of autophagy and lipid catabolism pathways, highlighting a coordinated shift from anabolic processes to catabolic and oxidative metabolism. Deep Kbhb profiling identified over 7500 modified lysine sites across 2000 proteins, with starvation triggering a global increase in Kbhb on key metabolic enzymes involved in glycolysis, TCA cycle, fatty acid β-oxidation, and amino acid metabolism. Notably, starvation-enhanced Kbhb preferentially targeted evolutionarily conserved lysines proximal to catalytic or cofactor-binding domains, implicating a regulatory role in enzymatic activity modulation. Conversely, Kbhb on structural and contractile proteins was downregulated, suggesting functional reprioritization of muscle physiology during fasting. Our findings uncover lysine β-hydroxybutyrylation as a dynamic, metabolically responsive PTM mediating gastrocnemius muscle adaptation to energy deficiency, expanding the paradigm of potentially metabolite-driven epigenetic and non-epigenetic regulatory mechanisms in muscle metabolism.

Tryptophan (TRP) is a proteinogenic and nutritionally essential amino acid involved in the formation of numerous bioactive substances. A crucial role in the TRP molecule is played by indole, a bicyclic ring formed by benzene and pyrrole, which confers hydrophobic and antioxidant properties and the ability to act as a ligand for aryl hydrocarbon and pregnane X receptors. The first parts of the article examine sources, nutritional requirements, and three pathways of TRP catabolism. Physiologically, ~5% of dietary TRP is catabolized through the pathway forming serotonin and melatonin in the brain and enterochromaffin cells of the gut, ~85% through the pathway resulting in the formation of nicotinamide nucleotides and kynurenine and its derivatives in the liver and immune cells, and ~10% in gut microbiota to indole derivatives. Alterations of individual TRP catabolism pathways in aging, alcoholism, inflammatory bowel disease, metabolic syndrome, renal insufficiency, liver cirrhosis, cancer, and nervous diseases, e.g., depression, Alzheimer's and Parkinson's diseases, multiple sclerosis, and schizophrenia, are examined in the central section. The final sections are devoted to the benefits and adverse effects of TRP supplementation, the therapeutic use of various TRP metabolites, and the pharmacological targeting of enzymes, transporters, and receptors involved in TRP catabolism. It is concluded that all pathways of TRP catabolism are altered across a broad spectrum of human illnesses, and further investigation is needed to understand their role in disease pathogenesis better. The goal for clinical research is to explore options for TRP-targeted therapies and their integration into new therapeutic strategies.

Effects of biomass feedstock and hydrothermal temperature on the molecular composition and bioavailability of invasive plant-based hydrochar-derived dissolved organic matter.

Abstract Osteoarthritis (OA) is a widespread degenerative condition marked by inflammation‐induced damage to chondrocytes and gradual breakdown of the cartilage extracellular matrix. Adipose‐derived mesenchymal stem cells (ADSCs) hold potential for treating OA due to their capacity to differentiate into various cell types and their paracrine signaling functions. However, the inflammatory environment in OA reduces ADSC viability post‐injection, while the absence of a supportive carrier causes significant cell loss, impairing their capacity for cartilage repair. To address these challenges, we improved the stemness and paracrine activity of ADSCs through hypoxia preconditioning and integrated them into an injectable small intestinal submucosa (SIS) tissue repair scaffold. This resulted in an SIS + ADSC composite material, designed for intra‐articular injection to enhance cartilage repair in arthritis. Our findings revealed that exposing ADSCs to 2% oxygen during hypoxia preconditioning and incorporating them into injectable SIS significantly increased the secretion of growth factors (VEGF, bFGF, EGF) and upregulated key hypoxia and stem cell markers (HIF‐1α, NANOG, SOX‐2, Oct‐4). In a rat OA model, hypoxia‐preconditioned SIS + ADSC composites markedly enhanced cartilage repair by stimulating anabolic activity, suppressing catabolic pathways, and reducing inflammation, thereby exhibiting strong protective and reparative effects. In summary, combining hypoxia preconditioning with injectable SIS offers an innovative and effective approach to optimize OA treatment by enhancing paracrine signaling, paving the way for new insights and technologies in cartilage repair within regenerative medicine.

The BES1/BZR1 transcriptional factor SlBES2 cross talks with abscisic acid to regulate fruit maturation in tomato.

Novel heterosteroids induce anabolic effects in human skeletal muscle cells: An integrated analysis of anabolic and catabolic signaling pathways.

Background/Objectives: Response to neoadjuvant chemotherapy (NAC) varies substantially among breast cancer patients and is only partially explained by tumor-intrinsic factors. The gut microbiome has emerged as a potential modulator of chemotherapy efficacy, yet its role in breast cancer remains underexplored. This study aimed to characterize gut microbial composition, functional potential, and microbially derived metabolites in breast cancer patients undergoing NAC. Methods: baseline stool samples from 39 chemotherapy-naïve breast cancer patients undergoing NAC were analyzed using shotgun metagenomic sequencing and targeted metabolomics. Patients were stratified by pathological complete response (pCR, n = 17; no pCR, n = 22). Microbial taxonomic and functional profiles, short-chain fatty acids (SCFAs) and bile acids were assessed, with subgroup analysis performed in triple-negative breast cancer (TNBC). Results: Patients achieving pCR exhibited significantly higher baseline microbial richness compared to non-responders (p = 0.040). Differential abundance analysis revealed enrichment of Dialister, Kineothrix, and Jutongia in responders, whereas Rothia, Leuconostoc, Klebsiella, Jingyaoa, Cuneatibacter, Youxingia, and Bittarella were enriched in non-responders. SCFAs (acetate, propionate and butyrate) positively correlated with microbial glucose catabolic pathways, while caproate was negatively associated with multiple amino acid, lipid, vitamin, and cell wall biosynthesis pathways, including peptidoglycan maturation. Metabolomic analysis identified higher deoxycholic acid (DCA) levels in non-responders and increased C6 levels in responders, although these associations did not remain significant after multiple testing correction. Similar trends were observed in the TNBC subgroup (n = 15). Conclusions: Baseline gut microbiome diversity, taxonomic composition, and functional metabolic potential are associated with response to neoadjuvant chemotherapy in breast cancer, supporting the gut microbiome and its produced metabolites as a potential biomarker of treatment efficacy.

Bioremediation of fluridone by Acinetobacter bereziniae FJ-5: Metabolic pathway, metabolomics mechanism and biotoxicity evaluation.

Abstract Background Enteric bacterial pathogens within the Enterobacteriaceae family, including Escherichia coli and Salmonella species, can cause acute gastroenteritis in humans. In the competitive gastrointestinal environment, these pathogens depend on specific metabolic adaptations to establish infections. The intestinal mucus barrier, composed primarily of the mucin Muc2, protects the epithelium while also serving as a nutrient reservoir rich in host-derived monosaccharides such as N-acetylglucosamine (GlcNAc) and N-acetylneuraminic acid (NeuNAc). How these mucus-derived sugars are metabolized during infection and how dysregulation of these pathways affects bacterial pathogen fitness remain poorly understood. Aims We sought to determine how Enterobacteriaceae exploit mucin-derived sugars for colonization and whether disrupting these pathways impairs their fitness. Citrobacter rodentium, a murine-specific enteric pathogen, was used as a model system and was hypothesized to be able to exploit GlcNAc and NeuNAc to fuel their pathogenesis. Methods C. rodentium mutants were generated, including ΔnagA lacking GlcNAc-6P deacetylase, its complemented strain, and Δmana lacking GlcNAc/NeuNAc import systems. Colonization and tissue pathology were examined in C57BL/6J mice. Intracellular GlcNAc-6P was quantified by the Morgan–Elson assay. Transcriptional responses were analyzed by RT-qPCR. Bacterial susceptibility to cell wall stress was tested using lysozyme, osmotic, and antibiotic challenges. Results Deletion of nagA severely attenuated colonization and pathology in mice, while Δmana remained fully infective, indicating that virulence loss was not solely due to nutrient deprivation. ΔnagA accumulated GlcNAc-6P, grew poorly in vitro, upregulated nagB transcription, suggesting a disrupted glucosamine-6-phosphate (GlcN-6P) synthesis. Functionally, ΔnagA exhibited increased sensitivity to lysozyme, osmotic stress, and cell wall-targeting antibiotics, indicating that cell wall integrity was compromised. Conclusions Disrupting nagA in C. rodentium causes GlcNAc-6P accumulation and disrupted GlcN-6P synthesis, compromising cell wall integrity and in vivo fitness. As these amino sugar catabolic pathways are conserved across Enterobacteriaceae, this work identifies a previously unrecognized metabolic vulnerability that could be exploited to weaken enteric pathogens such as pathogenic E. coli and Salmonella. Targeting sugar-phosphate stress pathways offers a promising approach to limit bacterial infections of the gastrointestinal mucosa. Funding Agencies CIHRNatural Sciences and Engineering Research Council of Canada

Tryptophan metabolism in health and disease- implications for non-communicable diseases.

Microbial remediation as a key pathway for pollutant removal in constructed wetlands: Mechanisms, bioaugmentation strategies, and perspectives.

White-rot fungi are key players in the global carbon cycle through lignin degradation, yet the intracellular pathways that catabolize lignin-derived aromatics remain largely unresolved. The hydroxyphenyl unit compound p-coumaric acid (p-CA) is a major lignin fragment, but the enzymes responsible for its conversion to caffeic acid (CFA) have not been previously identified in fungi. This study demonstrates that Trametes versicolor employs group A flavoprotein monooxygenases (FPMOs) TvMNX3 and TvMNX4 for the hydroxylation of p-CA and related metabolites, representing an unrecognized branch of the p-CA catabolic pathway. Beyond ecological significance, the capacity of TvMNX4 to generate bioactive phenolics such as CFA and piceatannol underscores its potential for biotechnological applications, including the sustainable synthesis of pharmaceuticals and polymer precursors.