14-3-3σ alleviates UVB-induced epidermal oxidative stress through the pentose phosphate pathway promotion.

Impact of Ganoderma lucidum fermentation and micro-pressure pulping on the structure, metabolism, and bioactivity of sugarcane bagasse.

Protocol for metabolic profiling of antigen-specific CD8+ T cells using spectral flow cytometry.

Effects of population density stress on fecal microbiota and metabolites of Qinghai-Tibet Plateau root voles (Microtus oeconomus)—A field experiment

Engineering of the glucose uptake system to increase 2,4-Dihydroxybutyric acid production in Escherichia coli.

Host analysis-guided selection and targeted engineering (HASTE) of Lipomyces tetrasporus for the conversion of CO2-derived feedstocks.

The Integrated Stress Response (ISR) is a vital cellular mechanism that regulates cell survival during various stress conditions, including hypoxia. Activating transcription factor 4 (ATF4) is recognized as a key regulator of ISR, however, its role in hypoxic stress responses remain underexplored. In the present study, we generated an Atf4a-deficient zebrafish model to investigate the role of Atf4a in hypoxia tolerance, mitochondrial homeostasis, and cellular stress adaptation. The results showed that atf4a knockout led to significant growth impairment, endoplasmic reticulum and mitochondrial dysfunction, and disrupted energy metabolism, particularly under hypoxic conditions. We observed an increase in mitochondrial DNA and impaired mitochondrial morphology in Atf4a-deficient zebrafish. Metabolomic analysis revealed significant alterations in the pentose phosphate pathway and TCA cycle following atf4a knockout. Additionally, we observed increased mitochondrial oxidative stress and reduced antioxidant capacity in atf4a mutants. Atf4a-deficiency also led to decreased expression of the mitophagy-related gene p62 and parkin. Atf4a transcriptionally regulates the expression of parkin, suggesting that Atf4a regulates mitochondrial homeostasis through parkin-mediated mitophagy in zebrafish. These results underscore the critical role of Atf4a in maintaining cellular homeostasis, mitochondrial integrity, and metabolic adaptation during hypoxic stress, highlighting its potential as a therapeutic target for stress-related diseases.

Exploration of pairwise interactions between grass carp spoilage bacteria and their occurring mechanisms using co-inoculation experiments and meta-transcriptomic analyses.

Recent evidence suggests that bronchial epithelial cells from individuals with asthma exhibit altered metabolic signatures. This metabolic shift of energetically demanding cells leads to increased inflammation, excessive reactive oxygen species production (ROS), and oxidative stress-all hallmarks of mitochondrial dysfunction. While mitochondrial dysfunction has been implicated in disruption in epithelial cell function in asthma, the mechanistic link between bronchoconstriction observed in asthma and these metabolic alterations remains poorly defined. Club cell secretory protein (CC16) is the most abundant protein found in the lung and exerts key anti-inflammatory and antioxidant functions contributing to protection against airway remodeling. Decreased levels of CC16 in both serum and bronchial alveolar lavage fluid (BALF) are characteristic of asthma and worsening respiratory disease. Using a well-established transmembrane compression system to model bronchoconstriction coupled with mass spectrometry and quantitative proteomics, we investigated how modeling bronchoconstriction in airway cells impacts CC16 expression and cell metabolic pathway changes over time. Using naive mouse tracheal epithelial cells (MTECs) and normal human bronchial epithelial cells (HBECs), we observed that recombinant (r)CC16 induces the expression of proteins related to various metabolic pathways, such as glycolysis, gluconeogenesis, and the pentose phosphate pathway and that compression of airway cells results in acute decreases in CC16 expression, as well as decreases in metabolic processes. MTECs deficient in CC16 (CC16-/-) had lower mitochondrial oxygen consumption rate (OCR) compared to WT cells. Exogenous addition of rCC16 significantly increased OCR of both WT and CC16 deficient MTECs. Our findings suggest a novel role for CC16 in mediating airway epithelial cell metabolic processes, which could be decreased by bronchoconstrictive events in human asthma. The mass spectrometry proteomics data are available via ProteomeXchange with identifier PXD067703.

In conclusion, the present study provides preliminary functional insights into the role of OsbHLH in promoting plant growth under low-nutrient conditions. Ectopic expression of OsbHLH in Arabidopsis was associated with improved plant performance at morphological, physiological, biochemical, and molecular levels under sub-optimal nutrient regimes. Taken together, the study indicates that OsbHLH could be a key component of the regulatory framework of plant-PGPR interactions and nutrient stress responses; further targeted studies are required to conclusively establish its precise functional role and underlying mechanisms. Plant growth-promoting rhizobacteria (PGPR) enhance plant performance under environmentally adverse conditions. In the present study, we analyzed the functional relevance of OsbHLH (OsbHLH63) gene that was notably upregulated in rice following SN13 inoculation under nutrient-deficient conditions. Ectopic expression of OsbHLH in Arabidopsis thaliana resulted in improved growth, and enhanced physio-biochemical attributes under nutrient-deficient conditions. Transgenic plants also exhibited modifications in tissue organization, cellular structure, and lignification patterns. Gene expression analysis revealed differential expression of genes involved in nutrient uptake and transport (IRT1, PHR1, ZNE, NRT, and KUP), lignin biosynthesis (CAD1, CCR1, and COMT), and carbohydrate metabolism (PK1, PEPC1, GDH, FBP, and ENO). Additionally, GC-MS-based metabolomic profiling revealed 40 significantly affected metabolites associated with galactose metabolism, propanoate metabolism, amino acid biosynthesis, the pentose phosphate pathway, the TCA cycle, and glycolysis/gluconeogenesis. Collectively, these findings affirm the potential involvement of OsbHLH in nutrient stress adaptation and in recapitulating key aspects of SN13-induced responses observed in rice, although further targeted investigations are required to validate its regulatory function in plant-microbe interactions and stress tolerance.

Biological systems exhibit intrinsic robustness, allowing cells to sustain growth despite diverse perturbations. We quantified the inherent robustness of the Saccharomyces cerevisiae genome-scale metabolic network by globally perturbing metabolite production fluxes using a hypothetical sink reaction. Among the 317 high-flux active metabolites, excluding macromolecular intermediates and highly connected cofactors, 85% were found to be robust. Of these robust metabolites, more than half (144/269) were overproduced under perturbation compared with minimal-media controls. These metabolites, mapped to a single central metabolic cluster within the metabolic network, were enriched in core biosynthetic pathways and were largely growth-essential, indicating that the network tolerates elevated biosynthetic demand for most key metabolites. Flux- and pathway-level analyses revealed a coordinated adaptive program involving activation of alternative routes at the network periphery and extensive flux redistribution within central metabolism. Central carbon metabolism and oxidative phosphorylation were broadly suppressed, whereas the pentose phosphate, shikimate, and lipid-related pathways were selectively reinforced to support NADPH generation and redox balance. This reorganization establishes an energy-efficient, redox-stabilized metabolic state that underlies system-wide resilience. Together, these findings show that metabolic robustness emerges from a hierarchical network architecture coupling a stable core with flexible peripheral adaptation. This framework explains cellular resilience and offers design principles for engineering robust, damage-resistant metabolic systems.IMPORTANCEIn this study, we investigated the intrinsic robustness of the metabolic network and uncovered a structured organization characterized by a conserved central core and a flexible, peripherally rewired subsystem. Our results suggest that this architecture reflects an evolutionary balance between stability and adaptability. By systematically perturbing more than 300 metabolites, we provide comprehensive and consistent evidence supporting the existence of this core-periphery organization. These findings advance our understanding of how metabolic systems maintain functional stability while retaining the capacity for adaptive rewiring.

Coal-dust, a persistent airborne pollutant, induces dose-related pulmonary fibrosis; however, plasma biomarkers for pre-clinical toxicity remain lacking. We enrolled 158 participants, including 28 healthy controls (HCs), 30 dust-exposed workers (DEWs), and 100 patients with coal workers' pneumoconiosis (CWP) at different stages (n CWP-I=40, n CWP-II=30, n CWP-III=30). Plasma proteomic profiling was performed via data-independent acquisition (DIA) mass spectrometry. Differentially expressed proteins were identified and functionally annotated. Key proteins were selected and multiple machine learning algorithms were employed to construct and validate predictive models. We identified 1,239 plasma proteins, including 645 high-confidence candidates. Functional enrichment revealed significant associations between disease progression and pathways such as PPAR signaling, cholesterol metabolism, Epstein-Barr virus infection, and the pentose phosphate pathway. These alterations converge on dysregulated lipid metabolism, chronic inflammatory signaling and virus-induced immune evasion, suggesting a metabolic-immune axis that orchestrates early fibrotic progression. We successfully constructed the first plasma proteomics-based machine learning models for pneumoconiosis grading and early screening. Notably, a single biomarker, PRSS3, demonstrated exceptional performance in distinguishing DEW patients from early-stage pneumoconiosis patients (CWP-I), achieving an area under the curve (AUC) of 1.00 and an accuracy of 1.00 in the training set and an AUC of 1.00 with an accuracy between 0.93 and 1.00 in the validation set. This study establishes innovative machine learning-based models for the grading and early screening of pneumoconiosis via plasma proteomics. The identification of PRSS3 as a potential biomarker highlights the clinical utility of our approach. These findings provide a foundation for noninvasive diagnostic strategies and future translational research in occupational lung diseases.

Sleep disruption is an early and prevalent feature of neurodegenerative disease, commonly attributed to neuronal circuit dysfunction or cell loss. However, sleep is tightly coupled to metabolic state, raising the possibility that systemic metabolic abnormalities contribute to disease-associated sleep phenotypes. UsingDrosophilamodels of TDP-43 proteinopathy, we investigated whether peripheral metabolic dysfunction plays a causal role in sleep disruption. We show that TDP-43 expression induces a chronic, starvation-like metabolic state characterized by depletion of peripheral carbohydrate stores despite normal feeding. Restoration of sleep fails to correct these metabolic defects, whereas improving peripheral metabolic state robustly rescues sleep. A modifier screen of ∼650 RNAi lines identified Salt-inducible kinase 3 (SIK3) as a potent suppressor of both sleep loss and starvation sensitivity. Transcriptomic and spatial metabolomic analyses reveal that SIK3 selectively remodels a peripheral metabolic program centered on the pentose phosphate pathway and redox-associated metabolites without globally restoring energy stores. Together, these findings identify systemic metabolic dysfunction as a key driver of sleep disruption in TDP-43 proteinopathy and highlight peripheral metabolism as a potential therapeutic entry point for sleep dysfunction in neurodegenerative disease.

Metabolic control of neuronal redox homeostasis:implications of pentose phosphate pathway loss in the nervous system.

Background 1. Senecio scandens Buch.-Ham. (SBH) is widely used in traditional Chinese medicine, yet its clinical application is constrained by hepatotoxic pyrrolizidine alkaloids (PAs). The relative toxic contributions of individual PAs in SBH and their in vivo metabolic consequences remain unclear. Purpose 2. This study sought to elucidate PAs-related hepatotoxicity of SBH by integrating network toxicology, LC-MS/MS fingerprinting, in vivo toxicity evaluation, and liver metabolomics. Methods 3. Network toxicology and molecular docking were used to prioritise hepatotoxic PAs and their putative targets. LC-MS/MS fingerprints of major PAs in 12 SBH samples were established. Spectrum–toxicity correlation analysis and untargeted metabolomics were used to assess hepatotoxicity-related associations and SPL-induced metabolic perturbations. Results 4. SPL, senecionine, adonifoline, and senkirkine were prioritised as candidate hepatotoxic PAs, with CYP3A4/CYP2C9 and DNA adduct-related pathways highlighted as potentially relevant toxicological nodes. Considerable regional variation in PAs levels was observed across SBH samples. Acute SBH exposure caused marked liver injury, and spectrum–toxicity modelling indicated that SPL showed the strongest association with hepatotoxicity among the detected PAs. Metabolomic profiling further showed that SPL exposure was associated with alterations in lipid and bile acid metabolism, glutathione metabolism, and the pentose phosphate pathway, together with enrichment of xenobiotic metabolism by cytochrome P450 and chemical carcinogenesis-DNA adduct pathways. Conclusion 5. SPL is closely associated with SBH-induced hepatotoxicity and produces a metabolic signature consistent with canonical PAs bioactivation. Although SPL appears to be the most influential PAs among those detected, definitive comparisons of toxic potency require further validation using equimolar pure-compound exposure models.

The pentose phosphate pathway contributes to excess lactate production in radiation-induced fibroblast to myofibroblast transdifferentiation.

Mycobiome-linked metabolomic changes reveal two cultivar-specific defense modes in field-infected date palm leaves.

Camptothecin (CPT), a monoterpene indole alkaloid widely used in anticancer therapy, faces production bottlenecks arising from its plant-based origin. In this study, we systematically investigated the metabolic network of the camptothecin-producing fungal endophyte Alternaria burnsii NCIM1409 using an integrative framework combining genome-scale metabolic modeling and 13C-based pathway analysis. A genome-scale metabolic model, AltGEM iDD1552, was reconstructed, encompassing 2,188 reactions, 2,148 metabolites, and 1,552 genes, and was manually curated to incorporate camptothecin biosynthetic pathways. Key enzymatic control points, including secologanin synthase and tryptophan decarboxylase, as potential targets were identified using flux balance for enhancing CPT production. Additionally, metabolic tracer analysis using 20% [U-13C6] glucose and 99% [1-13C] glucose labeling confirmed the active involvement of glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle in central carbon metabolism. Overall, this study establishes a systems-level framework for understanding and optimizing camptothecin biosynthesis in A. burnsii NCIM1409. Collectively, this integrative systems-level analysis elucidates the metabolic capabilities of A. burnsii NCIM1409 and provides rational strategies for optimizing camptothecin biosynthesis, laying the groundwork for sustainable microbial production of this high-value anticancer compound.

Efficient lipid production from macrofilamentous alga Vaucheria hamata FACHB-3853.

Tumor-associated macrophages (TAMs) are critical components of the immune cell population within the tumor microenvironment (TME), where they play dynamic and multifaceted roles throughout the progression of tumorigenesis. Recent evidence suggests that shifts in macrophage metabolic programs-including glycolysis, oxidative phosphorylation, fatty acid utilization, glutamine metabolism, and the pentose phosphate pathway, are closely associated with diverse and context-dependent functional states rather than fixed polarization phenotypes. During tumor progression toward invasion and metastasis, macrophage metabolic programs dynamically adapt to spatial and temporal variations within the TME, often contributing to immunoregulatory or tumor-supportive niches that facilitate angiogenesis, tumor dissemination, immune evasion, and metabolic crosstalk with tumor cells. However, the precise mechanisms underlying these context-dependent adaptations remain incompletely understood. This article reviews current evidence regarding TAM activation states and metabolic reprogramming by various signals in the TME during tumorigenesis and tumor progression, as well as dynamic alterations in TAM metabolic patterns. Furthermore, we explore how secondary metabolites present in the TME influence macrophage metabolic reprogramming and summarize current research on potential therapeutic agents targeting macrophage metabolism. We propose that modulating key metabolic regulators in TAMs or intervening in metabolic-immune crosstalk pathways may offer novel strategies for precision medicine in cancer therapy, providing a theoretical foundation for metabolic intervention-based immunotherapeutic approaches.