Search Results (152)

Alpha-ketoglutarate (aKG) is a central intermediate of cerebral energy metabolism and a precursor for glutamate synthesis in the brain. Alterations in aKG metabolism occur in pathological contexts, including isocitrate dehydrogenase (IDH) mutant astrocytomas and oligodendrogliomas, in which mutant IDH converts aKG to the oncometabolite 2-hydroxyglutarate. Given its central role in brain metabolism, non-invasive interrogation of aKG-dependent metabolic flux is needed. Hyperpolarized (HP) ¹³C MR enables real-time visualization of metabolic conversion by transiently enhancing signal intensity by several orders of magnitude. Leveraging this approach, we report the first-in-human feasibility and safety study of HP [1-¹³C]aKG MR spectroscopy in the healthy brain (n = 3). A standard operating procedure (SOP) was developed for sterile [1-¹³C]aKG dose production, achieving reproducible polarization levels averaging 30.5 ± 2.2%. Following intravenous administration, time-resolved ¹³C spectra in healthy volunteers demonstrated the detection of HP aKG resonance and a measurable downstream glutamate signal, consistent across repeat acquisitions, with a delayed temporal profile relative to aKG observed in a representative dataset. Although performed in healthy volunteers, these results establish feasibility for HP [1-¹³C]aKG metabolic imaging to open a new window into normal and pathological brain cellular metabolism. Full article

Background: Race walking, an Olympic discipline, produces an increase in energy cost and a change in the recruitment pattern of muscle fibres compared with running, yet the cardiorespiratory responses of elite race walkers to severe-intensity exercise remain poorly characterised. Objectives: (i) To determine whether exhaustive exercise performed at vΔ50 elicits VO₂max in young elite race walkers, and (ii) to compare the temporal and metabolic profiles of this effort with those of similarly trained runners. Methods: Fourteen elite junior athletes (seven race walkers and seven runners) completed an incremental test to determine velocity at the lactate threshold (vLT), vVO2max, and VO2max, followed by a constant-velocity trial at individual vΔ50 performed to voluntary exhaustion on a 400 m track. Breath-by-breath VO2, heart rate, capillary blood lactate concentration, and time to exhaustion, time limit (Tlim) were measured. Results: At vΔ50 (≈94% vVO2max), the race walkers reached VO2max, with no detectable VO2 slow component (SC) in six of seven participants. In contrast, runners exhibited a significant SC (8 ± 3% of total VO2). The energy cost (EC) was 16% higher in race walking than in running (p < 0.01). Conclusions: In elite junior race walkers, it seems that vΔ50 reliably elicits VO2max primarily due to a high baseline oxygen cost rather than a progressive VO2 SC, contrasting with the kinetic response observed in running. These discipline-specific responses suggest that interval training in race walking should be prescribed using walking-specific thresholds. This study is preliminary, given the small sample size; further studies with larger cohorts are warranted. Full article

Indigenous pigs constitute crucial genetic reservoirs. Adipose tissue is central to pig growth and metabolism, yet its molecular ontogeny remains poorly characterized in indigenous breeds such as the Ningxiang pig. We employed mass spectrometry to profile backfat proteomes across six postnatal stages (60–360 days). Proteomes clearly separated early (60–120 days) from late stages (300–360 days). Older pigs showed enrichment in processes linked to energy metabolism, translation, immune function, and mitochondrial activity. We identified 43 lipid metabolism proteins exhibiting significant age-dependent abundance. Weighted co-abundance network analysis revealed four protein modules significantly correlated with lean meat percentage, fat percentage, and carcass weight. Intramodular analysis identified four hub proteins—ALDH18A1, FABP4, FBP1, and HADHB—as putative candidates associated with lipid transport, gluconeogenesis, and fatty acid oxidation. This study links temporal proteomic profiles with key carcass traits, providing a data resource and a network-based framework for future research. Full article

Chicken manure and its potential to contaminate water systems through the dispersal of pathogenic bacteria are major concerns in environmental and public health. In this study, a metagenomic analysis was employed to systematically identify and compare bacterial assemblages in chicken manure (CM) and in a contaminated sample of chicken manure wastewater (CMW). Whole DNA was extracted from CM and CMW, followed by whole-genome shotgun sequencing; data analysis was done using online Galaxy software (ver. 26.0.1.dev1). Metagenomic analysis reveals a complex One Health challenge. Data showed that CM and CMW are different in their microbiota, as indicated by a distinct separation of beta diversity values and limited overlapping of species between sample types. In the current study, we found a greatly significant common functional set of adapted bacterial masses, including major pathogenic bacterial groups as well as opportunistic and environmental bacterial species, indicative of a direct contamination from CM and CMW. Notably, in both CM and CMW, a plethora of opportunistic, enteric, and environmental pathogens like Escherichia coli, Salmonella enterica, and Acinetobacter baumannii were found, coupled with an indication of a direct functional flow between both ecosystems as tangled reservoirs. Chicken manure samples showed differences in taxonomic composition and inferred functional profiles at the time of sampling: CM1 was pathogen-enriched, CM2 exhibited strong nitrogen-supportive metabolism, CM3 was dominated by fiber-degrading decomposers, and CM4 showed high methane-producing potential with environmental risk. Such findings underscore the raising of chickens as a potential source of harmful bacteria for the environment. It is important to note that this study represents a preliminary investigation with certain limitations, including the absence of biological replicates, lack of temporal sampling, and limited capacity to infer dynamic ecological interactions. Yet this metagenomic report is more about describing the taxonomy and functional potential of the bacteria, rather than discussing the actual ecological processes of these microorganisms in the environment. Future studies will be required to explore these aspects. Full article

Exercise adaptation and training maladaptation arise from overlapping metabolic, redox, inflammatory, endocrine, and tissue-remodeling processes, so the translational question is not whether biomarkers change but when, where, and for which decision they become informative. This narrative review develops a decision-linked framework for minimally invasive biomarkers across the recovery–overload continuum and treats biomarker meaning as a molecule–matrix–time–decision relationship rather than as a stand-alone peak. The framework is organized around five coupled layers: stimulus architecture, signaling and release biology, sampling matrix and pre-analytics, bout-relative kinetics, and the monitoring decision to be supported. Current evidence indicates that no single biomarker reliably separates productive remodeling from delayed recovery, tissue strain, non-functional overreaching, or early maladaptation. Classical chemistry remains useful for bounded tasks, especially delayed tissue strain and stress reactivity; cfDNA appears promising for rapid load sensitivity; targeted metabolite panels are strongest for recovery phenotyping; and circulating RNAs and extracellular-vesicle cargo add mechanistic depth but remain constrained by pre-analytical fragility and incomplete standardization. The central practical implication is that overload is better interpreted as progressive loss of signal resolution than as threshold-crossing and that sparse temporally staggered panels are more likely to aid monitoring decisions than isolated markers or untimed high-dimensional profiles. Progress will depend on purpose-specific panels, transparent analytical standards, and prospective validation against symptoms, performance, and established measures across sex, hormonal, circadian, and training contexts. Full article

Exercise adaptation depends on overload that is resolved by recovery, yet the same biology becomes maladaptive when immune, endocrine, metabolic, and muscle-centered stress signals fail to normalize. Exercise-induced maladaptation represents a systems-level failure of biological resolution, with direct relevance to disease-like dysregulation. Functional overreaching, non-functional overreaching, and overtraining syndrome remain difficult to diagnose because no single biomarker provides adequate specificity, temporal stability, or clinical portability. This narrative review synthesizes human and mechanistic evidence across proteomics, transcriptomics, metabolomics, endocrine profiling, extracellular vesicles, and mitochondrial quality-control biology to define the molecular architecture most relevant to athlete monitoring. Across these layers, the most coherent signatures cluster in immune-acute-phase activation, redox-buffering strain, endocrine drift, altered substrate availability, excitation–contraction dysfunction, integrated stress-response signaling, and defects in autophagy–mitophagy and lysosomal remodeling. Three translational elements emerge from this synthesis: a systems-convergence model of recovery failure, a staged biomarker deployment hierarchy, and a provisional recovery failure index. The practical priority is therefore not a solitary marker, but serial phenotype-anchored multimarker panels that connect circulating signals with muscle-centered biology and support decision-making before prolonged recovery failure becomes entrenched. Full article

With the continuous expansion of Pleurotus ostreatus cultivation, substantial quantities of post-harvest spent mushroom substrate (SMS) are generated. Improper disposal of this organic waste poses potential threats to soil health, including contamination and ecological imbalance. Consequently, a rigorous safety assessment is indispensable to support the sustainable and agronomically viable utilization of SMS as a soil amendment. In this study, P. ostreatus SMS was subjected to sterilized and non-sterilized treatments, and a controlled co-culture system integrating P. ostreatus mycelium with wheat was established. This system facilitated a comprehensive evaluation of residual mycelium impacts on wheat growth and development at phenotypic, cytological, and non-targeted metabolomics (LC-MS) levels. Results demonstrated that direct field application of non-sterilized SMS severely compromised wheat performance, inducing root necrosis and significantly reducing grain set. Comparative experiments confirmed that non-sterilized SMS—not its sterilized counterpart—exerted pronounced phytotoxic effects, markedly inhibiting seedling growth and triggering wilting symptoms. To elucidate the temporal dynamics of mycelial interaction, wheat seedlings were inoculated with viable P. ostreatus mycelium and co-cultured for seven days. Under these conditions, the mean root length of the control group (10.82 cm) was approximately threefold that of the treatment group. Histopathological analysis revealed a progressive infection pattern initiating at the root apex and extending basipetally; prolonged exposure ultimately caused complete root system collapse. Scanning electron microscopy further showed extensive mycelial colonization on infected root surfaces, accompanied by characteristic cellular damage—including severe cell wall wrinkling and widespread cell death. LC-MS profiling identified 1867 annotated compounds. Comparative analysis revealed significant dysregulation of secondary metabolism, with 495 metabolites upregulated and 419 metabolites downregulated in the treatment group. Collectively, these findings provide robust evidence that unprocessed P. ostreatus SMS poses tangible agronomic risks upon direct soil application. This study establishes a critical scientific foundation for developing safe, evidence-based protocols for the valorization and integrated management of SMS. Full article

Lentinula edodes (Berk.) Pegler, also known as Shiitake, is one of the most popular edible mushroom species containing high contents of polysaccharides, proteins and unique aroma, widely cultivated in China, Japan and Korea. A series of studies has been carried out on the extraction and active effect of the L. edodes polysaccharides, but the molecular mechanisms involved in the protein expression profiles during the whole life cycle are relatively unclear. This study employed an iTRAQ-MS/MS proteomic approach, combined with real-time quantitative PCR (qRT-PCR) and enzyme activity assays, to systematically analyze the protein expression profiles and their relationship with lignocellulose degradation in L. edodes across four key developmental stages: mycelia (SF), brown film formation (BF), primordia (YF), and fruiting bodies (MF). A total of 2043 proteins were identified, with 1188 being differentially expressed proteins (DEPs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that metabolic processes, carbohydrate metabolism, and related pathways were significantly active during development. The study specifically focused on carbohydrate-active enzymes (CAZymes), identifying 197 CAZyme proteins classified into 78 families. Key families such as glycoside hydrolases (GHs) and carbohydrate esterases (CEs) played crucial roles in lignocellulose degradation. The enzymatic activities of major lignin-degrading enzymes (laccase, manganese peroxidase, and lignin peroxidase) were dynamically regulated across the developmental stages. qRT-PCR results largely corroborated the proteomic data, confirming the reliability of the protein expression profiles. This study provides a comprehensive, stage-resolved proteomic landscape of lignocellulose degradation during L. edodes development, revealing species-specific temporal dynamics, offering a valuable basis for understanding its growth and development, with implications for edible fungus cultivation and biomass conversion applications. Full article

Background: Conventional analyses of physiological recovery often rely on discrete metrics that assume independence across time points, thereby ignoring intrinsic temporal continuity and masking substantial interindividual heterogeneity. This proof-of-concept study assesses the efficacy of Functional Data Analysis (FDA) as a promising framework for characterizing individual response dynamics following a functional threshold power (FTP) test. Methods: Physiological time-series data (including blood lactate, heart rate, blood pressure, and glucose levels) collected from 21 trained cyclists (10 professionals, 11 amateurs) were represented as functional objects using FDataGrid on the original sampling grid (0, 3, 5, 10, 20 min), without basis expansion or smoothing. We conducted unsupervised functional clustering (K-means; Fuzzy K-means) and supervised classification (Maximum Depth with Modified Band Depth, K-Nearest Neighbors, Nearest Centroid, functional QDA with parametric Gaussian covariance). Model performance was estimated via Repeated Stratified 5-Fold Cross-Validation with 10 repetitions (50 folds), reporting accuracy, balanced accuracy (mean ± SD), 95% CIs, permutation p-values, and sensitivity/specificity from aggregated confusion matrices. Results: Lactate (CL) and diastolic blood pressure (DBP) provided useful and statistically significant discrimination across several classifiers (e.g., KNN, Nearest Centroid, functional QDA), whereas heart rate showed modest discriminative value and glucose intermediate performance. Unsupervised analyses revealed distinct lactate recovery profiles and graded membership for hemodynamic/metabolic variables, supporting the value of FDA for resolving heterogeneity beyond group-average trends. Conclusions: FDA offers a feasible and informative approach for classifying recovery phenotypes while preserving temporal structure. Findings are promising but should be interpreted with caution due to the small sample size, sparse time points, and the need for external validation in larger, independent cohorts before translation into routine decision-making. Full article

Chandipura virus (CHPV) is a neurotropic rhabdovirus associated with recurrent outbreaks of acute encephalitis in children and a high case fatality rate, particularly in India. Despite its public health relevance, the host molecular processes governing CHPV infection and disease progression remain poorly defined. To address this gap, we conducted a time-resolved transcriptomic analysis to characterize host responses to CHPV infection and to explore host-directed therapeutic opportunities. Human HEK293T cells were infected with CHPV, followed by RNA sequencing (RNA-seq) at 6, 12, 18, and 24 h post infection (hpi). Transcriptome profiling revealed a temporally ordered host response. At 6 hpi, CHPV infection was dominated by strong activation of innate immune and inflammatory pathways, including interferon-stimulated genes and cytokine signaling. Antiviral responses persisted at 12 hpi, accompanied by suppression of metabolic and translational processes, indicating a shift in host cellular priorities. By 18 hpi, metabolic reprogramming—particularly involving lipid and sphingolipid metabolism—was observed alongside altered immune signaling, consistent with viral exploitation of host cellular machinery. At 24 hpi, repression of genes involved in chromatin organization, RNA processing, spliceosome assembly, and ribosome biogenesis reflected a global transcriptional shutdown associated with cytopathic effects. Integration of temporal transcriptomic signatures enabled identification of host pathways amenable to pharmacological targeting. Selected host-directed compounds were evaluated in vitro and exhibited antiviral activity against CHPV in a neuronal cell line. Collectively, this study provides the first time-resolved transcriptomic landscape of CHPV infection in human cells and identifies host-targeted strategies relevant for antiviral development. Full article

Background/Objectives: Trace metal homeostasis is regulated by nutritional status and is crucial for maintaining redox balance, vascular function, and neuroinflammation. Dysregulation of systemic copper (Cu) metabolism, especially an elevated level of non-ceruloplasmin-bound copper (NCC), has been linked to oxidative stress and early cognitive decline. However, the nutritional and molecular pathways that connect Cu imbalance to mild cognitive impairment (MCI) are not well understood. Methods: We compared the serum Cu and zinc levels of individuals with normal cognition (NC; n = 116) and MCI (n = 184). An exploratory serum proteomic analysis using pooled samples was conducted to investigate patterns related to Cu dysregulation. We identified proteins using pattern correlation analysis and then performed a protein–protein interaction analysis using STRING and functional annotation and biological and Kyoto Encyclopedia of Genes and Genomes pathways. Results: The individuals with MCI had higher NCC levels than those with NC, indicating disrupted Cu metabolism influenced by nutrition and metabolism. The proteomic analysis revealed changes in proteins related to lipid transport, metal balance, and inflammation, including transthyretin, transferrin, apolipoprotein A-I, alpha-1 antitrypsin, antithrombin III, and alpha-2-macroglobulin, which respond to oxidative stress and vascular injury. Conclusions: In this cross-sectional analysis of baseline data, NCC levels were associated with cognitive status and specific circulating proteomic profiles. These findings suggest a potential relationship between copper-related biomarkers and mild cognitive impairment; however, longitudinal studies are required to clarify temporal relationships and potential mechanistic pathways. Full article

In this study, Eurotium cristatum was used for the solid-state fermentation of Angelica dahurica, and the dynamic changes in metabolites during fermentation were investigated. The results showed that fermentation markedly altered the volatile metabolite profile, increasing the relative abundance of terpenoids while decreasing that of alcohols and aldehydes. In combination with principal component analysis (PCA), 24 key volatile compounds were screened. Liquid chromatography–mass spectrometry (LC–MS)-based untargeted metabolomics identified 892 differential annotated non-volatile metabolites and temporal clustering analysis was further applied to characterize their changes. The results showed metabolic fluctuations occurred during the initiation and early fermentation stages, during which carbohydrates and nucleotides were consumed. Secondary metabolites accumulated in the early and middle fermentation. Lipid compounds overall increased in the early fermentation but declined in the middle and late fermentation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 12 key metabolic pathways. This work systematically reveals the change pattern of the metabolite composition of A. dahurica driven by E. cristatum solid-state fermentation, providing a scientific basis for quality improvement and mechanistic studies of fermented A. dahurica products. Full article

Perennial deciduous trees such as Prunus avium undergo seasonal transitions, culminating in bud dormancy establishment that involves coordinated physiological and metabolic adjustments. Dormancy monitoring in orchard systems still relies primarily on temperature-based models and forcing assays, which rarely incorporate physiological or biochemical indicators. Here, we tested whether seasonal metabolic dynamics associated with dormancy progression differ between sweet cherry genotypes and whether these physiological differences are reflected in canopy-scale vegetation indices derived from satellite observations. Field measurements were conducted in two genotypes with contrasting chilling behavior (‘Regina’ and ‘210’) during the transition from vegetative growth to dormancy. Leaf gas exchange and chlorophyll fluorescence were monitored across the season, polar metabolites in floral buds were profiled by gas chromatography-mass spectrometry, and satellite-derived vegetation indices were used to characterize canopy dynamics. Dormancy progression was associated with declines in CO₂ assimilation, transpiration, PSII photochemical efficiency, and electron transport rate, accompanied by increases in intercellular CO₂ concentration and non-regulated energy dissipation. Metabolomic analysis revealed that genotype explained a larger proportion of metabolite variation than dormancy stage (PERMANOVA R² = 0.483, p = 0.001), while principal component analysis accounted for 79.7% of total variance. Fructose showed the strongest genotype difference during paradormancy I, corresponding to an approximately 9.5-fold increase in ‘Regina’. Pathway enrichment analysis highlighted starch and sucrose metabolism and pyruvate metabolism as the most represented pathways during dormancy progression. Satellite-derived vegetation indices captured seasonal canopy decline and were significantly associated with several physiological variables. These results provide an integrated description of physiological and metabolic adjustments during dormancy establishment in sweet cherry and highlight the potential of combining metabolomics, plant physiology, and open-access satellite observations to monitor phenological transitions in orchard systems at scalable spatial and temporal resolutions. Full article

Background: Cutaneous radiation injury arises when ionizing radiation disrupts epidermal barrier integrity, triggering persistent DNA damage, oxidative stress, and senescence-associated inflammatory signaling that drive extracellular matrix degradation and impaired regeneration. Clinical burden is rising due to dose-intensified radiotherapy, but also due to an increased use of energy-based aesthetic procedures that elicit radiation-like dermal injury. Dermal fibroblasts exhibit marked sensitivity to ionizing radiation and rapidly acquire senescence-associated secretory phenotypes that suppress collagen biosynthesis and promote chronic inflammation, underpinning the need for regenerative treatments that restore tissue homeostasis and regenerative competence. Mesenchymal stem cell–derived exosomes have emerged as a promising therapeutic strategy in this setting, with increasing preclinical evidence demonstrating their capacity to attenuate oxidative stress, enhance DNA damage-repair pathways, and normalize fibroblast metabolic function. Methods: In this study, we examine the expression profiles for 14 radiation response–associated genes of irradiated human dermal fibroblasts that were treated with bone marrow and umbilical cord MSC-derived exosomes at different timepoints using quantitative RT-PCR analysis. We also explore functional relationships among these genes through interaction network analysis, and outline a framework to organize pathway-level transcriptional responses to irradiation and exosome treatment. Results: MSC-derived exosome treatment was associated with attenuated early damage response signaling at 24 h, followed by increased expression of genes associated with DNA repair and oxidative stress recovery at intermediate timepoints. Exosome-treated cells also exhibited transcriptional changes consistent with modulation of cell-cycle regulatory pathways and reduced expression of pro-inflammatory markers by 5 d. These findings suggest that MSC-derived exosomes influence the temporal organization of the fibroblast transcriptional response to ionizing radiation and may contribute to molecular programs associated with tissue recovery following ionizing radiation exposure. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Lipid metabolism, especially phospholipids, has been reported to be altered in PD. The purpose of this study is to investigate the temporal expression and spatial distribution of phospholipids in the motor cortex and striatum at different time points of PD using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mouse model. Mice were injected with saline (NSS) or MPTP at two different time points to create acute and subacute models. Motor analysis was performed at 0, 3, 7, 14, and 21 days post-injection. Tyrosine hydroxylase (TH) staining revealed progressive damage of neurons in the substantia nigra compacta (SNc) and reduced striatal fibers in MPTP-treated animals. By using MALDI-MSI, we identified changes in phosphatidylcholine (PC) profiles in the brains of MPTP-treated animals. Polyunsaturated PCs, including PC 36:4 (16:0/20:4), PC 38:6 (16:0/22:6), and PC 40:8 (18:2/22:6), were decreased in the MPTP-treated groups. These reductions were time-dependent and were more pronounced in the subacute MPTP-treated group. The loss of dopamine neurons caused by MPTP may be associated with the selective loss of polyunsaturated PCs in brain membranes, indicating that lipid metabolism and membrane structural alterations may contribute to the pathology of PD. Full article