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17 pages, 2609 KB  
Article
Metabolomic Profiling of Heat Tolerance During Grain Filling in Rice: Comparative Analyses of Panicles and Roots in ‘Fusaotome’ and ‘Akitakomachi’
by Atsushi Ogawa, Saki Yoshino and Kyoko Toyofuku
Agriculture 2025, 15(21), 2255; https://doi.org/10.3390/agriculture15212255 - 29 Oct 2025
Viewed by 203
Abstract
High temperatures during grain filling degrade rice quality, yet the metabolite-level basis of varietal tolerance—particularly root contributions—remains unclear. We compared the heat-tolerant ‘Fusaotome’ and the widely grown ‘Akitakomachi’ under control and high-temperature conditions. Panicles and roots were sampled at heading and profiled by [...] Read more.
High temperatures during grain filling degrade rice quality, yet the metabolite-level basis of varietal tolerance—particularly root contributions—remains unclear. We compared the heat-tolerant ‘Fusaotome’ and the widely grown ‘Akitakomachi’ under control and high-temperature conditions. Panicles and roots were sampled at heading and profiled by capillary electrophoresis–mass spectrometry (CE–MS), followed by PCA, univariate testing, and KEGG pathway analysis. PCA resolved treatment and cultivar differences in an organ-specific manner. In panicles, ‘Fusaotome’ showed 8 increased metabolites (≥1.5-fold) and 11 decreased (≤1/1.5), whereas ‘Akitakomachi’ showed 19 increases and 6 decreases (p < 0.05). In roots, 12 metabolites increased in ‘Fusaotome’ and 9 in ‘Akitakomachi’; no significant decreases were detected. Pathway analysis indicated activation in ‘Fusaotome’ panicles of tryptophan, nicotinate/nicotinamide, arginine/proline, glycolysis/TCA, pyruvate, and vitamin B6 pathways, while ‘Akitakomachi’ emphasized phenylpropanoid, isoquinoline alkaloid, caffeine, and ubiquinone/terpenoid–quinone biosynthesis. In roots, ‘Fusaotome’ prioritized phenylalanine/phenylpropanoid, aromatic amino acids, lysine degradation, branched-chain amino acids, glycerophospholipids, and alkaloids, whereas ‘Akitakomachi’ favored nitrogen- and antioxidant-related routes. Collectively, the tolerant cultivar maintained antioxidant capacity and energy supply while coordinating root–panicle metabolism, whereas the susceptible cultivar shifted toward secondary defenses. These signatures nominate candidate metabolic markers and targets for breeding and management to stabilize rice production under warming climates. Full article
(This article belongs to the Section Crop Production)
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23 pages, 6892 KB  
Article
Built-Up Surface Ensemble Model for Romania Based on OpenStreetMap, Microsoft Building Footprints, and Global Human Settlement Layer Data Sources Using Triple Collocation Analysis
by Zsolt Magyari-Sáska and Ionel Haidu
ISPRS Int. J. Geo-Inf. 2025, 14(11), 420; https://doi.org/10.3390/ijgi14110420 - 28 Oct 2025
Viewed by 197
Abstract
Accurate and up-to-date data on built-up areas are crucial for urban planning, disaster management, and sustainable development, yet Romania still lacks a unified, official database. In this study we integrated the three widely used global data sources—OpenStreetMap (OSM), Microsoft Building Footprints (MSBFs), and [...] Read more.
Accurate and up-to-date data on built-up areas are crucial for urban planning, disaster management, and sustainable development, yet Romania still lacks a unified, official database. In this study we integrated the three widely used global data sources—OpenStreetMap (OSM), Microsoft Building Footprints (MSBFs), and Global Human Settlement Layer Built-up surface (GHS)—onto a 10 m resolution raster grid and applied this consistently at the national scale across 3181 settlement polygons to produce a more accurate, unified ensemble model for Romania. The methodological basis was Triple Collocation Analysis (TCA), extended with ETC/CTC to estimate per-settlement scale factors, enabling the quantification and optimal weighting of the relative errors and accuracy in the absence of independent reference data. Weight patterns vary by settlement type: OSM receives relatively higher weights in smaller rural settlements with less redundant error; in municipalities the stronger OSM–MSBF correlation reduces both of their weights and increases the GHS share; cities exhibit a more balanced weighting. At cell level, the ensemble provides uncertainty quantification via confidence intervals that typically range from 2% to 14% at settlement scale. The resulting model—like any model—does not perfectly reflect reality; however, the ensemble improves the accuracy and timeliness of the available data. The resulting model is replicable and updatable with newer data, making it suitable for numerous practical applications, especially in spatial development and risk analysis. Full article
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21 pages, 3483 KB  
Article
Field Validation of OTR-Modified Atmosphere Packaging Under Controlled Atmosphere Storage for Korean Melon Export to Vietnam
by Tae-Yeong Ko, Sang-Hoon Lee, Yoo-Han Roh, Jeong Gu Lee, Haejo Yang, Min-Sun Chang, Ji-Hyun Lee and Kang-Mo Ku
Horticulturae 2025, 11(11), 1295; https://doi.org/10.3390/horticulturae11111295 - 28 Oct 2025
Viewed by 292
Abstract
Korean melon (K-melon, Cucumis melo L. var. makuwa) is a key horticultural crop in the Republic of Korea, but its short shelf life restricts long-distance export. This study evaluated the modified atmosphere (MA) films of varying oxygen transmission rates (OTR) at controlled atmosphere [...] Read more.
Korean melon (K-melon, Cucumis melo L. var. makuwa) is a key horticultural crop in the Republic of Korea, but its short shelf life restricts long-distance export. This study evaluated the modified atmosphere (MA) films of varying oxygen transmission rates (OTR) at controlled atmosphere (CA) storage under real maritime export conditions to Vietnam. In the non-permeable OTR 0 (Control) treatment, internal O2 rapidly declined below the anaerobic compensation point (1.67% at 10d and 0.47% at 10+3d) while CO2 accumulated to 32–36%. This ultra-low oxygen environment induced anaerobic metabolism, evidenced by strong accumulation of fermentative metabolites such as lactic acid, acetoin, and 2,3-butanediol, along with glucose/fructose retention and increases in alanine and γ-Aminobutanoic acid (GABA). These changes disrupted glycolysis and the Tricarboxylic acid cycle (TCA), consistent with CA shock, and were accompanied by rind blackening, elevated weight loss, and hue angle shifts toward yellow-orange. By contrast, OTR 10,000 and OTR 30,000 films significantly suppressed weight loss and color changes. Partial least squares-discriminant analysis (PLS-DA) identified volatile organic compounds, namely acetoin, 2,3-butanediol, and hexanal, as key discriminant metabolites, with OTR 30,000 clearly separated from other treatments at 10+3d, indicating minimal fermentation and oxidative stress. Microbial assays revealed a dose-dependent reduction in bacterial counts with increasing OTR, while fungal growth was most strongly suppressed under OTR 10,000. Overall, OTR 30,000 maintained the lowest and most stable levels of stress-related metabolites, minimized microbial proliferation, and preserved metabolic stability throughout shipping. This study provides the first quantitative evidence of anaerobic metabolic transition and primary metabolite accumulation in K-melons under actual export trials. The findings demonstrate that optimizing MA film permeability, particularly OTR 30,000 films, offers a practical and cost-efficient strategy to extend shelf life, maintain quality stability, and enhance the global export potential of K-melons. Full article
(This article belongs to the Section Postharvest Biology, Quality, Safety, and Technology)
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14 pages, 4143 KB  
Article
Adipose Inositol Monophosphate Metabolism Is Associated with Fasting Regimen-Elicited Metabolic Benefits
by Chunqing Wang, Bilian Liu, Xin Yang, Xi Chen, Shuo Wang, Xing Zhang and Meilian Liu
Biomolecules 2025, 15(11), 1514; https://doi.org/10.3390/biom15111514 - 27 Oct 2025
Viewed by 222
Abstract
Intermittent fasting (IF) has emerged as a promising strategy for managing obesity and related metabolic disorders. Although metabolic adaptations in adipose tissue during IF are well documented, the specific reprogramming of white adipose tissue (WAT) under prolonged cycles of fasting and refeeding remains [...] Read more.
Intermittent fasting (IF) has emerged as a promising strategy for managing obesity and related metabolic disorders. Although metabolic adaptations in adipose tissue during IF are well documented, the specific reprogramming of white adipose tissue (WAT) under prolonged cycles of fasting and refeeding remains incompletely understood. Using mass spectrometry-based approaches, including liquid chromatography (LC) and capillary electrophoresis (CE), we identified a marked increase in inositol monophosphates (InsP1s) in obese adipose tissue following extended IF. Specifically, myo-inositol-1-phosphate and myo-inositol-3-phosphate, which are typically present at low levels in gonadal WAT (gWAT) of diet-induced obese mice, were significantly elevated after 15 cycles of IF. Additionally, extended IF upregulated the expression levels of inositol tetrakisphosphate 1-kinase (ITPK1) and inositol monophosphatase 1 (IMPA1), two key enzymes involved in InsP1 metabolism. These increases coincide with reductions in body weight and fat mass, as well as improved insulin sensitivity. This reprogramming was further supported by enhanced tricarboxylic acid (TCA) cycle activity. Collectively, these findings suggest the inositol monophosphate pathway as a novel mechanism underlying fasting-induced metabolic adaptation in adipose tissue and highlight the potential of these metabolites as biomarkers for obesity and related metabolic conditions. Full article
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30 pages, 5963 KB  
Review
Engineering Inorganic Nanoparticles to Induce Cuproptosis: A New Strategy for Cancer Therapy
by Zhenxing Jiang, Jianwei Dai, Juanjuan Jiang, Shenghe Deng, Junnan Gu, Jun Wang, Mian Chen, Wentai Cai, Ke Wu, Kaixiong Tao, Ke Liu and Kailin Cai
Pharmaceutics 2025, 17(11), 1383; https://doi.org/10.3390/pharmaceutics17111383 - 24 Oct 2025
Viewed by 656
Abstract
Cuproptosis is a newly identified type of copper (Cu)-dependent programmed cell death (PCD), triggered when Cu directly interacts with the lipoylated components of the tricarboxylic acid (TCA) cycle, and it has shown significant antitumor potential. However, challenges such as insufficient Cu accumulation in [...] Read more.
Cuproptosis is a newly identified type of copper (Cu)-dependent programmed cell death (PCD), triggered when Cu directly interacts with the lipoylated components of the tricarboxylic acid (TCA) cycle, and it has shown significant antitumor potential. However, challenges such as insufficient Cu accumulation in tumor cells, systemic toxicity, and the lack of specific carriers for effectively inducing cuproptosis hinder its practical application. Inorganic nanoparticles (INPs) present a promising solution due to their unique ability to target specific areas, potential for multifunctional modification, and controlled release capabilities. Their distinctive physicochemical properties also enable the integration of synergistic multimodal cancer therapies. Therefore, utilizing INPs to induce cuproptosis represents a promising strategy for cancer treatment. This review systematically elucidates the regulatory mechanisms of Cu homeostasis and the molecular pathways underlying cuproptosis, thoroughly discusses current INP-based strategies designed to trigger cuproptosis, and comprehensively examines the multi-modal synergistic antitumor mechanisms based on cuproptosis. Finally, we also address the current challenges and future perspectives in developing clinically applicable nanoplatforms aimed at harnessing cuproptosis for effective cancer therapy. Full article
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18 pages, 2322 KB  
Article
Iron Stress Reprograms Enterocyte Metabolism
by Shya E. Navazesh and Peng Ji
Metabolites 2025, 15(11), 691; https://doi.org/10.3390/metabo15110691 - 24 Oct 2025
Viewed by 264
Abstract
Objectives: This study utilized IPEC-J2, a neonatal pig jejunum-derived cell line, to assess how iron deficiency (ID) and excess (IE) alter enterocyte metabolism and the transcription of inflammatory markers. Methods: Cells were treated with deferiprone (DFP) or ferric ammonium citrate (FAC) [...] Read more.
Objectives: This study utilized IPEC-J2, a neonatal pig jejunum-derived cell line, to assess how iron deficiency (ID) and excess (IE) alter enterocyte metabolism and the transcription of inflammatory markers. Methods: Cells were treated with deferiprone (DFP) or ferric ammonium citrate (FAC) to induce ID or IE, respectively. The study evaluated: (1) transcriptional changes in iron-regulatory genes over 96 h under ID or IE; (2) the interaction between iron imbalance and lipopolysaccharide (LPS) exposure on mRNA expression of inflammation markers and iron transporters; and (3) cellular metabolic responses to ID, IE, and iron repletion using untargeted metabolomics. Results: ID triggered dynamic transcriptional changes in iron regulatory genes and suppressed cellular proliferation via impaired DNA replication. IE resulted in a persistent reduction in TFRC expression. LPS increased CYBRD1 (p < 0.001) and IL8 (p = 0.004) and tended to elevate TLR4 and TNF expression (p ≤ 0.07), while iron deficiency upregulated IL8 expression (p < 0.001). ID disrupted the TCA cycle, reduced glucuronic acid synthesis, and elevated glycolysis for energy production, whereas IE increased cholesterol biosynthesis and decreased alpha-tocopherol levels. Repletion of iron partially reversed ID-induced metabolic changes. Conclusions: ID impaired enterocyte proliferation and profoundly disrupted cellular metabolism, whereas IE enhanced cholesterol synthesis and depleted alpha-tocopherol levels. Restoration of cellular metabolism following iron repletion was observed, highlighting the resilience of enterocytes. Full article
(This article belongs to the Section Cell Metabolism)
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12 pages, 5513 KB  
Article
Sustainable Cyanobacterial Bloom Control: Inhibitory Effects of Nano Zero-Valent Iron on Microcystis aeruginosa and Metabolic Disruption
by Guoming Zeng, Zilong Ma, Xiaoling Lei, Yong Xiao, Da Sun and Yuanyuan Huang
Toxics 2025, 13(11), 915; https://doi.org/10.3390/toxics13110915 - 24 Oct 2025
Viewed by 276
Abstract
The bloom of cyanobacteria has severely disrupted ecological balances, posing significant risks to human health and safety. However, there is currently a lack of environmentally friendly methods that can sustainably suppress these blooms over the long term. This study integrates untargeted metabolomics, Fourier-transform [...] Read more.
The bloom of cyanobacteria has severely disrupted ecological balances, posing significant risks to human health and safety. However, there is currently a lack of environmentally friendly methods that can sustainably suppress these blooms over the long term. This study integrates untargeted metabolomics, Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) to systematically characterize the responses of Microcystis aeruginosa to nano zero-valent iron (nZVI). Exposure to nZVI reprograms lipid and amino acid metabolism, coincides with the suppression of protein biosynthesis, and perturbs central pathways—including the tricarboxylic acid (TCA) cycle, photosynthesis, and carbohydrate metabolism—leading to disruptions in energy balance and metabolic homeostasis. FTIR and SEM provide complementary evidence of membrane compromise, with attenuation of -OH, -C-H, and C=O functional group signals, abnormal cell morphology, and progressive oxidative injury culminating in cell lysis and solute leakage. Together, these results support the inhibitory effect of nZVI on M. aeruginosa and provide insights to guide metabolomics studies of M. aeruginosa using nZVI. Full article
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18 pages, 2314 KB  
Article
NMR-Based Metabolomics Reveals Position-Specific Signatures Associated with Physical Demands in Professional Soccer Players
by Suewellyn N. dos Santos, Glydiston E. O. Ananias, Edmilson R. da Rocha, Alessandre C. Carmo, Edson de S. Bento, Thiago M. de Aquino, Ronaldo V. Thomatieli-Santos, Luiz Rodrigo A. de Lima, Pedro Balikian, Natália de A. Rodrigues, Gustavo G. de Araujo and Filipe A. B. Sousa
Biomedicines 2025, 13(11), 2583; https://doi.org/10.3390/biomedicines13112583 - 22 Oct 2025
Viewed by 308
Abstract
Background: Soccer’s varied physical demands require meticulous load monitoring, which is now being advanced by combining GPS for external metrics and NMR-based metabolomics for internal metabolic profiling. This study aimed to investigate how player position influences the metabolomic profile (as a marker of [...] Read more.
Background: Soccer’s varied physical demands require meticulous load monitoring, which is now being advanced by combining GPS for external metrics and NMR-based metabolomics for internal metabolic profiling. This study aimed to investigate how player position influences the metabolomic profile (as a marker of internal load) under known match effort (external load). Methods: This was a longitudinal observational descriptive study involving 12 professional soccer players from the U-20 São Paulo Football Club, enrolled in the 2022 São Paulo State Under-20 Football Championship. Players were monitored across six matches during the season, culminating in a total of 49 individual match observations from those players (4-2-3-1 formation: Central Defenders [CD], n = 9; Full Backs [FB], n = 9; Central Midfielders [CM], n = 14; Wide Midfielders [WM], n = 12; Forwards [F], n = 5). Internal load was assessed via urinary metabolomics, with urine samples collected 24 h post-match. A non-targeted, global metabolomics approach was employed using nuclear magnetic resonance (NMR) spectroscopy. External load was monitored using GPS tracking devices. Multivariate analyses included partial least squares discriminant analysis (PLS-DA), and heat maps. Results: Metabolomic analysis identified 38 metabolites with a Variable Importance in Projection (VIP) score > 1.0, revealing perturbations in carbohydrate metabolism and the tricarboxylic acid (TCA) cycle, amino acid and peptide metabolism, pyrimidine metabolism, and ketone body pathways, and effectively discriminating post-match recovery metabolic profiles. External load metrics varied significantly by player position: CMs covered greater distances below 20 km/h (8702.93 ± 1271.89 m), exhibited higher relative distance (114.29 ± 7.67 m/min), total distance (9193.21 ± 1261.35 m), and player load (945.71 ± 135.82 a.u.); CDs achieved higher peak speeds (31.78 ± 1.20 m/s); and WMs performed greater sprint distances (168.11 ± 91.69 m). Metabolomic profiles indicated that CMs showed stronger associations with markers of muscle damage and inflammation, whereas CDs and WMs were more closely linked to energy metabolism and oxidative stress. Conclusions: These results highlight the importance of a personalized approach to training load monitoring and recovery strategies, considering the distinct physiological and metabolic demands associated with each player position. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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20 pages, 5998 KB  
Article
Land Use Shapes the Rhizosphere Microbiome and Metabolome of Naturally Growing Barbarea vulgaris
by Emoke Dalma Kovacs and Melinda Haydee Kovacs
Metabolites 2025, 15(11), 684; https://doi.org/10.3390/metabo15110684 - 22 Oct 2025
Viewed by 330
Abstract
Background: Land use change fundamentally alters soil microbial communities and biochemical processes, yet the integrated effects on rhizosphere microbiome–metabolome networks remained poorly understood. Objective: This study investigated land uses as forest, grassland and intermediary edge shape the rhizosphere biochemical networks of naturally grown [...] Read more.
Background: Land use change fundamentally alters soil microbial communities and biochemical processes, yet the integrated effects on rhizosphere microbiome–metabolome networks remained poorly understood. Objective: This study investigated land uses as forest, grassland and intermediary edge shape the rhizosphere biochemical networks of naturally grown Barbarea vulgaris. Methods: Rhizosphere soils of Barbarea vulgaris were analysed for microbial community structure abundance, and metabolomic profile applying phospholipid fatty acid (PLFA) profiling and mass spectrometric untargeted metabolomics (GC–MS/MS and MALDI–TOF/TOF MS). These were coupled with co–inertia analysis to assess microbiome–metabolome interactions. Results: Microbial community analysis revealed significant effects of land use on bacterial community structure (G+/G−, p < 0.001). Untargeted metabolomics identified 248 metabolites, of which 161 were mapped to KEGG pathways. Amino acids and derivatives (21.1%) followed by organic acids (16.8%) were the most representative among identified metabolites. Pathway enrichment analysis revealed coordinated reprogramming of central carbon and nitrogen metabolism across land use gradients, particularly in the amino acid metabolism, TCA cycle, and glycolysis/gluconeogenesis pathways. Microbiome–metabolome coupling analysis revealed distinct correlation patterns between microbial phenotypes and metabolite classes, with forest environments showing the strongest biochemical network integration (RV = 0.91). Edge habitats presented intermediate signatures, supporting their role as transitional zones with unique biochemical properties. Conclusions: The environmental context fundamentally shapes rhizosphere biochemical network organization through coordinated shifts in bacterial community structure and metabolic pathway activity. These habitat-specific metabolic signatures suggest that land use change triggers adaptive biochemical responses that may influence plant performance and ecosystem functioning across environmental gradients. Full article
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16 pages, 2501 KB  
Article
SIRT3 Mediates Coordination Between Energy Metabolism and SOD Activity in Melatonin-Enhanced Boar Sperm Motility
by Naisheng Lu, Hulong Lei, Xueyuan Jiang, Peng Jia, Bushe Li and Dong Xia
Cells 2025, 14(20), 1633; https://doi.org/10.3390/cells14201633 - 20 Oct 2025
Viewed by 329
Abstract
Previous studies have demonstrated that melatonin (MLT) enhances boar sperm motility by modulating energy metabolism status, yet the underlying mechanisms remain incompletely understood. This study aims to investigate whether sirtuin 3 (SIRT3), a key mitochondrial deacetylase, mediates MLT’s effects. Herein, the semen of [...] Read more.
Previous studies have demonstrated that melatonin (MLT) enhances boar sperm motility by modulating energy metabolism status, yet the underlying mechanisms remain incompletely understood. This study aims to investigate whether sirtuin 3 (SIRT3), a key mitochondrial deacetylase, mediates MLT’s effects. Herein, the semen of six Landrace boars (16–18 months of age) was treated with 1.0 μM MLT with/without the SIRT3 inhibitor 3-TYP, preserved at 17 °C for 3 days, and subsequently maintained at 37 °C for a duration of 10 min. We demonstrated that MLT upregulated SIRT3 protein expression and reduced the acetylation level in mitochondrial proteins. MLT significantly increased glucose uptake and suppressed lactate release in the sperm, while elevating levels of pyruvate and acetyl-CoA, the substrates of pyruvate dehydrogenase (PDH) and the tricarboxylic acid (TCA) cycle, respectively, and the protein expression of PDH, indicating enhanced metabolic flux. Notably, inhibition of SIRT3 reversed MLT’s effects: it blocked the increases in SIRT3 expression, glucose consumption, PDH expression, complex I activity, ATP content, and superoxide dismutase (SOD) activity, and prevented the decreases in the levels of acetylation and lactate, as well as pyruvate kinase (PK) activity, confirming the essential role of SIRT3. Functionally, the MLT-induced improvements in sperm motility parameters (total, progressive, fast motility, immotile) were also reversed by 3-TYP. Collectively, these findings demonstrate that the SIRT3-mediated pathway is essential for MLT to enhance boar sperm energy metabolism and antioxidant defense, thereby increasing ATP production and enhancing sperm motility. Targeting SIRT3 represents a promising therapeutic strategy for improving boar fertility and may also provide insights for research into human male infertility. Full article
(This article belongs to the Collection Research Advances in Cellular Metabolism)
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19 pages, 2531 KB  
Article
High-Seas Marine Microorganism Delivers an Extract That Dampens LPS-Driven Pro-Inflammatory Signaling: Galbibacter orientalis Strain ROD011
by Minji Kim, You-Jin Jeon, Bomi Ryu, Young-Mog Kim, Jae-Il Kim, Minkyeong Choi, Sohee Kim, Jihye Lee and Jimin Hyun
Mar. Drugs 2025, 23(10), 409; https://doi.org/10.3390/md23100409 - 18 Oct 2025
Viewed by 559
Abstract
An ethyl acetate extract from the deep-sea bacterium Galbibacter orientalis strain ROD011 (GOEE), collected from international waters, was investigated as a potential anti-inflammatory agent. In lipopolysaccharide (LPS)-stimulated murine macrophages, nitric oxide (NO) production fell by 72–87% at 5–20 µg/mL GOEE without detectable cytotoxicity. [...] Read more.
An ethyl acetate extract from the deep-sea bacterium Galbibacter orientalis strain ROD011 (GOEE), collected from international waters, was investigated as a potential anti-inflammatory agent. In lipopolysaccharide (LPS)-stimulated murine macrophages, nitric oxide (NO) production fell by 72–87% at 5–20 µg/mL GOEE without detectable cytotoxicity. Cyclooxygenase-2 (COX-2 protein abundance decreased in a dose-dependent manner and was nearly absent at 20 µg/mL. In zebrafish embryos, survival was maintained up to 40 µg/mL, and LPS-induced signals were attenuated; the cell-death rate declined from 10 µg/mL onward, and at 20 µg/mL GOEE, reactive oxygen species (ROS) and NO decreased by 85% and 27%, respectively. To explain these effects, untargeted metabolomics with pathway enrichment and network mapping were performed in LPS-driven macrophages. Of the 58 KEGG pathways evaluated, 18 reached significance, notably purine and pyrimidine metabolism, vitamin B6 metabolism, and the one-carbon pool via folate. Coordinated shifts also involved amino-acid/tricarboxylic acid (TCA)-cycle linkages, glutathione and glyoxylate/dicarboxylate, and sphingolipid pathways. Network analysis identified hubs that were concomitantly reprogrammed. Collectively, GOEE achieved multi-level suppression of inflammatory outputs while preserving viability, and the metabolomic signature provides a mechanistic scaffold for its action. These findings nominate a deep-sea microbial extract as a promising anti-inflammatory lead and motivate fractionation and targeted validation of the highlighted metabolic nodes. Full article
(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments III)
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19 pages, 1652 KB  
Review
Metabolic Hostile Takeover: How Influenza Virus Reprograms Cellular Metabolism for Replication
by Xianfeng Hui, Xiaowei Tian, Shihuan Ding, Ge Gao, Xin Zhao, Jiyan Cui, Yiru Hou, Tiesuo Zhao and Hui Wang
Viruses 2025, 17(10), 1386; https://doi.org/10.3390/v17101386 - 17 Oct 2025
Viewed by 470
Abstract
Influenza viruses are adept at hijacking host cellular machinery to facilitate their replication and propagation. A critical aspect of this hijacking involves the reprogramming of host cell metabolism. This review summarizes current findings on how influenza virus infection alters major metabolic pathways, including [...] Read more.
Influenza viruses are adept at hijacking host cellular machinery to facilitate their replication and propagation. A critical aspect of this hijacking involves the reprogramming of host cell metabolism. This review summarizes current findings on how influenza virus infection alters major metabolic pathways, including enhanced glycolysis, suppression of oxidative phosphorylation, diversion of TCA cycle intermediates for biosynthesis, and upregulation of lipid and amino acid metabolism. Key nutrients like glucose, glutamine, and serine are redirected to support viral RNA synthesis, protein production, and membrane formation. Moreover, these metabolic changes also modulate host immune responses, potentially aiding in immune evasion. We highlight the role of transcription factors such as SREBPs in lipid synthesis and the impact of one-carbon metabolism on epigenetic regulation. Finally, we discuss how targeting virus-induced metabolic shifts, using agents like 2-deoxyglucose or fatty acid synthesis inhibitors, offers promising avenues for antiviral intervention, while emphasizing the need for selective approaches to minimize harm to normal cells. Full article
(This article belongs to the Special Issue Interaction Between Influenza Virus and Host Cell)
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21 pages, 17502 KB  
Article
Metabolomics Reveals Abnormal Citrate Cycle and Phenylalanine Metabolism in Testes from Infertile Hybrid Dzo
by Jiaojiao Ding, Yan Dao, Lingqian Liang, Rui Hong, Huiyou Chen, Yi Yan, Ling Wang, Fuyuan Zuo and Gongwei Zhang
Animals 2025, 15(20), 3023; https://doi.org/10.3390/ani15203023 - 17 Oct 2025
Viewed by 285
Abstract
This study investigated the metabolomic profiles and molecular basis of hybrid male sterility (HMS) in dzo (the male F1 hybrid offspring of taurine cattle (Bos taurus, ♂) × domestic yak (Bos grunniens, ♀)). In total, 147 co-different metabolites were [...] Read more.
This study investigated the metabolomic profiles and molecular basis of hybrid male sterility (HMS) in dzo (the male F1 hybrid offspring of taurine cattle (Bos taurus, ♂) × domestic yak (Bos grunniens, ♀)). In total, 147 co-different metabolites were identified between liver and testis tissues. Metabolomics analysis linked testis-specific abnormal citrate cycle and phenylalanine metabolism to dzo male infertility. Specifically, α-ketoglutaric acid, L-malic acid, and succinic acid were specific elevated in dzo testes, but not significantly different in liver. The testis-specific metabolite phenyllactate was reduced in dzo. Moreover, genes encoding α-ketoglutarate-dependent oxygenases were dysregulated only in dzo testes, including histone demethylations and RNA m6A modifications. Reactive oxygen species and m6A content were significantly decreased in dzo testes. Multiomics data showed that testis-specific metabolic abnormalities in dzo were linked to upregulated IDH3A and IDH3G, and downregulated testis-specific OGDHL and PDHA2. MiRNA-15b targeting to IDH3A was downregulated in dzo testes. The promoter of PDHA2 was hypermethylated and showed lower chromatin accessibility in dzo testes. Notably, testis-specific LDHC downregulation was also associated with lower phenyllactate in dzo testes, which could be an outcome of male infertility. Overall, this study provides comprehensive insights into the citrate cycle as a key pathway associated with dzo sterility, shedding light on the potential mitochondrial–nuclear incompatibility pertinent to addressing this HMS challenge. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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11 pages, 1073 KB  
Article
Simultaneous Correction of Juvenile Hallux Valgus and Flexible Flatfoot in Children: Outcomes of Combined First Metatarsal Hemiepiphysiodesis and Calcaneal-Stop Procedure
by Giovanni Luigi Di Gennaro, Giovanni Trisolino, Marianna Viotto, Marco Todisco, Tosca Cerasoli and Gino Rocca
J. Clin. Med. 2025, 14(20), 7330; https://doi.org/10.3390/jcm14207330 - 17 Oct 2025
Viewed by 358
Abstract
Background/Objectives: Juvenile hallux valgus (JHV) and flexible flatfoot (FFF) often coexist in children, yet their combined surgical management remains poorly explored. This study evaluates clinical and radiographic outcomes following a simultaneous approach using lateral hemiepiphysiodesis of the first metatarsal (LHFM) and calcaneal-stop [...] Read more.
Background/Objectives: Juvenile hallux valgus (JHV) and flexible flatfoot (FFF) often coexist in children, yet their combined surgical management remains poorly explored. This study evaluates clinical and radiographic outcomes following a simultaneous approach using lateral hemiepiphysiodesis of the first metatarsal (LHFM) and calcaneal-stop (C-Stop) procedures in skeletally immature patients. Methods: A retrospective cohort of 24 bilateral patients (48 feet) aged 10–12 underwent LHFM and C-Stop between 2017 and 2023. Radiographic evaluation included Hallux Valgus Angle (HVA), Intermetatarsal Angle (IMA), Meary’s angle (MA), and transverse TaloCalcaneal (Kite’s) Angle (tTCA). The Foot and Ankle Disability Index (FADI) and the Tegner Activity Scale (TAS) were administered at the most recent follow-up and complications were recorded. Results: The mean follow-up was 3.7 years. Postoperative radiographs showed significant improvements in all parameters, with correction inversely correlated to baseline deformity severity. Full normalization of flatfoot parameters was achieved in 68.8% of feet, with mild residual deformity in the remainder. Males showed greater radiographic correction than females. IMA and HVA improved in most cases, reaching full normalization in 53.1% and 50% of feet, respectively. Clinically, all patients showed corrected hindfoot alignment and medial arch restoration; 90% achieved the maximum FADI score and 88% resumed recreational sports. Two cases of screw migration occurred, with one revision; no further complications were reported. Conclusions: Simultaneous correction of FFF and JHV using C-Stop and LHFM proved effective, yielding significant radiographic improvements and excellent functional outcomes in most cases, with minimal complications. However, full hallux alignment was achieved in only half of the cases, suggesting that additional distal metatarsal procedures may be needed for more severe deformities. Full article
(This article belongs to the Special Issue Updates in the Orthopedic Management of Foot Disorders: 2nd Edition)
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16 pages, 753 KB  
Article
Sodium Benzoate and Potassium Sorbate Inhibit Proteolysis and Promote Lipid Oxidation in Atlantic Herring Marinades Produced on an Industrial Scale
by Mariusz Szymczak, Patryk Kamiński, Barbara Szymczak, Ingrid Undeland and Izabela Dmytrów
Molecules 2025, 30(20), 4103; https://doi.org/10.3390/molecules30204103 - 15 Oct 2025
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Abstract
Cold-ripened fish marinades, produced mainly from Atlantic herring, represent one of the major seafood products in Northern and Central Europe. Because the shelf-life of these mildly acidified, salty products rarely surpasses 4 weeks, more than half of the commercial lots contain the preservatives [...] Read more.
Cold-ripened fish marinades, produced mainly from Atlantic herring, represent one of the major seafood products in Northern and Central Europe. Because the shelf-life of these mildly acidified, salty products rarely surpasses 4 weeks, more than half of the commercial lots contain the preservatives sodium benzoate (E211) and potassium sorbate (E202). However, the broader technological consequences of such additives remain poorly documented. This study evaluated the impact of 0.25 (w/w) benzoate + 0.10 g/100 g sorbate on the quality of industrial-scale marinades (200 kg fish; 7 d, 4 ± 1 °C). Physicochemical traits (mass loss, pH, proximate composition, salt content, colour, and texture), enzymatic indices of ripening (cathepsins, amino-peptidases, and TCA soluble nitrogen fractions), lipid oxidation, microbial growth, and sensory attributes were analyzed. Preservatives caused only marginal changes in pH and proximate composition (0.3–3.4% w/w differences) but markedly suppressed proteolysis. Free amino acid and peptide fractions in muscle decreased by 6.0% and 8.8%, in parallel to 45% and 22% reductions in leucine- and alanine-amino-peptidase activities in muscle. In the marinating brine, the levels of total nitrogen, peptides, and free amino acids were also lower in the samples with preservatives, confirming that sodium benzoate and potassium sorbate slowed down the enzymatic ripening of the marinades. Concomitantly, peroxide, p-anisidine, and TOTOXs increased by up to 9.4, 71.3, and 33.7%, respectively, indicating accelerated lipid oxidation despite the chelating capacity of benzoate/sorbate acids. Overall sensory acceptability declined slightly (−0.15 points on a five-point scale), mainly owing to chemical off-flavours and lower juiciness. Microbial counts remained <1.0 log CFU/g in the preservative batch versus 2.1 log in the control. Benzoate–sorbate combinations effectively stabilized the microbiota of marinated herring without appreciably altering basic physicochemical traits, but they retard enzymatic ripening, diminish antioxidant peptide pools, and thereby promote lipid oxidation—collectively lowering the nutritional value. The data supports a cautious, minimal-use approach to application of chemical preservatives in cold-ripened fish products. Full article
(This article belongs to the Section Food Chemistry)
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