Metabolites

17 pages, 4075 KB

Open AccessArticle

Metabolomic and Transcriptomic Analyses Reveal the Molecular Mechanism of Flower Color Variations in Rosa chinensis Cultivar ‘Rainbow’s End’

by Junfei Sun, Fengshan Ren, Xianshui Meng, Guizhi Dong, Xiaohong Zhang and Yi Li

Metabolites 2026, 16(1), 32; https://doi.org/10.3390/metabo16010032 - 27 Dec 2025

Abstract

Background: Rosa chinensis, commonly known as the Chinese rose, is one of the most economically significant ornamental plants worldwide. The Rosa chinensis cultivar ‘Rainbow’s End’ notably transitions in color from yellow to red throughout its blooming phase; however, the chemical and molecular foundations [...] Read more.

Background: Rosa chinensis, commonly known as the Chinese rose, is one of the most economically significant ornamental plants worldwide. The Rosa chinensis cultivar ‘Rainbow’s End’ notably transitions in color from yellow to red throughout its blooming phase; however, the chemical and molecular foundations underlying this floral color transformation remain inadequately understood. Methods: This study used the petals of the Rosa ‘Rainbow’s End’ cultivar at four developmental stages (R1, R2, R3, and R4) for targeted metabolomic and transcriptomic analyses. Results: Targeted metabolomic analyses revealed that the majority of anthocyanidin metabolites were highest at stages R2 and R3 and lowest at R1 and R4. In contrast, most carotenoid metabolites reached their highest levels at R1 and declined continuously from R2 to R4. These results were consistent with the color phenotype of Rosa ‘Rainbow’s End’ petals and suggested that both anthocyanins and carotenoids play critical roles in flower color variation. Specifically, an upregulation of CHS, ANS, and UGT genes in the anthocyanin biosynthesis pathway was observed in R2 and R3, coinciding with the expression of two MYB transcription factors (MYB14 and MYB54). Conversely, consistent downregulation of PSY, PDS, Z-ISO, ZDS, CHYB, and NCED genes in the carotenoid biosynthesis pathway was detected in R2 to R4 and was associated with four MYB transcription factors (MYB20, MYB43, MYB44, and MYB86). Conclusions: Rosa ‘Rainbow’s End’ is an excellent model for studying variations in flower color. The expression patterns of the identified structural genes involved in anthocyanin and carotenoid biosynthesis pathways, along with the related MYB transcription factors, were aligned with the levels of metabolite changes in the petals of four flowering stages. These genes and transcription factors are likely responsible for the color shifts in Rosa ‘Rainbow’s End’. This study clarifies the mechanisms underlying color changes in Rosa ‘Rainbow’s End’ and provides a theoretical basis for future flower breeding efforts. Full article

(This article belongs to the Special Issue Metabolomics and Plant Defence, 2nd Edition)

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22 pages, 13973 KB

Open AccessArticle

Smilax china L. Extract Alleviates Metabolic-Associated Fatty Liver Disease by Regulating Gut Microbiota and Bile Acid Metabolism

by Shiyuan Cheng, Huijun Li, Zhiying Sun, Yue Xiong, Jing Li, Jiaying Tian, Yue Shen, Li Shen, Jingyu Yang, Yuying Yang, Dan Liu, Qiong Wei, Chao Huang and Xiaochuan Ye

Metabolites 2026, 16(1), 31; https://doi.org/10.3390/metabo16010031 - 26 Dec 2025

Abstract

Background: Metabolic-associated fatty liver disease (MAFLD) is prevalent in individuals with liver disease; however, it lacks effective therapeutic approaches. Smilax china L., a traditional Chinese medicinal herb, possesses excellent anti-inflammatory and antioxidant activity. This research aimed to explore the therapeutic effects of Smilax [...] Read more.

Background: Metabolic-associated fatty liver disease (MAFLD) is prevalent in individuals with liver disease; however, it lacks effective therapeutic approaches. Smilax china L., a traditional Chinese medicinal herb, possesses excellent anti-inflammatory and antioxidant activity. This research aimed to explore the therapeutic effects of Smilax china L. extract (SCE) on MAFLD and to elucidate the pharmacological mechanisms. Methods: A rat model of MAFLD was induced through a high-fat diet (HFD), and the model rats subsequently received SCE as a therapeutic intervention for six weeks. The analysis involved 16S rDNA sequencing, untargeted fecal metabolomics, and targeted bile acid metabolomics to investigate the effects of SCE on the gut microbiota and bile acid metabolism. Results: Hepatic steatosis and lipid accumulation were significantly alleviated by the SCE treatment. SCE treatment modulated the gut microbiota disorder, by enhancing the relative abundance of the beneficial gut microbiota, including Clostridium, Oscillospira, and Romboutsia. Untargeted fecal metabolomics revealed a significant enrichment of the metabolites in secondary bile acid biosynthesis. Targeted bile acid metabolomics revealed that SCE reversed the abnormal fecal bile acid metabolic profile, such as HDCA, LCA, and T-β-MCA. These changes activated FXR and PPARα receptors to improve the lipid metabolism by regulating bile acid synthesis. Conclusions: Our study provides evidence that SCE alleviates MAFLD through regulation of the gut microbiota, bile acid metabolism, and activation of the FXR/PPARα pathway, illustrating the mechanism of action of SCE in MAFLD from a novel perspective, and further highlights its therapeutic potential. Full article

(This article belongs to the Special Issue Adipose Thermogenesis and Crosstalk: Signaling Networks in Obesity, Metabolic Disease and Beyond)

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21 pages, 940 KB

Open AccessArticle

Exploration of Key Flavor Compounds in Five Grilled Salmonid Species by Integrating Volatile Profiling and Sensory Evaluation

by Yuka Mori, Akimasa Hatanaka and Eiichiro Fukusaki

Metabolites 2026, 16(1), 30; https://doi.org/10.3390/metabo16010030 - 26 Dec 2025

Abstract

Background/Objectives: Salmonid species are globally popular and widely consumed in Japan, especially when grilled. Understanding their flavor characteristics from sensory and compositional perspectives is essential to improve the quality of processed salmonid products. However, scientific knowledge in this area remains limited. This [...] Read more.

Background/Objectives: Salmonid species are globally popular and widely consumed in Japan, especially when grilled. Understanding their flavor characteristics from sensory and compositional perspectives is essential to improve the quality of processed salmonid products. However, scientific knowledge in this area remains limited. This study aimed to explore compounds contributing delicious flavor of grilled salmon by performing correlation analysis between sensory evaluation and volatile profiles of five grilled salmonid species. Methods: To characterize each sample, sensory evaluation using paired comparisons and comprehensive analysis of volatile compounds by gas chromatography/mass spectrometry (GC/MS) were conducted. To select compounds strongly associated with the “delicious flavor of grilled salmon”, orthogonal partial least squares regression (OPLSR) and gas chromatography/olfactometry (GC/O) were performed. A subset of the selected candidate compounds was quantified, and additive tests on the samples were carried out based on their concentrations. Results: Sensory evaluation revealed clear differences in flavor profiles among the five salmonid species. A total of 344 peaks were detected in all samples, and principal component analysis (PCA) of these data showed grouping trends consistent with those obtained from sensory evaluation. OPLSR using sensory and volatile data as variables, and GC/O analysis identified 23 compounds, including trimethylamine, dimethyl sulfide, and 1-heptanol, as candidates contributing to the characteristic flavor of grilled salmonid species. Sensory evaluation of samples supplemented with a subset of these candidates showed that, particularly at the higher addition level, aroma and flavor tended to approach those of the highly preferred samples. Conclusions: These findings suggest that some of the selected candidate compounds contribute to the formation of delicious flavor of grilled salmon and may be useful for flavor design and quality improvement of processed products made from salmonid species. Full article

(This article belongs to the Section Food Metabolomics)

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23 pages, 1065 KB

Open AccessReview

The Emerging Roles of Metabolite-Activated GPCRs in Teleost Physiology and Aquaculture Development

by Guan-Yuan Wei, Ming-Yuan Wu, Lan Ding, Zhen-Fa Qin, Zheng-Xiang Zhang, Liang-Jia Wei and Zhi-Shuai Hou

Metabolites 2026, 16(1), 29; https://doi.org/10.3390/metabo16010029 - 26 Dec 2025

Abstract

Metabolites, once viewed mainly as energy substrates or structural precursors, are now increasingly recognized as key extracellular signaling mediators that regulate diverse physiological processes. This review synthesizes and systematizes current knowledge on metabolite-mediated signaling through G-protein-coupled receptors (GPCRs) in teleosts and, importantly, highlights [...] Read more.

Metabolites, once viewed mainly as energy substrates or structural precursors, are now increasingly recognized as key extracellular signaling mediators that regulate diverse physiological processes. This review synthesizes and systematizes current knowledge on metabolite-mediated signaling through G-protein-coupled receptors (GPCRs) in teleosts and, importantly, highlights new conceptual links between specific metabolite–GPCR axes and key physiological functions relevant to aquaculture. By integrating evidence across metabolite–GPCRs axes, including succinate–SUCNR1, aromatic amino acids (tryptophan and phenylalanine)–GPR142, basic amino acids (L-arginine)–GPRC6A, and lactate–GPR81. We clarify how metabolite–receptor interactions have the potential to modulate glucose homeostasis, immune responses, energy metabolism, and stress coping. A major contribution of this review is illustrating how metabolites act not only as nutrients but also as extracellular signaling molecules governing core physiological processes via GPCRs. Particularly from an evolutionary perspective, compared with peptide-activated GPCRs, metabolite-sensing GPCRs are relatively conserved across different species, suggesting that relevant findings from biomedical research could be translated to aquaculture applications. Therefore, understanding GPCR-mediated metabolite sensing provides a molecular foundation for improving nutrient formulation, developing functional feeds, and designing selective breeding strategies in precision aquaculture. Full article

(This article belongs to the Special Issue Nutrition, Metabolism and Physiology in Aquatic Animals)

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22 pages, 5872 KB

Open AccessArticle

Dried Blood Spots Capture a Wide Range of Metabolic Pathways and Biological Characteristics Associated with Fish Oil Supplementation, Fasting, and the Postprandial State

by Karen L. DeBalsi, Kelli D. Goodman, Laura J. Sommerville, Matthew W. Mitchell, Blair A. Lane, Anne M. Evans and Adam D. Kennedy

Metabolites 2026, 16(1), 28; https://doi.org/10.3390/metabo16010028 - 26 Dec 2025

Abstract

Background: Metabolomics is recognized as crucial technology for advancing our ability to diagnose, characterize, and monitor treatment of disease. Yet, metabolomics-based diagnostic testing has not been widely adapted into clinical practice because its technical requirements make it generally incompatible with operation at the [...] Read more.

Background: Metabolomics is recognized as crucial technology for advancing our ability to diagnose, characterize, and monitor treatment of disease. Yet, metabolomics-based diagnostic testing has not been widely adapted into clinical practice because its technical requirements make it generally incompatible with operation at the point of care. One way to expand the reach of metabolomics-based testing, and its clinical benefits, is to utilize dried blood spots (DBS) as a testing sample type. Their easy collection, ambient storage capability, and cost-effective shipment make DBSs ideal for diagnostic tests that require the use of a centralized technology. Methods: To date, relatively few studies have investigated the performance of DBSs at capturing the global metabolome and reporting changes associated with physiological processes. In this study, we investigated those factors by performing global metabolomic profiling on DBSs collected from study volunteers under fasted and postprandial states, with and without dietary fish oil supplementation. Results: DBSs demonstrated broad coverage of metabolic pathways and captured numerous metabolic changes associated with feeding, fasting, and fish oil supplementation that have been reported in plasma and serum. Conclusions: Our findings support the hypothesis that DBSs are a viable sample type for metabolomics-based diagnostic testing and justify follow-up validation studies. Full article

(This article belongs to the Special Issue Advances in Metabolomics for Precision Medicine: From Biomarker Discovery to Clinical Applications)

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13 pages, 1392 KB

Open AccessArticle

A Novel Single-Test Approach for GDM Diagnosis: Identification and Prediction of High-Risk Postprandial Hyperglycemia

by Hao Wu, Danqing Chen, Xue Li, Menglin Zhou and Qi Wu

Metabolites 2026, 16(1), 27; https://doi.org/10.3390/metabo16010027 - 25 Dec 2025

Abstract

Background: Early prediction of gestational diabetes mellitus (GDM) remains a major clinical challenge, and the current oral glucose tolerance test (OGTT) is time-consuming and inconvenient for clinical routine. This study aimed to develop a novel predictive model for postprandial hyperglycemia GDM (pp-GDM) and [...] Read more.

Background: Early prediction of gestational diabetes mellitus (GDM) remains a major clinical challenge, and the current oral glucose tolerance test (OGTT) is time-consuming and inconvenient for clinical routine. This study aimed to develop a novel predictive model for postprandial hyperglycemia GDM (pp-GDM) and postprandial glucose elevation using fasting serological and metabolic profiles. Method: We used High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) to analyze fasting plasma amino acid profiles at 24–28 weeks of gestation for 60 pp-GDM patients and 120 controls. Binary logistic regression model was constructed to identify potential biomarkers for pp-GDM prediction. Results: By incorporating amino acid indicators such as isoleucine, phenylalanine, threonine, and aspartate into the predictive model alongside traditional predictors (including BMI at sampling, fasting insulin, glycated hemoglobin, and uric acid), the overall predictive performance was significantly improved from 78.2% to 91.1%. A clinically practical nomogram for risk assessment was subsequently developed. Conclusions: This fasting metabolite-based model provides a reliable tool for early prediction of pp-GDM and postprandial hyperglycemia, which may reduce the need for OGTT and facilitate timely clinical decision making. Full article

(This article belongs to the Special Issue Early-Stage Biomarkers: Metabolomics in Preclinical and Prodromal Disease Detection)

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16 pages, 8769 KB

Open AccessArticle

Transcriptomic Analysis of the Regulatory Mechanism of Tea Polyphenol Biosynthesis in Chionanthus retusus and Functional Characterization of CrHSP70-14 in Terms of Its Effect on Tea Polyphenols

by Liyang Guo, Yuzhu Wu, Jihong Li, Haiyan Wang, Muge Niu, Mengmeng Wang, Shicong Zhao, Wenjing Song, Jiaxun Liu, Jingyu Wang and Jinnan Wang

Metabolites 2026, 16(1), 26; https://doi.org/10.3390/metabo16010026 (registering DOI) - 25 Dec 2025

Abstract

Background: Chionanthus retusus Lindl. et Paxt., a deciduous tree of the genus Chionanthus (Oleaceae), represents a significant native species and a widely cultivated ornamental. Its tender leaves can be processed into tea, traditionally consumed in southern China under the common name [...] Read more.

Background: Chionanthus retusus Lindl. et Paxt., a deciduous tree of the genus Chionanthus (Oleaceae), represents a significant native species and a widely cultivated ornamental. Its tender leaves can be processed into tea, traditionally consumed in southern China under the common name “Nuomi Cha”. Methods: Our team quantified the tea polyphenol content across 150 individual trees of C. retusus and selected three low-polyphenol (ZB_D_14, AQ_2, AQ_1) and three high-polyphenol (SX_3, SXG_D_8, TS_D_13) lines for transcriptome sequencing of their young leaves. The resulting data were analyzed to screen for candidate genes. Subsequently, transgenic plants were constructed, and their tea polyphenol content was determined. Results: A significant difference in tea polyphenol content was confirmed between the high- and low-polyphenol lines. Weighted Gene Co-expression Network Analysis (WGCNA) pinpointed a key module strongly associated with tea polyphenol synthesis, encompassing 432 DEGs, which were predominantly enriched in pathways like phenylpropanoid biosynthesis. A comparative transcriptomic analysis further yielded 84 DEGs (40 up- and 44 down-regulated). Enrichment analysis showed these were primarily involved in flavonoid and phenylpropanoid biosynthesis pathways. Expression profiling of genes in the tea polyphenol biosynthetic pathway indicated that several key genes (e.g., 4CL, CHS, DFR) were highly expressed in the high-content lines. A gene interaction network related to this synthesis identified 20 hub genes (e.g., CrHSP70-14, CrMYB44, CrbHLH92). Functional validation of four hubs (CrMYB44, CrHSP70-14, CrCDC6B, CrRAE1) via tobacco transient transformation assays demonstrated that all four significantly elevated tea polyphenol levels, with CrHSP70-14 overexpression yielding the highest content. Furthermore, stable CrHSP70-14 overexpression transgenic tobacco lines were generated, exhibiting significantly higher leaf tea polyphenol content versus controls. Conclusions: This study identifies multiple regulatory genes involved in C. retusus tea polyphenol biosynthesis, provides initial mechanistic insights, and establishes a molecular foundation for breeding specialized tea cultivars of this species. Full article

(This article belongs to the Special Issue LC-MS/MS Analysis for Plant Secondary Metabolites, 2nd Edition)

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18 pages, 1029 KB

Open AccessArticle

Associations Between Systemic Inflammatory Markers, Metabolic Dysfunction, and Liver Fibrosis Scores in Patients with MASLD

by Ragaey Ahmad Eid, Ahmed Moheyeldien Hamed, Sara O. Elgendy, Khalid M. Orayj, Ahmed R. N. Ibrahim, Ahmed M. Abdel Hamied, Engy A. Wahsh, Maha Youssif, Hoda Rabea, Yasmin M. Madney, Dina Attia and Shaymaa Nafady

Metabolites 2026, 16(1), 25; https://doi.org/10.3390/metabo16010025 - 25 Dec 2025

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global health challenge due to its complex pathophysiological processes. Systemic inflammation may profoundly affect disease progression, but the correlation between inflammatory markers and disease severity remains inadequately explored. This cross-sectional analysis within [...] Read more.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global health challenge due to its complex pathophysiological processes. Systemic inflammation may profoundly affect disease progression, but the correlation between inflammatory markers and disease severity remains inadequately explored. This cross-sectional analysis within a prospective cohort evaluated associations of inflammatory markers (IL-6, TNF-α, hsCRP) with MASLD severity (five non-invasive scores) and metabolic indices, primarily with early-stage disease (66.7% mild fibrosis by TE). Methods: We recruited 120 patients diagnosed with MASLD. Assessment included anthropometric measurements, laboratory analyses, and non-invasive fibrosis evaluation using five validated scoring systems (APRI, FIB-4, NAFLD fibrosis score, FAST score, and transient elastography). Inflammatory markers were quantified using high-sensitivity ELISA techniques. Medication/comorbidities were recorded (statins 23.3%, diabetes drugs 26.7%), and multivariate regressions and FDR correction were applied. Results: Patients showed remarkably elevated inflammatory markers compared to reference ranges: IL-6 (15.1 ± 9.3 pg/mL), TNF-α (38.8 ± 29.1 pg/mL), and hsCRP (12.3 ± 11.1 mg/L). No correlations were found between inflammatory markers and disease severity across any non-invasive scoring system. However, TNF-α correlated significantly with waist circumference (r = 0.28, p = 0.002) and ALT (r = 0.19, p = 0.03), while showing inverse correlations with total cholesterol (r = −0.27, p = 0.03) and LDL (r = −0.22, p = 0.02). In contrast, hsCRP correlated positively with LDL (r = 0.20, p = 0.02) and WBC count (r = 0.24, p = 0.008). Conclusion: This study reveals a dissociation between systemic inflammatory markers and hepatic fibrosis severity in MASLD. Inflammatory Markers showed stronger metabolic associations than fibrosis, limiting their utility as fibrosis surrogates in early MASLD. These findings support a dual-pathway approach to MASLD management, targeting metabolic and hepatic components independently. The divergent associations of TNF-α and hsCRP with lipid profiles suggest distinct inflammatory mechanisms in MASLD. Full article

(This article belongs to the Special Issue Metabolomics and MASLD: Pathways, Biomarkers, and Clinical Insights)

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18 pages, 2323 KB

Open AccessArticle

Evaluation of Callistemon citrinus Compounds to Reduce Brain Oxidative Stress in Rats Fed High-Fat-Sucrose Diet

by Aram Josué García-Calderón, Oliver Rafid Magaña-Rodríguez, Luis Alberto Ayala-Ruiz, José Armando Hernández-Soto, Jonathan Saúl Piñón-Simental, Luis Gerardo Ortega-Pérez, Asdrubal Aguilera-Méndez and Patricia Ríos-Chávez

Metabolites 2026, 16(1), 24; https://doi.org/10.3390/metabo16010024 - 25 Dec 2025

Abstract

Background: The association between oxidative stress and inflammation in obesity motivates investigation of the effects of d-limonene, gallic acid, ellagic acid, p-coumaric acid, and their mixture, which are major compounds of Callistemon citrinus, on oxidative stress and inflammation in the brains [...] Read more.

Background: The association between oxidative stress and inflammation in obesity motivates investigation of the effects of d-limonene, gallic acid, ellagic acid, p-coumaric acid, and their mixture, which are major compounds of Callistemon citrinus, on oxidative stress and inflammation in the brains of rats fed a high-fat-sucrose diet. This study aimed to identify the specific bioactive compounds in C. citrinus leaf extract responsible for its neuroprotective effects against diet-induced oxidative stress and neuroinflammation. Methods: Forty-eight male Wistar rats were randomly divided into eight groups (n = 6). Group 1 (control) received a standard diet, while group 2 received a high-fat, high-sucrose diet (HFSD). Groups 3, 4, 5, 6, 7, and 8 were also fed HFSD supplemented with C. citrinus extract, its main compounds, and a mixture of these compounds administered once daily via oral cannula for 23 weeks. The antioxidant and pro-inflammatory enzymes, along with oxidative biomarkers, were evaluated in the brains of the rats. Results:C. citrinus leaf extract and its four main components, both separately and together, modulated the activities of catalase, superoxide dismutase, glutathione peroxidase, and paraoxonase-1. They also affected levels of reduced glutathione while decreasing the amounts of advanced oxidative protein products, malondialdehyde, and 4-hydroxynonenal. Additionally, they decreased the activities of cyclooxygenase (COX-1 and COX-2), 5-lipoxygenase, xanthine oxidase, and myeloperoxidase in the brains of rats, despite a high-fat-sucrose diet. Conclusions: These results show that the main compounds in C. citrinus leaf extract are essential for its antioxidant and anti-inflammatory effects, which help protect against oxidative stress in the brains of rats on a high-calorie diet. Full article

(This article belongs to the Special Issue Bioactive Compounds in Obesity and Its Metabolic Complications)

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15 pages, 1294 KB

Open AccessArticle

From BIA to BMI: A New Look at Postpartum Recovery and Breastfeeding Outcomes

by Dominika Mazur, Kornelia Purc-Bandurko, Żaneta Kimber-Trojnar, Marcin Trojnar and Bożena Leszczyńska-Gorzelak

Metabolites 2026, 16(1), 23; https://doi.org/10.3390/metabo16010023 - 25 Dec 2025

Abstract

Background/Objectives: Successful and sustained breastfeeding depends on maternal, psychological, metabolic and obstetric factors including hydration status, body composition, gestational age at delivery and mode of delivery, which are rarely assessed together in routine postpartum care. Bioelectrical impedance analysis (BIA) provides a non-invasive assessment [...] Read more.

Background/Objectives: Successful and sustained breastfeeding depends on maternal, psychological, metabolic and obstetric factors including hydration status, body composition, gestational age at delivery and mode of delivery, which are rarely assessed together in routine postpartum care. Bioelectrical impedance analysis (BIA) provides a non-invasive assessment of hydration and tissue composition, yet its potential to support lactation outcomes remains insufficiently studied. This study aimed to evaluate the relationship between postpartum body composition, hydration status assessed with BIA, and breastfeeding duration. Methods: A total of 122 women in the early postpartum period after term singleton deliveries were enrolled, of whom 50 completed the full protocol, including a 7-month follow-up. BIA and anthropometric measurements were performed on postpartum days 2 and 3. Breastfeeding duration was assessed at 7 months via telephone interview and categorized as <6 months or ≥6 months. Two indices (PLBI and sPLBI) were calculated to describe BMI change from pre-pregnancy to 7 months postpartum. Results: Breastfeeding for ≥6 months was significantly associated with marital status, mode of delivery, lower BMI on postpartum day 2, and a positive change in the overhydration index (ΔOH). Women in this group exhibited significantly lower PLBI and sPLBI values, indicating more effective postpartum weight recovery and a greater return toward pre-pregnancy BMI. Hydration parameters derived from BIA differentiated between shorter and longer breastfeeding duration. Conclusions: Positive postpartum hydration balance (ΔOH ≥ 0) and efficient metabolic recovery, reflected by lower PLBI and sPLBI values, may support longer breastfeeding. BIA-based assessment of hydration and body composition could help identify women at higher risk of early breastfeeding cessation. Further longitudinal research is warranted to confirm the clinical utility of BIA in postpartum care and its potential role in early lactation support. Full article

(This article belongs to the Special Issue Obesity, Hormones, and Metabolic Complications in Pregnancy)

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22 pages, 2367 KB

Open AccessArticle

Harnessing the Potential of a Secondary Metabolite-Based Formulation for the Post-Harvest Disease Management and Shelf Life Extension of Banana

by Karma Beer, T. Damodaran, M. Muthukumar, Prasenjit Debnath, Akath Singh and Maneesh Mishra

Metabolites 2026, 16(1), 22; https://doi.org/10.3390/metabo16010022 - 25 Dec 2025

Abstract

Background: Post-harvest losses in bananas, particularly due to diseases such as anthracnose and stem-end rot, significantly limit their storage life and marketability. Developing effective and non-toxic treatments to prolong the shelf life of fruits while maintaining quality is crucial inenabling long-distance transport and [...] Read more.

Background: Post-harvest losses in bananas, particularly due to diseases such as anthracnose and stem-end rot, significantly limit their storage life and marketability. Developing effective and non-toxic treatments to prolong the shelf life of fruits while maintaining quality is crucial inenabling long-distance transport and facilitating exports. Methods: The most popular and commercial banana variety, ‘Grand Naine’, was treated with a proprietary secondary metabolite-based formulation (this refers to a solution containing natural compounds produced by living organisms, which are not directly involved in growth but can influence various biological processes, such as antimicrobial activity) and stored under cold conditions at 13 °C, using vacuum packaging (a method where air is removed from the packaging to reduce spoilage and prolong freshness). Untreated fruits were considered as controls, meaning that they were not subjected to the treatment and served as a baseline for comparison. Shelf life-related parameters such as ethylene production (a plant hormone responsible for triggering fruit ripening), ACC oxidase activity (an enzyme central to ethylene synthesis), respiration rate (the rate at which fruit consumes oxygen and produces carbon dioxide), firmness, total soluble solids (TSS; measures the sugar content in fruit), acidity, and metabolic composition were assessed, including indices of susceptibility to disease. These measurements were taken at regular intervals for both treated and control fruits. Results: Secondary metabolite-treated bananas maintained quality for 45 days, staying free from anthracnose and stem-end rot. Control fruits showed over-ripening and an 11.6% percent disease index (PDI). Treated fruits had lower ethylene production (7.80 μg/kg/s vs. 10.03 μg/kg/s in controls), reduced ACC oxidase activity, and a slower respiration rate, delaying ripening. They also had greater firmness (1.45 kg/cm²), optimal TSS (13.5 °Brix), balanced acidity (0.58%), and increased flavonoid and antioxidant levels compared to controls. Conclusions: Secondary metabolite-based treatment, combined with cold storage and vacuum packaging, extended banana shelf life to 45 days, minimized disease, and preserved fruit quality. This approach substantially reduced post-harvest losses, demonstrating export potential through extended storage. Full article

(This article belongs to the Section Food Metabolomics)

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17 pages, 1910 KB

Open AccessArticle

Untargeted Metabolomics Reveals Metabolic Reprogramming Linked to HCC Risk in Late Diagnosed Tyrosinemia Type 1

by Anna Sidorina, Cristiano Rizzo, María Jesús Leal-Witt, Carolina Arias, Ignacio Cortés, Verónica Cornejo, Elisa Sacchetti, Giulio Catesini, Sara Boenzi, Carlo Dionisi-Vici and Karen Fuenzalida

Metabolites 2026, 16(1), 21; https://doi.org/10.3390/metabo16010021 - 24 Dec 2025

Abstract

Background/Objectives: Tyrosinemia type 1 (HT-1) is a treatable inherited disorder characterized by disrupted tyrosine metabolism, leading to severe liver, renal, and occasionally neurological dysfunction. Early diagnosis by newborn screening markedly reduces the risk of hepatocellular carcinoma (HCC), the most serious complication. A [...] Read more.

Background/Objectives: Tyrosinemia type 1 (HT-1) is a treatable inherited disorder characterized by disrupted tyrosine metabolism, leading to severe liver, renal, and occasionally neurological dysfunction. Early diagnosis by newborn screening markedly reduces the risk of hepatocellular carcinoma (HCC), the most serious complication. A deeper understanding of HT-1 pathophysiology is necessary to prevent disease complications and improve diagnostic and therapeutic strategies. This study explored the untargeted serum metabolomic profiles of HT-1 patients. Methods: High-resolution untargeted metabolomics coupled with liquid chromatography was applied for serum analysis of 16 late-diagnosed Chilean HT-1 patients on nitisinone (NTBC) therapy and 16 age- and sex-matched controls. The statistically significant up- and down-regulated features were used for annotation and association with different metabolic pathways. Results: Untargeted metabolomics revealed 1066 features significantly changed in HT-1 patients. Increased metabolites included aromatic compounds, medium- and long-chain acyl-carnitines, bile acids (prevalently taurine-conjugated), indole-based compounds, modified nucleosides and nucleobases. Decreased metabolites were mainly related to lipid class, including lysophosphatidylcholines, lysophosphatidic acids, long-chain fatty acids, and acylglycerols. Conclusions: Untargeted metabolomics showed perturbation of tyrosine- and tryptophan-related pathways and described a novel HT-1 metabolomic pattern demonstrating net dysregulation of lipid and bile acid metabolism in NTBC-treated patients with delay diagnoses. Increased acylcarnitines, taurine-conjugated bile acids, modified nucleobases, and reduced lysophosphatidylcholines overlap with the metabolomic pattern previously reported in Wnt/β-catenin-associated HCC. Although direct mechanistic link cannot be established in this study, these alterations may reflect persistent disease-related metabolic adaptations and warrant further investigation to clarify their potential relevance with long-term complications. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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13 pages, 1246 KB

Open AccessArticle

Association Between the Visceral Adiposity Index and Arterial Stiffness: Results of the EVasCu Study and a Meta-Analysis Including EVasCu Data and Prior Studies

by Elena Rescalvo-Fernández, Iván Cavero-Redondo, María Medrano, Irene Martínez-García, Carla Geovanna Lever-Megina, Marta Fenoll-Morante and Alicia Saz-Lara

Metabolites 2026, 16(1), 20; https://doi.org/10.3390/metabo16010020 - 24 Dec 2025

Abstract

Objectives: This study aimed to examine the association between the visceral adiposity index and arterial stiffness in healthy adults via original data from the EVasCu study and to contextualize these findings through a meta-analysis of previously published studies in the general population. [...] Read more.

Objectives: This study aimed to examine the association between the visceral adiposity index and arterial stiffness in healthy adults via original data from the EVasCu study and to contextualize these findings through a meta-analysis of previously published studies in the general population. Methods: A cross-sectional analysis was conducted in 389 healthy adults from the EVasCu study. The visceral adiposity index was calculated on the basis of waist circumference, body mass index, triglycerides, and high-density lipoprotein cholesterol, integrating the anthropometric and metabolic components of visceral adiposity. Arterial stiffness was assessed by the aortic pulse wave velocity. These original findings were complemented by a meta-analysis, including EVasCu data and data from prior studies, to obtain pooled correlation coefficients and 95% confidence intervals (CIs) for the association between visceral adiposity and arterial stiffness. Results: In the EVasCu study, the visceral adiposity index showed a statistically significant moderate correlation with the aortic pulse wave velocity (r = 0.281, p < 0.001). In the meta-analysis, the pooled correlation coefficient was 0.34 (95% CI: 0.27, 0.42), supporting a consistent association between the visceral adiposity index and both central and peripheral arterial stiffness across diverse populations. Conclusions: These findings indicate a positive association between the visceral adiposity index and arterial stiffness in both healthy individuals and populations with cardiometabolic conditions. However, given the predominantly cross-sectional nature of the evidence and the heterogeneity among the included studies, the results should be interpreted with caution. Further longitudinal, multivariable, and mechanistic studies are needed to clarify the clinical relevance of the visceral adiposity index beyond correlation and to determine its potential role as a complementary marker in cardiovascular risk assessment. Full article

(This article belongs to the Special Issue Lipids and Fatty Acid Metabolism in Cardiovascular Diseases)

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22 pages, 1688 KB

Open AccessArticle

Maternal Vitamin D Status, Oxidative Stress, and Implications for Neonatal Development: A Cross-Sectional Study

by Tania Flores-Bazán, Jacqueline Scarlett Barreto-González, José Pedraza-Chaverri, Omar Noel Medina-Campos, Araceli Castañeda-Ovando, Jeannett Alejandra Izquierdo-Vega, Diego Estrada-Luna, Martha Eunice Rodríguez-Arellano and Angélica Saraí Jiménez-Osorio

Metabolites 2026, 16(1), 19; https://doi.org/10.3390/metabo16010019 - 24 Dec 2025

Abstract

Background: Vitamin D (VD) plays a central role in calcium homeostasis during pregnancy and has been implicated in redox-related biological processes. While VD deficiency (VDD) has been consistently associated with adverse pregnancy outcomes, the relationships between VD insufficiency (VDI), maternal antioxidant-related biomarkers, [...] Read more.

Background: Vitamin D (VD) plays a central role in calcium homeostasis during pregnancy and has been implicated in redox-related biological processes. While VD deficiency (VDD) has been consistently associated with adverse pregnancy outcomes, the relationships between VD insufficiency (VDI), maternal antioxidant-related biomarkers, and neonatal outcomes remain incompletely characterized, particularly during the third trimester. Objective: To determines the prevalence of VDI in third-trimester pregnant women and to examine its associations with antioxidant-related markers and selected neonatal outcomes. Methods: A cross-sectional study was conducted among pregnant women in the third trimester attending a tertiary referral hospital in Mexico City. Maternal serum 25-hydroxyvitamin D (25-OHD) concentrations were measured, along with a panel of redox-related markers, including 2,2-diphenyl-2-2picrylhydrazyl (DPPH) radical scavenging activity, reduced glutathione (GSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), and oxygen radical absorbance capacity (ORAC). Neonatal anthropometric parameters were recorded at birth. Associations between maternal VD status, redox-related markers, environmental factors, and neonatal outcomes were evaluated using appropriate statistical analyses. Results: A high prevalence of VDI was observed in the study population. Maternal VDI was associated with lower activities of GSH, GST, and GPx. Passive exposure to tobacco smoke and season of sampling were also associated with lower VD concentrations. Neonates born to women with VDI had higher birth weight compared with those born to women with sufficient VD concentrations. Maternal serum 25-OHD concentrations correlated positively with selected antioxidant enzyme activities. Conclusions: In this cohort of third-trimester pregnant women, VDI co-occurred with environmental factors, differences in maternal redox-related markers, and selected neonatal outcomes. These findings support an associative framework in which suboptimal VD status during the third trimester is accompanied by variations in redox-related markers. Longitudinal and mechanistic studies are needed to clarify the temporal sequence and biological relevance of these associations. Full article

(This article belongs to the Special Issue Obesity, Hormones, and Metabolic Complications in Pregnancy)

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27 pages, 1774 KB

Open AccessReview

TRP Channels from Sensory Coding to Physiology

by Muhammad Atif and Youngseok Lee

Metabolites 2026, 16(1), 18; https://doi.org/10.3390/metabo16010018 - 24 Dec 2025

Abstract

Sensory systems allow the detection of external and internal cues essential for adaptive responses. Chemosensation exemplifies this integration, guiding feeding, mating, and toxin avoidance while also influencing physiological regulation. Across taxa, chemical detection relies on diverse receptor families, and emerging evidence reveals that [...] Read more.

Sensory systems allow the detection of external and internal cues essential for adaptive responses. Chemosensation exemplifies this integration, guiding feeding, mating, and toxin avoidance while also influencing physiological regulation. Across taxa, chemical detection relies on diverse receptor families, and emerging evidence reveals that transient receptor potential (TRP) channels—traditionally associated with phototransduction, thermosensation, and mechanotransduction—also mediate chemosensory functions. Studies in Drosophila melanogaster and vertebrates demonstrate that TRPs detect tastants, odorants, and internal chemical states, highlighting their evolutionary conservation and functional versatility. This review synthesizes current insights into the roles of TRP channels across four major domains: taste, smell, internal state, and central circuit modulation. Using D. melanogaster and mammalian systems as comparative frameworks, we highlight how TRP channels function as polymodal sensors, signal amplifiers, and modulators embedded within canonical receptor pathways rather than as standalone chemoreceptors. Recognizing these integrative functions not only expands our understanding of how organisms coordinate behavior with internal states but also points to TRP channels as potential targets for addressing chemosensory disorders and metabolic diseases. This framework highlights key directions for future research into TRP-mediated sensory and homeostatic regulation. Full article

(This article belongs to the Section Animal Metabolism)

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22 pages, 947 KB

Open AccessSystematic Review

Metabolic Heterogeneity in High-Grade Glioma Assessed by Multi-Tracer PET and Ex Vivo Metabolomics: A Systematic Review and Meta-Analysis

by Julien Todeschi, Hélène Cebula, Caroline Bund and Izzie-Jacques Namer

Metabolites 2026, 16(1), 17; https://doi.org/10.3390/metabo16010017 - 24 Dec 2025

Abstract

Background/Objectives: High-grade glioma shows marked metabolic heterogeneity. We performed a PRISMA-guided systematic review and meta-analysis to quantify PET accuracy for pseudoprogression (PsP) and for recurrence/progression versus treatment-related change (TRC), assess pool baseline associations with overall (OS) and progression-free survival (PFS), summarize PET-based [...] Read more.

Background/Objectives: High-grade glioma shows marked metabolic heterogeneity. We performed a PRISMA-guided systematic review and meta-analysis to quantify PET accuracy for pseudoprogression (PsP) and for recurrence/progression versus treatment-related change (TRC), assess pool baseline associations with overall (OS) and progression-free survival (PFS), summarize PET-based prediction of molecular markers, and assess the PET–stereotactic biopsy–ex vivo metabolomics workflow. Methods: We searched PubMed/MEDLINE and the Web of Science Core Collection (Clarivate) from inception to 1 September 2025 for HGG cohorts with baseline PET. Eligibility: Adults with HGG; diagnostic syntheses required per-patient 2 × 2; prognostic syntheses required for HR with 95% CI. Risk of bias: QUADAS-2 (diagnostic) and QUIPS (prognostic). Random-effects models pooled log-HRs and sensitivity/specificity; molecular studies were summarized by AUCs. Imaging-to-omics concordance was reviewed narratively owing to the absence of co-registered PET–metabolite maps in human HGG. Results: The results included the following: OS k = 10; PFS k = 3; PsP k = 2 (N = 76); and TRC k = 3 (N = 152). For PsP, two amino acid PET cohorts yielded a sensitivity of 0.943 and a specificity of 0.826. For TRC, pooled FDOPA across two cohorts gave rise to a sensitivity of 0.879 and a specificity of 0.771. OS meta-analyses were non-significant under Hartung–Knapp modification—FDG HR of 1.09 (95% CI 0.69–1.73) and amino acid HR of 1.03 (0.72–1.46)—with substantial heterogeneity. PFS effects varied by tracer/metric; examples include FDOPA HR of 7.92 (2.17–28.90) and MET metabolic tumor volume HR of 1.60 (1.20–2.30). Conclusions: Amino acid PET is sensitive to PsP and, with FDOPA, aids TRC discrimination when MRI is equivocal, whereas baseline PET–survival associations are weak and heterogeneous. Prospective co-registered PET/MR with stereotactic biopsies and HR-MAS NMR spectroscopy/MALDI-MSI is required to quantify imaging-to-omics concordance and standardize spatial endpoints. Study registration: PROSPERO CRD420251113416. Funding: none. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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21 pages, 668 KB

Open AccessArticle

The Effect of Short-Term and High-Intensity Functional Circuit Training on Plasma Lipidome Profiles of People Living with and Without HIV

by Marcos Yukio Yoshinaga, Flávio Gomez Faria, Adriano de Britto Chaves-Filho, Sayuri Miyamoto, Tania Cristina Pithon-Curi, Giselle Cristina Bueno, Bruno Ferrari Silva, Sidney Barnabé Peres and Solange Marta Franzoi de Moraes

Metabolites 2026, 16(1), 16; https://doi.org/10.3390/metabo16010016 - 24 Dec 2025

Abstract

Background/Objectives: Both HIV infection and antiretroviral therapy contribute to dyslipidemia and abnormal body fat distribution in people living with HIV (PLWH). Exercise training is an effective intervention to protect against these metabolic changes. However, little is known about the mechanisms underlying the impact [...] Read more.

Background/Objectives: Both HIV infection and antiretroviral therapy contribute to dyslipidemia and abnormal body fat distribution in people living with HIV (PLWH). Exercise training is an effective intervention to protect against these metabolic changes. However, little is known about the mechanisms underlying the impact of exercise training on lipid metabolism in PLWH. This study aimed to comparatively evaluate the effect of high-intensity functional circuit training on the plasma lipidome of PLWH and HIV-negative subjects (control). Methods: PLWH (n = 13) and control (n = 14) were submitted to 8 weeks of exercise training. Body composition, anthropometric, and biochemical parameters were measured. Plasma was obtained in a fasting state for lipidomic analysis. Results: Anthropometric and biochemical parameters revealed lower levels of leptin, HDL-C, body fat %, and BMI combined with elevated aspartate transaminase (AST) and Homeostasis Model Assessment of β-cell function (HOMA_beta) in PLWH when compared to control subjects that persisted from baseline to post-exercise training. Nonetheless, contrasting levels of adiponectin, fasting insulin, and phosphatidylcholine-containing lipids observed at baseline were equalized after training in PLWH. In control subjects, significant reductions in concentrations of triglycerides alongside phosphatidylinositol and glycosylated ceramides were observed post-exercise training. By contrast, PWLH displayed an increase in diglycerides, acylcarnitines, and free cholesterol levels after exercise training, together with decreased concentrations of free fatty acids, cholesteryl esters, and glycosylated ceramides. Conclusions: In addition to specific lipidome alterations in each group, particularly driven by improved insulin resistance in PLWH, this study showed concomitant modulation of several glycerophospholipids and sphingolipids, suggesting health-promoting effects of short-term exercise training. Collectively, these modulated lipid species represent interesting targets for future lipidomic-based studies evaluating not only the effects of exercise training but also the molecular mechanisms resulting in a healthier plasma lipidome profile. Full article

(This article belongs to the Special Issue The Role of Lipid Metabolism in Health and Disease)

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17 pages, 3103 KB

Open AccessArticle

Multi-Analytical Insight into the Non-Volatile Phytochemical Composition of Coleus aromaticus (Roxb.) Benth.

by Chiara Toniolo, Martina Bortolami, Adriano Patriarca, Daniela De Vita, Fabio Sciubba and Luca Santi

Metabolites 2026, 16(1), 15; https://doi.org/10.3390/metabo16010015 - 23 Dec 2025

Abstract

Background/Objectives: Coleus aromaticus (Lamiaceae), also known as Cuban oregano or Indian borage, is a semi-succulent perennial species widely used in traditional medicine for its therapeutic and nutritional properties. While its essential oils and aromatic fraction have been extensively investigated, the characterization of [...] Read more.

Background/Objectives: Coleus aromaticus (Lamiaceae), also known as Cuban oregano or Indian borage, is a semi-succulent perennial species widely used in traditional medicine for its therapeutic and nutritional properties. While its essential oils and aromatic fraction have been extensively investigated, the characterization of its non-volatile metabolites remains limited. The aim of this study was to explore the chemical composition of fresh leaves with a focus on the non-volatile fraction. Methods: Fresh leaves of C. aromaticus were cryogenically treated with liquid nitrogen, ground, and subjected to three different extraction procedures: hydroalcoholic maceration, ethyl acetate maceration, and liquid–liquid partitioning to obtain a dichloromethane organic phase and a hydroalcoholic phase. Extracts and fractions were analyzed by HPTLC and HPLC for metabolic profiling. In addition, the Bligh–Dyer method was applied to separate polar and non-polar metabolites, which were subsequently characterized using NMR spectroscopy. Results: Chromatographic analyses highlighted the occurrence and distribution of organic acids, polyphenols (notably flavonoids), and proteinogenic amino acids. Spectroscopic data confirmed the presence of diverse polar and non-polar metabolites, providing a more detailed chemical fingerprint of C. aromaticus. This integrated approach broadened the phytochemical profile of the species beyond the well-documented essential oils. Conclusions: The results contribute to a better understanding of the non-volatile metabolites of C. aromaticus, offering novel insights into its chemical diversity. These findings highlight the potential of this plant as a valuable source of bioactive compounds, supporting its future application in nutraceutical and pharmaceutical research. Full article

(This article belongs to the Special Issue Advances in Secondary Metabolites: Phytochemical Analysis and Bioactivity Assays—2nd Edition)

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15 pages, 4045 KB

Open AccessArticle

Profiling Serum Oxylipin Metabolites Across Melanoma Subtypes and Immunotherapy Responders

by Alexander C. Goodman, Kylie M. Michel, Morgan L. MacBeth, Jaqueline A. Turner, Richard P. Tobin, William A. Robinson and Kasey L. Couts

Metabolites 2026, 16(1), 14; https://doi.org/10.3390/metabo16010014 - 23 Dec 2025

Abstract

Background/Objectives: Immunotherapy has significantly improved clinical outcomes for patients with late-stage melanoma, yet a substantial portion of patients fail to respond to these treatments. The variability in responses to immunotherapy, both among individual patients and across different melanoma subtypes, underscores the need to [...] Read more.

Background/Objectives: Immunotherapy has significantly improved clinical outcomes for patients with late-stage melanoma, yet a substantial portion of patients fail to respond to these treatments. The variability in responses to immunotherapy, both among individual patients and across different melanoma subtypes, underscores the need to explore the influence of circulating factors such as oxylipins on therapeutic outcomes. This study investigated the relationship between serum oxylipin profiles and response to immune checkpoint inhibitor therapy in melanoma subtypes to identify potential metabolic biomarkers for treatment response. Methods: In a retrospective cohort study, serum samples from 43 stage III and stage IV melanoma patients treated at the University of Colorado Hospital from 2010 to 2023 were analyzed via ultra-high-pressure liquid chromatography-mass spectrometry. Melanoma patients were treated with anti-PD-1 monotherapy or combination immune checkpoint inhibitor therapy, and response was assessed using RECIST 1.1 criteria. Results: We determined that global oxylipin metabolite profiles are largely uniform pre- and post-treatment across melanoma subtypes, including cutaneous, acral, mucosal, and uveal melanoma. Prostaglandin J₂ was more abundant in rare melanoma subtypes, including acral, mucosal, and uveal melanoma, compared to cutaneous melanoma. Conclusions: Despite limited variation in serum oxylipin molecular species by subtype and response status, we observed significant differences in prostaglandin J₂, which could serve as a potential biomarker for immune checkpoint inhibitor therapy response in melanoma. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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