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18 pages, 21969 KB  
Article
Single-Section Sequential MALDI-MSI Reveals Metabolic and N-Glycan Remodeling During Malignant Transformation in Hepatocellular Adenoma
by Jianfeng Xu, Jian Sui, Da Xu, Xiaoxue Zhou, Youhong Hu, Jie Yuan, Jia Liu and Lu Lu
Metabolites 2026, 16(4), 217; https://doi.org/10.3390/metabo16040217 - 26 Mar 2026
Abstract
Background/Objectives: Malignant transformation of hepatocellular adenoma (HCA) represents a clinically significant yet incompletely understood process. Although the pathological and clinical characteristics of HCA have been extensively described, its spatial molecular heterogeneity and spatially organized molecular variation at the tissue level remain insufficiently characterized. [...] Read more.
Background/Objectives: Malignant transformation of hepatocellular adenoma (HCA) represents a clinically significant yet incompletely understood process. Although the pathological and clinical characteristics of HCA have been extensively described, its spatial molecular heterogeneity and spatially organized molecular variation at the tissue level remain insufficiently characterized. This study aimed to establish a spatially integrated multi-omics workflow and to delineate spatially organized molecular variation across histologically defined regions from adenoma to carcinoma. Methods: A sequential dual-layer matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) workflow was developed to acquire small-molecule metabolomic and N-glycan spatial data from the same formalin-fixed paraffin-embedded (FFPE) tissue section. Four rare HCA specimens containing focal carcinoma transformation were included in this study. Pixel-level clustering, region-based co-localization analysis, and diffusion pseudotime modeling were applied to characterize spatial metabolic and N-glycan patterns across normal liver tissue (NL), hepatocellular adenoma (HCA), and carcinoma-transformed regions within adenoma (HCA-HCC). Results: Small-molecule MSI revealed spatial metabolic stratification within HCA, with variation observed in nucleotide-related, lipid-related, sulfur-related, and sugar nucleotide–associated metabolites. Pseudotime analysis revealed a spatial ordering of samples across NL, HCA, and HCA-HCC regions, showing differences in antioxidant-associated metabolites, lipid-related features, and bile acid-related metabolites across regions. N-glycan MSI identified independent glycosylation niches, with increasing structural complexity and enrichment of highly branched glycans in carcinoma-transformed regions. Integration of metabolomic and glycomic data suggested spatially associated patterns between metabolite features and glycan structures across regions. Conclusions: This study provides spatially resolved evidence of spatially organized patterns of molecular variation across histologically defined regions of HCA. The identified metabolic and N-glycan gradients provide insights into spatial molecular organization during malignant transformation of hepatocellular adenoma. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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30 pages, 2174 KB  
Review
Type 2 Diabetes Mellitus as a Multisystem Disease: From Insulin Resistance to Organ Crosstalk—A Narrative Review
by Héctor Fuentes-Barría, Raúl Aguilera-Eguía, Cherie Flores-Fernández, Lissé Angarita-Davila and Miguel Alarcón-Rivera
Biomedicines 2026, 14(4), 752; https://doi.org/10.3390/biomedicines14040752 - 26 Mar 2026
Abstract
Type 2 Diabetes Mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance, chronic low-grade inflammation, and progressive metabolic dysfunction affecting multiple organs. This review explores the molecular and physiological mechanisms underlying T2DM, emphasizing the role of intracellular metabolic signaling pathways, mitochondrial [...] Read more.
Type 2 Diabetes Mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance, chronic low-grade inflammation, and progressive metabolic dysfunction affecting multiple organs. This review explores the molecular and physiological mechanisms underlying T2DM, emphasizing the role of intracellular metabolic signaling pathways, mitochondrial function, and inter-organ communication in the development and progression of metabolic dysregulation. Particular attention is given to key regulatory pathways such as AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin (mTOR), which play central roles in cellular energy sensing, glucose metabolism, and lipid homeostasis. Dysregulation of these pathways contributes to impaired insulin signaling, mitochondrial dysfunction, oxidative stress, and altered adipogenesis, all of which are critical factors in the pathophysiology of T2DM. In addition, growing evidence highlights the importance of metabolic crosstalk between skeletal muscle, adipose tissue, liver, pancreas, and the gut microbiota through signaling molecules including adipokines, myokines, hepatokines, and gut-derived metabolites. These inter-organ networks influence systemic inflammation, metabolic flexibility, and glucose homeostasis. Lifestyle factors such as physical activity, nutritional patterns, and micronutrient status have also been shown to modulate these molecular pathways, improving mitochondrial function and insulin sensitivity while reducing inflammatory signaling. Despite significant advances in understanding the molecular basis of T2DM, important challenges remain, including heterogeneity in disease progression and variability in individual metabolic responses. In conclusion, T2DM should be understood as a multisystem metabolic disorder driven by complex interactions between molecular signaling pathways and systemic metabolic regulation. Future research integrating molecular mechanisms with clinical and lifestyle interventions may help develop more effective strategies for prevention and treatment. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Current Progress and Future Challenges)
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19 pages, 3100 KB  
Article
Genome-Wide Identification of WRKY Gene Family in Artemisia and Its Expression Analysis of Aphid Resistance
by Lanjie Xu, Sufang An, Qing Yang, Xiaohui Wu, Hongqi Yang, Junping Feng, Yazhou Liu, Zhansheng Nie, Yongliang Yu and Huizhen Liang
Int. J. Mol. Sci. 2026, 27(7), 2981; https://doi.org/10.3390/ijms27072981 (registering DOI) - 25 Mar 2026
Abstract
WRKY is a crucial transcription factor involved in plant growth, development, and responses to abiotic stress. In the present study, a total of 182 AaWRKY transcription factor members were identified across the Artemisia argyi genome and found to be distributed across 17 chromosomes. [...] Read more.
WRKY is a crucial transcription factor involved in plant growth, development, and responses to abiotic stress. In the present study, a total of 182 AaWRKY transcription factor members were identified across the Artemisia argyi genome and found to be distributed across 17 chromosomes. Evolutionary analysis revealed that segmental duplication served as the primary driver for family expansion, with the evolutionary trajectory shaped by strong purifying selection (Ka/Ks < 1.0). Phylogenetic classification categorized these members into seven highly conserved subgroups, while physicochemical analysis indicated that most AaWRKYs are unstable, hydrophilic proteins, consistent with the rapid turnover required for transcriptional switches. Transcriptomic profiling unveiled significant tissue-specific expression patterns, with over 50% of the members predominantly enriched in roots and specific genes, such as AaWRKY11, implicated in the regulation of leaf senescence. Protein–protein interaction (PPI) network analysis identified AaWRKY110 as a central regulatory hub linking the MAPK signaling pathway with the isoflavonoid biosynthetic machinery. Furthermore, comparative transcriptomic analysis between aphid-resistant (Ai20K) and susceptible (Ai72G) cultivars demonstrated that resistance is conferred by a priming mechanism involving high basal expression of key candidates, including AaWRKY82, 108, 128, and 71. In contrast, the susceptible genotype exhibited a delayed and ineffective hypersensitive-like response. Collectively, these findings elucidate the evolutionary dynamics of the AaWRKY family and provide critical genetic targets for the concurrent improvement of medicinal metabolite accumulation and biotic stress resilience in Artemisia argyi via molecular breeding. Full article
(This article belongs to the Section Molecular Plant Sciences)
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18 pages, 3050 KB  
Article
Differential Analysis of Sesquiterpenoids of Atractylodes macrocephalus from Different Origins Based on Transcriptomics
by Ao Sun, Xin Yu, Shan Lu, Tong Wu, Ke-Yi Meng, Jing-Wei Hao, Nan Zhao, Jun-Hong Chai and Ting-Ting He
Molecules 2026, 31(7), 1075; https://doi.org/10.3390/molecules31071075 - 25 Mar 2026
Abstract
Atractylodes macrocephala (A.M.) is a traditional Chinese medicinal and edible herb renowned for its spleen-tonifying, dampness-resolving, diuretic, and antiperspirant properties. Its primary bioactive constituents are terpenoids, which have demonstrated anti-inflammatory, antitumor, and immunomodulatory activities. However, transcriptomic studies focusing on terpenoid biosynthesis in A.M. [...] Read more.
Atractylodes macrocephala (A.M.) is a traditional Chinese medicinal and edible herb renowned for its spleen-tonifying, dampness-resolving, diuretic, and antiperspirant properties. Its primary bioactive constituents are terpenoids, which have demonstrated anti-inflammatory, antitumor, and immunomodulatory activities. However, transcriptomic studies focusing on terpenoid biosynthesis in A.M. from different geographical origins remain limited. To investigate the molecular mechanisms underlying differential sesquiterpenoid production, we performed transcriptome sequencing on samples collected from four distinct regions in China. Sesquiterpenoid biosynthesis predominantly proceeds through the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways. Comparative analysis revealed four key enzyme-encoding genes—HMGCR, ISPF, GCPE, and FDPS—whose differential expression patterns were further validated by quantitative real-time PCR (qRT-PCR). Samples from Shaanxi exhibited the highest upregulation of biosynthetic genes and the greatest enrichment of terpene-related metabolites, suggesting enhanced pharmacological potential. In contrast, samples from Fujian, Anhui, and Hebei displayed relatively lower activity, with only FDPS upregulated in the Hebei sample. High-performance liquid chromatography (HPLC) quantification confirmed regional differences in the levels of major terpenoids—including atractylodin, atractylenolide I, and atractylenolide III—which correlated well with the observed gene expression profiles. This study compared conspecific A.M. from different geographical regions and further revealed that the variation in terpenoid metabolites is closely related to environmental factors. These findings provide a theoretical basis for the further discovery of functional genes and offer important implications for the quality control of A.M. Full article
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38 pages, 774 KB  
Review
Plant-Based Biomaterials as Bio-Instructive Immunomodulators: Design Principles, Mechanisms, and Translational Challenges
by Stefania Lamponi
Life 2026, 16(4), 538; https://doi.org/10.3390/life16040538 - 24 Mar 2026
Viewed by 1
Abstract
Plant-based biomaterials are increasingly recognized as bio-instructive platforms capable of actively modulating immune responses rather than functioning solely as passive structural supports. In this context, the term plant-based refers to photosynthetic biomass-derived platforms, including both terrestrial plants and marine macroalgae, reflecting their shared [...] Read more.
Plant-based biomaterials are increasingly recognized as bio-instructive platforms capable of actively modulating immune responses rather than functioning solely as passive structural supports. In this context, the term plant-based refers to photosynthetic biomass-derived platforms, including both terrestrial plants and marine macroalgae, reflecting their shared richness in polysaccharides and secondary metabolites relevant to immune engineering and regenerative medicine. This review critically synthesizes current evidence on plant-derived polysaccharides and phytochemicals, including algal sulfated polysaccharides (fucoidan, alginate, carrageenan, and ulvan), terrestrial plant polysaccharides (e.g., Lycium barbarum and Aloe vera derivatives), polyphenols, and other secondary metabolites such as terpenoids and alkaloids, highlighting their roles as immunomodulators in biomedical contexts. Key mechanisms include macrophage polarization along an M1–M2 continuum, pattern recognition receptor engagement, redox and metabolic regulation, and crosstalk between innate and adaptive immunity, with emphasis on context-dependent signaling and structural heterogeneity. Material design parameters, including molecular weight and chemical functionalization, are critical determinants of immune responses. Advanced delivery systems, such as hydrogels, nanocomposites, phytosomes, and plant-derived extracellular vesicles (EVs), enable improved stability and spatiotemporal control. Applications in wound and musculoskeletal regeneration are discussed alongside translational challenges, including variability, reproducibility, regulatory issues, and the need for standardized characterization and immune validation. Full article
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22 pages, 3714 KB  
Article
Co-Culture Reveals the Quorum-Sensing Regulatory Mechanism of Bacteriocin PlnJK Synthesis in Lactiplantibacillus plantarum EL2
by Fengming Liu, Yixuan Lin, Qi Liang, Xuhui Chen and Baotang Zhao
Microorganisms 2026, 14(4), 730; https://doi.org/10.3390/microorganisms14040730 (registering DOI) - 24 Mar 2026
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Abstract
Lactiplantibacillus plantarum EL2, isolated from traditional fermented yak milk in the high-altitude Gannan Tibetan Autonomous Prefecture, produces the class IIb bacteriocin PlnJK. This study established three distinct cultivation models that critically influenced bacteriocin yield. Microbial co-culture was found to enhance the stress tolerance [...] Read more.
Lactiplantibacillus plantarum EL2, isolated from traditional fermented yak milk in the high-altitude Gannan Tibetan Autonomous Prefecture, produces the class IIb bacteriocin PlnJK. This study established three distinct cultivation models that critically influenced bacteriocin yield. Microbial co-culture was found to enhance the stress tolerance of EL2, significantly boosting PlnJK production. The optimal inducing strain, Enterococcus faecalis MH2, increased the bacteriocin inhibition zone diameter from 15.38 mm to 25.58 mm. Following optimization of key parameters—initial inoculum concentration (107 CFU/mL), inoculation ratio (3:1, EL2:MH2), and initial pH (6.0)—the inhibition zone diameter reached 30.32 mm, representing a 1.97-fold increase over pure culture. Co-culture not only advanced the onset but also extended the duration of bacteriocin synthesis. Throughout the 24 h incubation, cell density, AI-2 autoinducer concentration, and the expression of key regulatory genes were significantly elevated in co-culture compared to monoculture, aligning with a cell-density-dependent, quorum-sensing (QS) regulatory paradigm. Bacteriocin production was co-regulated by two QS pathways: the AI-2/luxS system and the plnA-mediated autoinducing peptide (AIP). Gene expression analysis revealed differential temporal regulation: luxS expression was higher during the exponential phase (2.29 vs. 1.42 in stationary phase), while plnA exhibited the opposite pattern (1.42 in exponential vs. 2.21 in stationary phase). This indicates that the AI-2/luxS pathway drives strong induction during active growth, whereas plnA/AIP-mediated promotion becomes predominant later. The stationary-phase effect is likely triggered by the accumulation of specific MH2 metabolites, which impose an environmental stress on EL2, stimulating the pln-encoded regulatory system and further enhancing bacteriocin yield. This work provides an economically viable strategy and a novel theoretical framework for optimizing microbial cultivation, enhancing bacteriocin production, and elucidating the complex QS-mediated regulatory mechanisms involved. Full article
(This article belongs to the Section Food Microbiology)
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26 pages, 871 KB  
Review
Physiological Regulation of Nutritional and Metabolic Biomarkers in Obesity: Implications for Precision Nutrition
by Girolamo Di Maio, Maria Giovanna Tafuri, Maria Casillo, Antonietta Messina, Salvatore Allocca, Ines Villano, Fiorenzo Moscatelli, Antonietta Monda, Marco La Marra and Vincenzo Monda
Nutrients 2026, 18(6), 1014; https://doi.org/10.3390/nu18061014 - 23 Mar 2026
Viewed by 123
Abstract
Obesity represents a heterogeneous metabolic disorder characterized by substantial interindividual variation in inflammatory status, insulin sensitivity, and cardiometabolic risk. Traditional anthropometric measures fail to capture this metabolic diversity, limiting risk stratification and personalized intervention strategies. This review critically examines nutritional and metabolic biomarkers [...] Read more.
Obesity represents a heterogeneous metabolic disorder characterized by substantial interindividual variation in inflammatory status, insulin sensitivity, and cardiometabolic risk. Traditional anthropometric measures fail to capture this metabolic diversity, limiting risk stratification and personalized intervention strategies. This review critically examines nutritional and metabolic biomarkers that reflect the physiological dysregulation underlying obesity, including adipokines (leptin, adiponectin, resistin), inflammatory markers (C-reactive protein, interleukin-6, TNF-α), insulin resistance indices (HOMA-IR, fasting insulin, HbA1c), and lipid metabolism indicators (LDL cholesterol, triglycerides, HDL cholesterol, and liver enzymes such as ALT and GGT). Among these, elevated CRP, reduced adiponectin, and increased HOMA-IR have demonstrated the strongest clinical utility for early metabolic risk identification. We further evaluate emerging biomarkers—including circulating microRNAs, gut microbiota-derived metabolites (short-chain fatty acids, TMAO, lipopolysaccharides), and bile acid profiles—which offer additional mechanistic insight into diet–microbiome–host interactions. We systematically assess the mechanistic basis, clinical relevance, and nutritional modulation of each biomarker class, emphasizing how dietary composition—particularly fatty acid quality, fiber intake, and overall dietary patterns such as the Mediterranean diet—influences biomarker profiles and metabolic outcomes. Furthermore, we explore how biomarker-based phenotyping enables precision nutrition approaches by identifying individuals most likely to benefit from specific dietary interventions. Integration of multi-biomarker panels with clinical and genetic data holds promise for advancing from population-based dietary guidelines toward individualized nutrition strategies that optimize metabolic health and prevent obesity-related complications. Future research should prioritize validating biomarker-guided intervention frameworks, establishing standardized thresholds across diverse populations, and developing clinically implementable tools for personalized nutritional medicine. Full article
(This article belongs to the Special Issue Nutritional and Metabolic Biomarkers in Obesity)
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19 pages, 2702 KB  
Article
Temporal Metabolomic Dynamics of Methyl Jasmonate-Induced Reprogramming in Vitis vinifera L. cv. Tempranillo Leaves
by Diego F. Paladines-Quezada and Cristina Cedeño-Pinos
Agronomy 2026, 16(6), 673; https://doi.org/10.3390/agronomy16060673 - 23 Mar 2026
Viewed by 129
Abstract
Methyl jasmonate (MeJA) is a defence-related phytohormone that triggers metabolic reprogramming in grapevines and modulates pathways associated with stress responses and secondary metabolism. However, the temporal organisation of leaf metabolic responses following MeJA elicitation remains insufficiently characterised. In this study, an untargeted metabolomic [...] Read more.
Methyl jasmonate (MeJA) is a defence-related phytohormone that triggers metabolic reprogramming in grapevines and modulates pathways associated with stress responses and secondary metabolism. However, the temporal organisation of leaf metabolic responses following MeJA elicitation remains insufficiently characterised. In this study, an untargeted metabolomic approach based on UPLC-QTOF-MS was applied to investigate the time-resolved metabolic response of Vitis vinifera L. cv. Tempranillo leaves following foliar application of 10 mM MeJA under controlled greenhouse conditions. Leaf samples were collected at 0, 3, 6, 18, 24, and 48 h post-treatment. After quality filtering, 2552 metabolite features were detected, of which 40 discriminant features met stringent statistical criteria (maximum fold change ≥ 2 and p ≤ 0.05). Putative annotation according to Metabolomics Standards Initiative guidelines (MSI levels 2–3) revealed modulation of several metabolite classes, including carbohydrate-derived conjugates, terpenoid-related metabolites, hydroxycinnamic acid derivatives, and flavonoid-associated compounds. Temporal profiling revealed structured and non-monotonic metabolic responses characterised by rapid early changes between 3 and 6 h, followed by delayed accumulation patterns peaking around 24 h. Early phases were mainly associated with carbohydrate-related metabolites, suggesting rapid redistribution of carbon resources after elicitor perception. These results indicate that MeJA-induced metabolic adjustment in Tempranillo leaves occurs through temporally differentiated response phases rather than a uniform metabolic shift, providing a time-resolved metabolomic framework for interpreting elicitor-driven defence responses in grapevine. Full article
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17 pages, 7121 KB  
Article
Habitat Filtering Shapes Root Endophytic Microbiome Assembly and Its Association with Fruit Quality in Lycium ruthenicum from the Tarim Basin
by Aihua Liang, Fengjiao Wang, Tianyi Liu, Yuting Liao and Zixin Mu
Plants 2026, 15(6), 979; https://doi.org/10.3390/plants15060979 - 22 Mar 2026
Viewed by 160
Abstract
Lycium ruthenicum is a typical desert halophyte with strong stress resistance and high medicinal value in the Tarim Basin. Root endophytic microbes play critical roles in host adaptation, nutrient cycling, and secondary metabolite accumulation. To clarify the diversity patterns of root endophytic bacteria [...] Read more.
Lycium ruthenicum is a typical desert halophyte with strong stress resistance and high medicinal value in the Tarim Basin. Root endophytic microbes play critical roles in host adaptation, nutrient cycling, and secondary metabolite accumulation. To clarify the diversity patterns of root endophytic bacteria and fungi and their relationships with environmental factors and fruit quality, high-throughput sequencing was used to analyze microbial community characteristics of Lycium ruthenicum collected from different habitats in the Tarim Basin. The results showed that rarefaction curves of alpha diversity indices (Chao1, Shannon, Pielou_e) tended to be saturated, indicating sufficient sequencing depth. Principal coordinate analysis (PCoA) revealed significant habitat-driven differentiation in both bacterial and fungal community structures. Community composition analysis showed that the relative abundance of dominant taxa at the phylum and genus levels differed significantly among sampling sites. Co-occurrence network analysis indicated that bacterial and fungal networks exhibited high modularity and were dominated by positive synergistic interactions, with Pseudomonas, Bacillus, Sphingomonas, Alternaria, and Fusarium as key hub genera. Moreover, root endophytic communities were significantly correlated with climatic variables, soil physicochemical properties, and fruit quality traits, including anthocyanin (AC), proanthocyanidin (PA), total flavonoids (TF), and total polyphenols (TP). Several keystone microbial genera were closely associated with the accumulation of functional metabolites in fruits. This study reveals the biogeographic distribution and co-occurrence characteristics of root endophytes in Lycium ruthenicum and provides a theoretical basis for understanding microbe–host–environment interactions and the quality improvement of desert medicinal plants. Full article
(This article belongs to the Special Issue Forage and Sustainable Agriculture)
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23 pages, 1917 KB  
Article
Sex-Driven Variation in Polar Metabolites and Lipid Motifs of Paracentrotus lividus Gonads Profiled by 1H NMR
by Ricardo Ibanco-Cañete, Estela Carbonell-Garzón, Sergio Amorós-Trujillo, Pablo Sanchez-Jerez and Frutos Carlos Marhuenda Egea
Metabolites 2026, 16(3), 211; https://doi.org/10.3390/metabo16030211 - 21 Mar 2026
Viewed by 156
Abstract
Background/Objectives: Sea urchin gonads (“roe”) are a valuable seafood product and a chemically complex matrix whose composition varies with physiology and environment. We present a biphasic extraction and 1H NMR workflow to build a reusable reference inventory of polar metabolites and apolar [...] Read more.
Background/Objectives: Sea urchin gonads (“roe”) are a valuable seafood product and a chemically complex matrix whose composition varies with physiology and environment. We present a biphasic extraction and 1H NMR workflow to build a reusable reference inventory of polar metabolites and apolar lipid features in Paracentrotus lividus. Methods: Gonads from 37 adults (23 males, 14 females) collected at two sites (Alicante and Jávea–Dénia, Spain; October 2024) were lyophilized, extracted with methanol/chloroform/water, and analyzed by 400 MHz 1H NMR in buffered aqueous solution (polar) and CDCl3 (apolar). Polar metabolite identification combined 1D patterns with database matching and 1H–13C HSQC confirmation on representative samples, yielding 71 annotated resonances corresponding to 37 metabolites spanning amino acids, osmolytes/quaternary amines, carbohydrates/aminosugars, and nucleoside/purine-related compounds. Results: Polar fingerprints enabled supervised modelling: PLS-LDA separated sexes with low cross-validated error, and SPA/COSS ranking highlighted glycine, alanine, creatine and osmolyte-associated signals as key discriminants; pathway mapping supported the enrichment of amino-acid and one-carbon/purine networks. Apolar spectra were annotated at the motif level and used for lipid-index estimation, indicating substantial unsaturation but low docosahexaenoic acid (DHA) and modest sex effects. Conclusions: The curated peak lists and reporting framework facilitate reproducible NMR annotation and future comparative studies of P. lividus gonads. Full article
(This article belongs to the Special Issue Nutrition, Metabolism and Physiology in Aquatic Animals)
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21 pages, 1817 KB  
Article
Physical Activity Is Associated with Gut Microbiome Features and Organic Acid Patterns in Adults Consuming Plant-Rich Diets: An Exploratory Cross-Sectional Study
by Ramona Alina Tomuța, Alexandra Caltea, Marc Cristian Ghitea, Evelin Claudia Ghitea, Maria Flavia Gîtea, Timea Claudia Ghitea and Florin Banica
Biology 2026, 15(6), 507; https://doi.org/10.3390/biology15060507 - 21 Mar 2026
Viewed by 143
Abstract
Background: Plant-rich dietary patterns are widely associated with metabolic and gastrointestinal health benefits. However, individuals consuming predominantly plant-based foods may also experience chronic low-dose exposure to dietary pesticide residues. At the same time, physical activity is recognized as an important lifestyle factor influencing [...] Read more.
Background: Plant-rich dietary patterns are widely associated with metabolic and gastrointestinal health benefits. However, individuals consuming predominantly plant-based foods may also experience chronic low-dose exposure to dietary pesticide residues. At the same time, physical activity is recognized as an important lifestyle factor influencing metabolic health and gut microbiome composition. How microbiome features and microbiome-related metabolic profiles vary according to physical activity level in adults consuming plant-rich diets and reporting gastrointestinal symptoms remains insufficiently characterized. Objective: To explore associations between physical activity level, gut microbiome characteristics, and urinary organic acid patterns in adults consuming predominantly plant-rich diets and experiencing gastrointestinal symptoms, within a cohort characterized by comparable estimated dietary pesticide exposure used as a contextual dietary background variable. Methods: This cross-sectional observational study included 93 adults consuming ≥50% plant-based foods for at least six months and reporting persistent gastrointestinal symptoms. Participants were stratified according to physical activity level using WHO-based thresholds (<150 vs. ≥150 min/week of moderate-intensity activity). Stool microbiota were assessed using a targeted quantitative PCR panel, and microbial diversity was summarized using a laboratory-derived Shannon index. A voluntary subgroup (n = 50) underwent targeted urinary organic acid analysis (LC–MS/MS). Dietary pesticide exposure was indirectly estimated using national surveillance data combined with individual dietary records and was applied uniformly across groups. Analyses were primarily descriptive and exploratory; results are presented as associations. Results: Estimated dietary pesticide exposure did not differ between physical activity groups. Participants with lower physical activity were older and exhibited lower microbial diversity and a higher prevalence of reduced abundance in selected commensal taxa. Differences were observed in selected intermediary organic acid markers, while no statistically significant difference was found for the bile acid-related indicator. Several cross-domain correlations were identified between microbial features and metabolite patterns. However, given the cross-sectional design, age imbalance between groups, and subgroup-based metabolomic analyses, the findings should be interpreted as hypothesis-generating rather than indicative of independent effects of physical activity. Conclusions: In adults consuming plant-rich diets and reporting gastrointestinal symptoms, physical activity level was associated with distinct microbiome and microbiome-related metabolic patterns under comparable estimated dietary pesticide exposure. These findings highlight the potential contribution of lifestyle factors to interindividual variability in gut microbial and metabolic profiles, while underscoring the need for age-adjusted, longitudinal, and biomarker-based studies to clarify directionality and mechanisms. Full article
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39 pages, 1850 KB  
Review
Food as Friend or Foe: A Decadal Narrative Review of Dietary Patterns as Determinants of Gastrointestinal Pathophysiology and Clinical Outcomes (2015–2025)
by Lavinia Cristina Moleriu, Raluca Lupusoru, Ruxandra-Cristina Marin, Călin Muntean, Teodora Piroș, Daliborca Cristina Vlad, Andrei Luca Dumitrașcu and Victor Dumitrașcu
Int. J. Mol. Sci. 2026, 27(6), 2837; https://doi.org/10.3390/ijms27062837 - 20 Mar 2026
Viewed by 132
Abstract
Diet is a major modifiable determinant of gastrointestinal (GI) health, influencing disease risk and progression through coordinated effects on the gut microbiome, immune regulation, epithelial barrier integrity, oxidative balance, and epigenetic mechanisms. This narrative review synthesizes epidemiological, mechanistic, and clinical evidence from the [...] Read more.
Diet is a major modifiable determinant of gastrointestinal (GI) health, influencing disease risk and progression through coordinated effects on the gut microbiome, immune regulation, epithelial barrier integrity, oxidative balance, and epigenetic mechanisms. This narrative review synthesizes epidemiological, mechanistic, and clinical evidence from the past decade to examine bidirectional relationships between dietary patterns and seven common GI disorders: celiac disease, irritable bowel syndrome (IBS), Crohn’s disease, ulcerative colitis, Helicobacter pylori-associated gastritis, peptic ulcer disease, and lactose intolerance. Western dietary patterns, characterized by high intake of ultra-processed foods and saturated fats and low fiber consumption, are consistently associated with microbial dysbiosis, impaired barrier function, and enhanced inflammatory signaling. In contrast, Mediterranean and plant-forward dietary patterns show protective associations across multiple GI conditions. Mechanistically, diet influences GI pathophysiology largely through microbiome-derived metabolites, particularly short-chain fatty acids, which regulate epithelial homeostasis, immune tolerance, and inflammatory pathways. Condition-specific dietary strategies remain clinically important. Gluten exclusion is essential in celiac disease, low- fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) approaches provide evidence-based symptom control in IBS, and exclusive enteral nutrition or targeted exclusion diets support remission induction in Crohn’s disease. Selected probiotics and emerging postbiotics may provide adjunctive benefits in specific contexts. Despite growing evidence, dietary research remains limited by methodological heterogeneity and interindividual variability. Precision nutrition approaches integrating microbiome profiling and artificial intelligence represent a promising translational direction. Overall, dietary patterns—rather than isolated nutrients—form the foundation of GI dietary therapy. Full article
(This article belongs to the Special Issue Inflammatory Bowel Disease and Microbiome)
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17 pages, 5350 KB  
Article
Dynamic Accumulation and Transcriptional Regulation of Alkylamides in Developing Zanthoxylum planispinum var. Dintanensis Fruits
by Hang Zhang, Ning Lv, Xinglin Wang, Huan Tian, Lunxian Liu, Tie Shen and Qingxiong Yang
Horticulturae 2026, 12(3), 386; https://doi.org/10.3390/horticulturae12030386 - 20 Mar 2026
Viewed by 103
Abstract
The accumulation dynamics and regulatory mechanisms of the alkylamides, the key pungent compounds in the fruits of Sichuan peppers, remain poorly understood. Using fruits of the Zanthoxylum planispinum var. dintanensis (Dintan) harvested at five key developmental stages, we comprehensively mapped the accumulation of [...] Read more.
The accumulation dynamics and regulatory mechanisms of the alkylamides, the key pungent compounds in the fruits of Sichuan peppers, remain poorly understood. Using fruits of the Zanthoxylum planispinum var. dintanensis (Dintan) harvested at five key developmental stages, we comprehensively mapped the accumulation of numbering compounds and their underlying molecular drivers by integrating HPLC-based metabolite profiling and de novo transcriptomics. Total alkylamide content increased during development, with hydroxyl-α-sanshool (HαSS) being predominant. The contributions of hydroxyl-β-sanshool (HβSS) and hydroxyl-ε-sanshool (HεSS) increased in later stages. Cluster and correlation analyses identified 51 candidate genes strongly correlated (|r| ≥ 0.6) with HαSS accumulation, predominantly enriched in fatty acid and branched-chain amino acid metabolism pathways. The expression patterns of five stearoyl-CoA desaturase (SCD) genes, one long-chain acyl-CoA synthetase (ACSL/fadD), and one S-(hydroxymethyl)glutathione dehydrogenase/alcohol dehydrogenase (frmA) gene closely mirrored HαSS accumulation. In contrast, 3-oxoacyl-[acyl-carrier-protein] synthase II (fabF) and one β-ketoacyl-CoA synthase (KCS) gene exhibited a negative correlation. Accordingly, a positive regulatory network was constructed for HαSS accumulation. These findings revealed key candidate targets for deciphering the molecular basis of its unique flavor and for breeding high-pungency cultivars. Full article
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16 pages, 1689 KB  
Article
Phenotypic and Metabolic Variations in High-Risk Clones of Multidrug-Resistant Pseudomonas aeruginosa
by Sonia J. Gutierrez, Juan David Escobar Prieto, Deninson Alejandro Vargas, Richard Burchmore, Karl Burguess and Adriana Correa
Microorganisms 2026, 14(3), 699; https://doi.org/10.3390/microorganisms14030699 - 20 Mar 2026
Viewed by 200
Abstract
The global spread of high-risk clo1nes (HRCs) of multidrug-resistant (MDR) Pseudomonas aeruginosa has hindered infection control and treatment strategies worldwide. In Colombia, globally relevant HRCs such as ST235 and ST111 have been widely reported. In this study, we evaluated phenotypic and metabolic variations [...] Read more.
The global spread of high-risk clo1nes (HRCs) of multidrug-resistant (MDR) Pseudomonas aeruginosa has hindered infection control and treatment strategies worldwide. In Colombia, globally relevant HRCs such as ST235 and ST111 have been widely reported. In this study, we evaluated phenotypic and metabolic variations associated with intracellular survival and dissemination in P. aeruginosa. A total of 100 clinical isolates were collected from 22 hospitals in Colombia. The isolates had been previously characterized and classified as MDR or susceptible strains (SSs), and their sequence types (STs) had been earlier determined. Based on this prior characterization, isolates were grouped in this study as multidrug-resistant high-risk clones (HRC, n = 50; corresponding to sequence types ST235 and ST111), multidrug-resistant non-high-risk clones (NHRCs, n = 27; non-ST235/ST111), and susceptible strains (SS, n = 23; also, non-ST235/ST111). Phenotypic traits, including motility, spontaneous mutation frequency, biofilm formation, and pigment production, were evaluated. In addition, a subset of 30 isolates was assessed for intracellular survival in vitro and metabolomic profiling using liquid chromatography-mass spectrometry. HRC isolates exhibited significantly reduced motility compared with NHRC and SS isolates (swarming: HRC vs. NHRC, p = 0.0032; HRC vs. SS, p = 0.010; swimming: HRC vs. NHRC and SS, p < 0.0001; twitching: HRC vs. SS, p = 0.0004), as well as lower pigment production (pyocyanin: HRC vs. NHRC and SS, p < 0.0001; pyoverdine: HRC vs. NHRC, p < 0.0001). Metabolomic analysis revealed increased concentrations of metabolites associated with iron acquisition and siderophore-related pathways in HRC isolates. Overall, these findings suggest that P. aeruginosa HRCs display distinct phenotypic and metabolic patterns that may contribute to persistence and dissemination in clinical settings, contributing to their epidemiological success. Full article
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Article
Rhizosphere Microbiota Shifts Correlate with Nutrient Composition of Soils and Fruit Metabolite Content in Highbush Blueberry (Vaccinium corymbosum L.) Under Different Cultivation Systems
by Mengjiao Wang, Duyen Bui, Yinku Liang and Zhimin Xu
Agronomy 2026, 16(6), 652; https://doi.org/10.3390/agronomy16060652 - 20 Mar 2026
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Abstract
This study investigated highbush blueberry (Vaccinium corymbosum L.) plants cultivated in distinct cultivation systems (greenhouse vs. open field) to determine if they exhibited significant differences in rhizosphere microbiota, soil nutrient profiles, and fruit metabolites. A clear metabolic trade-off was observed: open-field cultivation [...] Read more.
This study investigated highbush blueberry (Vaccinium corymbosum L.) plants cultivated in distinct cultivation systems (greenhouse vs. open field) to determine if they exhibited significant differences in rhizosphere microbiota, soil nutrient profiles, and fruit metabolites. A clear metabolic trade-off was observed: open-field cultivation significantly enhanced fruit secondary metabolites, including anthocyanins (9.5% higher), flavonoids (56.0% higher), and ascorbic acid (15.6% higher). In contrast, greenhouse fruits were enriched in primary metabolites such as water-soluble sugars (28.3% higher) and total organic acids (30.2% higher) (p < 0.01 for all comparisons). These divergent metabolite profiles were correlated with distinct rhizosphere microenvironments. The open field soil exhibited higher organic carbon and microbial α-diversity, while the greenhouse soil was characterized by a niche with high availability of cations, lower pH, higher electrical conductivity, and elevated levels of exchangeable Ca2+, Mg2+, and available potassium. These contrasting niches were correlated with shifts in the rhizosphere microbiota assembly. Notably, the greenhouse soil was associated with a higher relative abundance of copiotrophic bacterial taxa such as Streptomyces and Bacillus, whose abundances showed strong positive correlations with cation availability (e.g., Streptomyces vs. Ca2+, correlation coefficient r = 0.827, p < 0.01). Multivariate analysis integrated these patterns, revealing that soil cations were negatively correlated with fruit antioxidants but positively linked to sugars and acids. This correlative study suggests that cultivation systems are strongly associated with fruit quality, potentially through their association with functionally specific rhizosphere microbiota that covaries with a shift in the plant’s resource allocation between growth (primary metabolism) and defense (secondary metabolism). Our findings provide an integrative framework for understanding how agricultural practices are associated with the soil–plant–microbe continuum to correlate with crop quality in perennial systems and generate testable hypotheses for future mechanistic research. Full article
(This article belongs to the Special Issue Soil Health and Properties in a Changing Environment—2nd Edition)
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