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Keywords = metabolic pathway analysis

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22 pages, 5283 KiB  
Article
Transcriptome Analysis Reveals Candidate Pathways and Genes Involved in Wheat (Triticum aestivum L.) Response to Zinc Deficiency
by Shoujing Zhu, Shiqi Zhang, Wen Wang, Nengbing Hu and Wenjuan Shi
Biology 2025, 14(8), 985; https://doi.org/10.3390/biology14080985 (registering DOI) - 2 Aug 2025
Abstract
Zinc (Zn) deficiency poses a major global health challenge, and wheat grains generally contain low Zn concentrations. In this study, the wheat cultivar ‘Zhongmai 175’ was identified as zinc-efficient. Hydroponic experiments demonstrated that Zn deficiency induced the secretion of oxalic acid and malic [...] Read more.
Zinc (Zn) deficiency poses a major global health challenge, and wheat grains generally contain low Zn concentrations. In this study, the wheat cultivar ‘Zhongmai 175’ was identified as zinc-efficient. Hydroponic experiments demonstrated that Zn deficiency induced the secretion of oxalic acid and malic acid in root exudates and significantly increased total root length in ‘Zhongmai 175’. To elucidate the underlying regulatory mechanisms, transcriptome profiling via RNA sequencing was conducted under Zn-deficient conditions. A total of 2287 and 1935 differentially expressed genes (DEGs) were identified in roots and shoots, respectively. Gene Ontology enrichment analysis revealed that these DEGs were primarily associated with Zn ion transport, homeostasis, transmembrane transport, and hormone signaling. Key DEGs belonged to gene families including VIT, NAS, DMAS, ZIP, tDT, HMA, and NAAT. KEGG pathway analysis indicated that phenylpropanoid biosynthesis, particularly lignin synthesis genes, was significantly downregulated in Zn-deficient roots. In shoots, cysteine and methionine metabolism, along with plant hormone signal transduction, were the most enriched pathways. Notably, most DEGs in shoots were associated with the biosynthesis of phytosiderophores (MAs, NA) and ethylene. Overall, genes involved in Zn ion transport, phytosiderophore biosynthesis, dicarboxylate transport, and ethylene biosynthesis appear to play central roles in wheat’s adaptive response to Zn deficiency. These findings provide a valuable foundation for understanding the molecular basis of Zn efficiency in wheat and for breeding Zn-enriched varieties. Full article
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16 pages, 2407 KiB  
Article
Transcriptional Analysis of Spodoptera frugiperda Sf9 Cells Infected with Daphnis nerii Cypovirus-23
by Wendong Kuang, Jian Yang, Jinchang Wang, Chenghua Yan, Junhui Chen, Xinsheng Liu, Chunhua Yang, Zhigao Zhan, Limei Guan, Jianghuai Li, Tao Deng, Feiying Yang, Guangqiang Ma and Liang Jin
Int. J. Mol. Sci. 2025, 26(15), 7487; https://doi.org/10.3390/ijms26157487 (registering DOI) - 2 Aug 2025
Abstract
Daphnis nerii cypovirus-23 (DnCPV-23) is a new type of cypovirus that has a lethal effect on many species of Sphingidae pests. DnCPV-23 can replicate in Spodoptera frugiperda Sf9 cells, but the replication characteristics of the virus in this cell line are still unclear. [...] Read more.
Daphnis nerii cypovirus-23 (DnCPV-23) is a new type of cypovirus that has a lethal effect on many species of Sphingidae pests. DnCPV-23 can replicate in Spodoptera frugiperda Sf9 cells, but the replication characteristics of the virus in this cell line are still unclear. To determine the replication characteristics of DnCPV-23 in Sf9 cells, uninfected Sf9 cells and Sf9 cells at 24 and 72 h after DnCPV-23 infection were collected for transcriptome analysis. Compared to uninfected Sf9 cells, a total of 188 and 595 differentially expressed genes (DEGs) were identified in Sf9 cells collected at 24 hpi and 72 h, respectively. KEGG analyses revealed that 139 common DEGs in two treatment groups were related to nutrition and energy metabolism-related processes, cell membrane integrity and function-related pathways, detoxification-related pathways, growth and development-related pathways, and so on. We speculated that these cellular processes might be manipulated by viruses to promote replication. This study provides an important basis for further in-depth research on the mechanism of interaction between viruses and hosts. It provides additional basic information for the future exploitation of DnCPV-23 as a biological insecticide. Full article
13 pages, 3032 KiB  
Article
Combined Bioinformatic and Experimental Approaches to Analyze miR-182-3p and miR-24-3p Expression and Their Target Genes in Gestational Diabetes Mellitus and Iron Deficiency Anemia During Pregnancy
by Badr Alzahrani, Bisma Rauff, Aqsa Ikram and Mariya Azam
Curr. Issues Mol. Biol. 2025, 47(8), 610; https://doi.org/10.3390/cimb47080610 (registering DOI) - 2 Aug 2025
Abstract
Gestational diabetes mellitus (GDM) and iron deficiency anemia (IDA) are the most common pregnancy-related conditions resulting in adverse maternal and fetal complications. MicroRNAs (miRNAs), particularly miR-182-3p and miR-24-3p, are promising biomarkers as they act as regulatory elements in various diseases; however, their roles [...] Read more.
Gestational diabetes mellitus (GDM) and iron deficiency anemia (IDA) are the most common pregnancy-related conditions resulting in adverse maternal and fetal complications. MicroRNAs (miRNAs), particularly miR-182-3p and miR-24-3p, are promising biomarkers as they act as regulatory elements in various diseases; however, their roles in GDM and IDA are unclear. The present study aimed to analyze the expression and functional relevance of miR-182-3p and miR-24-3p in GDM and IDA. Experimental validation via RT-PCR revealed significant upregulation of both miRNAs in GDM and IDA samples. We identified common target genes and signaling pathways associated with these miRNAs, using a combination of data mining, bioinformatic tools (miRDB, TargetScan, miRTarBase, and miRWalk), and differentially expressed gene (DEGs) analysis using the GEO, OMIM, MalaCards, and GeneCards datasets. GO and KEGG pathway analyses revealed that the shared miRNA–mRNA in target genes were enriched in insulin signaling, apoptosis, and inflammatory pathways—key mechanisms implicated in GDM and IDA. Furthermore, hub genes such as IRS1, PIK3CA, CASP3, MAPK7, and PDGFRB were identified, supporting their central role in metabolic dysregulation during pregnancy. These findings demonstrate the potential of miR-182-3p and miR-24-3p as diagnostic biomarkers and therapeutic targets in managing GDM and IDA, offering new insights into the molecular interplay underlying pregnancy complications. Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
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16 pages, 1867 KiB  
Article
Duplicated Genes on Homologous Chromosomes Decipher the Dominant Epistasis of the Fiberless Mutant in Cotton
by Yu Le, Xingchen Xiong, Zhiyong Xu, Meilin Chen, Yuanxue Li, Chao Fu, Chunyuan You and Zhongxu Lin
Biology 2025, 14(8), 983; https://doi.org/10.3390/biology14080983 (registering DOI) - 2 Aug 2025
Abstract
Cotton fiber initiation determines the fiber yield, yet the genetic basis underlying lint and fuzz initiation has still not been fully uncovered. Here, map-based cloning was carried out to identify the fiberless mutant genes derived from a cross between Gossypium hirsutum acc. WT [...] Read more.
Cotton fiber initiation determines the fiber yield, yet the genetic basis underlying lint and fuzz initiation has still not been fully uncovered. Here, map-based cloning was carried out to identify the fiberless mutant genes derived from a cross between Gossypium hirsutum acc. WT and a natural fiberless mutant, fblSHZ. The 12:3:1 segregation ratio in F2 populations (including 1848 and 3100 individuals that were developed in 2016 and 2018, respectively) revealed dominant epistasis, with the fuzz gene exerting dominance over the lint gene. Genetic linkage analysis revealed that GhMYB25like_A12 controls fuzz fiber initiation, while both GhMYB25like_A12 and GhMYB25like_D12 regulate lint fiber development. Sequencing analyses showed that the fblSHZ mutant exhibited a K104M mutation in the R2R3 domain of GhMYB25like_A12 and a transposable element insertion in GhMYB25like_D12, leading to fiberless seeds. Knockout of GhMYB25like_A12 produced fuzzless seeds, knockout of GhMYB25like_D12 led to no obvious change in seeds, and knockout of both (GhMYB25like_A12&D12) resulted in fiberless seeds. The 12:3:1 ratio reappeared in the F2 population developed from the GhMYB25like_A12&D12 mutated plants as female and Jin668 as the male, which further confirmed the genetic interaction observed in fblSHZ. RNA-seq analysis revealed that GhMYB25like regulates cotton fiber initiation through multiple pathways, especially fatty acid metabolism. This study elucidates the key genes and their genetic interaction mechanisms governing cotton fiber initiation, providing a theoretical foundation for genetic improvement of cotton fiber traits. Full article
(This article belongs to the Special Issue Cotton: Genomics, Biotechnology and Molecular Breeding)
21 pages, 3959 KiB  
Article
Unveiling Stage-Specific Flavonoid Dynamics Underlying Drought Tolerance in Sweet Potato (Ipomoea batatas L.) via Integrative Transcriptomic and Metabolomic Analyses
by Tao Yin, Chaoyu Song, Huan Li, Shaoxia Wang, Wenliang Wei, Jie Meng and Qing Liu
Plants 2025, 14(15), 2383; https://doi.org/10.3390/plants14152383 (registering DOI) - 2 Aug 2025
Abstract
Drought stress severely limits the productivity of sweet potato (Ipomoea batatas L.), yet the stage-specific molecular mechanisms of its adaptation remain poorly understood. Therefore, we integrated transcriptomics and extensive targeted metabolomics analysis to investigate the drought responses of the sweet potato cultivar [...] Read more.
Drought stress severely limits the productivity of sweet potato (Ipomoea batatas L.), yet the stage-specific molecular mechanisms of its adaptation remain poorly understood. Therefore, we integrated transcriptomics and extensive targeted metabolomics analysis to investigate the drought responses of the sweet potato cultivar ‘Luoyu 11’ during the branching and tuber formation stage (DS1) and the storage root expansion stage (DS2) under controlled drought conditions (45 ± 5% field capacity). Transcriptome analysis identified 8292 and 13,509 differentially expressed genes in DS1 and DS2, respectively, compared with the well-watered control (75 ± 5% field capacity). KEGG enrichment analysis revealed the activation of plant hormone signaling, carbon metabolism, and flavonoid biosynthesis pathways, and more pronounced transcriptional changes were observed during the DS2 stage. Metabolomic analysis identified 415 differentially accumulated metabolites across the two growth periods, with flavonoids being the most abundant (accounting for 30.3% in DS1 and 23.7% in DS2), followed by amino acids and organic acids, which highlighted their roles in osmotic regulation and oxidative stress alleviation. Integrated omics analysis revealed stage-specific regulation of flavonoid biosynthesis under drought stress. Genes such as CYP75B1 and IF7MAT were consistently downregulated, whereas flavonol synthase and glycosyltransferases exhibited differential expression patterns, which correlated with the selective accumulation of trifolin and luteoloside. Our findings provide novel insights into the molecular basis of drought tolerance in sweet potato and offer actionable targets for breeding and precision water management in drought-prone regions. Full article
(This article belongs to the Section Plant Response to Abiotic Stress and Climate Change)
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23 pages, 1603 KiB  
Article
Impact of Heat Stress on Rumen Fermentation Patterns and Microbiota Diversity and Its Association with Thermotolerance in Indigenous Goats
by Mullakkalparambil Velayudhan Silpa, Veerasamy Sejian, Chinnasamy Devaraj, Artabandhu Sahoo and Raghavendra Bhatta
Fermentation 2025, 11(8), 450; https://doi.org/10.3390/fermentation11080450 (registering DOI) - 1 Aug 2025
Abstract
Goats are considered to be the ideal climate-resilient animal species in the tropics. Fewer studies are documented assessing the heat stress response of caprine ruminal microbiota, which can also be a crucial indicator of the resilience and/or adaptability of animals. This study was [...] Read more.
Goats are considered to be the ideal climate-resilient animal species in the tropics. Fewer studies are documented assessing the heat stress response of caprine ruminal microbiota, which can also be a crucial indicator of the resilience and/or adaptability of animals. This study was conducted to comparatively assess the heat stress responses of two indigenous goat breeds, Nandidurga and Bidri, based on changes associated with the rumen fermentation pattern and distribution pattern of rumen microbiota. A total of 24 adult animals were randomly allocated into four groups of six animals each, NC (n = 6; Nandidurga control), NHS (n = 6; Nandidurga heat stress), BC (n = 6; Bidri control) and BHS (n = 6; Bidri heat stress). The animals were reared in climate chambers for a duration of 45 days wherein the NC and BC animals were maintained under thermoneutral temperature while the NHS and BHS animals were subjected to simulated heat stress. Heat stress was observed to significantly reduce the rumen ammonia, extracellular CMCase, intracellular carboxy methyl cellulase (CMCase) and total CMCase both in Nandidurga and Bidri goats. In addition to this, a significant reduction in acetate, propionate and total volatile fatty acids (VFAs) was observed in Nandidurga goats. The V3–V4 16s rRNA sequencing further revealed a significant alteration in the rumen microbiota in heat-stressed Nandidurga and Bidri goats. While both the breeds exhibited nearly similar responses in the rumen microbial abundance levels due to heat stress, breed-specific differences were also observed. Furthermore, the LEFSe analysis revealed a significant alteration in the abundances of microbes at the genus level, which were observed to be relatively greater in Bidri goats than Nandidurga goats. Furthermore, these alterations were predicted to impair the functional pathways, especially pathways associated with metabolism. This study therefore provided an insight into the rumen microbial dynamics in heat-stressed goats. Though both the breeds exhibited excellent resilience to the subjected heat stress, there were relatively less ruminal alterations in Nandidurga goats than in Bidri goats. Full article
(This article belongs to the Special Issue Research Progress of Rumen Fermentation)
26 pages, 13311 KiB  
Article
A Spatiotemporal Atlas of the Gut Microbiota in Macaca mulatta brevicaudus: Implications for Health and Environment
by Jingli Yuan, Zewen Sun, Ruiping Sun, Jun Wang, Chengfeng Wu, Baozhen Liu, Xinyuan Zhao, Qiang Li, Jianguo Zhao and Keqi Cai
Biology 2025, 14(8), 980; https://doi.org/10.3390/biology14080980 (registering DOI) - 1 Aug 2025
Abstract
The gut microbiota of macaques, highly homologous to humans in biological characteristics and metabolic functions, serves as an ideal model for studying the mechanisms of human intestinal diseases and therapeutic approaches. A comprehensive characterization of the macaque gut microbiota provides unique insights into [...] Read more.
The gut microbiota of macaques, highly homologous to humans in biological characteristics and metabolic functions, serves as an ideal model for studying the mechanisms of human intestinal diseases and therapeutic approaches. A comprehensive characterization of the macaque gut microbiota provides unique insights into human health and disease. This study employs metagenomic sequencing to assess the gut microbiota of wild M. mulatta brevicaudus across various ages, sexes, and physiological states. The results revealed that the dominant bacterial species in various age groups included Segatella copri and Bifidobacterium adolescentis. The predominant bacterial species in various sexes included Alistipes senegalensis and Parabacteroides (specifically Parabacteroides merdae, Parabacteroides johnsonii, and Parabacteroides sp. CT06). The dominant species during lactation and non-lactation periods were identified as Alistipes indistinctus and Capnocytophaga haemolytica. Functional analysis revealed significant enrichment in pathways such as global and overview maps, carbohydrate metabolism and amino acid metabolism. This study enhances our understanding of how age, sex, and physiological states shape the gut microbiota in M. mulatta brevicaudus, offering a foundation for future research on (1) host–microbiome interactions in primate evolution, and (2) translational applications in human health, such as microbiome-based therapies for metabolic or immune-related disorders. Full article
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16 pages, 1632 KiB  
Article
Meloidogyne incognita Significantly Alters the Cucumber Root Metabolome and Enriches Differential Accumulated Metabolites Regulating Nematode Chemotaxis and Infection
by Naicun Chen, Qianqian Sun, Zhiqun Chen and Xu Zhang
Horticulturae 2025, 11(8), 892; https://doi.org/10.3390/horticulturae11080892 (registering DOI) - 1 Aug 2025
Abstract
Root-knot nematode (Meloidogyne incognita) is a globally destructive plant-parasitic nematode that severely impedes the sustainable production of horticultural crops. Metabolic reprogramming in plant roots represents the host response to M. incognita infection that can also be exploited by the nematode to [...] Read more.
Root-knot nematode (Meloidogyne incognita) is a globally destructive plant-parasitic nematode that severely impedes the sustainable production of horticultural crops. Metabolic reprogramming in plant roots represents the host response to M. incognita infection that can also be exploited by the nematode to facilitate its parasitism. In this study, untargeted metabolomics was employed to analyze metabolic changes in cucumber roots following nematode inoculation, with the goal of identifying differentially accumulated metabolites that may influence M. incognita behavior. Metabolomic analysis revealed that M. incognita significantly altered the cucumber root metabolome, triggering an accumulation of lipids and organic acids and enriching biotic stress-related pathways such as alkaloid biosynthesis and linoleic acid metabolism. Among differentially accumulated metabolites, myristic acid and hexadecanal were selected for further study due to their potential roles in nematode inhibition. In vitro assays demonstrated that both metabolites suppressed egg hatching and reduced infectivity of M. incognita, while pot experiments indicated a correlation between their application and reduced root gall formation. Chemotaxis assays further revealed that both metabolites exerted repellent effects on the chemotactic migration of M. incognita J2 and suppressed the transcriptional expression of two motility-and feeding-related neuropeptides, Mi-flp-1 and Mi-flp-18. In conclusion, this study demonstrates the significant potential of differentially accumulated metabolites induced by M. incognita infection for nematode disease control, achieved by interfering with nematode chemotaxis and subsequent infection. This work also provides deeper insights into the metabolomic mechanisms underlying the cucumber-M. incognita interaction. Full article
(This article belongs to the Special Issue 10th Anniversary of Horticulturae—Recent Outcomes and Perspectives)
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15 pages, 2979 KiB  
Article
A Metabolomics Exploration of Young Lotus Seeds Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging
by Ying Chen, Xiaomeng Xu and Chunping Tang
Molecules 2025, 30(15), 3242; https://doi.org/10.3390/molecules30153242 (registering DOI) - 1 Aug 2025
Abstract
Lotus (Nelumbo nucifera Gaertn.) is a quintessential medicinal and edible plant, exhibiting marked differences in therapeutic effects among its various parts. The lotus seed constitutes a key component of this plant. Notably, the entire seed and the plumule display distinct medicinal properties. [...] Read more.
Lotus (Nelumbo nucifera Gaertn.) is a quintessential medicinal and edible plant, exhibiting marked differences in therapeutic effects among its various parts. The lotus seed constitutes a key component of this plant. Notably, the entire seed and the plumule display distinct medicinal properties. To investigate the “homologous plants with different effects” phenomenon in traditional Chinese medicine, this study established a Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) method. This study employed immature lotus seeds as the experimental material, diverging from the mature seeds conventionally used. Conductive double-sided tape was employed for sample preparation, and complete longitudinal sections of the seeds were obtained, followed by MALDI-MSI analysis to identify and visualize the spatial distribution of characteristic secondary metabolites within the entire seeds. The results unveiled the diversity of metabolites in lotus seeds and their differential distribution across tissues, with pronounced distinctions in the plumule. A total of 152 metabolites spanning 13 categories were identified in lotus seeds, with 134, 89, 51, and 98 metabolites discerned in the pericarp, seed coat, cotyledon, and plumule, respectively. Strikingly, young lotus seeds were devoid of liensinine/isoliensinine and neferine, the dominant alkaloids of mature lotus seed plumule, revealing an early-stage alkaloid profile that sharply contrasts with the well-documented abundance found in mature seeds and has rarely been reported. We further propose a biosynthetic pathway to explain the presence of the detected benzylisoquinoline and the absence of the undetected bisbenzylisoquinoline alkaloids in this study. These findings present the first comprehensive metabolic atlas of immature lotus seeds, systematically exposing the pronounced chemical divergence from their mature counterparts, and thus lays a metabolomic foundation for dissecting the spatiotemporal mechanisms underlying the nutritional and medicinal value of lotus seeds. Full article
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21 pages, 7215 KiB  
Article
Transcriptome Profiling Reveals Mungbean Defense Mechanisms Against Powdery Mildew
by Sukanya Inthaisong, Pakpoom Boonchuen, Akkawat Tharapreuksapong, Panlada Tittabutr, Neung Teaumroong and Piyada Alisha Tantasawat
Agronomy 2025, 15(8), 1871; https://doi.org/10.3390/agronomy15081871 (registering DOI) - 1 Aug 2025
Viewed by 97
Abstract
Powdery mildew (PM), caused by Sphaerotheca phaseoli, severely threatens mungbean (Vigna radiata) productivity and quality, yet the molecular basis of resistance remains poorly defined. This study employed transcriptome profiling to compare defense responses in a resistant genotype, SUPER5, and a [...] Read more.
Powdery mildew (PM), caused by Sphaerotheca phaseoli, severely threatens mungbean (Vigna radiata) productivity and quality, yet the molecular basis of resistance remains poorly defined. This study employed transcriptome profiling to compare defense responses in a resistant genotype, SUPER5, and a susceptible variety, CN84-1, following pathogen infection. A total of 1755 differentially expressed genes (DEGs) were identified, with SUPER5 exhibiting strong upregulation of genes encoding pathogenesis-related (PR) proteins, disease resistance proteins, and key transcription factors. Notably, genes involved in phenylpropanoid and flavonoid biosynthesis, pathways associated with antimicrobial compound and lignin production, were markedly induced in SUPER5. In contrast, CN84-1 showed limited activation of defense genes and downregulation of essential regulators such as MYB14. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted the involvement of plant–pathogen interaction pathways, MAPK signaling, and reactive oxygen species (ROS) detoxification in the resistant response. Quantitative real-time PCR validated 11 candidate genes, including PAL3, PR2, GSO1, MLO12, and P21, which function in pathogen recognition, signaling, the biosynthesis of antimicrobial metabolites, the production of defense proteins, defense regulation, and the reinforcement of the cell wall. Co-expression network analysis revealed three major gene modules linked to flavonoid metabolism, chitinase activity, and responses to both abiotic and biotic stresses. These findings offer valuable molecular insights for breeding PM-resistant mungbean varieties. Full article
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21 pages, 3146 KiB  
Article
TnP as a Multifaceted Therapeutic Peptide with System-Wide Regulatory Capacity
by Geonildo Rodrigo Disner, Emma Wincent, Carla Lima and Monica Lopes-Ferreira
Pharmaceuticals 2025, 18(8), 1146; https://doi.org/10.3390/ph18081146 (registering DOI) - 1 Aug 2025
Viewed by 52
Abstract
Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling [...] Read more.
Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article
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14 pages, 31608 KiB  
Article
Primary Metabolic Variations in Maize Plants Affected by Different Levels of Nitrogen Supply
by The Ngoc Phuong Nguyen, Rose Nimoh Serwaa and Jwakyung Sung
Metabolites 2025, 15(8), 519; https://doi.org/10.3390/metabo15080519 (registering DOI) - 1 Aug 2025
Viewed by 99
Abstract
Background/Objectives: Nitrogen (N) is an essential macronutrient that strongly influences maize growth and metabolism. While many studies have focused on nitrogen responses during later developmental stages, early-stage physiological and metabolic responses remain less explored. This study investigated the effect of different nitrogen-deficient [...] Read more.
Background/Objectives: Nitrogen (N) is an essential macronutrient that strongly influences maize growth and metabolism. While many studies have focused on nitrogen responses during later developmental stages, early-stage physiological and metabolic responses remain less explored. This study investigated the effect of different nitrogen-deficient levels on maize seedling growth and primary metabolite profiles. Methods: Seedlings were treated with N-modified nutrient solution, which contained 0% to 120% of the standard nitrogen level (8.5 mM). Results: Nitrogen starvation (N0) significantly reduced plant height (by 11–14%), shoot fresh weight (over 30%) compared to the optimal N supply (N100). Total leaf nitrogen content under N0–N20 was less than half of that in N100, whereas moderate N deficiency resulted in moderate reductions in growth and nitrogen content. Metabolite analysis revealed that N deficiency induced the accumulation of soluble sugars and organic acids (up to threefold), while sufficient N promoted the synthesis of amino acids related to nitrogen assimilation and protein biosynthesis. Statistical analyses (PCA and ANOVA) showed that both genotypes (MB and TYC) and tissue type (upper vs. lower leaves) influenced the metabolic response to nitrogen, with MB displaying more consistent shifts and TYC exhibiting greater variability under moderate stress. Conclusions: These findings highlight the sensitivity of maize seedlings to early nitrogen deficiency, with severity influenced by nitrogen level, tissue-specific position, and genotype; thus underscore the close coordination between physiological growth and primary metabolic pathways in response to nitrogen availability. These findings expand current knowledge of nitrogen response mechanisms and offer practical insights for improving nitrogen use efficiency in maize cultivation. Full article
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17 pages, 3272 KiB  
Review
Timing Is Everything: The Fungal Circadian Clock as a Master Regulator of Stress Response and Pathogenesis
by Victor Coca-Ruiz and Daniel Boy-Ruiz
Stresses 2025, 5(3), 47; https://doi.org/10.3390/stresses5030047 (registering DOI) - 1 Aug 2025
Viewed by 54
Abstract
Fungi, from saprophytes to pathogens, face predictable daily fluctuations in light, temperature, humidity, and nutrient availability. To cope, they have evolved an internal circadian clock that confers a major adaptive advantage. This review critically synthesizes current knowledge on the molecular architecture and physiological [...] Read more.
Fungi, from saprophytes to pathogens, face predictable daily fluctuations in light, temperature, humidity, and nutrient availability. To cope, they have evolved an internal circadian clock that confers a major adaptive advantage. This review critically synthesizes current knowledge on the molecular architecture and physiological relevance of fungal circadian systems, moving beyond the canonical Neurospora crassa model to explore the broader phylogenetic diversity of timekeeping mechanisms. We examine the core transcription-translation feedback loop (TTFL) centered on the FREQUENCY/WHITE COLLAR (FRQ/WCC) system and contrast it with divergent and non-canonical oscillators, including the metabolic rhythms of yeasts and the universally conserved peroxiredoxin (PRX) oxidation cycles. A central theme is the clock’s role in gating cellular defenses against oxidative, osmotic, and nutritional stress, enabling fungi to anticipate and withstand environmental insults through proactive regulation. We provide a detailed analysis of chrono-pathogenesis, where the circadian control of virulence factors aligns fungal attacks with windows of host vulnerability, with a focus on experimental evidence from pathogens like Botrytis cinerea, Fusarium oxysporum, and Magnaporthe oryzae. The review explores the downstream pathways—including transcriptional cascades, post-translational modifications, and epigenetic regulation—that translate temporal signals into physiological outputs such as developmental rhythms in conidiation and hyphal branching. Finally, we highlight critical knowledge gaps, particularly in understudied phyla like Basidiomycota, and discuss future research directions. This includes the exploration of novel clock architectures and the emerging, though speculative, hypothesis of “chrono-therapeutics”—interventions designed to disrupt fungal clocks—as a forward-looking concept for managing fungal infections. Full article
(This article belongs to the Collection Feature Papers in Plant and Photoautotrophic Stresses)
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17 pages, 4219 KiB  
Article
Identification of Differentially Expressed Genes and Pathways in Non-Diabetic CKD and Diabetic CKD by Integrated Human Transcriptomic Bioinformatics Analysis
by Clara Barrios, Marta Riera, Eva Rodríguez, Eva Márquez, Jimena del Risco, Melissa Pilco, Jorge Huesca, Ariadna González, Claudia Martyn, Jordi Pujol, Anna Buxeda and Marta Crespo
Int. J. Mol. Sci. 2025, 26(15), 7421; https://doi.org/10.3390/ijms26157421 (registering DOI) - 1 Aug 2025
Viewed by 82
Abstract
Chronic kidney disease (CKD) is a heterogeneous condition with various etiologies, including type 2 diabetes mellitus (T2D), hypertension, and autoimmune disorders. Both diabetic CKD (CKD_T2D) and non-diabetic CKD (CKD_nonT2D) share overlapping clinical features, but understanding the molecular mechanisms underlying each subtype and distinguishing [...] Read more.
Chronic kidney disease (CKD) is a heterogeneous condition with various etiologies, including type 2 diabetes mellitus (T2D), hypertension, and autoimmune disorders. Both diabetic CKD (CKD_T2D) and non-diabetic CKD (CKD_nonT2D) share overlapping clinical features, but understanding the molecular mechanisms underlying each subtype and distinguishing diabetic from non-diabetic forms remain poorly defined. To identify differentially expressed genes (DEGs) and enriched biological pathways between CKD_T2D and CKD_nonT2D cohorts, including autoimmune (CKD_nonT2D_AI) and hypertensive (CKD_nonT2D_HT) subtypes, through integrative transcriptomic analysis. Publicly available gene expression datasets from human glomerular and tubulointerstitial kidney tissues were curated and analyzed from GEO and ArrayExpress. Differential expression analysis and Gene Set Enrichment Analysis (GSEA) were conducted to assess cohort-specific molecular signatures. A considerable overlap in DEGs was observed between CKD_T2D and CKD_nonT2D, with CKD_T2D exhibiting more extensive gene expression changes. Hypertensive-CKD shared greater transcriptomic similarity with CKD_T2D than autoimmune-CKD. Key DEGs involved in fibrosis, inflammation, and complement activation—including Tgfb1, Timp1, Cxcl6, and C1qa/B—were differentially regulated in diabetic samples, where GSEA revealed immune pathway enrichment in glomeruli and metabolic pathway enrichment in tubulointerstitium. The transcriptomic landscape of CKD_T2D reveals stronger immune and metabolic dysregulation compared to non-diabetic CKD. These findings suggest divergent pathological mechanisms and support the need for tailored therapeutic approaches. Full article
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Article
Gut Microbiome Structural Dynamics in Japanese Quail Across Developmental Stages
by Daniela da Silva Gomes, Alexandre Lemos de Barros Moreira Filho, Wydemberg José de Araújo, Gustavo Felipe Correia Sales, Hemilly Marques da Silva, Thalis José de Oliveira, Antonio Venício de Sousa, Celso José Bruno de Oliveira and Patrícia Emília Naves Givisiez
Microbiol. Res. 2025, 16(8), 167; https://doi.org/10.3390/microbiolres16080167 - 1 Aug 2025
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Abstract
The cecal microbiota is essential for intestinal health and performance. This study describes the succession patterns of the cecal microbiota in Japanese quail (Coturnix japonica) until 42 days of age. Sixty quails were raised using standard conditions and fed corn–soybean meal [...] Read more.
The cecal microbiota is essential for intestinal health and performance. This study describes the succession patterns of the cecal microbiota in Japanese quail (Coturnix japonica) until 42 days of age. Sixty quails were raised using standard conditions and fed corn–soybean meal diets. Cecal contents were sampled from five birds weekly from 7 to 42 days of age and submitted to Illumina 16S rRNA sequencing for metabarcoding analysis. Diversity and functional prediction were carried out with QIIME2, PICRUSt2, STAMP and MicrobiomeAnalyst 2.0. Firmicutes increased from 50% at 7 days to more than 80% at 42 days, whereas Bacteroidota decreased from 45% to 12% in the same period. Alpha diversity progressively increased with age, indicating a richer and more balanced microbiota at later ages. Genera such as Bacteroides were predominant in the beginning and later were replaced by Lachnospiraceae, Ruminococcus and Faecalibacterium. These developmental taxonomic features aligned with significant shifts in ten metabolic pathways identified by prediction, revealing a transition from biosynthetic functions to complex carbohydrate metabolism and cell wall biosynthesis. The first seven days are considered a critical window for probiotics intervention, which may favor the establishment of a microbiota that is more stable and beneficial to quail performance. Full article
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