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23 pages, 2073 KB  
Article
Melatonin at Crossroads with Phytohormones: Interactions Under High Light Stress
by Ivan A. Bychkov, Natalia V. Kudryakova, Victoria V. Shitikova and Victor V. Kusnetsov
Int. J. Mol. Sci. 2025, 26(21), 10531; https://doi.org/10.3390/ijms262110531 - 29 Oct 2025
Abstract
Melatonin (MT), an antioxidant and growth regulator, interacts with almost all phytohormones, but the molecular mechanisms of these interactions are poorly understood. Using mRNA sequencing (mRNA-seq) technology, we analysed the global regulation of MT-induced expression of genes involved in metabolism, signalling and responses [...] Read more.
Melatonin (MT), an antioxidant and growth regulator, interacts with almost all phytohormones, but the molecular mechanisms of these interactions are poorly understood. Using mRNA sequencing (mRNA-seq) technology, we analysed the global regulation of MT-induced expression of genes involved in metabolism, signalling and responses to major phytohormones under prolonged high-intensity light (HL) stress. Plants respond to MT through the activation of auxin and brassinosteroid (BS) response genes, which were identified among the enriched categories of differentially expressed genes (DEGs) with increased expression, and the suppression of abscisic acid and ethylene signalling and response genes, which were among the enriched downregulated categories. MT also suppressed growth-inhibiting genes involved in jasmonic acid (JA) and salicylic acid (SA) signalling and response and activated genes encoding the growth-promoting hormones gibberellins and cytokinins (CKs), which is consistent with the role of MT in stress alleviation. However, the expression of some unique genes, which are positively or negatively modulated by stress, was reinforced by MT treatment, illustrating the extraordinary type of regulation that enhances the action of specific hormone-mediated mechanisms. The study of signal integration between MT and hormones with the involvement of signalling mutants revealed that some interactions are regulated at the transcriptional level and require the activity of relevant signalling pathways. Disruption of CAND2 completely abolished melatonin-dependent activation of the mitogen-activated protein kinases MAP3K17 and MKK7, suggesting that the MAP3K17-MKK7 module is an important player in the MT-triggered MAPK pathway, acting downstream of CAND2. Full article
(This article belongs to the Special Issue Emerging Insights into Phytohormone Signaling in Plants)
13 pages, 1647 KB  
Article
Analysis of the Dirigent Pan-Gene Family in 26 Diverse Inbred Lines Reveals Genomic Diversity in Maize
by Zhihao Liu, Yingjie Xue, Yuxi Xie, Yikun Zhao, Wei Yang, Weiguang Yang, Fengge Wang and Xuejiao Ren
Genes 2025, 16(11), 1285; https://doi.org/10.3390/genes16111285 - 29 Oct 2025
Abstract
Background: Dirigent genes play crucial roles in regulating plant architecture development and responses to environmental stress. However, the pan-genomic attributes of these genes remain poorly characterized. Method: The dirigent pan-gene family was reconstructed using the public genome assemblies from the 26 maize Nested [...] Read more.
Background: Dirigent genes play crucial roles in regulating plant architecture development and responses to environmental stress. However, the pan-genomic attributes of these genes remain poorly characterized. Method: The dirigent pan-gene family was reconstructed using the public genome assemblies from the 26 maize Nested Association Mapping project founder lines. Orthogroup classification based on multiple sequence alignment revealed both core and variable family members. Evolutionary pressures were assessed through Ka/Ks ratio analysis, and promoter regions were examined for cis-acting regulatory elements. Haplotype, transcriptomic and genome-wide association study (GWAS) analyses were integrated to explore genetic diversity and functional relevance. Results: Most dirigent members were under purifying selection, whereas a subset may have undergone positive selection. Promoter analysis demonstrated enrichment of stress- and phytohormone-responsive cis-acting regulatory elements, suggesting that regulatory divergence was associated with environmental adaptation. Haplotype analysis revealed allelic diversity among heterotic clusters, potentially contributing to heterosis. Integration with public genome-wide association study datasets identified candidate genes significantly associated with plant architecture and kernel-quality-related traits. Transcriptome profiles indicated that several dirigent genes were preferentially expressed in the roots, suggesting their involvement in root development and nutrient uptake. In addition, public gene expression data showed that certain dirigent genes are induced in response to salt stress, supporting their putative roles in abiotic stress tolerance. Conclusions: These findings provide insights into the molecular mechanisms underlying dirigent gene functions and reveal candidate genes with potential utility for improving maize performance and stress resilience through molecular breeding. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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14 pages, 2167 KB  
Article
Comparative Transcriptomic and Proteomic Analyses Identify Byssogenesis-Associated Genes in the Mediterranean Mussel Mytilus galloprovincialis Lamarck, 1819
by Xiuwei Zhen, Yiwen Chen, Wei Zhang, Yongren Li, Li Li, Haigang Qi and Shoudu Zhang
Int. J. Mol. Sci. 2025, 26(21), 10511; https://doi.org/10.3390/ijms262110511 - 29 Oct 2025
Abstract
Mussels’ byssus and their adhesion ability play a crucial role in their attachment and artificial cultivation of mussels. In this study, transcriptomic and proteomic analyses were performed to identify byssogenesis-associated genes in the Mediterranean mussel Mytilus galloprovincialis Lamarck, 1819, seeking to advance our [...] Read more.
Mussels’ byssus and their adhesion ability play a crucial role in their attachment and artificial cultivation of mussels. In this study, transcriptomic and proteomic analyses were performed to identify byssogenesis-associated genes in the Mediterranean mussel Mytilus galloprovincialis Lamarck, 1819, seeking to advance our knowledge of the molecular basis of byssal secretion in mussels. Transcriptomic analysis identified 1742 and 1498 differentially expressed genes in the foot tissue of M. galloprovincialis at 9 h and 24 h post-byssal ablation, respectively. Meanwhile, proteomic analysis revealed 1254 and 484 differentially expressed proteins at the same two time points. Integrated analysis identified 121 genes differentially expressed at both transcript and protein levels. Among these genes, 44 were significantly upregulated, and they may constitute high-confidence gene sets associated with mussel byssogenesis. Notably, they included genes encoding tyrosinase-like protein, low affinity immunoglobulin epsilon Fc receptor, and O-methyltransferase MdmC. They were enriched in KEGG pathways, including metabolism of amino acids, lipid metabolism, nucleotide metabolism, and immune system. Quantitative real-time PCR was performed on seven selected genes, confirming that their expression patterns were consistent with those observed in transcriptomic and proteomic sequencing. This study provides novel data and insights for understanding the molecular basis involved in byssus development of M. galloprovincialis. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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14 pages, 2505 KB  
Article
Coupling Granular Activated Carbon with Waste Iron Scraps Enhances Anaerobic Digestion of PBAT Wastewater: Performance Improvement and Mechanistic Insights
by Chunhua He, Jingjing Wen, Zhiqiang Huang, Qilong Jin, Ziyao Li, Hua Zhang, Houyun Yang, Jian Huang, Wei Wang and Hao Hu
Fermentation 2025, 11(11), 614; https://doi.org/10.3390/fermentation11110614 - 28 Oct 2025
Abstract
Poly(butylene adipate-co-terephthalate) (PBAT) wastewater, characterized by high chemical oxygen demand (COD) and acidity, poses significant challenges to anaerobic digestion (AD) due to toxicity and volatile fatty acids (VFAs) accumulation. This study coupled granular activated carbon (GAC) and waste iron scraps (WISs) to synergistically [...] Read more.
Poly(butylene adipate-co-terephthalate) (PBAT) wastewater, characterized by high chemical oxygen demand (COD) and acidity, poses significant challenges to anaerobic digestion (AD) due to toxicity and volatile fatty acids (VFAs) accumulation. This study coupled granular activated carbon (GAC) and waste iron scraps (WISs) to synergistically enhance AD performance. Batch experiments demonstrated that, compared with the control, the GAC/WISs group achieved a COD removal efficiency of 53.18% and a methane production of 207.53 ± 5.80 mL/g COD, which were 5.48- and 12.14-fold increases, respectively, while reducing the accumulation of total VFAs by 98.48% (to 15.09 mg/L). Mechanistic analysis revealed that GAC adsorbed inhibitors and enriched methanogens, while WISs buffered pH and promoted direct interspecies electron transfer (DIET) through hydrogenotrophic methanogenesis. Metagenomic sequencing showed shifts in microbial communities, with enrichment of syntrophic bacteria (Syntrophobacter) and functional genes (pta, bcd, and pccA), indicating metabolic reprogramming. This study provided a theoretical foundation and engineering strategy for the anaerobic treatment of PBAT wastewater. Full article
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19 pages, 4473 KB  
Article
Exosomal microRNA Panels for Detecting Early-Stage Non-Small Cell Lung Cancer
by Young Jun Kim, Da Hyun Kang, Hyunmin Cho, Chaeuk Chung, Jeong Eun Lee and Yong-Beom Shin
Diagnostics 2025, 15(21), 2735; https://doi.org/10.3390/diagnostics15212735 - 28 Oct 2025
Abstract
Background: Early diagnosis of lung cancer requires lung nodule biopsies, which can lead to severe complications. This study aimed to identify optimized panels of exosomal microRNAs (miRNAs) for non-invasive diagnosis of early-stage non-small cell lung cancer (NSCLC). Materials and Methods: This [...] Read more.
Background: Early diagnosis of lung cancer requires lung nodule biopsies, which can lead to severe complications. This study aimed to identify optimized panels of exosomal microRNAs (miRNAs) for non-invasive diagnosis of early-stage non-small cell lung cancer (NSCLC). Materials and Methods: This study comprised four phases: discovery, validation, optimization, and confirmation. In the discovery phase, next-generation sequencing profiled 2656 exosomal miRNAs in serum samples (n = 76) from patients with benign lung nodules and stage-specific NSCLC. The validation phase used qPCR to analyze selected miRNAs in serum samples (n = 75). The optimization phase employed a self-devised diagnostic platform, the “up-down ratio (UDR),” to identify miRNA panels. The confirmation phase involved miRNA–target gene interaction and enrichment analyses. Results: The discovery phase identified 15 candidate miRNAs, of which six were validated by qPCR: miR-1976, miR-150-5p, miR-301b-3p, miR-369-3p, miR-497-5p, and miR-610. UDR platform identified a panel of four miRNAs optimized for early detection of NSCLC with ROC over 0.93. Bioinformatics analysis revealed 20 target genes, with VEGFA, BCL2, and PTEN showing strong interactions with the miRNAs, particularly with miR-150-5p, miR-205-5p, miR-1976, miR-301b-3p, and miR-497-5p. Conclusions: This four-phase study suggests that exosomal miRNA panels have potential diagnostic value for early-stage lung cancer. The UDR platform enabled the selection of a four-miRNA panel (miR-150-5p, miR-301b-3p, miR-369-3p, and miR-497-5p), with bioinformatics analyses providing supportive evidence. Full article
(This article belongs to the Special Issue Liquid Biopsy: Cancer Diagnostic Biomarkers of the Future)
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18 pages, 1545 KB  
Article
Identification of Gut Microbiome Signatures Associated with Serotonin Pathway in Tryptophan Metabolism of Patients Undergoing Hemodialysis
by Tien-Hsiang Kuo, Ping-Hsun Wu, Po-Yu Liu, Yun-Shiuan Chuang, Chi-Jung Tai, Mei-Chuan Kuo, Yi-Wen Chiu and Yi-Ting Lin
Int. J. Mol. Sci. 2025, 26(21), 10463; https://doi.org/10.3390/ijms262110463 - 28 Oct 2025
Abstract
Serotonin, a tryptophan metabolite, exerts a significant influence on both brain and gut functionality. While previous research has elucidated the intricate dynamics of the gut–brain axis, the interplay between serotonin pathway metabolites and gut microbiota in individuals undergoing hemodialysis remains largely unexplored. Therefore, [...] Read more.
Serotonin, a tryptophan metabolite, exerts a significant influence on both brain and gut functionality. While previous research has elucidated the intricate dynamics of the gut–brain axis, the interplay between serotonin pathway metabolites and gut microbiota in individuals undergoing hemodialysis remains largely unexplored. Therefore, this study aimed to investigate gut microbiota composition corresponding to serotonin pathway metabolite levels among patients with hemodialysis. A total of 85 patients undergoing hemodialysis were selected. Their gut microbiota was analyzed using shotgun metagenomic sequencing profiling. The serotonin pathway metabolites, including 5-hydroxytryptophan (5-HTP), serotonin, 5-methoxytryptophan (5-MTP), 5-methoxytryptamine, melatonin, and 6-hydroxymelatonin, were analyzed with the liquid chromatograph–tandem mass spectrometer. The robust linear discriminant analysis Effect Size (LEfSe) was employed to reveal the gut microbiota signature according to levels of serotonin pathway metabolites. A significant β-diversity difference in 5-Methoxytryptamine (p = 0.037) was found, while no variance in α-diversity was detected. Using LefSe analysis, we identified an enriched Tannerellaceae family in the high-hydroxytryptophan (5-HTP) group, the Odoribacteraceae family in the high-serotonin group, the Eubacteriales order in the high-5-methoxytryptophan (5-MTP) group, the Prevotella copri species in the high-5-Methoxytryptamine group, and the Clostridium genus in the high-melatonin group. In contrast, an enriched Clostridiaceae family in the low-5-HTP group, the Clostridiaceae family in the low-serotonin group, and the Bacteroides ovatus species in the low-5-MTP group were found. Distinct gut microbiota signatures linked to serotonin pathway metabolites were identified in patients undergoing hemodialysis. These findings provide insights for future gut–brain axis research and may guide methods to modulate gut microbiota to influence serotonin metabolites. Full article
(This article belongs to the Section Molecular Microbiology)
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14 pages, 2559 KB  
Article
Changes in the Structure of Strawberry Leaf Surface Bacterial and Fungal Communities by Plant Biostimulants
by Ji Yoon Lee, Hyeran Shin, Juhyun Yu and Hyun Gi Kong
Microorganisms 2025, 13(11), 2461; https://doi.org/10.3390/microorganisms13112461 - 28 Oct 2025
Abstract
The application of plant biostimulants to enhance fruit quality is increasing, yet their impact on the phyllosphere microbiome remains understudied. This study investigated the effects of a sugar-based biostimulant on the bacterial and fungal communities on strawberry leaf surfaces using Illumina MiSeq sequencing. [...] Read more.
The application of plant biostimulants to enhance fruit quality is increasing, yet their impact on the phyllosphere microbiome remains understudied. This study investigated the effects of a sugar-based biostimulant on the bacterial and fungal communities on strawberry leaf surfaces using Illumina MiSeq sequencing. The sweetener treatment significantly decreased bacterial alpha diversity (Shannon and Simpson indices). Compositional analysis revealed a lower relative abundance of the phylum Pseudomonadota, whereas the fungal phylum Ascomycota increased and Basidiomycota decreased. At the family level, Sphingobacteriaceae, Bacillaceae, and Micrococcaceae were significantly enriched in the treated group. Furthermore, we isolated bacterial strains, including Sphingomonas zeae St1 and Frigoribacterium faeni TSAY2, which increased in abundance post-treatment and demonstrated enhanced growth using the sweetener as a sole nutrient source. These findings suggest that sugar-based biostimulants directly reshape the composition and functional potential of the phyllosphere microbiome, which may, in turn, influence nutrient uptake, plant growth, and immunity. Full article
(This article belongs to the Section Microbiomes)
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24 pages, 3179 KB  
Article
Growth-Promoting Effects and Mechanisms of Synthetic Plant Growth-Promoting Rhizobacteria on Maize Seedlings
by Shuang Yu, Minlong Mao, Hengfei Zhang, Huanyu Song and Yu Sun
Microorganisms 2025, 13(11), 2460; https://doi.org/10.3390/microorganisms13112460 - 28 Oct 2025
Abstract
With the development of microbial fertilizers, efforts have been made to enrich the strain resources of plant growth-promoting rhizobacteria (PGPR) in maize and to compare the growth-promoting effects of synthetic microbial communities (SynComs) with those of single strains. To achieve this, phenotypic measurements [...] Read more.
With the development of microbial fertilizers, efforts have been made to enrich the strain resources of plant growth-promoting rhizobacteria (PGPR) in maize and to compare the growth-promoting effects of synthetic microbial communities (SynComs) with those of single strains. To achieve this, phenotypic measurements and RNA sequencing (RNA-seq) were performed on maize roots treated with SynComs and single-strain bacterial suspensions, aiming to investigate the regulatory influence of PGPR on differential gene expression and key metabolic pathways in maize roots. In this study, 59 PGPR strains were selected, representing genera including Bacillus, Pseudomonas, Burkholderia sp., Curtobacterium pusillum, Acidovorax, Sphingobium, Mitsuaria, Bacterium, Rhodanobacter, Variovorax, Ralstonia, Brevibacillus, Terrabacter, Flavobacterium, Comamonadaceae, Achromobacter, Paraburkholderia, and Massilia. Based on the growth-promoting effects observed in pot experiments, optimal bacterial strains were selected according to the principles of functional complementarity and functional superposition to construct the SynCom. The selected strains included Burkholderia sp. A2, Pseudomonas sp. C9, Curtobacterium pusillum E2, and Bacillus velezensis F3. The results demonstrated that individual strains exerted measurable growth-promoting effects on seedlings; however, the growth-promoting capability of the SynCom was significantly stronger than that of single strains. The synthetic microbial community ALL group markedly increased root length, shoot fresh weight, shoot dry weight, number of branches, and number of root tips in maize seedlings. RNA-seq analysis of maize roots treated with the SynCom (ALL group) was conducted in comparison with CK, A2, C9, E2, and F3 treatment groups. A total of 5245 differentially expressed genes (DEGs) were identified, of which only 133 were common across treatments. GO and KEGG analyses revealed that DEGs were enriched in multiple biological processes, including cellular amide biosynthetic and metabolic processes, flavonoid biosynthetic and metabolic processes, carbohydrate metabolism, amino acid metabolism, lipid metabolism, and translation. The majority of enriched pathways were associated with primary and secondary metabolism, indicating that these bacterial strains promote plant growth by modulating a wide range of metabolic pathways in plant cells. Overall, this study provides a molecular framework for understanding the mechanisms underlying the growth-promoting effects of SynComs on maize roots and offers valuable insights for future research aimed at identifying key regulatory genes. Full article
(This article belongs to the Special Issue Plant Growth-Promoting Bacteria)
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25 pages, 5442 KB  
Article
Physiological, Biochemical and Gene Expression Analyses of Halimodendron halodendron Responding to Drought Stress
by Huanqiong Hu, Panpan Zhang, Ling Wang, Hailian Liang, Jiye Liang and Ruiheng Lyu
Genes 2025, 16(11), 1274; https://doi.org/10.3390/genes16111274 - 28 Oct 2025
Abstract
Background: As a typical xerophyte, H. halodendron can not only grow in desert sandy areas but also serves as an excellent nectar source and ornamental plant. However, research on its molecular and physiological mechanisms underlying drought tolerance remains limited. Methods: This study [...] Read more.
Background: As a typical xerophyte, H. halodendron can not only grow in desert sandy areas but also serves as an excellent nectar source and ornamental plant. However, research on its molecular and physiological mechanisms underlying drought tolerance remains limited. Methods: This study systematically investigated its drought resistance characteristics by integrating physiological parameters and Illumina transcriptome sequencing, and further validated key genes involved in the drought resistance mechanisms. Results: A total of 46,305 functional genes were identified, among which 6561 were differentially expressed genes (DEGs). These DEGs were significantly enriched in chloroplast function, photosynthesis, proline biosynthesis, and peroxidase activity. Under drought stress, the net photosynthetic rate, stomatal conductance, chlorophyll content, and transpiration rate decreased. Under severe drought conditions, only 5 out of 80 photosynthesis-related DEGs were up-regulated, while the rest were down-regulated, indicating that reduced chlorophyll content impaired light absorption, carbon reactions, and photosynthetic efficiency. Additionally, the contents of proline, soluble sugars, and soluble proteins, as well as the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), increased. The identification of 35 osmotic regulation-related and 39 antioxidant enzyme-related DEGs suggests that H. halodendron enhances osmotic adjustment substance synthesis and reactive oxygen species (ROS) scavenging capacity to counteract osmotic stress. Conclusions: Physiological, biochemical and gene expression analyses under drought stress provide a basis for the study of the drought tolerance characteristics of H. halodendron, which is of great significance for ecological environment governance using H. halodendron. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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27 pages, 3006 KB  
Review
Pathological and Functional Brain Amyloids: A New Concept Explaining the Differences
by Alexey P. Galkin, Vladimir A. Mitkevich, Alexander A. Makarov, Anna A. Valina and Evgeniy I. Sysoev
Int. J. Mol. Sci. 2025, 26(21), 10459; https://doi.org/10.3390/ijms262110459 - 28 Oct 2025
Abstract
In recent years, amyloid proteins that perform vital functions in the brain have been characterized. The question of why some amyloids are neurotoxic while others are harmless remains open. Here, we provide a brief overview of pathological and functional brain amyloids and present [...] Read more.
In recent years, amyloid proteins that perform vital functions in the brain have been characterized. The question of why some amyloids are neurotoxic while others are harmless remains open. Here, we provide a brief overview of pathological and functional brain amyloids and present a comparative analysis of their amino acid sequences based on the percentage of hydrophobic and charged residues, as well as their enrichment in glutamine, asparagine, serine, and glycine. We demonstrate that pathological and functional brain amyloid proteins, along with their amyloidogenic fragments, do not differ in amino acid composition, contrary to previous assumptions. The ability of an amyloid to cause toxicity can instead be explained by the concept of “available targets”. Evidence from studies of pathological amyloids demonstrate that their toxicity is determined not only by a loss of function but also by aberrant interactions with specific targets, such as PrPC or mitochondrial membranes. Binding to these targets triggers pathological cascades that ultimately lead to cell death. In contrast, such targets are inaccessible to functional amyloids, either because of localized translation and protein sequestration within specialized cellular structures, or because their interactions with physiological partners prevent binding to dangerous targets. Full article
(This article belongs to the Special Issue Protein Folding, Misfolding, and Related Diseases)
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12 pages, 4176 KB  
Article
Myocardium miRNA Analysis Reveals Potential Biomarkers of Sudden Coronary Death in Rats
by Chunmei Zhao, Xinyu Zhou, Yaqin Bai, Zhenxiang Zhao, Huaping Zhang, Cairong Gao, Keming Yun and Xiangjie Guo
Curr. Issues Mol. Biol. 2025, 47(11), 889; https://doi.org/10.3390/cimb47110889 (registering DOI) - 28 Oct 2025
Abstract
This study aims to provide potential biomarkers and reveal the molecular mechanism of sudden coronary death (SCD). Rat models of atherosclerotic death (ASD), coronary atherosclerosis (AS), and acute myocardial ischemia (AMI) and sham groups were established via the gavage of high-fat emulsion and [...] Read more.
This study aims to provide potential biomarkers and reveal the molecular mechanism of sudden coronary death (SCD). Rat models of atherosclerotic death (ASD), coronary atherosclerosis (AS), and acute myocardial ischemia (AMI) and sham groups were established via the gavage of high-fat emulsion and left coronary artery ligation. The myocardium was collected, and transcriptome sequencing was performed. Differentially expressed miRNAs (DEmiRNAs) were identified using edeR software. The target genes were predicted using TargetScan, and functional enrichment analysis was performed via KEGG. Then, an miRNA–mRNA interaction network was constructed using Cytoscape. The key miRNAs with biomarker potential were identified using LASSO regression. A total of 217, 224, and 86 DEmiRNAs were identified in the ASD, AS, and AMI groups compared with the sham group, respectively. The Ras and Rap1 pathways were mainly expressed in ASD. The β-alanine and sphingolipid metabolisms were expressed in AMI. Finally, miR-106b, miR-195, miR-33, miR-652, miR-466b, and miR-6321 were identified as biomarkers of ASD. MiR-205, miR-877, miR-325, and miR-344b were identified as biomarkers of AMI. miR542-Atg12 was involved in the RIG-I-like receptor signaling pathway, miR6328-Gstz1 was involved in tyrosine metabolism, and miR483-Dusp5 was involved in the MAPK signaling pathway. This study provides a reference for the identification of SCD in forensic pathology. Full article
(This article belongs to the Special Issue Molecules at Play in Cardiovascular Diseases)
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17 pages, 1275 KB  
Article
miRNA Signatures in Endometrial Cancer: Implications for Oncogenesis and Polymerase Epsilon (POLE) Mutation Status
by Alexandros Lazaridis, Nikolas Dovrolis, Hector Katifelis, Despoina Myoteri, Iakovos Vlahos, Nikos F. Vlahos and Maria Gazouli
Int. J. Mol. Sci. 2025, 26(21), 10438; https://doi.org/10.3390/ijms262110438 - 27 Oct 2025
Abstract
MicroRNAs (miRNAs) are key regulators of gene expression with critical roles in oncogenic signaling. Endometrial cancer (EC) has been redefined with the identification of POLE-ultramutated tumors which, despite their hypermutated phenotype, show more favorable prognosis. We profiled miRNA expression in tumor tissues from [...] Read more.
MicroRNAs (miRNAs) are key regulators of gene expression with critical roles in oncogenic signaling. Endometrial cancer (EC) has been redefined with the identification of POLE-ultramutated tumors which, despite their hypermutated phenotype, show more favorable prognosis. We profiled miRNA expression in tumor tissues from forty (40) EC patients and twenty (20) healthy controls using qPCR panels. POLE exonuclease domain mutations (P286R, V411L) were genotyped, and subgroup analyses were conducted between POLE-mutated (n = 7) and POLE-wild-type (n = 33) tumors. Bioinformatic analyses included validated miRNA–mRNA interactions, target enrichment, and Gene Ontology (GO) pathway mapping. Comparison of EC versus healthy endometrium revealed 50 significantly dysregulated (∣log2 (FoldReg)∣ > 1 and BH FDR < 0.05) miRNAs, including up-regulation of the oncogenic hsa-miR-181a-5p, hsa-miR-23a-3p, hsa-miR-200c-3p, and down-regulation of tumor-suppressive let-7 family members. Target enrichment implicated canonical oncogenic regulators such as MYC, TP53, and VEGFA. POLE-mutated tumor analysis demonstrated a miRNA signature, with 19 miRNAs significantly down-regulated, including let-7f-5p and hsa-miR-200b-3p. Findings for the EC versus healthy endometrium comparison were validated against TCGA-UCEC sequencing data which confirmed concordant dysregulation of key miRNAs across platforms. Our findings reveal that EC is characterized by widespread miRNA deregulation, with a unique global down-regulation signature in POLE-mutated tumors. These results highlight the potential of miRNAs as complementary biomarkers for classification and potential targets in EC. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Oncology)
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17 pages, 3899 KB  
Article
Genomic and Biological Characterization of a Novel Proteus mirabilis Phage with Anti-Biofilm Activity
by Yan Liang, Nana Li, Shenghui Wan, Yanfang Li, Yuwan Li and Yonggang Qu
Viruses 2025, 17(11), 1419; https://doi.org/10.3390/v17111419 - 25 Oct 2025
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Abstract
The emergence of multidrug-resistant (MDR) Proteus mirabilis poses a significant threat in porcine farming and public health, highlighting the need for alternative biocontrol agents. This study aimed to isolate and characterize a lytic bacteriophage with therapeutic potential against MDR P. mirabilis. Using [...] Read more.
The emergence of multidrug-resistant (MDR) Proteus mirabilis poses a significant threat in porcine farming and public health, highlighting the need for alternative biocontrol agents. This study aimed to isolate and characterize a lytic bacteriophage with therapeutic potential against MDR P. mirabilis. Using the clinical MDR P. mirabilis strain Pm 07 as host, a bacteriophage, vB_Pmc_P-07 (P-07), was successfully isolated from fecal and sewage samples via an enrichment protocol. Phage P-07 forms plaques surrounded by a distinct translucent “halo,” suggesting the production of depolymerase. It achieved high titers of up to 1.40 × 108 PFU/mL and exhibited a narrow host range, high stability across a broad range of temperatures (40–60 °C) and pH (4–12), as well as considerable anti-biofilm activity. An optimal multiplicity of infection (MOI) of 0.001 was determined. Whole-genome sequencing revealed a linear double-stranded DNA genome of 58,582 bp with a GC content of 46.91%, encoding 63 open reading frames. Crucially, no virulence or antibiotic resistance genes were detected, supporting its safety profile. Phylogenetic analysis classified P-07 within the Casjensviridae family, closely related to phages PM87 and pPM01. These findings indicate that phage P-07 is a novel, safe, and effective lytic phage with strong potential as a biocontrol agent against biofilm-forming MDR P. mirabilis in swine. Full article
(This article belongs to the Section Bacterial Viruses)
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10 pages, 1217 KB  
Article
Functional and Compositional Changes in Ileal Microbiota in Piglets During the Nursing Period Revealed by 16s rRNA Gene and Metagenomics
by Boxuan Yang, Pengfei Shen, Zhijian Xu, Jianbo Yang, Bo Song, Hui Jiang, Jianmin Chai, Jiangchao Zhao, Feilong Deng and Ying Li
Animals 2025, 15(21), 3102; https://doi.org/10.3390/ani15213102 - 25 Oct 2025
Viewed by 160
Abstract
In piglets, the gut microbiota matures in a segment-specific manner during the nursing period, while fecal-based studies provide limited functional resolution across intestinal sites. We profiled the ileum using 16s rRNA gene sequencing and assessed segmental functions by shotgun metagenomics at selected ages. [...] Read more.
In piglets, the gut microbiota matures in a segment-specific manner during the nursing period, while fecal-based studies provide limited functional resolution across intestinal sites. We profiled the ileum using 16s rRNA gene sequencing and assessed segmental functions by shotgun metagenomics at selected ages. Ileal species richness and diversity were relatively stable across days. Lactobacillus were prominent from day 7, with stage-associated taxa including Lactobacillus johnsonii, Lactobacillus delbrueckii, Ligilactobacillus salivarius, and Limosilactobacillus pontis. Through metagenomic functional analysis, at 21 days, genes were enriched in butanoate metabolism, and Limosilactobacillus pontis as a potential probiotic played an important role in it. At day 28, metagenomic analysis indicated higher relative abundance in the ileum of pathways linked to cysteine and methionine metabolism and lysine biosynthesis, largely carried by Limosilactobacillus mucosae, Limosilactobacillus oris, and Limosilactobacillus pontis. These data describe the composition and function of the ileum in the intestines of piglets and indicate a differentiation period around day 21 to day 28. Full article
(This article belongs to the Section Pigs)
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8 pages, 1274 KB  
Brief Report
Identification and Full-Genome Characterisation of Genomoviruses in Cassava Leaves Infected with Cassava Mosaic Disease
by Olabode Onile-ere, Oluwagboadurami John, Oreoluwa Sonowo, Pakyendou Estel Name, Ezechiel Bionimian Tibiri, Fidèle Tiendrébéogo, Justin Pita, Solomon Oranusi and Angela O. Eni
Viruses 2025, 17(11), 1418; https://doi.org/10.3390/v17111418 - 25 Oct 2025
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Abstract
This study identified and characterised three Genomoviruses during a circular DNA-enriched sequencing project aimed at assessing the evolution of Cassava mosaic begomoviruses in Nigeria. Using a combination of rolling circle amplification, Oxford Nanopore Sequencing and targeted amplicon sequencing, three full-length Genomovirus genomes were [...] Read more.
This study identified and characterised three Genomoviruses during a circular DNA-enriched sequencing project aimed at assessing the evolution of Cassava mosaic begomoviruses in Nigeria. Using a combination of rolling circle amplification, Oxford Nanopore Sequencing and targeted amplicon sequencing, three full-length Genomovirus genomes were recovered. The recovered genomes ranged from 2090 to 2188 nucleotides in length, contained two open reading frames (Rep and CP) in an ambisense orientation and shared between 84.81 and 95.37% nucleotide similarity with isolates in the NCBI GenBank repository. Motif analyses confirmed the presence of conserved rolling circle replication (RCR) and helicase motifs in all three isolates; however, one isolate lacked the RCR II motif. Phylogenetic inference using Rep and CP nucleotide sequences suggested that the isolates belonged to a divergent lineage within the Genomovirus family. These findings expand current knowledge of Genomovirus diversity and highlight the potential of cassava as a source for identifying novel CRESS-DNA viruses. Full article
(This article belongs to the Special Issue Economically Important Viruses in African Crops)
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