Mol. Genet. Genomics [JOURNAL]
Sun
200 papers
Lineage-specific diversification and tissue-specialized jasmonate defense roles of OPR genes in tea (Camellia sinensis).
Nath M, Kundu BK, Regon P … +4 more , Bordoloi KS, Baruah PM, Agarwala N, Tanti B
Mol Genet Genomics · 2026 Mar · PMID 41843199 · Publisher ↗
Defense-associated gene families in long-lived perennials evolve under continuous biotic pressure, yet the forces shaping their diversification and tissue-specialized roles remain poorly understood. Here, we provide the...
Defense-associated gene families in long-lived perennials evolve under continuous biotic pressure, yet the forces shaping their diversification and tissue-specialized roles remain poorly understood. Here, we provide the first comprehensive evolutionary and regulatory analysis of the 12-oxo-phytodienoate reductase (OPR) gene family in tea (Camellia sinensis), a woody perennial that experiences recurrent herbivory and pathogen attacks. Through an integrative framework combining genome-wide identification, phylogenetics, gene structure and motif analyses, cis-regulatory profiling, selective pressure estimation, multi-stress transcriptomics, and RT-qPCR validation, we identified seven CsOPR genes grouped into three well-supported lineages. All CsOPRs retain conserved FMN-binding residues, while localized motif divergence, including the loss of motif 2 in CsOPR3 suggests potential subfunctionalization under strong purifying selection. Promoter composition reveals extensive jasmonate-abscisic acid-light cross-regulation, consistent with tissue-specific stress responses: CsOPR1/2 function as strongly associated with foliar defense, whereas CsOPR7 displays root-biased and stress-modulated expression. Multi-predictor subcellular localization analyses suggest putative vacuolar or endomembrane association for several CsOPRs, pending experimental validation. Collectively, this study establishes a high-resolution framework for OPR evolution and regulatory innovation in tea and identifies structurally divergent, stress-responsive members as high-priority targets for functional genomics. These insights advance understanding of how perennial species tailor jasmonate-mediated defense across tissues and provide molecular entry points for breeding strategies aimed at strengthening biotic stress resilience in long-lived crops.
Morinda officinalis polysaccharide improves osteoporosis by enhancing m⁶A-modified SOCS5 mRNA stability via regulating the hsa_circ_0001165/IGF2BP2 axis.
Zhu Z, Yang Y, Liu Y … +1 more , Liao L
Mol Genet Genomics · 2026 Mar · PMID 41843192 · Publisher ↗
Osteoporosis (OP) is a prevalent bone metabolic disorder. Bone marrow mesenchymal stem cells (BMSCs) serve as key cellular mediators in bone remodeling through their capacity to differentiate into bone-forming osteoblast...
Osteoporosis (OP) is a prevalent bone metabolic disorder. Bone marrow mesenchymal stem cells (BMSCs) serve as key cellular mediators in bone remodeling through their capacity to differentiate into bone-forming osteoblasts, positioning them as promising targets for therapeutic intervention. Morinda officinalis polysaccharide (MOP) is a bioactive compound with medicinal potential. This study aimed to investigate the role and molecular mechanism of MOP in the progression of OP in vitro and in vivo, specifically through promoting osteogenic differentiation of BMSCs. An OP cell model was established by treating BMSCs with 4 µM dexamethasone (DEX). Following DEX induction, cells were treated with various concentrations of MOP. Cell viability was assessed using the Cell Counting Kit-8 assay, while proliferation was assessed through Ki67 immunostaining. Apoptotic and cell cycle distribution were analyzed by flow cytometric. Osteogenic differentiation was examined using Alkaline Phosphatase staining and Alizarin Red S staining. The regulatory relationships among hsa_circ_0001165, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), and suppressor of cytokine signaling 5 (SOCS5) were validated through RNA Immunoprecipitation, RNA pull-down, and methylated RNA immunoprecipitation quantitative PCR assays. Furthermore, an OP rat model was established by intramuscular injection of 5 mg/kg DEX twice weekly for 6 weeks. Rats were subsequently treated with different doses of MOP by gavage for 8 weeks, after which bone mineral density, bone histomorphology, and osteogenic marker expression were evaluated. MOP dose-dependently reversed the DEX-induced suppression of BMSC proliferation, cell cycle progression, and osteogenic differentiation, and also reduced apoptosis. MOP upregulated hsa_circ_0001165 expression; knockdown of hsa_circ_0001165 attenuated these promotive effects of MOP on BMSC proliferation and osteogenic differentiation. Hsa_circ_0001165 directly interacted with the IGF2BP2 protein, thereby enhancing the stability of SOCS5 mRNA. Similarly, knockdown of SOCS5 diminished the enhancing effects of MOP on BMSC proliferation and osteogenic differentiation. Additionally, in vivo results demonstrated that MOP significantly improved bone mineral density (BMD), trabecular bone structure, and osteogenic marker expression in OP rats. MOP alleviates OP by upregulating an hsa_circ_0001165/IGF2BP2 axis, which stabilizes m⁶A-modified SOCS5 mRNA and consequently promotes BMSC osteogenic differentiation.
Unleashing lncRNA THOR: roles in cancer progression and clinical outlook.
Chong ZX
Mol Genet Genomics · 2026 Mar · PMID 41843189 · Publisher ↗
Testis-associated highly conserved oncogenic long non-coding RNA (lncRNA THOR) is highly expressed in normal testis tissue and in at least 15 types of tumours. Since its discovery in 2017, more than 20 studies have inves...
Testis-associated highly conserved oncogenic long non-coding RNA (lncRNA THOR) is highly expressed in normal testis tissue and in at least 15 types of tumours. Since its discovery in 2017, more than 20 studies have investigated its potential tumour-regulatory functions; however, a comprehensive review of these findings remains unavailable. This review aims to address this gap by synthesizing current research to provide an overview of the mechanisms through which lncRNA THOR regulates tumourigenesis and its potential clinical applications. In addition to enhancing insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) expression or activity, lncRNA THOR modulates several pathways, including protein kinase B (AKT), AMP-activated protein kinase (AMPK), ß-catenin, interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3), and Yes-associated protein (YAP), thereby promoting tumourigenesis. In contrast to several other well-characterized lncRNAs, current literature does not clearly indicate that lncRNA THOR functions as a microRNA (miRNA) sponge or is involved in the progression of haematological malignancies, which warrants further investigation. Nonetheless, its consistent upregulation in diverse tumours and its association with poor clinical outcomes suggest that lncRNA THOR may serve as a diagnostic and prognostic biomarker. Targeting lncRNA THOR could also inhibit tumourigenesis. Consequently, large-scale clinical trials and mechanistic studies are required to validate the sensitivity, reliability, and specificity of lncRNA THOR as a biomarker or therapeutic target in cancer management.
Mining of candidate genes regulating Gray leaf spot resistance in maize through integrative biological analysis.
Zhu Y, Zhang X, Wen X … +3 more , Yang L, He Y, He W
Mol Genet Genomics · 2026 Mar · PMID 41843182 · Publisher ↗
Gray leaf spot (GLS) is a devastating foliar disease that causes substantial yield losses in maize. The identification and utilization of GLS resistance genes in hybrid cultivation is a critical strategy for GLS-resistan...
Gray leaf spot (GLS) is a devastating foliar disease that causes substantial yield losses in maize. The identification and utilization of GLS resistance genes in hybrid cultivation is a critical strategy for GLS-resistance breeding. The mapped quantitative trait loci (QTLs), the genome-wide associated quantitative trait nucleotides (QTNs), and multi-omics datasets provide foundational resources for gene discovery. Here, we integrated GLS resistance QTLs and QTNs to identify 164 QTL hotspots, 13 meta-QTL (MQTL) regions, and 86 QTN hotspots. We further extracted a total of 1,343 recurrent differentially expressed genes (DEGs) from multiple transcriptomic studies, including 200 high-confidence DEGs. These DEGs exhibited significant enrichment in key biological pathways, including ‘metabolic pathways’ and ‘plant-pathogen interaction’, implicating them in defense resistance. Through integrative analysis, we identified 340 high-confidence candidate genes in multiple dimensions, with five locating in both QTL hotspots and MQTL regions. Key candidate genes function within known resistant network, such as chitinase (chn2, chn7, chn17), wall-associated kinase-like (WAKLs) (wakl23, wakl56, and wakl27), and calcium-dependent protein kinase (CPKs) (cpk20, cpk36, and cpk25). Expression profiling revealed that most candidate genes were consistently down- or up-regulated at the reproductive stage. These findings provide novel genetic resources and mechanistic insights for GLS-resistance breeding in maize.
Exploring the potential mechanisms of the Prunus mume-Prunella vulgaris herb pair in treating endometrial polyps based on network pharmacology and molecular docking.
Zhang WY, Yuan Y, Fan L … +3 more , Huang GR, Pan SY, Xiao J
Mol Genet Genomics · 2026 Mar · PMID 41843163 · Publisher ↗
Endometrial polyps (EP) are a common benign hyperplastic disease in gynecology, characterized by high postoperative recurrence rates. As a classic herb pair, the molecular mechanism of Prunus mume (Wumei) and Prunella vu...
Endometrial polyps (EP) are a common benign hyperplastic disease in gynecology, characterized by high postoperative recurrence rates. As a classic herb pair, the molecular mechanism of Prunus mume (Wumei) and Prunella vulgaris (Xiakucao) in intervening against EP has not been systematically elucidated. This study aimed to predict the potential active ingredients, core targets, and key pathways of the Prunus mume-Prunella vulgaris herb pair for the treatment of EP based on network pharmacology and molecular docking technology, thus providing a theoretical basis for multi-target therapeutic strategies against EP. Active ingredients of Prunus mume-Prunella vulgaris and their protein targets were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. Corresponding gene names were obtained from the UniProt database. EP-related to EP were retrieved from the GeneCards and Online Mendelian Inheritance in Man databases. The intersection between the herb pair’s target genes and EP-related genes was identified, visualized with a Venn diagram, yielding 12 key target proteins. A protein–protein interaction network was constructed for these key targets to identify the core components and core targets. R software was employed for Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the core targets. Molecular docking was performed to validate the binding between key active ingredients and core targets. Network pharmacology identified quercetin, kaempferol, β-sitosterol, and luteolin as primary active ingredients. Core targets included peroxisome proliferator activated receptor gamma (PPARG), Ak strain transforming 1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caspase 8 (CASP8), etc., were identified as core targets. Molecular docking results demonstrated strong binding affinity between key active ingredients and the core targets. Enrichment analysis indicated that the tumor necrosis factor signaling pathway and the tumor protein p53 signaling pathway are likely core pathways for the herb pair’s intervention in EP. Based on network pharmacology and molecular docking predictions, the Prunus mume-Prunella vulgaris herb pair may intervene in EP by regulating key proteins such as PPARG, AKT1, PTGS2, and CASP8, thereby modulating biological processes including inflammation, apoptosis, and metabolism. The findings provide directions for further in vivo and in vitro experimental validation. Future wet-lab experiments are required to confirm its actual mechanism and efficacy.
Mapping the evolutionary and translational landscape of antibiotic resistance genes in Elizabethkingia anopheles.
Dahal U, Bansal A, Kour B … +2 more , Aryal MR, Gautam A
Mol Genet Genomics · 2026 Mar · PMID 41817869 · Publisher ↗
Elizabethkingia anophelis is an emerging multidrug-resistant pathogen of significant clinical concern, yet little is known about the evolutionary and translational dynamics of its resistance genes. This study aimed to an...
Elizabethkingia anophelis is an emerging multidrug-resistant pathogen of significant clinical concern, yet little is known about the evolutionary and translational dynamics of its resistance genes. This study aimed to analyze codon and amino acid usage patterns in the genome of E. anophelis strain 502 and three resistance genes (blaB-11, blaCME-1, and blaGOB-6) to understand the forces shaping their evolution and expression. The genome exhibited moderate codon usage bias, while resistance genes displayed distinct patterns, reflecting gene-specific selection pressures. Nucleotide composition favoured adenine and thymine at synonymous positions, and relative synonymous codon usage revealed strong preference for specific codons, with exclusive usage of the UAA stop codon in resistance genes. Neutrality analysis indicated minimal mutational influence, suggesting that natural selection predominantly shapes codon choice, and translational selection indices indicated moderate optimization of highly expressed genes. Amino acid composition analysis highlighted hydrophilic profiles with moderate aromaticity, and correlation analysis linked codon bias with GC content, translational selection, and protein properties. These findings provide insights into the evolutionary constraints and translational optimization of antibiotic resistance genes in E. anophelis, offering a framework for understanding their adaptation and persistence under antimicrobial pressure and establish the first codon usage landscape of this organism as a reference for future studies.
Small but big player: the important role of microRNAs in legume crops.
Thiebaut F, Urquiaga MC, de Araújo PM … +2 more , de Carvalho Vivarini A, Grativol C
Mol Genet Genomics · 2026 Mar · PMID 41811515 · Full text
Legumes are essential components of global cropping systems due to their nutritional value and contribution to sustainable agriculture. Among the regulatory molecules, small RNAs (sRNAs), particularly microRNAs (miRNAs),...
Legumes are essential components of global cropping systems due to their nutritional value and contribution to sustainable agriculture. Among the regulatory molecules, small RNAs (sRNAs), particularly microRNAs (miRNAs), play crucial roles in plant development and in responses to biotic and abiotic stresses. miRNAs regulate genes involved in diverse developmental processes, including nodule formation, which is fundamental for the nitrogen-fixing symbiosis that characterizes legumes. Functional studies have demonstrated that miRNAs are key modulators of plant defense, contributing to resistance against pathogens and environmental challenges. Moreover, miRNAs also participate in cross-kingdom communication, such as plant-bacteria interactions, influencing symbiotic efficiency. Advances in molecular biology have enabled the manipulation of miRNAs and their targets for crop improvement. Current approaches include the design of artificial miRNAs (amiRNA), modulation of miRNA expression through miRNA-encoded peptides, genome editing of non-coding genes using CRISPR/Cas9, and the application of RNA interference (RNAi) technology. Together, these strategies highlight the potential of miRNA-based tools in plant biotechnology. A deeper understanding of the molecular mechanisms governing miRNA-mediated gene silencing will provide powerful resources for optimizing legume productivity and resilience within sustainable agricultural systems.
Multi-task molecular representation learning based on soft prompting of the important subgraph.
Liu Y, Zhang H, Hu R … +2 more , Zhang H, Zhang X
Mol Genet Genomics · 2026 Mar · PMID 41806220 · Publisher ↗
Understanding the intricate relationship between molecular structure and biological activity is fundamental to modern drug discovery and genomic research. However, capturing the full geometric and functional complexity o...
Understanding the intricate relationship between molecular structure and biological activity is fundamental to modern drug discovery and genomic research. However, capturing the full geometric and functional complexity of molecules remains a significant challenge. To address this, we introduce a Multi-task Molecular Representation Learning framework based on Soft Prompting of the Important Subgraph (MMRL). In molecular generation, retrosynthetic prediction, and molecular property prediction tasks, the model utilizes the important subgraph information to generate soft prompts, which help these tasks obtain the better molecular representations through the shared encoding. Additionally, the model addresses the issue that graph neural networks mainly focus on neighboring atoms and connectivity information and do not effectively utilize holistic molecular geometry structure for molecular encoding. The model achieves significant performance improvements compared to many classical baseline systems on ZINC250K and QM9 dataset in molecular generation task, USPTO-50K dataset (unknown and known reaction classes) in retrosynthetic prediction task, and eight benchmark datasets in molecular property prediction. These results demonstrate that MMRL not only achieves superior computational performance but also provides more biologically meaningful representations, offering a promising tool for accelerating the identification and optimization of novel therapeutic candidates in complex biological systems.
Functional characterization of a CFEM domain-containing protein in the mycoparasitic fungus Clonostachys rosea reveals antimicrobial activity and a role in conidiation.
Iliopoulos I, Samaras A, Sigdel S … +4 more , Forslund L, Karlsson M, Tzelepis G, Dubey M
Mol Genet Genomics · 2026 Mar · PMID 41806193 · Full text
Common fungal extracellular membrane (CFEM) domain-containing proteins are small cysteine-rich proteins exclusive to fungi. They are shown to contribute to fungal virulence by promoting appressorium development and suppr...
Common fungal extracellular membrane (CFEM) domain-containing proteins are small cysteine-rich proteins exclusive to fungi. They are shown to contribute to fungal virulence by promoting appressorium development and suppressing plant immune response. This study aimed to investigate the role of CFEM-domain-containing proteins in fungal antagonism and beneficial fungus-plant interactions using the mycoparasitic fungus Clonostachys rosea IK726, a biocontrol agent against several fungal pathogens. Gene expression analysis of 21 C. rosea IK726 CFEM-encoding genes during in vitro interactions with fungal hosts Botrytis cinerea and Rhizoctonia solani showed that their expression patterns depend on the host and interaction stage. CFEM10, predicted to have antimicrobial activity, was expressed in Escherichia coli and purified. An in vitro assay using purified CFEM10 protein revealed its antimicrobial activity against E. coli and Saccharomyces cerevisiae. Functional analysis of CFEM10 using gene deletion strains showed a significant difference (P = 0.01) in conidial production between the WT and Δcfem10 strains. However, no significant difference was found in fungal antagonisms against B. cinerea, Fusarium graminearum or R. solani, root colonization ability and biocontrol of fusarium foot and root rot between the WT and Δcfem10 strains. Similarly, transient expression of cfem10 in tobacco leaves failed to suppress hypersensitive response (HR) induced by Avr4/Cf4 complex. In summary, our results demonstrated the antimicrobial activity of CFEM10 and its involvement in fungal conidiation. Functional analysis of several CFEM-domain-containing proteins is needed to comprehensively evaluate their roles in fungal antagonism and beneficial interactions with plant hosts.
Staphylococcus aureus resistance to non-β-lactam antibiotics: global genomic epidemiology and machine learning feasibility assessment.
Chaki SSG, Najim MA, Hassan LA … +7 more , AlAbdulhadi SAS, Al-Khafaji ZA, Sharma MK, Ahmed AS, Ahmed AB, Alazzam MB, Sholeh M
Mol Genet Genomics · 2026 Mar · PMID 41806067 · Publisher ↗
Staphylococcus aureus is increasingly resistant to β-lactam antibiotics, making non-β-lactam cell-wall-targeting drugs crucial alternatives. Growing resistance to these agents highlights the need to identify genomic fact...
Staphylococcus aureus is increasingly resistant to β-lactam antibiotics, making non-β-lactam cell-wall-targeting drugs crucial alternatives. Growing resistance to these agents highlights the need to identify genomic factors influencing susceptibility. Machine learning can integrate genomic and phenotypic data to predict minimum inhibitory concentrations (MICs) and uncover resistance mechanisms across time and regions. We obtained 112,360 S. aureus genomes from NCBI GenBank (March 2024), applying quality filters and standardizing metadata. Resistance genes and mutations were identified using AMRFinderPlus and CARD, focusing on glycopeptide, lipopeptide, bacitracin, and fosfomycin resistance. MICs for five antibiotics were compiled, standardized, and log₂-transformed for analysis. Allelic profiles for seven housekeeping genes were assigned using PubMLST's BIGSdb and MLST CLI v2.19.0. Temporal and geographic resistance trends were modeled using logistic regression and statistical tests. Machine learning models (Random Forest, XGBoost, Elastic Net, Partial Least Squares (PLS)) predicted MICs from genomic features, with performance assessed via cross-validation. Statistical analyses and visualizations were performed in R, with all data and scripts provided for reproducibility. We analyzed 111,350 S. aureus genomes from 137 countries, with 78% from clinical sources, 10% from environmental, veterinary, or food-related origins, and some from animals. Glycopeptide MICs were low across all sources: vancomycin (0.96 µg/mL) and teicoplanin (0.52 µg/mL), while daptomycin showed more variability (0.44 µg/mL). Fosfomycin resistance genes, particularly fosB, were detected in 65.3% of genomes overall, with significantly higher prevalence in clinical isolates (32.5%) compared to environmental (2.1%), food (4.0%), and animal sources (7.5%). Bacitracin resistance genes (bcrAB) were detected in 6.2% of clinical isolates versus 1.3% environmental and 2.8% animal sources. However, phenotypic MIC data were severely limited (fosfomycin n = 1, bacitracin n = 1), precluding validation of genotype-phenotype correlations and limiting epidemiological interpretation to genetic prevalence alone. Resistance to glycopeptides and lipopeptides remained rare (< 0.1%). Fosfomycin resistance protein B (fosB) resistance increased by 0.20% annually, especially in clinical and animal sources, while other mutations like glpT_V213I and murA_D278E declined. Geographic trends showed fosB resistance exceeded 50% in North America, Europe, and South America, with MurA_G257D most prevalent in the Middle East. Machine learning models showed moderate predictive performance for daptomycin MICs (R² = 0.49), with mprF mutations as key predictors, but demonstrated poor accuracy for glycopeptides (vancomycin R² = 0.05; teicoplanin R² = -0.13) due to extremely limited MIC variability in the dataset. Fosfomycin and bacitracin models could not be trained due to insufficient phenotypic data (n = 1 each). This study highlights the growing challenge of S. aureus resistance, especially to non-β-lactam antibiotics such as fosfomycin and bacitracin, with clinical isolates showing the highest resistance. Geographic and temporal trends indicate an increasing prevalence of fosB resistance, particularly in clinical and animal sources. Machine learning models failed to predict glycopeptide MICs (vancomycin R² = 0.05; teicoplanin R² = -0.13) due to limited phenotypic variability, achieved moderate success for daptomycin (R² = 0.49), and could not be trained for fosfomycin and bacitracin (n = 1 MIC measurement each) despite high genetic prevalence of resistance determinants. These findings emphasize the critical need for integrated genomic and phenotypic surveillance, and highlight fundamental data requirements for ML-based resistance prediction.
AI-powered radiogenomics: imaging-driven diagnosis and discovery of cancer's molecular and cellular landscape.
Qiu HF, Zhu JK
Mol Genet Genomics · 2026 Mar · PMID 41806059 · Publisher ↗
Radiogenomics seamlessly integrates radiological imaging phenotypes with molecular and cellular data, offering a powerful, noninvasive means to decipher the underlying biology of cancer. In recent years, artificial intel...
Radiogenomics seamlessly integrates radiological imaging phenotypes with molecular and cellular data, offering a powerful, noninvasive means to decipher the underlying biology of cancer. In recent years, artificial intelligence (AI), including machine learning and deep learning approaches, has revolutionized radiogenomics by automating the extraction of high-dimensional quantitative imaging features and enabling their robust correlation with multiomics profiles. This narrative review summarizes current advances in AI-powered radiogenomics, focusing on clinical relevance, molecular and cellular insights, and laboratory-based diagnostic implications guided by the principles of clinical chemistry. We explore the historical evolution from traditional imaging to data-driven, multiomics integration frameworks and highlight the rapidly growing application of AI methods (e.g., convolutional neural networks, generative adversarial networks, transformers) for feature extraction and integrative modeling and detail use cases across major cancer types, such as breast, lung, brain, and prostate cancer. By leveraging evidence from the latest peer-reviewed studies and open-access multi-institutional consortia, we illustrate how AI-enabled radiogenomics facilitates the discovery of imaging surrogates for genomic alterations, tumor heterogeneity, and the tumor microenvironment. Challenges, including data harmonization, standardization, ethical considerations, and validation across populations, are critically examined. Finally, we discuss future trends such as spatial transcriptomics integration, federated learning, and multiomics AI models, highlighting the transformative potential of radiogenomics in precision oncology and laboratory workflows. A growing body of evidence indicates that AI-powered radiogenomics holds promise in noninvasive biomarker discovery, therapy response prediction, and real-time disease monitoring, paving the way for individualized cancer management.
Integrative bioinformatics reveals complement dysregulation: critical insights into C1q, C1r, and C1s in aortic dissection pathogenesis.
Wu X, Qin J, Wang X … +4 more , Wang R, Li W, Liu K, Lu X
Mol Genet Genomics · 2026 Mar · PMID 41806029 · Publisher ↗
Aortic dissection (AD) is a life-threatening cardiovascular emergency in which delayed diagnosis and incomplete understanding of pathogenesis contribute to high mortality. To clarify the contribution of complement dysreg...
Aortic dissection (AD) is a life-threatening cardiovascular emergency in which delayed diagnosis and incomplete understanding of pathogenesis contribute to high mortality. To clarify the contribution of complement dysregulation to AD and to identify complement-related biomarkers with diagnostic and mechanistic relevance, we performed an integrative bioinformatics and clinical study focusing on C1q, C1r, and C1s. We identified four complement-related hub genes—C1R, C5, C9, and CFB—through differential gene expression analysis from GSE153434. C1R emerged as a key diagnostic marker with an area under the curve (AUC) of 88%, while Mendelian randomization revealed a causal relationship between genetically predicted C1R levels and AD incidence. Single-cell RNA sequencing revealed cell-type-specific expression patterns of C1r and C1s, highlighting their upregulation in smooth muscle cells and fibroblasts, indicating roles in vascular remodeling and extracellular matrix production. Serum C1q levels were significantly elevated in AD patients with a diagnostic threshold of 184.5 mg/L and demonstrated moderate diagnostic performance (AUC = 0.795). However, Mendelian randomization (MR) provided no evidence for a causal role of genetically predicted C1q, suggesting that elevated C1q may reflect reactive immune/inflammatory responses rather than direct pathogenic mechanisms. Immunofluorescence localized C1r expression to smooth muscle cells in the aortic wall, corroborating its involvement in AD pathology. These findings elucidate the contributions of complement activation, particularly C1r and C1q, in AD pathogenesis. Our study underscores the diagnostic potential of complement-related biomarkers and suggests avenues for targeted therapeutic interventions. Taken together, these findings indicate that complement dysregulation is a central feature of AD and support C1r as a promising mechanistic and diagnostic marker, while elevated C1q represents a clinically informative, non-causal biomarker. Our findings highlight the complement system as a critical player in AD, offering new insights into its molecular role and potential as a therapeutic target.
TAF15 promotes the healing of diabetic foot ulcers by mediating the transcriptional activation of APOE through CEBPB to regulate PTX3.
Lu X, Xu Y, Liu J … +1 more , Chen J
Mol Genet Genomics · 2026 Mar · PMID 41805994 · Publisher ↗
Diabetic foot ulcers (DFU) are a severe complication of diabetes. Although dysregulated M2 macrophage polarization is recognized as a key driver of chronic inflammation in DFU, the molecular checkpoints that can be thera...
Diabetic foot ulcers (DFU) are a severe complication of diabetes. Although dysregulated M2 macrophage polarization is recognized as a key driver of chronic inflammation in DFU, the molecular checkpoints that can be therapeutically targeted to restore M2 bias remain poorly defined. Here, we aimed to determine whether the RNA-binding protein TAF15 acts as a post-transcriptional stabilizer of the M2-promoting CEBPB/APOE/PTX3 axis, thereby accelerating DFU healing. First, we confirmed that APOE positively regulates PTX3, which supports M2 polarization and the proliferation and migration of HDF. CEBPB transcriptionally activated APOE and promoted M2 macrophage polarization. TAF15 stabilized CEBPB mRNA and affected HDF cell proliferation and migration by promoting M2 macrophage polarization. Additionally, TAF15 overexpression partially counteracted the disruption of M2 macrophage polarization caused by APOE silencing and facilitated DFU wound healing. Collectively, our findings establish TAF15-driven stabilization of CEBPB mRNA as a target point that sequentially activates APOE/PTX3 signaling to enforce M2 polarization and accelerate DFU closure. This study provides a preclinical rationale for the development of TAF15-targeted oligonucleotides or small-molecule strategies to reprogram wound macrophages and improve DFU outcomes in patients with diabetes.
Transcriptome analysis coupled with virus induced gene silencing delineates the unfolded protein response of tomato.
Rana A, Kaur N, Pandey AK … +1 more , Kandoth PK
Mol Genet Genomics · 2026 Mar · PMID 41805988 · Publisher ↗
The molecular details of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) and their functional significance in combating environmental stress in crop species remain inadequately elucidated. Tomat...
The molecular details of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) and their functional significance in combating environmental stress in crop species remain inadequately elucidated. Tomato (Solanum lycopersicum) is an important crop, sensitive to temperature, and serves as a model crop plant for studying these pathways. To establish a tomato UPR transcriptome profile, we performed RNA sequencing (RNA-seq) analysis of tomato seedlings under tunicamycin (Tm)-induced ER stress. The 339 differentially expressed genes encompassed traditional ER stress markers, ER-associated degradation elements, transcription factors, and novel candidate genes. Our functional analysis of key UPR genes, viz., SlIRE1A, SlIRE1B, SlbZIP60, and SlbZIP28, using Virus-Induced Gene Silencing (VIGS) revealed differential requirements for SlIRE1A and SlIRE1B in the Tm-induced upregulation of downstream genes. Additionally, we found that the expression of most of the downstream genes we analyzed was equally dependent on both the IRE1 and bZIP28 pathways. The expression analysis of several of these genes under environmental stress conditions indicated that their expression patterns did not align with those observed during ER stress. Furthermore, our analysis of VIGS plants subjected to heat stress revealed that the regulation of reactive oxygen species (ROS) levels in tomato depends on the IRE1-bZIP60 pathway. Overall, this study provides a comprehensive analysis of UPR pathways in tomato and offers essential molecular insights for developing resilient tomato cultivars that can withstand adverse environmental conditions.
TEffectBayes: a nextflow pipeline for exploring the potential effect of transposable elements in gene regulatory network with multi-omic Bayesian network model.
Kutlu NK, Güner H, Karakülah G
Mol Genet Genomics · 2026 Mar · PMID 41805929 · Publisher ↗
Transposable elements (TEs) are critical contributors to gene regulatory networks, yet their repetitive and abundant nature complicates efforts to elucidate their precise regulatory roles. While existing computational to...
Transposable elements (TEs) are critical contributors to gene regulatory networks, yet their repetitive and abundant nature complicates efforts to elucidate their precise regulatory roles. While existing computational tools facilitate systematic identification of associations between TEs and gene expression, these methods typically cannot account for confounding variables or capture causal and directional interactions. To address these limitations, we developed TEffectBayes, a Nextflow-based pipeline leveraging a multi-omic Bayesian network (BN) framework designed to systematically infer directional, probabilistic regulatory dependencies involving TEs. TEffectBayes integrates diverse omics datasets, including RNA-seq-derived gene and locus-specific TE expression, along with ChIP-seq-based histone modification data processed via custom R and Python scripts. Integrated multi-omic datasets are subsequently employed to build gene-centric Bayesian models, enabling robust inference of context-dependent, probabilistic relationships between TEs, chromatin modifications, and gene expression. TEffectBayes thus provides a reproducible and scalable computational framework for unraveling the complex regulatory landscape shaped by TEs. In summary, TEffectBayes supports systematic prioritization of TE–chromatin–gene regulatory candidates for downstream benchmarking and experimental validation, enabling hypothesis-driven follow-up studies in diverse biological contexts. The pipeline, along with comprehensive user tutorials and example datasets, is publicly accessible at https://github.com/nkaan-kutlu/TEffectBayes .
Genomic characterization of Pseudomonas aeruginosa infecting Abidjanvirus Lucjan.
Grygorcewicz B, Miłek D, Olszewska P … +4 more , Spietelun M, Czajkowski A, Lisman D, Ossowski A
Mol Genet Genomics · 2026 Mar · PMID 41805923 · Publisher ↗
Multidrug-resistant (MDR) Pseudomonas aeruginosa remains a major cause of hospital-acquired infections, and alternative antimicrobial strategies are urgently needed. Bacteriophages infecting P. aeruginosa are increasingl...
Multidrug-resistant (MDR) Pseudomonas aeruginosa remains a major cause of hospital-acquired infections, and alternative antimicrobial strategies are urgently needed. Bacteriophages infecting P. aeruginosa are increasingly explored as adjuncts or alternatives to antibiotic therapy, yet many newly isolated phages remain incompletely characterized. Here, we report the genomic and functional characterization of bacteriophage Lucjan, a lytic virus infecting clinical isolates of P. aeruginosa. Whole-genome sequencing revealed a 59,433 bp double-stranded DNA genome with 63.7% GC content encoding 81 predicted open reading frames. Comparative genomics and VIRIDIC analysis established Lucjan as a novel species within the genus Abidjanvirus. No antibiotic resistance genes, virulence factors, or canonical lysogeny-associated modules were detected. Lifestyle prediction and genomic architecture, including a canonical holin-endolysin cassette, support a lytic infection strategy. Biological characterization demonstrated adsorption to host cells, a latent period of approximately 60 min, and a burst size of 82 ± 14 PFU per infected cell. Lucjan infected 42% of tested clinical isolates and significantly reduced established P. aeruginosa biofilms in vitro. Combined treatment with selected antibiotics resulted in enhanced suppression of bacterial growth compared with single-agent exposure. Together, these findings position Lucjan as a genomically safe and functionally active representative of the Abidjanvirus lineage and highlight the potential of environmentally derived lytic phages as candidates for further evaluation in combinatorial antimicrobial strategies.
Transcriptome analysis identifies key regulatory genes and temporal expression dynamics during embryonic development in the Japanese eel (Anguilla japonica).
Zhong Z, Luo D, Lu Y … +5 more , Chen Z, Xi N, Shi S, Chen J, Jiang Y
Mol Genet Genomics · 2026 Mar · PMID 41787119 · Publisher ↗
The Japanese eel (Anguilla japonica), a commercially important species, has experienced severe population declines in the wild, underscoring the urgent need to improve artificial breeding techniques. However, the complex...
The Japanese eel (Anguilla japonica), a commercially important species, has experienced severe population declines in the wild, underscoring the urgent need to improve artificial breeding techniques. However, the complexity of embryonic development and the limited understanding of its molecular regulatory mechanisms have constrained progress in artificial reproduction. To elucidate the dynamics of gene expression during early development, we conducted a comprehensive transcriptomic analysis of eight key embryonic stages using RNA-Seq. A total of 16,728 differentially expressed genes (DEGs) were identified, with the most pronounced pluripotency-related changes observed during the multicellular-blastula and differentiation-related changes in gastrula-embryo body transitions. Functional enrichment revealed distinct stage-specific pathways: early stages (multicellular) dominated by Notch and Wnt signaling, involved early developmental decisions; mid-stages (blastula to gastrula), with enriched pathways like Cell cycle, supporting rapid cell division; mid-late stages (embryo-body-formation to somite appearance) featured extracellular matrix receptor (ECM-receptor) interaction and focal adhesion, contributing to cell connectivity and tissue morphogenesis; and late stages (muscle-effect to newly-hatched-larvae) highlighted calcium signaling and metabolic pathways, providing signaling and energy support for organogenesis and functional maturation. Weighted gene co-expression network analysis (WGCNA) identified four stage-specific modules that correlated with developmental progression. Additionally, key members of the Sox, Hox, and Wnt transcription factor families were screened and found to exhibit dynamic, stage-specific expression patterns. These factors likely form a synergistic regulatory network that coordinates the entire developmental progression. Collectively, these findings delineate the molecular landscape of A. japonica embryogenesis and establish a crucial baseline transcriptomic resource that will facilitate future investigations into the molecular regulation of early development in this species.
Global in silico genomic epidemiology of tetracycline resistance in Staphylococcus aureus: one health dynamics and genotype-phenotype associations.
AlAbdulhadi SAS, Hassan LA, Alrawi DDM … +7 more , Badr IH, El-Sehrawy AAMA, Panigrahi R, Singh AK, Jenifer DR, Sharma V, Sholeh M
Mol Genet Genomics · 2026 Mar · PMID 41787116 · Publisher ↗
Tetracyclines remain widely used in human and veterinary medicine for the treatment of Staphylococcus aureus, including methicillin-resistant strains, and are key agents at the human–animal–environment interface. However...
Tetracyclines remain widely used in human and veterinary medicine for the treatment of Staphylococcus aureus, including methicillin-resistant strains, and are key agents at the human–animal–environment interface. However, the global genomic epidemiology of tetracycline resistance mechanisms, their temporal stability, host structuring, and genotype–phenotype relationships across the tetracycline class remain incompletely resolved. We performed a large-scale in silico analysis to characterize tetracycline resistance determinants, minimum inhibitory concentration (MIC) patterns, and One Health dynamics in S. aureus. A total of 110,309 publicly available S. aureus genomes collected between 2000 and 2025 from 128 countries were retrieved from NCBI and subjected to rigorous quality control. Tetracycline resistance determinants including intrinsic efflux pumps (tet, mepA), acquired efflux genes (tet(K), tet(L)), ribosomal protection proteins (tet(M), tet(O), tet(S), tet(W)), rare tet alleles, and the ribosomal S10 mutation rpsJ Y58D were identified using AMRFinderPlus. Host source, geography, and multilocus sequence type (MLST) were integrated. Phenotypic MIC data for tetracycline, oxytetracycline, doxycycline, minocycline, and tigecycline were harmonized using Clinical and Laboratory Standards Institute/ European Committee on Antimicrobial Susceptibility Testing logic. Temporal trends, host enrichment, clonal structure, and gene–MIC associations were assessed using regression models and descriptive genomics. Intrinsic efflux determinants were nearly universal, with tet and mepA detected in > 99.9% of genomes, defining a fixed genomic background. Acquired resistance genes were less frequent and strongly host-structured: tet(K) (12.0%), tet(M) (11.0%), and tet(L) (1.9%) predominated, while other tet family members and rpsJ Y58D remained rare (< 1.1%). Environmental and animal isolates carried significantly higher frequencies of acquired determinants than human isolates (p < 0.001), consistent with One Health reservoirs of resistance. Temporal analyses revealed largely stable prevalence of tetracycline resistance mechanisms over two decades, with only modest declines in human-associated tet(M). MIC distributions showed preserved activity of tigecycline and minocycline (100% susceptible), high susceptibility to tetracycline (97%), and moderate non-susceptibility for doxycycline. Gene–phenotype alignment demonstrated that tet(K) and tet(M) were associated with elevated MIC tails, whereas isolates harboring only intrinsic efflux clustered at lower MICs. Global tetracycline resistance in S. aureus is characterized by a stable intrinsic efflux backbone with superimposed, host-structured acquisition of mobile tet genes that shape agent-specific MIC distributions. The persistence of higher resistance gene burdens in animal and environmental reservoirs underscores the importance of One Health surveillance. Despite widespread gene carriage, tetracyclines particularly tigecycline and minocycline retain strong phenotypic activity, highlighting opportunities for informed stewardship guided by genome-based monitoring.
HDAC7 aggravates malignant proliferation of hepatocellular carcinoma cells via the TRIM26/CBX4 axis.
Sun X, Zhang J, Yan Q … +1 more , Deng X
Mol Genet Genomics · 2026 Mar · PMID 41779201 · Publisher ↗
Hepatocellular carcinoma (HCC) is a highly malignant tumor with aggressive progression and poor clinical outcomes, posing a severe threat to global health. Histone deacetylase 7 (HDAC7) has been implicated in the progres...
Hepatocellular carcinoma (HCC) is a highly malignant tumor with aggressive progression and poor clinical outcomes, posing a severe threat to global health. Histone deacetylase 7 (HDAC7) has been implicated in the progression of multiple cancers, but the underlying mechanism in HCC cell proliferation remains incomplete. The present study aimed to elucidate the functional contribution of HDAC7 to HCC progression and explore the downstream regulatory network. HDAC7, TRIM26, and CBX4 expression in cells were measured. After silencing HDAC7 expression, HCC cell proliferation was detected. Histone acetylation and HDAC7 enrichment on the TRIM26 promoter were assessed. The binding between TRIM26 and CBX4 was detected. The ubiquitination level of CBX4 was measured. HDAC7 expression was upregulated in HCC cell lines. HDAC7 inhibition suppressed HCC cell proliferation. HDAC7 inhibited TRIM26 expression by mediating histone deacetylation. TRIM26 bound to CBX4 and degraded CBX4 via ubiquitination. Inhibiting TRIM26 or overexpressing CBX4 partially reversed the inhibitory effect of HDAC7 inhibition on HCC cell proliferation. HDAC7 inhibition suppressed the growth of HCC xenografts in vivo. In conclusion, HDAC7 is highly expressed in HCC cells and aggravates malignant proliferation of HCC cells via the TRIM26/CBX4 axis, highlighting HDAC7 as a potential therapeutic target for the development of anti-HCC strategies.
Activation of the PI3K/AKT pathway by EDIL3 induces EMT and promotes tumor progression in clear cell renal cell carcinoma.
Tao L, Xie W, Du Y … +1 more , Zhang R
Mol Genet Genomics · 2026 Mar · PMID 41779200 · Publisher ↗
EDIL3 is a secreted extracellular matrix protein implicated in tumor progression; however, its biological function in clear cell renal cell carcinoma (ccRCC) remains poorly defined. In this study, we systematically inves...
EDIL3 is a secreted extracellular matrix protein implicated in tumor progression; however, its biological function in clear cell renal cell carcinoma (ccRCC) remains poorly defined. In this study, we systematically investigated the expression profile, functional roles, and underlying mechanisms of EDIL3 in ccRCC. We found that EDIL3 was significantly upregulated in ccRCC tissues and cell lines. Functional assays demonstrated that EDIL3 markedly enhanced the proliferative, migratory, and invasive capacities of ccRCC cells. Mechanistically, EDIL3 promoted epithelial-mesenchymal transition (EMT), as evidenced by downregulation of E-cadherin and upregulation of N-cadherin and Vimentin. Further analyses revealed that EDIL3 activated the PI3K/AKT signaling pathway, and sustained activation of this pathway effectively reversed the suppression of EMT and malignant phenotypes induced by EDIL3 depletion.Collectively, our findings identify EDIL3 as a critical regulator of ccRCC cell malignancy by linking extracellular matrix dynamics to PI3K/AKT-driven EMT programs, thereby providing mechanistic insight into its role in ccRCC progression.
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