Search Results (3,441)

Arthrobotrys flagrans is a typical nematode-trapping fungus that captures nematodes by producing three-dimensional networks. FlbD is a DNA-binding protein containing a Myb domain, which plays a significant role in fungal development. However, the biological function of FlbD in nematode-trapping fungi remains unknown. In this study, we analyzed the physicochemical properties and conserved domains of AfFlbD and constructed the AfFlbD knockout strains (ΔAfFlbD) using homologous recombination. Our functional analysis revealed that the mutants produced more cottony aerial mycelia at the colony center. Additionally, the cell length of the mutants was reduced, indicating that AfFlbD regulates cell morphology in A. flagrans. Chemical stress tolerance assays of the mutants demonstrated reduced sensitivity to NaCl and sorbitol stresses but increased sensitivity to SDS and H₂O₂ stresses compared to the WT strain. Interestingly, the mutants spontaneously produced traps, and its pathogenicity to nematodes was significantly enhanced, suggesting that AfFlbD negatively regulates the pathogenicity of A. flagrans. Furthermore, the number of chlamydospores produced by the mutants was markedly reduced, though their morphology remained unchanged. Fluorescence localization analysis showed that AfFlbD localizes to the nuclei of chlamydospores, thereby regulating chlamydospore formation. This study provides important theoretical insights into the biological function of the FlbD transcription factor and offers new perspectives for the application of nematode-trapping fungi as a method of controlling plant-parasitic nematodes. Full article

The core perturbome is defined as a central response to multiple disturbances, functioning as a complex molecular network to overcome the disruption of homeostasis under stress conditions, thereby promoting tolerance and survival under stress conditions. Based on the biological and clinical relevance of Escherichia coli and Staphylococcus aureus, we characterized their molecular responses to multiple perturbations. Gene expression data from E. coli (8815 target genes—based on a pangenome—across 132 samples) and S. aureus (3312 target genes across 156 samples) were used. Accordingly, this study aimed to identify and describe the functionality of the core perturbome of these two prokaryotic models using a machine learning approach. For this purpose, feature selection and classification algorithms (KNN, RF and SVM) were implemented to identify a subset of genes as core molecular signatures, distinguishing control and perturbation conditions. After verifying effective dimensional reduction (with median accuracies of 82.6% and 85.1% for E. coli and S. aureus, respectively), a model of molecular interactions and functional enrichment analyses was performed to characterize the selected genes. The core perturbome was composed of 55 genes (including nine hubs) for E. coli and 46 (eight hubs) for S. aureus. Well-defined interactomes were predicted for each model, which are jointly associated with enriched pathways, including energy and macromolecule metabolism, DNA/RNA and protein synthesis and degradation, transcription regulation, virulence factors, and other signaling processes. Taken together, these results may support the identification of potential therapeutic targets and biomarkers of stress responses in future studies. Full article

Runt-related transcription factor-2 (RUNX2) is an integral player in osteogenesis and is highly expressed in osteosarcoma. Emerging evidence suggests that aberrant RUNX2 expression is a key factor in osteosarcoma oncogenesis. Patients with advanced stages of osteosarcoma overexpressing RUNX2 are more likely to have high tumour grades, metastasis, and lower overall or progression-free survival rates. Thus, RUNX2 is considered a potential candidate for targeted therapy of osteosarcoma. Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor involved in the regulation of cellular reprogramming in response to hypoxia. Overexpression of HIF-1α decreases overall survival, disease-free survival, and chemotherapy response and promotes tumour stage and metastasis. Hence, our review focused on highlighting the intricate network between RUNX2 and HIF-1α, which support each other or may work synergistically to develop resistance to therapy and osteosarcoma progression. An in-depth understanding of these two important tumour progression markers is required. Therefore, this review focuses on the role of RUNX2 and HIF-1α in the alteration of the tumour microenvironment, which further promotes angiogenesis, metastasis, and resistance to therapy in osteosarcoma. Full article

Sex-based immunological differences significantly influence the outcome of vaccination, yet the molecular mediators underpinning these differences remain largely elusive. MicroRNAs (miRNAs), key post-transcriptional regulators of gene expression, have emerged as critical modulators of innate and adaptive immune responses. In this study, we investigated the expression profile of selected circulating miRNAs as potential biomarkers of sex-specific humoral responses to the mRNA COVID-19 vaccine in a cohort of health care workers. Plasma samples were collected longitudinally at a defined time point (average 71 days) post-vaccination and analyzed using RT-qPCR to quantify a panel of immune-relevant miRNAs. Anti-spike (anti-S) IgG titers were measured by chemiluminescent immunoassays. Our results revealed sex-dependent differences in miRNA expression dynamics, with miR-221-3p and miR-148a-3p significantly overexpressed in vaccinated female HCWs and miR-155-5p overexpressed in vaccinated males. MiR-148a-3p showed a significant association with anti-S/RBD (RBD: receptor binding domain) IgG levels in a sex-specific manner. Bioinformatic analysis for miRNA targets indicated distinct regulatory networks and pathways involved in innate and adaptive immune responses, potentially underlying the differential immune activation observed between males and females. These findings support the utility of circulating miRNAs as minimally invasive biomarkers for monitoring and predicting sex-specific vaccine-induced immune responses and provide mechanistic insights that may inform tailored vaccination strategies. Full article

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Sea buckthorn is a vital woody oil species valued for its role in soil conservation and its bioactive seed oil, which is rich in unsaturated fatty acids and other compounds. However, low seed oil content and small seed size are the main bottlenecks restricting the development and utilization of sea buckthorn. In this study, we tested the seed oil content and seed size of 12 sea buckthorn cultivars and identified the key genes and transcription factors involved in seed development and lipid biosynthesis via the integration of UID RNA-seq (Unique Identifiers, UID), WGCNA (weighted gene co-expression network analysis) and qRT-PCR (quantitative real-time PCR) analysis. The results revealed five cultivars (CY02, CY11, CY201309, CY18, CY21) with significantly higher oil contents and five cultivars (CY10, CY201309, CY18, CY21, CY27) with significantly heavier seeds. A total of 10,873 genes were significantly differentially expressed between the S1 and S2 seed developmental stages of the 12 cultivars. WGCNA was used to identify five modules related to seed oil content and seed weight/size, and 417 candidate genes were screened from these modules. Among them, multiple hub genes and transcription factors were identified; for instance, ATP synthase, ATP synthase subunit D and Acyl carrier protein 1 were related to seed development; plastid–lipid-associated protein, acyltransferase-like protein, and glycerol-3-phosphate 2-O-acyltransferase 6 were involved in lipid biosynthesis; and transcription factors DOF1.2, BHLH137 and ERF4 were associated with seed enlargement and development. These findings provide crucial insights into the genetic regulation of seed traits in sea buckthorn, offering targets for future breeding efforts aimed at improving oil yield and quality. Full article

Early blight, caused by the pathogen Alternaria solani, is a major fungal disease impacting potato production globally, with reported yield losses of up to 40% in susceptible varieties. As one of the most common diseases affecting potatoes, its incidence has been steadily increasing year after year. This study aimed to elucidate the molecular mechanisms underlying resistance to early blight by comparing gene expression profiles in resistant (B1) and susceptible (D30) potato seedlings. Transcriptome sequencing was conducted at three time points post-infection (3, 7, and 10 dpi) to identify differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) and pathway enrichment analyses were performed to explore resistance-associated pathways and hub genes. Over 11,537 DEGs were identified, with the highest number observed at 10 dpi. Genes such as LOC102603761 and LOC102573998 were significantly differentially expressed across multiple comparisons. In the resistant B1 variety, upregulated genes were enriched in plant–pathogen interaction, MAPK signaling, hormonal signaling, and secondary metabolite biosynthesis pathways, particularly flavonoid biosynthesis, which likely contributes to biochemical defense against A. solani. WGCNA identified 24 distinct modules, with hub transcription factors (e.g., WRKY33, MYB, and NAC) as key regulators of resistance. These findings highlight critical molecular pathways and candidate genes involved in early blight resistance, providing a foundation for further functional studies and breeding strategies to enhance potato resilience. Full article

Botryosphaeria dothidea is the causative agent of Chinese hickory trunk canker, which poses significant threat to the production of Chinese hickory (Carya cathayensis Sarg.). Previous studies reported that endophytic–pathogenic phase transition, also referred to as latent infection, plays an important role in the interaction of Botryosphaeria dothidea with various host plants, including Chinese hickory. However, the mechanism underlying this phase transition is not well understood. Here, we employed RNA-Seq to investigate transcriptional changes in B. dothidea during its phase transition upon interaction with Chinese hickory. A co-expression network was generated based on 6391 differentially expressed genes (DEGs) identified from different infection stages and temperature treatments. One co-expressed module was found that highly correlated with temperature treatments which simulated conditions of B. dothidea latent infection in the field. Subsequently, 53 hub genes were detected, and gene ontology (GO) enrichment analysis revealed three categories of enriched GO terms: transmembrane transport or activity, ion homeostasis or transport, and carbohydrate metabolism. One PacC transcriptional factor (BDLA_00001555, an ambient pH regulator), and one endo-β-1,3-glucanase (BDLA_00010249) were specifically upregulated under temperature treatments that corresponded with the activation stage of B. dothidea’s pathogenic state. The knockout mutant strain of BDLA_00001555 demonstrated defective capability upon the activation of the pathogenic state. This confirmed that BDLA_00001555, the PacC transcriptional factor, plays an important role in the latent infection phase of B. dothidea. Our findings provide insights into the pathogenic mechanism of Chinese hickory trunk canker disease. Full article

Soil salinization is a major constraint to global crop productivity, highlighting the need to identify salt tolerance genes and their molecular mechanisms. Here, we integrated mRNA and miRNA profile analyses to investigate the molecular basis of salt tolerance of an elite Brassica napus cultivar S268. Time-course RNA-seq analysis revealed dynamic transcriptional reprogramming under 215 mM NaCl stress, with 212 core genes significantly enriched in organic acid degradation and glyoxylate/dicarboxylate metabolism pathways. Combined with weighted gene co-expression network analysis (WGCNA) and RT-qPCR validation, five candidate genes (WRKY6, WRKY70, NHX1, AVP1, and NAC072) were identified as the regulators of salt tolerance in rapeseed. Haplotype analysis based on association mapping showed that NAC072, ABI5, and NHX1 exhibited two major haplotypes that were significantly associated with salt tolerance variation under salt stress in rapeseed. Integrated miRNA-mRNA analysis and RT-qPCR identified three regulatory miRNA-mRNA pairs (bna-miR160a/BnaA03.BAG1, novel-miR-126/BnaA08.TPS9, and novel-miR-70/BnaA07.AHA1) that might be involved in S268 salt tolerance. These results provide novel insights into the post-transcriptional regulation of salt tolerance in B. napus, offering potential targets for genetic improvement. Full article

SnRK kinases, central regulators of plant stress response, remain uncharacterized in Taxus—an ancient gymnosperm valued for paclitaxel production. This study aimed to identify the Taxus SnRK family and elucidate its functional roles. Specifically, we identified SnRK genes through genomic analysis and assessed tissue-specific expression via transcriptomics, while regulatory networks were deciphered using WGCNA. To overcome experimental constraints, a PEG-mediated protoplast transient expression system was developed using calli, followed by dual-luciferase assays. Consequently, 19 SnRK genes (2 SnRK1, 4 SnRK2, 13 SnRK3) were identified, with tissue-specific expression revealing TaSnRK1.2 upregulation under methyl jasmonate (MeJA) and in stress-resilient tissues (bark/root). Subsequently, WGCNA uncovered a bark/root-specific module containing TaSnRK1.2 with predicted TF interactions (TaGRAS/TaERF). Critically, homologous dual-luciferase assays demonstrated TaSnRK1.2 activates TaGRAS and TaERF promoters (4.34-fold and 3.11-fold induction, respectively). This study establishes the Taxus SnRK family and identifies TaSnRK1.2 as a hub integrating stress signals (e.g., MeJA) to modulate downstream TF networks, while the novel protoplast system enables future functional studies in this medicinal plant. Full article

Brain organoid technology has revolutionized in vitro modeling of human neurodevelopment and disease, providing unprecedented insights into cortical patterning, neural circuit assembly, and pathogenic mechanisms of neurological disorders. Critically, human brain organoids uniquely recapitulate human-specific developmental processes—such as the expansion of outer radial glia and neuromelanin—that are absent in rodent models, making them indispensable for studying human brain evolution and dysfunction. However, a major bottleneck persists: Extended culture periods (≥6 months) are empirically required to achieve late-stage maturation markers like synaptic refinement, functional network plasticity, and gliogenesis. Yet prolonged conventional 3D culture exacerbates metabolic stress, hypoxia-induced necrosis, and microenvironmental instability, leading to asynchronous tissue maturation—electrophysiologically active superficial layers juxtaposed with degenerating cores. This immaturity/heterogeneity severely limits their utility in modeling adult-onset disorders (e.g., Alzheimer’s disease) and high-fidelity drug screening, as organoids fail to recapitulate postnatal transcriptional signatures or neurovascular interactions without bioengineering interventions. We summarize emerging strategies to decouple maturation milestones from rigid temporal frameworks, emphasizing the synergistic integration of chronological optimization (e.g., vascularized co-cultures) and active bioengineering accelerators (e.g., electrical stimulation and microfluidics). By bridging biological timelines with scalable engineering, this review charts a roadmap to generate translationally relevant, functionally mature brain organoids. Full article

Stomata, highly specialized structures that evolved on the aerial surfaces of plants, play a crucial role in regulating hydration, mitigating the effects of abiotic stress. Stomatal lineage development involves a series of coordinated events, such as initiation, stem cell proliferation, and cell fate determination, ultimately leading to the differentiation of guard cells. While core transcriptional regulators and signaling pathways controlling stomatal cell division and fate determination have been characterized over the past twenty years, the molecular mechanisms linking stomatal development to dynamic environmental cues remain poorly understood. Therefore, stomatal development is considered an active and compelling frontier in plant biology research. On the one hand, this review aims to provide an understanding of the molecular networks governing stomatal ontogenesis, which relies on the activation and function of the transcription factors SPEECHLESS (SPCH), MUTE, and FAMA; the EPF–TMM and ERECTA receptor systems; and downstream MAPK signaling. On the other hand, it synthesizes current discoveries of how hormonal signaling pathways regulate stomatal development in response to environmental changes. As the climate crisis intensifies, the understanding of the complex interplay between stress stimuli and key factors regulating stomatal development may reveal key mechanisms that enhance plant resilience under adverse environmental conditions. Full article

The use of informal language on social media and the sheer volume of information make it difficult for a computer system to analyse it automatically. The aim of this work is to design a new group decision-making method that applies two new consensus methods based on sentiment analysis. This method is designed for application in the analysis of texts on social media. To test the method, we will use posts from the so called social network X. The proposed model differs from previous work in this field by defining a new degree of subjectivity and a new degree of reliability associated with user opinions. This work also presents two new consensus measures, one focused on measuring the number of words classified as positive and negative and the other on analysing the percentage of occurrence of those words. Our method allows us to automatically extract preferences from the transcription of the texts used in the debate, avoiding the need for users to explicitly indicate their preferences. The application to a real case of public investment demonstrates the effectiveness of the approach in collaborative contexts that used natural language. Full article

Microalgae, with their unparalleled capabilities for sunlight-driven growth, CO₂ fixation, and synthesis of diverse high-value compounds, represent sustainable cell factories for a circular bioeconomy. However, industrial deployment has been hindered by biological constraints and the inadequacy of conventional genetic tools. The advent of CRISPR-Cas systems initially provided precise gene editing via targeted DNA cleavage. This review argues that the true transformative potential lies in moving decisively beyond cutting to harness CRISPR as a versatile synthetic biology “Swiss Army Knife”. We synthesize the rapid evolution of CRISPR-derived tools—including transcriptional modulators (CRISPRa/i), epigenome editors, base/prime editors, multiplexed systems, and biosensor-integrated logic gates—and their revolutionary applications in microalgal engineering. These tools enable tunable gene expression, stable epigenetic reprogramming, DSB-free nucleotide-level precision editing, coordinated rewiring of complex metabolic networks, and dynamic, autonomous control in response to environmental cues. We critically evaluate their deployment to enhance photosynthesis, boost lipid/biofuel production, engineer high-value compound pathways (carotenoids, PUFAs, proteins), improve stress resilience, and optimize carbon utilization. Persistent challenges—species-specific tool optimization, delivery efficiency, genetic stability, scalability, and biosafety—are analyzed, alongside emerging solutions and future directions integrating AI, automation, and multi-omics. The strategic integration of this CRISPR toolkit unlocks the potential to engineer robust, high-productivity microalgal cell factories, finally realizing their promise as sustainable platforms for next-generation biomanufacturing. Full article

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new technology such as single-nuclei sequencing (snRNAseq) and spatial transcriptomics, led to a better understanding of the glioma cells’ plasticity and their ability to transition between diverse cellular states. GBM cells can mimic neurodevelopmental programs to resemble oligodendrocyte or neural progenitor behavior and hitchhike the local neuronal network to support their growth. The tumor microenvironment, especially under hypoxic conditions, drives the tumor cell clonal selection, which then reshapes the immune cells’ functions. These adaptations contribute to immune evasion by progressively disabling T cell and myeloid cell functions, ultimately establishing a highly immunosuppressive tumor milieu. This complex and metabolically constrained environment poses a major barrier to effective antitumor immunity and limits the success of conventional therapies. Understanding the dynamic interactions between glioma cells and their microenvironment is essential for the development of more effective immunotherapies and rational combination strategies aimed at overcoming resistance and improving patient outcomes. Full article