Search Results (13,609)

Influenza viruses are adept at hijacking host cellular machinery to facilitate their replication and propagation. A critical aspect of this hijacking involves the reprogramming of host cell metabolism. This review summarizes current findings on how influenza virus infection alters major metabolic pathways, including enhanced glycolysis, suppression of oxidative phosphorylation, diversion of TCA cycle intermediates for biosynthesis, and upregulation of lipid and amino acid metabolism. Key nutrients like glucose, glutamine, and serine are redirected to support viral RNA synthesis, protein production, and membrane formation. Moreover, these metabolic changes also modulate host immune responses, potentially aiding in immune evasion. We highlight the role of transcription factors such as SREBPs in lipid synthesis and the impact of one-carbon metabolism on epigenetic regulation. Finally, we discuss how targeting virus-induced metabolic shifts, using agents like 2-deoxyglucose or fatty acid synthesis inhibitors, offers promising avenues for antiviral intervention, while emphasizing the need for selective approaches to minimize harm to normal cells. Full article

Background: Self-amplifying mRNA (saRNA) holds promising application prospects. However, due to the inclusion of a replicase sequence, its extended length leads to premature termination during in vitro transcription (IVT), resulting in poor product integrity. This study aims to optimize the IVT process for saRNA vaccines to enhance integrity, thereby addressing the key challenge in saRNA vaccine manufacturing. Method: Guided by the Quality by Design (QbD) framework, Design of Experiment (DoE) methodology was employed to design diverse combinations of process parameters for IVT reactions. Predictive models were established to identify critical process parameters (CPPs) influencing integrity and yield. An optimized parameter set and process design space, meeting predefined yield and integrity standards, were developed. The impact of integrity on the immunogenicity of saRNA vaccines was further investigated. Results: Mg²⁺ concentration exerted the most pronounced effect on saRNA integrity. Under optimized IVT conditions, integrity exceeded 85%. Mathematical modeling simulations defined the IVT design space, meeting the preset criteria of ≥80% integrity and ≥600 μg/100 μL yield while accommodating longer saRNA constructs. Notably, murine model data revealed that higher saRNA integrity significantly enhanced antigen-specific antibody and T-cell responses. Conclusion: This study successfully established a multivariate IVT design space fulfilling preset integrity and yield criteria, providing critical data references for the industrialization and quality specification development of saRNA vaccines. Full article

Muscle growth is a critical determinant of meat yield and quality in livestock. Although follistatin (FST) is recognized as a key regulator of skeletal muscle development and fat metabolism, its specific function in geese remains largely unexplored. In this study, we identified two transcript variants of goose FST (gFST) in Zhedong White geese: gFST-X1 (1125 bp), encoding a 343-amino acid protein with a 28-amino acid signal peptide and four conserved domains, and gFST-X2, which contains a 243 bp insertion within the gFST-X1 transcript. RT-qPCR analysis revealed that gFST mRNA expression varied across tissues from female embryos (25 days), adults (70 days), and laying geese (270 days), as well as in skeletal muscle satellite cells (SMSCs) at embryonic day 16 (E16d). Overexpression of gFST in SMSCs resulted in 3596 differentially expressed genes (DEGs), including 2247 upregulated and 1349 downregulated genes (padj < 0.01). Key stemness markers (PAX7, PAX3) and myogenic regulators (MYOG, MYOD, MYF5) were significantly downregulated, whereas genes associated with lipid metabolism (PPARG, FABP5, ACSL5) and myosin-related processes (MYO1D, MYO1F, MYO1E) were markedly upregulated (padj < 0.01). Functional enrichment analysis linked these DEGs to the TGF-β, PPAR signaling, fatty acid metabolism, and Notch signaling pathways. These transcriptomic findings were further validated by qRT-PCR. Collectively, our results demonstrate the dual regulatory role of gFST in skeletal muscle development and provide new mechanistic insights into muscle development in geese. Full article

Non-coding RNAs (ncRNAs) are involved in many biological processes, making their identification and functional characterization a priority. Among them, long non-coding RNAs (lncRNAs) have been shown to regulate diverse cellular processes, such as cell development, stress response, and transcriptional regulation. The continued identification of new lncRNAs highlights the demand for reliable methods for their detection, with structural analysis offering insightful information. Currently, lncRNAs are identified using tools such as LncFinder, whose database has a large collection of lncRNAs from humans, mice, and chickens, among others. In this work, we present a graph-based algorithm to represent and compare RNA secondary structures. Rooted tree graphs were used to compare two groups of Saccharomyces cerevisiae RNA sequences, lncRNAs and not lncRNAs, by searching for structural similarities between each group. When applied to a novel candidate sequence dataset, the algorithm evaluated whether characteristic structures identified in known lncRNAs recurred. If so, the sequences were classified as likely lncRNAs. These results indicate that graph-based structural analysis offers a complementary methodology for identifying lncRNAs and may complement existing sequence-based tools such as lncFinder or PreLnc. Recent studies have shown that tumor cells can secrete lncRNAs into human biological fluids forming circulating lncRNAs which can be used as biomarkers for cancer. Our algorithm could be applied to identify novel lncRNAs with structural similarities to those associated with tumor malignancy. Full article

Background/Objectives: Cytochrome 1B1 (CYP1B1) is overexpressed in several cancers, contributing to carcinogenesis, cancer progression, and chemoresistance. Despite its known oncogenic role, its expression in bone sarcomas remains unknown. Methods: This study assessed CYP1B1 expression in osteosarcoma and chondrosarcoma using immunohistochemistry on tissue microarrays and analyzed corresponding transcriptomic profiles from public RNA-seq datasets. Associations with clinicopathological features, survival, drug sensitivity, and protein–protein interaction networks were also investigated. Results: CYP1B1 was overexpressed in 72.3% of bone sarcomas (78% of osteosarcomas and 82.1% of chondrosarcomas) and was significantly underexpressed in normal bone (12.5%, p < 0.001). Importantly, high CYP1B1 expression was found in younger patients (≤34 years; p = 0.013), but no other associations with tumor grade, size, or metastasis were observed. The mean survival rate of CYP1B1-positive patients was insignificantly shorter than that of negative patients (58.8 vs. 62.8 months; p = 0.170). Although not confirmed in the multivariate analysis, CYP1B1-positive patients had poorer survival in the univariate analysis, which may reflect tumor aggressiveness rather than prognostic value. Transcriptomic data showed significantly lower CYP1B1 mRNA in osteosarcoma versus normal bone, suggesting post-transcriptional or translational regulation. Drug sensitivity analysis revealed both positive and negative correlations between CYP1B1 expression and response to various compounds in the GDSC dataset, highlighting potential therapeutic implications. Conclusions: Despite low mRNA levels, CYP1B1 protein is consistently and selectively overexpressed in bone sarcomas, particularly in younger patients. While not prognostic, its expression profile warrants further investigation and evaluation as a therapeutic target or diagnostic biomarker, especially in refractory or advanced cases. Full article

The diamondback moth, Plutella xylostella, is a major pest of brassica vegetables and oilseed crops, posing a serious threat to China’s grain and oil production. RNA interference (RNAi) has been developed as an efficient strategy to control pests. In this study, the effects of RNAi on P. xylostella were evaluated by injecting two doses of synthesized dsPxvATPasea. The transcripts of PxvATPasea were widely transcribed during different developmental stages from egg to adult. They were abundantly expressed in the hindgut and Malpighian tubules, compared with other tissue types. Introduction of 800 ng dsPxvATPasea in the fourth-instar larvae greatly reduced corresponding mRNA levels by 3.1 and 1.4 times on day 2 and 3, respectively, causing 66.6% mortality and 33.4% treated larvae pupated. Silencing PxvATPasea by injecting 1200 ng dsRNA significantly decreased the expression level by 5.0 and 2.0 times on the second and third day, leading to 79.2% larval lethality and 20.8% depleted larvae pupated. Moreover, introducing 800 ng or 1200 ng dsPxvATPasea finally reduced larval fresh weight by 22.1% and 28.8%, respectively. The results indicated that the silencing efficiency of PxvATPasea worked in a dose-dependent way. Consequently, PxvATPasea is a potential molecular target gene. Our findings will facilitate the application of RNAi technology to manage P. xylostella. Full article

Background/Objectives: Most studies investigating prognostic biomarkers in cervical cancer (CC) analyze patients irrespective of FIGO stage, potentially masking molecular features that underlie the aggressiveness of some FIGO II tumors. To address this, we investigated differential gene expression in a FIGO II CC cohort to identify a gene signature predictive of progression-free survival (PFS) within five years of treatment initiation. Methods: Tumor samples from 15 CC patients were analyzed using RNA sequencing, bioinformatics, and machine learning to identify differentially expressed genes (DEGs) associated with prognosis. Findings were validated in an independent CC cohort (n = 174). Results: High expression of B3GALT1 (HR = 5.11), GTF3C2-AS1 (HR = 18.73), and ZKSCAN4 (HR = 5.18) was significantly associated with an increased risk of recurrence in our cohort. Elevated expression of these transcripts is also associated with shorter PFS in the external dataset. Notably, GTF3C2-AS1 expression alone was sufficient to classify all fifteen patients into their respective prognostic groups using a decision tree model, achieving 93.3% accuracy in leave-one-out cross-validation (LOOCV). Additional candidates, including RCAN2-DT, MYH9-DT, IGKC, IGHG1, and IGHG3, were associated with PFS in our cohort but could not be externally validated due to a lack of available data. Conclusions: Transcriptomic profiling revealed potential biomarkers that refine prognostic stratification in cervical cancer beyond FIGO staging. Among them, GTF3C2-AS1 consistently emerged as a potential predictor of recurrence risk. Additional candidates, including B3GALT1, ZKSCAN4, and immunoglobulin transcripts, provided complementary insights but require further validation. These preliminary results highlight intra-stage heterogeneity in FIGO II CC and underscore the promise of molecular markers to improve risk assessment. Full article

Avian reovirus (ARV), a highly pathogenic agent in poultry, causes severe economic losses through immunosuppression and secondary infections. Traditional diagnostic methods like reverse transcription quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) face limitations in resource-limited settings due to equipment dependency and prolonged processing. To address this, we developed a rapid, portable detection method integrating reverse transcription–recombinase-aided amplification (RT-RAA) with CRISPR/Cas12a. By targeting the conserved P17-coding region of the ARV S1 gene, this assay amplifies viral RNA isothermally (37 °C) within 20 min, followed by Cas12a-mediated collateral cleavage of fluorescent or lateral flow reporters for visual readout. The method achieved a sensitivity of 1 copy/μL, surpassing RT-qPCR (10 copies/μL), and completed detection in 40 min. Specificity tests against non-target pathogens confirmed zero cross-reactivity. Utilizing a portable incubator and low-cost visual tools, this platform eliminates reliance on thermocyclers and skilled personnel. Its field-deployable design enables on-site diagnosis, facilitating early ARV detection to mitigate outbreaks and economic losses in poultry farming. This study provides a paradigm shift in avian pathogen surveillance, combining speed, sensitivity, and accessibility for global agricultural and public health applications. Full article

Background/Objectives: Glioblastoma (GBM), the most aggressive primary malignant brain tumor, has a dismal prognosis and limited treatment options. The dried rhizome of Ligusticum chuanxiong Hort. (Chuanxiong, CX) is a traditional Chinese medicinal herb frequently prescribed in formulas intended to invigorate blood circulation. CX also exhibits anti-glioma activity, but its molecular mechanisms remain incompletely understood. Methods: In this study, we combined transcriptomics and Raman spectroscopy to investigate the effects of reconstituted CX-dispensing granules (hereafter referred to as CXG solution) on U87MG cells, suggesting their dual role in promoting cell death and modulating collagen deposition and lipid metabolism. Results: Mechanistically, we demonstrated that the CXG solution downregulates hsa-miR-10a-5p, which directly targets BCL2L11, known to induce pro-apoptotic effects, as validated by qPCR and dual-luciferase reporter assays. Furthermore, the CXG solution and hsa-miR-10a-5p suppress lipid metabolism through a coherent feed-forward loop via targeting transcription factors SREBF1 and E2F1. An electrophoretic mobility shift assay (EMSA) confirmed E2F1 binds to the hsa-miR-29a promoter, leading to the synergistic repression of hsa-miR-29a-3p by SREBF1 and E2F1. Network pharmacology analysis combined with molecular docking suggested that the ferulic acid and adenosine in CX potentially modulate EGFR-the E2F1-hsa-miR-10a-5p axis. Conclusions: These findings elucidate CX’s multi-target anti-GBM mechanisms and propose a novel therapeutic strategy combining metabolic intervention with miRNA-targeted therapy, providing novel insights into feed-forward loop regulation in miRNA networks. Full article

In numerous coffee-producing areas, coffee plants are routinely exposed to a low chilling temperature on a seasonal cycle. Despite the well-established significance of NAC transcription factors in mediating plant responses to abiotic stresses, their functions in Coffea arabica remain underexplored. This study identified 161 CaNAC genes and classified them into 15 distinct subgroups distributed across 22 chromosomes, with chromosome 11 harboring the largest number of these genes. Furthermore, a total of 1077 cis-elements were detected in the promoter regions of the 161 CaNAC genes. Among these, MYB-binding sites and ABA-responsive elements (ABREs) were the most prevalent. RNA-seq analysis under chilling stress revealed 16,767 differentially expressed genes, which were grouped into four clusters. GO enrichment analysis highlighted biological processes such as the abscisic acid-activated signaling pathway, response to cold, and response to salicylic acid, providing fundamental insights into the transcriptional response of C. arabica to chilling stress. Expression pattern analysis of CaNACs under chilling stress showed that 38 CaNACs were differentially expressed; 15 genes, including CaNAC46/49/116/125, were downregulated, while 12 genes, including CaNAC56/64, were upregulated. This study enhances our understanding of the CaNAC gene family’s role in cold responses, potentially bolstering molecular breeding programs for C. arabica. Full article

C-type natriuretic peptide (CNP), encoded by the NPPC (Natriuretic Peptide Precursor C), has been recognized as the principal endogenous factor sustaining oocyte meiotic arrest in mammalian follicles. Yet its influence on porcine ovarian granulosa cell fate and the regulatory mechanism of NPPC expression within these cells remain poorly understood. Here, utilizing an in vitro culture model of primary porcine ovarian granulosa cells and immature oocytes, we examined the impact of CNP on granulosa cell apoptosis and oocyte meiotic resumption, and elucidated the molecular circuitry governing NPPC expression. We found that follicular atresia in pigs was accompanied by a marked decline in the CNP receptor NPR2 (natriuretic peptide receptor 2). Correspondingly, exogenous CNP suppressed apoptosis in cultured porcine granulosa cells. Estradiol can significantly promote the expression level of NPPC in porcine ovarian granulosa cells and, by enhancing NPR2 levels, it can synergize with CNP to inhibit oocyte meiotic resumption in vitro. Conversely, EGF signaling can significantly downregulate NPPC mRNA expression in porcine granulosa cells, an effect likely mediated by ERK-activated tristetraprolin (TTP). Collectively, these findings broaden our understanding of CNP in follicular development and delineate the endocrine network that controls NPPC transcription in the porcine ovary. Full article

Myocardial infarction triggers limited repair in adult mammals but robust regeneration in zebrafish. Epigenetic regulation and immune responses are recognized as critical for successful regeneration. However, the molecular links between these processes have not been fully elucidated. By performing single-cell RNA sequencing of zebrafish ventricular cardiomyocytes after injury, we identified a regeneration-induced immunomodulatory cluster that specifically expressed the histone demethylase gene kdm7aa. Functional perturbations, including CRISPR/Cas9-mediated kdm7aa mutation and pharmacological inhibition of Kdm7aa activity using TC-E5002, impaired cardiac regeneration. Bulk RNA sequencing showed that kdm7aa drives an inflammatory transcriptional program, prominently activating chemokines such as cxcl8a and cxcl19 that coordinate immune cell recruitment. Cross-species analyses revealed injury-induced Kdm7a upregulation in regeneration-competent neonatal mouse hearts but not in adult mouse or human hearts. These data identified Kdm7aa as a regeneration-induced epigenetic regulator that enabled cardiomyocytes to adopt a transient immune-activating phenotype, linking histone demethylation to chemokine signaling and suggesting a potential therapeutic strategy to enhance mammalian cardiac repair. Full article

Background: Enhancer RNAs (eRNAs), a subclass of long non-coding RNAs transcribed from enhancer regions, have emerged as dynamic regulators of gene expression, tumor progression, and therapeutic response. In gliomas, their biological and clinical significance is only recently being elucidated. This systematic review aimed to synthesize current evidence regarding the role of eRNAs in gliomagenesis, chemoresistance, and prognosis. Methods: We conducted a systematic review following PRISMA 2020 guidelines. PubMed/MEDLINE and Scopus databases were searched on September 2025 using a predefined strategy. Eligible studies included clinical or pre-clinical analyses of eRNAs in gliomas, reporting associations with tumorigenicity, survival, or resistance to temozolomide (TMZ). Risk of bias was assessed using ROBINS-I (Version 2), and findings were qualitatively synthesized. Results: From 26 retrieved records, 10 studies were included, encompassing 22 unique eRNAs. Two studies demonstrated that TMZR1-eRNA and LINC02454* modulate TMZ sensitivity by regulating STAT3, SORBS2, and DDR1 pathways. Seven studies evaluated prognostic implications: 12 eRNAs (e.g., AC003092.1, CYP1B1-AS1, CRNDE) were consistently associated with poor survival, while seven (e.g., LINC00844, ENSR00000260547) correlated with favorable outcomes, particularly in low-grade gliomas. One mechanistic study showed that HOXDeRNA directly promotes gliomagenesis by displacing PRC2 repression at key transcription factor promoters and activating oncogenic super-enhancers. Conclusions: eRNAs are not passive transcriptional by-products but active modulators of glioma biology. They influence tumor initiation, therapeutic resistance, and survival outcomes, underscoring their potential as prognostic biomarkers and therapeutic targets. Future research should validate these findings in larger clinical cohorts and explore strategies for eRNA-directed therapies in precision neuro-oncology. Full article

Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperactivation and dysregulated cytokine signaling, with nuclear factor kappa B (NF-κB), a master transcription factor that regulates immune and inflammatory gene expression, playing a central role. Adalimumab, a monoclonal antibody that inhibits tumor necrosis factor alpha (TNF-α), is widely used in psoriasis therapy, yet its molecular effects on NF-κB-associated genes and microRNAs (miRNAs) in keratinocytes remain insufficiently defined. In this study, immortalized human keratinocytes (HaCaT cells) were exposed to lipopolysaccharide (LPS) to induce inflammatory stress and treated with adalimumab for 2, 8, and 24 h. Transcriptome-wide profiling was performed using messenger RNA (mRNA) and miRNA microarrays, followed by validation with reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Bioinformatic analyses included prediction of miRNA–mRNA interactions, construction of protein–protein interaction (PPI) networks, and gene ontology (GO) enrichment. Adalimumab reversed LPS-induced upregulation of NF-κB-associated genes, including inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB), interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 2 (TRAF2), mitogen-activated protein kinase kinase kinase 7 (MAP3K7), and TNF alpha-induced protein 3 (TNFAIP3), with concordant changes observed at the protein level. Several regulatory miRNAs, notably miR-1297, miR-30a, miR-95-5p, miR-125b, and miR-4329, showed reciprocal expression changes consistent with anti-inflammatory activity. STRING analysis identified IKBKB as a central hub in the PPI network, while GO enrichment highlighted immune regulation, apoptosis, and NF-κB signaling. These findings demonstrate that adalimumab modulates NF-κB activity in keratinocytes through coordinated regulation of gene, protein, and miRNA expression, providing mechanistic insight into TNF-α blockade in psoriasis. Full article

N6-methyladenosine (m⁶A) is the most abundant and dynamic RNA modification in eukaryotic messenger and non-coding RNAs, playing a pivotal role in the post-transcriptional regulation of gene expression. The coordinated actions of m⁶A writers, erasers, and readers influence transcript stability, immune activation, and pathogen suppression. Growing evidence indicates that m⁶A fine-tunes the expression of defense-related genes, modulates RNA processing events, and is frequently hijacked by pathogens and pests to promote virulence. Notably, the dual role of m⁶A in enhancing plant defense and facilitating pathogen adaptation highlights its significance in the host–pathogen arms race. This review emphasizes recent advances in our understanding of m⁶A-mediated epitranscriptomic regulation in plants, with a focus on its role in responses to biotic stresses, including fungi, bacteria, virus infections, insects, and nematode attacks. This regulatory layer offers novel opportunities for crop protection through targeted manipulation of the epitranscriptomic mechanism. Full article