Frontiers in Molecular Biosciences最新文献

Background: Intraoperative hypothermia frequently occurs during surgery and can negatively impact patient outcomes. The study focuses on establishing a clinical prediction model to identify the risk of intraoperative hypothermia in patients undergoing endoscopic thyroidectomy for thyroid cancer.

Methods: Univariate analysis was performed to identify potential indicators associated with intraoperative hypothermia. Multivariable logistic regression analysis was employed to select the independent predictors for model construction. The predictive performance and clinical utility of the model were assessed using receiver operating characteristic (ROC) curve, calibration plots and decision curve analysis (DCA). External validation was conducted to evaluate its generalizability.

Results: Univariate analysis revealed that age, body mass index (BMI), anesthesia duration, duration of surgery, infusion volume, intraoperative irrigation volume, irrigation fluid temperature and intraoperative blood loss were significantly associated with the occurrence of intraoperative hypothermia (all P < 0.05). Multivariate logistic regression analysis identified infusion volume and irrigation fluid temperature were independent risk factors for intraoperative hypothermia in patients undergoing endoscopic radical thyroidectomy for thyroid cancer, whereas BMI was an independent protective factor (P < 0.05). ROC curve indicated excellent predictive accuracy of the model (AUC = 0.945). The calibration plot demonstrated a high degree of concordance between the actual incidence and the predicted probabilities. The results of DCA indicated that this predictive model has high clinical application value. When applied to the validation cohort, the model maintained strong predictive performance and stability, with an AUC of 0.831.

Conclusion: The nomogram model developed in this study exhibits strong predictive performance and high clinical utility in assessing the risk of intraoperative hypothermia among patients undergoing endoscopic thyroid cancer radical surgery, serving as a valuable reference for operating room nurses in identifying high-risk individuals.

Liquid biopsy has emerged as a transformative tool in precision oncology, offering a minimally invasive approach for cancer detection, monitoring, and treatment guidance. Unlike traditional tissue biopsies, which are invasive and limited by tumor accessibility and sampling bias, liquid biopsy enables real-time tumor assessment through the analysis of circulating biomarkers in blood and other biofluids. This review provides a comprehensive overview of recent advances in liquid biopsy, with a focus on circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), non-coding RNAs, extracellular vesicles (exosomes), and secreted proteins. These biomarkers offer valuable insights into tumor biology, supporting applications in early diagnosis, prognosis, treatment response monitoring, and minimal residual disease detection across various cancer types. We also discuss state-of-the-art methodologies, including next-generation sequencing, digital PCR, microfluidics, proteomics, and emerging artificial intelligence-based approaches that enhance the sensitivity, specificity, and scalability of liquid biopsy assays. Clinical studies demonstrate the potential of liquid biopsy for tailoring targeted therapies, predicting resistance mechanisms, and identifying tumor recurrence earlier than conventional methods. Furthermore, FDA-approved assays and ongoing phase III and IV clinical trials highlight its growing integration into routine clinical practice. Beyond technical innovations, this review examines the global landscape of liquid biopsy, emphasizing opportunities and challenges for implementation across diverse healthcare settings. Disparities in access, particularly between high-income and low- and middle-income countries, underscore the need for strategies that ensure equitable adoption of liquid biopsy technologies worldwide. In summary, liquid biopsy represents a paradigm shift in oncology, bridging innovations in cancer diagnostics with clinical applications. By enabling dynamic, personalized, and less invasive cancer management, it holds great promise for improving patient outcomes and advancing precision medicine.

Cell senescence is triggered by stressful stimuli, including telomere attrition, genotoxic agents, and strong mitogenic signals. This state is characterized by proliferation arrest and acquisition of a senescence-associated secretory phenotype. Senescent cells secrete growth factors, chemokines, cytokines, proteases, and other factors that can impact the cell's microenvironment, promoting aging and the development of age-associated diseases. These discoveries have emphasized the need for a detailed analysis of the senescent phenotype. Redox alterations are one of the hallmarks of cellular senescence, and are required to maintain the senescent phenotype. Here, we review current information on senescent cell's redox metabolism, with a special focus on metabolomic profiling of human fibroblasts. We describe metabolic pathways involved in redox homeostasis, in particular glutathione metabolism, that undergo reprogramming in cell senescence, and links with the senescent phenotype.

Endophytic fungi are an uncharted source of bioactive metabolites with varied therapeutic characteristics. In this research, an endophytic Aspergillus sp. (HAG1) was collected from Phragmites australis and identified using morphological and molecular methods. The large-scale fermentation, chromatographic purification, and spectroscopic approaches (FT-IR, UV-Vis, ¹H NMR, and ESI-MS) resulted in the identification of three metabolites: vaccenic acid (C1), pipericine (C2), and guaiacylglycerol (C3). Of these, C3 is reported here for the first time as an endophyte-derived metabolite from P. australis. All the metabolites exhibited significant antioxidant, antibacterial, antibiofilm, and anti-inflammatory activity. The activities of C3 were the most effective in DPPH and ABTS scavenging, COX-1/COX-2 inhibition, and suppression of biofilm for bacteria, although C3 was inactive against acetylcholinesterase activity. Molecular docking and molecular dynamics (MD) simulations underscored a favorable binding with a high binding conformation stability of C3 for antioxidant (1DGF), anti-inflammatory (3NLO), and antibiofilm (5TZ1) targets. In addition, density function theory (DFT) calculations delivered insights regarding electronic structure, explaining observed reactivity and hydrogen bonding ability. Moreover, ADMET predictions indicated that C3 has favorable solubility, metabolic stability, and low toxicity when compared to C1 and C2.

Caenorhabditis elegans encode two synaptic proteins linked to the Rim/Piccolo/Fife-family, through conserved motifs: 1) Clarinet (CLA-1), has 3 isoforms (short(S), medium(M) and long(L)) that are anchored at the active zone through a common C-terminal domain and 2) UNC-10/Rim that is also highly enriched at the presynaptic density. Both the cla-1 and unc-10 mutants have demonstrable effects on synaptic transmission and in combination produce a synergistic impact that virtually eliminates synaptic transmission and that has yet to be fully understood. Recently, CLA-1L and UNC-10 were shown to differentially regulate key active zone components, culminating in reduced Ca²⁺ channels and UNC-13 levels, but these changes cannot account for the severity of the release defects in the double mutants. CLA-1L extends far beyond the synaptic active zone and has been implicated in recycling of the key autophagy protein ATG-9. In this study, we show that cla-1L and unc-10 mutants negatively impact proteins involved in endocytic processing (ITSN-1 and AP-2) and endolysosomal maturation (RAB-5 and RAB-7). These abnormalities correlate with an accumulation of synaptic pleiomorphic vesicles by EM, in both cla-1L and unc-10 mutants. In addition, unc-10 mutants accumulate dense core vesicles, due to a dramatic reduction in neuropeptide release. These observations are accompanied by significant decreases in lifespan in both cla-1L and unc-10 mutants, which are exacerbated in the double mutants. Together these data suggest that the cumulative effects on synaptic transmission that result from distinct roles of CLA-1L and UNC-10 have an impact on survival.

Sepsis poses a significant threat to preterm infants and is a leading cause of white matter injury (WMI); however, effective therapeutic strategies remain limited. Recent studies suggest that gut microbiota dysbiosis contributes to sepsis-induced systemic inflammation and neurological damage. After treating mice with LPS-induced sepsis with glycine, we evaluated pathological changes in the brain and ileum by HE staining and analyzed gut microbiota composition by 16S rRNA gene sequencing. Inflammatory cytokine levels in brain and ileal tissues were quantified by ELISA. Transcriptomic profiling was performed to identify differentially expressed genes and enriched pathways in the brains of septic mice with WMI. Additionally, protein expression levels of occludin, Iba-1, BMP, and C5aR1 were assessed by IHC and Western blotting. The study demonstrates that sepsis induces WMI. Glycine alleviated intestinal dysbiosis, restored the expression and function of intestinal tight junction proteins, and reduced pro-inflammatory cytokine levels in both ileal and brain tissues. Moreover, glycine attenuated microglial activation, as evidenced by decreased Iba-1 expression, and preserved myelin integrity by preventing the loss of MBP in the brain. Transcriptomic analysis revealed significant upregulation of C5aR1 in brain tissue associated with sepsis-induced WMI. Collectively, these findings indicate that glycine represents a promising therapeutic strategy for the prevention and treatment of sepsis-associated WMI, and that targeting the C5aR1-mediated complement pathway may offer a novel approach to mitigate neuroinflammation and white matter damage.

Background: Bladder cancer (BLCA) is a highly heterogeneous malignancy with an unpredictable prognosis. Tumour progression is closely linked to the complex tumour microenvironment (TME), particularly the role of epithelial cells. This study aims to identify key epithelial cell-derived signature genes driving tumour progression, construct a reliable prognostic model, and further explore the biological functions of a pivotal gene, OAS1, in BLCA.

Methods: Single-cell RNA sequencing (scRNA-seq) data from public cohorts were analyzed to identify epithelial cell subpopulations and delineate their malignant progression trajectory. Genes significantly associated with this progression were identified through pseudotime analysis. Bulk RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) BLCA cohort were utilized for least absolute shrinkage and selection operator (LASSO) Cox regression to build a prognostic risk model. The model's predictive efficacy was validated in an independent Gene Expression Omnibus (GEO) cohort. Furthermore, in vitro experiments including CCK-8, transwell, and wound healing assays were conducted to investigate the impact of OAS1 on the proliferation, migration, and invasion capabilities of BLCA cells.

Results: scRNA-seq analysis revealed a distinct epithelial cell subpopulation with high tumor-suppressive activity. A four-gene signature associated with tumor progression was successfully constructed into a prognostic model. Patients in the high-risk group exhibited significantly poorer overall survival in both the TCGA and validation cohorts. Multivariate Cox analysis confirmed the model as an independent prognostic factor. The risk score was significantly correlated with immune infiltration patterns and response to immunotherapy. Among the signature genes, OAS1 was identified as a critical factor. In vitro functional experiments demonstrated that knockdown of OAS1 markedly promoted the proliferation, migration, and invasion of BLCA cells.

Conclusion: We established a novel prognostic model for BLCA based on epithelial cell tumor progression-associated genes, which serves as a robust predictor for patient outcomes and immunotherapeutic responsiveness. Our findings further highlight OAS1 as a key gene that suppresses the aggressive phenotypes of BLCA cells, suggesting it is a potential therapeutic target. This study provides valuable insights for precise prognosis and treatment stratification of BLCA patients.

Background: The Golden Mussel, Limnoperna fortunei, represents one of the most successful aquatic invaders in South America, causing significant ecological and economic impacts. Repetitive DNA sequences, particularly satellite DNAs (satDNAs), play crucial roles in genome architecture and evolution, yet the satDNA landscape of this invasive species remains largely uncharacterized. This study aimed to comprehensively analyze the satellitome of L. fortunei using integrated computational and cytogenetic approaches.

Methods: We employed a read-clustering approach (RepeatExplorer2) to identify satDNA families from short-read genomic data. The identified families were then mapped onto the chromosome-level reference genome in silico to determine their chromosomal distribution. The physical localization of two representative satDNA families with contrasting distribution patterns was validated through fluorescence in situ hybridization (FISH) on meiotic chromosomes.

Results: Our analysis identified 129 distinct satDNA families, which were estimated to comprise approximately 9.1% of the genome based on read clustering. Subsequent in silico mapping successfully localized 126 of these families to the reference genome, where they collectively represented approximately 5.3% of the assembled chromosomes. Most families showed low divergence levels (0%-5% Kimura substitutions), suggesting recent amplification events. While most satDNAs were distributed across all 15 chromosomes, FISH analysis of two distinct families revealed contrasting distribution patterns: LfoSat025 showed preferential localization to pericentromeric regions, while LfoSat004 exhibited localized enrichment in specific chromosomal regions, demonstrating diverse organizational strategies within the satellitome. Meiotic analysis revealed normal chromosome pairing (15 bivalents), with no evidence of differentiated sex chromosomes, consistent with the species' predominantly gonochoristic reproductive mode.

Conclusion: This study provides the first comprehensive characterization of the L. fortunei satellitome, revealing a diverse and recently amplified repetitive landscape. The discrepancy between the genome-wide abundance (9.1%) and the mapped abundance (5.3%) highlights the challenges of assembling repetitive regions and underscores the value of using complementary methodologies. The identification of chromosome-specific satDNA markers establishes a foundation for developing molecular tools for invasion monitoring, including population genetic analyses to trace invasion routes and identify source populations. These findings contribute to understanding the role of repetitive DNA in genome evolution and the adaptive success of invasive species.

Background: Given the lack of effective treatment for chronic nonbacterial prostatitis (CNP) and the anti-inflammatory property of natural bioactive compound forsythiaside A (FTA), the therapeutic potential of FTA on CNP is worthy of investigation.

Methods: CNP rat models were established using complete Freund's adjuvant, followed by a 4-week administration of FTA at different concentrations (40 and 80 mg/kg/d). The body and prostate of rats were weighed to calculate the prostatic index. Prostate damage and inflammatory infiltration were assessed using histological analysis and immunohistochemistry staining. Levels of inflammation-related cytokines, autophagic markers as well as the protein kinase C alpha (PKCα)/NF-κB pathway in prostate tissues were detected using enzyme-linked immunosorbent assay and western blot.

Results: No significant change was observed in the body weight of CNP rat models administered with or without FTA. FTA treatment reduced the prostatic index and mitigated prostate damage and inflammatory infiltration of CNP rat models. FTA treatment decreased the number of CD3-positive cells and CD45-positive cells, while downregulating interleukin 1 beta (IL-1β), IL-2, IL-6, IL-17A, monocyte chemoattractant protein-1, and tumor necrosis factor alpha in prostate tissues of CNP rat models. FTA treatment promoted Beclin-1 and LC3B II/LC3B I expressions, and inhibited PKCα and p-p65/p65 expressions in prostate tissues of CNP rat models.

Conclusion: FTA alleviates inflammation and facilitates autophagy in CNP rat models by blocking the PKCα/NF-κB pathway.