Frontiers in Molecular Biosciences最新文献

{"title":"Influence of expression and purification protocols on Gα biochemical activity: kinetics of plant and mammalian G protein cycles.","authors":"Timothy E Gookin, David Chakravorty, Sarah M Assmann","doi":"10.3389/fmolb.2025.1513660","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1513660","url":null,"abstract":"<p><p>Heterotrimeric G proteins, composed of Gα, Gβ, and Gγ subunits, are a class of signal transduction complexes with broad roles in human health and agriculturally relevant plant physiological and developmental traits. In the classic paradigm, guanine nucleotide binding to the Gα subunit regulates the activation status of the complex. We sought to develop improved methods for heterologous expression and rapid purification of Gα subunits, initially targeting GPA1, the sole canonical Gα subunit of the model plant species, <i>Arabidopsis thaliana.</i> Compared to conventional methods, our expression methodology and rapid StrepII-tag mediated purification facilitates substantially higher yield, and isolation of protein with increased GTP binding and hydrolysis activities. Human GNAI1 purified using our approach displayed the expected binding and hydrolysis activities, indicating our protocol is applicable to mammalian Gα subunits, potentially including those for which purification of enzymatically active protein has been historically problematic. We subsequently utilized domain swaps of GPA1 and human GNAO1 to demonstrate that the inherent instability of GPA1 is a function of the interaction between the Ras and helical domains. Additionally, we found that GPA1-GNAO1 domain swaps partially uncouple the instability from the rapid nucleotide binding kinetics displayed by GPA1. In summary, our work provides insights into methods to optimally study heterotrimeric G proteins, and reveals roles of the helical domain in Gα kinetics and stability.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1513660"},"PeriodicalIF":3.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic readouts of tumor instructed normal tissues (TINT) identify aggressive prostate cancer subgroups for tailored therapy.","authors":"Ilona Dudka, João Figueira, Pernilla Wikström, Anders Bergh, Gerhard Gröbner","doi":"10.3389/fmolb.2025.1426949","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1426949","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer (PC) diagnosis relies on histopathological examination of prostate biopsies, which is restricted by insufficient sampling of all tumors present. Including samples from non-PC but tumor instructed normal tissues (TINT) may increase the diagnostic power by displaying the adaptive responses in benign tissues near tumors.</p><p><strong>Methods: </strong>Here, we applied high-resolution magic angle spinning nuclear magnetic resonance (HR MAS NMR) to identify metabolomic biomarkers of possible diagnostic value in benign prostate tissues near low/high-grade tumors.</p><p><strong>Results: </strong>Benign samples near high-grade tumors (B ISUP 3 + 4) exhibited altered metabolic profiles compared to those close to low-grade tumors (B ISUP 1 + 2). The levels of six metabolites differentiated between the two groups; myo-inositol, lysine, serine and combined signal of lysine/leucine/arginine were increased in benign samples near high-grade tumors (B ISUP 3 + 4) compared to near low-grade tumors (B ISUP 1 + 2), while levels of ethanolamine and lactate were decreased. Additionally, we revealed metabolic differences in non-cancer tissues as a function of their distance to the nearest tumor. Eight metabolites (glutathione, glutamate, combined signal of glutamate/glutamine - glx, glycerol, inosine, ethanolamine, serine and arginine) differentiated between benign tissue located close to the tumor (d ≤ 5 mm) compared to those far away (d ≥ 1 cm).</p><p><strong>Conclusion: </strong>Our HR MAS NMR-based approach identified metabolic signatures in prostate biopsies that reflect the response of benign tissues to the presence of nearby located tumors in the same prostate and confirmed the power of the TINT concept for improved PC diagnostics and understanding of tumor-tissue interactions.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1426949"},"PeriodicalIF":3.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UPLC-Q-TOF-MS-based unbiased serum metabolomics investigation of cholangiocarcinoma.","authors":"Xiaowei Wang, Xuefeng Xu, Ran Jia, Yuanhong Xu, Ping Hu","doi":"10.3389/fmolb.2025.1549223","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1549223","url":null,"abstract":"<p><strong>Objective: </strong>Cholangiocarcinoma (CCA) is a highly aggressive malignancy, and early diagnosis remains challenging. Metabolic biomarkers are increasingly recognized as promising tools for the early detection of cancer. However, a comprehensive exploration of metabolic alterations in CCA, especially from a global metabolic perspective, has yet to be fully realized. To identify reliable metabolic markers for the early diagnosis of CCA and to explore its potential pathogenesis through an in-depth analysis of global metabolism.</p><p><strong>Methods: </strong>Serum samples from 30 CCA patients and 31 healthy individuals were analyzed using an unbiased UPLC-Q-TOF-MS based metabolomics approach. Principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) were applied to identify potential biomarkers. High-resolution MS/MS and available standards were used to further confirm the identified metabolites. A systematic metabolic pathway analysis was conducted to interpret the biological roles of these biomarkers and explore their relevance to CCA progression.</p><p><strong>Results: </strong>A total of 25 marker metabolites were identified, including lysophosphatidylcholines (LysoPCs), phosphatidylcholines (PCs), organic acids, sphinganine, and ketoleucine. These metabolites effectively distinguished CCA patients from healthy controls, with an AUC of 0.995 for increased biomarkers and 0.992 for decreased biomarkers in positive mode. In negative mode, the AUC for increased and decreased biomarkers was 0.899 and 0.976, respectively. The metabolic pathway analysis revealed critical biological functions linked to these biomarkers, offering insights into the molecular mechanisms underlying CCA initiation and progression.</p><p><strong>Conclusion: </strong>This study identifies novel metabolic biomarkers for the early diagnosis of CCA and provides a deeper understanding of the metabolic alterations associated with the disease. These findings could contribute to the development of diagnostic strategies and therapeutic interventions for CCA.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1549223"},"PeriodicalIF":3.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXOs and their roles in acute and chronic neurological disorders.","authors":"Yasin Asadi, Rozenn K Moundounga, Anand Chakroborty, Augustina Pokokiri, Hongmin Wang","doi":"10.3389/fmolb.2025.1538472","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1538472","url":null,"abstract":"<p><p>The forkhead family of transcription factors of class O (FOXOs) consisting of four functionally related proteins, FOXO1, FOXO3, FOXO4, and FOXO6, are mammalian homologs of daf-16 in <i>Caenorhabditis elegans</i> and were previously identified as tumor suppressors, oxidative stress sensors, and cell survival modulators. Under normal physiological conditions, FOXO protein activities are negatively regulated by phosphorylation via the phosphoinositide 3-kinase (PI3K)-Akt pathway, a well-known cell survival pathway: Akt phosphorylates FOXOs to inactivate their transcriptional activity by relocalizing FOXOs from the nucleus to the cytoplasm for degradation. However, under oxidative stress or absent the cellular survival drive of growth factors, FOXO proteins translocate to the nucleus and upregulate a series of target genes, thereby promoting cell growth arrest and cell death and altering mitochondrial homeostasis. FOXO gene expression is also regulated by other transcriptional factors such as p53 or autoregulation by their activities and end products. Here we summarize the structure, posttranslational modifications, and translocation of FOXOs linking to their transcriptional control of cellular functions, survival, and death, emphasizing their role in regulating the cellular response to some acute insults and chronic neurological disorders. This review will conclude with a brief section on potential therapeutic interventions that can be used to modulate FOXOs' activities when treating acute and chronic neurological disorders.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1538472"},"PeriodicalIF":3.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated multi-omics analysis reveals the functional and prognostic significance of lactylation-related gene PRDX1 in breast cancer.","authors":"Qinqing Wu, Heng Cao, Jiangdong Jin, Dongxu Ma, Yixiao Niu, Yanping Yu, Xiang Wang, Yiqin Xia","doi":"10.3389/fmolb.2025.1580622","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1580622","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BRCA) is a significant threat to women's health worldwide, and its progression is closely associated with the tumor microenvironment and gene regulation. Lactylation modification, as a key epigenetic mechanism in cancer biology, has not yet been fully elucidated in the context of BRCA. This study examines the regulatory mechanisms of lactylation-related genes (LRGs), specifically PRDX1, and their prognostic significance in BRCA.</p><p><strong>Methods: </strong>We integrated data from multiple databases, including Genome-Wide Association Study (GWAS) summary statistics, single-cell RNA sequencing, spatial transcriptomics, and bulk RNA sequencing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Using Summary-based Mendelian Randomization (SMR) analysis, we identified LRGs associated with BRCA and comprehensively analysed the expression patterns of PRDX1, cell-cell communication networks, and spatial heterogeneity. Furthermore, we constructed and validated a prognostic model based on the gene expression profile of PRDX1-positive monocytes, evaluating it through Cox regression and LASSO regression analyses.</p><p><strong>Results: </strong>PRDX1 was identified as a key LRG significantly associated with BRCA risk (p_SMR = 0.0026). Single-cell RNA sequencing analysis revealed a significant upregulation of PRDX1 expression in monocytes, with enhanced cell-cell communication between PRDX1-positive monocytes and fibroblasts. Spatial transcriptomics analysis uncovered heterogeneous expression of PRDX1 in the tumor nest regions, highlighting the spatial interaction between PRDX1-positive monocytes and fibroblasts. The prognostic model constructed based on the gene expression profile of PRDX1-positive monocytes demonstrated high accuracy in predicting patient survival in both the training and validation cohorts. High-risk patients exhibited immune-suppressive microenvironment characteristics, including reduced immune cell infiltration and upregulation of immune checkpoint gene expression.</p><p><strong>Conclusion: </strong>This study reveals the key role of PRDX1 in BRCA progression, mainly through the regulation of the tumor microenvironment and immune escape mechanisms. The survival prediction model based on PRDX1 shows robust prognostic potential, and future research should focus on integrating PRDX1 with other biomarkers to enhance the precision of personalised medicine.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1580622"},"PeriodicalIF":3.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Crosstalk between metabolism and immunity.","authors":"Jie Xiong","doi":"10.3389/fmolb.2025.1599219","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1599219","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1599219"},"PeriodicalIF":3.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Live cell optical super-resolution microscopy of dystroglycan mutants as a model for dystroglycanopathies in multiple cell lines.","authors":"Francesca Sciandra, Manuela Bozzi, Alina Witt, Paul Goffing, Sonia Covaceuszach, Sandra Blaess, Alberto Cassetta, Maria Giulia Bigotti, Thomas Huser, Andrea Brancaccio, Wolfgang Hübner","doi":"10.3389/fmolb.2025.1558170","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1558170","url":null,"abstract":"<p><strong>Introduction: </strong>Dystroglycan (DG) is an adhesion complex comprising two subunits, α-DG and β-DG, which interact non-covalently at the plasma membrane. As a component of the dystrophin-glycoprotein complex DGC, DG plays a crucial role in linking the cytoskeleton to the surrounding basement membranes. Rare primary point mutations in the <i>DAG1</i> gene have been identified in patients with various forms of neuromuscular dystrophy, ranging in phenotype from mild to severe.</p><p><strong>Methods: </strong>To gain a deeper understanding of the molecular mechanisms underlying these pathologies, we have designed a series of chimeric GFP-tagged full-length α/β-DG constructs and expressed them in three different cell lines (U-2OS, HEK-293T and C2C12). Wild-type DG constructs were compared to their counterparts carrying pathologic missense mutations previously described in patients, namely, L84F, T190M and C667F and with the mutant I591D, i.e., the topological equivalent of V567D identified in zebrafish.</p><p><strong>Results: </strong>Live super-resolution fluorescence microscopy showed that the C667F mutant is retained within the ER/Golgi while the T190M and wild-type proteins are correctly localized to the plasma membrane in all 3 cell lines. The L84F mutant exhibits a delay in trafficking to the plasma membrane in two of the cell lines, while localizing strongly at the plasma membrane in the high-expression HEK-293T cells. Similarly, the I591D mutant accumulated at the plasma membrane in the HEK-293T cells, in contrast to the clear retention in the endoplasmic reticulum/Golgi apparatus observed in U-2OS and C2C12 cells.</p><p><strong>Discussion: </strong>Our data demonstrate the importance of using a range of different cell lines for a comprehensive study of DG mutants or variants by live cell optical super-resolution microscopy.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1558170"},"PeriodicalIF":3.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paritaprevir as a pan-antiviral against different flaviviruses.","authors":"R P Yadav, N R Jena","doi":"10.3389/fmolb.2025.1524951","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1524951","url":null,"abstract":"<p><strong>Introduction: </strong>The flavivirus infections caused by the Zika virus (ZIKV), Dengue virus (DENV), and West Nile virus (WNV) cause mild to serious pathological conditions, such as fever, joint pain, shock, internal bleeding, organ failure, nausea, breathlessness, brain tissue damage, neurodegenerative diseases, and deaths. As currently no efficient vaccine or drug is available to prevent or treat these diseases in humans, it is essential to identify potential drug-like molecules to treat these diseases. For these reasons, several known anti-viral drugs are repurposed against the proteases of ZIKV, WNV, and DENV to inhibit their activities.</p><p><strong>Methods: </strong>The GOLD 5.0 molecular docking program was used to dock 20 HIV and HCV drugs against the ZIKV protease. Based on docking scores, 5 drugs were found to bind to the ZIKV protease with high affinities. Subsequently, the AMBER ff14SB force field was employed to simulate these drug-bound complexes of ZIKV protease. The MM/PBSA free energy method was utilized to compute the binding free energies of these complexes. Consequently, the two best ZIKV protease inhibitors were repurposed against the proteases of DENV and WNV.</p><p><strong>Results and discussion: </strong>It is found that out of the 5 drugs, Ritonavir and Paritaprevir bind to the NS2B-NS3 protease of the ZIKV strongly with the Gibbs binding free energies (∆G_bind) of -17.44±3.18 kcal/mol and -14.25±3.11 kcal/mol respectively. Remarkably, Ritonavir binds to the ZIKV Protease about 12 kcal/mol more strongly compared to its binding to the HIV protease. It is further found that Paritaprevir binds to DENV and WNV proteases as strongly as it binds to the ZIKV protease. Hence it is proposed that Paritaprevir may act as a potent pan-antiviral against the Zika, West Nile, and Dengue viral diseases.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1524951"},"PeriodicalIF":3.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of sample stability for a broad panel of coagulation parameters and factor assays on the Cobas t 711 analyzer starting from fresh-never-frozen plasma.","authors":"Michael Hoffmann, Norbert Gottschalk, Philipp Huber, Vanessa Scheling, Nicole von Allmen, J Kolja Hegel","doi":"10.3389/fmolb.2025.1491239","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1491239","url":null,"abstract":"<p><strong>Background: </strong>Preanalytical procedures can affect the accuracy of coagulation assay results. Recommended plasma storage temperatures and durations need to be defined for individual coagulation assays. Here, we evaluated the effect of commonly applied plasma storage conditions for a broad panel of 23 basic coagulation parameters as well as specialized factor assays developed for the Cobas^® t 711 analyzer (Roche Diagnostics International Ltd., Rotkreuz, Switzerland).</p><p><strong>Methods: </strong>This single-center, prospective, observational study used anonymized, residual, platelet-poor plasma samples as well as pseudonymized plasma samples to obtain rare ranges of certain analytes. Fresh-never-frozen plasma samples processed within 4 h were tested in triplicate at time zero (t₀), with measurements repeated at various predefined timepoints after storage at 18-25°C, 2-8°C, or under freezing and deep freezing. Mean deviation from t₀, expressed as a percentage or as absolute change in signal at very low analyte levels, was assessed against predefined, assay-specific acceptance criteria for each analyte.</p><p><strong>Results: </strong>The sample stability results under the examined storage conditions for all 23 assays met or exceeded the requirements for routine laboratory coagulation testing and the respective acceptance criteria for each individual assay were fulfilled. Fresh-never-frozen samples were used to reflect real-life laboratory settings, enabling the early detection of out-of-specification results.</p><p><strong>Conclusion: </strong>Sample stability was determined for a broad panel of assays on the t 711 analyzer, for application in routine coagulation testing practice.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1491239"},"PeriodicalIF":3.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LT-YOLO: long-term temporal enhanced YOLO for stenosis detection on invasive coronary angiography.","authors":"Jiaxin Li, Xiang Tang, Xuesong Wang","doi":"10.3389/fmolb.2025.1558495","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1558495","url":null,"abstract":"<p><p>Coronary artery stenosis detection by invasive coronary angiography plays a pivotal role in computer-aided diagnosis and treatment. However, it faces the challenge of stenotic morphology confusion stemming from coronary-background similarity, varied morphology, and small-area stenoses. Furthermore, existing automated methods ignore long-temporal information mining. To address these limitations, this paper proposes a long-term temporal enhanced You Only Look Once (YOLO) method for automatic stenosis detection and assessment in invasive coronary angiography. Our approach integrates long-term temporal information and spatial information for stenosis detection with state-space models and YOLOv8. First, a spatial-aware backbone based on a dynamic Transformer and C2f Convolution of YOLOv8 combines the local and global feature extraction to distinguish the coronary regions from the background. Second, a spatial-temporal multi-level fusion neck integrates the long-term temporal and spatial features to handle varied stenotic morphology. Third, a detail-aware detection head leverages low-level information for accurate identification of small stenoses. Extensive experiments on 350 invasive coronary angiography (ICA) video sequences demonstrate the model's superior performance over seven state-of-the-art methods, particularly in detecting small stenoses (<50%), which were previously underexplored.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1558495"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}