Frontiers in Cell and Developmental Biology最新文献

{"title":"Tcirg1 deficiency delays osteoarthritis progression by impairing lysosome acidification and peripheral accumulation in osteoclasts.","authors":"Rui Sun, Yang Yang, Qi Ma, Gang Wu, Zhibin Lan, Di Xue, Zhirong Chen, Yajing Su, Zhaopu Tuo, Jiangbo Yan, Long Ma, Xin Zhao, Kuanmin Tian, Xiaoxin He, Ye Ma, Xue Lin, Qunhua Jin","doi":"10.3389/fcell.2025.1621648","DOIUrl":"10.3389/fcell.2025.1621648","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoarthritis (OA) is a chronic degenerative joint disease characterized by articular cartilage loss and aberrant subchondral bone remodeling. \"T-cell immune regulator 1\" (<i>Tcirg1</i>), which encodes the a3 subunit of the V-ATPase, has been demonstrated to inhibit the formation of large osteoclasts by reducing intracellular calcium oscillations. Mutations in the <i>Tcirg1</i> gene sequence have been associated with osteopetrosis by impairing lysosomal transport in osteoclasts. This study aims to assess the impact of <i>Tcirg1</i> on OA progression and to explore its therapeutic potential for the disease treatment.</p><p><strong>Methods: </strong>Proteomic comparison of weight-bearing region (WBR) <i>versus</i> non-weight-bearing region (NWBR) of the subchondral bone was performed in 20 OA patients undergoing total knee arthroplasty. OA was then surgically induced in wild-type and Tcirg1-knockout mice by destabilization of the medial meniscus; disease severity and subchondral bone architecture were evaluated by histology and micro-CT. <i>In vitro</i>, primary bone marrow macrophages were differentiated into osteoclasts to assess the role of Tcirg1 in osteoclastogenesis, focusing on cell fusion, bone resorption, and lysosome acidification and distribution.</p><p><strong>Results and discussion: </strong>Proteomic analysis revealed that TCIRG1 was significantly upregulated in the WBR compared to NWBR of subchondral bone in OA patients, with functional enrichment analysis indicating TCIRG1 correlation with lysosome-related biological processes. In the murine OA model, Tcirg1 expression increased in parallel with osteoclast activity, peaking at 4 weeks post-surgery, which coincided with severe subchondral bone loss. <i>Tcirg1</i> deficiency in knockout mice delayed OA progression, as evidenced by reduced cartilage damage, improved subchondral bone mass, and decreased osteoclast activity. <i>In vitro</i>, Tcirg1 expression increased during osteoclast differentiation, and its knockdown inhibited osteoclast fusion and bone resorption by impairing lysosome acidification and peripheral accumulation.</p><p><strong>Conclusion: </strong>Tcirg1 regulates lysosome acidification and peripheral accumulation, thereby influencing osteoclast activity in the subchondral bone. Given that <i>Tcirg1</i> knockdown was found to slow down the progression of OA, targeting Tcirg1 may serve as a potential therapeutic strategy for treating OA.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1621648"},"PeriodicalIF":4.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: Studying rare diseases using induced pluripotent stem cell (iPSC)-based model systems.","authors":"Kevin R Francis, Guokai Chen, Erkan Kiris","doi":"10.3389/fcell.2025.1686438","DOIUrl":"10.3389/fcell.2025.1686438","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1686438"},"PeriodicalIF":4.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 metabolomics and network pharmacology to investigate the anti-hyperlipidemia effect of geniposidic acid on high-fat diet induced mice.","authors":"Ruiting Tang, Kun Li, Mengting Liang, Pengwei Wang, Zeyun Li","doi":"10.3389/fcell.2025.1655114","DOIUrl":"10.3389/fcell.2025.1655114","url":null,"abstract":"<p><strong>Background: </strong>Geniposidic acid (GPA) has been reported to possess hypoglycemic, hypolipidemic, and choleretic properties. However, its efficacy against hyperlipidemia and the associated mechanisms remain inadequately defined.</p><p><strong>Methods: </strong>A hyperlipidemia model was established in mice using a high-fat diet, followed by a 12-week intervention with GPA or lovastatin (positive control). Serum biochemical parameters and Oil Red O staining were assessed to evaluate lipid-lowering effects. Furthermore, NMR- and MS-based metabolomics, network pharmacology, and molecular docking approaches were employed to explore the underlying mechanisms.</p><p><strong>Results: </strong>Biochemical analysis confirmed the lipid-lowering efficacy of GPA. Urinary metabolomics revealed that both GPA and lovastatin restored disturbed metabolic profiles, notably involving the TCA cycle, glycolysis, amino acid metabolism, and ketone body synthesis. Over 40 differential metabolites were identified, constructing a comprehensive metabolic network. Network pharmacology further enriched relevant metabolic pathways and screened key targets. Molecular docking demonstrated strong binding affinities between GPA and several core proteins, including ALB, CAT, ACACA, ACHE, and SOD1, suggesting these may be potential therapeutic targets.</p><p><strong>Conclusion: </strong>This study confirmed the anti-hyperlipidemic efficacy of GPA and, through integrated metabolomics and target prediction, elucidated its potential mechanisms of action. These findings provide a scientific basis for further research and offer a promising strategy for the development of novel antihyperlipidemic agents.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1655114"},"PeriodicalIF":4.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m6A: a novel strategy for osteoporosis treatment.","authors":"Chunlu Yan, Xiaolong Xiao, Fan Yang, Yangyang Shi, Qiao Wan, Yan Zhang, Fangyu An","doi":"10.3389/fcell.2025.1603068","DOIUrl":"10.3389/fcell.2025.1603068","url":null,"abstract":"<p><p>Osteoporosis (OP) is a systemic metabolic disease characterised by increased bone fragility, with bone loss being the primary cause of its onset and progression. Regulating the dynamic balance between osteoblast (OB) formation and osteoclast-mediated bone resorption is crucial for preventing bone loss in OP. N6-methyladenosine (m6A), the most abundant and common RNA modification, is regulated by various proteins, including m6A methyltransferases, demethylases, and binding proteins. m6A methylation plays a key role in bone metabolism in OP, influencing the osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs), the osteogenic differentiation and bone formation capacity of OBs, as well as osteoclastic differentiation and resorptive activity. However, the specific molecular mechanisms through which m6A methylation regulates bone metabolism in OP remain incompletely understood. In this review, we comprehensively discuss the structure and function of m6A and summarise the roles of m6A methyltransferases, demethylases, and binding proteins. We also examine the regulatory mechanisms of m6A in MSCs, OBs, and osteoclasts, and discuss associated targeted therapies. This overview of the research on m6A is expected to highlight valuable insights and the translational potential for developing treatment strategies for OP.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1603068"},"PeriodicalIF":4.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay of replication stress response and immune microenvironment in high-grade serous ovarian cancer.","authors":"Laura Venegas, Stephanie Lheureux","doi":"10.3389/fcell.2025.1638964","DOIUrl":"10.3389/fcell.2025.1638964","url":null,"abstract":"<p><p>High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy. Therapeutic options remain limited for patients lacking predictive biomarkers, particularly those with BRCA wild-type tumors or those who have acquired resistance to both PARP inhibitors and platinum-based chemotherapy. Replication stress, TP53 mutations, and genomic instability characterize HGSOC. The cellular response to replication stress is primarily mediated by checkpoint kinases; however, this mechanism is frequently impaired in tumor cells. Consequently, cancer cells become increasingly dependent on the replication stress response (RSR) pathway for survival, and susceptible to therapies targeting the ATR-CHK1-WEE1 axis-a key regulator of genomic integrity. Inhibition of these checkpoint kinases can disrupt cell cycle control, inducing mitotic catastrophe and subsequent cancer cell death. Another defining feature of HGSOC is its immunosuppressive tumor microenvironment (TME), which has limited the efficacy of immune checkpoint inhibitors. Emerging evidence suggests that inhibition of the RSR pathway may not only exploit intrinsic tumor vulnerabilities but also modulate the TME to enhance anti-tumor immune responses. This provides rationale for combination approaches integrating RSR pathway inhibitors with innovative immune checkpoint blockade (ICB). This review examines the mechanistic rationale and therapeutic potential of such combinations, drawing on both preclinical and clinical data.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1638964"},"PeriodicalIF":4.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis and bone metabolic diseases: the dual regulatory role of the Nrf2/HO-1 signaling axis.","authors":"Wei Nan, Wen-Ming Zhou, Jian-Lan Zi, Yong-Qiang Shi, Yan-Bo Dong, Wei Song, Yan-Chao Ma, Hai-Hong Zhang","doi":"10.3389/fcell.2025.1615197","DOIUrl":"10.3389/fcell.2025.1615197","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a pivotal mechanism in bone disorders including osteoporosis and osteonecrosis. The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling axis plays a paradoxical role-contributing to cytoprotection under oxidative stress, yet potentially promoting ferroptosis through excessive iron accumulation. This review summarizes how the Nrf2/HO-1 pathway modulates ferroptosis across osteoblasts, osteoclasts, and osteocytes, and its impact on bone homeostasis. We explore the pathway's involvement in the shift from physiological bone remodeling to pathological bone loss. Given its dual role, the Nrf2/HO-1 axis represents both a challenge and an opportunity for therapeutic intervention. Understanding its context-specific functions is essential for developing precise, ferroptosis-targeted strategies in bone disease treatment.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1615197"},"PeriodicalIF":4.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amelioration of pregnancy outcomes in a pregnant rat model with deep venous thrombosis following the transplantation of bone marrow mesenchymal stem cells.","authors":"Yuanyuan Xie, Junrong Zhang, Rong Du, Jingjing Ji, Jingjing Lu, Haoxuan Li, Yunzhao Xu, Yuquan Zhang, Xi Cheng","doi":"10.3389/fcell.2025.1650614","DOIUrl":"10.3389/fcell.2025.1650614","url":null,"abstract":"<p><strong>Objective: </strong>We investigated the effects of bone marrow mesenchymal stem cells (BM-MSCs) on pregnancy outcomes in pregnant Sprague-Dawley rats with deep venous thrombosis (DVT) and explored the potential mechanisms involved.</p><p><strong>Methods: </strong>Eighteen pregnant rats were randomly divided into three groups: sham, DVT and BM-MSCs. The BM-MSCs were transfected with lentivirus carrying luciferase and cell membrane staining reagent CM-Dil to analyze the location and survival of BM-MSCs <i>in vivo</i>. We also compared the weight and length of the thrombus, the embryo absorption rate, the complete blood count, coagulation function, and D-dimer concentration of pregnant rats between the groups. Thereafter, placental blood flow was monitored by Doppler ultrasound and the number of placental blood vessels was determined by CD31 staining 7 days following BM-MSC transplantation. Finally, the expression of placental growth factor (PlGF), vascular endothelial growth factor A (VEGFA), soluble fms-like tyrosine kinase 1 (sFlt1), VEGF receptor 2 (VEGFR2) both in mRNA and protein levels were detected.</p><p><strong>Results: </strong>Reduced thrombus and improved pregnancy outcomes were observed in the BM-MSCs group. Furthermore, BM-MSCs survived and migrated to the lungs, liver, spleen, and thrombotic tissues, rather than the placenta. Doppler ultrasound indicated insufficient placental perfusion in the DVT group, which was reversed by the transplantation of BM-MSCs. BM-MSCs promoted placental angiogenesis by upregulating VEGFA and VEGFR2, and by reducing sFlt1 protein levels in the placenta.</p><p><strong>Conclusion: </strong>Our analysis suggested that BM-MSCs improve pregnancy outcomes associated with obstetric DVT by alleviating placental hypoperfusion and regulating the balance of placental pro-/anti-angiogenic factors.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1650614"},"PeriodicalIF":4.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-transcriptomics analysis of ferroptosis related genes reveals CAFs exosomal COX4I2 as a novel therapeutic target in osteosarcoma.","authors":"Xiaoying Niu, Xinxin Zhang, Zhongyi Li, Wen Tian","doi":"10.3389/fcell.2025.1620648","DOIUrl":"10.3389/fcell.2025.1620648","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma is a primary malignant tumor, characterized by its high incidence and recurrence rate in children and adolescents. Ferroptosis, an iron-dependent form of regulated cell death, has recently been recognized as a potential therapeutic vulnerability in cancer treatment. However, its prognostic significance and underlying regulatory mechanisms in osteosarcoma remain largely unexplored.</p><p><strong>Materials and methods: </strong>We constructed a prognostic model based on 12 ferroptosis-related genes using LASSO regression and validated across independent GEO cohorts (GSE21257 and GSE39055). We identified hub genes via machine learning algorithms (SVM, RF, XGBoost, BORUTA) and single-cell RNA sequencing. The exosomal transfer of COX4I2 protein from CAFs to 143B osteosarcoma cells was evaluated by Western blot, confocal microscopy, and transmission electron microscopy. Ferroptosis indicators, including Fe²⁺, MDA, ACSL4, and ROS levels, were assessed <i>in vitro</i>. We performed tumorigenicity assays <i>in vivo</i> in nude mice to validate biological function.</p><p><strong>Results: </strong>The ferroptosis-based risk model exhibited robust prognostic performance. We identified COX4I2 as a stromal hub gene, highly enriched in cancer-associated fibroblasts (CAFs). Functional experiments demonstrated that exosome-mediated delivery of COX4I2 suppressed ferroptosis in osteosarcoma cells and enhancd cell proliferation and mitochondrial integrity. Studies <i>in vivo</i> further revealed that overexpression of exosomal COX4I2 markedly promoted tumor growth while inhibiting ferroptosis.</p><p><strong>Conclusion: </strong>These findings underscore the potential of exosomal COX4I2 as a biomarker and therapeutic target for ferroptosis-based interventions in osteosarcoma.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1620648"},"PeriodicalIF":4.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay of KIR2DL5, nitric oxide, and tobacco smoking in predisposition to bladder cancer.","authors":"Inmaculada Ruiz-Lorente, Lourdes Gimeno, Alicia López-Abad, Pedro López Cubillana, Tomás Fernández Aparicio, Lucas Jesús Asensio Egea, Juan Moreno Avilés, Gloria Doñate Iñiguez, Pablo Luis Guzmán Martínez-Valls, Gerardo Server, Belén Ferri, José Antonio Campillo, Francisco Galindo, Francisco Boix, María Victoria Martínez-Sánchez, María Dolores Martínez-Hernández, Alfredo Minguela","doi":"10.3389/fcell.2025.1632101","DOIUrl":"10.3389/fcell.2025.1632101","url":null,"abstract":"<p><strong>Introduction: </strong>Tobacco smoking is the most significant risk factor for bladder cancer (BC), followed by other environmental and dietary exposures. However, major genetic determinants remain unidentified. The objective of this work was to investigate the potential association of killer-cell immunoglobulin-like receptor 2DL5 (KIR2DL5) with BC risk, its interaction with tobacco smoking, and the underlying immune mechanisms.</p><p><strong>Methods: </strong>This case-control study analyzed KIR genotype in patients with BC (n = 325), as well as in healthy controls (HC, n = 925) and patients with other cancers (n = 862) as control groups. Immune assays assessed proliferation, cytotoxicity, cytokine, and intracellular nitric oxide (icNO) production by NK and T cells after anti-CD3/CD28 or <i>Bacillus</i> Calmette-Guérin (BCG) stimulation in 24 donors stratified by KIR2DL5 genotype. Multivariate logistic regression was used to evaluate BC predisposition.</p><p><strong>Results: </strong>The frequency of KIR2DL5 was higher in BC patients than in HC (64.6% vs. 53.6%, p = 0.004). Linear regression analysis revealed that, independent of other aKIRs within the B haplotype, KIR2DL5 was associated with BC susceptibility (HR = -1.167, p = 0.050), alongside other significant factors such as sex (HR = -1.465, p < 0.001), age (HR = -0.181, p < 0.001), and tobacco smoking (HR = -2.454, p < 0.001). The frequency of KIR2DL5 was higher among non-smokers compared to smokers in both healthy controls (61.4% vs. 44.6%, p < 0.05) and BC patients (72.9% vs. 60.8%, p < 0.05). Among non-smoking BC patients, KIR2DL5 was more frequently observed in small-sized (<3 cm), solid-pattern, non-muscle-invasive BC cases. Immune profiling revealed that KIR2DL5 was associated with increased icNO production by NK and T cells but showed no association with proliferation, cytokine secretion, or cytotoxicity.</p><p><strong>Discussion: </strong>KIR2DL5 is independently associated with BC, regardless of age, sex, or tobacco smoking status. While the immunological mechanisms remain unclear, enhanced nitric oxide production by immune effector cells may play a role in this association.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1632101"},"PeriodicalIF":4.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence applications facilitate decision-making in cataract surgery for highly myopic patients.","authors":"Kaimeng Su, Wenwen He, Haifeng Jiang, Keke Zhang, Jiao Qi, Jiaqi Meng, Yu Du, Kaiwen Cheng, Xiaoxin Hu, Dongling Guo, Haike Guo, Yong Wang, Yi Lu, Xiangjia Zhu","doi":"10.3389/fcell.2025.1613634","DOIUrl":"10.3389/fcell.2025.1613634","url":null,"abstract":"<p><strong>Background: </strong>Surgical decision-making for highly myopic cataracts requires a high level of expertise. We, therefore, aimed to develop a preliminary artificial intelligence (AI) model for surgical decision-making in highly myopic cataracts, based on previous deep learning models.</p><p><strong>Materials and methods: </strong>We first established a highly myopic cataract decision-making AI model by integrating cataract grading and postoperative visual acuity prediction models of highly myopic eyes, which we had developed previously, with surgical decision logic. The outcomes of surgical decision-making were classified into four categories: surgery not advised, cataract surgery recommended, retinal surgery recommended, and combined cataract-retinal surgery recommended. The gold standard for surgical decision is defined as the decision jointly made by two professional ophthalmologists together (X.Z. and Y.W.). If the decision-makings regarding highly myopic cataract surgery were not fully consistent, a final judgment was made by a third expert (Y.L.). Subsequently, we evaluated the accuracy of AI model's surgical decision-making against the gold standard and doctors at different levels, using both internal (107 highly myopic eyes from Eye and ENT Hospital, Fudan University) and external (55 highly myopic eyes from Wuhan Aier Eye Hospital) test datasets.</p><p><strong>Results: </strong>In the internal and external datasets, according to the Lens Opacities Classification System (LOCS) III international standards for cataract grading, 99.07% and 87.27% of automatic nuclear grading, along with 88.79% and 61.82% of automatic cortical grading, respectively, had an absolute prediction error of ≤1.0 compared with the gold standard. The mean postoperative visual acuity prediction error was 0.1560 and 0.3057 logMAR in the internal and external datasets, respectively. Finally, the consistency of the AI model's surgical decisions with the gold standard for highly myopic cataract patients in the internal and external datasets was 96.26% and 81.82%, respectively. AI demonstrated substantial agreement with the gold standard (Kappa value = 0.811 and 0.556 in the internal and external datasets, respectively).</p><p><strong>Conclusion: </strong>The AI decision-making model for highly myopic cataracts, based on two deep learning models, demonstrated good performance and may assist doctors in complex surgical decision-making for highly myopic cataracts.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1613634"},"PeriodicalIF":4.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}