Interdisciplinary Medicine最新文献

{"title":"Holistic bone developing microenvironment engineered apoptotic extracellular vesicles recapitulate multidimensional developmental signatures in adult and senile bone repair","authors":"Xiaoran Yu,&nbsp;Jieyun Xu,&nbsp;Yuan Zhao,&nbsp;Xinyu Guo,&nbsp;Hongcheng Chen,&nbsp;Junlong Xue,&nbsp;Yong Ao,&nbsp;Linjun Zhang,&nbsp;Xiaomeng Gao,&nbsp;Xueli Mao,&nbsp;Songtao Shi,&nbsp;Zetao Chen","doi":"10.1002/inmd.70109","DOIUrl":"https://doi.org/10.1002/inmd.70109","url":null,"abstract":"<p>Owing to the rich repertoire of bioactive cargos inherited from parent cells, apoptotic extracellular vesicles (ApoEVs) have emerged as powerful biological agents in regenerative medicine. To augment ApoEVs regenerative potency, microenvironment-engineered ApoEVs (ME-ApoEVs) have been proposed, which mainly focused on embedding a single microenvironment factor within the vesicle cargo. Since the microenvironment operates as a system composed of multiple factors that collectively govern regeneration, we introduce a novel holistic microenvironment-engineered ApoEVs (hME-ApoEVs) for superior ME-ApoEVs. To validate the hME-ApoEV concept, we endowed ApoEV with a bone developing microenvironment, aiming to recapitulate developing features in adult bone repair. In the study, the developing bone microenvironment was first identified as an M2a-like macrophage driven immune microenvironment accounting for multidimensional developmental signatures. Based on these findings, we successfully fabricated hME-ApoEVs via stimulating the M2a-like developing microenvironment in vitro and confirmed its recapitulation of developmental signatures. Thirdly, we found that hME-ApoEVs recapitulated multidimensional developmental signatures in bone marrow-derived mesenchymal stem cell (BMSC) likely through activating Wnt/β-catenin signaling pathway. Finally, hME-ApoEVs were verified to retain development signatures in adult and senile cranial bone repair, improving bone regeneration. Instead of engineering a single microenvironment factor, the hME-ApoEV strategy effectively recapitulated the key features of the desired microenvironment in themselves, target cells and animal models via imprinting key features onto a simulated microenvironment generated by key cells in vitro. This strategy equips ApoEVs with complex microenvironment cues, amplifying their potency in regeneration medicine and providing a promising foundation for future microenvironment-inspired ApoEV engineering strategies.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148532787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tiny carriers, big impact: How Fusobacterium nucleatum extracellular vesicles drive oral diseases and beyond","authors":"Rongyang Ma,&nbsp;Jiahui Huang,&nbsp;Yitong Chen,&nbsp;Haoxuan Wang,&nbsp;Hang Zou,&nbsp;Wanghong Zhao,&nbsp;Zilong Deng","doi":"10.1002/inmd.70131","DOIUrl":"https://doi.org/10.1002/inmd.70131","url":null,"abstract":"<p><i>Fusobacterium nucleatum</i> (<i>F</i>. <i>nucleatum</i>), recognized for its opportunistic pathogenicity, is a prevalent pathogen implicated in several diseases. Emerging evidence highlights the crucial role of <i>F</i>. <i>nucleatum</i>–derived extracellular vesicles (<i>F</i>. <i>nucleatum</i> EVs) in mediating virulence and serving as carriers of diverse bioactive components that facilitate host–pathogen interactions. <i>F</i>. <i>nucleatum</i> EVs can disseminate from the oral cavity to the gastrointestinal tract and joints, promoting the onset and progression of oral inflammatory diseases, head and neck squamous cell carcinoma, rheumatoid arthritis, inflammatory bowel disease, and colorectal cancer through various signaling pathways. A deeper understanding of <i>F</i>. <i>nucleatum</i> EVs will advance the understanding of the pathogenesis of related diseases and inform the development of effective infection control strategies. This review systematically summarizes recent progress in the biogenesis, molecular composition, and pathogenic roles of <i>F</i>. <i>nucleatum</i> EVs across various disease contexts and evaluates potential strategies for the diagnosis, treatment, and management of conditions involving <i>F</i>. <i>nucleatum</i> and its EVs.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning-based prediction of cervical lymph node metastasis and genetic alterations from whole-slide images of thyroid cancer frozen sections","authors":"Mingxing Qiu,&nbsp;Jinbang Li,&nbsp;Shujing Guo,&nbsp;Danyi Li,&nbsp;Chengyu Lu,&nbsp;Chenglong Zhao,&nbsp;Jiankun He,&nbsp;Hanxi Wang,&nbsp;Qiao Bai,&nbsp;Aihetaimu Aimaier,&nbsp;Zhijian Cen,&nbsp;Rui Mao,&nbsp;Zimo Ye,&nbsp;Jiaxue Zang,&nbsp;Zhining Zhuo,&nbsp;Lijuan Qu,&nbsp;Yueping Liu,&nbsp;Jing Cui,&nbsp;Xiaohong Yao,&nbsp;Xiuwu Bian,&nbsp;Li Liang","doi":"10.1002/inmd.70098","DOIUrl":"https://doi.org/10.1002/inmd.70098","url":null,"abstract":"<p>Precise evaluation of cervical lymph node metastasis (CLNM) and genetic mutations (BRAF^V600E/TERT promoter, TERTp) is pivotal for tailoring surgical and prognostic evaluation and adjuvant strategies in thyroid cancer (TC). Although current methods have limitations, we aim to develop deep learning (DL) models to predict CLNM and genetic mutations from TC frozen sections. We developed a DL framework using 2499 frozen-section whole-slide images from 2176 TC patients across five centers. The model was trained with a transfer learning-based feature extractor and an attention-based multiple instance learning (MIL) classifier, and validated on both internal and external cohorts. StyleGAN3-based data augmentation was employed to tackle class imbalance for TERTp prediction, while interpretability was assessed via attention heatmaps and Leiden clustering. The CLNM prediction model achieved a patient-level AUROC of 0.918 internally and 0.803–0.885 across three external validation datasets. For BRAF^V600E prediction, AUROCs attained 0.814 internally and spanned 0.750––0.811 in external validation. In TERTp mutation prediction, GAN-based augmentation increased the AUROC to 0.804 (internal) and 0.732 (external), up from 0.782 and 0.724, respectively. Attention maps visualized CLNM correlations with invasive tumor margins, while mutations localized to specific cellular morphology features. Our DL models accurately predict CLNM and genetic mutations from TC frozen sections, potentially reducing unnecessary procedures and providing a rapid alternative to traditional molecular testing.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A compendium of extracellular vesicle biogenesis inhibitors: From bench to bedside","authors":"Stefano Vecchione,&nbsp;Ana Talamillo,&nbsp;Juan M. Falcón-Pérez","doi":"10.1002/inmd.70144","DOIUrl":"https://doi.org/10.1002/inmd.70144","url":null,"abstract":"<p>Extracellular vesicles (EVs) are cell-derived particles delimited by a lipid bilayer and containing a wide variety of cargos that cannot replicate independently. Their key role as mediators of intercellular communication implicates them in a broad spectrum of physiological and pathological processes. In recent years, EVs have gained increasing attention as potential biomarkers, therapeutic targets and drugs delivery vehicles. However, the successful translation of EV-based strategies from bench to bedside requires a deeper understanding of EV composition and the biogenesis mechanisms. A particularly promising and actively investigated avenue in EV research is the targeted inhibition of EV biogenesis. Modulating these processes not only provides valuable tools for dissecting EV functions in vitro and in vivo, but also opens new therapeutic possibilities, especially in diseases where EVs contribute to pathogenesis, such as cancer, neurodegeneration, inflammation and infectious diseases. Identifying and characterizing compounds that interfere with EV biogenesis is therefore of high relevance, both for fundamental research and clinical applications. This review aims to contribute to the field by offering a comprehensive overview of the most studied EV inhibitors, highlighting their mechanisms of action, experimental utility, and potential for therapeutic exploitation. Particular attention is given to their advantages and limitations as modulators of EV biogenesis, with the goal of guiding future research toward more effective and selective strategies.</p>","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 4","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/inmd.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 3","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148092252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 3","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148092253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 3","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148092250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 3","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148092251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ordered assembly of Cas12a for better performance of CRISPR/Cas system with application to the diagnosis of dental caries","authors":"Yining Zhao, Panpan Qiao, Yujing Zeng, Murtaza Sayed, Qin Mi, Juan Zhang, Genxi Li","doi":"10.1002/inmd.70146","DOIUrl":"https://doi.org/10.1002/inmd.70146","url":null,"abstract":"Abstract Dental caries is the most common chronic infectious disease among the world, which is mainly caused by Streptococcus mutans ( S. mutans ). Herein, a strategy is explored in this work based on tetrahedral DNA frameworks (TDFs)‐mediated Cas12a ordered assembly (TCOA) for the development of a new method to diagnose dental caries. Specifically, TDFs arrange Cas12a into a highly ordered assembly in a controllable manner, thereby conferring high catalytic efficiency to the protein. Meanwhile, the confined TDFs can maintain an appropriate spatial interval on the surface to prevent excessive local crowding of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a, ensuring efficient substrate diffusion across the interface. Thus, by immobilizing Cas12a orderly, the catalytic efficiency can be greatly enhanced through the formation of localized Cas12a hotspots, and the CRISPR/Cas system can be performed more perfectly. Moreover, the TCOA strategy can be used to sensitively analyze S. mutans with a detection limit as low as 16.59 CFU/mL without pre‐amplification steps. Consequently, with high reproducibility and stability, the TCOA strategy‐based method can be successfully applied to detect 120 clinical saliva samples, demonstrating its robust potential to be a simple, rapid, and highly sensitive diagnosis tool for dental caries.","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148305742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":100686,"journal":{"name":"Interdisciplinary Medicine","volume":"4 3","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148078114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}