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As membrane structural bodies secreted by cells, extracellular vesicles (EVs) have become a hot topic in the field of plant science in recent years. Plant-derived extracellular vesicles (PDEVs) play a key role in both plant physiological activities and the interaction between plants and the environment. These vesicles are involved in plant growth, development, and response to adversity by delivering signaling molecules, proteins, and other bioactive substances. Current studies have shown that PDEVs also exhibit promising potential for clinical applications, including as drug carriers, vaccine development, and biomarkers for disease diagnosis. In this paper, we review studies related to compositional characterization, isolation and purification methods, biological roles, and clinical applications of PDEVs. We aim to provide a systematic theoretical basis and practical guidance for future studies to promote their application in biomedical fields.

Extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication and have attracted considerable scientific interest in recent years owing to their critical roles in tumor immunity and drug resistance. This review offers a comprehensive overview of the mechanisms by which EVs function within the tumor microenvironment, focusing on their involvement in immune evasion, tumor progression, and the development of resistance to therapeutic agents. By summarizing recent research advances, this review highlights the potential of EVs as diagnostic biomarkers and therapeutic targets and emphasizes their significance in improving treatment efficacy and overcoming clinical resistance. This review also outlines future research directions to clarify the multifaceted roles of EVs in cancer biology and facilitate the development of novel therapeutic approaches to enhance patient outcomes.

Background The accuracy of the latest reasoning-enhanced large language models on national medical licensing examinations remains unknown, which is crucial for determining how close they are to serving as effective knowledge sources for medical education. This study aimed to evaluate the performance of four reasoning-enhanced large language models (LLMs)—GPT-5, Grok-4, Claude Opus 4.1, and Gemini 2.5 Pro—on the Japanese National Medical Examination (JNME), providing insights into their potential as educational resources and their future applicability in medical practice. Methods We evaluated LLM performance using the 2019 and 2025 JNME ( n  = 793). Questions were entered into each model with chain-of-thought prompting enabled. Accuracy was assessed overall and by question type. Incorrect responses were qualitatively reviewed by a licensed physician and a medical student. Results From highest to lowest, the overall accuracies of the four LLMs were 97.2% for Gemini 2.5 Pro, 96.3% for GPT-5, 96.1% for Claude Opus 4.1, and 95.6% for Grok-4, with no significant pairwise differences. For image-based and non-image-based items, Gemini 2.5 Pro achieved the highest accuracy of 96.1% and 97.6%, with no significant difference, whereas accuracy was significantly lower on image-based items for the other three LLMs. Across difficulty levels, Gemini 2.5 Pro again achieved the highest accuracy (98.4% for easy, 97.3% for moderate, and 93.2% for difficult items). Within each LLM, accuracy on difficult questions was significantly lower than on easy questions. Common error patterns included providing unnecessary additional options in single-choice questions, misdiagnosis of X-ray or computed tomography images (primarily due to confusion regarding left–right laterality), and difficulties in prioritizing appropriate actions in clinical questions with complex contextual information. Conclusions Four LLMs released in 2025 surpassed the 95% benchmark on the JNME, and their near-perfect (approximately 99%) performance on basic medical knowledge questions highlights substantial potential for use as learning resources in foundational medical education. Gemini 2.5 Pro demonstrated the most consistent performance across question types, while Grok-4 showed greater variability. The concentration of incorrectness in clinical questions indicates that LLMs still require substantial refinement and validation before their use can be extended to clinical reasoning or patient care.

As the world’s population ages, neurodegenerative diseases are becoming more widely acknowledged as serious global health and socioeconomic issues. Although many resources have been devoted to the research of these illnesses, little progress has been made in the creation of novel diagnostic and therapeutic approaches. Extracellular vesicles (EVs) are released by all cell types and contain proteins, microRNAs, mRNAs, and other biologically active molecules. EVs play an important role in intercellular communication as well as in the regulation of neuroinflammation. Determining the mechanisms by which EVs contribute to the pathogenesis of neurodegenerative diseases will aid in the development of new therapeutic approaches and diagnostic tools. Mesenchymal stem cells (MSCs) have been shown in studies to control immunological responses, promote the growth of new brain connections, promote the production of blood vessels, and heal damaged tissues. There is growing evidence that MSCs’ ability to treat patients is mostly due to the neurotrophic compounds they secrete through EVs. Since their tiny size allows them to pass through biological barriers and reach injured parts of the central nervous system, MSC-derived extracellular vesicles (MSC-EVs) retain many of the therapeutic qualities of their parent MSCs. This review discusses the role of EVs in neurodegenerative diseases and highlights the potential of MSC-EVs in the treatment of neurodegenerative diseases. The paper also examines the challenges that still need to be overcome and the prospects for using MSC-EVs to treat neurodegenerative illnesses.

Mesenchymal stem cells (MSCs) are currently being used in clinical trials for the treatment of a wide range of diseases and have a wide range of applications in the fields of tissue engineering and regeneration. Exosomes are extracellular vesicles containing a variety of components such as proteins, nucleic acids and lipids, which are widely present in biological fluids and have the functions of participating in intercellular information transfer, immune response and tissue repair, and can also be used as carriers to target and deliver tumors to improve therapeutic effects. Mesenchymal stem cell-derived Exosomes (MSC-Exos), which have the advantages of low immunogenicity and high tumor homing ability, have attracted much attention in targeted drug delivery. Here, we review the current knowledge on the involvement of MSC-Exos in tumor progression and their potential as drug delivery systems in targeted therapies. It also discusses the advantages and prospects of MSC-Exos as a drug carrier and the challenges that still need to be overcome.

To delineate the distinct immunometabolic perturbations in HIV-associated acute exacerbation of chronic obstructive pulmonary disease (HIV-AECOPD) and to identify circulating biomarkers predictive of short-term prognosis. An integrated proteomic and metabolomic discovery analysis was conducted on serum from patients with HIV-AECOPD, AECOPD alone, and healthy controls (n=5 per group). Key differentially expressed molecules were subsequently validated via targeted assays in a larger, independent cohort (n=20 per group). The prognostic value of validated biomarkers for 3-month poor outcomes was evaluated using a Random Forest model and receiver operating characteristic (ROC) curve analysis. Multi-omics discovery revealed a unique serum profile in HIV-AECOPD, characterized by dysregulated humoral immunity, complement activation, neutrophil extracellular trap formation, and metabolic reprogramming. Validation assays were performed for six candidate biomarkers (CRP, SAA, IgG, TG, C3, and C4). Among these, CRP emerged as the most important predictor of poor 3-month prognosis (Random Forest Mean Decrease Gini = 1.33), demonstrating significant predictive value (AUC = 0.8125, 95% CI: 0.628-0.997). This study defines a specific immunometabolic signature in HIV-AECOPD and nominates CRP as a potential biomarker for risk-stratifying patients at high risk of adverse short-term outcomes, offering both mechanistic insight and a candidate tool for clinical prognostication.

Rheumatoid arthritis (RA) is characterized by bone destruction in the afflicted joints, and during the process of bone destruction, osteoclasts play a crucial role. Tanshinone IIA (Tan IIA) has shown anti-inflammatory effects in RA. However, the exact molecular mechanisms by which it delays bone destruction remain largely unexplained. Here, we found that Tan IIA decreased the severity of and ameliorated bone loss in an AIA rat model. In vitro, Tan IIA inhibited RANKL-induced osteoclast differentiation. By activity-based protein analysis (ABPP) combined with LC‒MS/MS, we discovered that Tan IIA covalently binds to the lactate dehydrogenase subunit LDHC and inhibits its enzymatic activity. Moreover, we found that Tan IIA inhibits the generation of osteoclast-specific markers by reducing the accumulation of reactive oxygen species (ROS), thus reducing osteoclast differentiation. Finally, our results reveal that Tan IIA suppresses osteoclast differentiation via LDHC-mediated ROS generation in osteoclasts. Tan IIA can thus be regarded as an effective drug for the treatment of bone damage in RA.

Extracellular vesicles (EVs) are nano-sized vesicles secreted by living cells and ubiquitously present in body fluids. They carry molecular cargo-including proteins, nucleic acids, and lipids-that accurately mirrors the physiological and pathological state of their parent cells, offering a highly promising novel source of biomarkers for liquid biopsy. This review systematically summarizes the progress in biomarker discovery and application of EVs in major diseases such as cancer, neurological disorders, and cardiovascular diseases. It provides an in-depth analysis of the key technical bottlenecks in current EV isolation, characterization, and detection methodologies, and discusses the challenges related to standardization and clinical translation. Finally, the review outlines the broad future prospects in this field, including integrated multi-omics analysis based on EVs, and their potential for early diagnosis, real-time therapeutic monitoring, and prognostic assessment.

Extracellular vesicles (EVs), serving as promising novel biomarkers for diseases, demonstrate extensive potential applications in disease diagnosis, prognosis evaluation, and treatment monitoring. Currently, EVs have made substantial advancements in the areas of disease diagnosis, prognosis, and treatment. Nevertheless, for EVs to be fully integrated into clinical laboratories, ongoing efforts are required in multi-omics integration and big data analysis, the development of clinically applicable separation and detection technologies, the establishment of standardized quality systems, as well as clinical trials and regulatory approval processes. This paper reviews the current status of the application of extracellular vesicles in disease diagnosis, prognostic assessment, and treatment monitoring, analyzes the challenges facing current research, and discusses future trends.

Esophageal cancer (EC) is a global health challenge with limited treatment and low efficacy. The role of vascular endothelial growth factor receptor 2 (VEGFR2) in EC has attracted significant attention. In this study, we found that anlotinib, an oral VEGFR2 inhibitor, exhibited a strong inhibitory effect on EC in vitro and in vivo. Moreover, VEGFR2 expression was positively correlated with infiltration levels of macrophages and dendritic cells (DCs) via comprehensive analysis and molecular experiment. Together, we evaluated the correlations between VEGFR2 expression and immune infiltration and explored the role of anlotinib on EC, providing a potential strategy for the intervention of EC.