21:T467,The imbalance between osteoblasts and osteoclasts is the cause of osteoporosis. Milk-derived extracellular vesicles (mEVs), excellent drug delivery nanocarriers, can promote bone formation and inhibit bone resorption. In this study, we conjugated bone-targeting peptide (AspSerSer, DSS)₆ to mEVs by click chemistry and then loaded with SRT2104, a SIRT1 (silent mating-type information regulation 2 homolog 1) agonist that was proofed to help reduce bone loss. The engineered (DSS)₆-mEV-SRT2104 had the intrinsic anti-osteoporosis function of mEVs and SRT2104 to reverse the imbalance in bone homeostasis by simultaneously regulating osteogenesis and osteoclastogenesis. Furthermore, we labelled mEVs with MnB nanoparticles that can be used for the in vivo magnetic resonance imaging (MRI) visualization. The obtained nanocomposites significantly prevented bone loss in osteoporosis mice and increased bone mineral density, exhibiting superior bone accumulation under MRI. We believe the proposed (DSS)₆-mEV-SRT2104/MnB provides a novel paradigm for osteoporosis treatment and monitoring.22:T4c3,Cardiac oxidative stress is a significant phenotype of myocardial infarction disease, a leading cause of global health threat. There is an urgent need to develop innovative therapies. Nanosized extracellular vesicle (nEV)-based therapy shows promise, yet real-time monitoring of cardiomyocyte responses to nEVs remains a challenge. In this study, a dynamic and label-free cardiomyocyte biosensing system using microelectrode arrays (MEAs) was constructed. Cardiomyocytes were cultured on MEA devices for electrophysiological signal detection and treated with nEVs from E. coli, gardenia, HEK293 cells, and mesenchymal stem cells (MSC), respectively. E. coli-nEVs and gardenia-nEVs induced severe paroxysmal fibrillation, revealing distinct biochemical communication compared to MSC-nEVs. Principal component analysis identified variations and correlations between nEV types. MSC-nEVs enhanced recovery without inducing arrhythmias in a H₂O₂-induced oxidative stress injury model. This study establishes a fundamental platform for assessing biochemical communication between nEVs and cardiomyocytes, offering new avenues for understanding nEVs' functions in the cardiovascular system.23:T4af,Psoriasis is a chronic inflammatory dermatosis driven by excessive activation of the immune system. Recent studies have demonstrated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) to psoriasis because of their immunomodulation functions. Yet, the outcome of MSC-EVs alone is still unsatisfactory and the underlying mechanisms are also unclear. Here, it is uncovered that arginase1 (Arg1)/polyamine is overexpressed in psoriasis patients and murine, inducing the in-situ accumulation of self-antigens. Engineered nor@MSC-EVs are fabricated by loading Arg1 inhibitor nor-NOHA into MSC-EVs for studying the therapeutic effect and mechanism of psoriasis. The nor@MSC-EVs exhibited profound suppression of the NF-κB signaling pathway by targeting Arg1/polyamine-mediated DCs/Th17 axis through scavenging self-antigens, resulting in superior mitigation of skin lesions and modulation of local and systemic metabolic and immunological disorders compared to the MSC-EVs and clinically used anti-IL17A both in vitro and in vivo. Together, the results highlight a novel perspective for psoriasis therapy by nor@MSC-EVs with broad clinical translational potential.

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