Accumulating evidence has demonstrated that apoptotic vesicles(apoVs)derived from mesenchymal stem cells(MSCs;MSC-apoVs)are vital for bone regeneration,and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs(such as exosomes).The osteoinductive effect of MSC-apoVs is attributed to their diverse contents,especially enriched proteins or microRNAs(miRNAs).To optimize their osteoinduction activity,it is necessary to determine the unique cargo profiles of MSC-apoVs.We previously established the protein landscape and identified proteins specific to MSC-apoVs.However,the features and functions of miRNAs enriched in MSC-apoVs are unclear.In this study,we compared MSCs,MSC-apoVs,and MSC-exosomes from two types of MSC.We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes,which we classified as apoV-specific miRNAs.Among these seven specific miRNAs,hsa-miR-4485-3p was the most abundant and stable.Next,we explored its function in apoV-mediated osteoinduction.Unexpectedly,hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway.Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs.Like releasing the brake,we acquired more powerful osteoinductive apoVs.In summary,we identified the miRNA cargos,including miRNAs specific to MSC-apoVs,and generated tailored apoVs with high osteoinduction activity,which is promising in apoV-based therapies for bone regeneration.

Accumulating evidence has demonstrated that apoptotic vesicles(apoVs)derived from mesenchymal stem cells(MSCs;MSC-apoVs)are vital for bone regeneration,and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs(such as exosomes).The osteoinductive effect of MSC-apoVs is attributed to their diverse contents,especially enriched proteins or microRNAs(miRNAs).To optimize their osteoinduction activity,it is necessary to determine the unique cargo profiles of MSC-apoVs.We previously established the protein landscape and identified proteins specific to MSC-apoVs.However,the features and functions of miRNAs enriched in MSC-apoVs are unclear.In this study,we compared MSCs,MSC-apoVs,and MSC-exosomes from two types of MSC.We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes,which we classified as apoV-specific miRNAs.Among these seven specific miRNAs,hsa-miR-4485-3p was the most abundant and stable.Next,we explored its function in apoV-mediated osteoinduction.Unexpectedly,hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway.Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs.Like releasing the brake,we acquired more powerful osteoinductive apoVs.In summary,we identified the miRNA cargos,including miRNAs specific to MSC-apoVs,and generated tailored apoVs with high osteoinduction activity,which is promising in apoV-based therapies for bone regeneration.

Objective: To evaluate the residual radioactivity after ¹³¹I treatment in postoperative inpatients with differentiated thyroid carcinoma (DTC) using service robot in nuclear medicine ward, and assess the time for patients to be released from isolation. Methods: From September 2017 to June 2018, 297 patients (94 males, 203 females, age: 19-80 years) with DTC who underwent ¹³¹I treatment after surgery were included. According to the purpose of treatment and the prescription dosage of ¹³¹I, patients were divided into 8 groups: 4 groups accepted ¹³¹I remnant ablation therapy (RAT) with different dosages, which were 3 700 MBq (RAT1, n=34), 4 440 MBq (RAT2, n=122), 5 550 MBq (RAT3, n=81) and 7 400 MBq (RAT4, n=27), respectively; 4 groups had ¹³¹I treatment for recurrent/metastatic lesions (RMLT), and the dosages were 3 700 MBq (n=1), 4 440 MBq (n=2), 5 550 MBq (n=14) and 7 400 MBq (n=16). At 4, 24, 48 and 72 h after ¹³¹I administration, the dose equivalent rates at 2 cm away from the patient′s neck and at 1 m away from the body were measured by the robot designed for nuclear medicine ward. Kruskal-Wallis rank sum test and Mann-Whitney U test were used to analyze the data. Results: Neck dose equivalent rates for patients with RAT at different time points (4, 24, 48 and 72 h) after ¹³¹I administration were significantly different among 4 groups (H values: 20.889-46.410, all P<0.05), as well as the body dose equivalent rates (H values: 27.181-35.497, all P<0.05). The neck dose equivalent rates at 24, 48 and 72 h after ¹³¹I administration were statistically different between group 3 and 4 for patients with RMLT (z values: 2.328-3.076, all P<0.05; data in group 1 and 2 were too limited to be compared), while there was no statistical difference for the body dose equivalent rates (z values: 0.333-1.621, all P>0.05). The radioactivity retention in patients decreased rapidly within 24 h, then slowed down gradually and became extremely low at 72 h. At 72 h after ¹³¹I administration, 96.6%(255/264) patients with RAT and 100%(33/33) patients with RMLT were lower than 23.3 μSv/h, which meant the patients could be discharged from hospitalization. Conclusions Nuclear medicine ward service robots may dynamically measure residual radioactivity in DTC patients who take ¹³¹I treatment, providing individualized isolation solutions.