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| 1 | Exercise promotes angiogenesis by enhancing endothelial cell fatty acid utilization via liver-derived extracellular vesicle miR-122-5p显示文摘Background:Angiogenesis constitutes a major mechanism responsible for exercise-induced beneficial effects.Our previous study identified a cluster of differentially expressed extracellular vesicle microRNAs(miRNAs)after exercise and found that some of them act as exerkines.However,whether these extracellular vesicle miRNAs mediate the exercise-induced angiogenesis remains unknown.Methods:A 9-day treadmill training was used as an exercise model in C57BL/6 mice.Liver-specific adeno-associated virus 8 was used to knock down microRNA-122-5p(miR-122-5p).Human umbilical vein endothelial cells were used in vitro.Results:Among these differentially expressed extracellular vesicle miRNAs,miR-122-5p was identified as a potent pro-angiogenic factor that activated vascular endothelial growth factor signaling and promoted angiogenesis both in vivo and in vitro.Exercise increased circulating levels of miR-122-5p,which was produced mainly by the liver and shuttled by extracellular vesicles in mice.Inhibition of circulating miR-122-5p or liver-specific knockdown of miR-122-5p significantly abolished the exercise-induced pro-angiogenic effect in skeletal muscles,and exerciseimproved muscle performance in mice.Mechanistically,miR-122-5p promoted angiogenesis through shifting substrate preference to fatty acids in endothelial cells,and miR-122-5p upregulated endothelial cell fatty-acid utilization by targeting 1-acyl-sn-glycerol-3-phosphate acyltransferase(AGPAT1).In addition,miR-122-5p increased capillary density in perilesional skin tissues and accelerated wound healing in mice.Conclusion:These findings demonstrated that exercise promotes angiogenesis through upregulation of liver-derived extracellular vesicle miR-122-5p,which enhances fatty acid utilization by targeting AGPAT1 in endothelial cells,highlighting the therapeutic potential of miR-122-5p in tissue repair. | Jing Lou Jie Wu Mengya Feng Xue Dang Guiling Wu Hongyan Yang Yan Wang Jia Li Yong Zhao Changhong Shi Jiankang Liu Lin Zhao Xing Zhang Feng Gao | 2022 | Journal of Sport and Health Science2022,11,4: | 4 |
| 2 | Orchestrating antigen delivery and presentation efficiency in lymph node by nanoparticle shape for immune response显示文摘Activating humoral and cellular immunity in lymph nodes(LNs)of nanoparticle-based vaccines is critical to controlling tumors.However,how the physical properties of nanovaccine carriers orchestrate antigen capture,lymphatic delivery,antigen presentation and immune response in LNs is largely unclear.Here,we manufactured gold nanoparticles(AuNPs)with the same size but different shapes(cages,rods,and stars),and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas.Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes.On lymphatic delivery,both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention.A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity,which is mediated by CD4^(+)T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study.Interestingly,cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8^(+)T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study.These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs,and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines. | Hongjuan Zhao Yatong Li Beibei Zhao Cuixia Zheng Mengya Niu Qingling Song Xinxin Liu Qianhua Feng Zhenzhong Zhang Lei Wang | 2023 | Acta Pharmaceutica Sinica B2023,13,9: | 1 |
| 3 | Luminescence interference-free lifetime nanothermometry pinpoints in vivo temperature显示文摘Luminescence nanothermometry makes non-invasive and real-time temperature readings possible in living animals.However,the spectral fluctuation in tissues and fluids,as well as the interaction between fluorophores and environment hinders accuracy of the thermometry.Here,we report a luminescence lifetime-based nanothermometry which specifically addresses this problem.A temporal based calibration(lifetime sensing)in the NIR range,an endogenous thermal response as well as a polymer encapsulation evading environmental factors,altogether help to pinpoint temperature in vivo.Thanks to the highly condensed NdYb ions in a well-protected tiny core-shell nanocrystal(overall 11 nm),a temperature sensitivity about 2.07%K^(-1)(with 5%Yb^(3+)doped nanoparticles)and an accuracy of 0.27 K(with 25%Yb^(3+)doped nanoparticles)in biological fluids are achieved.Hopefully,combining thermally activated energy transfer nanothermometer with anti-interference lifetime thermometry would provide a more accurate temperature measurement for biological and preclinical studies. | Mengya Kong Yuyang Gu Yingjie Chai Jiaming Ke Yulai Liu Xincheng Xu Zhanxian Li Wei Feng Fuyou Li | 2021 | Science China Chemistry2021,64,6: | 1 |
| 4 | Measuring Thermal Conductivity of an Individual Carbon Nanotube Using Raman Spectroscopy显示文摘In this paper,a non-contact method based on Raman spectroscopy was used to measure the thermal conductivity of an individual single-walled carbon nanotube(SWCNT)and a multi-walled carbon nanotube(MWCNT).The effect of laser-induced heating on carbon nanotubes(CNTs)was considered.The local temperatures along the longitudinal direction of carbon nanotube were determined by Raman shift,combined with one-dimensional heat conduction model,and the thermal conductivity was finally obtained.The thermal conductivity of the SWCNT with a length of 25μm and a diameter of 1.34 nm decreases as the temperature increases in the measuring temperature range(316 K–378 K).The corresponding thermal conductivities change from 1651 W/(m·K)to 2423 W/(m·K);the thermal conductivities of the MWCNT with 40μm length and 9.2 nm diameter are within 1109–1700 W/(m·K)at 316 K–445 K.To further analyze the size effect on the thermal conductivity,molecular dynamics simulation has been carried out.The result shows that the thermal conductivity of an individual carbon nanotube increases with increasing nanotube length and eventually converges.This work is expected to provide some reference data for the studies of thermal properties of individual CNTs. | LI Pei FENG Daili FENG Yanhui LIU Xiaofang XIONG Mengya ZHANG Xinxin LIU Jinhui | 2022 | Journal of Thermal Science2022,31,4: | 0 |
| 5 | Targeting macrophagic 17β-HSD7 by fenretinide for the treatment of nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis.However,which molecule regulates macrophage polarization in NAFLD remains unclear.Herein,we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7(17β-HSD7)expression in hepatic macrophages concomitantly with elevated M1 polarization.Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet(HFD)for 6 weeks revealed that lipid metabolism pathways were notably changed.Furthermore,17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis,insulin resistance and liver injury.Mechanistically,17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content,thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines.In addition,to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD,fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity.Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production,and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages.In conclusion,our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment. | Xiaoyu Dong Yiting Feng Dongqin Xu Mengya Zhang Xiao Wen Wenhao Zhao Qintong Hu Qinyong Zhang Hui Fu Jie Ping | 2023 | Acta Pharmaceutica Sinica B2023,13,1: | 0 |