Natural killer(NK)cells have been suggested to be associated with type 2 diabetes by regulating systemic inflammation.However,the mechanism by which NK cells regulate insulin sensitivity remains unknown.This study sho...Natural killer(NK)cells have been suggested to be associated with type 2 diabetes by regulating systemic inflammation.However,the mechanism by which NK cells regulate insulin sensitivity remains unknown.This study shows that NK-derived exosomes from lean mice attenuate obesity-induced insulin resistance and inflammation in mice of type 2 diabetes.Moreover,lean NK-derived exosomes enhance insulin sensitivity and relieve inflammation in adipocytes and hepatocytes.MiR-1249-3p,which is significantly upregulated in lean NK-derived exosomes,can be transferred from NK cells to adipocytes and hepatocytes via exosomes.NKderived exosomal miR-1249-3p dramatically induces cellular insulin sensitivity and relieves inflammation.Mechanistically,exosomal miR-1249-3p directly targets SKOR1 to regulate the formation of ternary complex SMAD6/MYD88/SMURF1,which mediates glucose homeostasis by suppressing the TLR4/NF-κB signaling pathway.This study reveals an emerging role for NK-derived exosomal miR1249-3p in remission of insulin resistance,and provides a series of potential therapeutic targets in type 2 diabetes.展开更多
To realize a fast,easy-operation and precise way using fluorescence probes to quantify analytes is a goal to facilitate detection,especially in situ.Herein,we are reporting an approach which can be generally employed ...To realize a fast,easy-operation and precise way using fluorescence probes to quantify analytes is a goal to facilitate detection,especially in situ.Herein,we are reporting an approach which can be generally employed for the differentiation and quantitation of analytes through fluorescence chromaticity and luminosity.Seven representative fluorescent probes,targeting p H,cysteine,hydrogen sulfide,hydrogen peroxide,palladium and hydrazine,were synthesized and tested.Without utilizing costly instrumentations,portable devices were employed to collect data of photographs from the fluorescence samples in responses to different analytes.Subsequently,the photographic images were digitally processed to generate calibration curves between chromaticity/luminosity verse concentrations after mapping to the CIE 1931 xy Y standard color space.Good linear calibration curves and quantitative analysis of unknown samples with low errors through the spectral technology demonstrated the reliability of this method.Thus,we showed the analytical method with a simple and on-site constructible/portable device which is promising for applications in more fluorescence probes.展开更多
基金This work was supported by grants from the Project Program of State Key Laboratory of Natural Medicines(SKLNMZZCX201821,SKLNMZZ202028)the National Science and Technology Major Projects of New Drugs(2019ZX09301124,2019ZX09201001,and 2019ZX09301-110)in China+2 种基金This work was also supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)China Postdoctoral Science Foundation(2017M621884,2020M681787)“Double First-Class”University project of China Pharmaceutical University(CPU2018GY13,CPU2018PZH03).
文摘Natural killer(NK)cells have been suggested to be associated with type 2 diabetes by regulating systemic inflammation.However,the mechanism by which NK cells regulate insulin sensitivity remains unknown.This study shows that NK-derived exosomes from lean mice attenuate obesity-induced insulin resistance and inflammation in mice of type 2 diabetes.Moreover,lean NK-derived exosomes enhance insulin sensitivity and relieve inflammation in adipocytes and hepatocytes.MiR-1249-3p,which is significantly upregulated in lean NK-derived exosomes,can be transferred from NK cells to adipocytes and hepatocytes via exosomes.NKderived exosomal miR-1249-3p dramatically induces cellular insulin sensitivity and relieves inflammation.Mechanistically,exosomal miR-1249-3p directly targets SKOR1 to regulate the formation of ternary complex SMAD6/MYD88/SMURF1,which mediates glucose homeostasis by suppressing the TLR4/NF-κB signaling pathway.This study reveals an emerging role for NK-derived exosomal miR1249-3p in remission of insulin resistance,and provides a series of potential therapeutic targets in type 2 diabetes.
基金the National Natural Science Foundation of China(No.21907080)Natural Science Foundationof Shaanxi(No.2020JM-069)+1 种基金Key Scientific Research Group of Shaanxi Province(No.2020TD-009)the Youth Innovation Team of Shaanxi Universities。
文摘To realize a fast,easy-operation and precise way using fluorescence probes to quantify analytes is a goal to facilitate detection,especially in situ.Herein,we are reporting an approach which can be generally employed for the differentiation and quantitation of analytes through fluorescence chromaticity and luminosity.Seven representative fluorescent probes,targeting p H,cysteine,hydrogen sulfide,hydrogen peroxide,palladium and hydrazine,were synthesized and tested.Without utilizing costly instrumentations,portable devices were employed to collect data of photographs from the fluorescence samples in responses to different analytes.Subsequently,the photographic images were digitally processed to generate calibration curves between chromaticity/luminosity verse concentrations after mapping to the CIE 1931 xy Y standard color space.Good linear calibration curves and quantitative analysis of unknown samples with low errors through the spectral technology demonstrated the reliability of this method.Thus,we showed the analytical method with a simple and on-site constructible/portable device which is promising for applications in more fluorescence probes.