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Manjiao Zhuang,1,* Lei Rao,2,3,* Yadi Chen,1 Shangying Xiao,1 Haishan Xia,1 Jiangyong Yang,2 Xiaohua Lv,1 Dongyun Qin,1 Chunjie Zhu1 1Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China; 2Medical College, Shaoguan University, Shaoguan, 512026, People’s Republic of China; 3Department of Biomedicine, Chengdu Medical College, Chengdu, 610500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Manjiao Zhuang, Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China, Email manjiao@163.com Chunjie Zhu, School of Basic Medicine, Guangdong Medical University, Dongguan, 523808, People’s Republic of China, Email zhuchunjie718@163.comIntroduction: Quercetin has an ideal therapeutic effect on islet function improvement in type 2 diabetes mellitus (T2DM). However, the therapeutic benefit of quercetin is hindered by its poor bioavailability and limited concentration in pancreatic islets. In this study, superparamagnetic iron oxide nanoparticle (SPION)-modified exosomes were prepared to load quercetin, hoping to endow quercetin with enhanced water solubility and active targeting capacity with the help of magnetic force (MF).Methods: Transferrin-modified SPIONs (Tf-SPIONs) were synthesized by exploiting N-hydroxysuccinimidyl (NHS) conjugation chemistry, and quercetin-loaded exosomes (Qu-exosomes) were acquired by electroporation. Tf-SPION-modified quercetin-loaded exosomes (Qu-exosome-SPIONs) were generated by the self-assembly of transferrin (Tf) and the transferrin receptor (TfR). The solubility of quercetin was determined by high-performance liquid chromatography (HPLC) analysis. The pancreatic islet targeting capacity and insulin secretagogue and antiapoptoti

Manjiao Zhuang,1 Honghong Qiu,2 Ping Li,2 Lihua Hu,2 Yayu Wang,3 Lei Rao2 1Department of Pharmacy, Sichuan University, Chengdu, People’s Republic of China; 2Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College, Chengdu, China; 3Department of Cell Biology, Institute of Biological Medicine, Jinan University, Guangzhou, People’s Republic of China Background and purpose: The traditional Chinese medicine – the flower of Edgeworthia gardneri – is reported as an effective therapeutic for type 2 diabetes mellitus (T2DM). Nevertheless, most constituents of the flowers of E. gardneri have not yet been studied. This study was conducted to investigate the effect of quercetin extracted from the flowers of E. gardneri on islet protection and amelioration in T2DM and explore its mechanism. Method: Quercetin was extracted from the flowers of E. gardneri and verified by high-performance liquid chromatography. Quercetin or crude extract’s effect on insulin secretion was investigated. ERK1/2 and phospho-ERK1/2 were detected by Western blot analysis, and fluo-3 AM was used to detect intracellular Ca2+. The anti-apoptosis effect of quercetin or crude extract on MIN-6 cells was investigated by thiazolyl blue tetrazolium bromide (MTT) assay and flow cytometry analysis. Activation of caspases and expression of Bcl-2 and BAX were tested by Western blot analysis. In addition, the mitochondrial membrane potential was determined by JC-1 probe. Moreover, in vivo activity was also tested in db/db mice. Results: A quercetin level of >10 μmol/L could induce insulin secretion. Intracellular Ca2+ and ERK1/2 were involved in the signaling pathway of quercetin-induced insulin secretion. We also observed that quercetin could inhibit palmitic acid-induced cell apoptosis via suppressing the activation of caspase-3, -9, -12; increasing the ratio of Bcl-2/BAX and reversing the impaired mitochondrial m

In vehicular cyber-physical systems (CPS), safety information, including vehicular speed and location information, is shared among vehicles via wireless waves at specific frequency. This helps control vehicle to alleviate traffic congestion and road accidents. However, Doppler shift existing between vehicles with high relative speed causes an apparent frequency shift for the received wireless wave, which consequently decreases the reliability of the recovered safety information and jeopardizes the safety of vehicular CPS. Passive confrontation of Doppler shift at the receiver side is not applicable due to multiple Doppler shifts at each receiver. In this paper, we provide a proactive Doppler shift compensation algorithm based on the probabilistic graphical model. Each vehicle pre-compensates its carrier frequency individually so that there is no frequency shift from the desired carrier frequency between each pair of transceiver. The pre-compensated offset for each vehicle is computed in a distributed fashion in order to be adaptive to the distributed and dynamic topology of vehicular CPS. Besides, the updating procedure is designed in a broadcasting fashion to reduce communication burden. It is rigorously proved that the proposed algorithm is convergence guaranteed even for systems with packet drops and random communication delays. Simulations based on real map and transportation data verify the accuracy and convergence property of the proposed algorithm. It is shown that this method achieves almost the optimal frequency compensation accuracy with an error approaching the Cram\'{e}r-Rao lower bound.

Lei Rao,* Yi Ma,* Manjiao Zhuang, Tianjie Luo, Yayu Wang, An Hong Department of Cell Biology, Guangdong Province Key Lab of Bioengineering Medicine, National Engineering Research Center of Gene Engineering Medicine, Institute of Biological Medicine, Jinan University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Purpose: As a potential protein therapeutic for type 2 diabetes mellitus (T2DM), BAY 55-9837 is limited by poor stability and a very short half-life in vivo. The purpose of this study was to construct a novel nanostructured biomaterial by conjugating BAY 55-9837 to chitosan-decorated selenium nanoparticles (CS-SeNPs) to prolong the in vivo half-life of BAY 55-9837 by reducing its renal clearance rate.Materials and methods: BAY 55-9837-loaded CS-SeNPs (BAY-CS-SeNPs) were prepared, and their surface morphology, particle size, zeta potential, and structure were characterized. The stability, protein-loading rate, and in vitro release of BAY 55-9837 from CS-SeNPs were also quantified. Additionally, a sensitive high-performance liquid chromatography (HPLC) assay was developed for the quantification of BAY 55-9837 in mouse plasma. Thereafter, mice were injected via the tail vein with either BAY 55-9837 or BAY-CS-SeNPs, and the plasma concentration of BAY 55-9837 was determined via our validated HPLC method at different time intervals postinjection. Relevant in vivo pharmacokinetic parameters (half-life, area under the curve from time 0 to last sampling point, observed clearance) were then calculated and analyzed.Results: BAY-CS-SeNPs were successfully synthesized, with diameters of approximately 200 nm. BAY-CS-SeNPs displayed good stability with a high protein-loading rate, and the release process of BAY 55-9837 from the CS-SeNPs lasted for over 70 hours, with the cumulative release reaching 78.9%. Moreover, the conjugation of CS-SeNPs to BAY 55-9837 significantly reduced its renal clearance to a r

Lei Rao,* Yi Ma,* Manjiao Zhuang, Tianjie Luo, Yayu Wang, An Hong Department of Cell Biology, Guangdong Province Key Lab of Bioengineering Medicine, National Engineering Research Center of Gene Engineering Medicine, Institute of Biological Medicine, Jinan University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Purpose: As a potential protein therapeutic for type 2 diabetes mellitus (T2DM), BAY 55-9837 is limited by poor stability and a very short half-life in vivo. The purpose of this study was to construct a novel nanostructured biomaterial by conjugating BAY 55-9837 to chitosan-decorated selenium nanoparticles (CS-SeNPs) to prolong the in vivo half-life of BAY 55-9837 by reducing its renal clearance rate.Materials and methods: BAY 55-9837-loaded CS-SeNPs (BAY-CS-SeNPs) were prepared, and their surface morphology, particle size, zeta potential, and structure were characterized. The stability, protein-loading rate, and in vitro release of BAY 55-9837 from CS-SeNPs were also quantified. Additionally, a sensitive high-performance liquid chromatography (HPLC) assay was developed for the quantification of BAY 55-9837 in mouse plasma. Thereafter, mice were injected via the tail vein with either BAY 55-9837 or BAY-CS-SeNPs, and the plasma concentration of BAY 55-9837 was determined via our validated HPLC method at different time intervals postinjection. Relevant in vivo pharmacokinetic parameters (half-life, area under the curve from time 0 to last sampling point, observed clearance) were then calculated and analyzed.Results: BAY-CS-SeNPs were successfully synthesized, with diameters of approximately 200 nm. BAY-CS-SeNPs displayed good stability with a high protein-loading rate, and the release process of BAY 55-9837 from the CS-SeNPs lasted for over 70 hours, with the cumulative release reaching 78.9%. Moreover, the conjugation of CS-SeNPs to BAY 55-9837 significantly reduced its renal clearance to a r