MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head

Zhang Ying,Li Chuan,Wei Qiushi,Yuan Qiang,He Wei,Zhang Ning,Dong Yiping,Jing Zhenhao,Zhang Leilei,Wang Haibin,Cao Xiangyang 한국조직공학과 재생의학회 2024 조직공학과 재생의학 Vol.21 No.1

BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH. BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

Molybdenum Trioxide Dihydrate-Graphene Composite for Electrochemical Detection of Thiourea Molecule

Xinmeng Zhang,Kezhi Li,Hejun Li,Jinhua Lu,Leilei Zhang 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2016 NANO Vol.11 No.3

A novel electrochemical sensing platform was constructed based on a facile self-assembly procedure synthetic laminar molybdenum trioxide dihydrate (MoO3 · 2H2O)-graphene composite. Field emission scanning electron microscopy (FESEM), X-ray spectroscopy, X-ray diffraction (XRD) and Raman spectroscopy were employed to characterize the morphology and composition of the MoO3 · 2H2O-graphene composite. As a model molecule, thiourea was utilized to investigate the electrochemical behaviors of the MoO3 · 2H2O-graphene composite modified glass carbon electrode. The results show that the composite modified electrode has higher electron transfer rate than that of graphene modified electrode and bare glass carbon electrode meanwhile the peak currents of it has a good linear relationship with thiourea concentrations in the range of 2.40 X 10-3 − 19.3 X 10-3 M (R = 0.998) with detection limit of 4.99 µM (S/N = 3). This novel electrochemical sensor exhibits a higher absorption capacity (3.87 X 10-8 mol/cm2 ), a good reproducibility (1.41% relative standard deviation (RSD)), excellent anti-interference and a high stability. These excellent electrochemical properties of the MoO3 · 2H2O-graphene composite are attributed to the loose and porous structure and the synergistic effects between graphene and MoO3 · 2H2O, which make this composite material hold great potential applications for electrochemical sensor.

Mesenchymal Stem Cell-Derived Exosomes are Effective for Radiation Enteritis and Essential for the Proliferation and Differentiation of Lgr5+ Intestinal Epithelial Stem Cells by Regulating Mir-195/Akt/β-Catenin Pathway

Yang Leilei,Fang Chengfeng,Song Caifang,Zhang Yaya,Zhang Ruili,Zhou Shenkang 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.5

BACKGROUND: Radiation enteritis (RE) is a common complication of abdominal or pelvic radiotherapy, which when severe, could be life-threatening. Currently, there are no effective treatments. Studies have shown that mesenchymal stem cells (MSCs)-derived exosomes (MSC-exos) exhibit promising therapeutic effects in inflammatory diseases. However, the specific role of MSC-exos in RE and the regulatory mechanisms remain elusive. METHODS: In vivo assay was carried out by injecting MSC-exos into the total abdominal irradiation (TAI)-induced RE mouse model. For in vitro assay, Lgr5-positive intestinal epithelial stem cells (Lgr5? IESC) were extracted from mice, followed by irradiation along with MSC-exos treatment. HE staining was performed to measure histopathological changes. mRNA expression of inflammatory factors TNF-a and IL-6 and stem cell markers LGR5, and OCT4 were quantified by RT-qPCR. EdU and TUNEL staining was performed to estimate cell proliferation and apoptosis. MiR-195 expression in TAI mice and radiation-induced Lgr5? IESC was tested. RESULTS: We found that the injection of MSC-exos inhibited inflammatory reaction, increased stem cell marker expression, and maintained intestinal epithelial integrity in TAI mice. Furthermore, MSC-exos treatment increased the proliferation and simultaneously suppressed apoptosis in radiation-stimulated Lgr5? IESC. MiR-195 expression increased by radiation exposure was decreased by MSC-exos therapy. MiR-195 overexpression facilitated the progress of RE by counteracting the effect of MSC-exos. Mechanistically, the Akt and Wnt/b-catenin pathways inhibited by MSC-exos were activated by miR-195 upregulation. CONCLUSION: MSC-Exos are effective in treating RE and are essential for the proliferation and differentiation of Lgr5? IESCs. Moreover, MSC-exos mediates its function by regulating miR-195 Akt b-catenin pathways.

Multi-channel 5Gb/s/ch SERDES with Emphasis on Integrated Novel Clocking Strategies

Zhang, Changchun,Li, Ming,Wang, Zhigong,Yin, Kuiying,Deng, Qing,Guo, Yufeng,Cao, Zhengjun,Liu, Leilei The Institute of Electronics and Information Engin 2013 Journal of semiconductor technology and science Vol.13 No.4

Two novel clocking strategies for a high-speed multi-channel serializer-deserializer (SERDES) are proposed in this paper. Both of the clocking strategies are based on groups, which facilitate flexibility and expansibility of the SERDES. One clocking strategy is applicable to moderate parallel I/O cases, such as high density, short distance, consistent media, high temperature variation, which is used for the serializer array. Each group within the strategy consists of a full-rate phase-locked loop (PLL), a full-rate delay-locked loop (DLL), and two fixed phase alignment (FPA) techniques. The other is applicable to more awful I/O cases such as higher speed, longer distance, inconsistent media, serious crosstalk, which is used for the deserializer array. Each group within the strategy is composed of a PLL and two DLLs. Moreover, a half-rate version is chosen to realize the desired function of 1:2 deserializer. Based on the proposed clocking strategies, two representative ICs for each group of SERDES are designed and fabricated in a standard $0.18{\mu}m$ CMOS technology. Measurement results indicate that the two SERDES ICs can work properly accompanied with their corresponding clocking strategies.

Super-Twisting Sliding Mode Observer Based Speed Sensorless Torque Control for PMSG Used in Wind Turbines

Leilei Guo,Xing Zhang,Shuying Yang,Zhen Xie,Lifeng Qi,Lingxiang Wang 전력전자학회 2015 ICPE(ISPE)논문집 Vol.2015 No.6

A speed sensorless torque control method for permanent magnet synchronous generator (PMSG) based on super-twisting sliding mode observer (STSMO) is proposed in this paper. Active back electromotive force (BEMF) can be obtained based on the STSMO. With the observed active BEMF, the rotor position angle and the speed are estimated by a phase-locked loop. Besides, a stator flux and electromagnetic torque (EMT) observation method is proposed based on the observed active BEMF. Compared to the traditional method, the robustness of the proposed one to the parameters of PMSG is improved. Then a speed sensorless EMT closed-loop control system is established. The simulation and experimental results verify the effectiveness of the proposed algorithm.

Machine Health-Driven Dynamic Scheduling of Hybrid Jobs for Flexible Manufacturing Shop

Leilei Yin,Wenhui Zhang,Tong Zhou 한국정밀공학회 2023 International Journal of Precision Engineering and Vol.24 No.5

In the multi-type & small batch production mode, jobs of small quantity (i.e., hybrid jobs) are implemented in the job shop. The production scheduling is a significant activity and it is necessary to predict the disturbance in advance. Some methods and tools to tackle the production scheduling have been provided. From the perspective of duration, our work extends the method of dynamic scheduling with incorporation of machine health prediction. The primary result of this work is the efficient generation of feasible scheduling solution when the machine health is warned. The machining quality data-based method is proposed to predict the machine health status and the relation between machine and quality characteristic is established. Combination of K-means, data equalization algorithm and particle swarm optimization (PSO) is designed to predict the machine health. Mathematical model in terms of duration is proposed and improved genetic algorithm (GA) is applied to generate the feasible scheduling solution. A prototype system is developed and a case study of a metalworking workshop is implemented. The results show that the work can reduce the risk of machine health to production. Using the prototype system, the engineers can filter out infeasible scheduling solutions automatically and acquire a successful one efficiently.

Synergistic Protective Effects of Different Dietary Supplements Against Type 2 Diabetes via Regulating Gut Microbiota

Leilei Yu,Xingting Zhou,Hui Duan,Ying Chen,Shumao Cui,Yuzheng Xue,Renmei Guo,Yuzheng Xue,Fengwei Tian,Jianxin Zhao,Hao Zhang,Qixiao Zhai,Wei Chen 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.3

Diabetes mellitus is a global health problem, and its prevalence continues to increase. Dietary supplements, including probiotics, prebiotics, and plant extracts, have been shown to alleviate diabetes. In this study, the synergistic effects of two types of dietary supplements were investigated in a mouse model of type 2 diabetes mellitus (T2DM). Sixty mice were divided into the following six groups: control, model (induced by a high-fat diet and intraperitoneal injection of streptozotocin), drug (metformin), probiotic (Lactobacillus spp.), formula A (probiotics, plant extracts, and soybean peptide), and formula B (probiotics, prebiotics, and soybean peptide). All three dietary interventions (probiotic, formula A, and formula B groups) significantly reduced the blood glucose level and oral glucose tolerance level and effectively improved some biochemical parameters (e.g., chronic inflammation, oxidative stress, and blood lipid level) and regulated gut microbiota. Notably, formula B exhibited a better ability on reducing the blood glucose level, regulating the gut microbiota, and increasing the short-chain fatty acid levels compared with the probiotics alone and formula A. Thus, formula B may exert synergistic protective effects against T2DM through a mechanism involving probiotics and prebiotics of gut microbiota regulation. This study provides a theoretical basis for the application of probiotic dietary supplements to the treatment of T2DM.

Double-voltage vector-based model predictive control for three-phase grid-connected AC/DC converters

Guo, Leilei,Zhang, Kaixuan,Li, Yanyan,Jin, Nan The Korean Institute of Power Electronics 2020 JOURNAL OF POWER ELECTRONICS Vol.20 No.1

This paper presents a double-vector-based model predictive control method for three-phase grid-connected AC/DC converters. The conventional model predictive control (MPC) presents high steady-state ripples due to the application of only one voltage vector during one control period. To reduce the current ripples, a new MPC method is proposed. Double-voltage vectors are selected and applied it each control period in the proposed method. To reduce the calculation burden, the duration time of each voltage vector is calculated based on the principle of modulated MPC. Furthermore, the effectiveness of the proposed double-voltage vector-based MPC strategy is analyzed in theory for the first time. Then, it is further verified by comparative experiment studies.

Multi-channel 5Gb/s/ch SERDES with Emphasis on Integrated Novel Clocking Strategies

Changchun Zhang,Ming Li,Zhigong Wang,Kuiying Yin,Qing Deng,Yufeng Guo,Zhengjun Cao,Leilei Liu 대한전자공학회 2013 Journal of semiconductor technology and science Vol.13 No.4

Two novel clocking strategies for a high-speed multi-channel serializer-deserializer (SERDES) are proposed in this paper. Both of the clocking strategies are based on groups, which facilitate flexibility and expansibility of the SERDES. One clocking strategy is applicable to moderate parallel I/O cases, such as high density, short distance, consistent media, high temperature variation, which is used for the serializer array. Each group within the strategy consists of full-rate phase-locked loop (PLL), a full-rate delay-locked loop (DLL), and t재 fixed phase alignment (FPA) techniques. The other is applicable to more awful I/O cases such as higher speed, longer distance, inconsistent media, serious crosstalk, which is used for the deserializer array. Each group within the strategy is composed of a PLL and two DLLs. Moreover, a half-rate version is chosen to realize the desired function of 1:2 deserializer. Based on the proposed clocking strategies, two representative ICs for each group of SERDES are designed and fabricated in a standard 0.18㎛ CMOS technology. Measurement results indicate that the two SERDES ICs can work properly accompanied with their corresponding clocking strategies.

Identification of loci affecting teat number by genome-wide association studies on three pig populations

Tang, Jianhong,Zhang, Zhiyan,Yang, Bin,Guo, Yuanmei,Ai, Huashui,Long, Yi,Su, Ying,Cui, Leilei,Zhou, Liyu,Wang, Xiaopeng,Zhang, Hui,Wang, Chengbin,Ren, Jun,Huang, Lusheng,Ding, Nengshui Asian Australasian Association of Animal Productio 2017 Animal Bioscience Vol.30 No.1

Objective: Three genome-wide association studies (GWAS) and a meta-analysis of GWAS were conducted to explore the genetic mechanisms underlying variation in pig teat number. Methods: We performed three GWAS and a meta-analysis for teat number on three pig populations, including a White Duroc${\times}$Erhualian $F_2$ resource population (n = 1,743), a Chinese Erhualian pig population (n = 320) and a Chinese Sutai pig population (n = 383). Results: We detected 24 single nucleotide polymorphisms (SNPs) that surpassed the genome-wide significant level on Sus Scrofa chromosomes (SSC) 1, 7, and 12 in the $F_2$ resource population, corresponding to four loci for pig teat number. We highlighted vertnin (VRTN) and lysine demethylase 6B (KDM6B) as two interesting candidate genes at the loci on SSC7 and SSC12. No significant associated SNPs were identified in the meta-analysis of GWAS. Conclusion: The results verified the complex genetic architecture of pig teat number. The causative variants for teat number may be different in the three populations