High yield engineered nanovesicles from ADSC with enriched miR-21-5p promote angiogenesis in adipose tissue regeneration

Sun Di,Mou Shan,Chen Lifeng,Yang Jie,Wang Rongrong,Zhong Aimei,Wang Wei,Tong Jing,Wang Zhenxing,Sun Jiaming 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been found to have a great potential for soft tissue repair due to various biological functions, including pro-angiogenesis and low immunogenicity. However, the low yield and heterogeneity of MSC-EVs limited their clinical transformation. This study was designed to develop a novel adipose-derived stem cell engineered nanovesicles (ADSC-NVs) with high production and explore its pro-angiogenetic effect and application in adipose tissue regeneration. Methods: Adipose-derived stem cell-derived extracellular vesicles (ADSC-EVs) were isolated from an EVs-free culture medium for human ADSCs (hADSCs). ADSC-NVs were prepared by sequentially extruding ADSCs followed by iodixanol density gradient ultracentrifugation and were compared with ADSC-EVs in morphology, size distribution, protein contents and yield. The pro-angiogenetic effect of ADSC-NVs in different doses (0, 5, 20 and 80 μg/mL) in vitro was determined using transwell assay, tube formation assay, western blot and qRT-PCR. In vivo, BALB/c nude mice were administered injection of a mixture of fat granules and different dose of ADSC-NVs and grafts were harvested at 12 weeks post-transplantation for further analysis. By analyzing the weight and volume of grafts and histological evaluation, we investigated the effect of ADSC-NVs in vessel formation and adipose tissue regeneration. Results: Our results showed yield of purified ADSC-NVs was approximately 20 times more than that of ADSC-EVs secreted by the same number of ADSCs. In vitro, both ADSC-NVs and ADSC-EVs exhibited a dose-dependent proangiogenetic effect, despite their distinct miRNA profiles. These effects of ADSC-NVs may be mediated by enriched miR-21-5p via PTEN inhibition and PI3K/p-Akt signaling activation. Furthermore, after a mixed injection of ADSC-NVs, vessel formation and adipose regeneration were observed in vivo in fat implants. Conclusions: Our study developed a potent alternative of ADSC-EVs. ADSC-NVs have a high pro-angiogenesis potential and can be used as cell-free therapeutic biomaterials in soft tissue regeneration.

Vibration Characteristics of Cutter-Head in Soft-Hard Mixed Stratum: An Experimental Case Study on Su’ai Tunnel

Zhenxing Yang,Dongjiang Pan,Jianjun Zhou,Jian Chen,Zhenchuan Sun,Haining Liu 대한토목학회 2020 KSCE Journal of Civil Engineering Vol.24 No.4

This paper conducts a simulation experiment research on cutter-head vibration characteristics by evaluating a soft-hard mixed stratum (the upper layer is silty soil, whereas the lower layer is moderately weathered granite of maximum uniaxial compressive strength (UCS) 142.0 MPa and slightly weathered granite of maximum 210.0 MPa). The ratios of hard rock and soil within the tunnel face were designed to be 1:1 and 1:2. Then, the cutter-head and stratum model were subjected to vibration analysis by reasonably deployed accelerometers. Results show that: 1) different conditions of heterogeneous strata mainly affected the acceleration amplitude and frequency distribution of cutter-head, in other words, the stronger hard rock, the larger the strength difference between the hard rock and soil within a tunnel face, the larger the vibration acceleration and the more concentrated the vibration frequency distribution; 2) the radial and circumferential vibration acceleration of the cutter-head in different positions were not largely different; however, axial accelerations were largely different. The axial vibration accelerations first increased and then decreased along the radial direction of cutter-head. Considering the difference between Multi-Mode Boring Test System and real cutter-head structure, the radius of joint between the cutter-head and the flange plate should be reasonably increased according to the ratio of hard rock in tunnel face; 3) with the increasing difference between the strength of the hard rock and soil, the circumferential and axial vibration acceleration multiplied. Thus, the soil remarkably reduces the vibration of the cutter-head. These results can provide some evidence of potential application for advancing manufacturing practice for cutter-head and disc cutter of shield machine.

Construction of a resequencing-based high-density genetic map for grape using an interspecific population (Vitis amurensis × Vitis vinifera)

Shi Guangli,Sun Dan,Wang Zhenxing,Liu Xiaoying,Guo Jianhui,Zhang Susu,Zhao Ying,Ai Jun 한국원예학회 2022 Horticulture, Environment, and Biotechnology Vol.63 No.4

A high-density genetic map is a prerequisite for marker-assisted selection of crop species. Here, we developed a high-density genetic map of Vitis using 92 F1 progeny derived from the cross between two wine grape cultivars, ‘Shuanghong’ and ‘Italian Riesling’. Whole genome resequencing (WGS) technology was used to generate SNP markers for the map. The map consisted of 1351 recombination bin markers (210,873 SNPs), distributed on 19 linkage groups (LGs), with an average distance of 0.65 cM between adjacent bin markers and a map distance of 860.46 cM. The high levels of uniform coverage and collinearity between the 19 LGs and the grape reference genome indicated that the map is of high quality and can serve as a powerful platform for evaluating grapevines and deciphering the genetic mechanism of important economic and agronomic traits. Our findings will facilitate the process of mapping quantitative trait loci (QTL) that control important horticultural and economic traits of grape.

Increased Piezo1 channel activity in interstitial Cajal-like cells induces bladder hyperactivity by functionally interacting with NCX1 in rats with cyclophosphamide-induced cystitis

Qian Liu,Bishao Sun,Jiang Zhao,Qingqing Wang,Fan An,Xiaoyan Hu,Zhenxing Yang,Jie Xu,Mingjia Tan,Longkun Li 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

The Piezo1 channel is a mechanotransduction mediator, and Piezo1 abnormalities have been linked to several clinical disorders. However, the role of the Piezo1 channel in cystitis-associated bladder dysfunction has not been documented. The current study aimed to discover the functional role of this channel in regulating bladder activity during cyclophosphamide (CYP)-induced cystitis. One hundred four female rats were randomly assigned to the control, CYP-4h, CYP-48h and CYP-8d groups. CYP successfully induced acute or chronic cystitis in these rats. CYP treatment for 48h or 8d significantly increased Piezo1 channel expression in bladder interstitial Cajal-like cells (ICC-LCs), and the increase in CYP-8d rats was more prominent. In addition, 2.5 μM Grammostola spatulata mechanotoxin 4 (GsMTx4) significantly attenuated bladder hyperactivity in CYP-8d rats by inhibiting the Piezo1 channel in bladder ICCLCs. Furthermore, by using GsMTx4 and siRNA targeting the Piezo1 channel, we demonstrated that hypotonic stressinduced Piezo1 channel activation significantly triggered Ca2+ and Na+ influx into bladder ICC-LCs during CYPinduced chronic cystitis. In addition, the Piezo1 channel functionally interacted with the relatively activated reverse mode of Na+/Ca2+ exchanger 1 (NCX1) in bladder ICC-LCs from CYP-8d rats. In conclusion, we suggest that the functional role of the Piezo1 channel in CYP-induced chronic cystitis is based on its synergistic effects with NCX1, which can significantly enhance [Ca2+]i and result in Ca2+ overload in bladder ICC-LCs, indicating that the Piezo1 channel and NCX1 are potential novel therapeutic targets for chronic cystitis-associated bladder hyperactivity.

Uplink Achievable Rate analysis of Massive MIMO Systems in Transmit-correlated Ricean Fading Environments

Yixin Xu,Fulai Liu,Zixuan Zhang,Zhenxing Sun 한국인터넷정보학회 2023 KSII Transactions on Internet and Information Syst Vol.17 No.1

In this article, the uplink achievable rate is investigated for massive multiple-input multiple-output (MIMO) under correlated Ricean fading channel, where each base station (BS) and user are both deployed multiple antennas. Considering the availability of prior knowledge at BS, two different channel estimation approaches are adopted with and without prior knowledge. Based on these channel estimations, a two-layer decoding scheme is adopted with maximum ratio precoding as the first layer decoder and optimal second layer precoding in the second layer. Based on two aforementioned channel estimations and two-layer decoding scheme, the exact closed form expressions for uplink achievable rates are computed with and without prior knowledge, respectively. These derived expressions enable us to analyze the impacts of line-of-sight (LoS) component, two-layer decoding, data transmit power, pilot contamination, and spatially correlated Ricean fading. Then, numerical results illustrate that the system with spatially correlated Ricean fading channel is superior in terms of uplink achievable rate. Besides, it reveals that compared with the single-layer decoding, the two-layer decoding scheme can significantly improve the uplink achievable rate performance.

Cyclophosphamide-induced HCN1 channel upregulation in interstitial Cajal-like cells leads to bladder hyperactivity in mice

Qian Liu,Zhou Long,Xingyou Dong,Teng Zhang,Jiang Zhao,Bishao Sun,Jingzhen Zhu,Jia Li,Qingqing Wang,Zhenxing Yang,Xiaoyan Hu,Longkun Li 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is known about their possible role in cystitis-associated bladder dysfunction. The present study aimed to determine the functional role of HCN channels in regulating bladder function under inflammatory conditions. Sixty female wild-type C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to experimental and control groups, respectively. Cyclophosphamide (CYP)-induced cystitis models were successfully established in these mice. CYP treatment significantly enhanced HCN channel protein expression and Ih density and significantly altered bladder HCN1 channel regulatory proteins. Carbachol (CCH) and forskolin (FSK) exerted significant effects on bladder ICC-LC [Ca2+]i in CYP-treated wild-type (WT) mice, and HCN1 channel ablation significantly decreased the effects of CCH and FSK on bladder ICC-LC [Ca2+]i in both naive and CYP-treated mice. CYP treatment significantly potentiated the spontaneous contractions and CCH (0.001–10 μM)-induced phasic contractions of detrusor strips, and HCN1 channel deletion significantly abated such effects. Finally, we demonstrated that the development of CYP-induced bladder overactivity was reversed in HCN1 / mice. Taken together, our results suggest that CYP-induced enhancements of HCN1 channel expression and function in bladder ICC-LCs are essential for cystitis-associated bladder hyperactivity development, indicating that the HCN1 channel may be a novel therapeutic target for managing bladder hyperactivity.