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25. Genome Editing with AAV-BR1-CRISPR in Postnatal Mouse Brain Endothelial Cells

Author

Song, Xiaopeng, Cui, Yaxiong, Wang, Yanxiao, Zhang, Yizhe, He, Qi, Yu, Zhenyang, Xu, Chengfang, Ning, Huimin, Han, Yuying, Cai, Yunting, Cheng, Xuan, Wang, Jian, Teng, Yan, Yang, Xiao, and Wang, Jun

Subjects
Male, Mice, Transgenic, Applied Microbiology and Biotechnology, Gene Knockout Techniques, Mice, genome editing, Animals, CRISPR/Cas9, Molecular Biology, beta Catenin, Ecology, Evolution, Behavior and Systematics, Gene Editing, AAV-BR1, Endothelial Cells, High-Throughput Nucleotide Sequencing, Cell Biology, blood-brain barrier, Dependovirus, brain endothelial cell, Disease Models, Animal, Luminescent Proteins, NIH 3T3 Cells, CRISPR-Cas Systems, Research Paper, RNA, Guide, Kinetoplastida, Developmental Biology
Abstract

Brain endothelial cells (ECs) are an important component of the blood-brain barrier (BBB) and play key roles in restricting entrance of possible toxic components and pathogens into the brain. However, identifying endothelial genes that regulate BBB homeostasis remains a time-consuming process. Although somatic genome editing has emerged as a powerful tool for discovery of essential genes regulating tissue homeostasis, its application in brain ECs is yet to be demonstrated in vivo. Here, we used an adeno-associated virus targeting brain endothelium (AAV-BR1) combined with the CRISPR/Cas9 system (AAV-BR1-CRISPR) to specifically knock out genes of interest in brain ECs of adult mice. We first generated a mouse model expressing Cas9 in ECs (Tie2Cas9). We selected endothelial β-catenin (Ctnnb1) gene, which is essential for maintaining adult BBB integrity, as the target gene. After intravenous injection of AAV-BR1-sgCtnnb1-tdTomato in 4-week-old Tie2Cas9 transgenic mice resulted in mutation of 36.1% of the Ctnnb1 alleles, thereby leading to a dramatic decrease in the level of CTNNB1 in brain ECs. Consequently, Ctnnb1 gene editing in brain ECs resulted in BBB breakdown. Taken together, these results demonstrate that the AAV-BR1-CRISPR system is a useful tool for rapid identification of endothelial genes that regulate BBB integrity in vivo.

Published
2022

26. 18F‐FDG PET/CT predicts the role of neoadjuvant immunochemotherapy in the pathological response of esophageal squamous cell carcinoma.

Author

Wang, Shuohua, Di, Shouyin, Lu, Jing, Xie, Shun, Yu, Zhenyang, Liang, Yingkui, and Gong, Taiqian

Subjects
TREATMENT of esophageal cancer, CONFIDENCE intervals, CANCER chemotherapy, POSITRON emission tomography computed tomography, MANN Whitney U Test, RETROSPECTIVE studies, T-test (Statistics), RADIOPHARMACEUTICALS, RESEARCH funding, DESCRIPTIVE statistics, CHI-squared test, COMBINED modality therapy, PREDICTION models, DEOXY sugars, DATA analysis software, SQUAMOUS cell carcinoma, IMMUNOTHERAPY, ESOPHAGEAL cancer, LONGITUDINAL method
Abstract

Background: This study aimed to investigate the predictive value of 18F‐FDG PET/CT for pathological response after neoadjuvant immunochemotherapy (NICT) in patients with esophageal squamous cell carcinoma (ESCC). Methods: The clinical data of 54 patients with ESCC who underwent two cycles of NICT followed by surgery were retrospectively analyzed. NICT consisted of PD‐1 blockade therapy combined with chemotherapy. 18F‐FDG PET/CT scans were performed before and after NICT. The pathological results after surgery were used to assess the degree of pathological response. The scan parameters of 18F‐FDG PET/CT and their changes before and after NICT were compared with the pathological response. Results: Among the 54 patients, 10 (18.5%) achieved complete pathological response (pCR) and 21 (38.9%) achieved major pathological response (MPR). The post‐NICT scan parameters and their changes were significantly associated with the pathological response. In addition, the values of the changes in the scanned parameters before and after treatment can further predict the pathological response of the patient. Conclusion: 18F‐FDG PET/CT is a useful tool to evaluate the efficacy of NICT and predict pathological response in patients with ESCC. The post‐NICT scan parameters and their changes can help identify patients who are likely to achieve pCR or MPR. [ABSTRACT FROM AUTHOR]

Published
2023
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27. SO42−-ion induced synthesis of 3D porous hydrangea-shaped anatase TiO2 as high performance anode material for lithium/sodium-ion batteries.

Author

Wang, Wenqiang, Qiao, Zhijun, Zhao, Yuwen, Xie, Gang, Yan, Shenglong, Pang, Zhiheng, Chen, Yuefang, Yang, Huan, Zhang, Mengmeng, Zhang, Yifang, Li, Weijie, Jiang, Yong, Yu, Zhenyang, and Zhang, Zhijia

Abstract

TiO2 materials are considered one of the promising candidates for lithium/sodium-ion batteries (L/SIBs) due to its excellent safety and abundant resources. However, the low ion diffusion coefficient becomes a bottleneck in restrict its development. In this work, three-dimensional (3D) porous hydrangea-shaped anatase TiO2 (ATO) was synthesized through the synergistic effect of de-alloying and SO42− induced chemical synthesis. During the chemical synthesis process, SO42− and TiO62− octahedra are bound by static electricity, as the spatial effect of SO42− can influence the octahedral arrangement in favor of precipitating anatase TiO2. In the SIBs, ATO as anode material provided an excellent capacity of 190 mAh g−1 after 100 cycles at a current density of 50 mA g−1. Electrochemical kinetic tests show that the pseudocapacitive behavior contributes to 86% of the capacity at a scan rate of 1 mV s−1, mainly due to the high specific surface area provided by its unique microstructure, and also shows excellent electrochemical performance in the LIBs tests. This study provides a novel strategy for the simple and large-scale production of TiO2 anode materials with high-performance L/SIBs. [ABSTRACT FROM AUTHOR]

Published
2023
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31. Architecting Braided Porous Carbon Fibers Based on High‐Density Catalytic Crystal Planes to Achieve Highly Reversible Sodium‐Ion Storage

Author

Li, Chuanqi, primary, Zhang, Zhijia, additional, Chen, Yuefang, additional, Xu, Xiaoguang, additional, Zhang, Mengmeng, additional, Kang, Jianli, additional, Liang, Rui, additional, Chen, Guoxin, additional, Lu, Huanming, additional, Yu, Zhenyang, additional, Li, Wei‐Jie, additional, Wang, Nan, additional, Huang, Qin, additional, Zhang, Delin, additional, Chou, Shu‐Lei, additional, and Jiang, Yong, additional

Published
2022
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32. Preparation of PU/Fibrin Vascular Scaffold with Good Biomechanical Properties and Evaluation of Its Performance in vitro and in vivo

Author

Yang,Lei, Li,Xiafei, Wu,Yiting, Du,Pengchong, Sun,Lulu, Yu,Zhenyang, Song,Shuang, Yin,Jianshen, Ma,Xianfen, Jing,Changqin, Zhao,Junqiang, Chen,Hongli, Dong,Yuzhen, Zhang,Qiqing, and Zhao,Liang

Subjects
Male, Fibrin, Tissue Engineering, Tissue Scaffolds, small diameter, vascular remodeling, Myocytes, Smooth Muscle, Polyurethanes, PU/fibrin scaffold, Endothelial Cells, Gene Expression, Mesenchymal Stem Cells, in vitro biocompatibility, Blood Vessel Prosthesis, Rats, Sprague-Dawley, International Journal of Nanomedicine, Materials Testing, Cell Adhesion, Animals, biomechanical properties, Original Research
Abstract

Lei Yang,1,2,* Xiafei Li,3,* Yiting Wu,4 Pengchong Du,1,5 Lulu Sun,1 Zhenyang Yu,2 Shuang Song,1 Jianshen Yin,1 Xianfen Ma,1 Changqin Jing,1 Junqiang Zhao,3 Hongli Chen,1 Yuzhen Dong,2 Qiqing Zhang,1 Liang Zhao1,6,7 1College of Life Science and Technology, Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Department of Orthopedics, First Affiliated Hospital, Xinxiang Medical University, Xinxiang, People’s Republic of China; 3College of Medical Engineering, Xinxiang Medical University, Xinxiang, People’s Republic of China; 4Xiacun Community Health Service Center, Shenzhen Hospital, University of Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 5Department of Cardio-Thoracic Surgery, Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, People’s Republic of China; 6Key Laboratory of Cardiac Structure Research, Zhengzhou Seventh People’s Hospital, Zhengzhou, People’s Republic of China; 7The Central Lab, The Third People’s Hospital of Datong, Datong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Zhao; Yuzhen Dong Email zhaoliang4321@163.com; dongyuzhen1998@163.comPurpose: The development of tissue-engineered blood vessels provides a new source of donors for coronary artery bypass grafting and peripheral blood vessel transplantation. Fibrin fiber has good biocompatibility and is an ideal tissue engineering vascular scaffold, but its mechanical property needs improvement.Methods: We mixed polyurethane (PU) and fibrin to prepare the PU/fibrin vascular scaffolds by using electrospinning technology in order to enhance the mechanical properties of fibrin scaffold. We investigated the morphological, mechanical strength, hydrophilicity, degradation, blood and cell compatibility of PU/fibrin (0:100), PU/fibrin (5:95), PU/fibrin (15:85) and PU/fibrin (25:75) vascular scaffolds. Based on the results in vitro, PU/fibrin (15:85) was selected for transplantation in vivo to repair vascular defects, and the extracellular matrix formation, vascular remodeling, and immune response were evaluated.Results: The results indicated that the fiber diameter of the PU/fibrin (15:85) scaffold was about 712nm. With the increase of PU content, the mechanical strength of the composite scaffolds increased, however, the degradation rate decreased gradually. The PU/fibrin scaffold showed good hydrophilicity and hemocompatibility. PU/fibrin (15:85) vascular scaffold could promote the adhesion and proliferation of mesenchymal stromal cells (MSCs). Quantitative RT-PCR experimental results showed that the expression of collagen, survivin and vimentin genes in PU/fibrin (15:85) was higher than that in PU/fibrin (25:75). The results in vivo indicated the mechanical properties and compliance of PU/fibrin grafts could meet clinical requirements and the proportion of thrombosis or occlusion was significantly lower. The graft showed strong vasomotor response, and the smooth muscle cells, endothelial cells, and ECM deposition of the neoartery were comparable to that of native artery after 3 months. At 3 months, the amount of macrophages in PU/fibrin grafts was significantly lower, and the secretion of pro-inflammatory and anti-inflammatory cytokines decreased.Conclusion: PU/fibrin (15:85) vascular scaffolds had great potential to be used as small-diameter tissue engineering blood vessels.Keywords: PU/fibrin scaffold, small diameter, in vitro biocompatibility, biomechanical properties, vascular remodeling

Published
2020

38. DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction

Author

Pan, Pan, primary, Li, Geng, additional, Shen, Miaomiao, additional, Yu, Zhenyang, additional, Ge, Weiwei, additional, Lao, Zizhao, additional, Fan, Yaohua, additional, Chen, Keli, additional, Ding, Zhihao, additional, Wang, Wenbiao, additional, Wan, Pin, additional, Shereen, Muhammad Adnan, additional, Luo, Zhen, additional, Chen, Xulin, additional, Zhang, Qiwei, additional, Lin, Luping, additional, and Wu, Jianguo, additional

Published
2021
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43. Additional file 1 of Transgenerational effects of different sequential exposure to 2,2′,4,4′-tetra-brominated diphenyl ether (BDE47) and lead (Pb) on Caenorhabditis elegans

Author

Zhang, Jing and Yu, ZhenYang

Abstract

Additional file 1: Figure S1. The effects of individual Pb or BDE-47 (A, C) and their sequential exposure (B, D) on the activities of AChE (A, B) and the contents of GABA (C, D) in Caenorhabditis elegans. The sequential exposure was a 12 h-exposure to BDE47 and another 12 h exposure to Pb (or vice versa). Blank column: exposure effects; Shadow column: recovery effects; *Significantly different from the control, p

Published
2020
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46. Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis

Author

Wang, Jun, primary, Cui, Yaxiong, additional, Yu, Zhenyang, additional, Wang, Wenjing, additional, Cheng, Xuan, additional, Ji, Wenliang, additional, Guo, Shuyue, additional, Zhou, Qing, additional, Wu, Ning, additional, Chen, Yan, additional, Chen, Ying, additional, Song, Xiaopeng, additional, Jiang, Hui, additional, Wang, Yanxiao, additional, Lan, Yu, additional, Zhou, Bin, additional, Mao, Lanqun, additional, Li, Jin, additional, Yang, Huanming, additional, Guo, Weixiang, additional, and Yang, Xiao, additional

Published
2019
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47. Dengue Virus Infection Activates Interleukin-1β to Induce Tissue Injury and Vascular Leakage

Author

Pan, Pan, primary, Zhang, Qi, additional, Liu, Weiyong, additional, Wang, Wenbiao, additional, Yu, Zhenyang, additional, Lao, Zizhao, additional, Zhang, Wei, additional, Shen, Miaomiao, additional, Wan, Pin, additional, Xiao, Feng, additional, Shereen, Muhammad Adnan, additional, Zhang, Wen, additional, Tan, Qiuping, additional, Liu, Yuntao, additional, Liu, Xiaohong, additional, Wu, Kailang, additional, Liu, Yingle, additional, Li, Geng, additional, and Wu, Jianguo, additional

Published
2019
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