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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.

General anesthesia is an indispensable procedure in clinical practice. Anesthetic drugs induce dramatic changes in neuronal activity and cerebral metabolism. However, the age-related changes in neurophysiology and hemodynamics during general anesthesia remain unclear. Therefore, the objective of this study was to explore the neurovascular coupling between neurophysiology and hemodynamics in children and adults during general anesthesia. We analyzed frontal electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) signals recorded from children (6-12 years old, n = 17) and adults (18-60 years old, n = 25) during propofol-induced and sevoflurane-maintained general anesthesia. The neurovascular coupling was evaluated in wakefulness, maintenance of a surgical state of anesthesia (MOSSA), and recovery by using correlation, coherence and Granger-causality (GC) between the EEG indices [EEG power in different bands and permutation entropy (PE)], and hemodynamic responses the oxyhemoglobin (Δ[HbO]) and deoxy-hemoglobin (Δ[Hb]) from fNIRS in the frequency band in 0.01-0.1 Hz. The PE and Δ[Hb] performed well in distinguishing the anesthesia state (p > 0.001). The correlation between PE and Δ[Hb] was higher than those of other indices in the two age groups. The coherence significantly increased during MOSSA (p

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

Camera calibration is crucial for geometric vision-based three-dimensional (3D) deformation measurement tasks. Among existing calibration techniques, the one based on planar targets has attracted much attention in the community due to its flexibility and reliability. Our study proposes a calibration technique to obtain high-accuracy internal and external parameters based on low-cost ordinary planar patterns. The proposed method determines the optimal internal parameters for each camera by refining 3D coordinates of planar control points, where an analytic model of optics distortion is presented to enable lens distortion to be corrected directly in subsequent external calibration and underlying 3D reconstruction. External parameters are estimated by minimizing a bundle adjustment framework, which is carefully designed based on the proposed distortion correction model and depth parameterization. In contrast to the existing techniques, the proposed method is capable of obtaining a high-accuracy calibration with ordinary targets rather than the well-designed and fabricated ones. We experimented the proposed method with a calibration performance analysis and a displacement measurement; both results demonstrated the accuracy and robustness.

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

Surface nuclear magnetic resonance (SNMR) could provide direct insights for hydrological investigations but is often limited because of its low signal-to-noise ratio. Many types of residual noise remain after denoising procedures, including despiking, power harmonic noise cancellation, and random noise attenuation. This residual noise prevents the detection of valid signals, especially in strong noise environments, such as cities and industrial areas. In this work, a lock-in amplifier modeling recovery (LIAMR) method is proposed for extracting SNMR signals from high-level residual noise after denoising. The desired SNMR signals can be extracted directly by establishing a model of the SNMR signal passing through the lock-in amplifier and then transforming mathematically the output of the amplifier. The performance of the proposed method is tested on synthetic SNMR signals under varied average relaxation times, simulation noise at different levels, and field noise. Experiment results show that LIAMR can obtain good estimations of SNMR signal parameters with residual noise. Moreover, the proposed method can provide more precise parameters compared with traditional signal extraction methods. LIAMR provides theoretical support for the application of SNMR technology in strong noise environments.

The dynamic characteristic has an important effect on the motion precision of a robot and dynamic feedforward control is an effective approach to reduce the effect. However, it is difficult to realize the accurate dynamic feedforward control in an industrial servo system and determine the feedforward coefficients. This paper proposes a method to realize the accurate dynamic feedforward control of a spray-painting robot for airplane wings with large workspace and time-varying dynamics. The basic control method is still the feedback control system with dynamic feedforward compensation, which is the most widely used in industrial field. The control parameters of the closed-loop feedback control system are designed based on atlas method. Considering that only the acceleration and velocity feedforward compensations are provided in an industrial servo system, the mapping relationship between the complete dynamic model and the velocity and acceleration compensators is investigated. Then, the method to realize the accurate feedforward compensation in the industrial servo system is presented based on the complete dynamic model. For a complex robot without an accurate dynamic model, the approach to realize the accurate feedforward compensation is also discussed. The experiment on a physical prototype validates the effect of the proposed methods. This paper is very helpful for the practical control of robots in an industrial field.

With the process of miniaturization, modularization and integration in power electronic systems, the requirements for EMI filters are much higher than before. However, the large volume and parasitic parameters of passive components have great influence in the high frequency performance of conventional EMI filters. With the development of electromagnetic integration technologies, integrated EMI filter with its advantage of highly integrated volume and small parasitic parameters has become a new research direction. At present, the research directions of integrated EMI filter include the integrated EMI filter based on flexible multi-layer foil, planar EMI filter, bus-bar EMI filter and so on. The structures and principles of the integrated EMI filter above are analyzed in this paper, and based on the analysis; the applicable occasions and future trends of these EMI filters are investigated.

To obtain higher performance for hybrid robots subject to nonlinear dynamics and friction, feedforward compensations have been ubiquitously utilized in the industrial robotic field to attenuate these disturbances. However, due to the complex friction model and the coupling and time-varying dynamic of hybrid robots, there is no effective approach to realize accurate feedforward compensations in industrial control systems. This paper investigated an accurate dynamic modeling and control parameters design method to address these issues all at once. Taking the friction of each joint into account, the accurate dynamic model of the hybrid robot is developed and verified by experiments. With the accurate dynamic model, an exact control parameter design method is proposed based on the mapping relationship between the dynamic model and the feedforward compensations. Additionally, the control system designed by the method proposed in this paper is compared with the one tuned by an experienced engineer. Particularly, the robot's position and motion accuracy are also tested by a third-party inspection agency. The experimental and test results show that the position and velocity accuracy of the robot is improved significantly when the control system is designed by using the method proposed in this paper, which proves the effectiveness of the proposed method.