Human and Non-Human Primate Intestinal FcRn Expression and Immunoglobulin G Transcytosis

PURPOSE: To evaluate transcytosis of immunoglobulin G (IgG) by the neonatal Fc receptor (FcRn) in adult primate intestine to determine whether this is a means for oral delivery of monoclonal antibodies (mAbs). METHODS: Relative regional expression of FcRn and localization in human intestinal mucosa by RT-PCR, ELISA & immunohistochemistry. Transcytosis of full-length mAbs (sandwich ELISA-based detection) across human intestinal segments mounted in Ussing-type chambers, human intestinal (caco-2) cell monolayers grown in transwells, and serum levels after regional intestinal delivery in isoflurane-anesthetized cynomolgus monkeys. RESULTS: In human intestine, there was an increasing proximal-distal gradient of mucosal FcRn mRNA and protein expression. In cynomolgus, serum mAb levels were greater after ileum-proximal colon infusion than after administration to stomach or proximal small intestine (1–5 mg/kg). Serum levels of wild-type mAb dosed into ileum/proximal colon (2 mg/kg) were 124 ± 104 ng/ml (n = 3) compared to 48 ± 48 ng/ml (n = 2) after a non-FcRn binding variant. In vitro, mAb transcytosis in polarized caco-2 cell monolayers and was not enhanced by increased apical cell surface IgG binding to FcRn. An unexpected finding in primate small intestine, was intense FcRn expression in enteroendocrine cells (chromagranin A, GLP-1 and GLP-2 containing). CONCLUSIONS: In adult primates, FcRn is expressed more highly in distal intestinal epithelial cells. However, mAb delivery to that region results in low serum levels, in part because apical surface FcRn binding does not influence mAb transcytosis. High FcRn expression in enteroendocrine cells could provide a novel means to target mAbs for metabolic diseases after systemic administration

The Influence of the Internet on Regional Economic Development—An Empirical Study Based on China’s Provincial Panel Data

With the rapid development of the digital economy, the level of Internet development has become increasingly important to the national economy. The development and application of the Internet have brought new impetus to economic development. At present, China’s economic growth is slowing down. Finding new support points to maintain high-quality economic growth has become the focus of current research. Therefore, at the moment of Internet economic development, it is of great significance to study whether the Internet development level can promote economic development, how to promote economic development and the size of its influence on economic development. Based on this, this paper constructs an indicator system for evaluating the Internet development level from four dimensions: Internet popularization level, information infrastructure development level, scientific and cultural development level, and industrial development and application level. With the Internet development level as the core explanatory variable, this paper establishes a fixed effect model based on the Hausman test by analyzing China’s provincial panel data from 2010 to 2019. The research results show that the Internet development level in all regions of China has risen from 2010 to 2019. The Internet development level has a promoting effect on economic growth, and there are regional differences. The promoting effect on the eastern region is higher than that in the central and western regions. The Internet development level has a significantly higher role in promoting the per capital GDP in the eastern region than in the central and western regions. It is expected to provide valuable ideas for the government to fully harness the role of the Internet in promoting economic development

Research on the Three-phase Voltage Aviation Rectifier Based on Neural Network PID Control

Aimed to the selection of the PID parameters are very difficult in the rectifier design, and can’t realize the online self-turning function of the PID parameters, the three phase voltage source PWM aviation rectifier based on neural network PID control is designed in this paper. This paper analyzes the principle of the voltage source PWM rectifier based on traditional SVPWM, and improves the control algorithm, and completes the hardware design. In addition, the control algorithm, and the circuit are verified through actual experiments. In this rectifier, the PID parameters can realize the function of the online self-turning. The experimental results show that the three-phase PWM rectifier based on neural network control can decrease the harmonic distortion and the power factor reaches to 0.991, which can supply help for the design of the three-phase voltage high power factor aviation rectifier