Prevention of Diabetic Complications by Activation of Nrf2: Diabetic Cardiomyopathy and Nephropathy

Diabetic cardiomyopathy and nephropathy are two major causes of death of patients with diabetes. Extra generation of reactive oxygen species (ROS), induced by hyperglycemia, is considered as the main reason for the development of these diabetic complications. Transcription factor, NFE2-related factor 2 (Nrf2), is a master regulator of cellular detoxification response and redox status, and also provides a protective action from various oxidative stresses and damages. Recently we have demonstrated its important role in determining the susceptibility of cells or tissues to diabetes-induced oxidative stress and/or damage. Therefore, this review will specifically summarize the information available regarding the effect of Nrf2 on the diabetic complications with a focus on diabetic cardiomyopathy and nephropathy. Given the feature that Nrf2 is easily induced by several compounds, we also discussed the role of different Nrf2 activators in the prevention or therapy of various diabetic complications. These findings suggest that Nrf2 has a potential application in the clinic setting for diabetic patients in the short future

High levels of Notch signaling down-regulate Numb and Numblike

Inhibition of Notch signaling by Numb is critical for many cell fate decisions. In this study, we demonstrate a more complex relationship between Notch and the two vertebrate Numb homologues Numb and Numblike. Although Numb and Numblike at low levels of Notch signaling negatively regulated Notch, high levels of Notch signaling conversely led to a reduction of Numb and Numblike protein levels in cultured cells and in the developing chick central nervous system. The Notch intracellular domain but not the canonical Notch downstream proteins Hes 1 and Hey 1 caused a reduction of Numb and Numblike. The Notch-mediated reduction of Numblike required the PEST domain in the Numblike protein and was blocked by the proteasome inhibitor MG132. Collectively, these observations reveal a reciprocal negative regulation between Notch and Numb/Numblike, which may be of relevance for stabilizing asymmetric cell fate switches and for tumor development

Design and Fabrication of a MEMS Flow Sensor and Its Application in Precise Liquid Dispensing

A high speed MEMS flow sensor to enhance the reliability and accuracy of a liquid dispensing system is proposed. Benefitting from the sensor information feedback, the system can self-adjust the open time of the solenoid valve to accurately dispense desired volumes of reagent without any pre-calibration. First, an integrated high-speed liquid flow sensor based on the measurement of the pressure difference across a flow channel is presented. Dimensions of the micro-flow channel and two pressure sensors have been appropriately designed to meet the static and dynamic requirements of the liquid dispensing system. Experiments results show that the full scale (FS) flow measurement ranges up to 80 μL/s, with a nonlinearity better than 0.51% FS. Secondly, a novel closed-loop control strategy is proposed to calculate the valve open time in each dispensing cycle, which makes the system immune to liquid viscosity, pressure fluctuation, and other sources of error. Finally, dispensing results show that the system can achieve better dispensing performance, and the coefficient of variance (CV) for liquid dispensing is below 3% at 1 μL and below 4% at 100 nL

A Magnetically and Thermally Controlled Liquid Metal Variable Stiffness Material

Smart materials that can actively tune their stiffness are of great interest to many fields, including the construction industry, medical devices, industrial machines, and soft robotics. However, developing a material that can offer a large range of stiffness change and rapid tuning remains a challenge. Herein, a liquid metal variable stiffness material (LMVSM) that can actively and rapidly tune its stiffness by applying an external magnetic field or by changing the temperature is developed. The LMVSM is composed of three layers: a gallium–iron magnetorheological fluid (Ga–Fe MRF) layer for providing variable stiffness, a nickel–chromium wire layer for Joule heating, and a soft heat dissipation layer for accelerating heating and rapid cooling. The stiffness can be rapidly increased by 4 times upon the application of a magnetic field or 10 times by solidifying the Ga–Fe MRF. Finally, the LMVSM is attached to a pneumatically controlled soft robotic gripper to actively tune its load capacity, demonstrating its potential to be further developed into smart components that can be widely adopted by smart devices