Inducible miR-145 expression by HIF-1a protects cardiomyocytes against apoptosis via regulating SGK1 in simulated myocardial infarction hypoxic microenvironment

   Background: Myocardial infarction (MI) is partly due to myocardial cell damage caused by hypoxia. MicroRNAs (miRNAs) have been proved to be closely related to the development and progression of many cardiovascular diseases. This study investigated the role of miR-145 in cardiomyocytes under hypoxic condition. Methods: The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to test miR-145 expression in H9c2 cells with hypoxia-inducible factor (HIF)-a abnormal expression under hypoxic condition. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide (MTT), Tran­swell assay and flow cytometry were used to investigate the effects of miR-145 on cell viability, migration and apoptosis under normoxic or hypoxic condition, respectively. Meanwhile, reactive oxygen species (ROS) content in hypoxic H9c2 cells was analyzed. Western blotting was used to explore the potential mechanism of miR-145 protective effects on cardiomyocytes. Expression levels of miR-145 and SGK1 in rat MI model were also assessed. Results: Results showed that miR-145 was upregulated in H9c2 and HL-1 cells under hypoxic condi­tion, which was promoted by HIF-1a. MiR-145 overexpression enhanced cell viability and migration under normoxic condition. Under hypoxic condition, miR-145 overexpression promoted cell viability, inhibited apoptosis and ROS activity. Western blotting results proved that miR-145 overexpression inhibited the activation of apoptotic related factors, and promoted activation of PI3K/AKT signaling pathway via SGK1 upregulation. Expression levels of miR-145 and SGK1 were both upregulated in rat MI models. Conclusions: HIF-1a could induce miR-145 upregulation in hypoxic H9c2 and HL-1 cells. MiR-145 protected H9c2 cells against hypoxic damage. SGK1 upregulation and activated PI3K/AKT may have participated in the protective effects of miR-145 on cardiomyocytes

Adversarial Samples on Android Malware Detection Systems for IoT Systems

Many IoT(Internet of Things) systems run Android systems or Android-like systems. With the continuous development of machine learning algorithms, the learning-based Android malware detection system for IoT devices has gradually increased. However, these learning-based detection models are often vulnerable to adversarial samples. An automated testing framework is needed to help these learning-based malware detection systems for IoT devices perform security analysis. The current methods of generating adversarial samples mostly require training parameters of models and most of the methods are aimed at image data. To solve this problem, we propose a \textbf{t}esting framework for \textbf{l}earning-based \textbf{A}ndroid \textbf{m}alware \textbf{d}etection systems(TLAMD) for IoT Devices. The key challenge is how to construct a suitable fitness function to generate an effective adversarial sample without affecting the features of the application. By introducing genetic algorithms and some technical improvements, our test framework can generate adversarial samples for the IoT Android Application with a success rate of nearly 100\% and can perform black-box testing on the system

Substrate-Favored Lysosomal and Proteasomal Pathways Participate in the Normal Balance Control of Insulin Precursor Maturation and Disposal in β-Cells

Our recent studies have uncovered that aggregation-prone proinsulin preserves a low relative folding rate and maintains a homeostatic balance of natively and non-natively folded states (i.e., proinsulin homeostasis, PIHO) in β-cells as a result of the integration of maturation and disposal processes. Control of precursor maturation and disposal is thus an early regulative mechanism in the insulin production of β-cells. Herein, we show pathways involved in the disposal of endogenous proinsulin at the early secretory pathway. We conducted metabolic-labeling, immunoblotting, and immunohistochemistry studies to examine the effects of selective proteasome and lysosome or autophagy inhibitors on the kinetics of proinsulin and control proteins in various post-translational courses. Our metabolic-labeling studies found that the main lysosomal and ancillary proteasomal pathways participate in the heavy clearance of insulin precursor in mouse islets/β-cells cultured at the mimic physiological glucose concentrations. Further immunoblotting and immunohistochemistry studies in cloned β-cells validated that among secretory proteins, insulin precursor is heavily and preferentially removed. The rapid disposal of a large amount of insulin precursor after translation is achieved mainly through lysosomal autophagy and the subsequent basal disposals are carried out by both lysosomal and proteasomal pathways within a 30 to 60-minute post-translational process. The findings provide the first clear demonstration that lysosomal and proteasomal pathways both play roles in the normal maintenance of PIHO for insulin production, and defined the physiological participation of lysosomal autophagy in the protein quality control at the early secretory pathway of pancreatic β-cells

Multi-mode resonator-fed dual polarized antenna array with enhanced bandwidth and selectivity

A novel design concept of multi-mode filtering antenna, which is realized by integrating a multi-mode resonator and an antenna, has been applied to the design of dual-polarized antenna arrays for achieving a compact size and high performance in terms of broad bandwidth, high frequency selectivity and out-of-band rejection. To verify the concept, a 2×2 array at C-band is designed and fabricated. The stub-loaded resonator (SLR) is employed as the feed of the antenna. The resonant characteristics of SLR and patch as well as the coupling between them are presented. The method of designing the integrated resonator-patch module is explained. This integrated design not only removes the need for separated filters and traditional 50 Ω interfaces, but also improves the frequency response of the module. A comparison with the traditional patch array has been made, showing that the proposed design has a more compact size, wider bandwidth, better frequency selectivity and out-of-band rejection. Such low-profile light weigh broadband dual polarized arrays are useful for space-borne synthetic aperture radar (SAR) and wireless communication applications. The simulated and measured results agree well, demonstrating a good performance in terms of impedance bandwidth, frequency selectivity, isolation, radiation pattern and antenna gain

FPGA-Based Implementation of All-Digital QPSK Carrier Recovery Loop Combining Costas Loop and Maximum Likelihood Frequency Estimator

This paper presents an efficient all digital carrier recovery loop (ADCRL) for quadrature phase shift keying (QPSK). The ADCRL combines classic closed-loop carrier recovery circuit, all digital Costas loop (ADCOL), with frequency feedward loop, maximum likelihood frequency estimator (MLFE) so as to make the best use of the advantages of the two types of carrier recovery loops and obtain a more robust performance in the procedure of carrier recovery. Besides, considering that, for MLFE, the accurate estimation of frequency offset is associated with the linear characteristic of its frequency discriminator (FD), the Coordinate Rotation Digital Computer (CORDIC) algorithm is introduced into the FD based on MLFE to unwrap linearly phase difference. The frequency offset contained within the phase difference unwrapped is estimated by the MLFE implemented just using some shifter and multiply-accumulate units to assist the ADCOL to lock quickly and precisely. The joint simulation results of ModelSim and MATLAB show that the performances of the proposed ADCRL in locked-in time and range are superior to those of the ADCOL. On the other hand, a systematic design procedure based on FPGA for the proposed ADCRL is also presented