Objective Mediator 1 (MED1) interacts with transcription factors to regulate transcriptional machinery. The role of MED1 in macrophage biology and the relevant disease state remains to be investigated. Approach and Results To study the molecular mechanism by which MED1 regulates the M1/M2 phenotype switch of macrophage and the effect on atherosclerosis, we generated MED1/apolipoprotein E (ApoE) double-deficient (MED1ΔMac/ApoE−/−) mice and found that atherosclerosis was greater in MED1ΔMac/ApoE−/− mice than MED1fl/fl/ApoE−/− littermates. The gene expression of M1 markers was increased and that of M2 markers decreased in both aortic wall and peritoneal macrophages from MED1ΔMac/ApoE−/− mice, whereas MED1 overexpression rectified the changes in M1/M2 expression. Moreover, low-density lipoprotein receptor-deficient mice received bone marrow from MED1ΔMac mice showed greater atherosclerosis. Mechanistically, MED1 ablation decreased the binding of peroxisome proliferator-activated receptor γ (PPARγ) and enrichment of H3K4me1 and H3K27ac to upstream region of M2 marker genes. Furthermore, interleukin 4 induction of PPARγ and MED1 increased the binding of PPARγ or MED1 to the PPAR response elements of M2 marker genes. Conclusions Our data suggest that MED1 is required for the PPARγ-mediated M2 phenotype switch, with M2 marker genes induced but M1 marker genes suppressed. MED1 in macrophages has an anti-atherosclerotic role via PPARγ-regulated transactivation.

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Error factors of RV reducer are not completely considered, leads to backlash precision is limited, so an improved backlash estimation model is proposed. RV reducer structure and working principle is deeply analyzed, a variety of error factors are considered, and the backlash estimation model is improved according to error propagation. Furthermore, sensitivity of all the error factors are analyzed, RV reducer backlash is obtained through Monte-Carlo simulation, and the simulation results are compared with the traditional computation results. It is conductive to taking fix action in the design stage, reducing backlash, improving the transmission accuracy.

The less conservative co-design problem of dual security control and communication for CPS was studied for a class of nonlinear CPS with an actuator fault and DoS attack based on the DETCS. First, combining with the edge computing thought, data filtering and partial computing tasks were assigned to the network edge devices. The DoS attack with limited energy is converted into a special time delay; thus, the discrete event trigger condition, the actuator fault estimation and regulation, and the robustness for DoS attack can be considered uniformly. A dual security control framework of non-uniformly sampled data system was proposed under the DETCS for CPS, and the T-S fuzzy model of closed-loop nonlinear CPS with the coexistence of fault and attack was established. Second, with the help of time-delay system theory, a robust observer for state and fault estimation and the co-design method of dual security control and communication with the actuator fault and DoS attack were obtained by constructing an appropriate Lyapunov-Krasovskii function and using affine Bessel-Legendre inequality. Finally, the validity and feasibility of the theoretical results were verified by a classical quadruple-tank system. INDEX TERMS Co-design, DoS attack, dual security control, nonlinear CPS. I. INTRODUCTION Cyber-physical systems (CPSs) integrate the 3C technology of computer, communication and control, which is an intelligent system with highly integrated interaction between computing units and physical objects in the network environment [1]. Its emergence has promoted the rapid development of the aerospace, smart cities, smart grids, intelligent transportation and other fields. Furthermore, CPS realizes the information interaction for physical subsystems through various shared communication networks, so the cyber system and the physical system are deeply integrated. However, the diversified communication network in CPSs makes the system more vulnerable to external influences, including cyberattack, malicious code, data fraud, network eavesdropping and so on, which pose a serious threat to the security of the cyber system. In addition, physical system fault is another The associate editor coordinating the review of this manuscript and approving it for publication was Juntao Fei .