Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis.

ZBP1 senses viral Z-RNAs to induce necroptotic cell death to restrain viral infection. ZBP1 is also thought to recognize host cell-derived Z-RNAs to regulate organ development and tissue inflammation in mice. However, it remains unknown how the host-derived Z-RNAs are formed and how these endogenous Z-RNAs are sensed by ZBP1. Here, we report that oxidative stress strongly induces host cell endogenous Z-RNAs, and the Z-RNAs then localize to stress granules for direct sensing by ZBP1 to trigger necroptosis. Oxidative stress triggers dramatically increase Z-RNA levels in tumor cells, and the Z-RNAs then directly trigger tumor cell necroptosis through ZBP1. Localization of the induced Z-RNAs to stress granules is essential for ZBP1 sensing. Oxidative stress-induced Z-RNAs significantly promote tumor chemotherapy via ZBP1-driven necroptosis. Thus, our study identifies oxidative stress as a critical trigger for Z-RNA formation and demonstrates how Z-RNAs are directly sensed by ZBP1 to trigger anti-tumor necroptotic cell death.

A Local TR-MUSIC Algorithm for Damage Imaging of Aircraft Structures.

Lamb wave-based damage imaging is a promising technique for aircraft structural health monitoring, as enhancing the resolution of damage detection is a persistent challenge. In this paper, a damage imaging technique based on the Time Reversal-MUltiple SIgnal Classification (TR-MUSIC) algorithm is developed to detect damage in plate-type structures. In the TR-MUSIC algorithm, a transfer matrix is first established by exciting and sensing signals. A TR operator is constructed for eigenvalue decomposition to divide the data space into signal and noise subspaces. The structural space spectrum of the algorithm is calculated based on the orthogonality of the two subspaces. A local TR-MUSIC algorithm is proposed to enhance the image quality of multiple damages by using a moving time window to establish the local space spectrum at different times or different distances. The multidamage detection capability of the proposed enhanced TR-MUSIC algorithm is verified by simulations and experiments. The results reveal that the local TR-MUSIC algorithm can not only effectively detect multiple damages in plate-type structures with good image quality but also has a superresolution ability for detecting damage with distances smaller than half the wavelength.

Quantifying Hole-Edge Crack of Bolt Joints by Using an Embedding Triangle Eddy Current Sensing Film.

Hole-edge crack quantification of bolt joints is critical for monitoring and estimating structural integrity of aircraft. The paper proposes a new triangle eddy current sensor array for the purpose of increasing the level of quantifying hole-edge crack parameters, especially, the crack angle. The new senor array consists of triangular coils instead of planar rectangular coils. The configuration of the novel sensor array, including the excitation current directions and the excitation winding shape, is optimized by simulation. The ability of the proposed sensing film to identify the crack parameters has been verified by finite element simulations and experiments. Results shows that triangular coils with same current directions in circumferentially adjacent coils and opposite current directions in axially adjacent coils achieve better performance in sensor linearity and resolution compared to rectangular coils. In addition, it has also been proved that the sensing film has a good potential to identify the crack depth and length.

USP38 critically promotes asthmatic pathogenesis by stabilizing JunB protein.

Th2 immune response is critical for allergic asthma pathogenesis. Molecular mechanisms for regulating Th2 immunity are still not well understood. Here we report that the ubiquitin-specific protease USP38 is crucial for Th2-mediated allergic asthma. TCR stimulation up-regulated the USP38 level, and USP38 in turn mediated the protein stabilization of JunB, a transcription factor specific for Th2 development. Consequently, USP38 was specifically required for TCR-induced production of Th2 cytokines and Th2 development both in vitro and in vivo, and USP38-deficient mice were resistant to asthma pathogenesis induced by OVA or HDM. Mechanistically, USP38 directly associated with JunB, deubiquitinated Lys-48-linked poly-ubiquitination of JunB, and consequently blocked TCR-induced JunB turnover. USP38 represents the first identified deubiquitinase specifically for Th2 immunity and the associated asthma.

Anti-diabetic effect of Alpinia oxyphylla extract on 57BL/KsJ db-/db- mice.

Diabetes mellitus is characterized by high blood glucose levels. Increased levels of reactive oxygen species (ROS) may disrupt insulin signaling and result in insulin resistance. The Alpinia oxyphylla extract (AOE) possesses powerful antioxidant activity and may therefore inhibit the development of insulin resistance. The objective of the present study was to determine the effects of AOE on blood glucose, insulin and lipid levels in a type II diabetic nephropathy animal model (C57BIKsj db-/db-). All experiments were performed on male C57BL/Ks DB/DB and db-/db- mice that were left to acclimatize for 1 week prior to the experimental period. AOE was administered to these mice at different dosages (100, 300 and 500 mg/kg) for 8 weeks. The results demonstrated that AOE did not affect mouse weight, while blood glucose concentrations were found to significantly decrease in a dose-dependent manner (P<0.05). The effect of administering 500 mg/kg AOE (AOE500) to db-/db- mice was tested further. Treatment with AOE500 for 8 weeks led to improved glucose tolerance and reduced plasma insulin concentrations (P<0.05), as well as a significant decrease in triglyceride concentrations (P<0.05) and levels of total cholesterol (P<0.05) in db-/db- mice. Furthermore, treatment with AOE500 decreased the concentration of malondialdehyde, elevated the concentration of glutathione and increased the activities of the antioxidant enzymes superoxide dismutase and peroxidase (P<0.05) in the livers of db-/db- mice. Meanwhile, AOE-treated mice exhibited significantly reduced urine albumin, creatinine and blood urea nitrogen excretion (P<0.05). In parallel, the upregulated expression of phosphatase and tensin homolog (PTEN) in the liver and kidneys of db-/db- mice was impaired following AOE500 treatment. The results of the present study suggest that AOE regulates blood glucose and lipid levels and improves renal function by mediating oxidative stress and PTEN expression at the onset of type II diabetes mellitus.