Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15

IL-15 and NKG2D promote autoimmunity and celiac disease by arming cytotoxic T lymphocytes (CTLs) to cause tissue destruction. However, the downstream signaling events underlying these functional properties remain unclear. Here, we identify cytosolic phospholipase A2 (cPLA2) as a central molecule in NKG2D-mediated cytolysis in CTLs. Furthermore, we report that NKG2D induces, upon recognition of MIC+ target cells, the release of arachidonic acid (AA) by CTLs to promote tissue inflammation in association with target killing. Interestingly, IL-15, which licenses NKG2D-mediated lymphokine killer activity in CTLs, cooperates with NKG2D to induce cPLA2 activation and AA release. Finally, cPLA2 activation in intraepithelial CTLs of celiac patients provides an in vivo pathophysiological dimension to cPLA2 activation in CTLs. These results reveal an unrecognized link between NKG2D and tissue inflammation, which may underlie the emerging role of NKG2D in various immunopathological conditions and define new therapeutic targets

Monitoring System of Transmission Line in Mountainous Area Based on LPWAN

In light of the difficulty of the inspection and maintenance of a transmission line condition monitoring system in remote mountainous areas, this paper proposes a long-term online monitoring scheme based on a low power wide area network (LPWAN). Considering different failure rates, three monitoring periods of transmission lines in mountainous areas are proposed. An online monitoring framework of transmission lines in mountainous areas was designed based on long range radio (LoRa) and a cellular mobile network, and a dynamic group network model of LoRa was established. The multi-objective particle swarm optimization algorithm can be used to optimize the energy and delay of the system, and then the suitable working mode for the three monitoring periods can be obtained. The simulation results showed that the minimum packet loss rate of the system could be less than 1%, the energy consumption of the system was 80% lower than the existing monitoring system, and the service life of the system can reach 15.13 years under the normal failure rate. Compared with the existing schemes, the proposed work shows the advantages of high reliability transmission, low cost and long-term monitoring, which is especially for transmission line monitoring in mountainous areas

eIF4A1 Inhibitor Suppresses Hyperactive mTOR-Associated Tumors by Inducing Necroptosis and G2/M Arrest

Aberrantly activated mechanistic target of rapamycin (mTOR) signaling pathway stimulates translation initiation/protein synthesis and eventually causes tumors. Targeting these processes thus holds potential for treating mTOR-associated diseases. We tested the potential of eFT226, a sequence-selective inhibitor of eIF4A-mediated translation, in the treatment of mTOR hyperactive cells caused by the deletion of tuberous sclerosis complex 1/2 (TSC1/2) or phosphatase and TENsin homology (PTEN). eFT226 preferentially inhibited the proliferation of Tsc2- and Pten-deficient cells by inducing necroptosis and G2/M phase arrest. In addition, eFT226 blocked the development of TSC2-deficient tumors. The translation initiation inhibitor is thus a promising regimen for the treatment of hyperactive mTOR-mediated tumors

Parametric Study on Thermo-Hydraulic Performance of NACA Airfoil Fin PCHEs Channels

In this work, a discontinuous airfoil fin printed circuit heat exchanger (PCHE) was used as a recuperator in a micro gas turbine system. The effects of the airfoil fin geometry parameters (arc height, maximum arc height position, and airfoil thickness) and the airfoil fin arrangements (horizontal and vertical spacings) on the PCHE channel’s thermo-hydraulic performance were extensively examined by a numerical parametric study. The flow features, local heat transfer coefficient, and wall shear stress were examined in detail to obtain an enhanced heat transfer mechanism for a better PCHE design. The results show that the heat transfer and flow resistance were mainly increased at the airfoil leading edge owing to a flow jet, whereas the airfoil trailing edge had little effect on the thermo-hydraulic performance. The airfoil thickness was the most significant while the arc height and the vertical spacing were moderately significant to the performance. Moreover, only the airfoil thickness had a significant effect on the PCHE compactness. Based on a comprehensive investigation, two solutions NACA-6230 and -3220 were selected owing to their better thermal performance and smaller pressure drop, respectively, with horizontal spacings of 2 mm and vertical spacings of 2 or 3 mm

Dendritic cells pulsed with placental gp96 promote tumor-reactive immune responses.

Defining and loading of immunogenic and safe cancer antigens remain a major challenge for designing dendritic cell (DC)-based cancer vaccines. In this study, we defined a prototype strategy of using DC-based vaccines pulsed with placenta-derived heat shock protein gp96 to induces anti-tumor T cell responses. Placental gp96 was efficiently taken up by CD11c+ bone marrow-derived DCs (BMDCs) and resulted in moderate BMDC maturation. Splenocytes and cytotoxic T cells (CTLs) generated with mouse BMDCs pulsed with placental gp96 specifically lysed B16 melanoma and LLC lung carcinoma cells. In both transplantable melanoma and lung carcinoma mice models, immunization with placental gp96-stimulated BMDCs led to a significant decrease in tumor growth and mouse mortality with respect to mice treated with liver gp96-pulsed BMDCs or placental gp96 alone. This vaccine induced strong cross-reactive tumor-specific T cell responses. Our results revealed that DCs pulsed with placenta-derived gp96 represent an effective immunotherapy to induce tumor-reactive immune responses, possibly via loading DCs with its associated carcinoembryonic antigens