PPARγ modulates energy metabolism and inflammation. However, its specific functions in the balance of immunity in vivo have been explored incompletely. In this study, by the age of 14 mo, PpargC/− mice with PPARγ expression at 25% of the normal level exhibited high autoantibody levels and developed mesangial proliferative glomerulonephritis, which resembled systemic lupus erythematosus (SLE)-like autoimmune disease. These symptoms were preceded by splenomegaly at an early age, which was associated with increases in splenocyte accumulation and B-cell activation but not with relocation of hematopoiesis to the spleen. The mechanism of splenic lymphocyte accumulation involved reduced sphingosine-1-phosphate receptor 1 (S1P1) expression and diminished migration toward S1P in the PpargC/− splenocytes, which impeded lymphocyte egression. Mechanistically, increased Th17 polarization and IL-17 signaling in the PpargC/− CD4+ T cells contributed to B-cell hyperactivation in the spleen. Finally, the activation of the remaining PPARγ in PpargC/− mice by pioglitazone increased S1P1 levels, reduced the Th17 population in the spleen, and ameliorated splenomegaly. Taken together, our data demonstrated that reduction of Pparg expression in T-helper cells is critical for spontaneous SLE-like autoimmune disease development; we also revealed a novel function of PPARγ in lymphocyte trafficking and cross talk between Th17 and B cells.
The total synthesis of quebrachamine was achieved through the macrolactamization of cis‐2‐alkenylated indole 17, which was prepared by a Sonogashira reaction between indole 5b and piperidine 11 followed by cis‐hydrogenation. We found that stoichiometric copper(I) iodide limited the undesired Glaser‐type homocoupling of alkyne 11 that would otherwise take place during the Sonogashira coupling. This direct approach allowed the total synthesis in ten linear steps starting from commercially available chemicals. Conditions for the reduction of lactam 19 by lithium aluminiumhydride were adjustable, so that either (±)‐quebrachamine or the analogue (±)‐kopsiyunnanine D was prepared.
Due to the rapid development of Internet technology, the greater demand for multimedia services causes the traffic collisions increasing. 3rd Generation Partnership Project (3GPP) specified IP Multimedia Subsystem (IMS) for next generation network service. For the real-time multimedia service such as video streaming, it requires a large amount of bandwidth resource. Besides, the different ongoing media sessions may cause traffic collisions. In this paper, we propose a dynamic video streaming quality adaption method for IMS. The video quality will dynamic adjust according to the background traffic, reducing bandwidth congestion when overall network loading is high. The simulation results show that by adopting proposed video adaption method, the service quality and reliability can be maintained.
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