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Cyclic GMP–AMP (cGAMP) is a second messenger that activates the stimulator of interferon genes (STING) innate immune pathway to induce the expression of type I interferons (IFNs) and other cytokines. Pharmacological activation of STING is considered a potent therapeutic strategy in cancer. In this study, we employed a cell-based phenotypic screen and identified podophyllotoxin (podofilox), a microtubule destabilizer, as a robust enhancer of the cGAMP–STING signaling pathway. We found that podofilox enhanced the cGAMP-mediated immune response by increasing STING-containing membrane puncta and the extent of STING oligomerization. Furthermore, podofilox changed the trafficking pattern of STING and delayed trafficking-mediated STING degradation. Importantly, the combination of cGAMP and podofilox had profound antitumor effects on mice by activating the immune response through host STING signaling. Together, these data provide insights into the regulation of cGAMP–STING pathway activation and demonstrate what we believe to be a novel approach for modulating this pathway and thereby promoting antitumor immunity.

Understanding the characteristics of stochastic loading is the premise and foundation for structure analysis. Traditional amplitude spectrum and power spectral density (PSD) method based on Fourier transform (FT) has limitation, that is, it loses any information with time and can not reflect the non-stationary characteristics of stochastic loading. Wavelet transform possesses assembling ability in both time and frequency domain,and it possess stronger ability of analyzing non-stationary signal. In this paper, the method of estimating PSD and time-dependent PSD of stochastic loading using wavelet transform is researched. The calculating process is programmed and the method is validated by a numerical example. The analysis result of example indicates that the method presented in this paper is feasible.

This paper studies power allocation in coordinated multi-point (CoMP) transmission of 3GPP LTE-Advanced system with remote radio units(RRUs) power constraints. We apply block diagonal (BD) precoding to downlink transmission, and assume perfect knowledge of downlink channels and transmit messages at each transmit point. We propose a modified water-filling power (MWF) allocation algorithm in order to maximize the downlink sum capacity, at the same time the low complexity is achieved. The interior-point method is also used to solve the optimization problem. Simulations show that interior-point method converges after only a few iterative steps and the system capacity is near-optimal. As for complexity and power efficiency, MWF achieves a good compromise