Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) are essential components of the innate immune sensors to cytosolic DNA and elicit type I interferon (IFN). Recent studies have revealed that manganese (Mn) can enhance cGAS and STING activation to viral infection. However, the role of Mn in antitumor immunity has not been explored. Here, we designed a nanoactivator, which can induce the presence of DNA in cytoplasm and simultaneously elevate Mn 2+ accumulation within tumor cells. In detail, amorphous porous manganese phosphate (APMP) NPs that are highly responsive to tumor microenvironment were employed to construct doxorubicin (DOX)-loaded and phospholipid (PL)-coated hybrid nanoparticles (PL/APMP-DOX NPs). PL/APMP-DOX NPs were stably maintained during systemic circulation, but triggered to release DOX for inducing DNA damage and Mn 2+ to augment cGAS/STING activity. We found that PL/APMP-DOX NPs with superior tumor-targeting capacity boosted dendritic cell maturation and increased cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment into the tumor site. Furthermore, the NPs increased production of type I IFN and secretion of pro-inflammatory cytokines (for example, TNF-α and IL-6). Consequently, PL/APMP-DOX NPs exhibited excellent antitumor efficacy and prolonged the lifespan of the tumor-bearing mice. Collectively, we developed a PL-decorated Mn-based hybrid nanoactivator to intensify immune activation and that might provide therapeutic potential for caner immunotherapy.

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The software trustworthiness is an important feature for the safety and security of cyber-physical system. Therefore, how to assess software trustworthiness is the key issue. Tao has recently given five measurement models of software trustworthiness based on the attributes of software in his Doctoral Dissertation and his publications. After simulating these models with the Monte Carlo method, we find out that these models have a common shortcoming that the trustworthy degree would not be within the same range as the range in which all attributes' values are. In order to solve this problem, this paper introduces the stability rule with which measurement model of software trustworthiness is proposed. According to these rules, this paper proposes two models which are originally based on Tao's models. The succeeding mathematical proof and simulation demonstrate that these models meet all the rules. These two models have been applied to compute the degree of software trustworthiness in the software trustworthy measurement and evaluation tool.

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