Although serum amyloid A (SAA) is an excellent marker for coronary artery disease, its direct effect on atherogenesis in vivo is obscure. In this study we investigated the direct effect of SAA on promoting the formation of atherosclerosis in apolipoprotein E-deficient (ApoE -/-) mice. Murine SAA lentivirus was constructed and injected into ApoE -/-mice intravenously. Then, experimental mice were fed a chow diet (5% fat and no added cholesterol) for 14 wks. The aortic atherosclerotic lesion area was larger with than without SAA treatment. With increased SAA levels, the plasma levels of interleukin-6 and tumor necrosis factor-α were significantly increased. Macrophage infiltration in atherosclerotic regions was enhanced with SAA treatment. A migration assay revealed prominent dose-dependent chemotaxis of SAA to macrophages. Furthermore, the expression of monocyte chemotactic protein-1 and vascular cell adhesion molecule-1 (VCAM-1) was upregulated significantly with SAA treatment. SAA-induced VCAM-1 production was detected in human aortic endothelial cells in vitro. Thus, an increase in plasma SAA directly accelerates the progression of atherosclerosis in ApoE -/-mice. SAA is not only a risk marker for atherosclerosis but also an active participant in atherogenesis.

Traditional shape memory polymers (SMPs) are mostly thermoresponsive, and their applications in nano-optics are hindered by heat-demanding programming and recovery processes. By integrating a polyurethane-based shape memory copolymer with templating nanofabrication, reconfigurable/rewritable macroporous photonic crystals have been demonstrated. This SMP coupled with the unique macroporous structure enables unusual all-room-temperature shape memory cycles. "Cold" programming involving microscopic order-disorder transitions of the templated macropores is achieved by mechanically deforming the macroporous SMP membranes. The rapid recovery of the permanent, highly ordered photonic crystal structure from the temporary, disordered configuration can be triggered by multiple stimuli including a large variety of vapors and solvents, heat, and microwave radiation. Importantly, the striking chromogenic effects associated with these athermal and thermal processes render a sensitive and noninvasive optical methodology for quantitatively characterizing the intriguing nanoscopic shape memory effects. Some critical parameters/mechanisms that could significantly affect the final performance of SMP-based reconfigurable photonic crystals including strain recovery ratio, dynamics and reversibility of shape recovery, as well as capillary condensation of vapors in macropores, which play a crucial role in vapor-triggered recovery, can be evaluated using this new optical technology.

The existence of tumor heterogeneity and complex carcinogenic mechanisms in lung adenocarcinoma (LUAD) make the most commonly used TNM staging system unable to well-interpret the prognosis of patients. Using transcriptome profiling and clinical data from The Cancer Genome Atlas (TCGA) database, we constructed an immune signature based on a multivariate Cox analysis (stepwise model). We estimated the half-maximal inhibitory concentration (IC50) of chemotherapeutic drugs in patients according to the pRRophetic algorithm. Gene-set variation analysis (GSVA) was used to reveal pathway enrichment between groups. Moreover, immune microenvironment landscape was described by single-sample gene-set enrichment analysis (ssGSEA) and CIBERSORT and systematically correlated with genomic of these patients. A prognostic nomogram combining the immune signature and TNM stage to predict the prognosis was developed by multivariate Cox regression. The novel signature with four immune-related genes (MAL, MS4A1, OAS1, and WFDC2) had good robustness, which can accurately distinguish between high-and low-risk patients. Compared with low-risk patients, high-risk patients with a worse prognosis (5-year OS: 46.5 vs. 59.4%, p = 0.002) could benefit more from immunotherapy and the application of common chemotherapeutic agents such as cisplatin and paclitaxel (Wilcoxon test, all p < 0.05). There were significant differences in tumor immune microenvironment and metabolic pathways between the two groups. Additionally, the constructed nomogram had reliable predictive performance with the C-index of 0.725 (95% CI = 0.668-0.781) in the development set (n = 500), 0.793 (95% CI = 0.728-0.858) in the internal validation set (n = 250) and 0.679 (95% CI = 0.644-0.714) in the external validation set (n = 442). The corresponding calibration curves also showed good consistency. To sum up, we developed an immune-related gene signature and comprehensively evaluated LUAD immune landscape and metabolic pathways. Effective differentiation of high-and low-risk patients and accurate construction of nomogram would be helpful to the development of individualized treatment strategies.

No abstract

Lipid peroxides accumulation induced ferroptosis is an effective cell death pathway for cancer therapy. However, the hypoxic condition of tumor microenvironment significantly suppresses the efficacy of ferroptosis. Here, we design a novel nanoplatform to overcome hypoxia-induced ferroptosis resistance. Specifically, we synthesize a novel kind of perfluorocarbon (PFOB)@manganese oxide (MnOx) core-shell nanoparticles (PM-CS NPs). Owing to the good carrier of O 2 as fuel, PM-CS NPs can induce higher level of ROS generation, lipid peroxidation and GSH depletion, as well as lower activity of GPX4, compared with MnOx NPs alone. Moreover, the supplement of O 2 can relieve tumor hypoxia to break down the storage of intracellular lipid droplets and increase expression of ACSL4 (a symbol for ferroptosis sensitivity). Furthermore, upon stimulus of GSH or acidity, PM-CS NPs exhibit the "turn on" 19 F-MRI signal and activatable T 1 /T 2 -MRI contrast for correlating with the release of Mn. Finally, PM-CS NPs exert high cancer inhibition rate for ferroptosis based therapy via synergetic combination of O 2 -mediated enhancement of key pathways of ferroptosis.