Malignant tumors develop multiple mechanisms to impair and escape from antitumor immune responses, of which tumor-associated macrophages that often show immunosuppressive phenotype (M2), play a critical role in tumor-induced immunosuppression. Therefore, strategies that can reverse M2 phenotype and even enhance immune-stimulation function of macrophage would benefit tumor immunotherapy. In this paper, self-assembled glyco-nanoparticles (glyco-NPs), as artificial glycocalyx, have been found to be able to successfully induce the polarization of mouse primary peritoneal macrophages from M2 to inflammatory type (M1). The polarization change was evidenced by the decreased expression of cell surface signaling molecules CD206 and CD23, and the increased expression of CD86. Meanwhile, secretion of cytokines supported this polarization change as well. More importantly, this phenomenon is observed not only in vitro, but also in vivo. As far as we known, this is the first report about macrophage polarization being induced by synthetic nanomaterials. Moreover, preparation, characterization of these glyco-NPs and their interaction with the macrophages are also demonstrated.
In recent years, self-assembly of block or graft copolymers with sugar-containing component has drawn great attention. We just reported that protection−deprotection chemistry could initiate self-assembly of glycopolymers based on the high polarity change induced by the deprotection. Considering that the protection−deprotection is so common and its variety in glycochemistry, it is worth developing this finding into a new and general strategy of self-assembly of glyco-containing polymers. For this purpose, this article focuses on the kinetics and morphology control of the assemblies of glyco-block copolymers induced by the deprotection. Benzoyl (Bz) as the protective group was introduced, which has much lower deprotection rate than acetyl group (Ac) reported previously. Thus, the detailed kinetic study of the self-assembly of Bz copolymer by means of in situ light scattering and 1 H NMR, etc., became possible. The morphologies of all of the resultant assemblies were observed by cryo-TEM. Thus, we found that in the case of using an equivalent catalyst TBAOH, with the progress of deprotection of Bz, the copolymer follows three-stage assembly, i.e., fast initiation, steady growth, and then fission/reorganization into stable state. In most conditions, both Bz and Ac copolymers form stable vesicles, but the former is apparently larger than the latter. This is because that the slow deprotection of Bz makes the resultant assemblies assume structures closer to equilibrium, and the fast reaction of Ac makes the assemblies with more kinetic-trapped features.
Systemic immune-inflammation index (SII) emerged as a biomarker of chronic inflammation and an independent prognostic factor for many cancers. We aimed to investigate the associations of SII level with total and cause-specific mortality risks in the general populations, and the potential modification effects of lifestyle-related factors on the above associations. In this study, we included 30,521 subjects from the Dongfeng-Tongji (DFTJ) cohort and 25,761 subjects from the National Health and Nutrition Examination Survey (NHANES) 1999–2014. Cox proportional hazards regression models were used to estimate the associations of SII with mortality from all-cause, cardiovascular diseases (CVD), cancer and other causes. In the DFTJ cohort, compared to subjects in the low SII subgroup, those within the middle and high SII subgroups had increased risks of total mortality [hazard ratio, HR (95% confidence interval, CI) = 1.12 (1.03–1.22) and 1.26 (1.16–1.36), respectively) and CVD mortality [HR (95%CI) = 1.36 (1.19–1.55) and 1.50 (1.32–1.71), respectively]; those within the high SII subgroup had a higher risk of other causes mortality [HR (95%CI) = 1.28 (1.09–1.49)]. In the NHANES 1999–2014, subjects in the high SII subgroup had higher risks of total, CVD, cancer and other causes mortality [HR (95%CI) = 1.38 (1.27–1.49), 1.33 (1.11–1.59), 1.22 (1.04–1.45) and 1.47 (1.32–1.63), respectively]. For subjects with a high level of SII, physical activity could attenuate a separate 30% and 32% risk of total and CVD mortality in the DFTJ cohort, and a separate 41% and 59% risk of total and CVD mortality in the NHANES 1999–2014. Our study suggested high SII level may increase total and CVD mortality in the general populations and physical activity exerted a beneficial effect on the above associations.
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