Highlights d RBD and HR nanoparticle vaccines induce potent neutralizing antibody responses d Nanoparticle vaccines protect against SARS-CoV-2 infection in mice d HR antigens elicit both humoral and cellular immune responses d HR antigens within nanoparticles contribute to crossprotective immunity

Background The aging rate in Taiwan is the second highest in the world. As the population ages quickly, the prevalence of dementia increases rapidly. There are some studies that have explored the association between air pollution and cognitive decline, but the association between air pollution and dementia has not been directly evaluated. Methods This was a case-control study comprising 249 Alzheimer's disease (AD) patients, 125 vascular dementia (VaD) patients, and 497 controls from three teaching hospitals in northern Taiwan from 2007 to 2010. Data of particulate matter <10 μm in diameter (PM 10 ) and ozone were obtained from the Taiwan Environmental Protection Administration for 12 and 14 years, respectively. Blood samples were collected to determine the apolipoprotein E ( APOE ) ɛ4 haplotype. Bayesian maximum entropy was used to estimate the individual exposure level of air pollutants, which was then tertiled for analysis. Conditional logistic regression models were used to estimate adjusted odds ratios (AORs) and 95% confidence intervals between the association of PM 10 and ozone exposure with AD and VaD risk. Results The highest tertile of PM 10 (≥49.23 μg/m 3 ) or ozone (≥21.56 ppb) exposure was associated with increased AD risk (highest vs. lowest tertile of PM 10 : AOR = 4.17; highest vs. lowest tertile of ozone: AOR = 2.00). Similar finding was observed for VaD. The association with AD and VaD risk remained for the highest tertile PM 10 exposure after stratification by APOE ɛ4 status and gender. Conclusions Long-term exposure to the highest tertile of PM 10 or ozone was significantly associated with an increased risk of AD and VaD.

The inhibitory receptors PD-1, Tim-3, and Lag-3 are highly expressed on tumor-infiltrating lymphocytes and compromise their antitumor activity. For efficient cancer immunotherapy, it is important to prevent chimeric antigen receptor T (CAR-T)-cell exhaustion. Here we downregulate these three checkpoint receptors simultaneously on CAR-T cells and that show the resulting PTL-CAR-T cells undergo epigenetic modifications and better control tumor growth. Furthermore, we unexpectedly find increased tumor infiltration by PTL-CAR-T cells and their clustering between the living and necrotic tumor tissue. Mechanistically, PTL-CAR-T cells upregulate CD56 (NCAM), which is essential for their effector function. The homophilic interaction between intercellular CD56 molecules correlates with enhanced infiltration of CAR-T cells, increased secretion of interferon-γ, and the prolonged survival of CAR-T cells. Ectopically expressed CD56 promotes CAR-T cell survival and antitumor response. Our findings demonstrate that genetic blockade of three checkpoint inhibitory receptors and the resulting high expression of CD56 on CAR-T cells enhances the inhibition of tumor growth.