Highlights d Antibodies against SARS-CoV-2 S protein are isolated from an elite neutralizer d Receptor-binding domain (RBD) antibodies target four groups of non-overlapping epitopes d Group IV antibodies induce antibody-dependent enhancement (ADE) of entry in Raji cells d Group II/III antibodies neutralize SARS-CoV-2 without mediating ADE of entry in vitro

Background: Previous studies have shown race/ethnicity, particularly African American and/or Hispanic status, to be a predictor of overweight/obese status in children. However, these studies have failed to adjust for low socioeconomic status (SES). This study assessed whether race/ethnicity remained an independent predictor of childhood obesity when accounting for variations in SES (lowincome) among communities in Massachusetts.Methods: This study was based on 2009 summarized data from 68 Massachusetts school districts with 111,799 students in grades 1, 4, 7, and 10. We studied the relationship between the rate of overweight/obese students (mean = 0.32; range = 0.10-0.46), the rate of African American and Hispanic students (mean = 0.17; range = 0.00-0.90), and the rate of low-income students (mean = 0.27; range = 0.02-0.87) in two and three dimensions. The main effect of the race/ethnicity rate, the low-income rate, and their interaction on the overweight and obese rate was investigated by multiple regression modeling.Results: Low-income was highly associated with overweight/obese status ( p < 0.0001), whereas the effect of race/ethnicity ( p = 0.27) and its interaction ( p = 0.23) with low-income were not statistically significant. For every 1% increase in low-income, there was a 1.17% increase in overweight/obese status. This pattern was observed across all African American and Hispanic rates in the communities studied.Conclusions: Overweight/obese status was highly prevalent among Massachusetts students, varying from 10% to 46% across communities. Although there were higher rates of overweight/obese status among African American and Hispanic students, the relationship disappeared when controlling for family income. Our findings suggest low SES plays a more significant role in the nation's childhood obesity epidemic than race/ethnicity.

Astrocytes are involved in the neuroinflammation of neurodegenerative diseases, such as Parkinson's disease (PD). Among the numerous inflammatory cytokines, interleukin-1β (IL-1β) produced by astrocytic Nod-like receptor protein (NLRP) inflammasome is crucial in the pathogenesis of PD. β-arrestin2-mediated dopamine D2 receptor (Drd2) signal transduction has been regarded as a potential anti-inflammatory target. Our previous study revealed that astrocytic Drd2 suppresses neuroinflammation in the central nervous system. However, the role of Drd2 in astrocytic NLRP3 inflammasome activation and subsequent IL-1β production remains unclear. In the present study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mouse model to investigate whether Drd2 could suppress astrocytic NLRP3 inflammasome activation. We showed that Drd2 agonist inhibited NLRP3 inflammasome activation, evidenced by decreased caspase-1 expression and reduced IL-1β release in the midbrain of wild type mice. The anti-inflammasome effect of Drd2 was abolished in β-arrestin2 knockout and β-arrestin2 small interfering RNA-injected mice, suggesting a critical role of β-arrestin2 in Drd2-regulated NLRP3 inflammasome activation. We also found that Drd2 agonists suppressed the upregulation of caspase-1 and IL-1β expression in primary cultured mouse astrocytes in response to the activation of NLRP3 inflammasome induced by lipopolysaccharide plus adenosine triphosphate. Furthermore, we demonstrated that β-arrestin2 mediated the inhibitory effect of Drd2 on NLRP3 inflammasome activation via interacting with NLRP3 and interfering the inflammasome assembly. Collectively, our study illustrates that astrocytic Drd2 inhibits NLRP3 inflammasome activation through a β-arrestin2-dependent mechanism, and provides a new strategy for treatment of PD.

Highlights d Antibodies against HBsAg from different donors share sequence similarities d Broadly neutralizing antibodies (bNAbs) to HBsAg target 3 non-overlapping epitopes d Co-crystal structure reveals a hairpin loop that explains immune escape mutation d Combination of complementary bNAbs controlled HBV infection and prevented escape mutation