RESUMO
Identifying high-quality causal explanations is key to scientific understanding. This research (N = 202; 50% girls; Mage: 5.82 years; 64% Asian, 33% White, and 3% multiracial; data collected from 2018 to 2024) examined how explanation circularity and informants' social dominance impact children's learning preferences for causal explanations. Raised in a culture valuing circular logic, Chinese children still preferred non-circular explanations and learning from informants providing non-circular explanations (d ≥ 0.50). When informants with non-circular explanations were subordinate to those with circular explanations, Chinese and American children preferred non-circular over circular explanations (d = 1.10), but did not prefer learning new information from either informant. Although children weigh explanation quality over informant dominance when seeking explanations for given questions, they consider both cues when evaluating informants' credibility.
RESUMO
Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.
Assuntos
Cartilagem , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo , Selenoproteínas , Animais , Selenoproteínas/metabolismo , Selenoproteínas/genética , Camundongos , Cartilagem/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Condrócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem CelularRESUMO
Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10.6 million new cases and 1.4 million deaths in 2021. This global emergency is exacerbated by the emergence of multidrug-resistant MDR-TB and extensively drug-resistant XDR-TB; therefore, new drugs and new drug targets are urgently required. From a whole cell phenotypic screen, a series of azetidines derivatives termed BGAz, which elicit potent bactericidal activity with MIC99 values <10 µM against drug-sensitive Mycobacterium tuberculosis and MDR-TB, were identified. These compounds demonstrate no detectable drug resistance. The mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from the existing mycobacterial cell wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as antitubercular chemotherapies.