Poria cocos is an edible and medicinal fungus that is widely used in Traditional Chinese Medicines as well as in modern applications. Retinoid X receptor (RXR) occupies a central place in nuclear receptor signaling, and a pharmacological RXRdependent pathway is involved in myeloid cell function. Here, structural information for 82 triterpenes from P. cocos and 17 known RXR agonists was collected in a compound library and retrieved for a molecular docking study. Three triterpenes, 16α-hydroxytrametenolic acid (HTA), pachymic acid (PA), and polyporenic acid C (PPAC), were identified as novel RXR-specific agonists based on luciferase reporter assays and in silico evidence. Treatment with HTA, PA, and PPAC significantly induced differentiation of the human promyelocytic leukemia cell line HL-60 with EC50 values of 21.0 ± 0.52, 6.7 ± 0.37, and 9.4 ± 0.65 μM, respectively. These effects were partly blocked by the RXR antagonist UVI3003, suggesting that an RXRdependent pathway may play an important role in their anti-acute promyelocytic leukemia (APL) effects. Taken together, triterpenes from P. cocos are revealed as naturally occurring RXR selective agonists with the potential for anti-cancer activity.These results suggest a novel approach to the treatment or prevention of APL. K E Y W O R D Sacute promyelocytic leukemia, naturally occurring agonist, Poria cocos, retinoid X receptor, Traditional Chinese Medicines, triterpenes 494 | XU et al.

OBJECTIVE To assess the relationship of circulating fatty acids (FA) with risk of type 2 diabetes (T2D) and potential interactions with genetic risk. RESEARCH DESIGN AND METHODS A total of 95,854 participants with complete data on plasma FA from the UK Biobank were enrolled between 2006 and 2010 and were followed up to the end of 2020. Plasma concentrations of saturated FA (SFA), monounsaturated FA (MUFA), and polyunsaturated FA (PUFA) were analyzed by a high-throughput nuclear magnetic resonance-based biomarker profiling platform. The genetic risk scores (GRS) were calculated on the basis of 424 variants associated with T2D. Pathway-specific GRS were calculated based on robust clusters of T2D loci. RESULTS There were 3,052 instances of T2D documented after an average follow-up of 11.6 years. Plasma concentrations of SFA and MUFA were positively associated with T2D risk, while plasma PUFA were inversely associated. After adjustment for major risk factors, hazard ratios (95% CIs) of T2D for 1-SD increment were 1.03 (1.02–1.04) for SFA, 1.03 (1.02–1.05) for MUFA, 0.62 (0.56–0.68) for PUFA, 0.67 (0.61–0.73) for n-6 PUFA, 0.90 (0.85–0.95) for n-3 PUFA, and 1.01 (0.98–1.04) for n-6–to–n-3 ratio. Plasma MUFA had significant interactions with the overall GRS and GRS for proinsulin and liver/lipid clusters on T2D risk. The protective associations of n-3 PUFA with T2D risk were weaker among individuals with higher obesity GRS (P interaction = 0.040) and liver/lipid GRS (P interaction = 0.012). Additionally, increased plasma n-3 PUFA concentration was associated with more reductions in T2D risk among participants carrying more docosapentaenoic acid-associated alleles (P interaction = 0.007). CONCLUSIONS Plasma concentrations of SFA and MUFA were associated with a higher T2D risk, whereas plasma PUFA and n-6 and n-3 PUFA were related to a lower risk. Circulating MUFA and n-3 PUFA had significant interactions with genetic predisposition to T2D and FA-associated variants.

Tolerance of transgressions can influence the social cognitive and moral development of children and adolescents. Given the prevalent tolerance for bribery throughout the developing world and in China, the present research identified bribery as a serious transgression and investigated the various effects of moral evaluations and descriptive norms on transgression tolerance with increasing age. Thus, two studies examined these effects among primary, middle, and high school students (N = 972, 10-, 13-, and 16-year-olds). In Study 1, students' transgression tolerance was negatively influenced by moral evaluations, and no age trend emerged. However, students reported more transgression tolerance with age owing to their increasing understanding of descriptive norms. In Study 2, the descriptive norms were manipulated: individuals in the high descriptive norm condition showed greater transgression tolerance than those in the low descriptive norm condition. An increasing tolerance of transgressions was observed only for those in the high descriptive norm condition. The effect of descriptive norms was found to contribute to the transgression tolerance trend.

Environmental and dietary exposures to acrylamide (AA) have been linked with various metabolic-related outcomes, but the results are mixed. However, the association between long-term exposure to AA and the prevalence of metabolic syndrome (MetS) remains unknown. In this study, we aimed to assess the relationship between hemoglobin adducts of AA, biomarkers of internal exposure to AA, and MetS prevalence among a U.S. nationwide population. MetS patients were defined by meeting three or more of the following five characteristics: elevated blood pressure, high fasting glucose, abdominal obesity, hypertriglyceridemia, and lower high-density lipoprotein cholesterol (HDL-C). Multivariate-adjusted logistic regression models and restricted cubic spline models were used to analyze the associations between AA hemoglobin biomarkers and MetS prevalence. A total of 1552 MetS cases were documented. After adjustment for the potential confounders, the odds ratios (95% confidence intervals) of MetS prevalence in the highest quartile of AA hemoglobin biomarkers were 0.60 (0.40–0.89), 1.26 (0.84–1.89), 0.93 (0.71–1.21), and 1.61 (1.18–2.20) for HbAA, HbGA, the sum of HbAA and HbGA (HbAA + HbGA), and the ratio of HbGA to HbAA (HbGA/HbAA), compared with the lowest quartile, respectively. HbAA was significantly and inversely associated with blood pressure, fasting glucose, abdominal obesity, hypertriglyceridemia, and low HDL-C, while the HbGA/HbAA ratio was also positively associated with abdominal obesity, hypertriglyceridemia, and low HDL-C. The restricted cubic spline models revealed a positive relationship between the HbGA/HbAA ratio and the prevalence of MetS, while the HbAA level was inversely associated with MetS prevalence. Our current findings provided epidemiological evidence that HbAA and the HbGA/HbAA ratio were significantly associated with MetS prevalence among general U.S. adults. Further studies should be conducted to examine the association between internal exposure to AA and MetS prevalence.

Previous studies have found that when low-status group members are aware that their in-group is stereotyped as dependent by a specific out-group (i.e. a dependency meta-stereotype is salient), they are reluctant to seek help from the high-status out-group to avoid confirming the negative meta-stereotype. However, it is unclear whether low-status group members would seek more help in the context of a salient dependency meta-stereotype when there is low (vs. high) group boundary permeability. Therefore, we conducted two experiments to examine the moderating effect of permeability on meta-stereotype confirmation with a real group. In study 1, we manipulated the salience of the dependency meta-stereotype, measured participants' perceived permeability and examined their help-seeking behaviour in a real-world task. Participants who perceived low permeability sought more help when the meta-stereotype was salient (vs. not salient), whereas participants who perceived high permeability sought the same amount of help across conditions. In study 2, we manipulated the permeability levels and measured the dependency meta-stereotype. Participants who endorsed a high-dependency meta-stereotype sought more help than participants who endorsed a low-dependency meta-stereotype; this effect was particularly strong in the low-permeability condition. The implications of these results for social mobility and intergroup helping are discussed.