BackgroundThe choline‐derived metabolite trimethylamine N‐oxide (TMAO) has been demonstrated to contribute to atherosclerosis and is associated with coronary artery disease risk.Methods and ResultsWe explored the impact of TMAO on endothelial and smooth muscle cell function in vivo, focusing on disease‐relevant outcomes for atherogenesis. Initially, we observed that aortas of LDLR −/− mice fed a choline diet showed elevated inflammatory gene expression compared with controls. Acute TMAO injection at physiological levels was sufficient to induce the same inflammatory markers and activate the well‐known mitogen‐activated protein kinase, extracellular signal–related kinase, and nuclear factor‐κB signaling cascade. These observations were recapitulated in primary human aortic endothelial cells and vascular smooth muscle cells. We also found that TMAO promotes recruitment of activated leukocytes to endothelial cells. Through pharmacological inhibition, we further showed that activation of nuclear factor‐κB signaling was necessary for TMAO to induce inflammatory gene expression in both of these relevant cell types as well as endothelial cell adhesion of leukocytes.ConclusionsOur results suggest a likely contributory mechanism for TMAO‐dependent enhancement in atherosclerosis and cardiovascular risks.

The dictyostatins are a promising class of potential anticancer drugs because they are powerful microtubule stabilizing agents, but the complexity of their chemical structures is a severe impediment to their further development. Based on both synthetic and medicinal chemistry analyses, 25,26-dihydro-16-desmethyldictyostatin and its C6 epimer were chosen as potentially potent yet accessible dictyostatin analogs, and three new syntheses were developed. A relatively classical synthesis involving vinyllithium addition and macrocyclization gave way to a newer and more practical approach based on esterification and ring-closing metathesis reaction. Finally, aspects of these two approaches were combined to provide a third new synthesis based on esterification and Nozaki-Hiyama-Kishi reaction. This was used to prepare the target dihydro analogs and the natural product. All of the syntheses are streamlined because of their high convergence. The work provided several new analogs of dictyostatin including a truncated macrolactone and a C10 E-alkene, which were 400-fold and 50-fold less active than (−)-dictyostatin. In contrast, the targeted 25,26-dihydro-16-desmethyldictyostatin analogs retained almost complete activity in preliminary biological assays.

Background The COVID-19 has been a pandemic around the world, which affirmatively brought mental health problems to medical staff. We aimed to investigate the prevalence of anxiety in Chinese medical staff and examine the mediation effects of coping styles on the relationship between social support and anxiety. Methods A cross-sectional study via internet survey was conducted from 15 March to 30 March, 2020. The social demographic data, Self-rated Anxiety Scale, Social Support Rate Scale and Trait Coping Style Scale were collected. Pearson correlation and a structural equation model were performed to examine the relationships of these variables. The bootstrap analysis was conducted to evaluate the mediation effects. Results A total of 453 medical staff participated in this study. The mean score of SAS was 46.1 (SD = 10.4). Up to 40.8% of the participants had anxiety symptoms. The participants lived with family members had lower SAS score (45.1 ± 9.8 vs 49.6 ± 11.8). Social support was negatively associated with anxiety, mediated by positive coping and negative coping partially significantly with an effect size of − 0.183. Conclusions Chinese medical staff had a high level of anxiety during the COVID-19 pandemic. Coping styles had effects on the association between social support and anxiety. Sufficient social support and training on positive coping skills may reduce anxiety in medical staff.

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BackgroundAntenatal maternal mental health problems have numerous consequences for the well-being of both mother and child. This study aimed to test and construct a pertinent model of antenatal depressive symptoms within the conceptual framework of a stress process model.MethodsThis study utilized a cross-sectional study design. Inclusion criteria: participants were adult women (18 years or older) having a healthy pregnancy, in their third trimester (the mean weeks gestation was 34.71). Data collection: depressive and anxiety symptoms were measured by Zung’s Self-rating Depressive and Anxiety Scale, stress was measured by Pregnancy-related Pressure Scale, social support and coping strategies were measured by Social Support Rating Scale and Simplified Coping Style Questionnaire, respectively. Analysis: path analysis was applied to examine the hypothesized causal paths between study variables.ResultsA total of 292 subjects were enrolled. The final testing model showed good fit, with normed χ2 = 32.317, p = 0.061, CFI = 0.961, TLI = 0.917, IFI = 0.964, NFI = 0.900, RMSEA = 0.042. This path model supported the proposed model within the theoretical framework of the stress process model. Pregnancy-related stress, financial strain and active coping have both direct and indirect effects on depressive symptoms. Psychological preparedness for delivery, social support and anxiety levels have direct effects on antenatal depressive symptoms. Good preparedness for delivery could reduce depressive symptoms, while higher levels of anxiety could significantly increase depressive symptoms. Additionally, there were indirect effects of miscarriage history, irregular menstruation, partner relationship and passive coping with depressive symptoms.ConclusionThe empirical support from this study has enriched theories on the determinants of depressive symptoms among Chinese primipara, and could facilitate the formulation of appropriate interventions for reducing antenatal depressive symptoms, and enhancing the mental health of pregnant women.