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Abstract Background Health lifestyles exert a substantial influence on the quality of everyday life, primarily affecting health maintenance and enhancement. While health-related practices during the COVID-19 pandemic may have positively altered the health lifestyles of Canadians to a certain degree, government reports indicate that issues related to health behaviors, such as cigarette smoking, physical inactivity, and alcohol consumption, continue to pose challenges to the health of Canadians. Social determinants of these health behaviors thus hold significant academic value in the formulation of policy guidelines. Objective The aim of this study is to scrutinize the social determinants of health with respect to social factors that have may have impacts on the health-related behaviors of Canadians. We tested health behaviors including cigarette use, alcohol consumption, and participation in physical exercise, which are integral to the promotion and improvement of individual health. Methods To examine the social determinants of Canadians’ health lifestyles, we utilized nationally representative data from the 2017–2018 Canadian Community Health Survey annual component. Our data analysis involved the bootstrapping method with two-level mixed-effect logistic regressions, ordered logistic regressions, and negative binomial regressions. Additionally, we conducted several robustness checks to confirm the validity of our findings. Results The findings show that demographic background, socioeconomic status, social connections, and physical and mental health conditions all play a role in Canadians’ smoking, physical activity, and drinking behaviors. Noticeably, the association patterns linking to these social determinants vary across specific health lifestyles, shedding light on the complex nature of the social determinants that may influence young and middle-aged Canadians’ health lifestyles. Moreover, in the context of Canada, the health-region level demographic, socioeconomic, and working conditions are significantly linked to residents’ health lifestyles. Conclusions Investigating the social determinants of health lifestyles is pivotal for policymakers, providing them with the necessary insights to create effective interventions that promote healthy behaviors among specific demographic groups. It is recommended that health education and interventions at the community level targeting smoking, physical inactivity, and alcohol consumption be introduced. These interventions should be tailored to specific subgroups, considering their demographic and socioeconomic characteristics, social networks, and health status. For instance, it is imperative to focus our attention on individuals with lower educational attainment and socioeconomic status, particularly in relation to their smoking habits and physical inactivity. Conversely, interventions aimed at addressing alcohol consumption should be targeted towards individuals of a higher socioeconomic status. This nuanced approach allows for a more effective and tailored intervention strategy.

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects. The primary challenge is to integrate diverse pharmacophores within a single-molecule framework. To address this, we introduced DeepSA, a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine, a well-known local anesthetic. DeepSA integrates deep neural networks into metaheuristics, effectively constraining molecular space during compound generation. This framework employs a sophisticated objective function that accounts for scaffold preservation, anti-inflammatory properties, and covalent constraints. Through a sequence of local editing to navigate the molecular space, DeepSA successfully identified AT-17, a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal models. Mechanistic insights into AT-17 revealed its dual mode of action: selective inhibition of NaV1.7 and 1.8 channels, contributing to its prolonged local anesthetic effects, and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome pathway. These findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery, particularly within stringent chemical constraints.

Dyslipidemia often accompanies type 2 diabetes mellitus (T2DM). Elevated blood glucose in patients commonly leads to high levels of lipids. Lipid molecules can play a crucial role in early detection, treatment, and prognosis of T2DM with dyslipidemia. Previous lipid studies on T2DM mainly focused on Western diabetic populations with elevated blood glucose. In this research, we investigate both high blood sugar and high lipid levels to better understand changes in plasma lipid metabolism in newly diagnosed Chinese T2DM patients with dyslipidemia (NDDD). We used a plasma lipid analysis method based on ultra-high performance liquid chromatography coupled with mass spectrometry technology (UHPLC-MS) and statistical analysis to characterize lipid profiles and identify potential biomarkers in NDDD patients compared to healthy control (HC) subjects. Additionally, we examined the differences in lipid profiles between hyperlipidemia (HL) patients and HC subjects. We found significant changes in 15 and 23 lipid molecules, including lysophosphatidylcholine (LysoPC), phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), and ceramide (Cer), in the NDDD and HL groups compared to the HC group. These altered lipid molecules are associated with five metabolic pathways, with sphingolipid metabolism and glycerophospholipid metabolism being the most relevant to glucose and lipid metabolism changes. These lipid biomarkers are strongly correlated with traditional markers of glucose and lipid metabolism. Notably, Cer(d18:1/24:0), SM(d18:1/24:0), SM(d18:1/16:1), SM(d18:1/24:1), and SM(d18:2/24:1) were identified as essential potential biomarkers closely linked to clinical parameters through synthetic analysis of receiver operating characteristic curves, random forest analysis, and Pearson matrix correlation. These lipid biomarkers can enhance the risk prediction for the development of T2DM in individuals with dyslipidemia but no clinical signs of high blood sugar. Furthermore, they offer insights into the pathological mechanisms of T2DM with dyslipidemia.

Objectives: About four percent of Canadians used illegal drugs in 2019, but it remains unknown whether their living arrangements are a relevant factor.Methods: We use the public version of the 2015–2016 Canadian Community Health Survey Annual Component. The binary logit model and complementary log-log model are applied to investigate to what extent living arrangements predict Canadians’ recent illicit drug use.Results: Living alone is significantly associated with Canadians’ illicit drug use. For young and older Canadians, those living with spouses/partners, children, or both are less likely to use illicit drugs than their solo-living counterparts. Middle-aged Canadians who lived with spouses/partners only or with children have significantly lower likelihoods of using illicit drugs compared to those living alone. Additionally, differences between men and women have been found. Spouses/partners and children play more positive roles for young and middle-aged women than for men.Conclusion: Our findings suggest that living with core families is a type of collectivity that may have positive effects on Canadians’ health behaviours compared to those living alone, who, therefore, need more attention from health officials.

The proliferation and migration of vascular smooth muscle cells (VSMC) is extensively involved in pathogenesis of neointimal hyperplasia. All-trans-retinoic acid (ATRA) is a natural metabolite of vitamin A. Here, we investigated the involvement of AMP-activated protein kinase (AMPK) in the anti-neointimal hyperplasia effects of ATRA. We found that treatment with ATRA significantly reduced neointimal hyperplasia in the left common carotid artery ligation mouse model. ATRA reduced the proliferation and migration of VSMC, A7r5 and HASMC cell lines. Our results also demonstrated that ATRA altered the expression of proliferation-related proteins, including CyclinD1, CyclinD3, CyclinA2, CDK2, CDK4, and CDK6 in VSMC. ATRA dose-dependently enhanced the phosphorylation level of AMPKα (Thr172) in the left common carotid artery of experimental mice. Also, the phosphorylation level of AMPKα in A7r5 and HASMC was significantly increased. In addition, ATRA dose-dependently reduced the phosphorylation levels of mTOR and mTOR target proteins p70 S6 kinase (p70S6K) and 4E-binding protein 1 (4EBP1) in A7r5 and HASMC. Notably, the inhibition of AMPKα by AMPK inhibitor (compound C) negated the protective effect of ATRA on VSMC proliferation in A7r5. Also, knockdown of AMPKα by siRNA partly abolished the anti-proliferative and anti-migratory effects of ATRA in HASMC. Molecular docking analysis showed that ATRA could dock to the agonist binding site of AMPK, and the binding energy between AMPK and ATRA was -7.91 kcal/mol. Molecular dynamics simulations showed that the binding of AMPK-ATRA was stable. These data demonstrated that ATRA might inhibit neointimal hyperplasia and suppress VSMC proliferation and migration by direct activation of AMPK and inhibition of mTOR signaling.