Background: The cause of atherosclerosis is not known, and therefore the current treatment options are limited. In the present study, we aimed to investigate the effects of Phoenixin 20 and its receptor G protein-coupled receptor 173 (GPR173) against ox-LDL-induced endothelial dysfunction.Materials and Methods: Human aortic endothelial cells (HAECs) were treated with 10 μg/ml ox-LDL in the presence or absence of phoenixin 20. Gene expression of GPR173, ICAM-1, VCAM-1, IL-1β, IL-8, MCP-1, and NOX-4 were measured by real time PCR. Protein expression was assayed by western blot analysis. Secretions of pro-in ammatory cytokines were measured by ELISA. The attachment of THP-1 monocytes to HAECs was detected using calcein-AM staining. Transcriptional activity of NF-κB was measured using dual-luciferase reporter assay.Results: Our ndings indicate that ox-LDL signi cantly lowered the expression of GPR173 in HAECs and triggered an increase in ROS, NOX-4, and proin ammatory cytokine expression. Importantly, we demonstrate that agonism of GPR173 using phoenixin 20 signi cantly ameliorated these harmful effects of ox-LDL. We also show that agonism of GPR173 can prevent the attachment of monocytes to endothelial cells, which is an important therapeutic approach to prevent atherogenesis. Conclusion:Here, for the rst time to our knowledge, we provide a basis for future research on the role of GPR173 as a new potential treatment against atherosclerosis.

ObjectivesTo analyze the evolution of research on children and adolescents mental health issues during COVID-19 pandemic and discuss research hotspots and cutting-edge developments.MethodsThe literature obtained from the web of science core collection as of June 28, 2022, was analyzed using Citespace, VOSviewer bibliometric visualization mapping software.ResultsA total of 6,039 relevant papers were found, of which 5,594 were included in the study. The number of literatures is growing since 2020; and the country, institution, and journal publications were analyzed. The co-citation analysis shows that there are more research articles among the highly cited articles and a lack of systematic reviews that use critical thinking for review. In the cluster analysis, mental health and life change were the most representative. The timeline view of the keywords shows that Online learning (#0), Public health (#1), and Mental health (#2) are the three largest clusters and shows the change over time.ConclusionThis study helped analyze the mental health of children and adolescents during the COVID-19 pandemic and identified hot trends and shortcomings, which are important references for the theoretical basis of future research and decision making and technical guidance for systematic reviews.

BackgroundCircadian rhythm disruption (CRD) represents a critical contributor to the pathogenesis of Alzheimer’s disease (AD). Nonetheless, how CRD functions within the AD immune microenvironment remains to be illustrated.MethodsCircadian rhythm score (CRscore) was utilized to quantify the microenvironment status of circadian disruption in a single-cell RNA sequencing dataset derived from AD. Bulk transcriptome datasets from public repository were employed to validate the effectiveness and robustness of CRscore. A machine learning-based integrative model was applied for constructing a characteristic CRD signature, and RT-PCR analysis was employed to validate their expression levels.ResultsWe depicted the heterogeneity in B cells, CD4+ T cells, and CD8+ T cells based on the CRscore. Furthermore, we discovered that CRD might be strongly linked to the immunological and biological features of AD, as well as the pseudotime trajectories of major immune cell subtypes. Additionally, cell–cell interactions revealed that CRD was critical in the alternation of ligand-receptor pairs. Bulk sequencing analysis indicated that the CRscore was found to be a reliable predictive biomarker in AD patients. The characteristic CRD signature, which included 9 circadian‐related genes (CRGs), was an independent risk factor that accurately predicted the onset of AD. Meanwhile, abnormal expression of several characteristic CRGs, including GLRX, MEF2C, PSMA5, NR4A1, SEC61G, RGS1, and CEBPB, was detected in neurons treated with Aβ1-42 oligomer.ConclusionOur study revealed CRD-based cell subtypes in the AD microenvironment at single-cell level and proposed a robust and promising CRD signature for AD diagnosis. A deeper knowledge of these mechanisms may provide novel possibilities for incorporating “circadian rhythm-based anti-dementia therapies” into the treatment protocols of individualized medicine.

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