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Mounting evidence indicates that circular RNAs (circRNAs) have essential roles in several diseases, including periodontitis. Periodontal ligament stem cells (PDLSCs) exhibit potential for treating periodontitis accompanied by hypoxia. However, it is unclear how circRNA affects the osteogenesis of PDLSCs under hypoxia. In this study, a novel circRNA, hsa_circ_0003489, was found located at the gene for cyclin‐dependent kinase 8 (CDK8) and referred to as circCDK8. The expression levels of circCDK8 and hypoxia‐inducible factor‐1α were significantly increased in periodontitis tissues, and the expression of circCDK8 was further confirmed in a hypoxia model using cobalt chloride (CoCl2). Interestingly, the results showed that the expression levels of osteoblast markers (RUNX2, ALP, OCN, and COL1A1) were increased in CoCl2‐treated PDLSCs at 6 and 12 h, but decreased at 24, 48, and 72 h. On the basis of bioinformatics and functional experiments, CoCl2 also induced endoplasmic reticulum stress, autophagy, and apoptosis of PDLSCs; the inhibition of autophagy promoted the osteogenic differentiation of CoCl2‐treated PDLSCs. Furthermore, circCDK8 overexpression induced autophagy and apoptosis through mTOR signaling, and circCDK8 silencing reversed the inhibitory effects of CoCl2 on osteogenic differentiation of PDLSCs. In conclusion, our results indicate that circCDK8 represses the osteogenic differentiation of PDLSCs by triggering autophagy activation in a hypoxic microenvironment. CircCDK8 could be a new therapeutic target of periodontitis.

Accumulating evidence suggests that Foxp3 cells can downregulate the expression of Foxp3, but whether thymically derived regulatory T cells (tTregs; especially committed tTregs) are capable of downregulating Foxp3 expression and being reprogrammed into other T effector cells remains controversial. Using a novel tTreg lineage-tracing mouse line, we were able to label epigenetically stable Foxp3 cells derived from the thymus and demonstrate that mature tTregs are stable under homeostatic conditions. However, TCR engagement and sequential functional specialization of tTregs led to the generation of Foxp3 instability and reprogramming into the Th lineage. We further demonstrated that the signal switch from IL-2 to ICOS during Treg activation induced Treg instability and reprogramming. By using a dual lineage tracing model, we demonstrated that effector Tregs can revert to central Tregs, and this reversion is associated with increasing Foxp3 stability in vivo.

Background: The COVID-19 pandemic is our generation's greatest global challenge to our public health system. Vaccines are considered one of the most effective tools available for preventing COVID-19 infection and its complications and sequelae. Understanding and addressing the psychological stress related to COVID-19 vaccination may promote acceptance of these vaccines.Methods: We conducted an online survey from January 29 to April 26, 2021 to explore stress levels related to COVID-19 vaccination among the general public in China. Participants were asked to evaluate their psychological stress of considering whether or not to get vaccinated at the beginning period of the COVID-19 mass vaccination, after getting access to the information about the vaccine, as well as after getting vaccinated, using visual analog stress scale. Multiple linear regression analysis was performed to explore factors potentially associated with COVID-19-related psychological stress levels before and after getting vaccinated.Results: A total of 34,041 participants were included in the final analysis. The mean stress score concerning COVID-19 vaccination was 3.90 ± 2.60 among all participants, and significantly decreased over time. In addition, the vaccine-related stress level significantly decreased after accessing information about the COVID-19 vaccine (N = 29,396), as well as after getting vaccinated (N = 5,103). Multivariable regression analysis showed higher stress levels related to COVID-19 vaccination in participants who were younger, having lower education level, having history of chronic diseases, mistrusting vaccine's efficacy, experience of vaccine allergy events, being affected by the COVID-19 epidemic, and having mental illness symptoms. Moreover, mistrust in vaccine efficacy and experience of vaccine allergy events had a long-term impact on psychological stress levels about COVID-19 vaccination even after getting vaccinated.Conclusions: The current findings profiled the COVID-19 vaccine-related psychological stress among the general public in China. Population-specific management and interventions targeting the stress related to COVID-19 vaccination are needed to help governments and policy makers promote individual's willingness to get vaccinations for public well-being during the COVID-19 pandemic.

The present study assessed the willingness of the general population to receive COVID-19 vaccines and identified factors that influence vaccine hesitancy and resistance. A national online survey was conducted from 29 January 2021 to 26 April 2021 in China. Multinomial logistic regression analyses were conducted to identify factors that influence vaccine hesitancy and resistance. Of the 34,041 participants surveyed, 18,810 (55.3%) were willing to get vaccinated, 13,736 (40.3%) were hesitant, and 1495 (4.4%) were resistant. Rates of vaccine acceptance increased over time, with geographical discrepancies in vaccine hesitancy and resistance between provinces in China. Vaccine safety was the greatest concern expressed by most participants (24,461 [71.9%]), and the major reason for participants’ refusing vaccination (974 [65.2%]). Government agencies (23,131 [68.0%]) and social media (20,967 [61.6%]) were the main sources of COVID-19 vaccine information. Compared with vaccination acceptance, female, young and middle-aged, high income, and perceived low-risk of infection were associated with vaccine hesitancy. Histories of allergic reactions to other vaccines and depression symptoms were related to vaccine resistance. Common factors that influenced vaccine hesitancy and resistance were residing in cities and perceiving less protection with vaccines than with other protective measures. The results indicate that the rate of vaccine resistance is relatively low, but vaccine hesitancy is common. Individuals who are female, young and middle-aged, with a high income, and residing in cities are more likely to be hesitant for vaccination and should be the target populations for vaccination campaigns. Specific vaccine messaging from the government and social media could alleviate public concerns about vaccine safety and efficacy.

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