Enterococcus faecalis-Induced Macrophage Necroptosis Promotes Refractory Apical Periodontitis.

The persistence of residual bacteria, particularly Enterococcus faecalis, contributes to refractory periapical periodontitis, which still lacks effective therapy. The role of receptor-interacting protein kinase 3 (RIPK3)- and mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis, a highly proinflammatory form of regulated cell death, has recently drawn much attention. However, the role of necroptosis in the pathogenesis of refractory periapical periodontitis remains unclear. We investigated whether the RIPK3/MLKL signaling pathway was activated in periapical lesion specimens obtained from patients diagnosed with refractory periapical periodontitis. RIPK3-deficient mice were then used to determine the role of necroptosis under this condition in vivo. We found that the phosphorylation levels of RIPK3 and MLKL were elevated in periapical lesion specimens of patients with refractory periapical periodontitis. In addition, necroptosis was induced in an E. faecalis-infected refractory periapical periodontitis mouse model, in which inhibition of necroptosis by RIPK3 deficiency could markedly alleviate inflammation and bone destruction. Moreover, double-labeling immunofluorescence suggested that macrophage necroptosis may be involved in the development of refractory periapical periodontitis. Then, we established an in vitro macrophage infection model with E. faecalis. E. faecalis infection was found to induce necroptotic cell death in macrophages through the RIPK3/MLKL signaling pathway, which was markedly alleviated by the RIPK3- or MLKL-specific inhibitor. Our study revealed that RIPK3/MLKL-mediated macrophage necroptosis contributes to the development of refractory periapical periodontitis and suggests that inhibitors or treatments targeting necroptosis represent a plausible strategy for the management of refractory periapical periodontitis. IMPORTANCE Oral infectious diseases represent a major neglected global population health challenge, imposing an increasing burden on public health and economy. Refractory apical periodontitis (RAP), mainly caused by Enterococcus faecalis, is a representative oral infectious disease with considerable therapeutic challenges. The interplay between E. faecalis and the host often leads to the activation of programmed cell death. This study identifies an important role of macrophage necroptosis induced by E. faecalis in the pathogenesis of RAP. Manipulating RIPK3/MLKL-mediated necroptosis may represent novel therapeutic targets, not only for RAP but also for other E. faecalis-associated infectious diseases.

Identify and measure the degree of over-prevention behaviors in the post-COVID-19 era in China.

BACKGROUND: With the spread of vaccines, more and more countries have controlled the outbreak of the COVID-19. In this post-epidemic era, these countries began to revive their economy. However, pollution remains in the environment, and people's physical and psychological health has been under threat due to some over-prevention behaviors. Instruments for governmental agencies to manage these behaviors are not yet available. This study aims to develop a measurement model to identify and measure the degree of over-prevention behaviors during the COVID-19 epidemic in China. METHODS: A survey online was conducted to collect cognition from 1528 Chinese people, including descriptions of various over-prevention behaviors defined by health authorities. Factor analyses were used to develop the measurement model and test its validity. Logistic regression analyses were conducted to explore demographic characteristics, indicating people who are inclined to exhibit over-prevention behaviors. RESULTS: Four main factors were extracted to develop the model (eigenvalue = 7.337, 3.157, 1.447, and 1.059, respectively). The overall reliability (Cronbach's α = 0.900), the convergent (AVE > 0.5, CR > 0.8 for each factor) and discriminant validity is good. There is also a good internal consistency among these factors (Cronbach's α = 0.906, 0.852, 0.882, and 0.763, respectively). In Factor 1, gender has a negative effect (Beta = - 0.294, P <  0.05, OR = 0.745), whereas employment has a positive effect. Workers in institutions exhibit the greatest effect (Beta = 0.855, P <  0.001, OR = 2.352). In Factor 2, employment has a negative effect, with workers in institutions exhibit the greatest role (Beta = - 0.963, P <  0.001, OR = 0.382). By contrast, education level has a positive effect (Beta = 0.430, P <  0.001, OR = 1.537). In Factor 3, age plays a negative role (Beta = - 0.128, P < 0.05, OR = 0.880). CONCLUSIONS: People show a discrepancy in the cognition toward various over-prevention behaviors. The findings may have implications for decision-makers to reduce the contradiction between the epidemic and economic revival via managing these behaviors.

GO-based antibacterial composites: Application and design strategies.

Graphene oxide (GO), for its unique structure with high biocompatibility and designability, is widely used in the antibacterial field. Various strategies have been designed to fabricate GO-based composites with antibacterial properties. This review summarized these strategies, divided them into three types and interpreted their antibacterial mechanisms: (i) "GO*/non-GO" type in which GO acts as the single antibacterial core, (ii) "GO*/non-GO*" type in which GO and non-GO components function synergistically as dual antibacterial cores, (iii) "GO/non-GO*" type in which non-GO acts as the single antibacterial core, while GO component plays a supportive, not a dominant role in antibiosis. Besides, the fields suiting their applications and factors influencing their antibacterial properties were analyzed. Finally, the limitations and prospects in the current researches were discussed. In summary, GO-based composites have revolutionized antibacterial strategies. This review may serve as a reference to inspire further research on GO-based antibacterial composites.

Efficacy of i-PRF in regenerative endodontics therapy for mature permanent teeth with pulp necrosis: study protocol for a multicentre randomised controlled trial.

BACKGROUND: Dental pulp necrosis, a common health problem, is traditionally treated with root canal therapy; however, it fails in restoring the vitality of damaged pulp. Most studies regarding regenerative endodontic therapy (RET) are limited to the treatment of immature necrotic teeth. Given that injectable platelet-rich fibrin (i-PRF) has shown great potential in regenerative medicine as a novel platelet concentration, this study is designed to explore whether i-PRF can serve as a biological scaffold, extending the indications for RET and improving the clinical feasibility of RET in mature permanent teeth with pulp necrosis. METHODS: This is a randomised, double-blind, controlled, multicentre clinical trial designed to evaluate the clinical feasibility of RET for mature permanent teeth with pulp necrosis and to compare the efficacy of i-PRF and blood clots as scaffolds in RET. A total of 346 patients will be recruited from three centres and randomised at an allocation ratio of 1:1 to receive RET with either a blood clot or i-PRF. The changes in subjective symptoms, clinical examinations, and imaging examinations will be tracked longitudinally for a period of 24 months. The primary outcome is the success rate of RET after 24 months. The secondary outcome is the change in pulp vitality measured via thermal and electric pulp tests. In addition, the incidence of adverse events such as discolouration, reinfection, and root resorption will be recorded for a safety evaluation. DISCUSSION: This study will evaluate the clinical feasibility of RET in mature permanent teeth with pulp necrosis, providing information regarding the efficacy, benefits, and safety of RET with i-PRF. These results may contribute to changes in the treatment of pulp necrosis in mature permanent teeth and reveal the potential of i-PRF as a novel biological scaffold for RET. TRIAL REGISTRATION: ClinicalTrials.gov NCT04313010 . Registered on 19 March 2020.

Effects of Health Information Dissemination on User Follows and Likes during COVID-19 Outbreak in China: Data and Content Analysis.

Background: COVID-19 has greatly attacked China, spreading in the whole world. Articles were posted on many official WeChat accounts to transmit health information about this pandemic. The public also sought related information via social media more frequently. However, little is known about what kinds of information satisfy them better. This study aimed to explore the characteristics of health information dissemination that affected users' information behavior on WeChat. Methods: Two-wave data were collected from the top 200 WeChat official accounts on the Xigua website. The data included the change in the number of followers and the total number of likes on each account in a 7-day period, as well as the number of each type of article and headlines about coronavirus. It was used to developed regression models and conduct content analysis to figure out information characteristics in quantity and content. Results: For nonmedical institution accounts in the model, report and story types of articles had positive effects on users' following behaviors. The number of headlines on coronavirus positively impacts liking behaviors. For medical institution accounts, report and science types had a positive effect, too. In the content analysis, several common characteristics were identified. Conclusions: Characteristics in terms of the quantity and content in health information dissemination contribute to users' information behavior. In terms of the content in the headlines, via coding and word frequency analysis, organizational structure, multimedia applications, and instructions-the common dimension in different articles-composed the common features in information that impacted users' liking behaviors.