Objective: To examine the COVID-19 vaccination rate among a representative sample of adults from 31 provinces on the Chinese mainland and identify its influencing factors.Methods: We gathered sociodemographic information, data on people's awareness and behavior regarding COVID-19 and the COVID-19 vaccine, the accessibility of COVID-19 vaccination services, community environmental factors influencing people's awareness and behavior regarding the vaccination, information about people's skepticism on COVID-19 vaccine, and information about people's trust in doctors as well as vaccine developers through an online nationwide cross-sectional survey among Chinese adults (18 years and older). The odds ratios (OR) and 95% confidence intervals (CI) for the statistical associations were estimated using logistic regression models.Results: A total of 29,925 participants (51.4% females and 48.6% males) responded. 89.4% of the participants had already received a COVID-19 vaccination. After adjusting for demographic characteristics, awareness of COVID-19 pandemic/ COVID-19 vaccine, community environmental factors, awareness and behavior of general vaccinations, we discovered that having no religious affiliation, having the same occupational status as a result of coronavirus epidemic, being a non-smoker, always engaging in physical activity, having a lower social status, perceiving COVID-19 to be easily curable, and having easier access to vaccination are all associated with high vaccination rate (all P <0.05).Conclusions: 31 provinces in mainland China currently have a relatively high rate of COVID-19 vaccination. To further increase the rate of COVID-19 vaccination, we must remove barriers associated with the community context and improve access to COVID-19 vaccine services. In addition, taking proactive and effective measures to address the reasons for non-vaccination with COVID-19 will aid in epidemic prevention and control.

Fluoride is widely distributed, and excessive intake will lead to dental fluorosis. In this study, six offspring rats administrated 100 mg/L sodium fluoride were defined as the dental fluorosis group, and eight offspring rats who received pure water were defined as the control group. Differentially expressed proteins and metabolites extracted from peripheral blood were identified using the liquid chromatography tandem mass spectrometry and gas chromatography mass spectrometry, with the judgment criteria of fold change >1.2 or <0.83 and p < 0.05. A coexpression enrichment analysis using OmicsBean was conducted on the identified proteins and metabolites, and a false discovery rate (FDR) < 0.05 was considered significant. Human Protein Atlas was used to determine the subcellular distribution of hub proteins. The Gene Cards was used to verify results. A total of 123 up-regulated and 46 down-regulated proteins, and 12 up-regulated and 2 down-regulated metabolites were identified. The significant coexpression pathways were the HIF-1 (FDR = 1.86 × 10⁻³) and glycolysis/gluconeogenesis (FDR = 1.14 × 10⁻¹⁰). The results of validation analysis showed the proteins related to fluorine were mainly enriched in the cytoplasm and extrinsic component of the cytoplasmic side of the plasma membrane. The HIF-1 pathway (FDR = 1.01 × 10⁻⁷) was also identified. Therefore, the HIF-1 and glycolysis/gluconeogenesis pathways were significantly correlated with dental fluorosis.

To identify the role of the Hippo signaling pathway in the extracellular matrix degradation of chondrocytes induced by fluoride exposure. Environmental response genes (ERGs) of bone injury induced by fluoride exposure were obtained from the Comparative Toxicogenomics Database, and annotated by STRING for KEGG pathway enrichment analysis. The CCK-8 kit was used to measure the proliferation of ATDC5 cells. The malondialdehyde (MDA), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-PX) levels in ATDC5 cells were measured using oxidative stress detection kit. Western blot analysis was used to measure the p-MST1/2, p-LATS1/2, and p-YAP/YAP1 expression levels in the Hippo pathway and the COL2A1, ACAN and MMP13 expression levels in the cartilage matrix. Localizations of YAP1 and COL2A1 proteins in chondrocytes were performed using cell immunofluorescence. Continuous data from the multiple groups were compared using one-way analysis of variance, and then the differences between groups were tested with Dunnett's t-test, with the test level α = 0.05. The 145 ERGs of bone injury induced by fluoride exposure were identified, and KEGG enrichment analysis revealed Hippo signaling pathways significantly related to bone injury. A CCK-8 assay revealed that the viability of the ATDC5 cells was significantly decreased with increased fluorine concentration. The MDA content in 20 mg/L sodium fluoride (NaF) exposure group was significantly higher than that in the control group, the T-SOD, T-AOC and GSH-PX activities in 15 and 20 mg/L NaF exposure groups were significantly lower than those in the control group (P < 0.05). Western blot results showed the protein levels of p-MST1/2, p-LATS1/2 and p-YAP1 in 15 and 20 mg/L NaF exposure groups were significantly lower than those in the control group, while the YAP1 protein level in 20 mg/L NaF group was significantly higher than that in the control group. The COL2A1 and ACAN proteins in 20 mg/L NaF group were significantly decreased, while the MMP13 protein level in 15 and 20 mg/L NaF groups were significantly increased (P < 0.05). It was observed that the expression of YAP1 protein expression level in the cytoplasm decreased with the increased fluoride exposure, whereas that the expression level of YAP1 protein in the nucleus increased. Fluoride inhibited the proliferation of ATDC5 cells, induced oxidative stress, inhibited the activity of the Hippo pathway, and eventually led to cartilage matrix degradation.

Fluorosis is a serious global public health problem. Interestingly, so far, there is no specific drug treatment for the treatment of fluorosis. In this paper, the potential mechanisms of 35 ferroptosis-related genes in U87 glial cells exposed to fluoride were explored by bioinformatics methods. Significantly, these genes are involved in oxidative stress, ferroptosis, and decanoate CoA ligase activity. Ten pivotal genes were found by the Maximal Clique Centrality (MCC) algorithm. Furthermore, according to the Connectivity Map (CMap) and the Comparative Toxicogenomics Database (CTD), 10 possible drugs for fluorosis were predicted and screened, and a drug target ferroptosis-related gene network was constructed. Molecular docking was used to study the interaction between small molecule compounds and target proteins. Molecular dynamics (MD) simulation results show that the structure of the Celestrol–HMOX1 composite is stable and the docking effect is the best. In general, Celastrol and LDN-193189 may target ferroptosis-related genes to alleviate the symptoms of fluorosis, which may be effective candidate drugs for the treatment of fluorosis.

Since the opening up and reforms that began 40 years ago, China’s economy and society have developed rapidly. It is estimated that between 1978 and 2017, China’s Gross Domestic Product (GDP) increased on an average of 9.5% annually, and per-capita GDP growth was about 22.8-fold.1 During the same period, more than 700 million Chinese people were lifted out of poverty.2 Consequently, China has become a much healthier nation. The average life expectancy in China rose from 65.2 years in 1978 to 76 years in 2017.3 China did remarkably well in meeting the Millennium Development Goals of reducing infant mortality and improving maternal health.4 For example, under-five mortality dropped from 54·1 death per 1000 live births in 1990 to 12·5 per 1000 live births in 2015. Similarly, the maternal mortality ratio declined from 111·0 deaths per 100 000 live births to 21·8 per 100 000 live births during the same time.4 5