Gene therapy with small interfering RNA (siRNA) has been proved to be a promising technology to treat various diseases by hampering the production of target proteins. However, developing a delivery system that has high efficiency in transporting siRNA without obvious side effects remains a challenge. Herein, we designed a new survivin siRNA delivery system based on polyethyleneimine functionalized black phosphorus (BP) nanosheets which could suppress tumor growth by silencing survivin expression. Combined with the photothermal properties of the BP nanosheets, the presented delivery system shows excellent therapy efficiency for tumors. Therefore, the BP-based delivery system would be a promising tool for future clinical applications.

Background: Fetal growth restriction (FGR) is a worldwide problem, and a major cause of perinatal morbidity. The precise molecular mechanisms involved in placental development and function during FGR remain poorly understood. Circular RNAs (circRNAs) are important biological molecules associated with disease pathogenesis. However, the role of circRNAs in FGR has not been well studied. Methods: circRNA expression profiles in placental tissues with and without FGR were identified by circRNA microarray. circRNA expression was verified by quantitative reverse-transcription PCR (RT-qPCR) assay. The effect of hsa_circ_0000848 and hsa-miR-6768-5p on HTR-8 cell apoptosis, migration, and invasion was evaluated. The association between hsa_circ_0000848 and hsa-miR-6768-5p was confirmed by dual luciferase activity and anti-AGO2 RNA immunoprecipitation (RIP) assays. Protein levels were examined via western blotting. Results: RT-qPCR results showed that hsa_circ_0000848 expression was significantly down-regulated in FGR placenta. Hsa_circ_0000848 overexpression and hsa-miR-6768-5p inhibitor suppressed apoptosis, and promoted cell migration and invasion. In addition, hsa_circ_0000848 overexpression and hsa-miR-6768-5p inhibitor increased the protein abundance of BCL2, MMP2 and MMP9, and decreased the protein abundance of cleaved caspase-3, cleaved caspase-9, and BAX, whereas hsa_circ_0000848 knockdown caused the opposite effect. Moreover, a significant increase in hsa-miR-6768-5p expression and a negative correlation between hsa_circ_0000848 and hsa-miR-6768-5p were identified in the FGR tissues. Luciferase reporter and RIP assay results revealed binding of hsa-miR-6768-5p to hsa_circ_0000848. Furthermore, hsa-miR-6768-5p overexpression eliminated the effect of hsa_circ_0000848 overexpression in HTR-8 cells.

The aim of the study was to examine the correlation between COVID-19 vaccine coverage rates and outcomes of the COVID-19 epidemic in the case of COVID-19 variants based on real-world data. The data came from Our World in Data, which is building the international COVID-19 vaccination data set and is an open-source data set for everyone to use. The vaccination data set uses the most recent official numbers from governments and health ministries worldwide. We assessed the correlation between COVID-19 vaccine coverage rates and outcomes of the COVID-19 epidemic with existing variants by performing temporal analysis and spatial analysis. Overall, new cases per million population, the reproduction rate of COVID-19, new deaths from all causes per million population, excess mortality attributed to COVID-19 pandemic, and hospital patients or intensive care unit (ICU) patients per million population were not decreased with the time course. However, at the same time point, new cases per million population, the reproduction rate of COVID-19, new deaths per million population, and hospital patients or ICU patients per million population gradually decreased as the rate of vaccination coverage increased. High coverage percentages of COVID-19 vaccination were negatively correlated with the reproduction rate of COVID-19 (correlation coefficient −0.116) and ICU patients per million of the local population (correlation coefficient −0.055). Currently, there is no effective treatment for the COVID-19 pandemic, and prevention of the COVID-19 pandemic mainly depends on vaccines, especially when the rate of COVID-19 vaccine coverage is over 60%. The benefits of preventing severe disease and preventing transmission of infection are likely to be obvious.

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Human DNA polymerase iota (pol ι) possesses high error-prone DNA replication features and performs translesion DNA synthesis. It may be specialized and strictly regulated in normal mammalian cells. Dysregulation of pol ι may contribute to the acquisition of a mutator phenotype. However, there are few reports describing the transcription regulatory mechanism of pol ι, and there is controversy regarding its role in carcinogenesis. In this study, we performed the deletion and point-mutation experiment, EMSA, ChIP, RNA interference and western blot assay to prove that c-Jun activated by c-Jun N-terminal kinase (JNK) regulates the transcription of pol ι in normal and cancer cells. Xeroderma pigmentosum group C protein (XPC) and ataxia-telangiectasia mutated related protein (ATR) promote early JNK activation in response to DNA damage and consequently enhance the expression of pol ι, indicating that the novel role of JNK signal pathway is involved in DNA damage response. Furthermore, associated with elevated c-Jun activity, the overexpression of pol ι is positively correlated with the clinical tumor grade in 97 bladder cancer samples and may contribute to the hypermutagenesis. The overexpressed pol ι-involved mutagenesis is dependent on JNK/c-Jun pathway in bladder cancer cells identifying by the special mutation spectra. Our results support the conclusion that dysregulation of pol ι by JNK/c-Jun is involved in carcinogenesis and offer a novel understanding of the role of pol ι or c-Jun in mutagenesis.

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LincRNA FEZF1-AS1 has been identified to exert oncogenic functions in various biological processes of tumorigenesis. However, the function of FEZF1-AS1 in lung adenocarcinoma still remains unclear. Our findings revealed that FEZF1-AS1 was increased in lung adenocarcinoma tissues and cell lines and high level of FEZF1-AS1 was associated with poor prognosis of lung adenocarcinoma. Functional experiments and mechanistic investigations demonstrated that knockdown of FEZF1-AS1 significantly repressed proliferation through influencing the distribution of cell cycle. Besides, we also uncovered that FEZF1-AS1 could suppress p57 expression through recruiting EZH2 and LSD1 to the promoter of p57, thus influenced the cell cycle and proliferation. Collectively, our results suggested that FEZF1-AS1 was involved in the progression of lung adenocarcinoma and might be as a potential therapy target for human lung adenocarcinoma.