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The unprecedented coronavirus disease 2019 (COVID-19) pandemic has caused a disaster for public health in the last 2 years, without any sign of an ending. Various vaccines were developed rapidly as soon as the outbreak occurred. Clinical trials demonstrated the reactogenicity, immunogenicity and protection efficacy in humans, and some of the vaccines have been approved for clinical use. However, waves of infections such as the recently circulating Omicron variant still occur. Newly emerging variants, especially the variants of concern, and waning humoral responses pose serious challenges to the control of the COVID-19 pandemic. Previously, we summarized the humoral and cellular immunity, safety profiles and protection efficacy of COVID-19 vaccines with clinical data published by 21 May 2021. In this review, we summarize and update the published clinical data of COVID-19 vaccines and candidates up to 31 December 2021. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), one of the most lethal malignancies worldwide, has limited efficient therapeutic options. Here, we first demonstrated that simultaneously targeting poly (ADP-ribose) polymerase (PARP) and autophagy could evoke striking synergistic lethality in HCC cells. Specifically, we found that the PARP inhibitor Niraparib induced cytotoxicity accompanied by significant autophagy formation and autophagic flux in HCC cells. Further experiments showed that Niraparib induced suppression of the Akt/mTOR pathway and activation of the Erk1/2 cascade, two typical signaling pathways related to autophagy. In addition, the accumulation of reactive oxygen species was triggered, which was involved in Niraparib-induced autophagy. Blocking autophagy by chloroquine (CQ) in combination with Niraparib further enhanced cytotoxicity, induced apoptosis and inhibited colony formation in HCC cells. Synergistic inhibition was also observed in Huh7 xenografts in vivo. Mechanistically, we showed that autophagy inhibition abrogated Niraparib-induced cell-cycle arrest and checkpoint activation. Cotreatment with CQ and Niraparib promoted the formation of γ-H2AX foci while inhibiting the recruitment of the homologous recombination repair protein RAD51 to double-strand break sites. Thus, the present study developed a novel promising strategy for the management of HCC in the clinic and highlighted a potential approach to expand the application of PARP inhibitors. [ABSTRACT FROM AUTHOR]