Impact of food safety supervision efficiency on preventing and controlling mass public crisis.

Food safety has received unprecedented attention since the COVID-19 outbreak. Exploring food safety regulatory mechanisms in the context of cluster public crises is critical for COVID-19 prevention and control. As a result, using data from a food safety regulation survey in the Bei-jing-Tianjin-Hebei urban cluster, this paper investigates the impact of food safety regulation on the prevention and control of COVID-19. The study found that food safety regulation and cluster public crisis prevention and control have a significant positive relationship, with the ability to integrate regulatory resources acting as a mediator between the two. Second, industry groups argue that the relationship between regulatory efficiency and regulatory resource integration should be moderated in a positive manner. Finally, industry association support positively moderates the mediating role of regulatory re-source integration capacity between food safety regulatory efficiency and cluster public crises, and there is a mediating effect of being moderated. Our findings shed light on the mechanisms underlying the roles of regulatory efficiency, resource integration capacity, and industry association support in food safety, and they serve as a useful benchmark for further improving food safety regulations during the COVID-19 outbreak.

Micronucleus production, activation of DNA damage response and cGAS-STING signaling in syncytia induced by SARS-CoV-2 infection.

SARS-CoV-2 infection could cause severe acute respiratory syndrome, largely attributed to dysregulated immune activation and extensive lung tissue damage. However, the underlying mechanisms are not fully understood. Here, we reported that viral infection could induce syncytia formation within cells expressing ACE2 and the SARS-CoV-2 spike protein, leading to the production of micronuclei with an average rate of about 4 per syncytium (> 93%). Remarkably, these micronuclei were manifested with a high level of activation of both DNA damage response and cGAS-STING signaling, as indicated by micronucleus translocation of γH2Ax and cGAS, and upregulation of their respective downstream target genes. Since activation of these signaling pathways were known to be associated with cellular catastrophe and aberrant immune activation, these findings help explain the pathological effects of SARS-CoV-2 infection at cellular and molecular levels, and provide novel potential targets for COVID-19 therapy.

SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (~45.1 nm/s) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.

SARS-CoV-2 Targets by the pscRNA Profiling of ACE2, TMPRSS2 and Furin Proteases.

The cellular targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic, is still rudimentary. Here, we incorporated the protein information to analyze the expression of ACE2, the SARS-CoV-2 receptor, together with co-factors, TMPRSS2 and Furin, at single-cell level in situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary, and thyroid, whereas the kidney proximal tubule cells, cholangiocytes, and enterocytes are less likely to be the primary SARS-CoV-2 targets. Actually, the stomach may constitute a physical barrier against SARS-CoV-2 as the acidic environment (pH < 2.0) could completely inactivate SARS-CoV-2 pseudo-viruses. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling.