Paracrinal regulation of neutrophil functions by coronaviral infection in iPSC-derived alveolar type II epithelial cells.

Coronaviruses (CoVs) are enveloped single-stranded RNA viruses that predominantly attack the human respiratory system. In recent decades, several deadly human CoVs, including SARS-CoV, SARS-CoV-2, and MERS-CoV, have brought great impact on public health and economics. However, their high infectivity and the demand for high biosafety level facilities restrict the pathogenesis research of CoV infection. Exacerbated inflammatory cell infiltration is associated with poor prognosis in CoV-associated diseases. In this study, we used human CoV 229E (HCoV-229E), a CoV associated with relatively fewer biohazards, to investigate the pathogenesis of CoV infection and the regulation of neutrophil functions by CoV-infected lung cells. Induced pluripotent stem cell (iPSC)-derived alveolar epithelial type II cells (iAECIIs) exhibiting specific biomarkers and phenotypes were employed as an experimental model for CoV infection. After infection, the detection of dsRNA, S, and N proteins validated the infection of iAECIIs with HCoV-229E. The culture medium conditioned by the infected iAECIIs promoted the migration of neutrophils as well as their adhesion to the infected iAECIIs. Cytokine array revealed the elevated secretion of cytokines associated with chemotaxis and adhesion into the conditioned media from the infected iAECIIs. The importance of IL-8 secretion and ICAM-1 expression for neutrophil migration and adhesion, respectively, was demonstrated by using neutralizing antibodies. Moreover, next-generation sequencing analysis of the transcriptome revealed the upregulation of genes associated with cytokine signaling. To summarize, we established an in vitro model of CoV infection that can be applied for the study of the immune system perturbations during severe coronaviral disease.

Superrepellent Doubly Reentrant Geometry Promotes Antibiofouling and Prevention of Coronavirus Contamination.

The fomite transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drawn attention because of its highly contagious nature. Therefore, surfaces that can prevent coronavirus contamination are an urgent and unmet need during the coronavirus disease 2019 (COVID-19) pandemic. Conventional surfaces are usually based on superhydrophobic or antiviral coatings. However, these coatings may be dysfunctional because of biofouling, which is the undesired adhesion of biomolecules. A superhydrophobic surface independent of the material content and coating agents may serve the purpose of antibiofouling and preventing viral transmission. Doubly reentrant topology (DRT) is a unique structure that can meet the need. This study demonstrates that the DRT surfaces possess a striking antibiofouling effect that can prevent viral contamination. This effect still exists even if the DRT surface is made of a hydrophilic material such as silicon oxide and copper. To the best of our knowledge, this work first demonstrates that fomite transmission of viruses may be prevented by minimizing the contact area between pathogens and surfaces even made of hydrophilic materials. Furthermore, the DRT geometry per se features excellent antibiofouling ability, which may shed light on the applications of pathogen elimination in alleviating the COVID-19 pandemic.

Involvement of P38 and ERK1/2 in mitochondrial pathways independent cell apoptosis in oviduct magnum epithelial cells of layers challenged with vanadium.

Vanadium (V) can induce cell apoptosis in layers' oviduct resulting in egg quality reduction. In this study, we investigated the relationship between the mitogen-activated protein kinase (MAPK)-signaling pathway and V-induced apoptosis in poultry oviduct magnum epithelial cells (OMECs). Cultured OMECs were divided into 8 treatment groups: 0 µmol/L V (control), 100 µmol/L V (V100), V100 + P38MAPK inhibitor (SB203580), SB203580, V100 + extracellular signal-regulated kinases 1 and 2 (ERK1/2) inhibitor (U0126), U0126, V100 + c-JUN NH2 -terminal kinase (JNK) inhibitor (SP600125), and SP600125. The OMECs were pretreated with the MAPK inhibitors before their treatment with V100 for 12 h. V100 increased the apoptosis of OMECs (P < .05), while 3 MAPK inhibitors suppressed V100-induced apoptosis P < .05); V100 enhanced the depolarization of △ψm (P < .05), and SB203580 and U0126 alleviated the V100-induced △ψm decrease (P < .05); V100 downregulated B-cell lymphoma-2 (Bcl-2) and poly [Adenosine diphosphate ribose] polymerase 1 (PARP1) mRNA expression (P < .05), meanwhile it upregulated Bcl-2 associated x (Bax), Apaf1, cytochrome C (CytC) and cysteine aspartase (caspase) 3, 8, 9 mRNA expression (P < .05). All MAPKs inhibitors alleviated the up-regulation of V100 for Bax and caspase 3 mRNA expression and down-regulation of V100 for Bcl-2 expression (P < .05). SB203580 and U0126 upregulated CytC expression treated by V100 (P < .05), except SP600125, while SB203580 administration resulted in a similar upregulation of PARP1 expression (P < .05). SP600125 can alleviated V triggered p-P38MAPK (phosphor-P38), p-ERK1/2 (phosphor-ERK1/2), p-JNK (phosphor-JNK) increase on OME cells, and SB203580 and U0126 had a similar response to phosphor-P38 and p-JNK (P < .05). It concluded that V-induced apoptosis in OMECs through the activation of P38 and ERK1/2, and by increasing the ratio of Bax/Bcl-2, which resulted in △ψm decrease, CytC release into the cytosol; consequently caspase 3 is recruited and activated, PARP1 is cleaved, eventually leading to apoptosis.