Highlights d RBD and HR nanoparticle vaccines induce potent neutralizing antibody responses d Nanoparticle vaccines protect against SARS-CoV-2 infection in mice d HR antigens elicit both humoral and cellular immune responses d HR antigens within nanoparticles contribute to crossprotective immunity

When recruited to promoters, histone 3 lysine 4 (H3K4) methyltransferases KMT2 (KMT2A-D) activate transcription by opening chromatin through H3K4 methylation. Here we report that KMT2 mutations occur frequently in non-small cell lung cancer (NSCLC) and are associated with high mutation loads and poor survival. KMT2C regulated DNA damage responses (DDR) through direct recruitment to DNA damage sites by Ago2 and small noncoding DNA damage response RNA, where it mediates H3K4 methylation, chromatin relaxation, secondary recruitment of DDR factors, and amplification of DDR signals along chromatin. Furthermore, by disrupting homologous recombination (HR)-mediated DNA repair, KMT2C/D mutations sensitized NSCLC to Poly(ADP-Ribose) Polymerase inhibitors (PARPi), whose efficacy is unclear in NSCLC due to low BRCA1/2 mutation rates. These results demonstrate a novel, transcription-independent role of KMT2C in DDR and identify high-frequency KMT2C/D mutations as much-needed biomarkers for PARPi therapies in NSCLC and other cancers with infrequent BRCA1/2 mutations. STATEMENT OF SIGNIFICANCEThis study uncovers a critical role for KMT2C in DDR via direct recruitment to DNA damage sites, identifying high-frequency KMT2C/D mutations as biomarkers for response to PARP inhibition in cancer.

Cancer stem cells (CSCs) are recognized as the major source for cancer initiation and recurrence. Yet, the mechanism by which the cancer stem cell properties are acquired and maintained in a cancer cell population is not well understood. In the current study, we observed that the level of active p38 MAPK is downregulated, while the level of the stemness marker SOX2 is upregulated in lung cancer tissues as compared to normal tissues. We further demonstrated that inactivation of p38 is a potential mechanism contributing to acquisition and maintenance of cancer stem cell properties in non-small cell lung cancer (NSCLC) cells. p38, in particular the p38γ and p38δ isoforms, suppresses the cancer stem cell properties and tumor initiating ability of NSCLC cells by promoting the ubiquitylation and degradation of stemness proteins such as SOX2, Oct4, Nanog, Klf4 and c-Myc, through MK2-mediated phosphorylation of Hsp27 that is an essential component of the proteasomal degradation machinery. In contrast, inactivation of p38 in lung cancer cells leads to upregulation of the stemness proteins, thus promoting the cancer stem cell properties of these cells. These findings have demonstrated a novel mechanism by which cancer stem cell properties are acquired and maintained in a cancer cell population, and have revealed a new function of the p38 pathway in suppressing cancer development. These studies have also identified a new pathway that can potentially serve as a target for cancer therapies aimed at eliminating CSCs.

The aim of the study was to detect PPA1 expression in various tumors and to investigate the relationship between PPA1 expression and clinicopathological parameters to further analyze its clinical significance. Immunohistochemical staining detected PPA1 expression in 305 noncancerous tissues and 675 tumor tissues, which included 12 different tumor types. QPCR and western blot examined PPA1 expression in tumor‐derived cell lines including those derived from liver, breast, lung, and ovarian cancers. Cell proliferation and apoptosis assays were used to investigate PPA1‐regulated cell growth in tumor cells. Finally, a bioinformatics analysis was used to verify the role of PPA1 in carcinogenesis. Among the 12 types of tumors, PPA1 expression was significantly higher in lung and ovarian cancers (P < 0.001). In lung cancer, PPA1 expression was associated with tumor size, patients’ age, and smoking status, whereas in ovarian cancer, PPA1 expression was associated with pathological grade (P < 0.05). Moreover, we found that PPA1 expression was up‐regulated in lung and ovarian cancer cell lines compared with nontumor cells. In addition, suppression of PPA1 expression by RNA interference in lung and ovarian cancer cells showed increased cell apoptosis and decreased cell proliferation, which was mediated by TP53 and p21 signaling. Notably, a bioinformatics analysis was used to verify the function of PPA1 in the development and progression of tumors. PPA1 expression is significantly higher in many tumors, especially those of lung and ovarian origin, which suggests that PPA1 plays an important role in carcinogenesis and in the development of some tumors.

Since the outbreak of coronavirus disease 2019 (COVID-19), it has become a global pandemic. The spike (S) protein of etiologic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specifically recognizes human angiotensin-converting enzyme 2 (hACE2) as its receptor, which is recently identified as an interferon (IFN)-stimulated gene. Here, we find that hACE2 exists on the surface of exosomes released by different cell types, and the expression of exosomal hACE2 is increased by IFNα/β treatment. In particular, exosomal hACE2 can specifically block the cell entry of SARS-CoV-2, subsequently inhibit the replication of SARS-CoV-2 in vitro and ex vivo. Our findings have indicated that IFN is able to upregulate a viral receptor on the exosomes which competitively block the virus entry, exhibiting a potential antiviral strategy.

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Abstract:Here we reported the use of electropolymerization to achieve the transformation of aqueous hydroquinone to solid-phase polyhydroquinone (PHQ) with pseudocapacitive characteristics, and the application of this redox-active product to shuttle electron transfer in the anode system of a microbial fuel cell (MFC). The microscopic and spectroscopic results showed that the treatment of the graphite felt (GF) substrate with acids was effective in improving the amounts of surface-bound oxygen-containing groups, enabling better adhesion of PHQ onto the GF surfaces. The electrochemical measurements indicated that the resulting PHQ-AGF (acid treated GF) possessed high pseudocapacitance due to the fast and reversible redox cycling between hydroquinone and benzoquinone. The MFC equipped with the PHQ-AGF anode achieved a maximum power density of 633.6 mW m −2 , which was much higher than 368.2, 228.8, and 119.7 mW m −2 corresponding to the MFC with the reference PHQ-GF, AGF, and GF anodes, respectively. The increase in the power performance was attributed to the incorporation of the redox-active PHQ abundant in C-OH and C=O groups that were beneficial to the increased extracellular electron transfer and enhanced bacterial adhesion on the anode.

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