ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications.

Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. Recently, ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. Recent studies have also reported that ZBP1 induces necroptosis in non-viral infections and mediates necrotic signal transduction by a unique mechanism. This review highlights the discovery of ZBP1 and its novel findings in necroptosis and provides an insight into its critical role in the crosstalk between different types of cell death, which may represent a new therapeutic option.

Comparative Study on Online and Offline Teaching for Creative Idea Generation

Innovation is the soul of a nation’s progress and the inexhaustible driving force for a country’s prosperity. Cultivating students’ innovative abilities is an inevitable requirement for China to rejuvenate the country through science and education and build an innovative country, and it is also an important goal of the current education reform. In the internet era and the background of global epidemic prevention, the blended teaching model integrating online and offline will become a new normal mode. By comparing the advantages and disadvantages of online teaching and 8 traditional offline teachings, this paper discusses how to make full use of the online and offline blended teaching modes to better promote the cultivation of students’ ability for creative idea generation .

In vitro and in vivo anti-HMPV activity of JH001 isolated from Chinese medicinal herbs

OBJECTIVE Human metapneumovirus（h MPV） is semblable to respiratory syncytial virus（RSV） which causes respiratory infections typically characterized by cough, runny nose, fever, and nasal congestion but sometimes progressing to bronchiolitis and pneumonia. Whereas, there is no corresponding drug to inhabit the virus. Studies of new compounds with potential anti-HMPV activity could produce clinical value. Chinese herbal medicine played a great role during COVID-19, therefore we choose some small molecular（JH001） extracted from botany to investigate therapeutic effect on h MPV and the underlying mechanisms. METHODS In this study, 16 HBE cells were used as a model to explore in vitro antiviral effect. Cytotoxicity assays were performed before the antiviral tests, cell viability of 16 HBE cells handled by different concentration of JH001 was estimated by Cell Counting Kit-8（CCK-8）. Then RT-q PCR, immunofluorescence, and flow cytometer were used to test the viral titer after cells infected with h MPV. Eventually, 6-8 weeks mice were infected intranasally with 60 μL of h MPV, the control group was treated with 0.9% saline water, other groups were administered with JH001 and ribavirin, then the lung virus titer and protective effect in lung were judged. RESULTS The obtained JH001 exhibited no cytotoxicity to 16 HBE cells during 6.25-200 μmol · L-1. RT-QPCR demonstrated that JH001 showed obvious inhabitation to the viral replication and showed great significance compared with saline. And fluorescence exhibited distinct decrease of h MPV-N protein, flow cytometer results showed that MFI decrease evidently. Significant reduction of N-gene expression was observed in those mice treated with JH001 compared with saline group,which indicated that JH001 probably had protective and therapeutic effect on viral replication. CONCLUSION This study illustrated that JH001 might be a promising option for small molecular against h MPV and JH001 might be worthy of further development and used as a potential therapeutic strategy for other respiratory viruses in the future.

A false alarm of COVID-19 pneumonia in lung cancer with anti-PD-1 related pneumonitis: a case report and review of the literature.

BACKGROUND: Pneumonitis belongs to the fatal toxicities of anti-PD-1/PD-L1 treatments. Its diagnosis is based on immunotherapeutic histories, clinical symptoms, and the computed tomography (CT) imaging. The radiological features were typically ground-glass opacities, similar to CT presentation of 2019 Novel Coronavirus (COVID-19) pneumonia. Thus, clinicians are cautious in differential diagnosis especially in COVID-19 epidemic areas. CASE PRESENTATION: Herein, we report a 67-year-old Han Chinese male patient presenting with dyspnea and normal body temperature on the 15th day of close contact with his son, who returned from Wuhan. He was diagnosed as advanced non-small cell lung cancer and developed pneumonitis post Sintilimab injection during COIVD-19 pandemic period. The chest CT indicated peripherally subpleural lattice opacities at the inferior right lung lobe and bilateral thoracic effusion. The swab samples were taken twice within 72 hours and real-time reverse-transcription polymerase-chain-reaction (RT-PCR) results were COVID-19 negative. The patient was thereafter treated with prednisolone and antibiotics for over 2 weeks. The suspicious lesion has almost absorbed according to CT imaging, consistent with prominently falling CRP level. The anti-PD-1 related pneumonitis mixed with bacterial infection was clinically diagnosed based on the laboratory and radiological evidences and good response to the prednisolone and antibiotics. CONCLUSION: The anti-PD-1 related pneumonitis and COVID-19 pneumonia possess similar clinical presentations and CT imaging features. Therefore, differential diagnosis depends on the epidemiological and immunotherapy histories, RT-PCR tests. The response to glucocorticoid is still controversial but helpful for the diagnosis.