Molecular mechanism of SARS-Cov-2 components caused ARDS in murine model

COVID-19 has become a major challenge to global health, and until now, no efficient antiviral agents have been developed. The SARS-CoV-2 infection is characterized by pulmonary and systemic inflammation in severe patients, and acute respiratory distress syndrome (ARDS) caused respiratory failure contributes to most mortalities. There is an urgent need for developing effective drugs and vaccines against SARS-CoV-2 and COVID-19 caused ARDS. However, most researchers cannot perform SARS-CoV-2 related researches due to lacking P3 or P4 facility. We developed a non-infectious, highly safety, time-saving SARS-CoV-2 components induced murine model to study the SARS-CoV-2 caused ARDS and cytokine storm syndrome (CSS). We also investigated mAbs and inhibitors which potentially neutralize the pro-inflammatory phenotype of COVID-19, and found that anti-IL-1, anti-IL-6, anti-TNF, anti-GM-CSF mAbs, p38 inhibitor, and JAK inhibitor partially relieved CSS. Besides, anti-IL-6, anti-TNF, anti-GM-CSF mAbs and inhibitors of p38, ERK, and MPO somewhat reduced neutrophilic alveolitis in the lung. In all, we established the murine model mimic of COVID-19, opening a biosafety and less time-consuming avenue for clarifying the mechanism of ARDS and CSS in COVID-19 and developing the therapeutic drugs.

Preparation of Tilmicosin Imprinted Polymers and Its Application to Solid Phase Extraction / 分析化学

Molecularly imprinted polymers (MIPs) with high selectivity to tilmicosin (TIM) were prepared using tylosin(TYL) as dummy template, methacrylic acid(MAA) as monomer, ethylene glycol dimethacrylate (EGDMA) as cross-linker.The effects of 4 porogens including dimethyl formamide, methanol, acetone, and chloroform on the recognition capability of MIPs were investigated.Orthogonal test was used to optimize the preparation of MIPs, and the optimal composition was as follows; 1.0 mmol TYL, 8.0 mmol MAA, 20.0 mmol EGDMA, 6.0 mL chloroform, 20.0 mg azobisisobutyronitrile.The solid phase extraction condi tions and characteristics of MIPs as adsorptive material for the selective extraction and enrichment of TIM were also studied.The recovery of TIM was above 90% when the following procedure was applied to MIPs cartridge: conditioning with methanol and water(pH 9.0), loading with acetonitrile, cleaning with methanol and chloroform respectively, and eluting with 3 mL methanol-ammonia(95:5, V/V).The recovery of TIM on non-imprinted polymers cartridge was only 32%.