COVID-19 is a disease with heterogeneous clinical appearances. Most patients are asymptomatic or exhibit mild to moderate symptoms; approximately 15% progress to severe pneumonia and about 5% are eventually admitted to the intensive care unit (ICU) due to acute respiratory distress syndrome (ARDS), septic shock and/ or multiple organ failure. ICU patients respond poorly to currently available treatments and exhibit a high mortality rate. 1-3 Inadequate identification of the determinants of fatal outcomes is one of the major obstacles to the improvement of the outcomes in severe COVID-19 patients. A previous study reported a scoring system (COVID-GRAM) which accurately predicted the occurrence of critical illness in hospitalized COVID-19 patients. 4 Damage-associated molecular patterns (DAMPs), or alarmins, are a number of molecules, released by stressed cells undergoing microbial infection or sterile injury, that act as danger signals to promote and exacerbate the inflammatory response. 5,6 Of note, the serum level of S100A8/A9 and HMGB1 was found to be correlated with both the severity of pathogen-associated tissue damage and excessive cytokine storm. 7 Despite the hypothesis that S100A8/A9 and HMGB1 are significantly involved in COVID-19, so far, no study has yet tried to substantiate the hypothesis. In this study, we aimed to define the role of S100A8/ A9 and HMGB1 in progression to a fatal outcome and develop clinically relevant risk strata for COVID-19 patients. A total of 121 patients were enrolled in this retrospective study, of which 40 patients were in ICU and 81 patients in general wards at enrollment (Table S1). ICU Patients had much higher COVID-GRAM risk scores in comparison to those in general wards. Complications, including ARDS, sepsis, septic shock, secondary infection, acute renal injury, acute cardiac injury or failure, were more frequent in CCOVID-19 patients admitted to ICU. As of the cutoff date of April 30, 2020, most of non-ICU patients (96.3%) had been discharged alive, while 82.5% of ICU patients had died in ICU.

SummaryTwo novel MYB transcription factors are involved in lignin biosynthesis and flesh lignification in loquat fruit, which are manipulated by temperature condition and treatments.

SummaryLignin biosynthesis is regulated by many transcription factors, such as those of the MYB and NAC families. However, the roles of AP2/ERF transcription factors in lignin biosynthesis have been rarely investigated. Eighteen EjAP2/ERF genes were isolated from loquat fruit (Eriobotrya japonica), which undergoes postharvest lignification during low temperature storage. Among these, expression of EjAP2-1, a transcriptional repressor, was negatively correlated with fruit lignification. The dual-luciferase assay indicated that EjAP2-1 could trans-repress activities of promoters of lignin biosynthesis genes from both Arabidopsis and loquat. However, EjAP2-1 did not interact with the target promoters (Ej4CL1). Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays indicated protein-protein interactions between EjAP2-1 and lignin biosynthesis-related EjMYB1 and EjMYB2. Furthermore, repression effects on the Ej4CL1 promoter were observed with the combination of EjAP2-1 and EjMYB1 or EjMYB2, while EjAP2-1 with the EAR motif mutated (mEjAP2-1) lost such repression, although mEjAP2-1 still interacted with EjMYB protein. Based on these results, it is proposed that EjAP2-1 is an indirect transcriptional repressor on lignin biosynthesis, and the repression effects were manifested by EAR motifs and were conducted via protein-protein interaction with EjMYBs.