Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected Patients Through Single-Cell Transcriptome Sequencing

Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019(COVID-19)is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity.In this study,we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19samples including severe,moderate,and convalescent samples from three severely/critically ill and four moderately ill patients.We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19,with an increased proportion of monocytes and seriously reduced diversity.In addition,we discovered two novel severe-disease-specific monocyte subsets:Mono 0 and Mono 5.These subsets expressed amphiregulin(AREG),epiregulin(EREG),and cytokine interleukin-18(IL-18)gene,exhibited an enriched erythroblastic leukemia viral oncogene homolog(ErbB)signaling pathway,and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics.We also found metabolic changes in Mono 0 and Mono 5,including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1(HIF-1)signaling pathway.Notably,one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples.In conclusion,our study discovered two novel severedisease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19.Overall,this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.

Unraveling Interactions Between Gut Epithelium and Microbiota Using Models of Intestinal Organoids

Intestinal microbiota is an indispensable part of intestinal homeostasis and is closely related to human health.Intestinal microbiota participates in the development of a variety of intestinal diseases in a complex and diverse manner.Previous results have confirmed microbiota dysbiosis in a variety of diseases,while the mechanism is not clear.It is valuable to unravel these complex mechanisms,which would guide future therapies.A limiting factor of studies exploring interaction mechanisms between gut epithelium and microbiota was a lack of an in vitro organ model.The development of organoids has provided an indispensable tool for gastrointestinal studies.Here,we review the applications of organoids in exploring the roles of gut microbiota and its metabolites in diseases,summarize the advantages and limitations of organoid models,and discuss future prospective and challenges in this area.

Cytochrome P450 monooxygenase specific activity reduction in wheat Triticum aestivum induced by soil roxithromycin stress

Roxithromycin, livestock growth promoter, as widely used medicine and arouses concern because its occurrence and persistence in soil environments. However, effects of roxithromycin in higher plants are still vague. Accordingly, we hypothesized that roxithromycin-con- taminated soil may exhibits ecotoxicological effects in wheat （Triticum aestivum）. In this study, effects induced by a gradient concentration of roxithromycin stress （0.01, 0.1, 1, 10, and 100 mg.kg-1） was investigated in a 7-d soil test in T. aestivum. Results indicated that the specific activity of cytochrome P450 （CYP450） monooxygenase was decreased dramatically with the concentration of roxithro- mycin in soil. The IC50 value was 8.78mg.kg-1 of roxithromycin. On the contrary, the growth related endpoints （i.e., the germination percentage, the biomass and the height）, the content related endpoints （i.e., soluble protein content and CYP450 content）, and the superoxide dismutase （SOD） activity failed to reveal the roxithromy- cin-induced effects. Further analysis revealed that the CYP450 monooxygenase specific activity reduction was enzymatic mechanism mediated, other than oxidative stress induced. We conclude that the soil roxithromycin declined the CYP450 monooxygenase activity in T. aestivum by the inhibition of the enzymatic mechanism. Further efforts can include, but are not limited to, investigation of joint effects induced by combined exposure of roxithromycin and the pesticides and evalua- tion of the similar effects in other higher plants.

Assessment of potential soybean cadmium excluder cultivars at different concentrations of Cd in soils

The selection of cadmium-excluding cultivars has been used to minimize the transfer of cadmium into the human food chain. In this experiment, five Chinese soybean plants were grown in three soils with different concentrations of Cd（0.15, 0.75 and 1.12 mg/kg）.Variations in uptake, enrichment, and translocation of Cd among these soybean cultivars were studied. The results indicated that the concentration of Cd in seeds that grew at1.12 mg/kg Cd in soils exceeded the permitted maximum levels in soybeans. Therefore, our results indicated that even some soybean cultivars grown on soils with permitted levels of Cd might accumulate higher concentrations of Cd in seeds that are hazardous to human health. The seeds of these five cultivars were further assessed for interactions between Cd and other mineral nutrient elements such as Ca, Cu, Fe, Mg, Mn and Zn. High Cd concentration in soil was found to inhibit the uptake of Mn. Furthermore, Fe and Zn accumulations were found to be enhanced in the seeds of all of the five soybean cultivars in response to high Cd concentration. Cultivar Tiefeng 31 was found to fit the criteria for a Cd-excluding cultivar under different concentrations of Cd in soils.