Identification of serum metabolites enhancing inflammatory responses in COVID-19

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is characterized by a strong production of inflammatory cytokines such as TNF and IL-6,which underlie the severity of the disease.However,the molecular mechanisms responsible for such a strong immune response remains unclear.Here,utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages,we identified that 611 metabolites(of 1,039)were significantly altered in COVID-19 patients.Among them,two metabolites,agmatine and putrescine,were prominently elevated in the serum of patients;and 2-quinolinecarboxylate was changed in a biphasic manner,elevated during early COVID-19 infection but levelled off.When tested in mouse embryonic fibroblasts(MEFs)and macrophages,these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production.Importantly,these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice,but not in the mice lacking NF-κB.Intriguingly,these metabolites have little effects on the activation of interferon regulatory factors(IRFs)for the production of type I interferons(IFNs)for antiviral defenses.These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses,exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons.Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients.

Development background of Mesozoic high-quality source rocks: Evidence from microfossils in North Carnarvon Basin, Australia

Based on numerous microfossils in Mesozoic of North Carnarvon Basin in Australia,the Mesozoic paleoclimate and paleoenvironment were analyzed,the paleogeographic background and development model of Mesozoic high-quality source rocks were investigated and discussed.Variation of microfossil species and their relative contents in Mesozoic different intervals indicates changes of paleoclimate and paleoenvironment.The paleoclimate shows a cycle variation of aridehumidearidehumid,the regression occurred in the Early TriassiceLate Triassic and the transgression occurred in the Late TriassiceLate Cretaceous.Four sedimentary facieses including delta facies,littoral facies,restricted sea facies and open sea facies were developed in the Mesozoic.The open sea was mainly developed in the Early Triassic,the delta was distributed in the MiddleeLate Triassic,the restricted sea was especially well developed in the Jurassic,and the restricted sea and open sea were mainly distributed in the Cretaceous.Characteristics of microfossil assemblage in these four sedimentary facies are dramatically different.From the delta facies,littoral facies,restricted sea facies to open sea facies,content of pollen gradually decreases,but content of the dinoflagellate+acritarch gradually increases.The delta facies and littoral facies are dominated by the pollen.In the restricted sea facies,content of the pollen is equivalent to that of the dinoflagellate+acritarch.The open sea facies is dominated by the dinoflagellate and acritarch.Supply of sediment and formation of organic matter are influenced by the paleoclimate and paleoenvironment,and type of organic matter is controlled by the microfossil assemblage.Based on the palaeogeographic background,paleoclimatic condition and microfossil assemblage,two developmental models of the Mesozoic source rocks such as the development model of terrestrial organic matter under the background of large delta and the development model of mixed organic matter under the background of the restricted sea,were proposed.