Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.

Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.

Background: Cytoplasmic male sterility (CMS) is a complex phenomenon of plant sterility that can produce non-functional pollen. It is caused by mutation, rearrangement or recombination in the mitochondrial genome. So far, the systematic structural characteristics of the changes in the mitochondrial genome from the maintainer lines to the CMS lines have not been reported in tobacco. Results: The mitochondrial genomes of the flower buds from both CMS lines and maintainer lines of two Nicotiana tabacum cultivars (YY85, sYY85, ZY90, and sZY90) were sequenced using the PacBio and Illumina Hiseq technology, and several findings were produced by comparative analysis based on the de novo sequencing. (1) The genomes of the CMS lines were larger, and the different areas were mostly non-coding regions. (2) A large number of rearrangement regions were detected in the CMS lines, with many translocation regions. (3) Thirteen gene clusters were shared by the four mitochondrial genomes, among which two of the gene clusters, nad2-sdh3 and nad6-rps4, were far from each other in the CMS lines. (4) Thirty-three protein-coding genes were conserved in four mitochondrial genomes. However, nad3 was detected one additional copy in the maintainer lines, and sequence differences were revealed in the four candidate genes (atp6, cox2, nad2, and sdh3). Importantly, the evolutionary tree based on the four genes could be used to distinguish the CMS lines and the maintainer lines well for the sequenced mitochondrial genomes of the tobacco. (5) Sixteen CMSspecific open reading frames (ORFs) were found, three of which (orf91, orf115b, and orf100) were previously reported. (6) The differences in intensity of the protein-protein (PPI) interaction in ATP6 were further verified using the yeast two-hybrid analysis. Conclusion: Although the majority of the sequences, genes and gene clusters were shared by the mitochondrial genomes of the maintainer and the CMS lines in

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The environmental protection agency thinks that quantitative structure–activity relationship (QSAR) analysis can better replace toxicity tests.