SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia.

RATIONALE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 pneumonia. We hypothesize that SARS-CoV-2 causes alveolar injury and hypoxemia by damaging mitochondria in airway epithelial cells (AEC) and pulmonary artery smooth muscle cells (PASMC), triggering apoptosis and bioenergetic impairment, and impairing hypoxic pulmonary vasoconstriction (HPV), respectively. OBJECTIVES: We examined the effects of: A) human betacoronaviruses, SARS-CoV-2 and HCoV-OC43, and individual SARS-CoV-2 proteins on apoptosis, mitochondrial fission, and bioenergetics in AEC; and B) SARS-CoV-2 proteins and mouse hepatitis virus (MHV-1) infection on HPV. METHODS: We used transcriptomic data to identify temporal changes in mitochondrial-relevant gene ontology (GO) pathways post-SARS-CoV-2 infection. We also transduced AECs with SARS-CoV-2 proteins (M, Nsp7 or Nsp9) and determined effects on mitochondrial permeability transition pore (mPTP) activity, relative membrane potential, apoptosis, mitochondrial fission, and oxygen consumption rates (OCR). In human PASMC, we assessed the effects of SARS-CoV-2 proteins on hypoxic increases in cytosolic calcium, an HPV proxy. In MHV-1 pneumonia, we assessed HPV via cardiac catheterization and apoptosis using the TUNEL assay. RESULTS: SARS-CoV-2 regulated mitochondrial apoptosis, mitochondrial membrane permeabilization and electron transport chain (ETC) GO pathways within 2 hours of infection. SARS-CoV-2 downregulated ETC Complex I and ATP synthase genes, and upregulated apoptosis-inducing genes. SARS-CoV-2 and HCoV-OC43 upregulated and activated dynamin-related protein 1 (Drp1) and increased mitochondrial fission. SARS-CoV-2 and transduced SARS-CoV-2 proteins increased apoptosis inducing factor (AIF) expression and activated caspase 7, resulting in apoptosis. Coronaviruses also reduced OCR, decreased ETC Complex I activity and lowered ATP levels in AEC. M protein transduction also increased mPTP opening. In human PASMC, M and Nsp9 proteins inhibited HPV. In MHV-1 pneumonia, infected AEC displayed apoptosis and HPV was suppressed. BAY K8644, a calcium channel agonist, increased HPV and improved SpO2. CONCLUSIONS: Coronaviruses, including SARS-CoV-2, cause AEC apoptosis, mitochondrial fission, and bioenergetic impairment. SARS-CoV-2 also suppresses HPV by targeting mitochondria. This mitochondriopathy is replicated by transduction with SARS-CoV-2 proteins, indicating a mechanistic role for viral-host mitochondrial protein interactions. Mitochondriopathy is a conserved feature of coronaviral pneumonia that may exacerbate hypoxemia and constitutes a therapeutic target.

Mistura de sementes de Brachiaria brizantha com fertilizante NPK / Mixture of Brachiaria brizantha seeds with NPK fertilizer

As informações são contraditórias quanto ao tempo em que as sementes de Brachiaria brizantha podem ficar misturadas ao fertilizante NPK sem diminuir o poder germinativo das sementes. Assim, objetivou-se estudar o efeito de tempos de contato do adubo granulado NPK 04-14-08, com sementes dessa forrageira, na qualidade fisiológica (germinação e vigor). Empregou-se o delineamento inteiramente casualizado, com quatro repetições. Foram realizadas análise de variância e comparação das médias pelo teste de Tukey, a 5 por cento. Também foram realizadas análises de regressão polinomial. Observou-se efeito significativo em todas as variáveis. Além disso, com o transcorrer do tempo de contato com o fertilizante, o teor de água e a condutividade elétrica das sementes aumentaram, enquanto observou-se diminuição da percentagem de germinação, da primeira contagem, da emergência e do índice de velocidade de emergência. Destaca-se que, para essas variáveis, o comportamento foi linear. Assim, é permitida a mistura das sementes com o fertilizante NPK, desde que a semeadura seja imediata, reduzindo-se os danos à qualidade fisiológica das sementes da forrageira (germinação e vigor). Na prática, recomenda-se fazer a mistura de sementes de B. brizantha com NPK somente da quantidade que poderá ser semeada até 12h após a mistura.

Information is contradictory as to the time Brachiaria brizantha seeds can remain mixed with the NPK fertilizer without causing poorly formed stands. Therefore, the objective of this research was to study the effect of contact times of NPK granular fertilizer (04-14-08 rate) with seeds of this forage on physiological quality (germination and vigor). A completely randomized design with four replicates was employed. An analysis of variance was conducted and the means were compared by Tukey test at 5 percent. Polynomial regression analyses were also performed, and equations were fitted. A significant effect was observed in all variables. The water content and electric conductivity of seeds increased as contact time with the fertilizer increased, while decreases were observed in germination percentage, first count, emergence, and emergence velocity index. A linear behavior was observed for the variables. Consequently, seeds can be mixed with NPK fertilizer as long as seeding is performed immediately afterwards, thus reducing damages to the physiological quality of the forage seeds (germination and vigor). In practice, it is recommended that B. brizantha seeds should be mixed with NPK at quantities that can be seeded within 12 hours from mixing, at most.