In this study we report on the clinical and autoimmune characteristics of severe and critical novel coronavirus pneumonia caused by severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2). The clinical, autoimmune, and laboratory characteristics of 21 patients who had laboratory-confirmed severe and critical cases of coronavirus disease 2019 (COVID-19) from the intensive care unit of the Huangshi Central Hospital, Hubei Province, China, were investigated. A total of 21 patients (13 men and 8 women), including 8 (38.1%) severe cases and 13 (61.9%) critical cases, were enrolled. Cough (90.5%) and fever (81.0%) were the dominant symptoms, and most patients (76.2%) had at least one coexisting disorder on admission. The most common characteristics on chest computed tomography were ground-glass opacity (100%) and bilateral patchy shadowing (76.2%). The most common findings on laboratory measurement were lymphocytopenia (85.7%) and elevated levels of C-reactive protein (94.7%) and interleukin-6 (89.5%). The prevalence of anti-52 kDa SSA/Ro antibody, anti-60 kDa SSA/Ro antibody, and antinuclear antibody was 20%, 25%, and 50%, respectively. We also retrospectively analyzed the clinical and laboratory data from 21 severe and critical cases of COVID-19. Autoimmune phenomena exist in COVID-19 subjects, and the present results provide the rationale for a strategy of preventing immune dysfunction and optimal immunosuppressive therapy.

Long noncoding RNAs (lncRNAs) play important roles in various biological processes such as proliferation, cell death and differentiation. Here, we show that a liver-enriched lncRNA, named liver fibrosis-associated lncRNA1 (lnc-LFAR1), promotes liver fibrosis. We demonstrate that lnc-LFAR1 silencing impairs hepatic stellate cells (HSCs) activation, reduces TGFβ-induced hepatocytes apoptosis in vitro and attenuates both CCl4- and bile duct ligation-induced liver fibrosis in mice. Lnc-LFAR1 promotes the binding of Smad2/3 to TGFβR1 and its phosphorylation in the cytoplasm. Lnc-LFAR1 binds directly to Smad2/3 and promotes transcription of TGFβ, Smad2, Smad3, Notch2 and Notch3 which, in turn, results in TGFβ and Notch pathway activation. We show that the TGFβ1/Smad2/3/lnc-LFAR1 pathway provides a positive feedback loop to increase Smad2/3 response and a novel link connecting TGFβ with Notch pathway. Our work identifies a liver-enriched lncRNA that regulates liver fibrogenesis and suggests it as a potential target for fibrosis treatment.

Sustained energy starvation leads to activation of AMP-activated protein kinase (AMPK), which coordinates energy status with numerous cellular processes including metabolism, protein synthesis, and autophagy. Here, we report that AMPK phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the interaction between EZH2 and SUZ12, another core component of the polycomb repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed tumor cell growth both in cell culture and mouse xenografts. Pathologically, immunohistochemical analyses uncovered a positive correlation between AMPK activity and pT311-EZH2, and higher pT311-EZH2 correlates with better survival in both ovarian and breast cancer patients. Our finding suggests that AMPK agonists might be promising sensitizers for EZH2-targeting cancer therapies.