Individuals infected with SARS-CoV-2 who also display hyperglycemia suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome (ARDS), and increased mortality. Nevertheless, the pathophysiological mechanism of hyperglycemia in COVID-19 remains poorly characterized. Here, we show that hyperglycemia is similarly prevalent among patients with ARDS independent of COVID-19 status. Yet, among patients with ARDS and COVID-19, insulin resistance is the prevalent cause of hyperglycemia, independent of glucocorticoid treatment, which is unlike patients with ARDS but without COVID-19, where pancreatic beta cell failure predominates. A screen of glucoregulatory hormones revealed lower levels of adiponectin in patients with COVID-19. Hamsters infected with SARS-CoV-2 demonstrated a strong antiviral gene expression program in the adipose tissue and diminished expression of adiponectin. Moreover, we show that SARS-CoV-2 can infect adipocytes. Together these data suggest that SARS-CoV-2 may trigger adipose tissue dysfunction to drive insulin resistance and adverse outcomes in acute COVID-19.

It was brought to the authors' attention by readers that ARDS was not adequately defined. The STAR Methods have now been updated with specific clinical (ventilatory and oxygenation) parameters used to qualify for ARDS along with accompanying references.

Salvianolic acids, the most effective and abundant compounds extracted from Salvia miltiorrhiza (Danshen), are well known for its good anti-oxidative activity. Danshen has been extensively used as a traditional medicine to treat cardiovascular-related diseases in China and other Asian countries for hundreds of years. Recently, more and more studies have demonstrated that salvianolic acids also have a good effect on the alleviation of fibrosis disease and the treatment of cancer. In vivo and in vitro experiments have demonstrated that salvianolic acids can modulate signal transduction within fibroblasts and cancer cells. It is discovered that the cancer treatment of salvianolic acids is not only because salvianolic acids promote the apoptosis of cancer cells, but also due to the inhibition of cancer-associated epithelial-mesenchymal transition processes. In this article, we review a variety of studies focusing on the comprehensive roles of salvianolic acids in the treatment of fibrosis disease and cancer. These perspectives on the therapeutic potential of salvianolic acids highlight the importance of these compounds, which could be the novel and attractive drugs for fibrosis disease and cancer.

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Topography and rigidity are two typical biophysical cues in extracellular matrix mechanical microenvironment. Extracellular matrix can regulate cells biological behaviors, including epithelial-to-mesenchymal transition (EMT). A growing body of evidence suggests that EMT plays an important role in the development of tumor and fibrosis. Moreover, EMT also contributes to drug resistance in cancer cells. Currently, the majority of studies about EMT are based on the induction of growth factors or cytokines in vitro. Here, we adopt polydimethylsiloxane (PDMS)-micropillars-based matrix platform to culture human alveolar epithelial cells for studying the influence of topography and rigidity on EMT. This study reports a previously undefined role of mechanical microenvironment in EMT induction. Different topography and rigidity can induce EMT directly without the use of exogenous cytokines. Notably, rigidity-induced EMT activation is associated with the topography. Furthermore, we investigate preliminarily the role of PI3K/Akt signaling pathway in mechanical microenvironment regulation of EMT. These findings provide a fresh perspective to the researches of tumor and pulmonary fibrosis, and the potential platform for cell-based drug screening. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3165-3174, 2018.

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Objective: This thesis addresses a neglected aspect of bioinformatics research of hemifacial microsomia (HFM). Existing research stops short of prediction based on big data. This study combines multiple databases to explore underlying pathogenesis using bioinformatic approach. Methods: The research consisted of multiple bioinformatic methods, included pathogenic genes analyses, protein-protein interaction network construction, functional enrichment, and mining target genes related miRNA, for studying pathogenic genes of HFM.

Introduction: Non-small cell lung cancer (NSCLC) is a worldwide malignance threatening human life. TGF-β/Smad signaling is known to regulate cell proliferation, differentiation, migration and growth. As the only co-Smad playing crucial roles in TGF-β signaling, Smad4 is reported to be frequently mutated or to occur as alternatively spliced in tumor cells. Smad4 was reported to be involved in the TGF-β-induced EMT process. However, whether the alternative splicing occurs in the TGF-β-induced EMT process in NSCLC was not clear. Methods: In our current study, we explored the alternative splicing of Smad4 during the process of TGF-β-induced EMT in A549 cells. 10 ng/mL TGF-β was used to induce EMT. Then, nest-PCR and agarose electrophoresis were performed to detect the expression of Smad4 variants and sequencing to get the variant DNA sequences. For recombinant expression of variants of Smad4 in A549 cells, we used lentiviral variants to infect cells. In order to explore the effects of variants on the proliferation and migration of A549 cells, the MTT assay, colony formation assay and wound-healing assay were done. The effects of variants on E-cad and VIM protein expression were explored through Western blot. Results: There were several novel gene fragments expressed in TGF-β-induced A549 cells, and the sequencing results showed that they were indeed the Smad4 variants that were not reported. For recombinant expression of Smad4 variants in A549 cells, we found that they have significant effects on the proliferation and migration of cells, and also regulated the E-cad and VIM protein expression. Conclusion: Our results indicated that novel Smad4 variants were expressed in TGF-βinduced EMT process. The functional study showed that these novel variants regulate cell proliferation and migration and affect E-cad and VIM protein expression, showing the potential as targets for cancer therapy.