Marcuslyhne9382

In the last few weeks Italy first, and then several other countries across the world, have been swept up by the deadly wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the illness named COVID-19, from the acronym CO (corona) VI (virus) D (disease) and 19 (year of the virus identification). The medical community is working day and night to assist affected people and experts in communicable diseases are striving in multiple ways to understand the progression of events leading to the lethal respiratory syndrome. This article is protected by copyright. All rights reserved.Coronavirus Disease 2019 (COVID-19), triggered by the betacoronavirus SARS-CoV-2, has become one of the worst pandemics of our time that has already caused more than 183,470 deaths [JHU data-23/04/2020, https//www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6]. Effective therapeutic approaches are urgently needed to reduce the spread of the virus and its death toll. Here, we assess the possibility of using interferon lambda (IFNλ), a third type of interferon sharing low homology with type I IFNs and IL-10, for treating COVID-19 patients. We discuss the unique role of IFNλ in fine-tuning antiviral immunity in the respiratory tract to achieve optimal protection and minimal host damage and review early evidence that SARS-CoV-2 may impair IFNλ induction, leading to a delayed type I IFN-dominated response that triggers hyperinflammation and severe disease. We also consider the potential windows of opportunity for therapeutic intervention with IFNλ and potential safety considerations. We conclude that IFNλ constitutes a promising therapeutic agent for reducing viral presence and hyperinflammation in a single shot to prevent the devastating consequences of COVID-19 such as pneumonia and acute respiratory distress syndrome (ARDS). Eliglustat mw This article is protected by copyright. All rights reserved.Fras1 is an extracellular protein of the basement membranes that surround embryonic epithelia, choroid plexuses and meninges in fetal mouse brain. Depletion of Fras1 in knockout mice results in sub-epidermal blistering and, fusion of eye lids and digits as well as malformation of lungs and kidneys. Mutations in the human counterpart FRAS1 are responsible for the Fraser Syndrome with clinical manifestations similar to the murine phenotype. In addition, brain deformities or mental impairments have occasionally been reported in patients with Fraser Syndrome. In the present study, we explored the possible involvement of Fras1 in brain function, analyzing its expression pattern in mouse brain and investigating aspects of Fras1-/- mice behavior, related to the function of brain regions expressing Fras1. Transcripts were detected in choroid plexuses and in certain brain regions including cortical, hippocampal and amygdalar areas in juvenile mice. Behavioral tests revealed that Fras1-/- mice exhibit impaired egocentric spatial memory, aberrant olfactory learning and memory, markedly reduced fear memory in an auditory fear conditioning task, as well as reduced anxiety expression in open field and elevated plus maze tests. Moreover, the extracellular matrix organization has been severely affected in cortical and subcortical areas as demonstrated by Wisteria floribunda agglutinin immunolabelling. The widespread detection of Fras1 transcripts in the brain of both pre- and postnatal mice, as well as the behavioral and cellular disturbances exhibited by Fras1-/- adult mice provide evidence for the involvement of Fras1 in brain organization and function. This article is protected by copyright. All rights reserved.PURPOSE Fetal adrenal gland changes have previously been investigated as novel markers of preterm labor and small for gestational age (SGA) fetuses. We aimed to compare the fetal adrenal gland parameters in SGA and appropriate for gestational age (AGA) fetuses. METHODS A prospective cohort study was conducted on SGA fetuses with estimated fetal weight (EFW) ≤10th centile and AGA (EFW >10th centile) at 17 to 34 weeks gestation. Fetal adrenal total gland volume (TGV), TGV corrected for EFW (cTGV), fetal zone volume (FZV), FZV corrected for EFW (cFZV), and FZVTGV ratio were compared and correlated with gestational age and EFW. Receiver operator curves assessed FZVTGV ratio, cTGV, and cFZV in detecting SGA. RESULTS Ultrasound examinations from 103 AGA and 50 SGA fetuses showed that (a) SGA fetuses had higher TGV (P = .002), FZV (P = .001), and FZVTGV (P = .036) compared to AGA fetuses; (b) fetal adrenal TGV, FZV, cFZV, and FZVTGV increase with advancing gestational age and EFW while cTGV does not; (c) Fetal adrenal changes in cTGV, cFZV, and FZVTGV have ability to differentiate SGA; (d) FZVTGV ratio 10 and 25 may be used to identify or exclude SGA in antenatally suspected SGA. CONCLUSIONS We investigated the concept that SGA fetuses have measurable changes to the adrenal gland. We have shown that fetal TGV, TGV, and FZVTGV ratio show differences between AGA and SGA with TGV remaining significant after accounting for GA at scan. These findings may be useful as potential biomarkers for diagnosing or excluding SGA. © 2020 Wiley Periodicals, Inc.Interferon-α (IFN-α), composed of numerous subtypes, plays a crucial role in immune defense. As the most-studied subtype, IFN-α2 has been used for treating chronic hepatitis B virus (HBV) infection with advantages of finite treatment duration and sustained virological response, but its efficacy remains relatively low. Here, we aimed to screen for IFN-α subtype with the highest anti-HBV potency and to characterize new mechanism of IFN-α-mediated HBV restriction. Using cell culture-based HBV infection systems and a human liver chimeric mouse model, IFN-α subtypes-mediated antiviral response and signaling activation were comprehensively analyzed. IFN-α14 was identified as the most effective subtype in suppression of HBV cccDNA transcription and HBeAg/HBsAg production, with IC50 values approximately 100-fold lower than the conventional IFN-α2. IFN-α14 alone elicited IFN-α and -γ signaling crosstalk similarly to the combined use of IFN-α2 and IFN-γ, inducing multiple potent antiviral effectors, which synergistically restricted HBV replication.