elines’ recommendations in clinical practice.Ras GTPases act as molecular switches to control various cellular processes by coupling integrated signals in eukaryotes. Activities of Ras GTPases are triggered by Ras GTPase guanine nucleotide exchange factors (RasGEFs) in general, while the role of RasGEF in plant pathogenic fungi is largely unknown. In this study, we characterized the only RasGEF protein in Fusarium graminearum, FgCdc25, by combining genetic, cytological and phenotypic strategies. FgCdc25 directly interacted with RasGTPase FgRas2, but not FgRas1, to regulate growth and sexual reproduction. Mutation of the FgCDC25 gene resulted in decreased toxisome formation and deoxynivalenol (DON) production, which was largely depended on cAMP signaling. In addition, FgCdc25 indirectly interacted with FgSte11 in FgSte11-Ste7-Gpmk1 cascade and the ΔFgcdc25 strain totally abolished the formation of infection structures and was nonpathogenic in planta, which was partially recovered by addition of exogenous cAMP. In contrast, FgCdc25 directly interplayed with FgBck1 in FgBck1-MKK1-Mgv1 cascade to negatively control cell wall integrity. Collectively, these results suggest that FgCdc25 modulates cAMP and MAPK signaling pathways, and further regulates fungal development, DON production and plant infection in F. graminearum. This article is protected by copyright. All rights reserved.Objectives Integrin beta-like 1 (ITGBL1) is involved in the migration and invasion of several cancers; however, its roles in the development and progression of hepatocellular carcinoma (HCC) remain largely unknown. Materials and methods Immunohistochemistry staining was used to investigate the expression pattern of ITGBL1 and its prognostic values in HCC patients. The transwell, wound-healing assays, xenograft and orthotopic mouse models were employed to determine the effects of ITGBL1 on HCC cell migration and invasion in vitro and in vivo. The biological mechanisms involved in cell migration and invasion caused by ITGBL1 were determined with Western blotting and RT-PCR methods. Results ITGBL1 expression was significantly increased in HCC tissues compared to adjacent normal tissues. Patients with higher ITGBL1 expression were associated with more reduced overall survival. PEG300 supplier ITGBL1 overexpression promoted migration and invasion in SMMC-7721 and HepG2 cells in vitro and in vivo, whereas knockdown or knockout ITGBL1 in CSQT-2 cells significantly reduced cell migration and invasion abilities. In SMMC-7721 cells, ITGBL1 overexpression stimulated TGF-β/Smads signalling pathway, along with the KRT17 and genes involved in the epithelial-mesenchymal transition (EMT). In contrast, ITGBL1 knockout inhibited the TGF-β/Smads signalling pathway in CSQT-2 cells. Conclusions These findings suggested that ITGBL1 promoted migration and invasion in HCC cells by stimulating the TGF-β/Smads signalling pathway. ITGBL1 could be a promising prognostic biomarker, as well as a potential therapeutic target in HCC.The peridural membrane (PDM) is a well-defined structure between dura mater and the wall of the spinal canal. The spine may be viewed as a multi-segmented joint, with the epidural cavity and neural foramina as joint spaces and PDM as synovial lining. The objective of this investigation was to determine if PDM has histological characteristics of synovium. Samples of the PDM of the thoraco-lumbar spine were taken from 23 human cadavers and analyzed with conventional light microscopy and confocal microscopy. Results were compared to reports on similar analyses of synovium in the literature. Histological distribution of areolar, fibrous and adipose connective tissue in PDM was similar to synovium. The PDM has an intima and sub-intima. No basement membrane was identified. CD68, a marker for macrophage-like-synoviocytes, and CD55, a marker for fibroblast-like synoviocytes, were seen in the lining and sub-lining of the PDM. Multifunctional hyaluronan receptor CD44 and hyaluronic acid synthetase 2 marker HAS2, were abundantly present throughout the membrane. Marked presence of CD44, CD55 and HAS2 in the well-developed tunica muscularis of blood vessels and in the body of the PDM suggests a role in the maintenance and lubrication of the epidural cavity and neural foramina. Presence of CD68, CD55 and CD44 suggests a scavenging function and a role in the inflammatory response to noxious stimuli. Thus, the human peridural membrane has histological and immunohistochemical characteristics of synovium. This suggests that the PDM may be important for the homeostasis of the flexible spine and the neural structures it contains. This article is protected by copyright. All rights reserved.Serotonin (5-hydroxytryptamine, 5-HT) released by platelets, mast cells, and immunocytes is a potent inflammatory mediator which modulates pain and itch sensing in the peripheral nervous system. The serotonergic receptors expressed by primary afferent neurons involved in these sensory functions are not fully identified and appear to be to a large extent species dependent. Moreover, the mechanisms through which 5-HT receptor activation is coupled to changes in neuronal excitability have not been completely revealed. Using a combination of in vitro (calcium and voltage imaging and patch-clamp) and in vivo behavioral methods, we used both male and female Wistar rats to provide evidence for the involvement of two 5-HT receptor subtypes, 5-HT1A and 5-HT3, in mediating the sustained and transient effects, respectively, of 5-HT on rat primary afferent neurons involved in pain and itch processing. In addition, our results are consistent with a model in which sustained serotonergic responses triggered via the 5-HT1A receptor are due to closure of background potassium channels, followed by membrane depolarization and action potentials, during which the activation of voltage-gated calcium channels leads to calcium entry. Our results may provide a better understanding of mammalian serotonergic itch signaling.In the era of staggering speed in development of the novel coronavirus (CoV) pandemic (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), we have reviewed the dermatologists’ tools at hand for their utility (and potential risks) in patients affected by COVID-19. This review aims to shed light on the anti-viral and pro-viral potential of drugs routinely used in dermatology to modulate COVID-19. The literature search included peer-reviewed articles published in English language (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) from January 1990 to March 2020 and by reference lists of respective articles. Somewhat to our surprise, we have found that several of our drugs widely used in dermatology have antiviral potential. On the other hand, we also frequently use immunosuppressive drugs in our dermatologic patients that potentially pose them at increased risk for COVID-19. This article is protected by copyright. All rights reserved.