Conclusions Our study demonstrated that HIF downstream gene of NDRG1 may counteract the cancer-promoting effect of HIF. These results provided evidence that NDRG1 may be a potential prognostic biomarker as well as a therapeutic target in ccRCC.Intravascular imaging and coronary physiology can improve the outcomes of percutaneous coronary intervention but are currently underutilized. Longer procedure time, higher cost, and challenges with performance and interpretation are barriers to the use of intravascular imaging and physiology. Selective application of imaging and physiology in more complex interventions, education of how to use these modalities, and reimbursement of the equipment cost could increase adoption of these techniques in everyday clinical practice.Poor outcomes observed in cancer patients who sustain STEMI are due, in part, to advanced age, comorbidities, and underutilization of guidelines-based therapies. Coronary angiography in the cancer patient is more likely to demonstrate MINOCA, but the majority have critical disease and PCI success is similar to noncancer patients. We recommend primary PCI with stenting as the default strategy in STEMI patients with cancer.Seven percent of patients (with no history of intraventricular conduction abnormalities) experienced intraprocedural high-degree Atrioventricular (AV)/complete heart block. High-degree/complete heart block was persistent in 64% of patients who developed significant intraprocedural intraventricular conduction abnormalities. Ninety-seven percent of patients with persistent high-degree AV/complete block ultimately required pacemaker implantation.Patients with PAD have worse outcomes after TAVR. The extent and distribution of PAD are important considerations in determining TAVR feasibility and choosing an access site. Further research is needed to establish the best approaches to treating patients with aortic and iliofemoral disease severe enough to limit device delivery.This paper analyzes the negotiation process, which leads to basic research funding and price setting for new drugs in regulated health insurance markets. Its results bring answers to the following questions Should basic research be privately funded, publicly funded, or produced by an independent lab? Under which conditions is public integration of basic research efficient? How do pharmaceutical prices respond to different organizations of basic research? We show that efficiency and prices are higher when basic research is integrated in the firm that commercializes the drug as compared with independent basic research. In both organizations, the higher the negotiation power of the research labs relative to the one of the public health authority is, the higher the prices and the efficiency are. We thereby confirm the traditional trade-off between price containment and dynamic efficiency. We identify one important exception to this trade-off. Indeed, public integration of basic research can result in lowest prices and highest efficiency, as compared with the other possible organizations, in particular when basic and applied research are highly complementary.Recent developments in the area of plant-based hydrogels are introduced, especially those derived from wood as a widely available, multiscale, and hierarchical source of nanomaterials, as well as other cell wall elements. With water being fundamental in a hydrogel, water interactions, hydration, and swelling, all critically important in designing, processing, and achieving the desired properties of sustainable and functional hydrogels, are highlighted. A plant, by itself, is a form of a hydrogel, at least at given states of development, and for this reason phenomena such as fluid transport, diffusion, capillarity, and ionic effects are examined. These aspects are highly relevant not only to plants, especially lignified tissues, but also to the porous structures produced after removal of water (foams, sponges, cryogels, xerogels, and aerogels). Thus, a useful source of critical and comprehensive information is provided regarding the synthesis of hydrogels from plant materials (and especially wood nanostructures), and about the role of water, not only for processing but for developing hydrogel properties and uses.Objective The aim of the study was threefold Firstly, to investigate the adherence to clinical practice guidelines for low back pain (LBP) among Danish physiotherapists with regard to three key domains (a) activity, (b) work and (c) psychosocial risk factors. Secondly, to investigate whether adherence differed between physiotherapists working in private clinics (private physiotherapists) and physiotherapists working at public healthcare centres (public physiotherapists). Thirdly, to describe the physiotherapists’ treatment modalities for patients with LBP. Methods A cross-sectional online survey was conducted with 817 physiotherapists working in the Central Denmark Region. Adherence to the guideline domains was assessed using two vignettes. The difference in adherence between the groups was assessed using the Chi-squared test. Treatment modalities were reported using descriptive statistics. Results A total of 234 physiotherapists responded, hereof 163 private physiotherapists and 71 public physiotherapists (rg the current guidelines’ 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. 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.