These results provide novel insights into the physiologic function of Cxxc5 during hematopoiesis, and demonstrate for the first time that it plays a role in monocyte development. ©2020 Society for Leukocyte Biology.Enzyme replacement therapy (ERT) with recombinant α-galactosidase A (r-αGAL A) for the treatment of Fabry disease has been available for over 15 years. Long-term treatment may slow down disease progression, but cardiac, renal, and cerebral complications still develop in most patients. In addition, lifelong intravenous treatment is burdensome. Therefore, several new treatment approaches have been explored over the past decade. Chaperone therapy (Migalastat; 1-deoxygalactonojirimycin) is the only other currently approved therapy for Fabry disease. This oral small molecule aims to improve enzyme activity of mutated α-galactosidase A and can only be used in patients with specific mutations. Treatments currently under evaluation in (pre)clinical trials are second generation enzyme replacement therapies (Pegunigalsidase-alfa, Moss-aGal), substrate reduction therapies (Venglustat and Lucerastat), mRNA- and gene-based therapy. This review summarises the knowledge on currently available and potential future options for the treatment of Fabry disease. © 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.For over two decades, nitisinone (NTBC) has been successfully used to manipulate the tyrosine degradation pathway and save the lives of many children with hereditary tyrosinaemia type 1. More recently, NTBC has been used to halt homogentisic acid accumulation in alkaptonuria (AKU) with evidence suggesting its efficacy as a disease modifying agent. NTBC-induced hypertyrosinaemia has been associated with cognitive impairment and potentially sight-threatening keratopathy. In the context of a non-lethal condition (ie, AKU), these serious risks call for an evaluation of the wider impact of NTBC on the tyrosine pathway. We hypothesised that NTBC increases the tyrosine pool size and concentrations in tissues. In AKU mice tyrosine concentrations of tissue homogenates were measured before and after treatment with NTBC. In humans, pulse injection with l-[13 C9 ]tyrosine and l-[d8 ]phenylalanine was used along with compartmental modelling to estimate the size of tyrosine pools before and after treatment with NTBC. We found that NTBC increased tyrosine concentrations in murine tissues by five to nine folds. It also significantly increased the tyrosine pool size in humans (P  less then  .001), suggesting that NTBC increases tyrosine not just in serum but also in tissues (ie, acquired tyrosinosis). This study provides, for the first time, the experimental proof for the magnitude of NTBC-related acquired tyrosinosis which should be overcome to ensure the safe use of NTBC in AKU. © 2020 SSIEM.Last December 2019, a new virus, named novel Coronavirus (COVID-2019) causing many cases of severe pneumonia was reported in Wuhan, China. The virus knowledge is limited and especially about COVID-2019 pathogenesis. The Open Reading Frame 1ab (ORF1ab) of COVID-2019 has been analyzed to evidence the presence of mutation caused by selective pressure on the virus. For selective pressure analysis fast-unconstrained Bayesian approximation (FUBAR) was used. Homology modelling has been performed by SwissModel and HHPred servers. The presence of transmembrane helical segments in Coronavirus ORF1ab non structural protein 2 (nsp2) and nsp3 was tested by TMHMM, MEMSAT, and MEMPACK tools. Three-dimensional structures have been analyzed and displayed using PyMOL. FUBAR analysis revealed the presence of potential sites under positive selective pressure (P  less then  .05). Position 723 in the COVID-2019 has a serine instead a glycine residue, while at aminoacidic position 1010 a proline instead an isoleucine. Significant (P  less then  .05) pervasive negative selection in 2416 sites (55%) was found. The positive selective pressure could account for some clinical features of this virus compared with severe acute respiratory syndrome (SARS) and Bat SARS-like CoV. The stabilizing mutation falling in the endosome-associated-protein-like domain of the nsp2 protein could account for COVID-2019 high ability of contagious, while the destabilizing mutation in nsp3 proteins could suggest a potential mechanism differentiating COVID-2019 from SARS. These data could be helpful for further investigation aimed to identify potential therapeutic targets or vaccine strategy, especially in the actual moment when the epidemic is ongoing and the scientific community is trying to enrich knowledge about this new viral pathogen. © 2020 Wiley Periodicals, Inc.BACKGROUND AND AIM The aim of this study was to identify factors affecting persistent gastric regenerating atypia and determine the effect of Helicobacter pylori eradication on the course of this lesion. METHODS In cross-sectional setting, comprehensive health check-up subjects who underwent both endoscopy and H. pylori test from 2001 to 2009 were included. The association between H. pylori and gastric regenerating atypia was evaluated.  https://www.selleckchem.com/products/tegatrabetan.html  In cohort setting, patients with regenerating atypia who underwent H. pylori test from 2001 to 2013 were included. Factors affecting positive pathology (persistent regenerating atypia or new development of neoplasm) in patients with regenerating atypia at baseline were investigated. RESULTS In cross-sectional setting, regenerating atypia was observed in 1.1% (241/22 133). H. pylori infection was associated with gastric regenerating atypia (adjusted odds ratio, 1.47; 95% confidence interval [CI], 1.12-1.91). In cohort setting, 310 patients with regenerating atypia were finally eligible. Positive pathology rate during follow up was 16.1% (15/93) in the persistent infection group, 2.8% (3/106) in successful eradication group, and 4.5% (5/111) in baseline H. pylori-negative group. Persistent H. pylori infection increased the risk of positive pathology (adjusted risk ratio [RR], 7.18; 95% CI, 1.95-26.48) compared to H. pylori eradication group. Persistent H. pylori infection increased the risk of regenerative atypia (adjusted RR, 5.70; 95% CI, 1.46-22.17) and new neoplasm (adjusted RR, 10.74; 95% CI, 1.10-105.17) compared to baseline negative H. pylori. CONCLUSIONS H. pylori infection is an independent risk factor for gastric regenerating atypia. Eradication of H. pylori seems helpful for regression of regenerating atypia. © 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.