Mechanistically, IFN-γ -induced STAT1 expression and activation were involved in the regulation of trophoblast proliferation and apoptosis by SPRY4, and IFN-γ promoted SPRY4 expression and STAT1 phosphorylation through PI3K/AKT pathway. Additionally, both STAT1 and phosphorylated STAT (p-STAT) levels were also upregulated in trophoblasts from RM patients and positively correlated with SPRY4 expression. CONCLUSION Our findings indicate that SPRY4 may act as a negative regulator of trophoblast functions through upregulating IFN-γ/PI3K/AKT-induced STAT1 activation. High levels of SPRY4 and STAT1 may contribute to RM development and progression, and blocking of either target could be a novel therapeutic strategy for RM patients. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Although genome-wide association studies have identified a number of common variants associated with multiple sclerosis (MS) susceptibility, little is known about the relevance of rare variants. Here, we aimed to explore the role of rare variants in 14 MS risk genes (FCRL1, RGS1, TIMMDC1, HHEX, CXCR5, LTBR, TSFM, GALC, TRAF3, STAT3, TNFSF14, IFI30, CD40, and CYP24A1) by targeted resequencing in an Iberian population of 524 MS cases and 546 healthy controls. Four rare variants-enriched regions within CYP24A1, FCRL1, RGS1, and TRAF3 were identified as significantly associated with MS.  https://www.selleckchem.com/products/congo-red.html  Functional studies revealed significantly decreased regulator of G protein signaling 1 (RGS1) gene expression levels in peripheral blood mononuclear cells from MS patients with RGS1 rare variants compared to noncarriers, whereas no significant differences in gene expression were observed for CYP24A1, FCRL1, and TRAF3 between rare variants carriers and noncarriers. Immunophenotyping showed significant decrease in RGS1 expression in peripheral blood B lymphocytes from MS patients with RGS1 rare variants relative to noncarriers. Lastly, peripheral blood mononuclear cell from MS patients carrying RGS1 rare variants showed significantly lower induction of RGS1 gene expression by interferon-β compared to MS patients lacking RGS1 variants. The presence of rare variants in RGS1 reinforce the ideas of high genetic heterogeneity and a role of rare variants in MS pathogenesis. © 2020 Wiley Periodicals, Inc.PROBLEM To explore whether the thrombospondin-1(TSP1)-CD47-signal regulatory protein alpha (SIRPα) signaling pathway has impacts on the development of endometriosis. METHOD OF STUDY Endometrial stromal cells (ESCs) originated from ectopic and eutopic endometrial tissues with or without endometriosis. Monocytes (Macrophages) were isolated from peripheral blood and peritoneal fluids with or without endometriosis. The expression levels of molecules were investigated by flow cytometry (FCM), immunohistochemistry (IHC), and RT-qPCR. The concentration of TSP1 was assessed via ELISA. The capacities of angiogenesis and phagocytosis were measured via tube formation assay and phagocytic assay, respectively. RESULTS We confirmed the up-regulation of critical molecules within the pathway in endometriosis patients. TSP1 can encourage normal ESCs (NESCs) growth and fibrosis. It simultaneously promotes the secretion of inflammatory factors and inhibits the phagocytic abilities of macrophages. Moreover, the proliferation of vascular endothelial cells (VECs) may be improved by TSP1. These effects may be offset by CD47 blocking antibodies. In addition, ectopic ESCs (EESCs) directly improve SIRPα expression on macrophages, which may further exhaust their phagocytic ability. Phagocytosis efficiency of macrophages on EESCs significantly improve by blocking CD47-SIRPα pathway. CONCLUSIONS TSP1-CD47-SIRPα signaling pathway not only improves the viability of NESCs per se but also promotes their survival circumstances by affecting the function of macrophages and VECs, which are mutually reinforcing and jointly promote the development of endometriosis. This article is protected by copyright. All rights reserved.OBJECTIVES Extraembryonic endoderm (XEN) cells are isolated from primitive endoderm (PrE) of blastocysts. Just like PrE, XEN cells have the ability to differentiate into parietal endoderm (PE) and visceral endoderm (VE), and therefore, they are useful tools for studying mechanisms of PrE cells development and differentiation. Pig is an ideal model for studying human cardiovascular and metabolic diseases and a potential organ source for allotransplantation, while no XEN cell has been obtained from porcine embryos. MATERIALS AND METHODS Using a serum-free culture system, we directly derived porcine extraembryonic endoderm-like cells (pXEN-like cells) from day 6-7 blastocysts, which could maintain self-renewal for at least 30 passages. RESULTS The pXEN-like cells resembled mouse XEN cells with large and flat clone morphology and expressed XEN marker genes but not pluripotent genes. Upon in vitro induction, the cells could differentiate into VE and PE. FGF/MEK signalling was not only essential for the maintenance of pXEN-like cells, but also the induction of pXEN-like cells from porcine embryonic stem (pES) cells. CONCLUSIONS We directly obtained cell lines with XEN characteristics from porcine embryos for the first time. The cells will be helpful tools for studying embryonic development and cell differentiation, which also represent promising cell sources for human regenerative medicine. © 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.BACKGROUND One challenge a modern society faces is this providing those vulnerable and ageing groups of adults who have intellectual disabilities with appropriate support for improving static and dynamic balance. Balance is a crucial component of physical fitness and, consequently, of fall reduction and prevention. The aim of the present randomised controlled trial was to evaluate the efficacy, after 16 weeks, that three different Special Olympics physical activity programmes had on balance and on fall reduction in adults with intellectual disabilities. METHOD A convenience sample of 150 persons with mild and moderate intellectual disabilities was recruited from the accessible Special Olympics Slovenia population of physically inactive adults with intellectual disabilities. The sample was randomised to the experimental group 1 (multicomponent balance-specific exercise programme group with additional workshops on such social gerontology topics as active and healthy ageing; N = 50), the experimental group 2 (multicomponent wellness programme group; N = 50) and a control group (regular Special Olympics athletic training; N = 50).