Facioscapulohumeral muscular dystrophy (FSHD) is caused by a complex epigenetic mechanism finally leading to the misexpression of DUX4 in skeletal muscle. Detecting DUX4 and quantifying disease progression in FSHD is extremely challenging, thus increasing the need for surrogate biomarkers. We applied a shotgun proteomic approach with two different setups to analyze the protein repertoire of interstitial fluids obtained from 20 muscles in different disease stages classified by magnetic resonance imaging (MRI) and serum samples from 10 FSHD patients. A total of 1156 proteins were identified in the microdialysates by data independent acquisition, 130 of which only found in muscles in active disease stage. Proteomic profiles were able to distinguish FSHD patients from controls. Two innate immunity mediators (S100-A8 and A9) and Dermcidin were upregulated in muscles with active disease and selectively present in the sera of FSHD patients. Structural muscle and plasminogen pathway proteins were downregulated. Together with the upstream inhibition of myogenic factors, this suggests defective muscle regeneration and increased fibrosis in early/active FSHD. Our MRI targeted exploratory approach confirmed that inflammatory response has a prominent role, together with impaired muscle regeneration, before clear muscle wasting occurs. We also identified three proteins as tissue and possibly circulating biomarkers in FSHD.The human ileostomy model, widely considered the benchmark for determining in vivo starch digestibility, has disadvantages. The ileorectostomised rat model (IRM) is a possible surrogate but evidence as to its validity is scant. https://www.selleckchem.com/products/mizagliflozin.html In this preliminary study, the resistant starch (RS) content of test breads made from refined low (LAW-R) and high amylose wheat (HAW-R) flours was established in a randomised cross-over trial involving six human ileostomy participants. Starch digestibility of refined breads and diets made from these flours was then evaluated in ileorectostomised rats using a similar experimental format. Physical performance measures and other data were also collected for the rat model. The amount of RS in the low- and high-amylose breads as measured using the human model was 0.8 ± 0.1 and 6.5 ± 0.3 g/100 g, respectively. The RS level of HAW-R bread determined using ileorectostomised rats was 5.5 ± 0.8 g/100 g, about 15% less than that recorded in the human study, whereas for conventional wheat breads the models produced similar RS values. While offering promise, further validation using a wide variety of starchy food products is needed before the IRM can be considered an acceptable alternative for RS determination.Triple-negative breast cancer (TNBC) is one of the most common malignancies worldwide and shows maximum invasiveness and a high risk of metastasis. Recently, many natural compounds have been highlighted as a valuable source of new and less toxic drugs to enhance breast cancer therapy. Among them, S-adenosyl-L-methionine (AdoMet) has emerged as a promising anti-cancer agent. MicroRNA (miRNA or miR)-based gene therapy provides an interesting antitumor approach to integrated cancer therapy. In this study, we evaluated AdoMet-induced modulation of miRNA-34c and miRNA-449a expression in MDA-MB-231 and MDA-MB-468 TNBC cells. We demonstrated that AdoMet upregulates miR-34c and miR-449a expression in both cell lines. We found that the combination of AdoMet with miR-34c or miR-449a mimic strongly potentiated the pro-apoptotic effect of the sulfonium compound by a caspase-dependent mechanism. For the first time, by video time-lapse microscopy, we showed that AdoMet inhibited the in vitro migration of MDA-MB-231 and MDA-MB-468 cells and that the combination with miR-34c or miR-449a mimic strengthened the effect of the sulfonium compound through the modulation of β-catenin and Small Mother Against Decapentaplegic (SMAD) signaling pathways. Our results furnished the first evidence that AdoMet exerts its antitumor effects in TNBC cells through upregulating the expression of miR-34c and miR-449a.Cervical cancer is a common gynecological malignancy, accounting for 10% of all gynecological cancers. Recently, targeted therapy for cervical cancer has shown unprecedented advantages. Several studies have shown that ubiquitin conjugating enzyme E2 (UBE2C) is highly expressed in a series of tumors, and participates in the progression of these tumors. However, the possible impact of UBE2C on the progression of cervical squamous cell carcinoma (CESC) remains unclear. Here, we carried out tissue microarray analysis of paraffin-embedded tissues from 294 cervical cancer patients with FIGO/TNM cancer staging records. The results indicated that UBE2C was highly expressed in human CESC tissues and its expression was related to the clinical characteristics of CESC patients. Overexpression and knockdown of UBE2C enhanced and reduced cervical cancer cell proliferation, respectively, in vitro. Furthermore, in vivo experiments showed that UBE2C regulated the expression and activity of the mTOR/PI3K/AKT pathway. In summary, we confirmed that UBE2C is involved in the process of CESC and that UBE2C may represent a molecular target for CESC treatment.Urban green areas, such as parks, are becoming increasingly important in densifying cities. Urban parks encourage physical and social activity, recreation and relaxation, and thus eventually promote people's well-being. The aim of the current study is to examine which urban park attributes influence the preferences of park users, in order to offer recommendations regarding how urban parks of quality can be designed. To elicit the preferences of park visitors we designed an online stated-choice experiment. Seven park attributes, in particular the number and composition of trees and the presence of benches, side paths, a playground, litter, and flowers, were manipulated in a virtual park. In an online stated-choice task, videos of these park alternatives were presented and the preferences of 697 participants were measured. It is found that especially the number of trees and the presence of flowerbeds, particularly with a diversity of flowers, influenced participants' preferences. The presence of many benches and a playground were valued as well, but to a lesser extent.