STUDY QUESTION Can cytochrome P450 oxidoreductase deficiency (PORD) be revealed in adult women with menstrual disorders and/or infertility? SUMMARY ANSWER PORD was biologically and genetically confirmed in five adult women with chronically elevated serum progesterone (P) who were referred for oligo-/amenorrhea and/or infertility. WHAT IS KNOWN ALREADY PORD is an autosomal recessive disease typically diagnosed in neonates and children with ambiguous genitalia and/or skeletal abnormalities. It is responsible for the decreased activity of several P450 enzymes, including CYP21A2, CYP17A1 and CYP19A1, that are involved in adrenal and/or gonadal steroidogenesis. Little is known about the optimal way to investigate and treat patients with adult-onset PORD. STUDY DESIGN, SIZE, DURATION In this series, we report five adult females who were evaluated in three tertiary endocrine reproductive departments between March 2015 and September 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Five women aged 19-38 years were refercessful fertility induction is possible by IVF, providing that P levels be sufficiently suppressed by glucocorticoid therapy prior to implantation. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was used for this study. There are no potential conflicts of interest. TRIAL REGISTRATION NUMBER N/A. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.T-cell acute lymphoblastic leukemia (T-ALL) is a malignant disease arising from the abnormal proliferation of T lymphocyte in marrow. Long non-coding RNAs (lncRNA) are one kind of non-coding RNAs (ncRNAs), which were reported to modulate the initiation or progression of diverse cancers. However, the role of LINC00511 in T-ALL was unknown. To figure out the function and mechanism of LINC00511 in T-ALL, a series of experiments were carried out. Based on the experimental results, we discovered that LINC00511 boosted cell proliferation and invasion, but hindered cell apoptosis in T-ALL cells. Besides, based on bio-informatics tool, miR-195-5p was selected for further exploration. Then, miR-195-5p was validated to bind with LINC00511. Hereafter, LRRK1 was testified to serve as a target gene of miR-195-5p. At last, rescue assays suggested that LRRK1 overexpression restored sh-LINC00511#1-mediated effects on cell proliferation and apoptosis. All in all, LINC00511 exacerbated T-ALL progression via miR-195-5p/LRRK1 axis, implying a potential therapeutic clue for the patients with T-ALL. Copyright 2020 The Author(s).Several metals have carcinogenic properties, but their associations with breast cancer are not established. We studied cadmium, a metalloestrogen, and 9 other metals-arsenic, cobalt, chromium, copper, mercury, molybdenum, lead, tin, and vanadium--in relation to young-onset breast cancer (diagnosis age less then 50 years), which tends to be more aggressive than and have a different risk profile from later-onset disease. Recent metal exposure was measured by assessing element concentrations, via inductively coupled plasma mass spectrometry, in toenail clippings of 1,217 disease-discordant sister pairs in the US-based Sister (2003-2009) and Two Sister (2008-2010) studies. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After correcting for differential calendar time of sample collection, no statistically significant associations were observed between any metals and breast cancer. Vanadium had the largest odds ratio (for fourth vs. first quartile, odds ratio = 1.54, 95% confidence interval 0.75, 3.16; P for trend = 0.21). The association between cadmium and young-onset breast cancer was near null, with no evidence of a dose-response relationship (for fourth vs. first quartile, odds ratio = 0.95, 95% confidence interval 0.64, 1.43; P for trend = 0.64). Positive associations between urinary cadmium concentrations and breast cancer have been reported in case-control studies, but we observed no such association between young-onset breast cancer and toenail concentrations of any assessed metals. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019.Glutamine transport across cell membranes is performed by a variety of transporters, including the alanine serine cysteine transporter 2 (ASCT2). The substrate binding site of ASCT2 was proposed to be specific for small amino acids with neutral side chains, excluding basic substrates such as lysine. A series of competitive inhibitors of ASCT2 with low mM affinity were developed previously, on the basis of the 2,4-diaminobutyric acid (DAB) scaffold with a potential positive charge in the side chain. https://www.selleckchem.com/products/ly-345899.html Therefore, we tested whether basic amino acids with side chains shorter than lysine can interact with the ASCT2 binding site. Molecular docking of L-1,3-diaminopropionic acid (L-DAP) and L-DAB suggested that these compounds bind to ASCT2. Consistent with this prediction, L-DAP and L-DAB, but not ornithine, lysine or D-DAP, elicited currents when applied to ASCT2-expressing cells. The currents were carried by anions and showed the hallmark properties of ASCT2 currents induced by transported substrates. The L-DAP response could be eliminated by a competitive ASCT2 inhibitor, suggesting that binding occurs at the substrate binding site. The Km for L-DAP was weakly voltage dependent. Further, the pH dependence of the L-DAP response showed that the compound can bind in several protonation states. Together, these results suggest that the ASCT2 binding site is able to recognize L-amino acids with short, basic side chains, such as the L-DAP derivative β-N-methylamino-L-Alanine (BMAA), a well-studied neurotoxin. Our results expand the substrate specificity of ASCT2 to include amino acid substrates with positively charged side chains. Copyright 2020 The Author(s).Switchable Rh(iii)-catalyzed highly regioselective hydroarylation and oxidative arylation of maleimides with 2-arylindazoles via C-H activation have been demonstrated. The reaction affords 3-(2-(2H-indazol-2-yl)phenyl)succinimide and 3-(2-(2H-indazol-2-yl)phenyl)maleimide derivatives in high yields with wide functional group tolerance. A mechanistic study was performed to depict C-H bond cleavage that might be involved in the turnover limiting step.