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Chromosomal mosaicism is at high occurrence in early developmental-stage embryos, but much lower in those at prenatal stage. Recent studies provided evidence on the viability of mosaic embryos by reporting pregnancy outcomes. Expanded research is warranted to evaluate its clinical significance. This is a multi-center prospective cohort study on 137 mosaic, 476 euploid and 835 non-preimplantation genetic testing (non-PGT) embryos from three in vitro fertilization (IVF) providers of three countries in Asia, applying the same preimplantation genetic testing for aneuploidies (PGT-A) reporting criteria. Mosaic embryo transfers (METs) resulted in a significantly lower clinical pregnancy rate (40.1% versus 59.0% versus 48.4%), lower ongoing/live birth rate (27.1% versus 47.0% versus 35.1%) and higher miscarriage rate (33.3% versus 20.5% versus 27.4%) than euploid and non-PGT transfers, respectively. Pregnancy losses after METs were different between embryos carrying numerical and segmental chromosomal abnormalities (p = 0.04). Our meta-analysis concluded that METs gave rise to pregnancies but were associated with a reduced ongoing/live birth rate and a higher miscarriage rate. All 37 MET live births were confirmed viable, among which 8 completed prenatal genetic testing with normal results. Longitudinal investigation on one MET pregnancy evidenced the aneuploidy depletion hypothesis. This is the first multi-center prospective study reporting a full MET pregnancy outcome with complementary information from prenatal genetic testing as compared to euploid and non-PGT cohorts.

Aromatase, the rate-limiting enzyme that catalyzes the conversion of androgen to estrogen, plays an essential role in the development of estrogen-dependent breast cancer. Side effects due to aromatase inhibitors (AIs) necessitate the pursuit of novel inhibitor candidates with high selectivity, lower toxicity and increased potency. Designing a novel therapeutic agent against aromatase could be achieved computationally by means of ligand-based and structure-based methods. For over a decade, we have utilized both approaches to design potential AIs for which quantitative structure–activity relationships and molecular docking were used to explore inhibitory mechanisms of AIs towards aromatase. However, such approaches do not consider the effects that aromatase variants have on different AIs. In this study, proteochemometrics modeling was applied to analyze the interaction space between AIs and aromatase variants as a function of their substructural and amino acid features. Good predictive performance was achieved, as rigorously verified by 10-fold cross-validation, external validation, leave-one-compound-out cross-validation, leave-one-protein-out cross-validation and Y-scrambling tests. The investigations presented herein provide important insights into the mechanisms of aromatase inhibitory activity that could aid in the design of novel potent AIs as breast cancer therapeutic agents.

Antimicrobial resistance has become a prime global concern. An ability of the microbes to produce enzymes to destroy antimicrobial drugs is one of the well-known mechanisms underlying the resistance. 8-Hydroxyquinoline (8HQ) and derivatives were reported to exert diverse biological effects such as antimicrobial, antioxidant and antineurodegenerative activities. Herein, 8HQ (1), nitroxoline (NQ, 2) and 7 -Br-8HQ (3) were investigated for antimicrobial activity against Enterobacteriaceae including extended spectrum β-lactamase (ESBL)-producing and carbapenemase-producing strains as well as the effect of metal ions .These compounds (1-3) displayed the great antimicrobial activity against fifty-eight bacterial isolates of Escherichia coli, Providencia rettgeri and Klebsiella pneumoniae, in which NQ (2) exerted the highest antimicrobial activity with a MIC50 of 42.04 μM (8 μg/mL) and MBC50 of 168.28 μM (32 μg/mL). The MIC values of NQ (2) and 7-Br -8HQ (3) were significantly increased in the presence of Cu2+ and Fe3+. This finding reveals that NQ could be an effective compound to be further developed as an antimicrobial agent for combating Enterobacteriaceae infections. [ABSTRACT FROM AUTHOR]