The selenoprotein thioredoxin reductase (TrxR) plays a pivotal role in regulating cellular redox homeostasis and has attracted increasing attention as a promising anticancer drug target. We report here that 2-(4-aminophenyl)-1,3,2-dithiarsinane (PAO-PDT, 4), a potent and highly selective small molecule inhibitor of TrxR, stoichiometrically binds to the C-terminal selenocysteine/cysteine pair in the enzyme in vitro and induces oxidative stress-mediated apoptosis in HL-60 cells. The molecular action of 4 in cells involves inhibition of TrxR, elevation of reactive oxygen species, depletion of cellular thiols, and activation of caspase-3. Knockdown of TrxR sensitizes the cells to 4 treatment, whereas overexpression of the functional enzyme alleviates the cytotoxicity, providing physiological relevance for targeting TrxR by 4 in cells. The simplicity of the structure and the presence of an easily manipulated amine group will facilitate the further development of 4 as a potential cancer chemotherapeutic agent.

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Background:The aim of this study was to evaluate the prognostic role of neutrophil–lymphocyte ratio (NLR) in patients with acute ischemic stroke (AIS).Methods:PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure were searched for potential eligible literature. The study characteristics and relevant data were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the prognostic role of NLR in patients with AIS. Poor functional outcome was defined as modified Rankin Scale ≥ 3.Results:Nine studies with 2947 patients were included. The pooled OR of higher NLR for poor functional outcome at 3 months was 1.55 (95% CI, 1.21–2.00). The pooled ORs for death at 3 months, poor functional outcome at discharge, and symptomatic intracranial hemorrhage (sICH) were 2.35 (95% CI, 0.40–13.78), 2.38 (95% CI, 0.49–11.69), and 4.32 (95% CI, 2.46–7.61), respectively.Conclusion:For patients with AIS, higher NLR was associated with poorer functional outcome at 3 months and may be associated with a higher risk of developing sICH. This readily available and inexpensive marker may be helpful in future clinical and research work. However, due to the limited number of included studies, more well-designed studies are warranted to further clarify this issue.

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The catalytic enantioselective synthesis of all-carbon quaternary stereogenic centers in spirocyclic diketones has been achieved for the first time by an unprecedented asymmetric vinylogous alpha-ketol rearrangement in which an enantiocontrolled semipinacol-type 1,2-carbon migration was realized using multifunctional cinchona-modified primary amine catalysis.