Intermediate molecular phenotypes to identify genetic markers of anthracycline-induced cardiotoxicity risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex disease whose polygenic component is mainly unidentified. We propose that levels of intermediate molecular phenotypes in the myocardium associated with histopathological damage could explain CDA susceptibility; so that variants of genes encoding these intermediate molecular phenotypes could identify patients susceptible to this complication. A genetically heterogeneous cohort of mice generated by backcrossing (N = 165) was treated with doxorubicin and docetaxel. Cardiac histopathological damage was measured by fibrosis and cardiomyocyte size by an Ariol slide scanner. We determine intramyocardial levels of intermediate molecular phenotypes of CDA associated with histopathological damage and quantitative trait loci (ipQTLs) linked to them. These ipQTLs seem to contribute to the missing heritability of CDA because they improve the heritability explained by QTL directly linked to CDA (cda-QTLs) through genetic models. Genes encoding these molecular subphenotypes were evaluated as genetic markers of CDA in three cancer patient cohorts (N = 517) whose cardiac damage was quantified by echocardiography or Cardiac Magnetic Resonance. Many SNPs associated with CDA were found using genetic models. LASSO multivariate regression identified two risk score models, one for pediatric cancer patients and the other for women with breast cancer. Molecular intermediate phenotypes associated with heart damage can identify genetic markers of CDA risk, thereby allowing a more personalized patient management. A similar strategy could be applied to identify genetic markers of other complex trait diseases.

A simple method for the preparation of a nickel selenide and cobalt selenide mixed catalyst to enhance bifunctional oxygen activity for Zn-air batteries.

Developing a low-cost, simple, and efficient method to prepare excellent bifunctional electrocatalysts toward the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is critical in rechargeable zinc-air batteries. Non-stoichiometric M0.85Se (M = Ni or Co) nanoparticles are synthesized and modified on nitrogen-doped hollow carbon sphere (NHCS). The NHCS loaded Ni0.85Se (Ni0.85Se-NHCS) with rich Ni3+ presents higher OER activity, whereas the NHCS-loaded Co0.85Se (Co0.85Se-NHCS) with abundant Co2+ displays better ORR activity, respectively. When Co0.85Se-NHCS is mixed with Ni0.85Se-NHCS in a mass ratio of 1 : 1, the resulting mixture (Ni0.85Se/Co0.85Se-NHCS-2) shows better ORR and OER dual catalytic functions than a single selenide. Moreover, zinc-air batteries equipped with Ni0.85Se/Co0.85Se-NHCS-2 as the oxygen electrode catalyst exhibit excellent charge and discharge performance as well as improved stability over precious metals. This work has developed a simple and effective method to prepare excellent bifunctional electrocatalysts for ORR and OER, which is beneficial for the practical large-scale application of zinc-air batteries.

[Molecular analysis on the S gene of three Crimean-Congo hemorrhagic fever virus strains in China].

OBJECTIVE: To compare the molecular characteristics of 3 Crimean-Congo hemorrhagic fever viruses(CCHFV) isolated in Xinjiang province. METHODS: YL05035, YT05099 and LT05146 were isolated in 2005 from Hyalomma ticks and viral RNA was extracted from suckling mouse brains infected with these three strains respectively. The polymerase chain reaction(PCR) products of S segments from the 3 strains of CCHFV were directly sequenced. RESULTS: The full-length'S RNA from the 3 strains of CCHFV all comprised 1673 nucleotides with ORF of them including 1449 nucleotides and encoding a protein which comprised 482 amino acids in a viral complementary sense. The sequences indicated that the three strains of CCHFV isolated from ticks in Xinjiang province were highly homologenic. Data from the phylogenetic analysis showed that the obtained sequences were identical. The homology between 3 strains of CCHFV was 99.5%. Their homologies compared with that of the other strains isolated from other region of Xinjiang were also high at nucleotide levels (92.7%-99.8%). The three strains which were clustered together with 7001 strain and 79121 strain (isolated from patient and rat in Xinjiang respectively) was only different by 2%-3%. The genetic difference from the prototype CCHFV Nigerian strain IBAR10200 was 13%. In comparison, the Nigerian CCHFV tick isolate was more divergent when compared with the reference China strains 66019 and with the three variants mentioned above. CONCLUSION: The CCHFV isolated from China comprised a group of genetically high conserved strains.

[In situ UV-visible absorption spectrum monitoring the electrochemical degradation of PAn films].

Kinetic degradation process of PAn films during aniline polymerization was in situ monitored by UV-Visible absorption spectrum. The effects of anodic potential, acidity and monomer concentration on the degradation process were also investigated. The experiment results displayed that the more positive the anodic potential, the higher the acidity of the solution, the higher the concentration of aniline, the faster the PAn films degradation speed. Which was similar to the results obtained when the kinetic degradation process of PAn films was studied in blank solutions by cyclic voltammetry.