Effects of radiation dose and dose rate on alginate and the use of radiation degraded alginate for peanut.

Aqueous solutions of alginate (4 %) with or without hydrogen peroxide (0-2 % H2O2) were irradiated under a gamma Co-60 source. The effect of dose rate on the radiation scission yield (Gs) of resulting irradiated alginate was determined. At the dose of 20 kGy, the G(s) value of irradiated alginate decreased with the increase dose rate, suggesting that the irradiation at a suitable dose rate could further improve the radiation chemical yield of degradation. For the alginate irradiated at the same dose rate, G(s) value increased with the increase of H2O2 concentration. Average molecular weight (Mw) and polydispersity index (PI) of irradiated alginate rapidly decreased with the increase in dose and further decreased by addition of H2O2. The oligoalginate with Mw ~ 9800 g/mol was obtained by radiation degradation of 4 % alginate solution containing 2 % H2O2 at dose of 20 kGy. Radiation scission of glycoside bonds and formation of carbonyl groups (C=O) were indicated in UV and FTIR spectra of irradiated alginate. Peanut seedlings were fertilized with alginate and oligoalginate solutions, and the results showed that all growth parameters of the treated plants were better than those of the control. Furthermore, the oligoalginate prepared by gamma irradiation can be applied as a plant growth promoter for agriculture production.

Publisher Correction: Interplay between hypoxia and androgen controls a metabolic switch conferring resistance to androgen/AR-targeted therapy.

The original version of this Article contained errors in Fig. 7. In panels e and f, the graph titles incorrectly read 'LNCaP-AdtNs' and 'LAPC4-AdtNs', respectively. These errors have now been corrected in both the PDF and HTML versions of the Article.

Interplay between hypoxia and androgen controls a metabolic switch conferring resistance to androgen/AR-targeted therapy.

Despite recent advances, the efficacy of androgen/androgen receptor (AR)-targeted therapy remains  limited for many patients with metastatic prostate cancer. This is in part because prostate cancers adaptively switch to the androgen/AR-independent pathway for survival and growth, thereby conferring therapy resistance. Tumor hypoxia is considered as a major cause of treatment resistance. However, the exact mechanism is largely unclear. Here we report that chronic-androgen deprivation therapy (ADT) in the condition of hypoxia induces adaptive androgen/AR-independence, and therefore confers resistance to androgen/AR-targeted therapy, e.g., enzalutamide. Mechanistically, this is mediated by glucose-6-phosphate isomerase (GPI), which is transcriptionally repressed by AR in hypoxia, but restored and increased by AR inhibition. In turn, GPI maintains glucose metabolism and energy homeostasis in hypoxia by redirecting the glucose flux from androgen/AR-dependent pentose phosphate pathway (PPP) to hypoxia-induced glycolysis pathway, thereby reducing the growth inhibitory effect of enzalutamide. Inhibiting GPI overcomes the therapy resistance in hypoxia in vitro and increases enzalutamide efficacy in vivo.