Docosahexaenoic acid (DHA) has been reported to induce tumor cell death by apoptosis. However, little is known about the effects of DHA on autophagy, another complex well-programmed process characterized by the sequestration of cytoplasmic material within autophagosomes. Here, we show that DHA increased both the level of microtubule-associated protein light-chain 3 and the number of autophagic vacuoles without impairing autophagic vesicle turnover, indicating that DHA induces not only apoptosis but also autophagy. We also observed that DHA-induced autophagy was accompanied by p53 loss. Inhibition of p53 increased DHA-induced autophagy and prevention of p53 degradation significantly led to the attenuation of DHA-induced autophagy, suggesting that DHA-induced autophagy is mediated by p53. Further experiments showed that the mechanism of DHA-induced autophagy associated with p53 attenuation involved an increase in the active form of AMP-activated protein kinase and a decrease in the activity of mammalian target of rapamycin. In addition, compelling evidence for the interplay between autophagy and apoptosis induced by DHA is supported by the findings that autophagy inhibition suppressed apoptosis and further autophagy induction enhanced apoptosis in response to DHA treatment. Overall, our results demonstrate that autophagy contributes to the cytotoxicity of DHA in cancer cells harboring wild-type p53.

Docosahexaenoic acid (DHA) induces autophagy-associated apoptotic cell death in wild-type p53 cancer cells via regulation of p53. The present study investigated the effects of DHA on PC3 and DU145 prostate cancer cell lines harboring mutant p53. Results show that, in addition to apoptosis, DHA increased the expression levels of lipidated form LC3B and potently stimulated the autophagic flux, suggesting that DHA induces both autophagy and apoptosis in cancer cells expressing mutant p53. DHA led to the generation of mitochondrial reactive oxygen species (ROS), as shown by the mitochondrial ROS-specific probe mitoSOX. Similarly, pretreatment with the antioxidant N-acetyl-cysteine (NAC) markedly inhibited both the autophagy and the apoptosis triggered by DHA, indicating that mitochondrial ROS mediate the cytotoxicity of DHA in mutant p53 cells. Further, DHA reduced the levels of phospho-Akt and phospho-mTOR in a concentration-dependent manner, while NAC almost completely blocked that effect. Collectively, these findings present a novel mechanism of ROS-regulated apoptosis and autophagy that involves Akt-mTOR signaling in prostate cancer cells with mutant p53 exposed to DHA.

Deformation behavior of the Ag nanowire flexible transparent electrode under bending strain is studied and results in a novel approach for highly reliable Ag nanowire network with mechanically welded junctions. Bending fatigue tests up to 500,000 cycles are used to evaluate the in situ resistance change while imposing fixed, uniform bending strain. In the initial stages of bending cycles, the thermally annealed Ag nanowire networks show a reduction in fractional resistance followed by a transient and steady-state increase at later stages of cycling. SEM analysis reveals that the initial reduction in resistance is caused by mechanical welding as a result of applied bending strain, and the increase in resistance at later stages of cycling is determined to be due to the failure at the thermally locked-in junctions. Based on the observations from this study, a new methodology for highly reliable Ag nanowire network is proposed: formation of Ag nanowire networks with no prior thermal annealing but localized junction formation through simple application of mechanical bending strain. The non-annealed, mechanically welded Ag nanowire network shows significantly enhanced cyclic reliability with essentially 0% increase in resistance due to effective formation of localized wire-to-wire contact.

Compounds bearing an acyl group of a various size at 1'-OH of shikonin were synthesized as acyl analogues of shikonin, which was isolated from the root of Lithospermum erythrorhizon, and evaluated for inhibitory effect on topoisomerase-I activity. A selective acylation at 1'-OH of shikonin in the presence of dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine gave rise to a good yield of corresponding acylshikonin derivatives. In general, analogues with an acyl group of shorter chain lengths (C2-C6) exerted a stronger inhibitory action than those with longer chain lengths (C7-C20). While the halogen substitution at C-2 of the acetyl moiety failed to increase the inhibitory potency, the placement of double bonds in the acyl group (C5-C7) augmented the potency remarkably. Of the 32 derivatives evaluated, 15 compounds exhibited a higher inhibitory effect than shikonin. Noteworthy, the inhibitory potency of acetylshikonin, propanoylshikonin, and 4-pentenoylshikonin was approximately 4-fold greater than that of camptothecin. All these data suggest that the size of acyl moiety is important for the enhancement of potency, and the presence of olefinic double bonds is also beneficial.

There is an increasing demand in the flexible electronics industry for highly robust flexible/transparent conductors that can withstand high temperatures and corrosive environments. In this work, outstanding thermal and ambient stability is demonstrated for a highly transparent Ag nanowire electrode with a low electrical resistivity, by encapsulating it with an ultra-thin Al2O3 film (around 5.3 nm) via low-temperature (100 °C) atomic layer deposition. The Al2O3-encapsulated Ag nanowire (Al2O3/Ag) electrodes are stable even after annealing at 380 °C for 100 min and maintain their electrical and optical properties. The Al2O3 encapsulation layer also effectively blocks the permeation of H2O molecules and thereby enhances the ambient stability to greater than 1,080 h in an atmosphere with a relative humidity of 85% at 85 °C. Results from the cyclic bending test of up to 500,000 cycles (under an effective strain of 2.5%) confirm that the Al2O3/Ag nanowire electrode has a superior mechanical reliability to that of the conventional indium tin oxide film electrode. Moreover, the Al2O3 encapsulation significantly improves the mechanical durability of the Ag nanowire electrode, as confirmed by performing wiping tests using isopropyl alcohol.