Abbreviations: ANXA5, annexin A5; CASP3, caspase 3, apoptosis-related cysteine peptidase; CTSB, cathepsin B; DLS, dynamic light scattering; DMEM, Dulbecco's Modified Eagle's medium; EGFP-LC3, enhanced green fluorescent protein-tagged LC3; ICP-MS, inductively coupled plasma-mass spectrometry; I-MEF, immortalized mouse embryonic fibroblast; MDC, monodansylcadaverine; MTOR, mechanistic target of rapamycin; P-MEF, primary mouse embryonic fibroblast; PI, propidium iodide; PI3K, phosphoinositide 3-kinase; PtdIns3K, phosphatidylinositol 3-kinase; PVP, polyvinylpyrrolidone; RPS6KB, ribosomal protein S6 kinase, 70 kDa; s.c., subcutaneously; SQSTM1, sequestosome 1; TEM, transmission electron microscopy; TUNEL, terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTPdigoxigenin nick end labeling; UV-Vis, ultraviolet visible; XRD, X-ray diffraction.Silver nanoparticles (Ag NPs) are cytotoxic to cancer cells and possess excellent potential as an antitumor agent. A variety of nanoparticles have been shown to induce autophagy, a critical cellular degradation process, and the elevated autophagy in most of these situations promotes cell death. Whether Ag NPs can induce autophagy and how it might affect the anticancer activity of Ag NPs has not been reported. Here we show that Ag NPs induced autophagy in cancer cells by activating the PtdIns3K signaling pathway. The autophagy induced by Ag NPs was characterized by enhanced autophagosome formation, normal cargo degradation, and no disruption of lysosomal function. Consistent with these properties, the autophagy induced by Ag NPs promoted cell survival, as inhibition of autophagy by either chemical inhibitors or ATG5 siRNA enhanced Ag NPs-elicited cancer cell killing. We further demonstrated that wortmannin, a widely used inhibitor of autophagy, significantly enhanced the antitumor effect of Ag NPs in the B16 mouse melanoma cell model. Our results revealed a novel biological activity of Ag NPs in inducing cytoprotective autophagy, and inhibition of autophagy may be a useful strategy for improving the efficacy of Ag NPs in anticancer therapy.

Quantitative measurements of the oxygen precipitate rate as a function of annealing were made in Czochralski-grown silicon wafers that contained different initial concentrations of oxygen. All wafers were annealed at 1000 °C for 15 min to ensure that the initial cluster-size distributions were identical in all samples of the same composition prior to the multi-step annealing treatments used for the precipitation studies. The experimental data are compared with numerical predictions for time-dependent nucleation within the classical theory of nucleation. Quantitative agreement is obtained between the measured and calculated densities of oxygen precipitates for nucleation temperatures greater than 600 °C, but only over a narrow range of oxygen composition. Below 600 °C, the measured density for all samples is orders of magnitude larger than is predicted from the model. Further, the measured data show an anomalously small temperature dependence for the induction time for nucleation that does not scale with the diffusion coefficient, as expected from the classical theory of nucleation. Fundamentally, the classical theory of nucleation cannot explain the time-dependent nucleation of oxygen precipitates for temperatures below 650 °C. A possible reason is given.

Herein, a kind of novel monocomponent hydrophilic and paramagnetic manganese(II) oxide nanocrystal is prepared in polar solution by a one‐pot microwave‐assisted synthesis. This kind of nanocrystal can be taken up efficiently to serve as an excellent T1 magnetic resonance imaging (MRI) contrast agent with an enhanced r1 value of 0.81 mM−1 s−1. The key to the success of this method is that no additional capping agents are required for coating onto the surface via ligand exchange, facilitating research of their intrinsic biological activities. Furthermore, multiple lines of convincing evidence are presented to prove that MnO nanocrystals (NCs) elicit p53‐activation‐independent and authentic functional autophagy via inducing autophagosome formation. Notably, there are very few reports so far of the autophagy phenomenon induced by magnetic nanocrystals. Moreover, these results offer an indication for cancer therapy that MnO NCs combined with doxorubicin at a nontoxic concentration can have a definite synergistic effect, which is mediated through the genuine autophagy induction, on killing cancer cells in vitro and in vivo.

Autophagy, an evolutionally conserved intracellular process degrading cytoplasmic proteins and organelles for recycling, has become one of the most remarkable strategies applied in cancer research. The fullerene C60 nanoparticle (nC60) has been shown to induce autophagy and sensitize chemotherapeutic killing of cancer cells, but the details still remain unknown. Here we show that a water-dispersed nanoparticle solution of derivatized fullerene C60, C60(Nd) nanoparticles (nC60(Nd)), has greater potential in inducing autophagy and sensitizing chemotherapeutic killing of both normal and drug-resistant cancer cells than nC60 does in an autophagy-dependent fashion. Additionally we further demonstrated that autophagy induced by nC60/C60(Nd) and Rapamycin had completely different roles in cancer chemotherapy. Our results, for the first time, revealed a novel and more potent derivative of the C60 nanoparticle in enhancing the cytotoxicity of chemotherapeutic agents and reducing drug resistance through autophagy modulation, which may ultimately lead to novel therapeutic strategies in cancer therapy.

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Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights into future investigations aimed to explore the in-depth mechanisms of miRNAs and other small RNAs including piRNAs in penile carcinogenesis regulation and effective target-specific theragnosis.

Enhancing tumor chemotherapy and overcoming drug resistance through autophagy-mediated intracellular dissolution of zinc oxide nanoparticles.