Plasma exosomal miR-451a levels may be a useful minimally invasive biomarker for the prediction of recurrence and prognosis in PDAC patients.

RNA interference (RNAi) is a post-transcriptional gene-silencing phenomenon that is triggered by double-stranded RNA (dsRNA). Since many diseases are associated with the inappropriate production of specific proteins, attempts are being made to exploit RNAi in a clinical settings. However, before RNAi can be exploited as therapeutically, several obstacles must be overcome. For example, small interfering RNA (siRNA) is unstable in the blood stream so any effects of injected siRNA are only transient. Accordingly, methods must be developed to prolong its activity. Furthermore, the efficient and safe delivery of siRNA into target tissues and cells is critical for successful therapy. Any useful delivery method should be designed to target siRNA to specific cells and to promote gene-silencing activity once the siRNA is inside the cells. Recent chemical modifications of siRNA have overcome problems associated with the instability of siRNA, and various ligands, including glycosylated molecules, peptides, proteins, antibodies and engineered antibody fragments, appear to be very useful or have considerable potential for the targeted delivery of siRNA. The use of such ligands improves the efficiency, specificity and, as a consequence, the safety of the corresponding delivery systems.

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Poly(ethylene glycol) (PEG) is the most widely used polymer and also the gold standard in the field of drug delivery. Therapeutic oligonucleotides, for example, are modified with PEG at the terminus to increases nuclease resistance and the circulating half-lives. The surface of nanoparticle such as micelle and liposome has been also modified with PEG. At present, one PEGylated therapeutic oligonucleotide has been approved for the market and several more PEGylated products including oligonucleotide and liposome are being tested in clinical settings. This review summarizes the methods and effects of PEGylation on gene delivery. V C 2013Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40293.

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Tumor hypoxia, which is associated with poor prognosis in cancer, is known to lead to resistance to radiotherapy and anticancer chemotherapy. Impaired drug penetration in hypoxic regions has been recognized as an essential barrier to drug development in solid tumors. Here, we propose novel hypoxia-activated prodrugs, which drastically improved the penetration property of commonly used anticancer drugs in the hypoxic region. In this design, conventional anticancer drugs were modified with 2-nitroimidazole derivatives. The most important point of this study was that the prodrug designed formed a 6-membered cyclic structure to allow liberation of the active drug in the hypoxic region. This design markedly increased the selectivity of the hypoxia-targeted prodrug, resulting in significant reduction of adverse effects in the normoxic region. In vitro studies confirmed the selective activation under hypoxic conditions. In vivo studies showed drastic reduction of adverse effects associated with conventional anticancer drugs and improvement of the survival rate of mice. Immunofluorescence analyses confirmed that the designed prodrug had a tendency to localize at the hypoxic region, in contrast to conventional anticancer drugs, which localize only at the normoxic region.

Forced convection cooling is important in numerous technologies ranging from microprocessors in data centers to turbines and engines; active cooling is essential in these situations. However, active transfer of heat or thermal energy under a large temperature difference promptly destroys the exergy, which is the free-energy component of thermal energy, and this issue has remained unaddressed. Herein, we describe a thermoelectrochemical conversion to partially recover presently lost exergy in forced convection cooling. We design a test cell in which an electrolyte liquid is forced through a channel formed between two parallel electrodes and the hot-side electrode simulates an object to be cooled. Our investigations show that the narrower interelectrode channels afford higher cooling and power generation performances. The mass transfer resistance is the most dominant type of resistance for all the conditions tested and the charge transfer kinetics is likely to be controlled by viscosity. The dependence of the generated power on the flow rate is caused by the change in the diffusion coefficient of redox species with temperature. As an evaluation measure for such forced-flow thermocells, the gain ()-defined as the ratio of the generated power to the hydrodynamic pumping work required to force the liquid through the cellis introduced.  is above unity in a certain flow rate region. This demonstrates that such a system can generate more electric power than the pump work required to drive the liquid through the cell, suggesting its potential to partly recover presently lost exergy of thermal energy as electricity. Broader Context (maximum 200 words)In our present civilization, forced convection cooling is used in wide-ranging situations from cooling of microprocessors in data centers to that of heat engines including turbines and automobile engines. Active cooling is essential in such situations to avoid thermal failure (for microprocessors) and maximize fuel-to-work conversion efficiencies (heat engines). Here, "active cooling" means the prompt removal of a large quantity of thermal energy in the heat source by a working fluid under a large temperature difference. However, this causes rapid destruction of the exergy, which is the free-energy component of the thermal energy. This issue has remained unaddressed despite the widespread use of forced convection cooling. In this study, to partially recover presently lost exergy in such situations, we integrate thermoelectrochemical conversion, which has been mostly studied for stationary conditions, into forced convection cooling. Through experimental and numerical investigations of a test cell in which the hot-side electrode simulates an object to be cooled, several fundamental properties of such a forced-flow cell are obtained. Our results indicate that such a forced-flow thermocell can generate a larger electric power than the hydrodynamic pumping work required to force the liquid through the cell unit, justifying the concept of this kind of thermocell.