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Macrophages are white blood cells of the innate immune system that play disparate roles in homeostasis and immune responses. As a result, they have the capability to alter their phenotypes to pro-inflammatory (M1) or anti-inflammatory (M2) subtypes in response to their environment. 8-15% of the macrophage transcriptome has circadian oscillations, including genes closely related to their functioning. As circadian rhythms are also associated with cellular phenotypes, we hypothesized that the polarization of macrophages to opposing subtypes might differently affect their circadian rhythms. We tested this by tracking the circadian rhythms of the mouse model macrophage cell line, RAW 264.7, which was stably transfected with Bmal1:luc and Per2:luc reporters, representing a positive and a negative component of the core molecular clock. The strength of rhythmicity was assessed using three measures: the relative power of the circadian band in the power spectral density, the rhythmicity index computed as the height of the third peak of the correlogram, and the maximum value of the chi square periodorgram. The period and amplitudes of the de-trended, smoothed time-series were estimated both by fitting to a damped cosine curve and by identifying the peak and trough of each cycle. M1 polarization decreased amplitudes and rhythmicities of both Bmal1:luc and Per2:luc, but did not significantly affect periods, while M2 polarization increased periods and caused no substantial alterations to amplitudes or rhythmicity. As macrophage phenotypes are also altered in the presence of cancer cells, we then tested the circadian effects of conditioned media from two mouse breast cancer cell lines on macrophage circadian rhythms. Media from highly agressive 4T1 cells caused loss of rhythmicity, while media from less aggressive EMT6 cells yielded no changes. As macrophages are known to play roles in tumors, and oncogenic features are associated with circadian rhythms, we also tested whether conditioned media from macrophages can alter circadian rhythms of cancer cells. We found that conditioned media from RAW 264.7 cells resulted in lower circadian rhythmicities and periods, but higher circadian amplitudes in human osteosarcoma, U2OS-Per2:luc cells. Taken together, our study shows that different circadian characteristics exist based on macrophage phenotypes, and suggests further that there is an association between circadian rhythms and macrophage polarization state. Additionally, our data shows that macrophages treated with breast cancer-conditioned media have circadian phenotypes similar to those of the M1 subtype, and cancer cells treated with macrophage-conditioned media have circadian alterations, providing insight to another level of cross-talk between macrophages and cancer cells that merits further investigation.

Silicon (Si) has been recently reconsidered as a beneficial element due to its direct roles in stimulating the growth of many plant species and alleviating metal toxicity. This study aimed at validating the potential of an aquatic macrophyte Eleocharis acicularis for simultaneous removal of heavy metals from aqueous solutions under different dissolved Si. The laboratory experiments designed for determining the removal efficiencies of heavy metals were conducted in the absence or presence of Si on a time scale up to 21 days. Eleocharis acicularis was transplanted into the solutions containing 0.5 mg L−1 of indium (In), gallium (Ga), silver (Ag), thallium (Tl), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) with various Si concentrations from 0 to 4.0 mg L−1. The results revealed that the increase of dissolved Si concentrations enhanced removal efficiencies of E. acicularis for Ga, Cu, Zn, Cd, and Pb, while this increase did not show a clear effect for In, Tl, and Ag. Our study presented a notable example of combining E. acicularis with dissolved Si for more efficient removals of Cu, Zn, Cd, Pb, and Ga from aqueous solutions. The findings are applicable to develop phytoremediation or phytomining strategy for contaminated environment.

© 1997-2012 IEEE. This letter applies Han-Kobayashi (H-K) superposition signaling to a network of a multi-antenna transmitter serving two multi-antenna users. By making the rate of the common message for both users contribute to user individual rate, it shows that H-K superposition signaling clearly outperforms both state-of-the-art orthogonal multiaccess and nonorthogonal multiaccess schemes (NOMA) in terms of the worst user rate. More importantly, unlike NOMA, H-K superposition signaling does not require the user channels to be differentiated for efficient implementation.

KR Jyothi,1 Jagadish Beloor,2 Ara Jo,1 Minh Nam Nguyen,1 Tae Gyu Choi,1 Jin-Hwan Kim,1 Salima Akter,1 Sang-Kyung Lee,2 Chi Hoon Maeng,3 Hyung Hwan Baik,1 Insug Kang,1 Joohun Ha,1 Sung Soo Kim1 1Department of Biochemistry and Molecular Biology, School ofMedicine, Kyung Hee University, Seoul, Republic of Korea; 2Department of Bioengineering and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, Republic of Korea; 3Department ofMedical Oncology and Hematology, Kyung Hee University Hospital, Seoul, Republic of Korea Abstract: Therapeutic options for hepatitis C virus (HCV) infection have been limited by drug resistance and adverse side effects. Targeting the host factor cyclophilin A (CypA), which is essential for HCV replication, offers a promising strategy for antiviral therapy. However, due to its immunosuppressive activity and severe side effects, clinical application of cyclosporine A (CsA) has been limited as an antiviral agent. To overcome these drawbacks, we have successfully developed a liver-specific, sustained drug delivery system by conjugating the liver-targeting peptide (LTP) to PEGylated CsA-encapsulated poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Furthermore, our delivery system exhibited high specificity to liver, thus contributing to the reduced immunosuppressive effect and toxicity profile of CsA. Finally, targeted nanoparticles were able to effectively inhibit viral replication in vitro and in an HCV mouse model. As a proof of principle, we herein show that our delivery system is able to negate the adverse effects of CsA and produce therapeutic effects in an HCV mouse model.Keywords: HCV, liver-targeting peptide, targeted drug delivery

This article describes considerations for the design and conduct of therapeutic trials in dengue. We have recommended a minimum set of clinical and laboratory endpoints in the belief that the field will benefit from a standardized reporting approach. Whilst clear challenges exist in developing therapies for dengue, not least the self-limiting nature of the virus infection, it is hoped that the clinical trial template described here will help accelerate the clinical testing of antiviral and other therapeutic candidates.