Interleukin-6 (IL-6) has been reported to stimulate myeloid-derived suppressor cells (MDSCs) in multiple cancers, but the molecular events involved in this process are not completely understood. We previously found that cancer-derived IL-6 induces T cell suppression of MDSCs in vitro via the activation of STAT3/IDO signaling pathway. In this study, we aimed to elucidate the underlying mechanisms. We found that in primary breast cancer tissues, cancer-derived IL-6 was positively correlated with infiltration of MDSCs in situ, which was accompanied by more aggressive tumor phenotypes and worse clinical outcomes. In vitro IL-6 stimulated the amplification of MDSCs and promoted their T cell suppression ability, which were fully inhibited by an IL-6-specific blocking antibody. Our results demonstrate that IL-6-dependent suppressor of cytokine signaling 3 (SOCS3) suppression in MDSCs induced phosphorylation of the JAK1, JAK2, TYK2, STAT1, and STAT3 proteins, which was correlated with T cell suppression of MDSCs in vitro. Therefore, dysfunction in the SOCS feedback loop promoted long-term activation of the JAK/STAT signaling pathway and predominantly contributed to IL-6-mediated effects on MDSCs. Furthermore, IL-6-induced inhibition of SOCS3 and activation of the JAK/STAT pathway was correlated with an elevated expression of IL-6 receptor α (CD126), in which the soluble CD126-mediated IL-6 trans-signaling pathway significantly regulated IL-6-mediated effects on MDSCs. Finally, IL-6-induced SOCS3 dysfunction and sustained activation of the JAK/STAT signaling pathway promoted the amplification and immunosuppressive function of breast cancer MDSCs in vitro and in vivo, and thus blocking the IL-6 signaling pathway is a promising therapeutic strategy for eliminating and inhibiting MDSCs to improve prognosis.

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Abstract-We consider the capacity of a downlink Orthogonal Frequency Division Multiple Access (OFDMA) system with limited feedback rate RF per sub-channel and finite coherence time T . The feedback is used to relay channel state information (CSI) from K users to the base station. The order-optimal capacity growth with Rayleigh fading sub-channels is Θ(N log log K) as N and K increase with fixed ratio, where N is the number of sub-channels. However, to achieve this, previous work requires a feedback rate per subchannel that scales linearly with the system size. Here we explicitly include the feedback overhead when calculating the sum capacity, and study the tradeoff between feedback rate and sum capacity. We propose two limited feedback schemes, one based on sequential transmissions across users and the other based on random access, in which the each feedback bit requests the use of a sub-channel group containing multiple subchannels. With fixed RF T , the sum capacity for both schemes with optimized sub-channel groups increases as Θ(N ). If RF T grows faster than log K, then both schemes can achieve the orderoptimal capacity growth. We also show that when RF T is small, the random access scheme performs better than the sequential transmission scheme, whereas the reverse is true for large RF T .

Abstract-We consider the capacity of a downlink Orthogonal Frequency Division Multiple Access (OFDMA) system with limited feedback rate RF per sub-channel and finite coherence time T . The feedback is used to relay channel state information (CSI) from K users to the base station. The order-optimal capacity growth with Rayleigh fading sub-channels is Θ(N log log K) as N and K increase with fixed ratio, where N is the number of sub-channels. However, to achieve this, previous work requires a feedback rate per subchannel that scales linearly with the system size. Here we explicitly include the feedback overhead when calculating the sum capacity, and study the tradeoff between feedback rate and sum capacity. We propose two limited feedback schemes, one based on sequential transmissions across users and the other based on random access, in which the each feedback bit requests the use of a sub-channel group containing multiple subchannels. With fixed RF T , the sum capacity for both schemes with optimized sub-channel groups increases as Θ(N ). If RF T grows faster than log K, then both schemes can achieve the orderoptimal capacity growth. We also show that when RF T is small, the random access scheme performs better than the sequential transmission scheme, whereas the reverse is true for large RF T .

MicroRNAs (miRNAs) participate in almost all biological processes. Plenty of evidences show that some testis- or spermatozoa-specific miRNAs play crucial roles in the process of gonad and germ cell development. In this study, the spermatozoa miRNA profiles were investigated through a combination of illumina deep sequencing and bioinformatics analysis in zebrafish. Deep sequencing of small RNAs yielded 11,820,680 clean reads. By mapping to the zebrafish genome, we identified 400 novel and 204 known miRNAs that could be grouped into 104 families. Furthermore, we selected the six highest expressions of known miRNAs to detect their expression patterns in different tissues by stem-loop quantitative real-time polymerase chain reaction. We found that among the six miRNAs, dre-miR-202-5p displayed specific and high expression in zebrafish spermatozoa and testis. Fluorescence in situ hybridization analysis indicated that dre-miR-202-5p was predominantly expressed in all kind of germ cells at different spermatogenetic stages, including spermatogonia and spermatozoa, but barely expressed in the germ cells in the ovary. This sex-biased expression pattern suggests that dre-miR-202-5p might be related to spermatogenesis and the functioning of spermatozoa. The identification of miRNAs in zebrafish spermatozoa and germ cells offers new insights into the spermatogenesis and spermatozoa in the teleost and other vertebrates.