Radiation-induced bystander effects (RIBE) refer to a unique process, in which factors released by irradiated cells or tissues exert effects on other parts of the animal not exposed to radiation, causing genomic instability, stress responses, and altered apoptosis or cell proliferation1–3. Despite important implications in radioprotection, radiation safety and radiotherapy, the molecular identities of RIBE factors and their mechanisms of action remain elusive. Here we use C. elegans as an animal model to study RIBE and have identified a cysteine protease CPR-4, a human cathepsin B homolog, as the first RIBE factor in nematodes. CPR-4 is secreted from animals irradiated with ultraviolet (UV) or ionizing gamma rays (IR) and is the major factor in the conditioned medium that leads to inhibition of cell death and increased embryonic lethality in unirradiated animals. Moreover, CPR-4 causes these effects and stress response at unexposed sites distal to the irradiated tissue. The activity of CPR-4 is regulated by the p53 homolog cep-1 in response to radiation and CPR-4 appears to act through the insulin-like growth factor receptor, DAF-2, to exert RIBE. Our study provides critical insights into the elusive RIBE and will facilitate identification of additional RIBE factors and their mechanisms of action.

This study aims to investigate the mechanism by which resveratrol (RV) prevents sodium nitroprusside (SNP)-induced chondrocyte apoptosis, which is a characteristic feature of osteoarthritis (OA). Rabbit articular chondrocytes were pre-incubated with 100 μM RV for 18 h before 1.5 mM SNP co-treatment for 6 h. Cell viability was evaluated by CCK-8. Annexin V/PI double staining and Hoechst 33258 staining were used to determine the fashion of SNP-induced chondrocytes death. Mitochondrial membrane potential (ΔΨm) was measured by using flow cytometry (FCM) with TMRM and Rhodamine 123 staining. Intracellular reactive oxygen species (ROS) and nitric oxide (NO) levels were confirmed by FCM analysis with DCFH-DA and DAF-FM DA staining. Cytoskeleton proteins of chondrocytes co-stained with Actin-Trakcer Green and Tubulin-Trakcer Red were validated by confocal microscopy. SNP induced time- and dose-dependent chondrocytes apoptosis with decline of ΔΨm, activation of caspases as well as cytoskeletal remodeling. SNP induced a significant induction of both ROS and NO. RV remarkably prevented SNP-induced ROS production and apoptosis as well as cytoskeletal remodeling, but did not prevent SNP-induced NO production. Pretreatment with NO scavengers did not significantly prevent SNP-induced apoptosis and cytoskeletal remodeling. SNP induces NO-independent ROS production which dominates rabbit articular chondrocyte apoptosis, and RV protects chondrocytes against SNP-induced apoptosis via scavenging ROS instead of NO.

Abstract-Caching and multicasting are two promising methods to support massive content delivery in multi-tier wireless networks. In this paper, we consider a random caching and multicasting scheme with caching distributions in the two tiers as design parameters, to achieve efficient content dissemination in a two-tier large-scale cache-enabled wireless multicasting network. First, we derive tractable expressions for the successful transmission probabilities in the general region as well as the high SNR and high user density region, respectively, utilizing tools from stochastic geometry. Then, for the case of a single operator for the two tiers, we formulate the optimal joint caching design problem to maximize the successful transmission probability in the asymptotic region, which is nonconvex in general. By using the block successive approximate optimization technique, we develop an iterative algorithm, which is shown to coverage to a stationary point. Next, for the case of two different operators, one for each tier, we formulate the competitive caching design game where each tier maximizes its successful transmission probability in the asymptotic region. We show that the game has a unique Nash equilibrium (NE) and develop an iterative algorithm, which is shown to converge to the NE under a mild condition. Finally, by numerical simulations, we show that the proposed designs achieve significant gains over existing schemes.

In this paper, we present the notion of "mobile 3C systems in which the "Communications", "Computing", and "Caching" (i.e., 3C) make up the three primary resources/funcationalties, akin to the three primary colors, for a mobile system. We argue that in future mobile networks, the roles of computing and caching are as intrinsic and essential as communications, and only the collective usage of these three primary resources can support the sustainable growth of mobile systems. By defining the 3C resources in their canonical forms, we reveal the important fact that "caching" affects the mobile system performance by introducing non-causality into the system, whereas "computing" achieves capacity gains by performing logical operations across mobile system entities. Many existing capacity-enhancing techniques such as coded multicast, collaborative transmissions, and proactive content pushing can be cast into the native 3C framework for analytical tractability. We further illustrate the mobile 3C concepts with practical examples, including a system on broadcast-unicast convergence for massive media content delivery. The mobile 3C design paradigm opens up new possibilities as well as key research problems bearing academic and practice significance.Comment: submitted to IEEE Communications Magazine -- Feature Topic: Mobile 3C Network

In most eukaryotes, mitochondria are inherited maternally. The autophagy process is critical for paternal mitochondrial elimination (PME) in Caenorhabditis elegans, but how paternal mitochondria, but not maternal mitochondria, are selectively targeted for degradation is poorly understood. Here we report that mitochondrial dynamics have a profound effect on PME. A defect in fission of paternal mitochondria delays PME, whereas a defect in fusion of paternal mitochondria accelerates PME. Surprisingly, a defect in maternal mitochondrial fusion delays PME, which is reversed by a fission defect in maternal mitochondria or by increasing maternal mitochondrial membrane potential using oligomycin. Electron microscopy and tomography analyses reveal that a proportion of maternal mitochondria are compromised when they fail to fuse normally, leading to their competition for the autophagy machinery with damaged paternal mitochondria and delayed PME. Our study indicates that mitochondrial dynamics play a critical role in regulating both the kinetics and the specificity of PME.