Camelid single-domain antibodies (sdAbs, VHHs, or Nanobodies®) are types of antibody fragments that are composed of the heavy-chain variable domain only. These VHHs possess unique structural and functional features, as they are small in size and exhibit thermal stability and high solubility. Compared to conventional antibodies, VHHs can be manufactured in microorganisms to significantly save on cost, labor, and time since VHHs lack the Fc domain with its N-linked oligosaccharide. Until now, VHHs have been expressed in several kinds of production systems, ranging from prokaryotic cells, yeasts, fungi, insect cells, and mammalian cell lines, to plants. In this review, we focus on the recent production of VHHs, introduce different platforms, and summarize the current state of this area and its future trends. Finally, the first potential VHH product, produced in Pichia pastoris, will probably be available on the market in 2018; thus, it is of great importance to give this antibody fragment timely attention. This is the first review concerning the production of VHHs in laboratory settings.

Abstract-In this paper, cognitive routing coupled with spectrum sensing and sharing in a multi-channel multi-hop cognitive radio network (CRN) is investigated. Recognizing the spectrum dynamics in CRN, we propose an opportunistic cognitive routing (OCR) protocol that allows users to exploit the geographic location information and discover the local spectrum access opportunities to improve the transmission performance over each hop. Specifically, based on location information and channel usage statistics, a secondary user (SU) distributedly selects the next hop relay and adapts its transmission to the dynamic spectrum access opportunities in its neighborhood. In addition, we introduce a novel metric, namely, cognitive transport throughput (CTT), to capture the unique properties of CRN and evaluate the potential relay gain of each relay candidate. A heuristic algorithm is proposed to reduce the searching complexity of the optimal selection of channel and relay. Simulation results are given to demonstrate that our proposed OCR well adapts to the spectrum dynamics and outperforms existing routing protocols in CRN.Index Terms-Cognitive radio, multi-hop transmission, opportunistic routing, dynamic spectrum access.

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Epithelial-mesenchymal-mixed CTCs seem to play an important role in EMT transition in HCC, mixed CTCs might be a vital factor for intrahepatic metastasis, and mesenchymal CTCs had the potential to be a predictor of extrahepatic metastasis.

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2019) Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways, Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 626-635, ABSTRACT Shikonin, a botanical drug extracted from Lithospermum erythrorhizon, exhibits anti-cancer effects in various cancer cell lines. However, the mechanisms underlying these effects have not been completely elucidated yet. Here, we showed that Shikonin induces apoptosis and autophagy in A375 cells and inhibits their proliferation. Shikonin caused G2/M phase arrest through upregulation of p21 and downregulation of cyclin B1. Shikonin significantly triggered ER stress-mediated apoptosis by upregulating the expression of p-eIF2a, CHOP, and cleaved caspase-3. It also induced protective autophagy by activating the p38 pathway, followed by an increase in the levels of p-p38, LC3B-II, and Beclin 1. Upon suppression of autophagy by 3-methyladenine, Shikonin-induced apoptosis was enhanced in A375 cells. Moreover, after pretreatment with N-acetyl-cysteine, Shikonin increased the production of reactive oxygen species that are involved in regulating ER stress-mediated apoptosis and p38-activated autophagy, as evidenced by the reversion of cell viability and apoptosis and a decrease in p-eIF2a, CHOP, p-p38, LC3B-II, and Beclin 1 levels. Thus, we demonstrated that Shikonin induced apoptosis and autophagy in A375 cells via the activation of ROS-mediated ER stress and p38 pathways, indicating that Shikonin can serve as a potential agent for human melanoma therapy. ARTICLE HISTORY

Abstract-There is a growing interest in the use of renewable energy sources to power wireless networks in order to mitigate the detrimental effects of conventional energy production or to enable deployment in off-grid locations. However, renewable energy sources, such as solar and wind, are by nature unstable in their availability and capacity. The dynamics of energy supply hence impose new challenges for network planning and resource management. In this paper, the sustainable performance of a wireless mesh network powered by renewable energy sources is studied. To address the intermittently available capacity of the energy supply, adaptive resource management and admission control schemes are proposed. Specifically, the goal is to maximize the energy sustainability of the network, or equivalently, to minimize the failure probability that the mesh access points (APs) deplete their energy and go out of service due to the unreliable energy supply. To this end, the energy buffer of a mesh AP is modeled as a G/G/1(/N ) queue with arbitrary patterns of energy charging and discharging. Diffusion approximation is applied to analyze the transient evolution of the queue length and the energy depletion duration. Based on the analysis, an adaptive resource management scheme is proposed to balance traffic loads across the mesh network according to the energy adequacy at different mesh APs. A distributed admission control strategy to guarantee high resource utilization and to improve energy sustainability is presented. By considering the first and second order statistics of the energy charging and discharging processes at each mesh AP, it is demonstrated that the proposed schemes outperform some existing state-of-the-art solutions.Index Terms-Energy sustainability, resource management, wireless mesh networks, renewable energy supply.