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.