Extracellular lysophosphatidate （LPA） is a potent bioactive lipid that signals through six G-protein-coupled receptors. This signaling is required for embryogenesis, tissue repair and remodeling processes. LPA is pr...Extracellular lysophosphatidate （LPA） is a potent bioactive lipid that signals through six G-protein-coupled receptors. This signaling is required for embryogenesis, tissue repair and remodeling processes. LPA is produced from circulating lysophosphatidylcholine by autotaxin （ATX）, and is degraded outside cells by a family of three enzymes called the lipid phosphate phosphatases （LPPs）. In many pathological conditions, particularly in cancers, LPA concentrations are increased due to high ATX expression and low LPP activity. In cancers, LPA signaling drives tumor growth, angiogenesis, metastasis, resistance to chemotherapy and decreased efficacy of radiotherapy. Hence, targeting the ATX-LPA-LPP axis is an attractive strategy for introducing novel adjuvant therapeutic options. In this review, we will summarize current progress in targeting the ATX-LPA-LPP axis with inhibitors of autotaxin activity, LPA receptor antagonists, LPA monoclonal antibodies, and increasing low LPP expression. Some of these agents are already in clinical trials and have applications beyond cancer, including chronic inflammatory diseases.展开更多
We propose and demonstrate single fiber dual-functionality optical tweezers based on a graded-index multimode fiber. By using the multi-angle fiber grinding and polishing technology, we fabricate the multimode fiber t...We propose and demonstrate single fiber dual-functionality optical tweezers based on a graded-index multimode fiber. By using the multi-angle fiber grinding and polishing technology, we fabricate the multimode fiber tip to be a special tapered shape, contributing to focus the outgoing beam with a large intensity gradient for the first functionality--three-dimensional contactless trapping of a microparticle. By adjusting the radial direction offset between the lead-in single mode fiber and the graded-index multimode fiber, we perform the second functionality--axial shift of the trapped microparticle with respect to the fiber tip without need of moving the fiber probe itself. It is convenient for practical applications, The theoretical and experimental results about the relationship between the radial offset and the equilibrium positions of the microparticle have the good consistency. Tailoring the trap and axial shift of the microparticle based on the graded-index multimode fiber provides convenient avenues for fiber optical tweezers a~）Dlied in practical researches.展开更多
基金supported by grants from the CBCF, CIHR with WCHRI,and Ono Pharmaceuticals Ltd.
文摘Extracellular lysophosphatidate （LPA） is a potent bioactive lipid that signals through six G-protein-coupled receptors. This signaling is required for embryogenesis, tissue repair and remodeling processes. LPA is produced from circulating lysophosphatidylcholine by autotaxin （ATX）, and is degraded outside cells by a family of three enzymes called the lipid phosphate phosphatases （LPPs）. In many pathological conditions, particularly in cancers, LPA concentrations are increased due to high ATX expression and low LPP activity. In cancers, LPA signaling drives tumor growth, angiogenesis, metastasis, resistance to chemotherapy and decreased efficacy of radiotherapy. Hence, targeting the ATX-LPA-LPP axis is an attractive strategy for introducing novel adjuvant therapeutic options. In this review, we will summarize current progress in targeting the ATX-LPA-LPP axis with inhibitors of autotaxin activity, LPA receptor antagonists, LPA monoclonal antibodies, and increasing low LPP expression. Some of these agents are already in clinical trials and have applications beyond cancer, including chronic inflammatory diseases.
基金supported by the National Natural Science Foundation of China(Nos.11574061,61405043,and 61675053)the 111 Project(No.B13015)the Fundamental Research Funds for Harbin Engineering University of China
文摘We propose and demonstrate single fiber dual-functionality optical tweezers based on a graded-index multimode fiber. By using the multi-angle fiber grinding and polishing technology, we fabricate the multimode fiber tip to be a special tapered shape, contributing to focus the outgoing beam with a large intensity gradient for the first functionality--three-dimensional contactless trapping of a microparticle. By adjusting the radial direction offset between the lead-in single mode fiber and the graded-index multimode fiber, we perform the second functionality--axial shift of the trapped microparticle with respect to the fiber tip without need of moving the fiber probe itself. It is convenient for practical applications, The theoretical and experimental results about the relationship between the radial offset and the equilibrium positions of the microparticle have the good consistency. Tailoring the trap and axial shift of the microparticle based on the graded-index multimode fiber provides convenient avenues for fiber optical tweezers a~）Dlied in practical researches.
