Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical ...challenges. Here we design and synthesize a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2' position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX remains stable and inactive in the circulation. NucA facilitates the uptake of the conjugated PTX specifically in tumor cells. Once inside cells, the dipeptide bond linker of NucA-PTX is cleaved by cathepsin B and then the conjugated PTX is released for action. The NucA modification assists the selective accumulation of the conjugated PTX in ovarian tumor tissue rather than normal tissues, and subsequently resulting in notably improved antitumor activity and reduced toxicity.
The performance of proton exchange membrane fuel cell (PEMFC) is greatly influenced by the characteristics of gas diffusion layer (GDL). Herein, in situ grown carbon nanotubes (CNTs) on carbon paper ...as a gas diffusion layer (GDL) were fabricated by a plasma-enhanced chemical vapor deposition (PECVD) process. Fuel cells using CNT-based GDLs with nickel (II) nitrate loading of 1.6 mg cm−2 show better performance compared with the GDLs which employ Vulcan XC-72 as the MPL. The pore size distribution and the gas permeability results revealed that the increasing density of CNT layer had two main effects on the pore structure of GDL: firstly, the increasing density of CNT layer decreased the macro pore volume and the open through pore volume of CNT-based GDL; secondly, the increasing density of CNT layer decreased the micro pore diameter of CNT-based GDL. The data obtained from the vapor permeability and the fuel cell performance tests indicated that the water flooding can be reduced by applying CNT-based GDLs. The electrochemical impedance spectroscopy (EIS) confirmed that the CNT-based GDL can effectively promote the mass transfer in the FCs which was attributed to its suitable hydrophobicity and proper structure.
•The GDL with in-situ grown CNTs on the fibrous carbon paper is fabricated.•A CNT/GDL with proper hydrophobicity and pore structure is obtained.•PEMFC with CNT/GDL shows better performance than the one with CB/GDL.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Osteosarcoma (OS) is a bone cancer mostly occurring in pediatric population. Current treatment regime of surgery and intensive chemotherapy could cure about 60%-75% patients with primary ...osteosarcoma, however only 15% to 30% can be cured when pulmonary metastasis or relapse has taken place. Hence, novel precise OS-targeting therapies are being developed with the hope of addressing this issue. This review summarizes the current development of molecular mechanisms and targets for osteosarcoma. Therapies that target these mechanisms with updated information on clinical trials are also reviewed. Meanwhile, we further discuss novel therapeutic targets and OS-targeting drug delivery systems. In conclusion, a full insight in OS pathogenesis and OS-targeting strategies would help us explore novel targeted therapies for metastatic osteosarcoma.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The introduction of a new type of intelligent Outlast textile fabric is applied in top grade casual coat and children's coat. In this paper, the authors discuss the designing, developing, weaving, ...dyeing and finishing, and production. Also, to perform test on this kind of intelligent fabric temperature adjustment function, the authors can adopt test method like "warm model test", and "human being group test" in laboratory.
In contrast to Langerhans cells, which make interleukin (IL)-12, differentiated macrophages that infiltrate the epidermis 72 h after ultraviolet B (UV) irradiation potently produce IL-10 mRNA and ...secrete IL-10 protein. We asked whether differentiated UV macrophages in the epidermis acquired their activated, IL-10hi status as a result of entering the epidermis or as a result of encountering UV-induced changes in the dermal microenvironment. In this study, sequential section immunostaining directly showed dynamic and reciprocal changes of infiltrating CD11b+ macrophages and CD1a+ Langerhans cell loss in human epidermis and dermis after in vivo UV exposure in relation to the microanatomic localization of newly appearing dermal cells that stain for IL-10 mRNA by in situ hybridization. Using quantitative reverse transcriptase polymerase chain reaction on purified dermal cell subsets, the first significant rise in IL-10 mRNA occurred 6 h after UV in the dermal CD11b+ (CD1–, 3–, 24–, 56–) monocytic/macrophagic population. Significant induction of IL-10 mRNA 24 h post-UV was limited to the CD11b+ CD1– subset (p = 0.006). The fold increase of IL-10 mRNA relative to 0 h by the CD11b+ dermal monocytic/macrophagic population peaked at 24–48 h and tapered thereafter. Intense IL-10 production by macrophages in the epidermis appeared to follow dermal changes, with maximum production at 72 h, indicating migration/activation of this population from the dermis, and the remainder of dermal cells, depleted of monocyte/macrophages and Langerhans cell-like antigen-presenting cells, showed no increase in IL-10 at any time point post-UV. IL-10 protein-producing CD11b+ macrophages in the dermis were also documented by flow cytometry. IL-12 mRNA was differentially regulated from IL-10 after UV, in that IL-12 was consistently downregulated in the CD11b+ monocytic/macrophagic population (p < 0.0002). Taken together, monocytic/macrophagic cells with high IL-10 and low IL-12 expression initially appear in the dermis as early as 6 h, and then appear in the epidermis, implicating the dermis as the primary site of activation/signaling for IL-10 upregulation in cutaneous antigen-presenting cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The effect of mass transport on the growth characteristics of large-area vapor-grown carbon nanofibers (CNFs) was investigated by adjusting the substrate deposition angle (α). The catalyst precursor ...solution was coated onto one side of a 2D porous carbon paper substrate via a decal printing method. The results showed that the CNFs were grown on only one side of the substrate and α was found to significantly affect the growth uniformity. At α = 0°, the growth thickness, the density, the microstructure and the yield of the CNF film were uniform across the substrate surface, whereas the growth uniformity decreased with increasing α, suggesting that the large-area CNF deposition processes were mass-transport-controlled. Computational fluid dynamics simulations of the gas diffusion processes revealed the homogeneous distributions of the carbon-source-gas concentration, pressure, and velocity near the substrate surface at α = 0°, which were the important factors in achieving the mass-transport-limited uniform CNF growth. The homogeneity of the field distributions decreased with increasing α, in accordance with the variation in the growth uniformity with α. When used as a micro-porous layer, the uniform CNF film enabled higher proton exchange membrane fuel cell performance in comparison with commercial carbon black by virtue of its improved electronic and mass-transport properties confirmed by the electrochemical impedance spectroscopy results.
CD11b+ monocytic/macrophagic cells (Mo/Mph), which infiltrate into skin after UV irradiation, play an important role in UV-induced immunosuppression. Because in mice, blockade of CD11b (iC3b ...receptor) on monocytes and depletion of its ligand, iC3b, reverses UV-induced immunosuppression, we asked whether iC3b is deposited in human skin after UV, and whether iC3b can modulate the cytokine profile of Mo/Mph. Immunofluorescence studies revealed that iC3b was newly deposited in UV-exposed skin and was localized in apposition to infiltrating CD11b+ Mo/Mph. In addition, in situ hybridization studies showed that TNF-alpha mRNA was also induced in a similar microanatomic localization. To model the effects of these complex signals on infiltrating Mo/Mph following UV exposure, we then tested the effects of immobilized iC3b and TNF-alpha on resting blood monocytes. Both IL-10 mRNA synthesis and protein secretion were significantly induced by binding of iC3b in vitro and were synergistically increased by the presence of TNF-alpha. The effect was abrogated by a blocking Ab to CD11b, indicating CD11b-iC3b interaction. In contrast, iC3b binding resulted in suppression of IL-12 p40 mRNA and significantly inhibited the production of IL-12 p70 protein. Our studies thus define a novel mechanism for induction of tissue Mo/Mph into an IL-10high/IL-12low state via iC3b in combination with TNF-alpha.
The effect of mass transport on the growth characteristics of large-area vapor-grown carbon nanofibers (CNFs) was investigated by adjusting the substrate deposition angle (
α
). The catalyst ...precursor solution was coated onto one side of a 2D porous carbon paper substrate
via
a decal printing method. The results showed that the CNFs were grown on only one side of the substrate and
α
was found to significantly affect the growth uniformity. At
α
= 0°, the growth thickness, the density, the microstructure and the yield of the CNF film were uniform across the substrate surface, whereas the growth uniformity decreased with increasing
α
, suggesting that the large-area CNF deposition processes were mass-transport-controlled. Computational fluid dynamics simulations of the gas diffusion processes revealed the homogeneous distributions of the carbon-source-gas concentration, pressure, and velocity near the substrate surface at
α
= 0°, which were the important factors in achieving the mass-transport-limited uniform CNF growth. The homogeneity of the field distributions decreased with increasing
α
, in accordance with the variation in the growth uniformity with
α
. When used as a micro-porous layer, the uniform CNF film enabled higher proton exchange membrane fuel cell performance in comparison with commercial carbon black by virtue of its improved electronic and mass-transport properties confirmed by the electrochemical impedance spectroscopy results.
Large-area carbon nanofibers, deposited by adjusting the deposition angle and on one side of carbon paper, improved fuel cell performance.
The extracellular matrix protein, Fn, has critical functions in cell attachment, migration, differentiation, and proliferation. We have previously shown that fibronectin (Fn) is abnormally expressed ...and potentiates entry into the cell cycle of basal keratinocytes in uninvolved psoriatic skin, in combination with T cell lymphokines. It is not known what type of Fn is present in psoriatic skin, however, and how this Fn may regulate signaling. Embryonic forms of cellular Fn containing extra domains, designated EDA and EDB, are generated by alternative splicing and are seen in proliferating, developing tissue and in wound healing. Because the EDA segment enhances the integrin binding sequence Arg, Gly, Asp (RGD), which, when present, has been shown to be critical in integrin–extracellular matrix signaling, we were particularly interested in determining whether or not EDA-containing Fn (EDA+Fn) represented the aberrantly expressed Fn in psoriasis. Increased EDA+ Fn protein was demonstrated by immunostaining at the dermal–epidermal junction in clinically uninvolved skin from six of six patients with psoriasis, but not in skin from control subjects. Using reverse transcription polymerase chain reaction an increased ratio of EDA+ Fn versus EDA− Fn mRNA was present in epidermal samples from psoriatic but not control individuals. Interestingly, the EDA+Fn in the psoriatic epidermis had the IIICS region spliced out (EDA+, FDB−, IIICS−, III9+), which was shared with normal epidermis (EDA−, EDB−, IIICS−, III9+). These results suggest a selective predominance of the EDA+ Fn isoform at the dermal–epidermal junction of psoriatic skin. The consistent aberrant localization of EDA+ Fn at the dermal–epidermal junction in uninvolved skin of psoriatics may confer the hyperresponsiveness of psoriatic uninvolved basal keratinocytes for rapid cellular proliferation in response to T cell signals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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