The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses. 相似文献
Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major components of the glycocalyx. The secreted GAG and CD44 ligand hyaluronic acid (HA), and the cell surface PG syndecan-1 (Sdc-1) modulate the expression and activity of cytokines, chemokines, growth factors, and adhesion molecules, acting as critical regulators of tumor cell behavior. Here, we studied the effect of Sdc-1 siRNA depletion and HA treatment on hallmark processes of cancer in breast cancer cell lines of different levels of aggressiveness. We analyzed HA synthesis, and parameters relevant to tumor progression, including the stem cell phenotype, Wnt signaling constituents, cell cycle progression and apoptosis, and angiogenic markers in luminal MCF-7 and triple-negative MDA-MB-231 cells. Sdc-1 knockdown enhanced HAS-2 synthesis and HA binding in MCF-7, but not in MDA-MB-231 cells. Sdc-1-depleted MDA-MB-231 cells showed a reduced CD24-/CD44+ population. Furthermore, Sdc-1 depletion was associated with survival signals in both cell lines, affecting cell cycle progression and apoptosis evasion. These changes were linked to the altered expression of KLF4, MSI2, and miR-10b and differential changes in Erk, Akt, and PTEN signaling. We conclude that Sdc-1 knockdown differentially affects HA metabolism in luminal and triple-negative breast cancer model cell lines and impacts the stem phenotype, cell survival, and angiogenic factors. 相似文献
Metallurgical and Materials Transactions A - A high $$\gamma ^{\prime }$$ volume fraction CoNi-base superalloy with roughly equal amounts of cobalt and nickel was successfully processed through... 相似文献
Pyrolysis in air at 800°C of [{NP(OC12H10)}0.6{NP(OC6H4PPh2·(π-CH3C5H4)−Mn(CO)2)2}0.4]n (1) in the solid state affords product 2 containing nanoclusters of Mn2P2O7 with sizes ranging from 50 to 90 nm and averaging about 74 nm. The egg-shape of the unpyrolyzed organometallic polymer is
retained but with increased particle size after pyrolysis. The pyrolytic material shows near-infrared photoluminescence attributed
to the emission of tetrahedral Mn2+ embedded in a matrix of Mn2P2O7. The solid-state pyrolysis of organometallic derivatives of polyphosphazenes may be a useful and general route to nano-structured
Mn2P2O7.
An erratum to this article can be found at 相似文献
CoMo and NiMo supported Al2O3 catalysts have been investigated for hydrotreating of model molecule as well as industrial feedstock. Activity studies were carried out for thiophene and SRGO hydrodesulfurization (HDS) in an atmospheric pressure and batch reactor respectively. These activities on sulfided catalysts were evaluated as a function of promoter content [M/(M + Mo) = 0.30, 0.34, 0.39; M = Co or Ni] using fixed (ca. 8 wt.%) molybdenum content. The promoted catalysts were characterized by textural properties, XRD, and temperature programmed reduction (TPR). TPR spectra of the Co and Ni promoter catalysts showed that Ni promotes the easy reduction of Mo species compared with Co. With the variation of promoter content NiMo catalyst was found to be superior to CoMo catalyst for gas oil HDS, while at low-promoter content the opposite trend was observed for HDS of thiophene. The behavior was attributed to the several reaction mechanisms involved for gas oil HDS. A nice relationship was obtained for hydrodesulfurized gas oil refractive index (RI) and aromatic content, which corresponds to the Ni hydrogenation property. 相似文献
The evaluation of the microbiological charge present in Costa Rican samples as the evaluation of its antimicrobial activity over different microorganisms, including those associated to wound infections, will allow to emit criteria referred to its use in therapeutic treatments, specially as alternative therapy for cases involving antibiotic resistant bacteria. The microbiological charge of 25 honey samples, acquired in Costa Rican markets was evaluated through several indicators including total plate aerobic count, total plate anaerobic count, total aerobic spore count, total anaerobic spore count and molds and yeast count. Also, samples were inoculated in tubes with chopped meat media and plated in egg yolk agar in order to determine the presence of Clostridium botulinum. For the antimicrobial activity evaluation, the diffusion method in Muller Hinton agar was performed, testing different honey concentrations (100, 75, 50, 25, 12,5 and 6,25 % v/v) against Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (UCR 2902), Pseudomonas aeruginosa (ATCC 9027), Escherichia coli (ATCC25922), Salmonella enteritidis (ATCC 13076), Listeria monocytogenes (ATCC 19116) and Aspergillus niger. The results obtained for the microbiological characterization of honey show that 91% of samples had counts equal or lower than 1,0 x 10(1) CFU/g. No positive result was obtained for the isolation of C. botulinum. 24 of the samples analyzed inhibited the growth of S. aureus even in a 25% v/v concentration, nevertheless, A. niger was no inhibited by any of the samples tested. 相似文献
A novel gene fusion system to express and purify small recombinantproteins in Escherichia coli has been constructed. The conceptallows for affinity purification of soluble gene products bysequential albumin- and Zn2+-affinity chromatography. The dual-affinitysystem is well suited for expression of unstable proteins asonly full-length protein is obtained after purification andproteins gain proteolytic stability in the fusion protein. Herewe show that the dual-affinity approach can be used for theexpression of various unstable derivatives of a single IgG-bindingdomain based on staphylococcal protein A. Analysis of the proteolyticstabilities and the IgG-binding properties of the differentmutant proteins suggest that the model for the structure ofan IgG-binding domain must be re-evaluated. 相似文献
For an autonomous system to perform maintenance tasks in a networking device or a radio base station (RBS), it has to deal with a series of technological challenges ranging from identifying hardware-related problems to manipulating connectors. This paper describes the development of a robot maintenance system dedicated to detect and resolve faulty links caused by unplugged or poorly connected cables. Although the maintenance system relies on four subsystems, we significantly focus on our low-cost and efficient custom gripper solution developed to handle RJ45 Ethernet connectors. To examine our gripper, we conducted three experiments. First, a qualitative questionnaire was submitted to 30 users in the case of the teleoperated scenario of the gripper attached to a robotic arm. Similarly, we also tested the automatic operation mode. The results showed that our system is reliable and delivers a highly efficient maintenance tool in both teleoperated and autonomous operation modes. The practical experiment containing the removal or unplugging of connectors demonstrated our gripper’s ability to adequately handle these, whereas the feedback from the questionnaire pointed to a positive user experience. The automatic test assessed the gripper’s robustness against the continuous operation.
The electric discharge across a varistor granule filled air gap under a fast-rising voltage pulse was investigated for surge protection applications. The effects of temperature and pressure on the arc and the electrical conduction were analyzed by the characteristic changes in voltage waveforms triggered by a fast-rising high voltage pulse. In addition to the gap size, experimental results show that competing mechanisms among arc conduction, conduction through the varistor granule network, thermionic emission from Joule heating at granule-to-granule contact points, and the magnitude of the switching voltage dictate the maximum surge protection voltage for the filled air gap. Experimental evidence indicated that accumulated degradation was created at small contact points between varistor granules by repetitive assaults from longer duration, high voltage pulses. The uniqueness of using varistor over other dielectric granules in an air gap for surge protection is identified and discussed. 相似文献