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61.
Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewisx has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewisx and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.  相似文献   
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Glyco‐mimicking nanoparticles (glyco‐NPs) with Förster resonance energy transfer (FRET) donor and acceptor groups formed via dynamic covalent bond of benzoboroxole and sugar from two complementary polymers are prepared. The glyco‐NPs are proved to be quite stable under physiological conditions but sensitive to pH. So the glyco‐NPs can be internalized by dendritic cells with integrity and nontoxicity and then dissociate within the acidic organelles. This particle dissociation is directly observed and visualized in vitro, for the first time via the FRET measurements and fluorescent microscopy. This feature makes controlled release of drug or protein by glyco‐NPs possible, i.e., when model antigen Ovalbumin is loaded in the glyco‐NPs, the released Ovalbumin in dendritic cells stimulates T cells more efficiently than the free Ovalbumin itself as a result of the enhanced antigen processing and presentation. Thus, the results enlighten a bright future of the glyco‐NPs in immunotherapy.  相似文献   
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The extensive research interests in environmental temperature can be linked to human productivity / performance as well as comfort and health; while the mechanisms of physiological indices responding to temperature variations remain incompletely understood. This study adopted a physiological sensory nerve conduction velocity (SCV) as a temperature‐sensitive biomarker to explore the thermoregulatory mechanisms of human responding to annual temperatures. The measurements of subjects’ SCV (over 600 samples) were conducted in a naturally ventilated environment over all four seasons. The results showed a positive correlation between SCV and annual temperatures and a Boltzmann model was adopted to depict the S‐shaped trend of SCV with operative temperatures from 5°C to 40°C. The SCV increased linearly with operative temperatures from 14.28°C to 20.5°C and responded sensitively for 10.19°C‐24.59°C, while tended to be stable beyond that. The subjects’ thermal sensations were linearly related to SCV, elaborating the relation between human physiological regulations and subjective thermal perception variations. The findings reveal the body SCV regulatory characteristics in different operative temperature intervals, thereby giving a deeper insight into human autonomic thermoregulation and benefiting for built environment designs, meantime minimizing the temperature‐invoked risks to human health and well‐being.  相似文献   
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Geosynthetic clay liners (GCLs), which have a very low permeability to water and a considerably high self-healing capacity, are widely used in liner systems of landfills. In this study, a series of experimental tests were carried out under complex conditions on typical commercial GCLs from China. In particular, the effects of pH values and lead ions (Pb2+) were tested in addition to other factors. The swelling properties of natural bentonite encapsulated between geotextile components in the GCLs were tested first. The swelling capacity was reduced rapidly at pH values < 3 and concentrations of Pb2+ >40 mM. Permeability tests on GCLs with different concentrations of lead ions were then performed by using the self-developed multi-link flexible wall permeameter, and data showed that increases in lead ion concentrations greatly improved the permeability. Finally, self-healing capacity tests were conducted on needle-punched GCLs under different levels of damage. Results showed that the GCLs have a good self-healing capacity with small diameter damage holes (2 mm, close to three times the original aperture), but with a damage aperture larger than 15% of the sample area, the self-healing capacity could not prevent leakage; hence, in certain situations it will be necessary to repair the damage to meet the anti-seepage requirement.  相似文献   
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The construction of nonlinear optical materials featuring asymmetric transmission of light is of great technological importance for various applications, including optical switching and optical power limiting. A significant challenge is the scalable fabrication of material candidates with good photochemical stability, high optical transmittance, and excellent optical limiting performance. Here, we present a nanocrystallization avenue for constructing hybrid optical limiting materials that exhibit ultrafast and robust optical limiting performance. The experimental results show that the controllable relaxation of a niobate glass may lead to the clustering of Nb-O units and contracting of the bandgap. It results in the notable improvement in nonlinear optical properties, including the enhanced saturation irradiance (380 GW/cm2), doubly increased nonlinear coefficient, and decreased limiting threshold (200 GW/cm2). Our results suggest a promising material that exhibits promising applications for protecting eyes and sensitive components from laser-induced damage.  相似文献   
70.
Microwave lignite drying with assistance of biomass-derived char was addressed and effect of bio-char on drying rate and energy consumption was investigated in this work. Effective diffusion coefficient and activation energy for the drying process were also analyzed. The results indicated the drying process was largely dependent on the variation of sample temperature. Bio-char originated from pine wood was most favorable for lignite drying, considering its better promoting effect and advanced security. There existed an optimal bio-char addition ratio for drying process at different power. The corresponding optimal ratio was 10% at 231?W and 15% at 385?W, at which the biggest drying rate and the least energy consumption were reached. It was compared lignite drying initiated at 385?W was better for energy conservation. Effective diffusivity was improved and activation energy was simultaneously reduced, with the addition of bio-char. The minimum activation energy was 15.54?W?·?g?1, which was gained at bio-char addition ratio of 10%. The results revealed the effect of bio-char on depressing activation energy could rival that of metal-based additives. The drying process with assistance of microwave and bio-char could present technical and economical benefits on lignite upgrading.  相似文献   
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