In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.
The mammalian innate immune system retains from Drosophila a family of homologous Toll-like receptors (TLRs) that mediate responses to microbial ligands. Here, we show that TLR2 activation leads to killing of intracellular Mycobacterium tuberculosis in both mouse and human macrophages, through distinct mechanisms. In mouse macrophages, bacterial lipoprotein activation of TLR2 leads to a nitric oxide-dependent killing of intracellular tubercle bacilli, but in human monocytes and alveolar macrophages, this pathway was nitric oxide-independent. Thus, mammalian TLRs respond (as Drosophila Toll receptors do) to microbial ligands and also have the ability to activate antimicrobial effector pathways at the site of infection.
EBV in patients with homogeneous emphysema without collateral ventilation results in clinically meaningful benefits of improved lung function, exercise tolerance, and quality of life.
One-way endobronchial valves (EBVs) have been shown to relieve symptoms of emphysema, particularly in patients without collateral ventilation (CV) between the target and adjacent lobes. In this study, we investigated the ability of the bronchoscopic Chartis TM Pulmonary Assessment System to predict treatment response by determining the presence of CV.80 EBV patients underwent a pre-treatment Chartis assessment. Before and 30 days after implantation, high-resolution computed tomography scans were taken to determine target lobe volume reduction (TLVR). A pre-to post-treatment reduction of o350 mL was defined as significant. In addition, clinical outcomes (forced expiratory volume in 1 s (FEV1), 6-min walk test and St George's Respiratory Questionnaire) were compared over the same time period.Of the 51 patients classified as having an absence of CV according to their Chartis reading, 36 showed a TLVR o350 mL. 29 patients were classified as having CV, and of these 24 did not meet this TLVR cut-off. Chartis showed an accuracy level of 75% in predicting whether or not the TLVR cut-off would be reached. Those predicted to respond showed significantly greater TLVR (p,0.0001) and FEV1 improvement (p50.0013) than those predicted not to respond.Chartis is a safe and effective method of predicting response to EBV treatment.
Summary: Vinylphosphonic acid is polymerized at 80 °C by free radical polymerization to give a high‐molecular‐weight polymer ($\overline M _{\rm w}$ of 6.2 × 104) as determined by static light scattering. High‐resolution NMR spectroscopy is used to gain microstructure information. Information based on tetrad probabilities is utilized to deduce an almost atactic configuration. In addition, 13C NMR spectroscopy gives evidence for the presence of head‐to‐head and tail‐to‐tail links. Refined analysis of the 1H NMR spectra allows for the quantitative determination of the fraction of these links (23.5% of all links). Experimental evidence suggests that the polymerization proceeds via cyclopolymerization of the vinylphosphonic acid anhydride as an intermediate. Titration curves indicate that high‐molecular‐weight poly(vinylphosphonic acid) PVPA behaves as a monoprotic acid.Radical polymerization of vinylphosphonic acid proceeds by cyclopolymerization of its anhydride.magnified imageRadical polymerization of vinylphosphonic acid proceeds by cyclopolymerization of its anhydride.
Porous polymers [1] with porosity at the nanoscale have attracted tremendous attention since their porous features are associated with prominent physical properties and since they have potential applications in, for example, light harvesting, [2] sensing, [3] gas separation [4] and storage, [5] catalysis, [6] and energy storage and conversion. [7] There are several classes of micro-/mesoporous polymers, such as hyper-crosslinked polymers (HCPs), polymers of intrinsic microporosity (PIMs), and covalent organic frameworks (COFs). Porous polymers can be also classified according to their structural conformations as amorphous-(HCPs and PIMs) or crystalline-type (COFs) materials. [1e] Conjugated microporous polymers (CMPs) represent one of the fastest developing types of porous materials not only because of their efficient synthesis by conventional metal-catalyzed polymerization techniques and the availability of a large number of commercially available functional monomers but also due to their controllable and adaptable physical properties. [1d] Unlike COFs, CMPs are formed under kinetic control, and thus are amorphous and show no longrange structural order. [8] For this reason, most of the previous work on CMPs has been focused on developing new chemical strategies and tuning the pore size distribution and surface area of these polymers by varying the length of the organic linkers rather than through morphology control. Very recently, efforts have been made to synthesize CMPs with controlled nanostructures, such as quasi-zero-dimensional microspheres, [9] and one-dimensional nanofibers [10] and nanotubes [11] as well as three-dimensional monoliths. [12] However, the synthesis of porous polymers with two-dimensional (2D) sheet structures remains little explored. Dichtel et al. employed a solvothermal method to grow oriented 2D COF thin films on substrate-supported graphene by the dynamic assembly of boronic acid and hexahydroxytriphenylene monomers, [13] but the large-scale production of free-standing 2D porous polymer networks has not yet been achieved.Graphene, because of its single-atom thickness, large aspect ratio, high surface area, and many intriguing physical properties, has proved to be a promising template for the highly efficient construction of 2D porous nanohybrid materials, such as 2D porous silica, [14] metal oxides, [15] metal sulfides, [16] carbon nitride, [17] and carbon-coated graphene/ metal oxide sheets. [18] All these approaches typically rely on the use of a graphene-based porous silica template in nanocasting technology or the nucleation of metal oxide or sulfide nanostructures on the graphene surface. Nevertheless, the porous structures of these graphene-based hybrid materials cannot be tailored at the molecular level, as has been done for organic porous materials. [1] We report herein on a graphene-inspired synthetic approach to the large-scale production of 2D sandwichlike conjugated microporous polymers in which each graphene sheet is fully separated by a porous polymer shell. Thiophene...
The ability to pattern functional moieties with well-defined architectures is highly important in material science, nanotechnology and bioengineering. Although two-dimensional surfaces can serve as attractive platforms, direct patterning them in solution with regular arrays remains a major challenge. Here we develop a versatile route to pattern two-dimensional free-standing surfaces in a controlled manner assisted by monomicelle close-packing assembly of block copolymers, which is unambiguously revealed by direct visual observation. This strategy allows for bottom-up patterning of polypyrrole and polyaniline with adjustable mesopores on various functional free-standing surfaces, including two-dimensional graphene, molybdenum sulfide, titania nanosheets and even on one-dimensional carbon nanotubes. As exemplified by graphene oxide-based mesoporous polypyrrole nanosheets, the unique sandwich structure with adjustable pore sizes (5–20 nm) and thickness (35–45 nm) as well as enlarged specific surface area (85 m2 g−1) provides excellent specific capacitance and rate performance for supercapacitors. Therefore, this approach will shed light on developing solution-based soft patterning of given interfaces towards bespoke functions.
We report a novel red-light-responsive supramolecule. The tetra-ortho-methoxy-substituted azobenzene (mAzo) and β-cyclodextrin (β-CD) spontaneously formed a supramolecular complex. The substituted methoxy groups shifted the responsive wavelength of the azo group to the red light region, which is in the therapeutic window and desirable for biomedical applications. Red light induced the isomerization of mAzo and the disassembly of the mAzo/β-CD supramolecular complex. We synthesized a mAzo-functionalized polymer and a β-CD-functionalized polymer. Mixing the two polymers in an aqueous solution generated a supramolecular hydrogel. Red light irradiation induced a gel-to-sol transition as a result of the disassembly of the mAzo/β-CD complexes. Proteins were loaded in the hydrogel. Red light could control protein release from the hydrogel in tissue due to its deep penetration depth in tissue. We envision the use of red-light-responsive supramolecules for deep-tissue biomedical applications.
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