Our findings provide direct in vitro and in vivo evidence for spreading of β-amyloid through neuronal connections, and suggest possible therapeutic approaches to blocking this spread.
Thermoresponsive polymers that are pH tunable were successfully synthesized by a combination of atom transfer radical polymerization (ATRP) and Cu(I)-catalyzed 1,3-dipolar cycloaddition of azide and alkynes (click chemistry). ATRP was employed to synthesize poly(2-hydroxyethyl methacrylate) (PHEMA), followed by introduction of alkyne groups using pentynoic acid, leading to PHEMA-alkyne. 2-Azidoethylamine, 2-azido-N,N-dimethylethylamine, and 2-azido-N,N-diethylethylamine were added to the PHEMA-alkyne backbone via click chemistry. Molecular weight, molecular weight distribution, and click reaction efficiency were determined by gel permeation chromatography (GPC) and 1H NMR spectroscopy. The average molecular weight (M
n) of the resulting polymers ranged from 5.6 × 104 to 7.0 × 104 depending on the molecular architecture. The molecular weight distribution was low (M
n/M
n = 1.25−1.35). The transmission spectra of the 0.1 wt % aqueous solutions of the resulting polymers with different pH values at 650 nm were measured as a function of temperature. Results showed that the lower critical solution temperature (LCST) could be dramatically affected by solution pH. To give additional evidence for pH-responsive thermal transition, in-situ temperature-dependent 1H NMR measurements in deuterated water (0.01 wt %) were conducted. The LCST values measured by in-situ 1H NMR correlated well with those determined by turbidimetry.
Considering the increase in antibiotic-resistant microorganisms related to SBP, measures to prevent the in-hospital spread of resistant strains and the indiscriminate use of antibiotics should be instituted more stringently.
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