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Abstract Amyloid-β (Aβ) peptide aggregation plays a central role in the progress of Alzheimer’s disease (AD), of which Aβ-deposited extracellular amyloid plaques are a major hallmark. The brain micro-environmental variation in AD patients, like local acidification, increased ionic strength, or changed metal ion levels, cooperatively modulates the aggregation of the Aβ peptides. Here, we investigate the multivariate effects of varied pH, ionic strength and Zn 2+ on Aβ 40 fibrillation kinetics. Our results reveal that Aβ fibrillation kinetics are strongly affected by pH and ionic strength suggesting the importance of electrostatic interactions in regulating Aβ 40 fibrillation. More interestingly, the presence of Zn 2+ ions can further alter or even reserve the role of pH and ionic strength on the amyloid fibril kinetics, suggesting the importance of amino acids like Histidine that can interact with Zn 2+ ions. Both pH and ionic strength regulate the secondary nucleation processes, however regardless of pH and Zn 2+ ions, ionic strength can also modulate the morphology of Aβ 40 aggregates. These multivariate effects in bulk solution provide insights into the correlation of pH-, ionic strength- or Zn 2+ ions changes with amyloid deposits in AD brain and will deepen our understanding of the molecular pathology in the local brain microenvironment.more » « less
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One key objective in electrocatalysis is to design selective catalysts, particularly in cases where the desired products require thermodynamically unfavorable pathways. Electrochemical synthesis of hydrogen peroxide (H 2 O 2 ) via the two-electron water oxidation reaction (2e − WOR) requires a +0.54 V higher potential than four-electron O 2 evolution. So far, best-performing electrocatalysts require considerable overpotentials before reaching peak faradaic efficiency. We present Mn-alloyed TiO 2 coatings prepared by atomic layer deposition (ALD) and annealing as a stable and selective electrocatalyst for 2e − WOR. Faradaic efficiency of >90% at < 150 mV overpotentials was achieved for H 2 O 2 production, accumulating 2.97 mM H 2 O 2 after 8 hours. Nanoscale mixing of Mn 2 O 3 and TiO 2 resulted in a partially filled, highly conductive Mn 3+ intermediate band (IB) within the TiO 2 mid-gap to transport charge across the (Ti,Mn)O x coating. This IB energetically matched that of H 2 O 2 -producing surface intermediates, turning a wide bandgap oxide into a selective electrocatalyst capable of operating in the dark. However, the high selectivity is limited to the low overpotential regime, which limits the system to low current densities and requires further research into increasing turn-over frequency per active site.more » « less
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Abstract Small‐molecule drugs are used extensively in clinics for cancer treatment; however, many antitumor chemical drugs dissolve poorly in aqueous solution. Their poor solubility and nonselective delivery in vivo often cause severe side effects. Here, the application of RNA nanotechnology to enhance the solubility of hydrophobic drugs, using camptothecin (CPT) for proof‐of‐concept in targeted delivery for cancer treatment is reported. Multiple CPT prodrug molecules are conjugated to RNA oligos via a click reaction, and the resulting CPT‐RNA conjugates efficiently self‐assemble into thermodynamically stable RNA three‐way junction (3WJ) nanoparticles. The RNA 3WJ is covalently linked with seven hydrophobic CPT prodrug molecules through cleavable ester bonds and a folic acid ligand for specific tumor targeting while remaining soluble in aqueous solutions without detectable aggregation at therapeutic dose. This CPT‐RNA nanoparticle exhibits efficient and specific cell binding and internalization, leading to cell apoptosis. Tumor growth is effectively inhibited by CPT‐RNA nanoparticles; the targeted delivery, strengthened by tumor ligand, further enhances tumor suppression. Compared with the traditional formulation, solubilization of CPT in aqueous buffer using RNA nanoparticles as a carrier is found to be safe and efficacious, demonstrating that RNA nanoparticles are a promising platform for the solubilization and the delivery of hydrophobic antitumor drugs.
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Abstract Increasing performance demand associated with the short lifetime of consumer electronics has triggered fast growth in electronic waste, leading to serious ecological challenges worldwide. Herein, a robust strategy for judiciously constructing flexible perovskite solar cells (PSCs) that can be conveniently biodegraded is reported. The key to this strategy is to capitalize on meniscus‐assisted solution printing (MASP) as a facile means of yielding cross‐aligned silver nanowires in one‐step, which are subsequently impregnated in a biodegradable elastomeric polyester. Intriguingly, the as‐crafted hybrid biodegradable electrode greatly constrains the solvent evaporation of the perovskite precursor solution, thereby generating fewer nuclei and in turn resulting in the deposition of a large‐grained dense perovskite film that exhibits excellent optoelectronic properties with a power conversion efficiency of 17.51% in PSCs. More importantly, the hybrid biodegradable electrode‐based devices also manifest impressive robustness against mechanical deformation and can be thoroughly biodegraded after use. These results signify the great potential of MASP for controllably assembling aligned conductive nanomaterials for biodegradable electrodes. As such, it represents an important endeavor toward environmentally friendly, multifunctional and flexible electronic, optoelectronic, photonic, and sensory materials and devices.