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Abstract Misfolding and aggregation of amyloid peptides into β‐structure‐rich fibrils represent pivotal pathological features in various neurodegenerative diseases, including Alzheimer's disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). The development of effective amyloid detectors and inhibitors for probing and preventing amyloid aggregation is crucial for diagnosing and treating debilitating diseases, yet it poses significant challenges. Here, an aggregation‐induced emission (AIE) molecule of ROF2 with multifaceted functionalities as an amyloid probe and a screening tool for amyloid inhibitors using different biophysical, cellular, and worm assays, are reported. As an amyloid probe, ROF2 outperformed ThT, demonstrating its superior sensing capability in monitoring, detecting, and distinguishing amyloid aggregates of different sequences (Amyloid‐β, human islet amyloid polypeptide, or human calcitonin) and sizes (monomers, oligomers, or fibrils). More importantly, the utilization of ROF2 as a screening molecule to identify and repurpose cardiovascular drugs as amyloid inhibitors is introduced. These drugs exhibit potent amyloid inhibition properties, effectively preventing amyloid aggregation and reducing amyloid‐induced cytotoxicity both in cells and nematode. The findings present a novel strategy to discovery AIE‐based amyloid probes and to be used to repurpose amyloid inhibitors, expanding diagnostic and therapeutic options for neurodegenerative diseases while addressing vascular congestion and amyloid aggregation risks.
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Not as simple as we thought: a rigorous examination of data aggregation in materials informatics
Prompted by limited available data, we explore data-aggregation strategies for material datasets, aiming to boost machine learning performance. Our findings suggest that intuitive aggregation schemes are ineffective in enhancing predictive accuracy.
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- Award ID(s):
- 1651668
- PAR ID:
- 10500965
- Publisher / Repository:
- Digital Discovery
- Date Published:
- Journal Name:
- Digital Discovery
- Volume:
- 3
- Issue:
- 2
- ISSN:
- 2635-098X
- Page Range / eLocation ID:
- 337 to 346
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract We present a fundamental study that supports the feasibility of delaying the onset of presbyopia and age‐related cataracts via the utilization of surface‐functionalized poly(amidoamine) (PAMAM) dendrimers. These PAMAM derivatives are known to have the added benefit of permeating the human cornea with possible absorption/distribution into the crystalline lens, indicating the potential for use in a topically applied eye solution. Mature onset cataract formation occurs because of γ‐crystallin and β‐crystallin aggregation in the human lens over time. As the molecular chaperone α‐crystallin becomes saturated with unfolded γ‐crystallins, the ability to prevent aggregation becomes limited. PAMAM dendrimers containing either sodium carboxylate‐ or succinamic acid‐surface functionality are employed as synthetic chaperones to evaluate the effect of structure and local concentration on γ‐crystallin aggregation. The chaperone/γ‐crystallin blends are examined via DLS, zeta potential measurements, and fluorescence spectroscopy. DLS studies show a reduction in hydrodynamic size for γ‐crystallin in the presence of PAMAM dendrimers and their small molecule counterparts compared to the control. Structural identity and local concentration of functionality are found to impact solution behavior. Zeta potential measurements and fluorescence studies indicate that synthetic chaperones can have multiple modes of non‐covalent interactions and are the most effective in preventing or reducing γ‐crystallin aggregation.more » « less
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D3DD00207A
