Amalgamation of DNAzymes and Nanozymes in a Coronazyme.

Artificial enzymes such as nanozymes and DNAzymes are economical and stable alternatives to natural enzymes. By coating Au nanoparticles (AuNPs) with a DNA corona (AuNP@DNA), we amalgamated nanozymes and DNAzymes into a new artificial enzyme with catalytic efficiency 5 times higher than AuNP nanozymes, 10 times higher than other nanozymes, and significantly greater than most of the DNAzymes on the same oxidation reaction. The AuNP@DNA demonstrates excellent specificity as its reactivity on a reduction reaction does not change with respect to pristine AuNP. Single-molecule fluorescence and force spectroscopies and density functional theory (DFT) simulations indicate a long-range oxidation reaction initiated by radical production on the AuNP surface, followed by radical transport to the DNA corona, where the binding and turnover of substrates take place. The AuNP@DNA is named coronazyme because of its natural enzyme mimicking capability through the well-orchestrated structures and synergetic functions. By incorporating different nanocores and corona materials beyond DNAs, we anticipate that the coronazymes represent generic enzyme mimics to carry out versatile reactions in harsh environments.

Submolecular dissection reveals strong and specific binding of polyamide-pyridostatin conjugates to human telomere interface.

To modulate biological functions, G-quadruplexes in genome are often non-specifically targeted by small molecules. Here, specificity is increased by targeting both G-quadruplex and its flanking duplex DNA in a naturally occurring dsDNA-ssDNA telomere interface using polyamide (PA) and pyridostatin (PDS) conjugates (PA-PDS). We innovated a single-molecule assay in which dissociation constant (Kd) of the conjugate can be separately evaluated from the binding of either PA or PDS. We found Kd of 0.8 nM for PA-PDS, which is much lower than PDS (Kd ∼ 450 nM) or PA (Kd ∼ 35 nM). Functional assays further indicated that the PA-PDS conjugate stopped the replication of a DNA polymerase more efficiently than PA or PDS. Our results not only established a new method to dissect multivalent binding into actions of individual monovalent components, they also demonstrated a strong and specific G-quadruplex targeting strategy by conjugating highly specific duplex-binding molecules with potent quadruplex ligands.

Decreased water activity in nanoconfinement contributes to the folding of G-quadruplex and i-motif structures.

Due to the small size of a nanoconfinement, the property of water contained inside is rather challenging to probe. Herein, we measured the amount of water molecules released during the folding of individual G-quadruplex and i-motif structures, from which water activities are estimated in the DNA nanocages prepared by 5 × 5 to 7 × 7 helix bundles (cross-sections, 9 × 9 to 15 × 15 nm). We found water activities decrease with reducing cage size. In the 9 × 9-nm cage, water activity was reduced beyond the reach of regular cosolutes such as polyethylene glycol (PEG). With this set of nanocages, we were able to retrieve the change in water molecules throughout the folding trajectory of G-quadruplex or i-motif. We found that water molecules absorbed from the unfolded to the transition states are much fewer than those lost from the transition to the folded states. The overall loss of water therefore drives the folding of G-quadruplex or i-motif in nanocages with reduced water activities.

Correlation of Cognitive Status and Atrophy Score in Alzheimer's Disease Among the Bangladeshi Population.

BACKGROUND: Alzheimer's disease (AD) patients suffer from cognitive dysfunction. This study assessed the structural magnetic resonance imaging (MRI) scoring among Alzheimer's patients (age ≥18 years) to correlate with dementia severity according to mini-mental state exam (MMSE) scores. METHODS: This cross-sectional study evaluated Bangladeshi adult AD patients from January 2018 to December 2022 who attended with subjective memory complaints and fulfilled the diagnostic and statistical manual of mental disorders criteria (DSM 5) for diagnosing dementia. The medial temporal lobe atrophy (MTA) and Koedam's score of the atrophy were measured utilising the 1.5 and 3 Tesla Magnetom symphony MRI systems. RESULTS: Of the 62 patients enrolled, the majority (39 cases; 62.9%) were aged over 60 years. Males were more predominant than females, with a male-to-female ratio of 2.6:1, and the moderate MMSE group consisted of 35.6% males and 64.7% females (P = 0.01). Further, MTA score severity is paradoxically associated with the MMSE score (P = 0.005). Additionally, we found a statistically significant negative correlation between the severity of the MMSE and only MTA scores (r = -0.350; 95% CI -0.551 to -0.110; P = 0.005). CONCLUSION: Structural magnetic resonance imaging among Alzheimer's patients is significantly correlated with the severity of dementia as per mini-mental state exam scores.

Single-Molecule Spectroscopy Reveals the Plasmon-Assisted Nanozyme Catalysis on AuNR@TiO2.

Gold nanoparticles are frequently employed as nanozyme materials due to their capacity to catalyze various enzymatic reactions. Given their plasmonic nature, gold nanoparticles have also found extensive utility in chemical and photochemical catalysis owing to their ability to generate excitons upon exposure to light. However, their potential for plasmon-assisted catalytic enhancement as nanozymes has remained largely unexplored due to the inherent challenge of rapid charge recombination. In this study, we have developed a strategy involving the encapsulation of gold nanorods (AuNRs) within a titanium dioxide (TiO2) shell to facilitate the efficient separation of hot electron/hole pairs, thereby enhancing nanozyme reactivity. Our investigations have revealed a remarkable 10-fold enhancement in reactivity when subjected to 530 nm light excitation following the introduction of a TiO2 shell. Leveraging single-molecule kinetic analyses, we discovered that the presence of the TiO2 shell not only amplifies catalytic reactivity by prolonging charge relaxation times but also engenders additional reactive sites within the nanozyme's intricate structure. We anticipate that further enhancements in nanozyme performance can be achieved by optimizing interfacial interactions between plasmonic metals and semiconductors.