Yan Cheng

Compact benzothiazole derivatives were developed as specific probes for aggregated α-synuclein protein. Among them, fluoropegylated azobenzothiazole [¹⁸F]NN-F exhibits efficient brain uptake and specific labeling of α-synuclein aggregates.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder with long preclinical and prodromal phases in older people. Molecular imaging is a promising approach for noninvasive in vivo identification and tracking pathophysiological changes. In particular, nuclear neuroimaging in AD has extended beyond traditional evaluation of brain perfusion and glucose metabolism, and has achieved substantial progress over the past 2 decades. To gain a comprehensive understanding of nuclear neuroimaging with different targets in the brain, this review provides an overview of the literature on the current status and recent progress of the development of radioligands for definitive and differential diagnosis of AD.

Protein aggregation has been found in a wide range of neurodegenerative protein-misfolding diseases. The demand for in vivo technologies to identify protein aggregation is at the leading edge for the pathogenic study, diagnostic development, and therapeutic intervention of these devastating disorders. Herein, we report a series of luminol analogues to construct a facile chemiluminescence (CL)-based approach for in vivo detection and imaging of β-sheet protein aggregates. The synthesized compounds exhibited a distinct chemiluminescent response with long emission wavelengths toward reactive oxygen species under physiological conditions and displayed signal amplification in the presence of β-sheet protein aggregates, including α-synuclein, β-amyloid, and tau. Among them, CyLumi-3 was further evaluated as a chemiluminescent probe in preclinical models. By intravenous administration into the model mice via the tail vein, in vivo CL imaging noninvasively detected the specific CL of the probe targeting the α-synuclein aggregates in the brains of living mice. Based on its structural characteristics, CyLumi-3 can readily interact with α-synuclein aggregates with significantly enhanced fluorescence and can identify α-synuclein aggregates in vivo via distinctive CL amplification, which could pave the way for a more comprehensive understanding of protein aggregation in preclinical studies and would provide new hints for developing small-molecule chemiluminophores for protein aggregates.

A screening platform based on epitope alteration for drug discovery (SPEED).

Paid Q&A is in great popularity because it provides askers with the right to choose satisfying knowledge contributors to consult independently, and it has faster responding speed and higher answer quality than traditional nonpaid Q&A. Based on social capital theory, this paper summarizes influencing factors of payment attractiveness, explores the relationship among payment decision, payment attractiveness and influencing factors such as interactive behaviors in the community by constructing a hidden Markov model. Function of each part of the model is set to reveal the dynamic process of knowledge contributors' payment attractiveness and specific effect of each influencing factor. Data crawled from Zhihu.com are used for model training and parameter estimation. The results show that the state of payment attractiveness can be divided into three (high, medium and low) to best optimize the model. Influencing factors of number of likes, followers, public answers and reviews will play a positive effect on the transition of payment attractiveness state except for a few special cases. Number of honor labels will play a positive effect on the transition of medium and high attractiveness state to payment decision while price plays a negative effect. The results of the study are expected to provide a reference for community operators to efficiently manage knowledge contributors and promote paid Q&A service to develop better.

Aberrant brown adipose tissue (BAT) metabolism is linked to obesity as well as other metabolic disorders. However, the paucity of imaging tools limits the study of in vivo BAT metabolism in animal models. The current work evaluated a heptamethine dye (CyHF-8) in living mice as a dual-modality BAT-avid molecular probe for two imaging approaches, including near-infrared fluorescence imaging (NIRF) and photoacoustic imaging (PAI). CyHF-8 exhibited favorable spectral properties in the near-infrared window (786/787/805 nm), and accumulated in the subcellular mitochondria of brown adipocytes. After intravenous injection of CyHF-8, NIRF and PAI were both capable of non-invasively detecting interscapular BAT at early timepoints in living mice. Quantitative analysis of NIRF and PAI images showed that CyHF-8 signals respond to dynamic BAT changes in mice stimulated by norepinephrine (NE) and in diabetic mice induced by streptozotocin (STZ). In summary, dual-modality NIRF/PAI probe CyHF-8 can be used for both NIRF and PAI to non-invasively assess BAT metabolism in living animals.

The interaction between an antibody and its epitope has been daily utilized in various biological studies; however it has been rarely explored whether small molecules can alter the interaction. We discovered that small molecules could alter/edit surface properties of amyloid beta (Aβ) epitopes, and consequently inhibit or enhance corresponding antibody recognition. Remarkably, this editing effect could generate functional changes including protein aggregation behaviors, cell cytokine secreting and in vivo microglia activation. According to this discovery, we proposed a s creen p latform based on e pitope e diting for d rug discovery (SPEED). With a small library of compounds, we validated that SPEED could be used to seek new leads for Aβ species. We also demonstrated that this platform could potentially be extended to other targets including tau protein and PD-L1 protein. The SPEED is a simple, fast and label-free screening method. We believe that the SPEED strategy could be universally applicable for seeking and validating drug candidates and imaging ligands.

A series of pyrazine and quinoxaline probes (QNNs) were synthesized and evaluated. The quinoxaline derivative 3b, with high affinity and selectivity for tau aggregates, favorable fluorescence turn-on capability and brain kinetics, was successfully applied to the detection of tau tangles both in vitro and in mice in vivo.