Ping Li

DBCO-BOD-NH is a dual-channel probe that harnesses bioorthogonal chemistry for in situ NO/H ₂ S imaging in atherosclerotic plaques. It reveals that plaque progression elevates NO while depleting H ₂ S, and diabetes worsens this redox imbalance.

As the primary risk factor for cardiovascular events, early diagnosis of atherosclerosis (AS) is essential for reducing their incidence. Abnormal accumulation of lipid droplets (LDs) and excessive production of superoxide anion (O2•–) are key synergistic drivers that promote the early progression of AS. This study developed a dual-functional fluorescent nanoprobe, termed LDN-O, for simultaneous imaging and assessment of changes in LDs and O2•– levels during the onset and progression of AS. LDN-O was fabricated via nanoprecipitation to encapsulate two responsive molecules: LDB-O-ME enables high-fidelity targeted imaging of LDs, while LN-SF-O allows highly selective detection of O2•–. In vitro experiments confirmed that LDN-O exhibits excellent sensitivity and specificity for both targets. Dynamic monitoring with LDN-O revealed that during foam cell formation, the levels of LDs and O2•– were positively correlated with the duration of oxidized low-density lipoprotein (ox-LDL) stimulation, providing direct experimental evidence for understanding the intrinsic drivers driving early pathological progression in AS. Ex vivo imaging of aortas was further performed in mouse models of early-stage AS and in a combined model of AS with steatohepatitis. The results showed that LDs and O2•– levels in aortic tissue were significantly higher in the model groups than in the control group, with an even more pronounced increase in the group with concurrent steatohepatitis. Overall, LDN-O enables visualization of lipid deposition and oxidative stress in early AS, offering a new strategy for its early diagnosis.

Depression is closely associated with dysregulation of monoamine neurotransmitter metabolism, in which monoamine oxidase A (MAO-A), located on the outer mitochondrial membrane, plays a key role by catalyzing monoamine degradation coupled with hydrogen peroxide (H2O2) generation. This process links neurotransmitter imbalance with mitochondrial oxidative stress; however, the spatiotemporal dynamics of mitochondrial MAO-A activity in vivo remain poorly understood due to the lack of effective imaging tools. Herein, we report a mitochondria-targeted small-molecule fluorescent probe, BAT, for real-time imaging of MAO-A activity in living systems. BAT integrates a propylamine recognition unit with a 2′-hydroxychalcone fluorophore featuring aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT), enabling low-background fluorescence activation upon MAO-A-catalyzed oxidative deamination. BAT enables sensitive visualization of MAO-A activity in SH-SY5Y cells, primary neurons, and mouse brains. In vivo imaging further reveals elevated MAO-A activity accompanied by increased H2O2 levels in stress-susceptible mice, highlighting mitochondrial oxidative stress associated with MAO-A dysregulation. Collectively, this work provides a robust chemical imaging tool for investigating MAO-A-related pathological process.

Protein post‐translational modification (PTM) plays a significant role in the progression of atherosclerosis (AS). However, the role of O‐GlcNAcylation, as an important O‐glycosylation modification, in the formation of foam cells remains unclear, limiting early diagnosis and mechanistic studies. Here, utilizing two bioorthogonal reactions, we developed a ratiometric fluorescent nanoprobe‐based tracker for O‐GlcNAcylation. This tracker (BORFI) enables dynamic tracing, relative quantification, and multi‐scale in situ visualization of protein O‐GlcNAcylation during cellular events, and images the regulation of O‐GlcNAcylation during foam cell formation. Using BORFI, we successfully achieved spatiotemporal co‐imaging of O‐GlcNAcylation and reactive oxygen species (ROS), and found that there is a significant positive correlation between O‐GlcNAcylation and ROS during the transition from macrophages to foam cells. Treatment with the OGT enzyme inhibitor (OSMI‐1) to affect the O‐GlcNAcylation level in foam cells effectively alleviates foam cell formation, accompanied by suppression of the overall increase in ROS levels, modulation of key cholesterol metabolism‑related proteins (downregulation of ACAT1 and upregulation of ABCA1), and downregulation of the scavenger receptor MSR1. Furthermore, BORFI was successfully applied to in situ imaging of the aorta in a mouse AS model, and we found that hyperglycemia participates in AS progression by specifically upregulating vascular O‐GlcNAcylation.

Foam cell formation of macrophages is a core pathological event in the progression of atherosclerosis. Investigating the changes in active molecules during macrophage foaming is critical for the early warning and mechanistic research of atherosclerosis. Superoxide anion (O₂^•−) and nitric oxide (NO) are two typical representatives of these active species; evaluating the fluctuations of O₂^•− and NO during macrophage foaming is vital for understanding the early diagnosis and pathological mechanisms of atherosclerosis. Herein, we report a fluorescent probe for the detection of O₂^•− and NO concentration changes based on the quenching effect of the urea bond and trifluoromethanesulfonate group on the fluorophore. MB-ROS features favorable sensitivity, selectivity and biocompatibility, enabling imaging of O₂^•− and NO fluctuations in macrophages. It was further validated in ox-LDL-stimulated foam cell models to visually track abnormal ROS/RNS changes during foam formation. This work offers a reliable chemical imaging tool to uncover redox imbalance underlying early atherosclerotic macrophage foaming.

Investigating the correlation between changes in multiple active molecule levels and the progression of atherosclerosis holds significant practical value for achieving early disease monitoring. To this end, this study constructed a fluorescence nanoprobe for monitoring superoxide anion (O₂^•-), hydrogen peroxide (H₂O₂), and protein phosphorylation, which enabled the synchronous detection and imaging of the three molecules at both the cellular and in vivo levels, thereby systematically exploring the correlation between their level changes and early disease progression. Two-photon fluorescence imaging was used to monitor changes in the levels of the three molecules in the aorta of model, which showed that the levels of protein phosphorylation, O₂^•-, and H₂O₂ in vascular tissues of the disease group were significantly elevated. More importantly, deep tissue imaging (approximately 140 μm) was achieved utilizing the two-photon imaging. Meanwhile, changes in active molecules in the blood during different disease stages were observed, and as the disease progressed, all three indicators showed a marked increase; among them, hydrogen peroxide exhibits the most pronounced fluorescence response. Serum testing combined with two-photon imaging provides support for early monitoring of atherosclerosis.

The vicious cycle of oxidative stress and cellular senescence is closely associated with the development and progression of atherosclerosis. Targeting the vicious cycle of “oxidative stress-cell senescence” as a combined biological target for atherosclerosis and developing dual-functional probes holds significant importance for the early monitoring and risk assessment of this disease. Therefore, fluorescent nanoprobe GL-1-NPs, capable of simultaneously imaging the aging markers β-galactosidase (β-gal) and peroxynitrite (ONOO^–) were synthesized via nanoprecipitation. GL-1-NPs serve as a live-cell imaging tool that enables effective monitoring of changes in β-gal activity and ONOO^– levels during the formation process of foam cells. Notably, in the aortas of ApoE^–/– mice fed a high-fat diet for 12 weeks, traditional methods such as Oil Red O staining and immunofluorescence revealed no plaque formation or upregulation of the associated proteins CD36 and CD68. Whereas, GL-1-NPs successfully detected enhanced fluorescence signals in the β-gal and ONOO^– channels, highlighting their potential for achieving early warning of atherosclerosis.

β ‐Amino acids are crucial building blocks for bioactive peptides and pharmaceuticals, wherein the stereochemistry of C ² , C ³ ‐disubstituted β ^2,3 ‐amino acids dictates the secondary structure of β ‐peptides. However, the diastereoselective synthesis of these scaffolds remains a formidable challenge. Herein, we report a novel photocatalytic cascade enabling the one‐pot hydrogenation, carboxylation, and epimerization of α , β ‐unsaturated imines. This method provides direct and highly diastereoselective (d.r. up to 35:1) access to valuable syn ‐ β ^2,3 ‐amino acids. Time‐course analysis and DFT calculations reveal a unique light‐driven dynamic kinetic epimerization process that ensures stereoconvergence to the thermodynamically favored syn ‐isomer. Notably, this strategy also facilitates the facile synthesis of ¹³ C‐labeled syn ‐ β ^2,3 ‐amino acids using commercially available ¹³ C‐sodium formate, achieving exceptional isotope incorporation (93%–98%) that surpasses existing ¹³ CO ₂ ‐based methods. Furthermore, the system's utility is demonstrated through the gram‐scale synthesis of N‐unprotected α ‐amino acids from imines (11 g, 75% yield), more significantly, via a one‐pot procedure directly from diaryl ketones.