Development of a Highly Specific Fluorescent Probe based on Thiol-ene Click Nucleophilic Cascade Reactions for Delving into the Action Mechanism of Serotonin in Depression.

The intrinsic correlation between depression and serotonin (5-HT) is a highly debated topic, with significant implications for the diagnosis, treatment, and advancement of drugs targeting neurological disorders. To address this important question, it is of utmost priority to understand the action mechanism of serotonin in depression through fluorescence imaging studies. However, the development of efficient molecular probes for serotonin is hindered by the lack of responsive sites with high selectivity for serotonin at the present time. Herein, we developed the first highly selective serotonin responsive site, 3-mercaptopropionate, utilizing thiol-ene click cascade nucleophilic reactions. The novel responsive site was then employed to construct the powerful molecular probe SJ-5-HT for imaging the serotonin level changes in the depression cells and brain tissues. Importantly, the imaging studies reveal that the level of serotonin in patients with depression may not be the primary factor, while the ability of neurons in patients with depression to release serotonin appears to be more critical. Additionally, this serotonin release capability correlates strongly with the levels of mTOR (intracellular mammalian target of rapamycin). These discoveries could offer valuable insights into the molecular mechanisms underpinning depression and furnish mTOR as a novel direction for the advancement of antidepressant therapies.

A fluorescence probe for imaging lipid droplet and visualization of diabetes-related polarity variations.

Diabetes mellitus is a disorder that affects lipid metabolism. Abnormalities in the lipid droplets (LDs) can lead to disturbances in lipid metabolism, which is a significant feature of diabetic patients. Nevertheless, the correlation between diabetes and the polarity of LDs has received little attention in the scientific literature. In order to detect LDs polarity changes in diabetes illness models, we created a new fluorescence probe LD-DCM. This probe has a stable structure, high selectivity, and minimal cytotoxicity. The probe formed a typical D-π-A molecular configuration with triphenylamine (TPA) and dicyanomethylene-4H-pyran (DCM) as electron donor and acceptor parts. The LD-DCM molecule has an immense solvatochromic effect (λem = 544-624 nm), fluorescence enhancement of around 150 times, and a high sensitivity to polarity changes within the linear range of Δf = 0.28 to 0.32, all due to its distinctive intramolecular charge transfer effect (ICT). In addition, LD-DCM was able to monitor the accumulation of LDs and the reduction of LDs polarity in living cells when stimulated by oleic acid, lipopolysaccharide, and high glucose. More importantly, LD-DCM has also been used effectively to detect polarity differences in organs from diabetic, drug-treated, and normal mice. The results showed that the liver polarity of diabetic mice was lower than that of normal mice, while the liver polarity of drug-treated mice was higher than that of diabetic mice. We believe that LD-DCM has the potential to serve as an efficient instrument for the diagnosis of disorders that are associated with the polarity of LDs.

Strategy for Fluorescence/Photoacoustic Signal Maximization Using Dual-Wavelength-Independent Excitation.

Dual-mode imaging of fluorescence-photoacoustics has emerged as a promising technique for biomedical applications. However, conventional dual-mode imaging is based on single-wavelength excitation, which often results in opposing fluorescence and photoacoustic signals due to competing photophysical processes in one agent, rendering the maximization of both signals infeasible. To meet this challenge, we herein propose a new strategy by using the dual-excitation approach, where one excitation wavelength generates a fluorescence signal and the other produces a photoacoustic signal, thus achieving simultaneous maximization of both signals in one fluorescence-photoacoustic molecule. Based on this strategy, three dye molecules were employed for comparison, and it was surprising to find that QHD dye with two types of excitation wavelengths could generate fluorescence and photoacoustic signals, respectively. Furthermore, this strategy was successfully implemented in dual-mode imaging of rheumatoid arthritis mice. Importantly, this study emphasizes a new design guideline for the maximization of fluorescence-photoacoustic signals by using dual-wavelength-independent excitation.

Elevated hypochlorous acid levels in asthmatic mice were disclosed by a near-infrared fluorescence probe.

Asthma is a respiratory inflammatory disease that seriously threatens human health. A growing body of evidence suggests that hypochlorous acid (HClO) plays an instrumental role in inflammation-related diseases, and therefore we hypothesize that it may be associated with asthma. Unfortunately, tracking HClO levels in asthma remains challenging due to the lack of effective measures for in vivo imaging. Herein, we exquisitely designed a near-infrared fluorescence probe dicyanomethylene-4H-pyran-dimethylthiocarbamyl (DCM-DMTC) for exploring the relationship between HClO and asthma, which has high sensitivity (about 76 times), a low limit of detection (44 nM), and great selectivity for HClO. In addition, the probe DCM-DMTC was successfully employed in tracing exogenous and endogenous HClO in living cells. Notably, the higher levels of HClO in the lungs of asthmatic mice than in normal mice were visualized by fluorescence imaging for the first time, indicating a remarkably intimate association between asthma and the overproduction of HClO.

Revealing the Effects of Endoplasmic Reticulum Stress on Ferroptosis by Two-Channel Real-Time Imaging of pH and Viscosity.

Endoplasmic reticulum (ER) is sensitive to changes in the intracellular environment such as pH and viscosity, and slight changes may trigger stress response. Besides, different from apoptosis and necrosis, ferroptosis is the result of lipid peroxidation accumulation. There is evidence that ferroptosis is closely related to endoplasmic reticulum stress (ERS). However, the possible changes in the pH and viscosity of the ER during the ferroptosis process have not yet been studied. Therefore, we used a new type of ER-targeted dual-excitation fluorescent probe (DSPI-3) to investigate the possible changes of pH and viscosity of ER during the ferroptosis. The novel probe DSPI-3 exhibited a highly sensitive and selective response to pH and viscosity. During the bioimaging process, it was found that the ER acidified and viscosity increased during the ferroptosis process induced by erastin, while the cells treated with ferrostatin-1 did not alter significantly. In addition, when dithiothreitol (DTT) and erastin stimulated the cells at the same time, we discovered that ER was acidified considerably at short notice, but the pH was slightly increased in the later stage. Besides, the change of the viscosity enhanced slowly with the passage of time, and there was a noteworthy decline in the later stage, demonstrating that the DTT-induced ERS accelerated the process of ferroptosis. We hope that this unique fluorescent probe can provide an effective method for studying the relationship between ERS and ferroptosis.

Determination of melamine in milk based on ß-cyclodextrin modified carbon nanoparticles via host-guest recognition.

Illegal addition of melamine (MEL) to milk has caused serious food safety accident. It is urgent to develop a highly sensitive method for detecting MEL in milk. ß-Cyclodextrin with inner hydrophobic and outer hydrophilic cavities have been widely used in smart sensors design. In this study, an "ON-OFF-ON" sensor for MEL detection was constructed based on ß-cyclodextrin modified carbon nanoparticles (ß-CD-CNPs). The sensor is switched "OFF" when Fe3+ interacts with ß-CD-CNPs and switched "ON" when MEL replaces Fe3+. Fluorescence recovery of ß-CD-CNPs exhibits good linear correlations with MEL concentration ranging from 10.00 ng/mL ~ 180.00 ng/mL and 180.00 ~ 1000.00 ng/mL, the detection limit is 6.82 ng/mL. The sensor was applied to analysis melamine in milk samples with recovery between 94.80% ~ 102.05%, and RSD bellow 12.61%. The results show that this method can meet the requirements of real sample analysis.