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G-quadruplex structures within the nuclear genome (nG4) is an important regulatory factor, while the function of G4 in the mitochondrial genome (mtG4) still needs to be explored, especially in human sperms. To gain a better understanding of the relationship between mtG4 and mitochondrial function, it is crucial to develop excellent probes that can selectively visualize and track mtG4 in both somatic cells and sperms. Herein, based on our previous research on purine frameworks, we attempted for the first time to extend the conjugated structure from the C-8 site of purine skeleton and discovered that the purine derivative modified by the C-8 aldehyde group is an ideal platform for constructing near-infrared probes with extremely large Stokes shift (>220 nm). Compared with the compound substituted with methylpyridine (PAP), the molecule substituted with methylthiazole orange ( PATO ) showed better G4 recognition ability, including longer emission (∼720 nm), more significant fluorescent enhancement (∼67-fold), lower background, and excellent photostability. PATO exhibited a sensitive response to mtG4 variation in both somatic cells and human sperms. Most importantly, PATO helped us to discover that mtG4 was significantly increased in cells with mitochondrial respiratory chain damage caused by complex I inhibitors (6-OHDA and rotenone), as well as in human sperms that suffer from oxidative stress. Altogether, our study not only provides a novel ideal molecular platform for constructing high-performance probes but also develops an effective tool for studying the relationship between mtG4 and mitochondrial function in both somatic cells and human sperms.

Parkinson's disease (PD) represents the second most widespread neurodegenerative disease, and early monitoring and diagnosis are urgent at present. Tyrosine hydroxylase (TH) is a key enzyme for producing dopamine, the levels of which can serve as an indicator for assessing the severity and progression of PD. This renders the specific detection and visualization of TH a strategically vital way to meet the above demands. However, a fluorescent probe for TH monitoring is still missing. Herein, three rationally designed wash-free ratiometric fluorescent probes were proposed. Among them, TH-1 exhibited ideal photophysical properties and specific dual-channel bioimaging of TH activity in SH-SY5Y nerve cells. Moreover, the probe allowed for in vivo imaging of TH activity in zebrafish brain and living striatal slices of mice. Overall, the ratiometric fluorescent probe TH-1 could serve as a potential tool for real-time monitoring of PD in complex biosystems.

Accurate detection of target analytes and generation of high-fidelity fluorescence signals are particularly critical in life sciences and clinical diagnostics. However, the majority of current NIR-I fluorescent probes are vulnerable to pH effects resulting in signal distortion. In this work, a series of fluorescence-tunable and pH-independent probes are reported by combining optically tunable groups of unsymmetric Si-rhodamines and introducing the methoxy instead of the spiro ring on the benzene ring at position 9. To validate the concept, the leucine aminopeptidase response site was introduced into Si-2,6OMe-NH 2 with the best optical properties to synthesize Si-LAP for monitoring the intrahepatic LAP in vivo. Therefore, the design approach may provide a new and practical strategy for designing innovative functional fluorescent probes and generating high-stability and high-fidelity fluorescent signals.

Aberrant lysosomal alkalization is associated with various biological processes, such as oxidative stress, cell apoptosis, ferroptosis, etc. Herein, we developed a novel aminofluorene-based fluorescence probe named FAN to monitor the lysosomal alkalization-related biological processes by its migration from lysosome to nucleus. FAN possessed NIR emission, large Stokes shift, high pH stability, and high photostability, making it suitable for real-time and long-term bioimaging. As a lysosomotropic molecule, FAN can accumulate in lysosomes first and then migrate to the nucleus by right of its binding capability to DNA after lysosomal alkalization. In this manner, FAN was successfully used to monitor these physiological processes which triggered lysosomal alkalization in living cells, including oxidative stress, cell apoptosis, and ferroptosis. More importantly, at higher concentrations, FAN could also serve as a stable nucleus dye for the fluorescence imaging of the nucleus in living cells and tissues. This novel multifunctional fluorescence probe shows great promise for application in lysosomal alkalization-related visual research and nucleus imaging.

An "AND" logic gate-based NIR fluorescent probe Si-NH2-Glu was developed based on novel meso -amine Si-Rhodamine, which combined γ-glutamyl transpeptidase and pH dual-responsive sites. The features of Si-NH2-Glu enable it to be applied in orthotopic tumor imaging and fluorescence-guided surgery.

Non-invasive dynamic tracking of lysosomes and their interactions with other organelles is important for the study of lysosomal function and related diseases. However, many fluorescent dyes developed so far to target lysosomes cannot be used to monitor these processes due to the high concentrations required for imaging, long cell penetration times, and non-ideal photostability. In this regard, we synthesized three lysosomal targeting probes with large Stokes shifts, good stability, and high brightness. The Q-P-ARh dye, developed by us for the first time, can stain lysosomes at ultra-low concentrations (1.0 nM) without affecting the physiological functions of the lysosomes. More importantly, its excellent anti-interference ability and ultrafast lysosomal staining ability (within 1.0 min) clearly monitored the entire dynamic process of lipophagy. Ultimately, this method can greatly contribute to the study of autophagy pathways. This novel fluorescence platform shows great promise for the development of biological probes for application in pathological environments., (© 2021 Wiley-VCH GmbH.)

Different chemical states of nitrogen are present in many freshwater and marine ecosystems, and nitrite ions are one of the most toxic water-soluble nitrogen species. Developing an effective and convenient sensing method to constantly detect the concentration of nitrite has become a wide concern. Here, a novel near-infrared fluorescent probe (AAC) was designed and synthesized via the "covalent assembly" principle, showing excellent selectivity and high sensitivity for nitrite. A new nitrite-quantitative method was established with the help of AAC, and the detection limit of nitrite using the new method was as low as 6.7 nM. AAC was successfully applied for the quantitative detection of nitrite in real-world environmental and food samples (including river water and Chinese sauerkraut), and the detection results were essentially identical to the results obtained from the traditional Griess assay. Moreover, AAC was successfully applied for tracking nitrite in Escherichia coli by fluorescence imaging. Since nitrite can have devastating effects, the method established with AAC allowed us to "see" effectively about the water quality, food quality, etc., (Copyright © 2020. Published by Elsevier Ltd.)

The abnormality of the plasma membrane (PM) is an important biomarker for cell status and many diseases. Hence, visualizing the PM, especially in complex systems, is an emerging field in the life sciences, especially in low-resource settings. Herein, we developed a water-soluble PM-specific probe utilizing electrostatic and hydrophobic interaction strategies with aggregation-induced emission as the signal output. The probe could image the PM with many advanced features (wash-free, ultrafast staining process, excellent PM specificity, and good biocompatibility), which were demonstrated by the PM imaging of neurons. The probe allowed for the first time the imaging of erythrocytes in the complex brain environment through a fluorescence-based method. Moreover, the PM of the epidermal and partial view of the eyeball structure of live zebrafish are also revealed., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Inspired by the natural properties of the phospholipid bilayer (PB), three probes that could assemble with phospholipid bilayer through hydrophobic and electrostatic interactions are reported for rapid and accurate specific imaging of plasma membrane in 2D and 3D cell models. What's more, we have captured the picture of probe assembly with the phospholipid bilayer in cells for the first time.

In the field of drug delivery, the controlled release of drugs is continuously one of the highly prioritized research domains. Stimuli-responsive polymers are being investigated as drug delivery vehicles that modulate pharmaceutical effect via tumor specific mechanisms. In this work, a biocompatible graft copolymer (denoted as PSNC-g-mPEG/TPE) was constructed, which comprised a triple-responsive polycarbonate backbone coupled with fluorescent TPE and hydrophilic methoxypoly(ethylene glycol) (mPEG) segments. This multifunctional amphiphilic copolymer was able to self-assemble in aqueous solutions and acted as a drug delivery vehicle that releases cargo in response to multiple biological stimuli (ROS, pH and enzymes). And the results of confocal laser scanning microscopy (CLSM) suggested that these micelles could be rapidly internalized by cells and achieve more effective drug release in cancer cells. Furthermore, the cytotoxicity assays proved the safety of this material. It is anticipated that this strategy has enormous potential in constructing novel anticancer therapeutics., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A mitochondria targeting and immobilized fluorescent probe ( Rd1 ) using triphenylphosphonium as the targeting group and methoxymaleimide as the fixed site is designed for the detection of ClO - . The methoxymaleimide fixed group can react with nucleophiles, such as the reactive thiol groups present in mitochondrial polypeptides and proteins, and form covalent bonds to immobilize the probe within mitochondria. The immobilization of Rd1 enhances its ability to withstand the risk of leakage from mitochondria. Methoxymaleimide shows better reactivity toward Cys than glutathione (GSH), which decreases the ineffective labeling of GSH when it covalently bonds with the reactive thiol residues of mitochondrial proteins; furthermore, it can resist hydrolysis during a long-term storage in water, compared with the classic benzyl chloride fixed unit. The imaging results indicate that Rd1 displays enhanced retention within the mitochondria of cells and tissues upon the decrease of mitochondrial membrane potential (MMP) caused by different stimulations. Furthermore, it possesses the ability to visualize exogenous and endogenous ClO - in living cells, tissues, and zebrafishes.

The chemically selective detection of natural nucleobase modifications has been regarded as the key step in understanding their important roles in epigenetics. Herein, for the first time, we introduce a Wittig reaction into the design of reaction-based fluorescent probes for ratiometrically detecting 5fU, selectively labelling 5fU-modified DNA and imaging intracellular 5fU produced by γ-irradiation.

A novel reaction-based fluorescent probe (ATC-Hg) was designed and synthesized via the "covalent assembly" principle, which exhibited excellent selectivity and high sensitivity for Hg2+ and CH3Hg+. Moreover, it is the first Hg(ii) sensitive fluorescent probe that has been successfully applied in imaging in both cells and Escherichia coli.

The viscosity of lysosome is reported to be a key indicator of lysosomal functionality. However, the existing mechanical methods of viscosity measurement can hardly be applied at the cellular or subcellular level. Herein, a BODIPY-based two-photon fluorescent probe was presented for monitoring lysosomal viscosity with high spatial and temporal resolution. By installing two morpholine moieties to the fluorophore as target and rotational groups, the TICT effect between the two morpholine rings and the main fluorophore scaffold endowed the probe with excellent viscosity sensitivity. Moreover, Lyso-B succeeded in showing the impact of dexamethasone on lysosomal viscosity in real time.

A novel chromenylium-based fluorescent probe was exploited for sulphur dioxide (SO₂) detecting. The probe displayed a remarkable fluorescence turn-on response towards SO₂ based on the nucleophilic addition reaction to the carbon-carbon double bond with 105 nm Stock shift. The probe was successfully applied for the quantification of SO₂.The linear detection range was from 0-160 μM with the detection limit as low as 99.27 nM. It also exhibited high selectivity for SO₂ than other reactive species and amino acids. Furthermore, cell staining experiments indicated that the probe was cell membrane permeable and could be used for high-performance imaging of SO₂ in living cells. The superior properties of the probe made it highly promising for use in chemical and biological applications., Competing Interests: The authors declare no conflict of interest.

Here we report two novel red emission fluorescent probes for the highly sensitive and selective detection of monoamine oxidase (MAO) with large Stokes shift (227 nm). Both of the probes possess solid state fluorescence and can accomplish the identification of MAO on test papers. The probe MAO-Red-1 exhibited a detection limit down to 1.2 μg mL(-1) towards MAO-B. Moreover, the cleavage product was unequivocally conformedby HPLC and LCMS and the result was in accordance with the proposed oxidative deamination mechanism. The excellent photostability of MAO-Red-1 was proved both in vitro and in vivo through fluorescent kinetic experiment and laser exposure experiment of confocal microscopy, respectively. Intracellular experiments also confirmed the low cytotoxity and exceptional cell imaging abilities of MAO-Red-1. It was validated both in HeLa and HepG2 cells that MAO-Red-1 was capable of reporting MAO activity through the variation of fluorescence intensity.

A near-infrared ratiometric fluorophore (NIR-HBT) was rationally designed and constructed by expanding both the excitation and emission wavelength of the classical ratiometric fluorophore 2-(benzothiazol-2-yl)phenol (HBT) into the near-infrared region. The NIR-HBT was easily synthesized by incorporating the HBT module into the hemicyanine skeleton and showed evident NIR ratiometric fluorophore characteristics. Further application of the new fluorophore for pH detection demonstrated that NIR-HBT possesses superior overall analytical performance and NIR-HBT was successfully applied for detection of acidosis caused by inflammation in living animal tissue, which indicated the potential application value of NIR-HBT in biological imaging and sensing.

A ratiometric fluorescent probe for SO2 derivatives based on the conjugate of carbazole and indolium was presented, which could selectively respond to HSO3(-) over other thiol compounds. More importantly, CZ-Id is a novel mitochondria-targeted ratiometric fluorescent probe to image exogenous SO2 derivatives.

A ratiometric fluorescent probe () for ClO(-) based on the conjugate of coumarin-rhodamine was presented, which could sense ClO(-) with fast response (within 5 s), high sensitivity and excellent selectivity. More importantly, is the first mitochondria-targeted ratiometric fluorescent probe to image exogenous and endogenous ClO(-).

The terpyridine anthracene ligand was synthesized and characterized. is a ratiometric fluorescent probe for Cd(2+) with a recognition mechanism based on intramolecular charge transfer (ICT). An complex was isolated, and its structure was established using single-crystal XRD. The complex was able to serve as a novel reversible chemosensing ensemble to allow ratiometric response to pyrophosphate (PPi) in aqueous media. Moreover, the fluorescence imaging in living cells from these two emission channels suggested that was a ratiometric probe for Cd(2+), and the in situ generated complex was also a ratiometric ensemble for PPi detection in living cells.

Pyridinium functioned 7-hydroxy coumarin was presented as the first mitochondria-targeted ratiometric fluorescent probe CP for real time monitoring pH in living cells. Compared with commercially available mitochondrial trackers, CP possesses high specificity to mitochondria in living cells as well as good biocompatibility. Meanwhile, CP displays excellent pH sensitivity and anti-interference capability. Confocal image experiments confirm that CP can monitor mitochondrial pH changes associated with the mitochondrial acidification, cellular apoptosis and stress response efficiently in real time., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Non‐invasive dynamic tracking of lysosomes and their interactions with other organelles is important for the study of lysosomal function and related diseases. However, many fluorescent dyes developed so far to target lysosomes cannot be used to monitor these processes due to the high concentrations required for imaging, long cell penetration times, and non‐ideal photostability. In this regard, we synthesized three lysosomal targeting probes with large Stokes shifts, good stability, and high brightness. The Q‐P‐ARh dye, developed by us for the first time, can stain lysosomes at ultra‐low concentrations (1.0 nM) without affecting the physiological functions of the lysosomes. More importantly, its excellent anti‐interference ability and ultrafast lysosomal staining ability (within 1.0 min) clearly monitored the entire dynamic process of lipophagy. Ultimately, this method can greatly contribute to the study of autophagy pathways. This novel fluorescence platform shows great promise for the development of biological probes for application in pathological environments. [ABSTRACT FROM AUTHOR]