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Drug-induced liver injury (DILI) poses a severe threat to public health. Endoplasmic reticulum (ER) stress contributes significantly to DILI pathogenesis, with peroxynitrite (ONOO - ) identified as a pivotal indicator. However, the temporal and spatial fluctuations of ONOO - associated with ER stress in the pathogenesis of DILI remain unclear. Herein, a novel ER-specific near-infrared (NIR) probe (QM-ONOO) with aggregation-induced emission (AIE) features for monitoring ONOO - fluctuations in DILI was elaborately constructed. QM-ONOO exhibited excellent ER-targeting specificity, a large Stoke's shift, and a low detection limit (26.9 nM) toward ONOO - . QM-ONOO performed well in imaging both exogenous and endogenous ONOO - in HepG2 cells. Furthermore, molecular docking calculations validated the ER-targeting mechanism of QM-ONOO. Most importantly, using this probe allowed us to intuitively observe the dynamic fluctuations of ONOO - during the formation and remediation processes of DILI in the acetaminophen (APAP)-induced mouse model. Consequently, this work provides a promising tool for in-depth research of ONOO - associated pathological processes in DILI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Adenosine triphosphate (ATP), mainly produced in mitochondria, plays an important role in various pathological processes such as inflammation and acute liver injury. Fluorescence imaging is a powerful tool for imaging tissue structure and function in vivo . To date, the lack of biocompatible ATP probes with bright fluorescence emission has hindered their application in basic research and clinical trials. Here, we report a method for preparing ATP probes using a ZIF-90 potting dye, which produces bright ATP probes by encapsulating a modified high fluorescence quantum yield dye into a ZIF-90 skeleton. The nanoprobe does not fluoresce due to the coating. ATP can cooperate with Zn 2+ to decompose the nanoprobe structure, release the dye and restore the fluorescence. Both nanoprobes ORhBSO 2 @ZIF-90 and SiRhBSO 2 @ZIF-90 showed higher sensitivity than the reported ATP nanoprobes with detection limits of 7.56 μM and 6.6 μM, and with lower doses (10 μg mL -1 ) of probes for cell imaging. In addition, SiRhBSO 2 @ZIF-90 has also been successfully used in the liver injury model. The ZIF-90 encapsulation strategy can retain the high fluorescence quantum yield and improve the biocompatibility of the dye.

Cell death plays a vital role in body development, maintenance of tissue function, and homeostasis. Accurate evaluation of cell death types is of great importance for pharmacological and pathological research. However, there is a lack of efficient fluorescent probes to discriminate various cell states. Here, we design and synthesize a novel activatable fluorescent probe PNE-Lyso to detect intracellular pH and hexosaminidases with two kinds of fluorescence signals. PNE-Lyso could distinguish dead cells from healthy cells based on a dual-color mode by targeting the lysosome and evaluating lysosomal hexosaminidase activity. Significantly, PNE-Lyso could also discriminate apoptotic and necrotic cells through visualizing lysosome morphology that is adjusted by the integrity of the lysosome membrane. Moreover, probe PNE-Lyso was successfully applied to investigate the drug-induced cell death process. To the best of our knowledge, this work is the first time cell death types have been distinguished based on a single fluorescent probe.

During biological detection, the toxicity caused by probes to living organisms is neglected. In this study, an analyte-compensated fluorescent probe (NP-SN 3 ) was constructed for the detection of H 2 S. Through experiments with HepG2 cells and zebrafish embryos and larvae, the NP-SN 3 probe showed no significant difference in imaging performance compared with the traditional probe (NP-N 3 ) but exhibited lower detection-induced toxicity in the imaging of liver fibrosis in activated HSC-T6 cells. During the development of zebrafish embryos and continuous administration in rats, NP-SN 3 showed a lower death rate, higher hatchability and lower malformation in zebrafish embryos and milder pathological symptoms in stained rat tissues.

Hydrogen sulfide (H 2 S) is a typical gas signal molecule that plays a vital role in various pathological courses. Despite having the accumulated knowledge on the physiological functions of H 2 S in many diseases, the process in the measurement of its level in mitochondria during oxidative stress is still far away from the expectation. In this regard, it is great significant to design a fluorescent probe for accurately monitoring the dynamics of H 2 S during oxidative stress. In this work, we firstly synthesized an oxidative stress activated fluorescence probe QM-RSH for tracking H 2 S level in mitochondria. It exhibited high selectivity and sensitivity for detecting H 2 S with lower limit of detection (LOD = 44.6 nM) in the presence of H 2 O 2 . QM-RSH can be successfully applied to accurately monitor the fluctuation of H 2 S level during oxidative stress without interference from other physiological processes in living cells and zebrafish. Therefore, this multifunctional probe QM-RSH has great potential as an image tool in biological research. It also provides a novel strategy for designing fluorescent probe to investigate biomolecular information and signaling pathways under specific physiological conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

As a signal molecule involved in autophagy, hydrogen sulfide (H 2 S) is considered to be essential in the development and treatment of diseases. In order to clarify the complex role of H 2 S in organism and the participation of H 2 S in disease process, it is urgently needed to visualize the dynamics of H 2 S. In this contribution, a water-soluble near-infrared (695 nm emission) self-immolative fluorescent probe CySO 3 N 3 was constructed for H 2 S detection. The ability of self-immolative strategy to detect H 2 S was verified to increase the metabolic capacity and reduce the toxicity of probe. This probe can not only be used to detect H 2 S in living cell and mice, but also shows great potential in detecting H 2 S changes to monitor cell self-repair during inflammation and myocardial injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This is great significant to establish a method that extends the small molecules fluorescence emission wavelength to the near-infrared region (NIR) for in vivo imaging. Hence, we firstly reported a novel fluorogenic scaffold QOH that could extend its fluorescence wavelength from (λ em  = 555 nm) to NIR (λ em  = 720 nm) with a large Stokes shift (120 nm) by forming its N-quaternization product (QMOH). In addition, the effect of the introduction of substituent at different modification sites and the properties of substituent on the optical properties of QOH were fully discussed by theoretical calculation. To investigate the possibility of QOH as probe construction, the compound Q-SH and QM-R were synthesized and applied to detect H 2 S and H 2 O 2 in vitro and in vivo, respectively. This study provided an efficient strategy to extend fluorescence emission to NIR and design fluorescence probes with large ratio variation for accurately imaging biomarkers in biological system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hypochlorous acid (HOCl), mainly generated in mitochondria, plays a critical role in various physiological processes. To better understand the role and function of HOCl in mitochondria, herein, we present the design and synthesis of a Mito-QL reporter for probing the HOCl within mitochondria without other interference generated in living cells. Through the combination of TICT/ICT mechanisms, probe Mito-QL, with large stokes shift (203 nm) and low background fluorescence, exhibited excellent sensitivity (900-fold fluorescence enhancement) and selectivity towards HOCl (LOD = 2.4 nM). The co-location experiments confirmed that probe Mito-QL can firstly localize in the mitochondria and then react with HOCl in mitochondria. Also, the probe is capable of imaging endogenous and exogenous HOCl even the generation of HOCl during the ferroptosis of cells, which is beneficial for more efficient application in biological imaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Understanding the complex relationship between active small molecules is of great significance in various physiological processes. Herein, we present the design and synthesis of a sequential responsive Lysosome-Naphthalene imide-Azido (lyso-NP-N 3 ) reporter for probing the H 2 S and HOBr within organelle (lysosome) in living cells. Probe lyso-NP-N 3 exhibited high selectivity and sensitivity towards H 2 S (LOD = 23.5 nM) and HOBr (LOD = 254 nM). Additionally, lyso-NP-N 3 possessed an excellent lysosome targeting ability and was utilized to visualize the exogenous/endogenous H 2 S and HOBr in RAW 264.7, Hela and HepG2 cells. Facilitated by this sequentially activated mechanism, the probe was successfully applied to confirm that the reported scavenger of HOBr, N-acetyl-L-cysteine (NAC) mainly relied on its metabolite H 2 S to eliminate excess HOBr, thereby playing the role of cell regulation and protection. These results establish the crosstalk between H 2 S and HOBr in lysosome and provide a promising tool to study metabolite interactions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The single signal amplification strategy is significant for detecting various disease biomarkers but is restricted by its limited accuracy. The multi-signal and multi-mode methods have overcome this deficiency. Acid phosphatase (ACP) is an important intracellular enzyme but one-step cell imaging material-based probes are scarce for ACP. Herein, we designed a one-step self-assembled polymer probe using neutral red (NR), modified-(pyridoxal-5'-phosphate (PLP)) and Eu 3+ . The polymer exhibited non-emission and excellent stability. Upon the catalytic hydrolysis reaction of ACP, the polymer exhibited two strong fluorescence signals at 373 nm and 613 nm and an appreciable decline of absorbance at 395 nm. The probe has excellent selectivity and higher sensitivity with a limit of detection as low as 0.02 mU mL -1 . It possesses favorable biocompatibility and has been successfully used to detect and image intracellular ACP in several living cells.

Acid phosphatase has become a significant indicator of prognostic and medical diagnosis, and its dysfunction may lead to a series of diseases. A novel dual-signal fluorescence method for acid phosphatase detection based on europium polymer (europium-pyridine dicarboxylicacid-adenine) and pyridoxal phosphate (PLP) was proposed. PLP coordinated with europium polymer via Eu 3+ and P-O bonds, and the fluorescence of europium polymer was quenched due to the photoinduced electron transfer (PET) effect between aldehyde and europium polymer. Upon addition of acid phosphatase, the PLP was transformed to phosphate (Pi) and pyridoxal (PL). The PL was released from the surface of europium polymer, and the blue emission was enhanced due to the formation of internal hemiacetal, while the fluorescence of europium polymer recovered. The blue (PL) and red emission (Eu 3+ ) were positively correlated with acid phosphatase activity; thus the sensitive assay of acid phosphatase was effectively achieved. The two signals were applied to determine the acid phosphatase with limits of detection (LOD) of 0.04 mU/mL and 0.38 mU/mL, and the linear ranges were 0.13-5.00 mU/mL and 1.25-20.00 mU/mL, respectively. The probe can be used to trace the acid phosphatase in biological systems and holds promise for use in clinical diagnosis and early prevention.

As the most abundant and significant anions in biosystem, chloride ions (Cl - ) participate in many important physiological processes. Thus, designing and synthesizing of a simple, sensitive, selective and long wavelength turn-on sensor for the detection and imaging of Cl - in vitro and in vivo is very necessary. Herein, we have developed a simple porphyrin turn-on sensor 5, 10, 15, 20-Tetrakis (4-hydroxyphenyl) porphyrin (THPP) with near infrared emission wavelength (657 nm) for sensing chloride ions with remarkable sensitivity and selectivity. The detection of chloride ions was according to metal displacement assay (MDA) under physiological condition with a detection limit of 7.5 μM, and was applied to image Cl - in vitro and in vivo successfully., Competing Interests: Declaration of competing interest We enjoy Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy very much, and would like to submit the enclosed manuscript entitled “A NIR Turn-on Fluorescent Sensor For Detection of Chloride Ions in Vitro and in Vivo”, which was to be considered for publication in Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. No conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for the submission. The corresponding author is Dr Haixia Zhang, the co-authors are Fengyuan Zhang, Chen Ma, Zhijuan Jiao, Shuai Mu, Yida Zhang, Xiaoyan Liu. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this paper, a Merocyanine-based turn-on probe (McyA) has been developed for colorimetric and fluorescent dual-mode detection of N 2 H 4 via an intra-molecular charge transfer (ICT) mechanism. In the presence of N 2 H 4 , the probe shows an obvious chromogenic response and fluorescent enhancement. Based on this feature, the synthesized McyA can be applied to quantify N 2 H 4 concentration from 0.12 to 5.0 μM and 0.5-10 μM with a detection limit of 0.042 μM (1.3 ppb, S/N = 3) and 0.140 μM (4.5 ppb, S/N = 3), respectively. Moreover, McyA has also be successfully employed for imaging analysis of N 2 H 4 distribution in different organs from the N 2 H 4 ingested mice model, revealing the potential application of McyA as a powerful fluorescent sensor for tracking detection and risk assessment of hydrazine in vivo., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Dipeptidyl peptidase IV (DPP-IV) is a transmembrane glycoprotein known to regulate T cell activation, which is related to various pathological processes and has become a potential target to treat type 2 diabetes mellitus. Therefore, it is significant for the evaluation of endogenous DPP-IV activity in various biological systems. Herein, a water-soluble near-infrared (NIR) fluorescent probe HCA-D based on cyanine dyes as the fluorophore and glycyl-prolyl peptide as the specific recognition sequence was developed for the assay of dipeptidyl peptidase IV (DPP-IV) activity. Upon addition of DPP-IV, HCA-D can emit a significant turn-on NIR fluorescence signal under physiological conditions and exhibit high selectivity toward DPP-IV. This feature was available for quantifying DPP-IV in the range from 0.62 to 10 ng mL -1 with a detection limit of 0.19 ng mL -1 . Furthermore, the present probe was successfully employed for monitoring DPP-IV in serum samples from diabetic and healthy people, and imaging of DPP-IV in living cells and tumor mice models. These results demonstrate that the designed probe provides a promising tool to explore the relationship between DPP-IV and diabetes mellitus or other diseases. Perhaps, it may become a prospective image-guided tumor resection indicator based on the abnormal expression of DPP-IV activity in the future.

It is found that hypobromous acid (HOBr) can affect the activity of type IV collagen. Herein, we synthesized a lysosome-targeted fluorescence probe NA-lyso based on Suzuki coupling reaction with naphthalimide as a fluorescent group. HOBr can oxidize the amino group and methylthio group, which increased the degree of conjugation of the probe, thereby affecting its optical properties. Accordingly, it can establish a method for the specific detection of HOBr. NA-lyso has the properties including fast response, high fluorescence quantum yield (Φ = 59.17%), high selectivity, low cytotoxicity and good membrane-permeability. The probe can locate to lysosome of cells. The potential of the probe as biosensor for HOBr was demonstrated by imaging of exogenous and endogenous HOBr in living cells and in mice. In consequence, NA-lyso is expected to be a powerful tool to detect HOBr in complex biosystem and provides a means of exploring physiological functions associated with HOBr in living organisms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

As one of the most widespread anions, chloride ion largely existed in the water sources as well as living organism. Therefore, determination of chloride ions in biological samples is evidently important. Herein, we developed two analogous fluorescence probes BeQ1 and BeQ2 for the sensitive detection of chloride ions. The chloride ions in biological samples were determined by a direct and simple method with the detection limit of 46 and 66 μM respectively. In addition, the probes were found having the two-photon excitation property., (Copyright © 2018 Elsevier B.V. All rights reserved.)

As chloride ions (Cl - ) play a vital role in maintaining normal physiological activity, detection of chloride ions is quite urgent. Hence, we developed chloride fluorescence probes to highly selectively and sensitively monitor chloride ions. The probe M2 with single emission has a high fluorescence quantum yield (Φ = 45%), and it is capable of quantitative detection of Cl - under physiological conditions (pH = 7.4) and pH = 5.0 with a linear range of 0.1-4.0 mM; nevertheless, it is of the switch-off type. We further synthesized a ratiometric fluorescent probe MY with M2 as raw material, which featured excellent selectivity and anti-interference, and large two-photon cross section (555 GM). The probe is conveniently used to detect Cl - in water samples and biological samples including human sweat, serum, and urine samples, indicating it holds great promise for chloride detection and biological application. Graphical abstract ᅟ.

The detection of tyrosinase, a biomarker for melanoma, is of great significance. Herein, a fluorescent tyrosinase probe, with resorufin as the fluorophore and m-tolylboronic acid pinacol ester as the receptor, is proposed. The response relies on the tyrosinase-catalyzed hydroxylation of phenylboronic acid pinacol ester at an adjacent position followed by 1,6-rearrangement elimination to release resorufin. This probe well quantifies tyrosinase in the range from 1 to 100 U mL -1 with a detection limit of 0.5 U mL -1 . Importantly, the probe exhibits high selectivity for tyrosinase over other biological substances including reactive oxygen species. In addition, it is successfully applied to the imaging of tyrosinase in cells. This probe provides a novel platform for selective detection of tyrosinase in biosystems.

A two-photon ratiometric fluorescent probe (Mito-N) has been developed for monitoring mitochondrial nitric oxide (NO) in vivo. Mito-N exhibited excellent selectivity and sensitivity toward NO among various ROS/RNS. The successful two-photon imaging of mitochondrial NO proved that Mito-N is a powerful noninvasive imaging tool in living systems.

We have prepared a near-infrared (NIR) turn-on fluorescent probe (NFC) based on chloroacetate modified naphthofluorescein for specific detection of cysteine (Cys) and homocysteine (Hcy) over glutathione (GSH) and other amino acids (AAs) with the detection limits of 0.30 μM and 0.42 μM, respectively. The fluorescence intensity of the naphthofluorescein (NF) chromophore is modulated by an internal charge transfer (ICT) process. The probe NFC is readily available and weakly fluorescent, but of observably enhanced fluorescence after reacting with Cys or Hcy. We assumed and then demonstrated that the fluorescence off-on process involves a conjugate nucleophilic substitution/cyclization sequence. Furthermore, the probe has been successfully applied for detecting the total content of Cys and Hcy in human plasma and imaging in living cells with low toxicity.

The 4-N,N-dimethyl-1,8-naphthalimide based fluorescent probes have been explored for selective detection of Au(3+). Both probes show a pronounced fluorescence enhancement response to Au(3+). Hydroxy is introduced as ligand of Au(3+) for Probe 1 and the newly designed Probe 2 contains an alkyne moiety to recognize Au(3+) through an irreversible C≡C bond hydrolysis reaction. Probe 1 exhibits higher performance such as faster response, lower detection limit of 0.050μM and the better responsive effect in 99.5% water system compared with most of probes published. The Probe 2 displays high stability to pH, suitable water solubility, wider linear range (0-100μM) to Au(3+), and live-cells imaging with low cytotoxicity., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A new biothiol-selective fluorescent probe 1 based on photoinduced electron transfer (PET) mechanism was designed and synthesized. The UV-Vis absorption and fluorescent emission properties of probe 1 towards various analytes were studied in detail. The probe exhibited a large stokes shift (~200nm) after reacted with biothiols and could selectively detect cysteine (Cys) in dimethyl sulfoxide (DMSO)/H2O solution (9:1, v/v, 10mM phosphate buffer saline, pH3.5) over glutathione (GSH), homocysteine (Hcy) and other analytes with a detection limit of 0.117μM. In addition, probe 1 responded well to GSH, Hcy and Cys in the same above solution with pH5.5 and got the detection limits of 0.151μM, 0.128μM and 0.037μM, respectively. Probe 1 was of very low cytotoxicity and successfully applied for imaging of thiols in living cells., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A two-photon (TP) fluorescence imaging probe (Z1) was designed to detect biothiols through a photoinduced electron transfer pathway utilizing N-butyl-naphthalimide as the fluorophore and 2,4-dinitrobenzene-sulfonyl as the responsive group, which were linked together by piperazine. The synthesized Z1 displayed high selectivity to biothiols, significant fluorescence off-on properties, and a marked two-photon absorption cross section (δ = 110 GM). Moreover, Z1 showed good biocompatibility and insensitivity toward changes in the biologically relevant pH range (7.2-8.4), which enabled the utilization of Z1 to monitor biothiol levels not only in live cells but also in tissues at depths of 50-250 μm.

A novel near-infrared (NIR), turn-on fluorescence probe containing a phosphinate group as a recognizing moiety for the selective detection of O2˙(-) with a low limit of detection (LOD, 9.9 nM) was developed. has good cell-membrane permeability, intracellular stability, and low cytotoxicity. In addition, we successfully applied the to visualize O2˙(-) in live zebrafish, mouse and, for the first time, in mouse liver.

Hydrazine has been applied diffusely in most of the chemical industry; however, it is a hazardous environmental pollutant and highly toxic to organisms. Selective, rapid, and sensitive detection of hydrazine thus becomes absolutely necessary in both biological and environmental sciences. Accordingly, fluorescence probes for hydrazine have been paid great attention in recent years. Disclosed here is the near-infrared (NIR) fluorescence probe with a turn-on fluorescent probe CyJ based on the structure-emission property relationships of the NIR dyes containing an acetyl group as the recognizing moiety. This new probe not only can be readily prepared, but also shows excellent sensing properties. First and most important of all, CyJ is highly selective for N2H4 over various anions, cations, and other amino compounds and has a low limit of detection (LOD) of hydrazine (5.4 ppb as fluorescence sensor and 6.1 ppb as UV sensor). Besides, CyJ exhibited a dramatic increase in fluorescence at λmax = 706 nm in the presence of N2H4, and it offers a rapid, colorimetric and vapor sensing detection process for N2H4 in both aqueous solution and diluted human serum. Furthermore, CyJ has good cell-membrane permeability and low cytotoxicity. In addition, we have successfully applied the CyJ to visualize N2H4 in live mouse and, for the first time, in tissues such as the liver, lung, kidney, heart, and spleen.

A reaction-based two-photon (TP) ratiometric fluorescence probe Z2 has been developed and successfully applied to detect and image fluoride ion in living cells and tissues. The Z2 probe was designed designed to utilize an ICT mechanism between n-butylnaphthalimide as a fluorophore and tert-butyldiphenylsilane (TBDPS) as a response group. Upon addition of fluoride ion, the Si-O bond in the Z2 would be cleaved, and then a stronger electron-donating group was released. The fluorescent changes at 450 and 540 nm, respectively, made it possible to achieve ratiometric fluorescence detection. The results indicated that the Z2 could ratiometrically detect and image fluoride ion in living cells and tissues in a depth of 250 μm by two-photon microscopy (TPM).

The near-infrared (NIR) fluorescence sensor for rapid, selective, and sensitive detection of cystenine (Cys) is of great importance in both biological and environmental sciences. Herein, we report a specific probe with turn-on fluorescence property, visible color change with naked-eye, and large wavelength shift on UV spectra for highly selective detection of Cys over homocysteine (Hcy) and glutathione (GSH) in both HEPES buffer (10 mM, pH 7.4) and diluted human serum. The probe based on the conjugate addition-cyclization reaction has a low limit of detection to Cys (0.16 μM as NIR fluorescence sensor and 0.13 μM as UV sensor). Kinetic study indicated that the probe has a very rapid response to Cys, owing to the much higher pseudo-first-order reaction constant with Cys (299 M(-1) s(-1)) than with Hcy (1.29 M(-1) s(-1)) or GSH (0.53 M(-1) s(-1)). Upon addition of Cys to a solution of the probe, the color changed from purple to cyan, with the maximum wavelength shifting from 582 to 674 nm in the UV spectrum and a fluorescence emission at 697 nm appearing. It has been successfully applied for determination of Cys in diluted serum and bioimaging of Cys in living cells with low cell toxicity.