Publications by authors named "Caixia Yin"

108 Publications

Comparing the abundance of HClO in cancer/normal cells and visualizing using a mitochondria-targeted ultra-fast fluorescent probe.

Analyst 2021 Apr 16. Epub 2021 Apr 16.

Research Institute of Applied Chemistry, Shanxi University, Taiyuan 030006, China.

Organisms are operating and evolving with a highly sophisticated and intelligent defense mechanism to resist bacterial and viral infections. This process involves a variety of reactive oxygen species (ROS), and they coordinate with each other to support different physiological activities. Due to its strong oxidizing properties, hypochlorous acid (HClO), a part of ROS, is a powerful antimicrobial agent in living organisms and exerts a crucial role in the immune system. However, the excessive production of HClO can cause cell damage and even cell death. Herein, we combined benzene-conjugated benzopyrylium as the fluorophore and dimethylthiocarbamoyl chloride as the recognition site to rationally design a probe (BBD). The fluorescence of the probe was quenched based on an effective PET molecular mechanism. Surprisingly, BBD exhibited a turn-on red fluorescence signal for HClO with ultra-fast response (5 s) and high selectivity. Moreover, BBD located mitochondria well and it was found that the abundance of HClO is higher in HeLa cells compared to that in normal cells. Finally, BBD was successfully applied to the visualization of HClO in zebrafish and nude mice.
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http://dx.doi.org/10.1039/d1an00375eDOI Listing
April 2021

A Pyrene-Based Fluorescent Probe for Specific Detection of Cysteine and its Application in Living Cell.

J Fluoresc 2021 May 20;31(3):727-732. Epub 2021 Feb 20.

Scientific Instrument Center, Shanxi University, Taiyuan, 030006, China.

Cysteine (Cys) is an essential amino acid in organism, which is transformed from methionine in vivo and participates in protein synthesis and cell redox process. Therefore, the detection of Cys is of great significance. In this work, a novel fluorescent probe, (E)-3-(2-chloroquinolin-3-yl)-1-(pyren-3-yl) prop-2-en-1-one (PAQ) was designed and synthesized to specifically detect Cys. The response mechanism of the reaction between PAQ and Cys was due to the addition reaction of Cys to α,β-unsaturated ketone of PAQ. Interestingly, the addition of Cys induced significant fluorescence intensity enhancement at 462 nm. PAQ exhibited favorable sensing properties towards Cys such as the low limit of detection (0.27 μM) and fast response speed (2 min). In addition, PAQ displayed high selectivity and anti-interference ability toward Cys among various analytes. Notably, PAQ has been successfully used to image exogenous and endogenous Cys in HeLa cells.
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http://dx.doi.org/10.1007/s10895-021-02703-6DOI Listing
May 2021

High-Specific Fluorescence Probe for SO Detection and Bioimaging.

J Fluoresc 2021 Mar 4;31(2):363-371. Epub 2021 Jan 4.

Scientific Instrument Center, Shanxi University, Taiyuan, 030006, People's Republic of China.

It is well known that sulfite (SO) plays an indispensable role in various physiological processes. Abnormal levels of SO can trigger a wide variety of diseases involving respiratory, nervous and cardiovascular systems. Hence, it is necessary to find an efficient approach for detection of SO. In this study, a pyrene derivative, (E)-4-(3-oxo-3-(pyren-1-yl)prop-1-en-1-yl)phenyl acrylate (PPA), was designed and synthesized for monitoring SO. The probe possessed simple synthetic steps, excellent anti-interference ability and specific response to SO in the presence of other substances. The reaction between PPA and SO was ascribed to Michael addition and the detection mechanism was confirmed by HRMS spectra analysis and FTIR analysis. Additionally, PPA responded linearly to detect SO within the rang of 0-100 μM. The limit of detection was calculated as low as 0.17 μM in accordance with the recommendation of IUPAC (CDL =3sb/m). Notably, PPA was further applied in biological imaging in HepG2 cells, which provided a possibility to monitor SO in vivo.
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http://dx.doi.org/10.1007/s10895-020-02662-4DOI Listing
March 2021

Rapid Reaction, Slow Dissociation Aggregation, and Synergetic Multicolor Emission for Imaging the Restriction and Regulation of Biosynthesis of Cys and GSH.

J Am Chem Soc 2021 Jan 24;143(1):318-325. Epub 2020 Dec 24.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

Biosynthesis is a necessary process to maintain life. In recent years, research has fully shown that three kinds of biothiols (Cys, Hcy, GSH) mainly play the role in oxidative stress and maintaining cell homeostasis in cells, and that abnormal concentrations will lead to the occurrence of cardiovascular diseases, cancers, etc. Various fluorescent probes have shown unprecedented advantages in detecting their concentrations and studying their biological functions. As a matter of fact, these three kinds of biothiols are generated in the process of biosynthesis in vivo. It is of great significance to understand their biosynthetic pathways and elucidate their synthetic relationships. In this work, to α,β-unsaturated ketones conjugated ethylenediamine coumarin and pyrandione was introduced boron fluoride and, through its strong electron deficiency effect, afforded a molecule having near-infrared emission and regulated the rigidity of molecules. At the same time, the conjugated double bond is used to respond to molecular rigidity. The rapid response of the probe to biothiols and the slow dissociation aggregation of the probe itself through the response environment could monitor the absence of biothiols in cells. In addition, based on the difference in sensitivity of response of Cys and GSH to the probe, this work studied the interaction between biosynthetic pathways of Cys and GSH in cells through enzyme inhibition for the first time. The relationship of restriction and regulation of biosynthesis in vivo was revealed.
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http://dx.doi.org/10.1021/jacs.0c10840DOI Listing
January 2021

An ESIPT-induced NIR fluorescent probe to visualize mitochondrial sulfur dioxide during oxidative stress .

Chem Commun (Camb) 2021 Jan;57(5):655-658

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

Based on the change in electron distribution of the benzopyrylium unit before and after sulfite addition, a 2-(2'-hydroxyphenyl)benzothiazole (HBT)-based fluorophore generated the excited state intramolecular proton transfer (ESIPT) process with a near-infrared enhanced emission at 836 nm and a large Stokes shift (286 nm). The probe was applied to image SO2 derivatives in cells and mice. Our data will provide new ideas for the development of ESIPT-based fluorescence probe with longer wavelength emission.
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http://dx.doi.org/10.1039/d0cc07398aDOI Listing
January 2021

Discovery of a potent β-catenin destabilizer for overcoming the resistance of 5-fluorouracil in colorectal cancer.

Bioorg Med Chem 2021 Jan 9;30:115929. Epub 2020 Dec 9.

Institute of Molecular Science, Shanxi University, Taiyuan, Shanxi 030006, China.

Wnt/β-catenin signalling is frequently activated in colorectal cancer, in which nuclear β-catenin accumulation contributes to tumour initiation and progression. However, therapeutic agents in clinical use targeting this pathway are lacking. In this report, we describe the synthesis of novel stemona alkaloid analogues and their biological evaluation, among which compound 3 was identified to efficiently inhibit various CRC cells, including 5-fluorouracil-resistant CRC cells. Mechanistically, this study revealed that compound 3 reduced the protein level of β-catenin without affecting its mRNA level, which suggests an alternative mechanism for β-catenin degradation. The expression of downstream proteins, including c-myc, survivin, and cyclin D1, was also significantly inhibited, even in Wnt-activated CRC cells. Briefly, our data highlight the potential of compound 3 as a destabilizer of β-catenin for the treatment of CRC patients.
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http://dx.doi.org/10.1016/j.bmc.2020.115929DOI Listing
January 2021

Thiol "Click" Chromene Ring Opening and Subsequent Cascade Nucleophilic Cyclization NIR Fluorescence Imaging Reveal High Levels of Thiol in Drug-Resistant Cells.

Anal Chem 2020 12 23;92(24):15936-15942. Epub 2020 Nov 23.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

As the structural unit of natural products, chromene derivatives show a wide range of biological activity and pharmacological activity due to their unique photophysical and chemical properties. Ten years ago, our research group discovered the "thiol-chromene" click reaction, which achieved the selective detection of thiols through the change of the optical spectrum. Afterward, we attempted to develop various chromene-based fluorescent probes for imaging including near-infrared (NIR) probe, ratiometric probe, and multifunctional probe. However, how to integrate the fluorophore and reaction sites into the chromene-based skeleton remains challenging. In this work, we connected the chromene motif with the NIR fluorophore methylene blue utilizing a carbamate spacer to provide a new fluorescent probe (CM-NIR), which is triggered by thiols to open the pyran ring followed by attacking the carbamate by phenolate to releases the methylene blue. This novel cascade mechanism avoids the formation of para-quinone methides, which proved to be toxic to normal cells. CM-NIR also showed the specific imaging of thiols in living cells and mice. More importantly, the thiols level in drug-resistant cancer cells was found to be significantly higher than that in the corresponding cancer cell, which indicated that the thiols level may have an important role in cancer cells developing drug resistance.
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http://dx.doi.org/10.1021/acs.analchem.0c03362DOI Listing
December 2020

The reduction performance of double bonds regulated by the competition of push-pull electron groups to realize the colorimetric and fluorescence recognition of hypochlorous acid.

Analyst 2020 Nov;145(22):7297-7302

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

Based on its reducibility, the double bond can act as a reaction site for hypochlorous acid (HOCl), which had been demonstrated by a great deal of work. Nevertheless, the reactivity is influenced by the adjacent chemical environment. Therefore, in this work, we constructed a probe (QI) by methoxy-substituted quinoline conjugating dicyanoisoflurone, in which dicyano and pyridine N act as electron-withdrawing groups and the methoxy acts as an electron-donating group, to regulate their adjacent C[double bond, length as m-dash]C reactivity. The "push-pull" electron effect between the methoxy group and the pyridine N led to the C[double bond, length as m-dash]C bond being passivated. On the other hand, another C[double bond, length as m-dash]C bond was activated by the strong electron-pulling effect of the dicyano group. Thus, the previously weak intramolecular charge transfer became stronger after the dicyano adjacent to the C[double bond, length as m-dash]C was oxidized by HOCl, and showed a strong emission shifted from 570 to 520 nm along with a color change. The reaction mechanism was verified by mass spectrometry, NMR and theoretical calculation, and further bioimaging demonstrated the practical application of the probe.
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http://dx.doi.org/10.1039/d0an01551bDOI Listing
November 2020

A New Strategy: Distinguishable Multi-substance Detection, Multiple Pathway Tracing Based on a New Site Constructed by the Reaction Process and Its Tumor Targeting.

J Am Chem Soc 2020 10 13;142(43):18706-18714. Epub 2020 Oct 13.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, P. R. China.

In recent years, it has become a trend to employ organic molecular fluorescent probes with multireaction sites for the distinguishable detection and biological imaging of similar substances. However, the introduction of multireaction sites brought great challenges to organic synthesis, and at the same time, often destroyed the conjugated structure of the molecules, leading to an unsatisfactory fluorescence emission wavelength not conducive to practical application. As the eternal theme of life, metabolism goes on all the time. Metabolism is a series of ordered chemical reactions that occurs in the organism to maintain life. Chemical reactions in metabolism can be summarized as metabolic pathways. Simultaneous monitoring of different metabolic pathways of the same substance poses a lofty challenge to the probe. Here, we developed a new strategy: to construct new sites through the preliminary reactions between probes and some targets, which can be used to further distinguish among targets or detect their metabolites, so as to realize the simultaneous visualization tracer of multiple metabolic pathways. By intravenous injection, it revealed that the probe containing benzopyrylium ion can target tumors efficiently, and thiols are highly expressed in tumors compared to other tissues (heart, lung, kidney, liver, etc.). The consumption of thiols by the probe could not prevent tumor growth, suggesting that the tumor cure was not correlated with thiol concentration. The construction of new sites in the reaction process is a novel idea in the pursuit of multiple reaction sites, which will provide more effective tools for solving practical problems.
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http://dx.doi.org/10.1021/jacs.0c10210DOI Listing
October 2020

Specific Fluorescent Probe Based on "Protect-Deprotect" To Visualize the Norepinephrine Signaling Pathway and Drug Intervention Tracers.

J Am Chem Soc 2020 10 1;142(41):17751-17755. Epub 2020 Oct 1.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

In recent years, increased social pressure and other factors have led to a surge in the number of people suffering from depression: studies show that quite a few people will experience major depression in their lifetime. Currently, it is widely believed that the internal cause of major depression is reduced levels of norepinephrine (NE) in brain tissue. Norepinephrine is very similar in structure and chemical properties to the other two catecholamine neurotransmitters, epinephrine (EP) and dopamine (DA). These three neurotransmitters are synthesized sequentially through enzymatic reactions in the biological system. Therefore, design of a norepinephrine-specific fluorescent probe is very challenging. In this work, we utilized a "protect-deprotect" strategy: longer emission wavelength cyanine containing water-soluble sulfonate was protected by a carbonic ester linking departing group thiophenol; the β-hydroxy ethyl amine moiety of norepinephrine may react with the carbonic ester via nucleophilic substitution and intramolecular nucleophilic cyclization to release the fluorophore. The process realized the specific red fluorescence detection of norepinephrine. Imaging of the norepinephrine nerve signal transduction stimulated by potassium ion was studied. More importantly, real-time fluorescence imaging of norepinephrine levels in the brain of rats stimulated by antidepressant drugs was studied for the first time.
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http://dx.doi.org/10.1021/jacs.0c08956DOI Listing
October 2020

A review: Red/near-infrared (NIR) fluorescent probes based on nucleophilic reactions of H S since 2015.

Luminescence 2020 Dec 21;35(8):1156-1173. Epub 2020 Sep 21.

Department of Chemistry, Xinzhou Teachers University, Xinzhou, Shanxi, China.

The topics of human health and disease are always the focus of much attention. Hydrogen sulfide (H S), as a double-edged sword, plays an important role in biological systems. Studies have revealed that endogenous H S is important to maintain normal physiological functions. Conversely, abnormal levels of H S may contribute to various diseases. Due to the importance of H S in physiology and pathology, research into the effects of H S has been active in recent years. Fluorescent probes with red/near-infrared (NIR) emissions (620-900 nm) are more suitable for imaging applications in vivo, because of their negligible photodamage, deep tissue penetration, and maximum lack of interference from background autofluorescence. H S, an 'evil and positive' molecule, is not only toxic, but also produces significant effects; a 'greedy' molecule, is not only a strong nucleophile under physiological conditions, but also undergoes a continuous double nucleophilic reaction. Therefore, in this tutorial review, we will highlight recent advances made since 2015 in the development and application of red/NIR fluorescent probes based on nucleophilic reactions of H S.
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http://dx.doi.org/10.1002/bio.3831DOI Listing
December 2020

A practical pH-compatible fluorescent sensor for hydrazine in soil, water and living cells.

Analyst 2020 Nov 15;145(22):7380-7387. Epub 2020 Sep 15.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

The excellent water solubility of hydrazine (NH) allows it to easily invade the human body through the skin and respiratory tract, thereby damaging human organs and the central nervous system. To realize the monitoring of NH effectively, first, coumarin was used to construct an inner alicyclic ring as the reaction site, extending the conjugation and strengthening the rigidity of the probe Co-Hy to improve its luminescence performance and enhance its ability to resist acids and alkalis. Second, we introduced a carboxyl group at the ortho position of the inner alicyclic ring to improve the water solubility of Co-Hy, and its strong electron pulling effect increased the activity of the reaction site. Spectroscopy experiments showed that Co-Hy featured excellent water solubility, high pH resistance (pH 4-11), excellent selectivity, fast analysis speed (within 5 minutes), and a low detection limit toward NH (69 nM, 2.2 ppb). In addition, test-strip, spray, and cell-imaging experiments confirmed the outstanding application potential of Co-Hy for convenient NH analysis in a variety of environments.
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http://dx.doi.org/10.1039/d0an01633kDOI Listing
November 2020

Malononitrile as the 'double-edged sword' of passivation-activation regulating two ICT to highly sensitive and accurate ratiometric fluorescent detection for hypochlorous acid in biological system.

Sens Actuators B Chem 2020 Dec 25;325:128793. Epub 2020 Aug 25.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, China.

Hypochlorous acid (HOCl) as one of the most important reactive oxygen species in the organism, its role is more and more recognized. In fact, in recent years, various HOCl fluorescent probes have been developed unprecedentively based on various mechanisms. However, because most of the mechanisms are based on the oxidation characteristics of HOCl, the excellent detection performance of probes depends on the activation ability of some functional groups to reaction sites. The C[bond, double bond]C bond in the probe is often oxidized by HOCl to realize HOCl detection. However, due to the break of conjugated structure, the probe often present as a quenchable or turning on fluorescence emission. In this work, malononitrile was introduced as the "double-edged sword" of passivation-activation when in HOCl fluorescent probe was designed. Passivation-activation regulated two ICT (Intermolecular Charge Transfer, ICT) processes to ratiometric fluorescent detection for HOCl. Highly sensitive and accurate detection realized efficient application in biological imaging.
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http://dx.doi.org/10.1016/j.snb.2020.128793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446621PMC
December 2020

Carbazole-conjugated-coumarin by enone realizing ratiometric and colorimetric detection of hypochlorite ions and its application in plants and animals.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Dec 11;243:118813. Epub 2020 Aug 11.

Institute of Molecular Science, Shanxi University, Taiyuan 030006, PR China. Electronic address:

Detection of hypochlorite ions (ClO) in the organisms is of great significance for finding effective treatments for inflammations and diseases. Recently, fluorescent probes have aroused wide public concern as one of the effective tools for detecting molecules and ions. Nevertheless, due to low sensitivity and poor biocompatibility, the effect of fluorescent probes for biological imaging is still not ideal. For this, we developed a novel ratiometric fluorescent probe, 7-(diethylamino)-3-((E)-3-(9-ethyl-9H-carbazol-3-yl)acryloyl)-2H-chromen-2-one (DCC), which could be used for colorimetric detection of ClO. Study showed that, the detection mechanism of DCC is that probe can be rapidly oxidized to an enoic acid by ClO, resulting in a series of changes in spectral properties. This mechanism was confirmed experimentally and verified by theoretical calculations. It is worth mentioning that DCC has not only been successfully applied to the detection of exogenous and endogenous OCl in living cells, but also used for the detection of ClO in zebrafish, and Arabidopsis.
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http://dx.doi.org/10.1016/j.saa.2020.118813DOI Listing
December 2020

Independent bi-reversible reactions and regulable FRET efficiency achieving real-time visualization of Cys metabolizing into SO.

Chem Commun (Camb) 2020 Sep;56(77):11453-11456

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

In this work, we synthesized an independent bi-reversible reaction sensor BPC for simultaneously detecting cysteine (Cys) and sulfur dioxide (SO2), showing multi-fluorescence signal modes due to the regulable FRET efficiency, and finally achieving real-time process visualization of Cys metabolizing into SO2 in subcellular organelles and tumors.
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http://dx.doi.org/10.1039/d0cc04839aDOI Listing
September 2020

Mutual correlation evaluation of Cys and Hcy in serum through reaction activity regulated fluorescence quantification.

Chem Commun (Camb) 2020 Aug;56(64):9146-9149

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

We report herein a strategy involving using a single fluorescent probe with the assistance of two pH conditions to simultaneously detect cysteine and homocysteine quantitatively. The concentrations of Cys and Hcy in human serum samples were found to display a positive correlation, which might promote a further understanding of thiol-related diseases.
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http://dx.doi.org/10.1039/d0cc03457fDOI Listing
August 2020

Fluorescent probe for detecting hydrogen sulfide based on disulfide nucleophilic substitution-addition.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Sep 3;238:118437. Epub 2020 May 3.

Department of Chemistry, Xinzhou Teachers University, Xinzhou 034000, Shanxi, China; Institute of Molecular Science, Shanxi University, Taiyuan 030006, China. Electronic address:

In view of the importance of hydrogen sulfide (HS) in the organism, a fast, noninvasive method for the detection of HS in situ is needed. Fluorescent probes based on disulfide-bond nucleophilic substitution-addition can selectively detect HS in vivo, which is very popular because it allows quick response for HS, thus it will be a useful tool for monitoring HS in the vivo. We developed a dicyanoisopentanone-based HS fluorescent probe (EW-H) that used a disulfide group as a self-destructive linker reaction site. Under the nucleophilic substitution of HS, the disulfide bond of EW-H was cleaved, and then nucleophilic addition took place intramolecularly to release the fluorophore (at 580 nm). The response to HS, EW-H had high sensitivity (86 nM of the detection limit), large Stokes shift (155 nm) and a fast response time. More importantly, the probe was also applied for bioimaging in HepG2 cells, indicating its potential applications in biological organism.
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http://dx.doi.org/10.1016/j.saa.2020.118437DOI Listing
September 2020

Dual-site functionalized NIR fluorescent material for a discriminative concentration-dependent response to SO in cells and mice.

J Mater Chem B 2019 03 18;7(11):1945-1950. Epub 2019 Feb 18.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy, Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

Sulfur dioxide (SO), as an important anti-oxidant and gaseous signaling molecule, plays fundamental roles in the regulation of intracellular signaling and cell death cellular bioenergetics. The accurate determination of the SO levels in an organism is a critical step in establishing its biological functions. Therefore, there is a high demand for developing efficient analytical methods for monitoring the wide range of concentration changes of SO in living systems. Herein, for the first time, we have successfully constructed a dual-site functionalized NIR fluorescent material (NIR-SP), which is capable of monitoring low concentrations of SO with red fluorescence responses and high concentrations of SO with blue fluorescence enhancements. Further studies absolutely confirmed that the discriminative response was due to the fact that the reactivity of the unsaturated C[double bond, length as m-dash]C double bond (site I) in NIR-SP was superior to that of the aldehyde group (site II). Furthermore, detection in a concentration-dependent manner was demonstrated by fluorescent imaging in cells and mice. We envision that this strategy would lead to insights into SO concentration-dependent biological effects and cell signals.
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http://dx.doi.org/10.1039/c8tb03253jDOI Listing
March 2019

Fluorescent Imaging of Resveratrol Induced Subcellular Cysteine Up-Regulation.

Anal Chem 2020 05 13;92(9):6598-6603. Epub 2020 Apr 13.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.

Even through many physiological pathways of resveratrol have been established since its association with the "French paradox" in 1992, its exact pathological roles are still ambiguous and disputable. To understand how resveratrol exerts its effects would not only enlighten the pathogenesis study of related diseases, but also promote the development of more potent molecules. Focusing on the reported cellular directly and indirectly ROS scavenging processes of resveratrol, we evaluated the activation effect of the inherent antioxidation thiols system in subcellular level by two cysteine (Cys) specific fluorescent probes mitochondria targetable and lysosomes targetable . We found that 50 μM resveratrol treatment could induce distinct Cys up-regulation in both mitochondria and lysosomes which might be a general biological phenomenon in various cell lines for the first time.
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http://dx.doi.org/10.1021/acs.analchem.0c00363DOI Listing
May 2020

Mitochondria-targeted reversible ratiometric fluorescent probe for monitoring SO/HCHO in living cells.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Jun 12;234:118253. Epub 2020 Mar 12.

Research Institute of Applied Chemistry, Shanxi University, Taiyuan 030006, China. Electronic address:

Sulfur dioxide (SO) maintains a certain steady state balance in the body, high concentration SO will be harmful to human health. Seeking a suitable detection method to monitor sulfur dioxide in real time becomes an urgent requirement owing to the transient nature of sulfur dioxide in organisms. Here, a novel NIR ratiometric fluorescent probe for detection of SO was developed based on a conjugation of coumarin and indol salt with excellent water solubility. The probe Mito-CI displayed highly sensitive (69 nM), fast response time (30 s), large Stokes shift (174 nm) and the NIR fluorescence emission wavelength (655 nm). In the reversibility process of the SO-probe Mito-CI system induced by HCHO in vitro was also detected. Besides, cell imaging showed that Mito-CI possesses mitochondria-targeted ability. Particularly, Mito-CI was proved to reversibly detect SO/HCHO in living cells.
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http://dx.doi.org/10.1016/j.saa.2020.118253DOI Listing
June 2020

Employing an ICT-FRET Integration Platform for the Real-Time Tracking of SO Metabolism in Cancer Cells and Tumor Models.

J Am Chem Soc 2020 04 17;142(13):6324-6331. Epub 2020 Mar 17.

Key Laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, P. R. China.

Glutathione (GSH) mediates a wide variety of biological events and human diseases. Although it has been the subject of intense study in recent years, a further understanding of its molecular mechanisms and metabolism routes in living cells has remained limited due to a lack of appropriate analytical tools. Sulfur dioxide (SO), an important metabolite of GSH, is usually associated with the symptoms of neurological disorders, cardiovascular diseases, and lung cancer. Herein, a novel multisignal fluorescent probe was rationally designed and exploited for the simultaneous detection of GSH and its metabolite SO via an ICT-FRET synergetic mechanism. The probe shows completely reversed fluorescence responses toward GSH (enhanced red emission) and SO (annihilated red fluorescence) with high selectivity and sensitivity. In particular, the probe displayed completely different fluorescent signals (blue-shift) with SO in the presence of GSH, thereby allowing the imaging of the metabolism process of GSH to SO in two independent channels without spectral cross interference. Given these advantages, this probe has been successfully applied to the real-time monitoring of the SO metabolic process in living cells and mice models, and it has thus been found that GSH can metabolize SO by enzymatic reaction with TST (thiosulfate sulphurtransferase); additionally, SO was transformed into sulfate under SUOX (sulfite oxidase). We anticipate that this research will provide a convenient and efficient tool for understanding the interrelated physiological functions of GSH and SO in more biosystems.
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http://dx.doi.org/10.1021/jacs.0c00992DOI Listing
April 2020

A copper-mediated on-off-on gold nanocluster for endogenous GSH sensing to drive cancer cell recognition.

J Mater Chem B 2019 04 27;7(13):2169-2176. Epub 2019 Feb 27.

Department of Chemistry, College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, P. R. China.

The sensitive and selective detection of endogenous glutathione (GSH) is of great significance due to its key role in physiological and pathological processes. Herein, we report a novel on-off-on transferrin (Tf)-coated gold nanocluster (AuNCs@Tf) with low toxicity, good stability and intense red fluorescence which can enter living cells and is mainly located in lysosomes. In addition, the fluorescence of AuNCs@Tf is quenched by Cu, indicating its sensitivity to Cu with a detection limit of 0.23 μM at pH 4.5. Interestingly, we found that the quenched AuNCs@Tf-Cu system only has a special affinity for GSH with a detection limit of 2.86 μM so that invisible AuNCs@Tf-Cu can be gradually illuminated by endogenous GSH in the lysosomal environment of tumor cells with increase in time. More excitingly, the AuNCs@Tf-Cu system can illuminate tumor cells rather than normal cells, resulting in its successful application in cancer cell recognition, which implies its great potential application in cancer diagnosis. Moreover, the AuNCs@Tf was also applied in Cu strips and encryption/decryption of information.
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http://dx.doi.org/10.1039/c8tb03184cDOI Listing
April 2019

Heat Stroke in Cell Tissues Related to Sulfur Dioxide Level Is Precisely Monitored by Light-Controlled Fluorescent Probes.

J Am Chem Soc 2020 02 29;142(6):3262-3268. Epub 2020 Jan 29.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science , Shanxi University , Taiyuan 030006 , China.

Heat stroke (HS) can cause serious organism damage or even death. Early understanding of the mechanism of heat cytotoxicity can prevent or treat heat stroke related diseases. In this work, probe was synthesized, characterized, and used for sulfur dioxide (SO) detection in lysosomes. PBS solutions of probe at pH 5.0 present a marked broad emission band in the green zone (535 nm). After UV irradiation, the spiropyran group in isomerizes to the merocyanine form (), which presented a weak red-shifted emission at 630 nm. In addition, photocontrolled isomerization of to generated a C═C-C═N fragment able to react, through a Michael addition, with SO to yield a highly emissive adduct with a marked fluorescence in the green channel (535 nm). In vitro studies showed a remarkable selectivity of photoactivated to SO with a limit of detection as low as 4.7 μM. MTT viability assays demonstrated that the is nontoxic to HeLa cells and can be used to detect SO in lysosomes. Taking advantage of this, the sensor is successfully applied to image increasing SO values in lysosomes during heat shock for the first time. Moreover, we also confirmed that the increased SO can protect the small intestine against damage induced by heat shock through regulating oxidative stress in cells and mice.
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http://dx.doi.org/10.1021/jacs.9b13936DOI Listing
February 2020

Fast detecting hypochlorous acid based on electron-withdrawing group promoted oxidation and its biological applications in cells and root tips of plants.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Mar 28;229:118001. Epub 2019 Dec 28.

Institute of Molecular Science, Shanxi University, Taiyuan 030006, China. Electronic address:

Hypochlorous acid, a type of reactive oxygen species, has been shown to play an important role in organisms. Nowadays, there are many kinds of fluorescence detecting mechanisms to detect hypochlorous acid in vivo. Due to the high selectivity, the mechanism of using the strong oxidation of hypochlorous acid to break carbon‑carbon double bonds has been favored by many scientists. However, the reported probes of breaking carbon‑carbon double bonds still had drawback such as slow response. Based on this, we introduced electron-withdrawing group malonitrile to accelerate the oxidation of hypochlorous acid, resulting in reaction time less than 150 s. Meanwhile, the probe exhibited excellent selectivity, optical stability, high sensitivity and the detection limit as low as 0.19 μM. More importantly, we also successfully proved the potential application of the probe for the detection of intracellular ClO living cells and Arabidopsis root tip by fluorescence imaging.
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http://dx.doi.org/10.1016/j.saa.2019.118001DOI Listing
March 2020

A novel strategy: A consecutive reaction was used to distinguish in the presence of statins between normal cells and cancer cells.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Mar 23;229:117987. Epub 2019 Dec 23.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China. Electronic address:

Statins, as the most commonly drugs could reduce the concentration of low-density lipoprotein cholesterol, have been proved to elevate the HS generation in cells. Besides, the abnormal levels of biothiols might lead to cancer. Therefore, it is worth considering how to combine the characteristics of the two diseases to realize the detection of cancer cells. Based on this view, we developed a multiresponse fluorescent probe for the detection of hydrogen sulfide (HS) and biothiols successively based on theoretical calculation. It is interesting that the fluorescence intensity of the probe reacting HS and biothiols successively was significantly higher than that of probe reacting either of them. Based on this view, we further explored the biological application of the probe and found that the probe had obvious signal response to cancer cells than the normal cells in the presence of fluvastatin. This interesting finding might provide a new insight into cancer cell recognition.
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http://dx.doi.org/10.1016/j.saa.2019.117987DOI Listing
March 2020

Thiol-Chromene "Click" Reaction Triggered Self-Immolative for NIR Visualization of Thiol Flux in Physiology and Pathology of Living Cells and Mice.

J Am Chem Soc 2020 01 10;142(3):1614-1620. Epub 2020 Jan 10.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science , Shanxi University , Taiyuan 030006 , P. R. China.

Understanding the pathological process of biological systems can greatly improve the prevention and treatment of diseases. The study of pathological processes has now reached the molecular level, and molecular fluorescent probes have become a powerful tool. Chromene, also known as benzo-pyran molecule, is a structural element of natural products with good biological compatibility and was developed as a fluorescent probe. The thiol-chromene "click" nucleophilic pyran ring-opening reaction allows the quick detection of thiol. In this work, the chromene alcohol can function as an efficient self-immolative spacer, which covalently links NIR fluorophore via a carbonyl ester. Due to its favorable characteristics and superior applicability, the self-immolative amplifier achieves the specific, rapid, sensitive, NIR fluorescent detection of thiols. Furthermore, the indoles iodized salt in the system can specifically target thiols in mitochondria. Thus, this probe was used to visualize the fluctuations of thiols during oxidative stress and cell apoptosis, cerebral ischemia reperfusion, demonstrating that it is valuable for elucidating pathophysiology process in living organism. This discovery provides an effective means for studying the pathological process of thiol related diseases.
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http://dx.doi.org/10.1021/jacs.9b12629DOI Listing
January 2020

A water-soluble fluorescent probe for the detection of thiophenols in water samples and in cells imaging.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Mar 7;229:117905. Epub 2019 Dec 7.

Research Institute of Applied Chemistry, Shanxi University, Taiyuan 030006, China. Electronic address:

Water pollution is the main cause of death of aquatic organisms such as fish et al. Content of thiophenols in water samples is an important indicator for assessing the degree of water pollution. The development of fluorescent probes with high selectivity and high sensitivity to detect thiophenols in water samples is extremely important in both environmental and life sciences. Although several fluorescent probes for thiophenols detection have been reported in recent years, most of them required the assistance of organic solvents to remedy the restriction caused by the poor water solubility of the probe, which did not fully reflect the actual situation of thiophenols in actual water samples. To fully overcome this shortage, we modified the 1,8-naphthylimide moiety with carboxyl to obtain a water-soluble fluorescent probe which could react with thiophenols specifically through nucleophilic aromatic substitution reaction (SAr) reaction with turn-on fluorescent responses. The corresponding detection limit was 71 nM. Supported by the spectroscopic changes, test strips based on the probe could detect thiophenols quantificationally and conveniently. At the same time, the probe could detect thiophenols in water sample with quantitative recovery. Besides, cell imaging experiments demonstrated the possibility of the probe to detect thiophenols in living cells.
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http://dx.doi.org/10.1016/j.saa.2019.117905DOI Listing
March 2020

The relationship between urinary kidney injury molecule-1 and blood bone metabolism markers in patients with chronic kidney disease
.

Clin Nephrol 2020 Feb;93(2):65-76

Objective: The aim of this study was to evaluate the changes of urinary kidney injury molecule-1(uKIM-1) in chronic kidney disease (CKD) at different stages, and to determine the relationships between uKIM-1 and circulating bone metabolism markers.

Materials And Methods: This cross-sectional study included CKD patients (n = 121) and controls (n = 65). CKD stages were assigned to each individual according to their estimated glomerular filtration rate (eGFR), which was calculated with the modification of diet in renal disease (MDRD) equation. We evaluated the relationships of bone metabolism markers (including calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D (25(OH)D), alkaline phosphatase (ALP), fibroblast growth factor 23 (FGF23), and α-Klotho), uKIM-1, and eGFR. We also compared the levels of bone metabolism markers and uKIM-1 at different CKD stages. The uKIM-1 level was standardized with urine creatinine (uCr).

Results: Compared with healthy controls, CKD patients had higher levels of uKIM-1/uCr, serum creatinine, urea, phosphorus, iPTH, and plasma FGF23, whereas they had lower levels of serum calcium, α-Klotho, and plasma 25(OH)D. In CKD patients, eGFR was positively correlated with levels of serum calcium, α-Klotho, and plasma 25(OH)D, whereas it was negatively correlated with serum phosphorus, iPTH, plasma FGF23, and uKIM-1/uCr. Serum calcium and α-Klotho were significantly decreased in patients with stage 5 CKD compared to those with stage 1 CKD. Serum phosphorus, iPTH, and plasma FGF23 were significantly elevated in patients with stage 4 CKD when compared to those with stage 1 CKD. UKIM-1/uCr was significantly elevated in patients with stage 5 CKD when compared to those with stage 1 CKD. In CKD patients, uKIM-1/uCr levels were positively correlated with levels of serum phosphorus and plasma FGF23, whereas they were negatively correlated with serum calcium and plasma 25(OH)D.

Conclusion: UKIM-1/uCr levels are increased with the deterioration of CKD stage and are correlated with the development of CKD-mineral and bone disorder (CKD-MBD).
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http://dx.doi.org/10.5414/CN109763DOI Listing
February 2020

CZYH Alleviates -Amyloid-Induced Cognitive Impairment and Inflammation Response via Modulation of JNK and NF-B Pathway in Rats.

Behav Neurol 2019 4;2019:9546761. Epub 2019 Nov 4.

Key Laboratory of Basic Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, Guizhou 563000, China.

Cu-Zhi-Yi-Hao (CZYH), an empirical formula of traditional Chinese medicine (TCM), has been used for amnesia treatment in clinical practice. However, its underlying pharmacological mechanism has not been fully illuminated. The current study was designed to investigate the neuroprotective effect of CZYH on a -amyloid 25-35- (A-) induced learning and memory deficit rat model. CZYH (200, 400, or 800 mg/kg), donepezil (1.0 mg/kg), or distilled water was given to A-stimulated animals for 17 days consecutively. The Morris water maze test revealed that CZYH (400 or 800 mg/kg) administration improved the A-induced cognitive impairments in rats, and Nissl staining demonstrated that CZYH mitigated the A-caused neuron loss. In addition, CZYH treatment markedly inhibited the activation of microglia as evidenced by a decreased level of IBA-1 and increased YM-1/2 protein expression. The protein expression levels of TNF-, IL-1, and COX-2 were also repressed by CZYH. Besides, CZYH treatment alleviated A-induced IB- degradation and NF-B p65 phosphorylation, as well as reduced the JNK phosphorylation level. In conclusion, the present study suggests that CZYH could improve learning and memory abilities and relieve neuron loss in A-induced rats, at least partly through inhibition of the neuroinflammatory response via inhibiting the JNK-dependent NF-B activation, indicating that CZYH might be a promising formula for the treatment of AD.
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http://dx.doi.org/10.1155/2019/9546761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875391PMC
April 2020

A new strategy for the fluorescence discrimination of Cys/Hcy and GSH/HS simultaneously colorimetric detection for HS.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Feb 26;227:117537. Epub 2019 Oct 26.

School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, 030006, China; Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Key Laboratory of Materials for Energy Conversion and Storage of Shanxi Province, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, China. Electronic address:

The development of fluorescent probes enabling distinguishable detection Cys, Hcy, GSH and HS is still a considerable challenge owing to their similar functional group with comparable reactivity. In this work, a novel fluorescent probe FHC-O-NBD has been synthesized, and a practicable strategy for the fluorescence discrimination of Cys/Hcy and GSH/HS, especially the colorimetric detection for HS have been presented. FHC-O-NBD reacted with Cys/Hcy to produce two fluorescent emissions at 486 nm and 550 nm, while for GSH/HS, only one fluorescent signal at 486 nm appeared. And, only upon addition of HS, the color of the system changed from colorless to pink. So it can serve as a colorimetric probe for HS by "naked eye". Furthermore, FHC-O-NBD can selectively distinguish Cys/Hcy and GSH/HS in living cells, meaning it has great potential in biological applications.
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http://dx.doi.org/10.1016/j.saa.2019.117537DOI Listing
February 2020