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Acute kidney injury (AKI) can result in a sudden decline in kidney function and, if not promptly diagnosed and treated, can lead to a high mortality rate. Therefore, there is a critical need for the development of a non-invasive and dependable early diagnostic method for AKI to prevent its progression and deterioration. To address the risk of misdiagnosis or overlooked diagnosis due to reliance on a single biomarker, we developed a novel molecular fluorescent probe (HX-GP) to simultaneously detect and image two biomarkers, γ-Glutamyl transpeptidase (γ-GGT) and Peroxynitrite (ONOO-), in the AKI process. HX-GP can specifically detect γ-GGT in the red fluorescence channel (λem = 613 nm) and ONOO- in the green fluorescence channel (λem = 518 nm). HX-GP demonstrated high sensitivity, selectivity, and rapid response, showing excellent biocompatibility and detection performance. In addition, HX-GP was successful in imaging experiments in a cell model of cisplatin-induced AKI, a result that highlights its potential application value in early diagnosis of AKI.

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Nitric oxide (NO) is a highly reactive signaling molecule involved in diverse biological processes. Simultaneous profiling of NO and associated metabolic fingerprints in a single assay allows more accurate assessments of cell states and offers the possibility to better understand its exact biological roles. Herein, a multiplexing LC-MS workflow was established for simultaneous detection of intracellular NO and various metabolites based on a novel "iridium signature" mass spectrometric probe (Ir-MSP841). This Ir-MSP841 can convert highly liable NO to a stable permanently charged triazole product (Ir-TP852), enabling direct MS detection of NO. This 191/193Ir-signature mass spectrometric probe-based approach is endowed with overwhelming advantages of interference-free, high quantitative accuracy, and great sensitivity (limit of detection down to 0.14 nM). It also reveals good linearity over a wide concentration range 12.5-500 nM and has been successfully employed for exploring the release behaviors of three representative NO donors in cells. Meanwhile, metabolic profiling results reveal that varying the concentrations of NO has distinct effects on various cellular metabolites. This study provides a robust, sensitive, and versatile method for simultaneous detection of NO and numerous metabolites in a single LC-MS run and expands its applications in biomedical research.

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Chemiluminescence (CL) probes that possess near-infrared (NIR) emission are highly desirable for in vivo imaging due to their deeper tissue penetration ability and intrinsically high sensitivity. Herein, a novel iridium-based CL probe (NIRIr-CL-1) with direct NIR emission was reported as the result of hypochlorous acid (HClO)-initiated oxidative deoximation. To improve its biocompatibility and extend the CL time for in vivo imaging applications, this NIRIr-CL-1 was prepared as a CL nanoparticle probe (NIRIr-CL-1 dots) through encapsulation by an amphiphilic polymer Pluronic F127 (F127). All results demonstrate that the NIRIr-CL-1 dots have good selectivity and sensitivity for visualization of HClO even at the depth of 1.2 cm. Owing to these advantages, the CL imaging of exogenous and endogenous HClO in mice was achieved. This study could provide new insights into the construction of new NIR emission CL probes and expand their applications in biomedical imaging.

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Sepsis is a serious systemic inflammatory disease that frequently results in death. Early diagnosis and timely targeted interventions could improve the therapeutic effect. Recent work has revealed that the reactive oxygen species (ROS) in the endoplasmic reticulum (ER) and hypoxia-induced endothelial injury play significant roles in sepsis. However, the relationship between the levels of peroxynitrite (ONOO-) and hypoxia-induced endothelial injury as well as different states of sepsis remain unexplored. Herein, we developed a unique two-photon fluorescent probe (ER-ONOO-) for detecting ONOO- in aqueous solution that has high sensitivity, high selectivity, and ultrafast response time. In addition, ER-ONOO- was successfully used to evaluate the levels of ONOO- at the ER with three kinds of methods in a hypoxia-induced endothelial injury model. Furthermore, ER-ONOO- is capable of monitoring the changes in organ fluorescence through ONOO- variation in different stages of a cecum ligation and puncture (CLP) mouse model. Moreover, we also confirmed that the endoplasmic reticulum stress and oxidative stress participated in the CLP model. Consequently, this research can provide a reliable tool for studying ONOO- fluctuation in sepsis and provide new insights into the pathogenic and therapeutic mechanisms involved.

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Pyroptosis is a newly identified form of cell death that is closely correlated with many diseases. Recent studies have indicated that the inflammation in pyroptosis would accelerate the generation of reactive oxygen species (ROS). In addition, intracellular viscosity is another key microenvironmental parameter that reflects many physiological and pathological states in the early stage, hypochlorous acid (HOCl), as an important ROS, also plays significant roles in a variety of pathologies. However, the fluctuation of viscosity and HOCl in the process of pyroptosis is still unknown. Herein, we present a dual-responsive fluorescent probe (Lyso-VH) for simultaneously detecting viscosity and HOCl. Lyso-VH was successfully used to image the fluctuation of HOCl and viscosity in the lysosome of three kinds of cells with dependent and independent channels. Moreover, Lyso-VH can be employed to investigate the changes of HOCl and viscosity during the process of pyroptosis in living cells and acute lung injury (ALI). Thus, this work can not only serve as a powerful tool to simultaneously visualize the fluctuation of HOCl and viscosity in lysosomes, but also provide a new insight into drug-induced pyroptosis in living cells and acute lung injury.

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Hypochlorite (ClO-), as a type of reactive oxygen species (ROS), plays a crucial role in the process of oxidative stress and is closely related to many diseases. Thus, developing a method for detecting and imaging of ClO- with high sensitivity and selectivity is of great significance. However, the applications of most luminescent probes are limited to the fact that the excitation and emission wavelengths of them are in the visible light region rather than in the near-infrared (NIR) region. Hence, an NIR iridium(III) complex (Mul-NIRIr) with two-photon excitation is designed for the detecting and imaging of ClO-. In the presence of ClO-, the luminescent intensity and lifetime of Mul-NIRIr are remarkably enhanced. Interestingly, Mul-NIRIr also exhibits excellent electrochemiluminescence (ECL) properties, and the ECL signal is significantly enhanced with the addition of ClO-. What is more, Mul-NIRIr is also suitable for the detection and analysis ClO- by flow cytometry. Therefore, Mul-NIRIr is developed to detect multiple signals and is successfully applied to detect exogenous and endogenous ClO- in living cells with one-photon, two-photon, and phosphorescence lifetime image microscopy (PLIM). In addition, Mul-NIRIr was successfully used for imaging of ClO- in tissues and inflammatory mouse models. All of the above results indicate that Mul-NIRIr is highly effective in detecting ClO- in living systems.

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Intracellular polarity is an essential feature of cell physiological state and abnormal polarity changes of various organelles are related to many diseases. Thus, monitoring of polarity changes of multiple subcellular in living cells contributes to understanding different physiological and pathological processes more accurately. However, most of the previous reports on polarity probes mainly monitored the polarity of a single organelle. Therefore, we designed and synthesized two unique polarity-sensitive fluorescent probes LDs-TPFP and Lyso-TPFP, which can be selectively located in lipid droplets (LDs) and lysosomes respectively, to obtain more subcellular information in living cells. Thanks to the strong intramolecular-charge-transfer (ICT) characteristics of probes, the fluorescence intensity and emission wavelength would change with the polarity of the surroundings of cells. Moreover, LDs-TPFP and Lyso-TPFP exhibits large Stokes shift and excellent biocompatibility. Through fluorescence imaging, the probes can effectively distinguish normal cells from cancer cells. In addition, the results of two-photon confocal fluorescence imaging indicated that LDs and lysosomes have discrepant polarity change behaviors under different physiological conditions.

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In this work, a multifunctional ratiometric fluorescence (FL) nanohybrid (CSCDs@DC) was synthesized from chitosan based carbon dots (CSCDs) and dansyl chloride (DC) at room temperature. The CSCDs@DC revealed strong FL intensity, great stability and excellent anti-photobleaching properties. Herein, CSCDs@DC was responsive to pH value in the range of 1.5-4.0 and exhibited color-switchable FL properties between acidic and alkaline environments. In addition, CSCDs@DC showed good selectivity and sensitivity towards Fe3+ ions. A good linear relationship for the Fe3+ ion detection was obtained in the range from 0 µM to 100 µM, with a detection limit of 1.23 µM. What's more, CSCDs@DC can be used as a fluorescent ink. It expressed superior optical properties after 3 months of storage or continuous exposure to UV light for 24 h. This study suggested that CSCDs@DC had potential in the detection of pH and metal ions, as well as showing promising application in the anti-counterfeiting field.

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Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with short survival time. However, owing to the unknown etiology and the lack of sensitive and noninvasive methods, the diagnosis of IPF in the early stage is still full of challenges. Since the levels of oxidative stress in mitochondria are relevant to pulmonary fibrosis, we herein present a simultaneous near-infrared (NIR)-Ia window and ratiometic fluorescent probe, rTPONOO-1, with two-photon and mitochondria-targeting abilities to explore the potential biological roles of peroxynitrite (ONOO-) in different states of lung slices from healthy to lung inflammation and pulmonary fibrosis, and there is a good linear relationship between ratiometric fluorescence changes and the rate of pulmonary fibrosis from hematoxylin and eosin (H&E) and Masson staining. In addition, the therapeutic efficacy of aminoguanidine hemisulfate salt (AG) was also investigated. Thus, rTPONOO-1 has great potential in quickly predicting the progression of pulmonary fibrosis in the early stage and improving effective treatment.

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Two new dinuclear Ru(II) polypyridyl complexes containing three and ten methylene chains in their bridging linkers are synthesized and characterized. Their calf thymus DNA-binding and plasmid DNA photocleavage behaviors are comparatively studied with a previously reported, six-methylene-containing analog by absorption and luminescence spectroscopy, steady-state emission quenching by [Fe(CN)6](4-), DNA competitive binding with ethidium bromide, DNA viscosity measurements, DNA thermal denaturation, and agarose gel electrophoresis analyses. Theoretical calculations applying the density functional theory (DFT) method for the three complexes are also performed to understand experimentally observed DNA binding properties. The results show that the two complexes partially intercalate between the base pairs of DNA. Cellular uptake and colocalization studies have demonstrated that the complexes could enter HeLa cells efficiently and localize within lysosomes. The in-vitro antitumor activity against HeLa and MCF-7 tumor cells of the complexes are studied by MTT cytotoxic analysis. A new method, high-content analysis (HCA), is also used to assess cytotoxicity, apoptosis and cell cycle arrest of the three complexes. The results show that the lengths of the alkyl linkers could effectively tune their biological properties and that HCA is suitable for rapidly identifying cytotoxicity and can be substituted for MTT assays to evaluate the cell cytotoxicity of chemotherapeutic agents.

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The multilayer films consisting of graphene oxide and a cobalt complex were fabricated though electrostatic layer-by-layer self-assembly technique and characterized by UV-Vis absorption spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and cyclic voltammetry. The results demonstrated that the hybrid films were successfully prepared and exhibited good electrochemical activity. The film was also subjected to photoelectrochemical studies and were found to exhibit large cathodic photocurrent density of 6.1 µA/cm(2) while irradiated with 100 mW/cm(2) polychromatic light (730 nm>λ>325 nm) at an applied potential of -0.4V versus saturated calomel electrode.

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In the title compound, [Zn(C(10)H(8)N(2))(C(12)H(8)N(2))(H(2)O)(2)](NO(3))(2)·0.5C(10)H(8)N(2)·H(2)O, the Zn(II) atom is coordinated in a distorted octa-hedral geometry by two N atoms from two 4,4'-bipyridine (4,4'-bipy) ligands, two N atoms from a chelating 1,10-phenanthroline ligand and two O atoms from two mutually cis water mol-ecules. The 4,4'-bipy ligands bridge the Zn(II) atoms into a chain structure along [100]. The uncoordinated 4,4'-bipy mol-ecule lies on an inversion center. O-H⋯O and O-H⋯N hydrogen bonds connect the cationic chains, the nitrate anions, the uncoordinated 4,4'-bipy mol-ecules and the water mol-ecules into tow-dimensional networks.

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In the title copper(II) salt, [Cu(C(6)H(6)N(4))(2)(C(2)H(6)OS)(2)](BF(4))(2), the Jahn-Teller distorted octa-hedral coordination sphere of copper is formed from four 2,2'-bi-1H-imidazole N atoms and two dimethyl sulfoxide O atoms. The Cu atom lies on a center of inversion. N-H⋯O and N-H⋯F hydrogen bonds give rise to a one-dimensional structure. The BF(4) (-) anion is disordered over two sites in a 0.671 (10):0.329 (10) ratio.