Search

A novel ratiometric luminescence "dual-key-and-lock" probe based on "ruthenium(II) complex-coumarin" scaffold was constructed for detection and imaging of formaldehyde in lysosomes of living cells and mouse brain tissues. [Display omitted] • A novel ratiometric luminescence probe Ru-COU for formaldehyde was constructed with a large emission shift (Δλ > 100 nm). • Ru-COU can specifically recognize formaldehyde under acidic microenvironment and localize lysosomes in living cells. • Ru-COU was successfully employed in the ratiometric imaging of formaldehyde in living cells and mouse brain tissues. Ratiometric luminescence probes have attracted widespread attention because of their self-calibration capability. However, some defects, such as small emission shift, severe spectral overlap and poor water solubility, limit their application in the field of biological imaging. In this study, a unique luminescence probe, Ru-COU , has been developed by combining tris(bipyridine)ruthenium(II) complex with coumarin derivative through a formaldehyde-responsive linker. The probe exhibited a large emission shift (Δλ > 100 nm) and good water solubility, achieving ratiometric emission responses at 505 nm and 610 nm toward formaldehyde under acidic conditions. Besides, ratiometric luminescence imaging of formaldehyde in living cells and Alzheimer disease mouse's brain slices demonstrates the potential value of Ru-COU for the diagnosis and treatment of formaldehyde related diseases. [ABSTRACT FROM AUTHOR]

The progression of Alzheimer's disease (AD) is accompanied by the increase of copper ions (Cu2+) concentration and decrease of hydrogen sulfide (H 2 S) level in brain tissue, thus, reversible detection of Cu2+ and H 2 S is regarded as an important strategy for the diagnosis and intervention of AD. However, reliable tools for reversible tracking of Cu2+ and H 2 S and demonstrate their dynamic changes in AD are still lacking. Herein, this work developed a novel NIR Ir(III) complex-based probe, named NIR-Ir-DA, for reversible tracking of Cu2+ and H 2 S in AD cells and brain tissues. The newly prepared NIR luminescence probe exhibited fast response, high sensitivity and selectivity, good biocompatibility, which makes it to be used for reversible sensing of Cu2+ and H 2 S in multiple cycles in living cells and assessing AD progression in vitro and in vivo. Furthermore, using NIR-Ir-DA as a probe, we screened the theaflavin-3,3′-digallate (TF3) from polyphenols with an outstanding ability to reduce neuroinflammation, which would be greatly beneficial for AD therapy. These results indicated that NIR-Ir-DA could be a useful tool for understanding the role of "Cu2+-H 2 S seesaw" phenomenon in amyloid-β deposition, as well as for assessing AD progression and screening anti-AD drugs. [Display omitted] • A NIR Ir(III) complex probe for reversible detection of Cu2+ and H 2 S was developed. • Fast response, high sensitivity and selectivity towards Cu2+ and H 2 S was achieved. • Reversible detection of Cu2+ and H 2 S in multiple cycles in living nerve cells. • Assess AD progression in vitro and in vivo was successfully demonstrated. • Screen anti-AD drugs through visualization of the "Cu2+-H 2 S seesaw" phenomenon.. [ABSTRACT FROM AUTHOR]

The development of reliable bioanalytical probes for sensitive and specific detection of hydrogen sulfide (H 2 S) plays important role for better understanding the roles of this biomolecule in living cells and organisms. Taking advantages of unique photophysical properties of ruthenium(II) (Ru(II)) complex, this work presents the development of a responsive Ru(II) complex probe, Ru-PNBD , for colorimetric and luminescent analysis of H 2 S in living cells and organisms. In aqueous solution, Ru-PNBD is yellow color and non-luminescent because of the photoinduced electron transfer (PET) process from Ru(II) complex luminophore to NBD moiety. The H 2 S-triggered specific nucleophilic substitution reaction with Ru-PNBD cleaves the NBD moiety to form pink NBD-SH and highly luminescent Ru-PH. The color of the solution thus changes from yellow to pink for colorimetric analysis and the emission intensity is about 65-fold increased for luminescent analysis. Ru-PNBD has high sensitivity and selectivity for H 2 S detection, low cytotoxicity and good permeability to cell membrane, which allow the application of this probe for H 2 S imaging in living cells, Daphnia magna , and larval zebrafish. Collectively, this work provides a useful tool for H 2 S analysis and expands the scope of transition metal complex probes. We present the development of a responsive ruthenium(II) complex probe, Ru-PNBD , for colorimetric and luminescent detection of hydrogen sulfide in living cells and organisms. Image 1 • A responsive ruthenium(II) complex, Ru-PNBD , is developed as the luminescence probe for hydrogen sulfide detection. • The Ru-PNBD can sensitively and selectively respond to H 2 S and give color change and luminescence enhancement. • Mechanisms of response reaction and luminescence "OFF-ON" response are investigated. • The application of Ru-PNBD for the detection of H 2 S in living cells and organisms is demonstrated. [ABSTRACT FROM AUTHOR]

In this work, a "two birds with one stone" ruthenium(II) complex probe, Ru‐NBD, is proposed as an effective tool for biothiols detection and discrimination in vitro and in vivo. Ru‐NBD is nonluminescent due to the quenching of Ru(II) complex emission by photoinduced electron transfer (PET) from Ru(II) center to NBD and the quenching of NBD emission through 4‐substitution with "O" ether bond. Ru‐NBD is capable of reacting with Cys/Hcy to form long‐lived red‐emitting Ru‐OH and short‐lived green‐emitting NBD‐NR, while reacting with GSH to produce Ru‐OH and nonemissive NBD‐SR. The long lifetime emission of Ru(II) complex allows elimination of short lifetime background and NBD‐NR fluorescence for total biothiols detection ("bird" one) by time‐gated luminescence (TGL) analysis, and the remarkable difference in luminescence color response allows discrimination GSH and Cys/Hcy ("bird" two) through steady‐state luminescence analysis. Ru‐NBD features high sensitivity and selectivity, rapid luminescence response, and low cytotoxicity, which enables it to be used as the probe for luminescence and background‐free TGL detection and visualization of biothiols in live cells, zebrafish, and mice. The successful development of this probe is anticipated to contribute to the future biological studies of biothiols roles in various diseases. [ABSTRACT FROM AUTHOR]

Emerging epidemiological and preclinical studies have focused on statins and mevalonate pathway to identify potential therapeutic target and clarify the underlying mechanism of the anti‐neoplastic effects. Reductions of mevalonate or isoprenoids, caused by statins, would further decrease the isoprenylation of Rho GTPases which is the crucial step for Rho GTPases to anchor on inner cellular membrane. Following anchoring, activated Rho GTPases can mediate a series of cellular activities such as cytoskeleton reprogramming, front–rear polarity, and cell‐ECM adhesion. These changes not only facilitate tumor cell detachment and migration but also bring great mechanical changes to directly activate YAP, the major nuclear mechanotransducer, to translocate into nucleus. Recently, statins have been identified as potent inhibitors of YAP. Once entering nucleus, YAP would combine TEADs to promote the transcription of about 100 genes, which are involved in cell proliferation, cell cycle regulation, stemness, invasion, and metastasis. Besides, statins are able to promote the degradation of misfolded mutant p53 (mutp53), which is an oncogene in a variety of human malignancies. Reduction in mevalonate‐5‐phosphate (MVP), also induced by statins, would impair the stability of DNAJA1‐mutp53 complex; then, elevated C terminus of Hsc70‐interacting protein (CHIP) mediates the nuclear export and degradation of misfolded mutp53 through ubiquitin–proteasome pathway. It is worth noted that YAP, mutp53, and mevalonate pathway form two positive feedback loops. It is reasonable to believe that Rho GTPases, YAP, and mutp53 are determinants for statins as anti‐cancer agents: tumor cells harboring mutp53 and nuclear‐located YAP would be more sensitive to statins. [ABSTRACT FROM AUTHOR]

• A folic acid-functionalized dual-emissive nanoprobe has been prepared. • The nanoprobe is monodisperse and highly stable in buffer displaying two emissions. • The nanoprobe is useful for steady-state and time-gated luminescence bioimaging. • Folate receptor-overexpressed cancer cells can be recognized by the nanoprobe. • Using the nanoprobe, the "double-check" imaging of HeLa cells was achieved. Development of luminescent probes for rapid and effective discrimination and detection of cancer cells has the potential to address the current challenges in early diagnosis and treatment monitoring of cancer diseases. In this work, we report the preparation of a unique folic acid (FA)-functionalized dual-emissive nanoprobe, CTMR@BHHBCB-Eu-FA , for steady-state and time-gated luminescence "double-check" imaging of cancer cells. The nanoprobe was engineered by covalently doping two luminescent dyes, 5-carboxytetramethylrhodamine (CTMR) and BHHBCB-Eu3+, in core and shell of silica nanoparticles, followed by surface modification of the nanoparticles with FA, a cancer cell-targeting molecule. As-prepared nanoprobe is monodisperse and highly stable in buffer displaying two strong emissions, short-lived emission from CTMR at 584 nm and long-lived emission from BHHBCB-Eu3+ at 612 nm. The nanoprobe is biocompatible, and can specifically recognize folate receptor (FR)-overexpressed cancer cells through the FA-FR binding interaction. Using the nanoprobe, the "double-check" imaging of HeLa cells was successfully achieved at steady-state and time-gated luminescence modes, indicating the capability of the nanoprobe for cancer cell imaging. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that devastatingly affects people's lives. Accumulating evidence indicates that the pathological progression of AD is inseparably connected with hypochlorous acid (HClO). However, further exploring the biological function remains an open challenging due to a lack of effective tools to image HClO in AD brains. To this end, a ruthenium(II) luminescence probe, Ru–HClO , is developed for quantitative detection and visualization of HClO in nerve cells and AD brains. Ru–HClO shows quenched luminescence due to the PET process (excited electron transfer from Ru(II) center to diaminomaleonitrile) and the C N bond isomerization in the excited state. The HClO-triggered specific cleavage reaction with Ru–HClO cleaves the C N bond to form highly luminescent Ru–COOH. Ru–HClO shows rapid response speed, high sensitivity and selectivity, excellent biocompatibility, which makes the probe to be applied to semi-quantitative analysis of HClO in nerve cells and high-throughput screening of anti-AD drugs in the AD cell model. Moreover, using Ru–HClO as a probe, present work further validated that the elevated levels of HClO secretion were accompanied by the AD progressed. These findings may provide valuable results for figuring out the biological roles that HClO played in AD but also for accelerating anti-AD therapeutic discovery. A ruthenium(II) complex-based luminescence probe (Ru–HClO) is developed for the detection of HClO. Ru–HClO features rapid response speed, high sensitivity and selectivity, which makes it to be applied to semi-quantitative analysis of HClO in nerve cells, high-throughput screening of anti-AD drugs in the AD cell model and in-situ imaging of the elevated levels of HClO in AD mice. [Display omitted] • A high performance Ru(II) complex-based luminescence probe for HClO was developed. • Semi-quantitative luminescence analysis of HClO in nerve cells was demonstrated. • High-throughput screening of anti-AD drugs was performed in the AD cell model. • Visualization of the elevated levels of HClO in the brain tissues of AD mice. [ABSTRACT FROM AUTHOR]

We report a novel ruthenium(II) complex-based long-lived and two-photon luminescence probe, Ru-NO 2 , for dynamic monitoring of GSTs fluxes in the process of drug-induced liver injury (DILI). Ru-NO 2 shows weak luminescence due to the strong photo-induced electron transfer (PET) process from the Ru(II) center to the electron-withdrawing 3,4-dinitrobenzene (DNB) group. As a result of the specific nucleophilic aromatic substitution triggered by GSTs in the presence of reduced glutathione (GSH), the 4-nitro group of Ru-NO 2 is substituted by GSH to form strongly emissive Ru-SG. Ru-NO 2 shows high selectivity and sensitivity for responding to GSTs. Notably, one- and two-photon luminescence imaging experiments were conducted to visualize GSTs in living cells and mouse tissues. In addition, Ru-NO 2 was applied for background-free time-gated luminescence (TGL) detection and luminescence imaging analysis of GSTs in DILI mouse sera and liver tissues, which showed that GSTs level in sera significantly increased accompanied by the decrease in liver in the DILI process, revealing the possible potential of the probe as an effective tool for clinical diagnosis and treatment monitoring of DILI. [Display omitted] • A novel Ru(II)-complex-based long-lived two-photon luminescence probe for GSTs detection. • TGL analysis of GSTs in biosamples without autofluorescence interference. • Visualization of GSTs in vitro and in vivo by one-/two-photon luminescence imaging. • Monitoring GSTs fluxes in the process of DILI by TGL and TP luminescence analysis. [ABSTRACT FROM AUTHOR]

Cell plasma membrane, the boundary between an individual live cell and its microenvironment, plays important roles in cellular communication and signaling, and associates with many physiological and pathological processes. For better understanding the membrane-related biological processes, a number of fluorescent probes have been developed in the past few years. According to their different functions and targeting mechanisms, we herein provide an overview of the advances in the development of fluorescent probes for cell plasma membrane biology and biophysics research. Fluorescent probes specific for cell plasma membrane labelling are initially discussed based on their different targeting mechanisms, which is followed by the summary of membrane-targeting responsive fluorescence probes for various biomolecules detection. Challenges and future research directions for the development of new generation fluorescent probes for cell plasma membrane dynamics investigations are outlined in the end. Image 1 • Cell plasma membrane structures and functions were introduced. • Fluorescence probes for cell plasma membrane labelling were reviewed. • Responsive probes for biomolecules detection on cell plasma membrane were summarized. • Challenges and future perspectives for the development of cell plasma membrane fluorescence probes were discussed. [ABSTRACT FROM AUTHOR]

Background: Metabolic inflammation is an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M1-like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Piperine has excellent anti-inflammatory activities and may be used in the treatment of a variety of inflammatory diseases. In this study, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in obese mice. Methods: Newborn mice were subcutaneously (s.c.) injected with monosodium glutamate (MSG) to establish a diabetes model. After 24 weeks, the MSG obese mice were divided into three groups and treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for 10 successive weeks, respectively. Results: The obesity model was successfully established, as the body weight, insulin resistance, fasting blood glucose (FBG) and dyslipidemia were significantly increased. The 10-week administration of piperine to the obese mice not only significantly decreased the elevated FBG (Model: 6.45 ± 0.41 mM; Piperine: 4.72 ± 0.44 mM, p < 0.01), serum TC (Model: 5.66 ± 0.66 mM; Piperine: 3.55 ± 0.30 mM, p < 0.01) and TG (Model: 1.41 ± 0.08 mM; Piperine: 0.94 ± 0.05 mM, p < 0.001), but also enhanced the glucose infusion rate in the hyperglycemic clamp experiment. Meanwhile, piperine improved glucose intolerance and insulin resistance in MSG obese mice. Piperine markedly decreased the total and differential white blood cell (WBC) count, the serum levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines such as galectin-3 (Gal-3) and interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of M1-like polarization marker CD11c and Gal-3 in adipose tissues. The in vitro study showed that piperine inhibited LPS-stimulated polarization of RAW 264.7 cells toward the M1 phenotype. Conclusions: Piperine served as an immunomodulator for the treatment of obesity-related diabetes through its anti-inflammatory effects, which might be achieved by inhibiting macrophages M1 polarization in adipose tissues. [ABSTRACT FROM AUTHOR]

• siRNA-mediated tetrahedral framework nucleic acid nanogel (FNA NG) was designed. • PDA-coated FNA NG (PP-FNA NG) achieves siRNA-mediated low-temperature PTT. • PP-FNA NG combined with its loaded DOX can achieve chemo-PTT synergistic therapy. • PP-FNA NG effectively induced immunogenic cell death and inhibited melanoma. To achieve a balance between antitumor efficacy in photothermal therapy (PTT) and high-temperature (>50℃) induced side effects, a novel tetrahedral framework nucleic acid (FNA) nanogel (FNA NG) coated with polydopamine (PDA) (abbreviation: PP-FNA NG) was designed to achieve siRNA-mediated low-temperature PTT. First, siRNA targeted heat shock protein 70 (HSP70) was used as crosslinker to guide FNA through nucleic acid hybridization to obtain FNA NG , and simultaneously loaded doxorubicin (DOX). The obtained FNA NG was coated with PEGylated PDA, which not only protected the FNA NG from enzymatic degradation, but also made the FNA NG have excellent photothermal conversion ability under near infrared (NIR) irradiation. FNA NG realized the effective delivery of siHSP70 and realized the low-temperature photothermal therapy mediated by siRNA. Notably, PP-FNA NG combined with its loaded DOX showed excellent synergistic effect, and could effectively induce the immunogenic cell death (ICD), promote the activation and infiltration of T lymphocyte, promote the maturation of dendritic cells and the secretion of related cytokines, and effectively inhibit melanoma. This study provided a simple and effective exploration strategy for new vector design based on FNA and collaborative therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] Diabetic retinopathy (DR) is one of the serious complications of diabetes, which has become the fourth leading cause of vision loss worldwide. Current treatment of DR relies on intravitreal injections of antiangiogenic agents, which has made considerable achievements in reducing visual impairment. However, long-term invasive injections require advanced technology and can lead to poor patient compliance as well as the incidence of ocular complications including bleeding, endophthalmitis, retinal detachment and others. Hence, we developed non-invasive liposomes (EA-Hb/TAT&isoDGR-Lipo) for efficiency co-delivery of ellagic acid and oxygen, which can be administered intravenously or by eye drops. Among that, ellagic acid (EA), as an aldose reductase inhibitor, could remove excessive reactive oxygen species (ROS) induced by high glucose for preventing retinal cell apoptosis, as well as reduce retinal angiogenesis through the blockage of VEGFR2 signaling pathway; carried oxygen could ameliorate DR hypoxia, and further enhanced the anti-neovascularization efficacy. Our results showed that EA-Hb/TAT&isoDGR-Lipo not only effectively protected retinal cells from high glucose-induced damage, but also inhibited VEGF-induced vascular endothelial cells migration, invasion, and tube formation in vitro. In addition, in a hypoxic cell model, EA-Hb/TAT&isoDGR-Lipo could reverse retinal cell hypoxia, thereby reducing the expression of VEGF. Significantly, after being administered as an injection or eye drops, EA-Hb/TAT&isoDGR-Lipo obviously ameliorated the structure (central retinal thickness and retinal vascular network) of retina by eliminating ROS and down-regulating the expression of GFAP, HIF-1α, VEGF and p-VEGFR2 in a DR mouse model. In summary, EA-Hb/TAT&isoDGR-Lipo holds great potentials in improvement of DR, which provides a novel approach for the treatment of DR. [ABSTRACT FROM AUTHOR]

The fabrication of various 3D tissue engineering tubular scaffolds with fibrous structures, to assist the human body in rapidly repairing a variety of ailments, is receiving more and more attention. Due to the inefficiency of the majority of fibrous preparation techniques, the question of how to rapidly produce the requisite three-dimensional tubular microfiber scaffold structures has become an urgent problem. In this study, an efficient polymer fiber preparation method was developed, using a high-speed airflow drive. Melt blending of polycaprolactone (PCL), polylactic acid (PLA), and tributyl citrate (TBC), was used for the printing material, to achieve the efficient preparation of tubular microfiber scaffolds with different structures. The scaffold diameter was as small as 2 mm, the wall thickness was up to 100 μm, and the fiber injection efficiency reached 15.48 g/h. By utilizing simulations to optimize the printing parameters and by adjusting the printing settings, it was possible to achieve a controlled fiber diameter in the range of 3 μm to 15 μm. In addition, plasma treatment was applied to the microfibers' surface, to increase their wettability, and the efficiency of the hydrophilic modification was demonstrated. Furthermore, the mechanical property test demonstrated that the fibers have a tensile strength of 1.36 ± 0.16 MPa and a tensile strain of 30.8 ± 3.5%. The radial compressive strain of the tubular scaffold could reach 60% of the original scaffold's diameter. Finally, the in vitro degradation of the fibers at various pH values was tested. The results showed that, under alkaline conditions, the surface of the fibers would be severely crushed and the rate of deterioration would increase. [ABSTRACT FROM AUTHOR]

n -Valeraldehyde is widely used in organic synthesis field as an important intermediate and feedstock, which makes it a significant class of environmental pollutants. In view of the high poisonous and harmful of n -valeraldehyde to human health and ecological environment, it is important to develop green and sustainable technology to reduce the pollution of n -valeraldehyde. In this work, electrocatalytic n -valeraldehyde oxidation using Zn-Co bimetallic oxides was applied to control n -valeraldehyde contamination and highly valuable octane production. To further improve the performance of Zn-Co bimetallic oxides, atomic level Zn vacancies were created across the Zn-Co bimetallic oxides (d x -ZnCo 2 O 4) by post-etching and oxygen vacancy filling methods. Electrochemical experiments results showed that d x -ZnCo 2 O 4 owned a much higher octane yield (1193.4 µmol g−1 h−1) and octane selectivity (octane/butene ≈10). Theoretical calculations demonstrated that the introduction of atomic level Zn vacancies in Zn-Co bimetallic oxide changed the electronic distribution around O, Co and Zn atoms, resulted in an alteration in n -valeraldehyde adsorption sites from Co to Zn, reduced the formation barrier of key intermediate *C 4 H 9 and facilitated the transfer of n -valeraldehyde to octane. This study provides a new idea for the development of high-performance electrocatalysts for controlling n -valeraldehyde pollution. [Display omitted] • d x -ZnCo 2 O 4 with varying degrees of deficiency were fabricated. • Oxygen vacancies in d x -ZnCo 2 O 4 were reoccupied by further heat treatment. • The atomic level defects in d x -ZnCo 2 O 4 were identified as Zn defects. • The atomic level Zn defects in d x -ZnCo 2 O 4 promoted octane generation. [ABSTRACT FROM AUTHOR]

Sensitive and selective quantification of specific analytes is of great significance in analytical and environmental sciences, as well as in the food industry. Herein, we report the design, synthesis, characterization, and application of a responsive ruthenium(II) complex probe, Ru-azo, for phosphorescence and time-gated luminescence (TGL) detection of bisulfite, an important additive in the food industry. Upon a specific nucleophilic addition reaction between bisulfite and the azo group of Ru-azo, a new ruthenium(II) complex, Ru-SO3, was obtained, which resulted in a remarkable increase in phosphorescence intensity, allowing the bisulfite detection to be achieved. In addition, long-lived emissions of Ru-azo (τ = 258 ns) and Ru-SO3 (τ = 261 ns) also enabled the TGL detection of bisulfite in autofluorescence-rich food samples. Through theoretical computations, the photoinduced electron transfer (PET) process within the ruthenium(II) complex was validated, which unveiled the rationality of the luminescence "off-on" response of Ru-azo to bisulfite. The probe showed advantages of good water solubility, and high sensitivity, selectivity and accuracy for responding to bisulfite, facilitating its application in phosphorescence and TGL detection of bisulfite in aqueous and food samples. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma accounts for a high proportion of lung cancers. Though efforts have been made to develop new and effective treatments for this disease, the mortality rate remains high. Gene expression microarrays facilitate the study of lung cancer at the molecular level. The present study aimed to detect differentially expressed protein-coding genes to identify novel biomarkers and therapeutic targets for lung adenocarcinoma. Aberrations in gene expression in lung adenocarcinoma were determined by analysis of mRNA microarray datasets from the Gene Expression Omnibus database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) networks and statistical analysis were used to identify the biological functions of the differentially expressed genes (DEGs). The results of the bioinformatics analysis were subsequently validated using reverse transcription-quantitative PCR. A total of 303 DEGs were identified in lung adenocarcinomas, and they were enriched in a number of cancer-associated GO terms and KEGG pathways. DNA topoisomerase 2α (TOP2A), cell division cycle protein homolog 20 (CDC20), mitotic checkpoint serine/threonine protein kinase BUB1 (BUB1) and mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) exhibited the highest degree of interaction in the PPI network. Survival analysis performed using Kaplan-Meier curves and Cox regression indicated that these four genes were all significantly associated with the survival of patients with lung adenocarcinomas. In conclusion, TOP2A, CDC20, BUB1 and MAD2L1 may be key protein-coding genes that may serve as biomarkers and therapeutic targets in lung adenocarcinomas. [ABSTRACT FROM AUTHOR]

This study reports an activatable iridium(III) complex probe for phosphorescence/time‐gated luminescence detection of cysteine (Cys) in vitro and in vivo. The probe, [Ir(ppy)2(NTY‐bpy)](PF6) [ppy: 2‐phenylpyridine; NTY‐bpy: 4‐methyl‐4′‐(2‐nitrovinyl)‐2,2′‐bipyridine], is developed by incorporating a strong electron‐withdrawing group, nitroolefin, into a bipyridine ligand of the IrIII complex. The luminescence of the probe is quenched owing to the intramolecular charge transfer (ICT) process, but switched on by a specific recognition reaction between the probe and Cys. [Ir(ppy)2(NTY‐bpy)](PF6) shows high sensitivity and selectivity for Cys detection and good biocompatibility. The long‐lived emission of [Ir(ppy)2(NTY‐bpy)](PF6) allows time‐gated luminescence analysis of Cys in cells and human sera. These properties make it convenient for the phosphorescence and time‐gated luminescence imaging and flow cytometry analysis of Cys in live samples. The Cys images in cancer cells and inflamed macrophage cells reveal that [Ir(ppy)2(NTY‐bpy)](PF6) is distributed in mitochondria after cellular internalization. Visualizations and flow cytometry analysis of mitochondrial Cys levels and Cys‐mediated redox activities of live cells are achieved. By using [Ir(ppy)2(NTY‐bpy)](PF6) as a probe, in vivo sensing and imaging of Cys in D. magna, zebrafish, and mice are then demonstrated. An activatable probe specific for Cys detection in the mitochondria of inflamed live cells and organisms is developed based on a unique IrIII complex. The probe, [Ir(ppy)2(NTY‐bpy)]+ [ppy: 2‐phenylpyridine; NTY‐bpy: 4‐methyl‐4′‐(2‐nitrovinyl)‐2,2′‐bipyridine], is capable of phosphorescence/time‐gated luminescence analysis of Cys in buffer, human sera, and live cells. Visualization of Cys‐mediated redox activities in mitochondria of inflamed cells and Cys in Daphnia magna, zebrafish, and mice are demonstrated (see figure). [ABSTRACT FROM AUTHOR]

A novel ruthenium(ii) complex–cyanine energy transfer scaffold has been established for the development of a ratiometric luminescence probe for ONOO− detection. The probe, Ru–Cy5, is localized in mitochondria of live cells, allowing ratiometric sensing and imaging of ONOO− therein. [ABSTRACT FROM AUTHOR]

Abstract: Development of novel bioanalytical methods for monitoring of H2S is key toward understanding the physiological and pathological functions of this gasotransmitter in live organisms. A ruthenium(II)‐complex‐based luminescence probe, Ru‐MDB (MDB: 4’‐methyl‐[2,2’‐bipyridine]‐4‐yl)methyl 2‐((2,4‐dinitrophenyl)thio)benzoate), was developed by introducing a new H2S responsive masking moiety to a red‐emitting RuII luminophore. Cleavage of this masking group by a H2S‐triggered reaction leads to a luminescence “off–on” response. The long‐lived emissions of Ru‐MDB and its reaction product with H2S allowed quantitative detection of H2S in autofluorescence‐rich human sera and adult zebrafish organs using the time‐gated luminescence mode. Ru‐MDB exhibits red emission, a large Stokes shift, high specificity and sensitivity for H2S detection, and low cytotoxicity, which enables imaging and flow cytometry analysis of lysosomal H2S generation in live inflamed cells under drug stimulation. Monitoring of H2S in live Daphnia magna, zebrafish embryos, adult zebrafish, and mice, was conducted by in vivo imaging using Ru‐MDB as a probe. [ABSTRACT FROM AUTHOR]

Abstract: Development of novel bioanalytical methods for monitoring of H2S is key toward understanding the physiological and pathological functions of this gasotransmitter in live organisms. A ruthenium(II)‐complex‐based luminescence probe, Ru‐MDB (MDB: 4’‐methyl‐[2,2’‐bipyridine]‐4‐yl)methyl 2‐((2,4‐dinitrophenyl)thio)benzoate), was developed by introducing a new H2S responsive masking moiety to a red‐emitting RuII luminophore. Cleavage of this masking group by a H2S‐triggered reaction leads to a luminescence “off–on” response. The long‐lived emissions of Ru‐MDB and its reaction product with H2S allowed quantitative detection of H2S in autofluorescence‐rich human sera and adult zebrafish organs using the time‐gated luminescence mode. Ru‐MDB exhibits red emission, a large Stokes shift, high specificity and sensitivity for H2S detection, and low cytotoxicity, which enables imaging and flow cytometry analysis of lysosomal H2S generation in live inflamed cells under drug stimulation. Monitoring of H2S in live Daphnia magna, zebrafish embryos, adult zebrafish, and mice, was conducted by in vivo imaging using Ru‐MDB as a probe. [ABSTRACT FROM AUTHOR]

Hypochlorous acid (HClO) plays a vital role in the immune system and is involved in various human diseases. To fully understand its biological functions in cellular signaling pathways, apoptosis and human diseases, effective chemical tools for directly tracing HClO at subcellular levels are greatly demanded. Herein, two mitochondria- and lysosome-targetable luminescent β-diketonate–Eu 3+ complexes, Mito-BHHBCB-Eu 3+ and Lyso-BHHBCB-Eu 3+ , were developed as probes for the time-gated luminescence detection of HClO inside mitochondria and lysosomes of living cells, respectively. The probes were designed by incorporating a mitochondria-anchoring (triphenylphosphonium) motif or a lysosome-anchoring (morpholine) motif with a strongly luminescent HOCl-responsive β-diketonate–Eu 3+ complex, BHHBCB-Eu 3+ , to ensure the probe molecules to be driven into mitochondria or lysosomes for responding to HOCl therein. Upon exposure to HClO, the probes exhibited a fast luminescence response (within 5 s) towards HClO with good selectivity and high sensitivity (<15 nM). In live cell experiments, both probes, Mito-BHHBCB-Eu 3+ and Lyso-BHHBCB-Eu 3+ , were successfully located in the corresponding organelles as expected, which enabled exogenous and endogenous HClO to be imaged at subcellular levels. Taking advantages of time-gated luminescence bioimaging technique, the uptake of exogenous HClO by Daphnia magna was also successfully imaged by time-gated luminescence microscopy. The results reveal that Mito-BHHBCB-Eu 3+ and Lyso-BHHBCB-Eu 3+ could serve as useful tools for real-time imaging of HClO at subcellular levels and in vivo with high specificity and contrast. [ABSTRACT FROM AUTHOR]

Bimodal photoluminescence-magnetic resonance (MR) imaging technique has attracted tremendous attention due to its great potential in biomedical researches and clinical practices. Herein a novel multifunctional magnetoluminescent nanocomposite, FA-Gd-Tb@SiO 2 , was found to serve as an effective probe for bimodal time-gated luminescence/MR imaging of cancer cells in vitro and in vivo. The nanoprobe was designed by integrating a luminescent Tb3+ complex, a Gd(III)-based contrast agent and a tumor-targeting molecule, folic acid (FA), into a silica nanoparticle. The integration of these functional moieties allows the nanoprobe to be employed for specific imaging of cancer cells with background-free TGL and non-invasive MR imaging modes. In addition, the optical and magnetic properties were dramatically improved after implicating the newly synthesized nanoarchitecture. In vitro cellular TGL imaging demonstrated that the FA-Gd-Tb@SiO 2 nanoprobe could recognize and accumulate in cancer cells overexpressing FA receptor. Furthermore, in vivo study revealed that the as-prepared nanoprobe was able to effectively enhance T 1 -weighted MR contrast and TGL intensity in tumor tissue, which might contribute to the precise detection and tracing of cancer cells, as well as diagnosis and therapy of tumor in clinical. Multifunctional magnetoluminescent silica nanoparticles for tumor-targeted time-gated luminescence/magnetic resonance imaging in vitro and in vivo. Image 1 • Multifunctional tumor-targetable silica nanoparticles for bimodal TGL/MR imaging of cancer cells were developed. • The nanoprobe can be employed for imaging of cancer cells with both background-free TGL and non-invasive MR imaging modes. • The nanoprobe can visualize tumors with various resolutions (from single cell to whole living body) and no depth limit. • The bimodal TGL/MR imaging method can improve the accuracy of cancer diagnosis and minimize potential artifacts. [ABSTRACT FROM AUTHOR]

An activatable iridium(III) complex probe for phosphorescence/time‐gated luminescence detection of cysteine (Cys) in vitro and in vivo is reported. The probe, [Ir(ppy)2(NTY‐bpy)][(PF6)] features large Stokes shift, long‐lived emission, good biocompatibility, high sensitivity and selectivity for Cys detection. Compound [Ir(ppy)2(NTY‐bpy)][(PF6)] is mitochondria targetable, which makes it convenient for the determination of Cys‐mediated redox activities in mitochondria. In vivo sensing and imaging of Cys in D. magna, zebrafish, and mice are demonstrated. More information can be found in the Full Paper by R. Zhang, W. Zhang, J. Yuan et al. on page 1498. [ABSTRACT FROM AUTHOR]