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Hypoxia, as a characteristic feature of solid tumor, can significantly adversely affect the outcomes of cancer radiotherapy (RT), photodynamic therapy, or chemotherapy. In this study, a strategy is developed to overcome tumor hypoxia‐induced radiotherapy tolerance. Specifically, a novel two‐dimensional Pd@Au bimetallic core–shell nanostructure (TPAN) was employed for the sustainable and robust production of O2 in long‐term via the catalysis of endogenous H2O2. Notably, the catalytic activity of TPAN could be enhanced via surface plasmon resonance (SPR) effect triggered by NIR‐II laser irradiation, to enhance the O2 production and thereby relieve tumor hypoxia. Thus, TPAN could enhance radiotherapy outcomes by three aspects: 1) NIR‐II laser triggered SPR enhanced the catalysis of TPAN to produce O2 for relieving tumor hypoxia; 2) high‐Z element effect arising from Au and Pd to capture X‐ray energy within the tumor; and 3) TPAN affording X‐ray, photoacoustic, and NIR‐II laser derived photothermal imaging, for precisely guiding cancer therapy, so as to reduce the side effects from irradiation. [ABSTRACT FROM AUTHOR]

We report here a single-benzene based fluorescent framework, amino-terephthalonitrile, denoted SB-Fluor. This scaffold displays versatile emission wavelength tunability via structure modification, covering the full visible light spectrum, both in the solution and solid state. Moreover, one molecule, SBF3, exhibits polymorphism-dependent reversible mechanochromic luminescence. [ABSTRACT FROM AUTHOR]

A highly selective lysosome-targeting NIR fluorescent probe (Lyso-SiR-2S) for HOCl was constructed based on Si-rhodamine B spirodithiolactone. This probe was very effectively employed to sense HOCl produced in various living cells and to visualize fluctuations of endogenous HOCl resulting from GEN-induced acute kidney injury in vivo for the first time. [ABSTRACT FROM AUTHOR]

Abstract A novel ratiometric and reversible chemosensor 4-((2-(Benzo[d]thiazol-2-yl)phenyl)ethynyl)- N,N -diethylaniline (BT-1) based on ortho -arylethynyl benzothiazole with large Stokes shift (Δλ≈190 nm) was designed and synthesized to recognize Cu2+. Copper ion induces a remarkable fluorescence enhancement and causes formation of a BT-1-Cu complex. The clamp-on coordination mode of BT-1 to Cu2+ was demonstrated using Job's plot, mass spectrum (MS) and DFT calculations. The calculations also indicate that Cu2+ was chelated to BT-1 through N and alkyne instead of S and alkyne. The probe could quantify Cu2+ with the detection limit of 3.2 × 10−9 M. The in vitro imaging results indicated that the probe BT-1 was membrane-permeable and could be applied into the recognition of Cu2+ ions in living cells. Graphical abstract Image 1 Highlights 1. A novel ratiometric and reversible fluorescence probe with a large stokes shift based on a new clamp-on unit. 2. It is the first example that utilizes aryl alkyne coordination in the determination of copper ions. 3. The probe BT-1 was membrane-permeable and could be applied into the recognition of Cu2+ ions in living cells. [ABSTRACT FROM AUTHOR]

Abstract In this work, we present a numerical model to deal with the fracture of damaged materials within the framework of the finite fracture mechanics (FFM). Continuum damage mechanics combined with the regularization techniques is first applied to determine the damage field. The transition from continuous damage field to discontinuous crack occurs when the coupled criterion (CC) is fulfilled. Special numerical algorithms were developed in crack path tracking and crack creation for the analysis of the entire failure process from damage development to crack creation. Both initiation and growth of one or multiple cracks can reasonably be simulated and efficiency and accuracy of the approach are illustrated through several numerical examples. [ABSTRACT FROM AUTHOR]

Fluorescent probes have become an indispensable tool in the detection and imaging of biological and disease‐related analytes due to their sensitivity and technical simplicity. In particular, fluorescent probes with far‐red to near‐infrared (FR‐NIR) emissions are very attractive for biomedical applications. However, many available FR‐NIR fluorophores suffer from small Stokes shifts and sometimes low quantum yields, resulting in self‐quenching and low contrast. In this work, we describe the rational design and engineering of FR‐NIR 2,4,6‐triphenylpyrylium‐based fluorophores (TPP‐Fluors) with the help of theoretical calculations. Our strategy is based on the appending of electron‐donating substituents and fusing groups onto 2,4,6‐triphenylpyrylium. In contrast to the parent TPP with short emission wavelength, weak quantum yields, and low chemical stability, the obtained novel TPP‐Fluors display some favorable properties, such as long‐wavelength emission, large Stokes shifts, moderate to high quantum yields, and chemical stability. TPP‐Fluors demonstrate their biological value as mitochondria‐specific labeling reagents due to their inherently positive nature. In addition, TPP‐Fluors can also be applied to develop ratiometric fluorescent probes, as the electron‐donating ability of the 2,6‐phenyl substituents is closely correlated with their emission wavelength. A proof‐of‐concept ratiometric probe has been developed by derivatizing the amino groups of TPP‐Fluor for the detection and imaging of nitroreductase in vitro and in hypoxic cells. [ABSTRACT FROM AUTHOR]

In this work, we report the first bioluminescent probe BP-PS for detecting H2Sn with high specificity and sensitivity. Owing to the bioluminescence imaging without requiring an excitation light source, tissue autofluorescence is eliminated and BP-PS shows a high signal-to-noise ratio. Moreover, BP-PS was successfully utilized to visualize endogenous H2Sn in live cells and a murine model of bacterial infection. [ABSTRACT FROM AUTHOR]

Precision diagnosis and effective treatment are the cores of early cancer therapy. Here, for the first time, we report a hybridization chain reaction-based nanoprobe for selective and sensitive cancer cell recognition and amplified photodynamic therapy. [ABSTRACT FROM AUTHOR]

A bioluminescent probe, BP-HNO, which exhibits a turn-on response to nitroxyl with high sensitivity and selectivity, is reported for the first time in this work. BP-HNO is free from the interference of biological autofluorescence to afford a high signal-to-noise ratio for bioimaging, and was successfully applied to imaging nitroxyl in live cells and mice. [ABSTRACT FROM AUTHOR]

Abnormal enzymatic activities are directly related to the development of cancers. Identifying the location and expression levels of these enzymes in live cancer cells have considerable importance in early-stage cancer diagnoses and monitoring the efficacy of therapies. Small-molecule fluorescent probes have become a powerful tool for the detection and imaging of enzymatic activities in biological systems by virtue of their higher sensitivity, nondestructive fast analysis, and real-time detection abilities. Moreover, due to their structural tailorability, numerous small-molecule enzymatic fluorescent probes have been developed to meet various demands involving real-time tracking and visualizing different enzymes in live cancer cells or in vivo. In this review, we provide an overview of recent advances in small-molecule enzymatic fluorescent probes mainly during the past decade, including the design strategies and applications for various enzymes in live cancer cells. We also highlight the challenges and opportunities in this rapidly developing field of small-molecule fluorescent probes for interventional surgical imaging, as well as cancer diagnosis and therapy. [ABSTRACT FROM AUTHOR]

This paper investigates the co-movement and asymmetric interactions between energy and grain prices, based on the evidence from the crude oil and corn markets, the most important energy and grain markets, respectively. Time series analysis indicates that there is a consistent trend between the crude oil price and corn price with a significant positive correlation coefficient 0.7471 during the sampling period, from January 2008 to February 2016. In addition, we find that there is a long-run equilibrium relationship between the two commodities' prices. Moreover, while linear Granger causality tests suggest that there is a two-way Granger causality relationship between the price changes in the two markets, non-linear Granger causality tests suggest that there is only a one-way causality relationship from corn to oil price. However, both linear and non-linear Granger causality tests indicate the asymmetry of causality relationship between the two markets (the price change in corn market can more significantly Granger cause the change in crude oil market). Further analysis suggests that the contribution of the corn market to price discovery in a large commodity market is larger than that of the crude oil market. [ABSTRACT FROM AUTHOR]

The development of selective and sensitive sensing systems for Cr(vi) anions (CrO42−/Cr2O72−) has been a growing interest because Cr(vi) anions are potent carcinogenic and mutagenic ions that have become serious potential threats to public health and safety. Herein, the selective and highly sensitive detection of toxic Cr(vi) anions in aqueous solution has been achieved by virtue of nanoscale zeolitic imidazole framework-90 (NZIF-90). NZIF-90 is the first individual MOF-based material which can selectively sense Cr(vi) anions from Fe3+ cations, and it also has the lowest detection limits among the reported fluorescent MOF-based probes for Cr(vi) anions: 1.41 μM (0.16 ppm) for CrO42− and 1.78 μM (0.38 ppm) for Cr2O72−. The detailed sensing mechanism study uncovered that the excellent sensing performance of NZIF-90 for Cr(vi) anions is based on the synergistic effect of the competitive energy absorption process and the electrostatic interaction between NZIF-90 and Cr(vi) anions. Moreover, as for a further potential application of this probe, the Förster resonance energy transfer (FRET)-based dual-excitation ratiometric fluorescent detection of Cr(vi) anions was also realized by Rhodamine B (RhB) encapsulated into NZIF-90 (RhB@NZIF-90). [ABSTRACT FROM AUTHOR]

Abstract: Two‐photon imaging is an emerging tool for biomedical research and clinical diagnostics. Electron donor–acceptor (D–A) type molecules are the most widely employed two‐photon scaffolds. However, current D–A type fluorophores suffer from solvatochromic quenching in aqueous biological samples. To address this issue, we devised a novel class of D–A type green fluorescent protein (GFP) chromophore analogues that form a hydrogen‐bond network in water to improve the two‐photon efficiency. Our design results in two‐photon chalcone (TPC) dyes with 0.80 quantum yield and large two‐photon action cross section (210 GM) in water. This strategy to form hydrogen bonds can be generalized to design two‐photon materials with anti‐solvatochromic fluorescence. To demonstrate the improved in vivo imaging, we designed a sulfide probe based on TPC dyes and monitored endogenous H2S generation and scavenging in the cirrhotic rat liver for the first time. [ABSTRACT FROM AUTHOR]

Abstract: Two‐photon imaging is an emerging tool for biomedical research and clinical diagnostics. Electron donor–acceptor (D–A) type molecules are the most widely employed two‐photon scaffolds. However, current D–A type fluorophores suffer from solvatochromic quenching in aqueous biological samples. To address this issue, we devised a novel class of D–A type green fluorescent protein (GFP) chromophore analogues that form a hydrogen‐bond network in water to improve the two‐photon efficiency. Our design results in two‐photon chalcone (TPC) dyes with 0.80 quantum yield and large two‐photon action cross section (210 GM) in water. This strategy to form hydrogen bonds can be generalized to design two‐photon materials with anti‐solvatochromic fluorescence. To demonstrate the improved in vivo imaging, we designed a sulfide probe based on TPC dyes and monitored endogenous H2S generation and scavenging in the cirrhotic rat liver for the first time. [ABSTRACT FROM AUTHOR]

Herein, we developed a strategy to attack the cancer cell defense system against reactive oxygen species to improve photodynamic therapy efficacy with a Ce6@MSN@MTH1 siRNA nanosystem, which was demonstrated to improve cellular sensitivity to reactive oxygen species through suppressing MTH1 protein in cancer cells. [ABSTRACT FROM AUTHOR]

Near-infrared (NIR) fluorescent probes have been considered as powerful tools for exploring bioactive species and biological processes in living systems by virtue of the substantial merits of the NIR window (such as minimal photo-toxicity, deep tissue penetration, and low background interference). However, the development of effective NIR fluorescent probes for biological application is still facing great challenges due to some weakness (for example, pH sensitivity, poor chemical and photo-stability) of mainly current NIR fluorophores. Herein, we synthesized a novel fluorine atom substituted NIR chromenylium-cyanine fluorophore, termed CCF-OH , with an optically tunable hydroxyl group. Compound CCF-OH possess several optical advantages, including high chemical stability, high photo-stability, and high fluorescence quantum yield (Φ = 0.47). Significantly, a low pK a value (6.3) of CCF-OH was obtained, making its fluorescence signal steady around the pH ranging from 6.8 to 8.1. To demonstrate the practicability of CCF-OH , a mitochondria-targeted near-infrared fluorescent probe, N-Cys , was developed by masking the hydroxyl group of CCF-OH with an acrylate group as the recognition unit for cysteine (Cys). N-Cys responded to Cys with an obvious ratiometric signal. Furthermore, N-Cys has also been successfully applied for ratiometric NIR imaging of Cys in living cells, suggesting the great potential of the new NIR fluorophore, CCF-OH , for practical applications in living systems. [ABSTRACT FROM AUTHOR]

Surface coating is an effective strategy to boost the application of LiNi 0.815 Co 0.15 Al 0.035 O 2 in the lithium ion batteries. The crystalline state of the coating layer is crucial for the transportation of lithium ions, the suppression of involved side reaction and the improvement of electrode structure stability, which ultimately determine the electrochemical performance. Here, the effects of crystalline state of Li 0.5 La 0.5 TiO 3 on the electrochemical performance of LiNi 0.815 Co 0.15 Al 0.035 O 2 are comparatively investigated. The Li 0.5 La 0.5 TiO 3 coating layer with a thickness of about 2 nm is introduced on the surface of LiNi 0.815 Co 0.15 Al 0.035 O 2 , and the crystalline state (crystalline or amorphous) of coating layer is successfully controlled by tuning post-annealing temperature. The structure stability, dynamics performance, reaction activity and electrochemical performance of the coated and pristine samples are investigated. Compared with the pristine sample, the coated materials both demonstrate superior electrochemical performance. And the crystalline Li 0.5 La 0.5 TiO 3 coated sample shows a better capacity retention (94.5%) than the amorphous Li 0.5 La 0.5 TiO 3 coated sample (88.0%). The improved electrochemical performance of crystalline Li 0.5 La 0.5 TiO 3 coated sample could be ascribed to a better interface between the electrolyte and active material, which facilitates intercalation/extraction of lithium ions during the charge/discharge processes. [ABSTRACT FROM AUTHOR]

For practical application, it is of importance to provide a precise description of the far field error on the basis of the source error. The “relative error volume”, instead of the local error, of the source is put forward to give the maximum error range of the far field error. In order to determine the off-center source error, the “critical point” of the far field phase error is obtained, dealt with and raised. Numerical results given are used to check up this method. It is indicated that the “off-center distance” together with the “relative error volume” should be used in describing the source error and analyzing the far field error, and the “critical points” is a useful parameter to analyze the source error for the inverse problem. [ABSTRACT FROM AUTHOR]

Superoxide anion radical (O 2 − ), the “primary” reactive oxygen species (ROS) in living systems, is linked to a variety of physiological and pathological processes. Therefore, developing an effective strategy to monitor the fluctuation of O 2 − in biological systems is of great importance. This paper describes a new turn-on two-photon fluorescent probe for endogenous O 2 − detection and imaging, which was rationally designed and synthesized via a non-redox strategy. In the presence of O 2 − , the probe exhibited notable fluorescence enhancement (∼235-fold) with a low detection limit down to 1 nM, indicating a high signal-to-background ratio and excellent sensitivity. In addition, short response time, good biocompatibility, low cytotoxicity, long-term stability against light illumination, specificity to O 2 − over general reductants, and pH stability were demonstrated, indicating that the requirements for cellular O 2 − determination are met. Furthermore, the probe was successfully applied in two-photon fluorescence imaging of endogenous O 2 − in living cells and tissues and showed high imaging resolution and a deep-tissue imaging depth of ∼150 μm, illustrating the promising potential for practical applications in complex biosystems and providing a valuable theoretical basis and technical support for the study of physiological and pathological functions of O 2 − . [ABSTRACT FROM AUTHOR]

Current enzyme-responsive, fluorogenic probes fail to provide in situ information because the released fluorophores tend to diffuse away from the reaction sites. The problem of diffusive signal dilution can be addressed by designing a probe that upon enzyme conversion releases a fluorophore that precipitates. An excited-state intramolecular proton transfer (ESIPT)-based solid-state fluorophore HTPQ was developed that is strictly insoluble in water and emits intense fluorescence in the solid state, with λex/em=410/550 nm, thus making it far better suited to use with a commercial confocal microscope. HTPQ was further utilized in the design of an enzyme-responsive, fluorogenic probe (HTPQA), targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion-resistant in situ detection of endogenous ALP in live cells. It was also employed in the visualizing of different levels of ALP in osteosarcoma cells and tissue, thus demonstrating its interest for the diagnosis of this type of cancer. [ABSTRACT FROM AUTHOR]

Current enzyme-responsive, fluorogenic probes fail to provide in situ information because the released fluorophores tend to diffuse away from the reaction sites. The problem of diffusive signal dilution can be addressed by designing a probe that upon enzyme conversion releases a fluorophore that precipitates. An excited-state intramolecular proton transfer (ESIPT)-based solid-state fluorophore HTPQ was developed that is strictly insoluble in water and emits intense fluorescence in the solid state, with λex/em=410/550 nm, thus making it far better suited to use with a commercial confocal microscope. HTPQ was further utilized in the design of an enzyme-responsive, fluorogenic probe (HTPQA), targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion-resistant in situ detection of endogenous ALP in live cells. It was also employed in the visualizing of different levels of ALP in osteosarcoma cells and tissue, thus demonstrating its interest for the diagnosis of this type of cancer. [ABSTRACT FROM AUTHOR]

Developing chemiluminescence probe with a slow kinetic profile, even a constant emission within analytical time, would improve the analytical sensitivity, but still remains challenging. This work reports a novel strategy to afford long-lasting in vivo imaging by developing a self-assembled chemiluminophore HPQCL-Cl via the introduction of the hydrogen-bond-driven self-assembled dye HPQ to Schaap's dioxetane. Compared with classical chemiluminophore HCL , self-assembled HPQCL-Cl was isolated from the physiological environment, thereby lowering its deprotonation and prolonging its half-life. Based on HPQCL-Cl , the long-lasting in vivo imaging of 9L-lacz tumor was achieved by developing a β-gal-responsive probe. Its signals remained constant (<5% change) for about 20 min, which may provide a wide time window for the determination of β-gal. This probe also showed high tumor-to-normal tissue ratio throughout tumor resection, highlighting its potential in image-guided clinical surgery. We report a novel strategy to afford long-lasting in vivo imaging by developing a self-assembled chemiluminophore HPQCL-Cl via the introduction of the hydrogen-bond-driven self-assembled dye HPQ to Schaap's dioxetane. In the assembles, the phenolic hydroxyl in HPQCL-Cl was isolated from the physiological environment, thereby lowering its deprotonation and prolonging the chemiluminescence half-life. Based on HPQCL-Cl , we achieved the long-lasting in vivo imaging and chemiluminescence imaging guided surgical resection of tumor by developing a β-galactosidase-responsive chemiluminescence probe. [Display omitted] • A strategy to prolong the chemiluminescence half-life is presented. • The self-assembled chemiluminophore provides a wide time window for the determination of the biomarkers. • The reported chemiluminescence probe exhibited high tumor-to-normal tissue ratio throughout the surgical operation. [ABSTRACT FROM AUTHOR]

A universal aptameric system based on the taking advantage of double-stranded DNA/perylene diimide (dsDNA/PDI) as the signal probe was developed for multiplexed detection of small molecules. Aptamers are single-stranded DNA or RNA oligonucleotides which are selected in vitro by a process known as systematic evolution of ligands by exponential enrichment. In this work, we synthesized a new kind of PDI and reported this aggregated PDI could quench the double-stranded DNA (dsDNA)-labeled fluorophores with a high quenching efficiency. The quenching efficiencies on the fluorescence of FAM, TAMRA and Cy5 could reach to 98.3%±0.9%, 97.2%±0.6% and 98.1%±1.1%, respectively. This broad-spectrum quencher was then adopted to construct a multicolor biosensor via a label-free approach. A structure-switching-triggered enzymatic recycling amplification was employed for signal amplification. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity towards small analytes. For other targets, changing the corresponding aptamer can achieve the goal. The quencher did not interfere with the catalytic activity of nuclease. The biosensor could be manipulated with similar sensitivity no matter in pre-addition or post-addition manner. Moreover, simultaneous and multiplexed analysis of several small molecules in homogeneous solution was achieved, demonstrating its potential application in the rapid screening of multiple biotargets. [ABSTRACT FROM AUTHOR]

Oxidative stress, a disturbance in the balance between oxidant/antioxidant ratios, is associated with cancer, aging, inflammation, neurodegenerative diseases and other conditions. γ-Glutamyltranspeptidase (GGT) is a redox-related enzyme that plays a key role in mitigating the effects of oxidative stress by maintaining cellular glutathione (GSH) metabolism and homeostasis. Therefore, oxidative stress will upregulate the intracellular GGT level. To better understand the major pathophysiological resist mechanism to oxidative injury in mediating many disease states, we designed and synthesized a novel two-photon (TP) fluorescent turn-on probe, Np-Glu, for GGT detection and bioimaging. Under the optimized conditions, Np-Glu exhibited remarkable fluorescence enhancement (150-fold), good selectivity and high sensitivity (LOD is 0.033 U L−1), with a wide linear concentration range (0–50 U L−1). More importantly, the probe Np-Glu was successfully applied in one-photon and TP fluorescence imaging of GGT activity in an oxidative stress model in living cells and tissues, suggesting Np-Glu as an ideal indicator for clinical and biological samples. [ABSTRACT FROM AUTHOR]

The monitoring of K + is very important and emergency because of their unique relationship in various disease diagnosis and treatment. G-quadruplex analogue is a classical recognition unit for K + detection and has been widely applied in K + relevant research. Common fluorescent dyes were employed for design of G-quadruplex structure-based K + probes which suffered from the aggregation-caused quenching effect, and possibly limited the biological applications in living systems. Herein, we report an aggregation-induced emission (AIE) effect-based fluorescent probe for cellular K + analysis and imaging. Benefitting from the K + triggered AIE phenomenon, the designed TPE derivative modified guanine (G)-rich oligonucleotide fluorescent probe (TPE-oligonucleotide probe) exhibits high sensitivity (∼10-fold higher than most reported G-quadruplex-based probes) with extended photostability which facilitates the prolonged fluorescence observations of K + in living cells. On the basis of these advantages, the TPE-oligonucleotide probe serves as a promising candidate for the functional study and analysis of K + . [ABSTRACT FROM AUTHOR]

Two-dimensional graphitic carbon nitride nanosheets (CNNSs) with planar graphene-like structure have stimulated increasingly research interest in recent years due to their unique physicochemical properties. CNNSs possess superior stability, high fluorescence quantum yield, low-toxicity, excellent biocompatibility, unique electroluminescent and photoelectrochemical properties, which make them appropriate candidates for biosensing. In this review, we first introduce the preparation and unique properties of CNNSs, with emphasis on their superior properties for biosensing. Then, recent advances of CNNSs in photoelectrochemical biosensing, electrochemiluminescence biosensing and fluorescence biosensing are highlighted. An additional attention is paid to the marriage of CNNSs and nucleic acids, which exhibits great potentials in both biosensing and intracellular imaging. Finally, current challenges and opportunities of this 2D material are outlined. Inspired by the unique properties of CNNSs and their advantages in biological applications, we expect that more attention will be drawn to this promising 2D material and extensive applications can be found in bioanalysis and diseases diagnosis. [ABSTRACT FROM AUTHOR]

Thiophenols are highly toxic industrial materials that, once released, will accumulate in the environment, and ultimately in human bodies, thereby causing serious health problems. To achieve their selective and sensitive detection, a novel near-infrared (NIR) fluorescent probe ( CCP-1) from a focused library was developed for thiophenol species. Our studies show that CCP-1 displays a thiophenol-triggered 28-fold fluorescence intensity enhancement at 706 nm, with a detection limit of 34 n m observed. It is also able to differentiate thiophenols from various other thiol-containing analytes including hydrogen sulfide, hydrogen persulfide, and aliphatic thiols. In total, the desirable properties (e.g., excitation/emission in the NIR region, good cell-membrane permeability, intracellular stability, and low cytotoxicity) make CCP-1 a potential candidate for thiophenol detection both in vitro and in vivo. In addition, CCP-1, for the first time, successfully visualized thiophenols in mice models of thiophenol inhalation. [ABSTRACT FROM AUTHOR]

A promising two-photon fluorescent probe MNAH for detecting 1O2 during the PDT process in mitochondria was proposed for the first time. MNAH was successfully applied for two-photon imaging of 1O2 in living cells and tissues during the PDT process with deep-tissue imaging depth. MNAH can be a powerful molecular tool for studying 1O2 generation in mitochondria during the PDT process. [ABSTRACT FROM AUTHOR]

Cellular self-regulation of reactive oxygen species (ROS) stress via antioxidant repair plays an important role in maintaining the redox balance. The redox balance between reducing and oxidizing species within cells is significant in the regulation of a signal pathway and is achieved by a series of elaborate mechanisms. In this work, we employed our previously reported D–π-A-structured naphthalene–BODIPY TBET platform to design an efficient two-photon fluorescent probe for dynamic monitoring of superoxide anion oxidative stress and the GSH reducing repair process. The probe displayed high energy transfer efficiency (91.4%), large pseudo-Stokes shifts upon one-photon excitation, and red fluorescence emission (λem = 596 nm), which is highly desirable for bioimaging applications. The probe exhibits reversibility, rapid response, good photostability, high selectivity and sensitivity for the superoxide anion and GSH. More importantly, the probe was successfully applied for visualizing the redox changes in living cells and tissues. [ABSTRACT FROM AUTHOR]

SO 2 and its derivatives (bisulfite/sulfite) play crucial roles in several physiological processes. Therefore, development of reliable analytical methods for monitoring SO 2 and its derivatives in biological systems is very significant. In this paper, a FRET-based two-photon fluorescent turn-on probe, A-HCy , was proposed for specific detection of SO 2 derivatives through the bisulfite/sulfite-promoted Michael addition reaction. In this FRET system, an acedan (2-acetyl-6-dialkylaminonaphthalene) moiety was selected as a two-photon donor and a hemicyanine derivative served as both the quencher and the recognition unit for bisulfite/sulfite. A-HCy exhibited excellent selectivity and rapid response to HSO 3 − with a detection limit of 0.24 μM. More importantly, probe A-HCy was first successfully applied in two-photon fluorescence imaging of biological SO 2 derivatives in living cells and tissues, suggesting its great potential for practical application in biological systems. [ABSTRACT FROM AUTHOR]

As an organelle in cells, lysosomes play an important role in the degradation of biological macromolecules and pathogens. To elucidate the function of lysosomes in normal or disease states, recently, various fluorescent probes have been reported for imaging lysosomal analytes. However, because of the particularity of the lysosomal environment, most of the reported lysosomal fluorescent probes suffered from a series of practical issues such as easy diffusion, low detection signal-to-background ratio and false signal. To address these issues, based on an optimized in situ ordered assembly solid-state fluorophore HDPQ, we herein put forward a new strategy for the design of lysosomal enzymes probes. As a proof concept, we synthesized a fluorescent probe HDPQ-GLU for lysosomal enzyme β-glucuronidase (GLU). Experiment results displayed that compared with general lysosomal probe, the novel lysosomal probe not only exhibited excellent anti -pH interference ability and high signal-to-noise ratio in aqueous solution, but also has excellent long-term in situ imaging ability in the living system. Using this probe, we have realized high-fidelity and long-term in situ tracking GLU in lysosomes of living cells and evaluated the dynamic changes of GLU during the growth period of zebrafish. We anticipate that the new strategy based on the novel in situ ordered assembly solid-state fluorophore HDPQ may be a potential platform for developing fluorescent probes for high-fidelity imaging of lysosomal enzymes. [ABSTRACT FROM AUTHOR]

Formaldehyde (FA) plays an important role in living systems as a reactive carbonyl species (RCS). An abnormal degree of FA is known to induce neurodegeneration, cognitive decrease and memory loss owing to the formation of strong cross-link DNA and protein and other molecules. The development of efficient methods for biological FA detection is of great biomedical importance. Although a few one-photon FA fluorescent probes have been reported for imaging in living cells, probes excited by two photons are more suitable for bio-imaging due to their low background fluorescence, less photobleaching, and deep penetration depth. In this study, a two-photon fluorescent probe FATP1 for FA detection and bio-imaging in living cells and tissues was reported. The detection is based on the 2-aza-Cope sigmatropic rearrangement followed by elimination to release the fluorophore, resulting in both one- and two-photon excited fluorescence increase. The probe FATP1 showed a high sensitivity to FA with a detection limit of 0.2 μM. Moreover, FATP1 enabled the two-photon bio-imaging of FA in live HEK-293 cells and tissues with tissue-imaging depths of 40–170 μm. Furthermore, FATP1 could be applied for the monitoring of endogenous FA in live MCF-7 cells, presaging its practical applications in biological systems. [ABSTRACT FROM AUTHOR]

The combination of nanostructures with biomolecules leading to the generation of functional nanosystems holds great promise for biotechnological and biomedical applications. As a naturally occurring biomacromolecule, DNA exhibits excellent biocompatibility and programmability. Also, scalable synthesis can be readily realized through automated instruments. Such unique properties, together with Watson–Crick base-pairing interactions, make DNA a particularly promising candidate to be used as a building block material for a wide variety of nanostructures. In the past few decades, various DNA nanostructures have been developed, including one-, two- and three-dimensional nanomaterials. Aptamers are single-stranded DNA or RNA molecules selected by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), with specific recognition abilities to their targets. Therefore, integrating aptamers into DNA nanostructures results in powerful tools for biosensing and bioimaging applications. Furthermore, owing to their high loading capability, aptamer-modified DNA nanostructures have also been altered to play the role of drug nanocarriers for in vivo applications and targeted cancer therapy. In this review, we summarize recent progress in the design of aptamers and related DNA molecule-integrated DNA nanostructures as well as their applications in biosensing, bioimaging and cancer therapy. To begin with, we first introduce the SELEX technology. Subsequently, the methodologies for the preparation of aptamer-integrated DNA nanostructures are presented. Then, we highlight their applications in biosensing and bioimaging for various targets, as well as targeted cancer therapy applications. Finally, we discuss several challenges and further opportunities in this emerging field. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer-MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer-MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery. [ABSTRACT FROM AUTHOR]

Cell-surface fluorescent probes are effective tools in cell biology and engineering. Here, we for the first time report a diacyllipid–aptamer conjugate-based fluorescent probe which could anchor on cell membrane for real-time tracking of potassium ions in the cell microenvironment. [ABSTRACT FROM AUTHOR]

In this work we use a water-soluble cationic perylene derivative (compound 1) as the G-quadruplex (G4) structure fluorescence indicator to construct a fluorescent biosensor for simple, rapid and label-free detection of Pb 2+ . In the absence of Pb 2+ , strong electrostatic interactions between compound 1 and the G-rich DNA probe (PW17) induced the aggregation of compound 1 and resulted in the fluorescence quenching. In the presence of Pb 2+ , the PW17 formed Pb 2+ -stabilized G4 structure, which reduced the aggregation of compound 1 and gave rise to high fluorescence. This allowed us to use convenient “mix-and-detect” protocol for quantitative analysis of Pb 2+ . Since Pb 2+ can specially induce PW17 to form compact DNA fold, our proposed biosensor displayed high selectivity for Pb 2+ . It also exhibited a high sensitivity to Pb 2+ , with a limit of detection of 5.0 nM observed. Furthermore, the biosensor was applied for the detection of Pb 2+ in urine and paint samples, and both showed satisfactory results. [ABSTRACT FROM AUTHOR]

A FRET-based two-photon fluorescent probe, P-Np-Rhod, which exhibited a fast and high selective ratiometric response to nitroxyl, was first proposed. P-Np-Rhod was successfully applied to two-photon dual-channel imaging of nitroxyl in living cells and tissues with less cross-talk between channels and satisfactory deep-tissue imaging depth. [ABSTRACT FROM AUTHOR]

DNAzyme-based catalytic beacons have been widely studied for both in vivo and in vitro molecular detection. However, only a few label-free catalytic beacons with excellent analytical performance have been reported so far. In this work, by combining a catalytic DNAzyme for amplified sensing through enzymatic turnover with cleavage-induced G-quadruplex formation, a label-free DNAzyme biosensor was developed for amplified “turn-on” fluorescence detection of Pb 2+ with a detection limit of 3 nM. The method is very competitive compared to many other labeled or label-free methods with or without signal amplification. Due to the inherent specificity of the GR-5 DNAzyme, the method also exhibits excellent selectivity. This biosensor successfully detected Pb 2+ in river water samples with high sensitivity and selectivity. Such a method might provide a universal DNAzyme-based sensing platform for sensitive detection of various targets both in environmental and biomedical fields. [ABSTRACT FROM AUTHOR]

Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly( l -lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue. [ABSTRACT FROM AUTHOR]

Lysosomes are acidic organelles (approximately pH 4.5–5.5) and tracking the changes in lysosomal pH is of great biological importance. To address this issue, quite a few of fluorescent probes have been developed. However, few of these probes can realize the tracking of dynamic changes in lysosomal pH. Herein, we report a new lysosome-targeted ratiometric fluorescent probe (FR-Lys) by hybridizing morpholine with a xanthane derivative and an o-hydroxy benzoxazole group. In this probe, the morpholine group serves as a targeting unit for lysosome, the xanthane derivative exhibits a pH-modulated open/close reaction of the spirocycle, while the o-hydroxy benzoxazole moiety shows a pH modulated excited-state intramolecular proton transfer (ESIPT) process. Such a design affords the probe a ratiometric fluorescence response towards pH with pH values ranging from 4.0 to 6.3. The response of the probe to pH was fast and reversible with high selectivity. Moreover, this probe possesses further advantages such as easy synthesis, high photostability and low cytotoxicity. These features are favorable for tracking dynamic pH changes in biosystems. It was then applied for dynamic imaging pH changes in lysosomes with satisfactory results. [ABSTRACT FROM AUTHOR]

By employing DNAzyme as a recognition group and amplifier, and DNA-stabilized silver nanoclusters (DNA/AgNCs) as signal reporters, we reported for the first time a label-free catalytic and molecular beacon as an amplified biosensing platform for highly selective detection of cofactors such as Pb2+ and l-histidine. [ABSTRACT FROM AUTHOR]

An automatic and efficient data analysis method for comprehensive metabolic profiling analysis is urgently required. In this study, a new chemometric-assisted method for metabolic profiling analysis (CAMMPA) was developed to discover potentially valuable metabolites automatically and efficiently. The proposed method mainly consists of three stages. First, automatic chromatographic peak detection is performed based on the total ion chromatograms of samples to extract chromatographic peaks that can be accurately quantified. Second, a novel peak-shift alignment technique based on peak detection results is implemented to resolve time-shift problems across samples. Consequently, aligned results, including aligned chromatograms, and peak area tables, among others, can be successfully obtained. Third, statistical analysis using results from unsupervised and supervised classification results, together with ANOVA and partial least square-discriminate analysis, is performed to extract potential metabolites. To demonstrate the proposed technique, a complex GC–MS metabolic profiling dataset was measured to identify potential metabolites in tobacco plants of different growth stages as well as different plant tissues after maturation. Results indicated that the efficiency of the routine metabolic profiling analysis procedure can be significantly improved and potential metabolites can be accurately identified with the aid of CAMMPA. [ABSTRACT FROM AUTHOR]

DNAzymes are a series of functional oligonucleotides obtained through in vitro selection and able to catalyze the reaction of substrates with the help of some special cofactors such as metal ions, L-histidine and hemin. Compared with naturally occurring bio-enzymes, DNAzymes are more stable and amenable to modification and preparation. Due to their outstanding properties, DNAzymes have been widely used in biological applications, such as target detection and signal amplification. Nanomaterials, with special characteristics including quantum size effect, high biocompatibility, large surface-to-volume ratio and overall structural robustness, exhibit important application prospects in nanotechnology. By combining with a variety of nanomaterials, DNAzyme achieves a lot of special applications in biochemistry. This review summarizes recent achievements in the field of DNAzyme-conjugated nanomaterials for biosensing applications. For a brief demonstration, nanomaterials including gold nanoparticles, carbon nanomaterials, magnetic nanoparticles and semiconductor quantum dots are taken as examples. [ABSTRACT FROM AUTHOR]

Peak detection and background drift correction (BDC) are the key stages in using chemometric methods to analyze chromatographic fingerprints of complex samples. This study developed a novel chemometric strategy for simultaneous automatic chromatographic peak detection and BDC. A robust statistical method was used for intelligent estimation of instrumental noise level coupled with first-order derivative of chromatographic signal to automatically extract chromatographic peaks in the data. A local curve-fitting strategy was then employed for BDC. Simulated and real liquid chromatographic data were designed with various kinds of background drift and degree of overlapped chromatographic peaks to verify the performance of the proposed strategy. The underlying chromatographic peaks can be automatically detected and reasonably integrated by this strategy. Meanwhile, chromatograms with BDC can be precisely obtained. The proposed method was used to analyze a complex gas chromatography dataset that monitored quality changes in plant extracts during storage procedure. [ABSTRACT FROM AUTHOR]

Abstract: Fluorescent sensing systems based on the quenching of fluorophores have found wide applications in bioassays. An efficient quencher will endow the sensing system a high sensitivity. The frequently used quenchers are based on organic molecules or nanomaterials, which usually need tedious synthesizing and modifying steps, and exhibit different quenching efficiencies to different fluorophores. In this work, we for the first time report that aggregated perylene derivative can serve as a broad-spectrum and label-free quencher that is able to efficiently quench a variety of fluorophores, such as green, red and far red dyes labeled on DNA. By choosing nucleases as model biomolecules, such a broad-spectrum quencher was then employed to construct a multiplexed bioassay platform through a label-free manner. Due to the high quenching efficiency of the aggregated perylene, the proposed platform could detect nuclease with high sensitivity, with a detection limit of 0.03U/mL for EcoRV, and 0.05U/mL for EcoRI. The perylene quencher does not affect the activity of nuclease, which makes it possible to design post-addition type bioassay platform. Moreover, the proposed platform allows simultaneous and multicolor analysis of nucleases in homogeneous solution, demonstrating its value of potential application in rapid screening of multiple bio-targets. [Copyright &y& Elsevier]

Abstract: In this work, by combining the enzymatic recycling reaction with the DNA functionalized gold nanoparticles (AuNPs)-based signal amplification, we have developed an electrochemical biosensor for label-free detection of DNA with high sensitivity and selectivity. In the new designed biosensor, a hairpin-structured probe HP was designed to hybridize with target DNA first, and an exonuclease ExoIII was chosen for the homogeneous enzymatic cleaving amplification. The hybridization of target DNA with the probe HP induced the partial cleavage of the probe HP by ExoIII to release the enzymatic products. The enzymatic products could then hybridize with the hairpin-structured capture probe CP modified on the electrode surface. Finally, DNA functionalized AuNPs was further employed to amplify the detection signal. Due to the capture of abundant methylene blue (MB) molecules by both the multiple DNAs modified on AuNPs surface and the hybridization product of capture DNA and enzymatic products, the designed biosensor achieved a high sensitivity for target DNA, and a detection limit of 0.6pM was obtained. Due to the employment of two hairpin-structured probes, HP and CP, the proposed biosensor also exhibited high selectivity to target DNA. Moreover, since ExoIII does not require specific recognition sequences, the proposed biosensor might provide a universal design strategy to construct DNA biosensor which can be applied in various biological and medical samples. [Copyright &y& Elsevier]

Objective The purpose of this study was to understand the incidence trend of sexually transmitted disease (STD) in Chuxiong Prefecture from 2010 to 2012, find out the epidemic characteristics and influence factors, in order to provide a scientific basis for the government to formulate relevant policies. Methods Descriptive analysis method was used to analyze STD epidemic report data and population data from 2010 to 2012 in Chuxiong Prefecture. Results 2010-2012, 1268 cases of STD were reported in the state (not including HIV and AIDS), with the annual incidence of 15.6/100000 and the maximum number of reported cases in 2011 (540 cases) . Women cases reported in 2010-2012 (653 cases) were higher than the man cases reported (615 cases) . The onset age were mainly concentrated in the 20-29 and 30-39 age groups, the occupation fields mainly were in farmers, houseworker and unemployed people, and were distributed mainly in Lufeng city (224 cases), Dayao city(127 cases), chuxiong city (107 cases), and Yaoan city (103 cases) . Conclusion 2010-2012, cases of STD reported in chuxiong mainly focused on women, young adults, farmers, houseworker and unemployed people. It is suggested to strengthen STD prevention knowledge and health education management work for these people. [ABSTRACT FROM AUTHOR]

Abstract: Carbon nanomaterials are typically used in electrochemical biosensing applications for their unique properties. We report a hollow graphitic nanocapsule (HGN) utilized as an efficient electrode material for sensitive hydrogen peroxide detection. Methylene blue (MB) molecules could be efficiently adsorbed on the HGN surfaces, and this adsorption capability remained very stable under different pH regimes. HGNs were used as three-dimensional matrices for coimmobilization of MB electron mediators and horseradish peroxidase (HRP) to build an HGN–HRP–MB reagentless amperometric sensing platform to detect hydrogen peroxide. This simple HGN–HRP–MB complex demonstrated very sensitive and selective hydrogen peroxide detection capability, as well as high reproducibility and stability. The HGNs could also be utilized as matrices for immobilization of other enzymes, proteins or small molecules and for different biomedical applications. [Copyright &y& Elsevier]

Abstract: In this work, based on the fact that pyrophosphate (PPi) could regulate the activity of Zn2+-dependent DNAzyme, we for the first time report a fluorescence turn-on sensing system for alkaline phosphatase (ALP) with improved sensitivity via nonprotein-enzymatic signal amplification. A catalytic and molecular beacon (CAMB) design was employed to further improve its sensitivity. Taking advantage of the strong interactions between PPi and the Zn2+, the cofactor Zn2+ was caged, and the DNAzyme activity was effectively inhibited. The introduction of ALP, however, could catalyze the hydrolysis of PPi and release free Zn2+, resulting in the activation of DNAzyme to catalyze the cleavage of the molecular beacon substrate with a remarkable increase of fluorescent signal. These optimized designs together allow a high sensitivity for ALP, with a detection limit of 20pM observed, much lower than previously reported methods. It has also been used for detection of ALP in human serum with satisfactory results, demonstrating its potential applications in clinical diagnosis. [Copyright &y& Elsevier]