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[Display omitted] • Outlined the significance of studying atherosclerosis (AS) and the advantages of molecular probes for researching AS. • Summarized the design strategies for AS-targeted molecular probes. • Emphasized the current applications of AS-targeted molecular probes in precise imaging, auxiliary diagnosis and treatment. • Discussed the shortcomings of current AS targeted molecular probes and the research prospects in AS related diseases. Atherosclerosis (AS) poses a significant threat to human life and health, with its pathophysiological processes involving a myriad of complex biological events that ultimately lead to various clinical complications, such as coronary heart disease and stroke. In the light of severity of AS, the precise identification, prevention, and treatment of AS have become exceptionally crucial. In recent years, molecular probe optical imaging has garnered widespread attention due to it allows for the detection of subtle changes in the concentration of biological targets at disease sites through optical signal detection, offering hope for non-invasive detection and imaging of AS. In this review, we first describe the mechanism of AS formation and discuss the design strategies of molecular optical probes. Moreover, we comprehensively summarize the progress of molecular probes in imaging, diagnosing and treating AS. Finally, we emphasize some challenges and prospects in the field of AS, especially in coronary heart disease. [ABSTRACT FROM AUTHOR]

Fluorescent probes have been powerful tools for visualizing and quantifying multiple dynamic processes in living cells. However, the currently developed probes are often constructed by conjugation a fluorophore with a recognition moiety and given signal‐output after triggering with one singly target interest. Compared with the single‐target‐activated fluorescent probes mentioned above, the dual‐target‐activated ones, triggering with one target under stimulus (such as photoirradiation, microenvironment) or another targets, have the advantages of advoiding nonspecific activation and "false positive" results in complicated environments. In recent years, many dual‐target‐activated fluorescent probes have been developed to detect various biologically relevant species. In view of the importance of a comprehensive understanding of dual‐target‐ activated fluorescent probes, a thorough summary of this topic is urgently needed. However, no comprehensive and critical review on dual target activated fluorescent probes has been published recently. In this review, we focus on the dual‐target‐activated fluorescent probes and briefly outline their types and current state of development. In each type, the chemical structure, proposed responsive mechanism and application of probes are highlighted. At last, the challenges and prospective opportunities of every type were proposed. [ABSTRACT FROM AUTHOR]

Highly efficient gene knockout (KO) editing of CRISPR–Cas9 has been achieved in iPSCs, whereas homology-directed repair (HDR)-mediated precise gene knock-in (KI) and high-level expression are still bottlenecks for the clinical applications of iPSCs. Here, we developed a novel editing strategy that targets introns. By targeting the intron before the stop codon, this approach tolerates reading frameshift mutations caused by nonhomologous end-joining (NHEJ)-mediated indels, thereby maintaining gene integrity without damaging the non-HDR-edited allele. Furthermore, to increase the flexibility and screen for the best intron-targeting sgRNA, we designed an HDR donor with an artificial intron in place of the endogenous intron. The presence of artificial introns, particularly an intron that carries an enhancer element, significantly increased the reporter expression levels in iPSCs compared to the intron-deleted control. In addition, a combination of the small molecules M3814 and trichostatin A (TSA) significantly improves HDR efficiency by inhibiting NHEJ. These results should find applications in gene therapy and basic research, such as creating reporter cell lines. [ABSTRACT FROM AUTHOR]

Small‐molecule‐based second near‐infrared (NIR‐II) activatable fluorescent probes can potentially provide a high target‐to‐background ratio and deep tissue penetration. However, most of the reported NIR‐II activatable small‐molecule probes exhibit poor versatility owing to the lack of a general and stable optically tunable group. In this study, we designed NIRII‐HDs, a novel dye scaffold optimized for NIR‐II probe development. In particular, dye NIRII‐HD5 showed the best optical properties such as proper pKa value, excellent stability, and high NIR‐II brightness, which can be beneficial for in vivo imaging with high contrast. To demonstrate the applicability of the NIRII‐HD5 dye, we designed three target‐activatable NIR‐II probes for ROS, thiols, and enzymes. Using these novel probes, we not only realized reliable NIR‐II imaging of different diseases in mouse models but also evaluated the redox potential of liver tissue during a liver injury in vivo with high fidelity. [ABSTRACT FROM AUTHOR]

Small‐molecule‐based second near‐infrared (NIR‐II) activatable fluorescent probes can potentially provide a high target‐to‐background ratio and deep tissue penetration. However, most of the reported NIR‐II activatable small‐molecule probes exhibit poor versatility owing to the lack of a general and stable optically tunable group. In this study, we designed NIRII‐HDs, a novel dye scaffold optimized for NIR‐II probe development. In particular, dye NIRII‐HD5 showed the best optical properties such as proper pKa value, excellent stability, and high NIR‐II brightness, which can be beneficial for in vivo imaging with high contrast. To demonstrate the applicability of the NIRII‐HD5 dye, we designed three target‐activatable NIR‐II probes for ROS, thiols, and enzymes. Using these novel probes, we not only realized reliable NIR‐II imaging of different diseases in mouse models but also evaluated the redox potential of liver tissue during a liver injury in vivo with high fidelity. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Fluorophores play a significant role in achieving high‐contrast imaging in complex physiological environment. Herein, we present the results of our studies on the development of various fluorophores, such as anti‐solvatochromic fluorophores, long wavelength emission two‐photon fluorophores, large Stokes shift fluorophores and solid‐state fluorophores, to achieve high‐contrast bioimaging in physiological environments. In this study, we have primarily focused on the design, optical performance, imaging mechanisms, and the applications of these fluorophores with respect to complex physiological conditions. What is the most favorite and original chemistry developed in your research group? Orderly assembly of small‐molecule dyes and their applications for long‐term in situ bioimaging. How do you get into this specific field? Could you please share some experiences with our readers? We have long been engaged in the field of fluorescence imaging for biomedical applications, and realized that obtaining the target's in situ information is urgent and challenging. Our exploration revealed that the orderly assembly of specific molecular dyes is an effective strategy to overcome this problem. Keeping curiosity and thinking is the key to solving problems in scientific research. What is the most important personality for scientific research? Clear mind and perseverance. What's your hobby? Communicating with Youngs. How do you keep balance between research and family? To make a proper allotment of time. How do you supervise your students? Let them know what they want and fight for it. [ABSTRACT FROM AUTHOR]

Stable and sensitive ctDNA biosensing in complex biological fluid is highly important but still remains a challenge. Herein, we develop a spherical nucleic acid reporter-based cascade CRISPR/Cas12a amplifier with improved stability and sensitivity (5 orders of magnitude). [ABSTRACT FROM AUTHOR]

We report here an activatable chemiluminescent probe CL-O3 for the high-contrast imaging of O3in vivo. CL-O3 exhibited a high selectivity toward O3 and was able to evaluate the degree of inflammation in mice by detecting endogenous O3 levels in acute inflamed mice. [ABSTRACT FROM AUTHOR]

Hemophilia A (HA) is a monogenic disease characterized by plasma clotting factor 8 (F8) deficiency due to F8 mutation. We have been attempting to cure HA permanently using a CRISPR-Cas9 gene-editing strategy. In this study, we induced targeted integration of BDDF8 (B-domain-deleted F8) gene into the albumin locus of HA mice by hydrodynamic tail vein injection of editing plasmid vectors. One week after treatment, a high F8 activity ranging from 70% to 280% of normal serum levels was observed in all treated HA mice but dropped to background levels 3–5 weeks later. We found that the humoral immune reaction targeting F8 is the predominant cause of the decreased F8 activity. We hypothesized that hydrodynamic injection-induced liver damage triggered the release of large quantities of inflammatory cytokines. However, coinjection of plasmids expressing a dozen immunomodulatory factors failed to curtail the immune reaction and stabilize F8 activity effectively. The spCas9 plasmid carrying a miR-142-3p target sequence alleviated the cellular immune response but could not deliver therapeutic efficacy. Strikingly, immunosuppressant cyclophosphamide virtually abolished the immune response, leading to a year-long stable F8 level. Our findings should have important implications in developing therapies in mouse models using the hydrodynamic gene delivery approach, highlighting the necessity of modulating the innate immune response triggered by liver damage. [ABSTRACT FROM AUTHOR]

Rapid, sensitive and selective biosensing is highly important for analyzing biological targets and dynamic physiological processes in cells and living organisms. As an emerging tool, clustered regularly interspaced short palindromic repeats (CRISPR) system is featured with excellent complementary-dependent cleavage and efficient trans-cleavage ability. These merits enable CRISPR system to improve the specificity, sensitivity, and speed for molecular detection. Herein, the structures and functions of several CRISPR proteins for biosensing are summarized in depth. Moreover, the strategies of target recognition, signal conversion, and signal amplification for CRISPR-based biosensing were highlighted from the perspective of biosensor design principles. The state-of-art applications and recent advances of CRISPR system are then outlined, with emphasis on their fluorescent, electrochemical, colorimetric, and applications in POCT technology. Finally, the current challenges and future prospects of this frontier research area are discussed. [ABSTRACT FROM AUTHOR]

Rhodamine fluorophore has attracted increasing attention due to its good stability and high fluorescence quantum yield. However, it is still a challenge to design long-wavelength rhodamine with high performance. In this work, by the reasonable design, we have constructed a novel rhodamine fluorophore YL602-F. YL602-F not only displays long absorption/emission (602/638 nm), but also possesses excellent chemical stability, high brightness (φ × ε/M-1 cm-1 = 26,450), environmental insensitive emission and easy synthesis, thus displaying a good potential for bioimaging application. As a proof-of-concept, based on dye YL602-F , we then designed and developed a nitric oxide-activated fluorescent probe YL602-F-NO. Experiment results showed that probe YL602-F-NO could respond to NO with a 35-fold fluorescence enhancement together with a high sensitivity and the detection limit was calculated to be 83.1 nM. Notably, YL602-F-NO has also been successfully used to sensitively recognize endogenous NO in cells and living mice, especially for real-time monitoring of NO levels in a mouse model of DSS-induced enteritis. We expect the YL602-F fluorophore to be a promising molecule that will help researchers develop activated fluorescent probes with even better performance. [Display omitted] • Constructing a novel rhodamine fluorophore YL602-F with long absorption/emission. • Possessing excellent chemical stability, high brightness, environmental insensitive emission and easy synthesis. • Developing a nitric oxide-activated fluorescent probe YL602-F-NO with a high sensitivity. • Real-time monitoring of NO levels in a mouse model of DSS-induced enteritis. [ABSTRACT FROM AUTHOR]

Two‐photon (TP) imaging with a donor‐acceptor (D−A) type fluorophore is an emerging tool for bioimaging and sensing. However, current TP probes suffer from serious solvatochromic quenching in aqueous solution due to their strong intramolecular charge transfer (ICT) in excited states. In this work, based on solvatochromism reversal, we report a novel strategy to develop TP probes for bioimaging. Specifically, compared with the normal two‐photon probes that showed a fluorescence off with ICT suppressed, the novel probes exhibited strong fluorescence in the aqueous solution when their ICT was inhibited. This strategy not only provides a new way for the design of high‐performance TP probes, but also expands the biological analysis toolbox for use in living systems. [ABSTRACT FROM AUTHOR]

While ex-ante evaluations of climate mitigation policies predict that co-benefits of improved air quality will enable the aggregate benefits of climate mitigation policies to outweigh their costs, there is little empirical evidence to support this assertion. In this study, we use data on weekly smokestack emissions of sulfur dioxide (SO2) from firms participating in Shanghai's carbon dioxide (CO2) emissions trading scheme (ETS) to deliver one of the first ex-post evaluations on the co-benefits of China's ETS. Using a panel-regression model in which all firms' characteristics and seasonal effects are controlled, we find a significant negative association between CO2 emissions prices and industrial SO2 emissions (elasticity of −0.13). A closer examination reveals that most of these effects were driven by specific sectors (iron and steel) and during months in which firms were required to balance their annual CO2 emissions. To ensure our results are not driven by confounding factors and our model's assumptions, we conducted several falsification checks using SO2 emissions from non-ETS firms and firms from a nearby city, using various model specifications. Our findings suggest that co-benefits from climate mitigation policies should not be taken for granted, and that policy designs and types of sector sources of emissions are important determinants of co-benefits. Key policy insights The study provides empirical evidence for air pollution co-benefits of a CO2 ETS using weekly smokestack-level data from Shanghai, China Evidence from the Shanghai ETS shows that a 1% increase in CO2 prices in Shanghai is associated with a 0.13% decrease in SO2 emissions These co-benefits, however, are limited to specific sectors (e.g. ferrous metals), and are not found in other major CO2 emitting sources or sectors (e.g. power utilities) The relationship between CO2 prices and co-benefits is also stronger during months in which firms are required to balance their annual CO2 emissions using permits [ABSTRACT FROM AUTHOR]

Nanozymes with intrinsic enzyme‐like characteristics have attracted enormous research interest in biological application. However, there is a lack of facile approach for evaluating the catalytic activity of nanozymes in living system. Herein, we develop a novel manganese‐semiconducting polymer‐based nanozyme (MSPN) with oxidase‐like activity for reporting the catalytic activity of itself in acid‐induced cancer therapy via ratiometric near‐infrared fluorescence (NIRF)‐photoacoustic (PA) molecular imaging. Notably, MSPN possess oxidase‐like activity in tumor microenvironment, owing to the mixed‐valent MnOx nanoparticles, which can effectively kill cancer cells. Because the semiconducting polymer (PFODBT) is conjugated with oxidase‐responsive molecule (ORM), the catalytic activity of nanozyme can be correlated with the ratiometric signals of NIRF (FL695/FL825) and PA (PA680/PA780), which may provide new ideas for predicting anticancer efficacy of nanozymes in living system. [ABSTRACT FROM AUTHOR]

Nanozymes with intrinsic enzyme‐like characteristics have attracted enormous research interest in biological application. However, there is a lack of facile approach for evaluating the catalytic activity of nanozymes in living system. Herein, we develop a novel manganese‐semiconducting polymer‐based nanozyme (MSPN) with oxidase‐like activity for reporting the catalytic activity of itself in acid‐induced cancer therapy via ratiometric near‐infrared fluorescence (NIRF)‐photoacoustic (PA) molecular imaging. Notably, MSPN possess oxidase‐like activity in tumor microenvironment, owing to the mixed‐valent MnOx nanoparticles, which can effectively kill cancer cells. Because the semiconducting polymer (PFODBT) is conjugated with oxidase‐responsive molecule (ORM), the catalytic activity of nanozyme can be correlated with the ratiometric signals of NIRF (FL695/FL825) and PA (PA680/PA780), which may provide new ideas for predicting anticancer efficacy of nanozymes in living system. [ABSTRACT FROM AUTHOR]

In situ monitoring of the location and transportation of bioactive molecules is essential for deciphering diverse biological events in the field of biomedicine. In addition, obtaining the in situ information of lesions will provide a clear perspective for surgeons to perform precise resection in clinical surgery. Notably, delivering drugs or operating photodynamic therapy/photothermal therapy in situ by labeling the lesion regions of interest can improve treatment and reduce side effects in vivo. In various advanced imaging and therapy modalities, optical theranostic agents based on organic small molecules can be conveniently modified as needed and can be easily internalized into cells/lesions in a non-invasive manner, which are prerequisites for in situ bioimaging and precision treatment. In this tutorial review, we first summarize the in situ molecular immobilization strategies to retain small-molecule agents inside cells/lesions to prevent their diffusion in living organisms. Emphasis will be focused on introducing the application of these strategies for in situ imaging of biomolecules and precision treatment, particularly pertaining to why targeting therapy in situ is required. [ABSTRACT FROM AUTHOR]

Abstract: The self-assembly of cyclodextrin (CD) functionalized graphene (GR) and adamantane-modified horseradish peroxidase (HRP-ADA) by host–guest supramolecular interaction into novel nanostructures in aqueous solution is reported in the present study. Electrochemical impedance spectroscopy and cyclic voltammetry were applied to characterize the self-assembly process and study the electrochemical behaviors of the immobilized proteins. UV–vis spectra indicated that the native structure of HRP was maintained after the assembly, implying good biocompatibility of CD-functionalized GR (CD-GR). Furthermore, the HRP-ADA/CD-GR composites were utilized for the fabrication of enzyme electrodes (HRP-ADA/CD-GR electrodes). The proposed biosensor showed good reproducibility and high sensitivity to H2O2 with the detection limit of 0.1μM. In the range of 0.7–35μM, the catalytic reduction current of H2O2 was proportional to H2O2 concentration. [Copyright &y& Elsevier]

Abstract: A universal sensing platform for fluorescence turn-on detection of biomolecules is developed based on Fenton reaction triggered molecular beacon cleavage. Due to its high quenching efficiency, molecular beacons (MBs)-based sensing systems usually show low background fluorescence and large signal-to-background ratio. Glucose is chosen as a model biomolecule for constructing an MB-based fluorescence sensing system. In the presence of glucose, the glucose oxidase will bind with it and catalyze the oxidation to generate H2O2, which is further decomposed to produce OH through the Fe2+-catalyzed Fenton reaction. Then, in-situ-generated OH can trigger the cleavage of the MB, and its fluorescence intensity will be dramatically increased because of the complete separation of the fluorophore from the quencher. By employing molecular beacon as both recognition and reporter probes to low background signal, the proposed biosensors showed high sensitivity to targets. It also exhibited high selectivity owing to the high specificity of the enzymatic oxidation, which make it valuable for the detection of target biomolecule in complex biological samples. [Copyright &y& Elsevier]

Abstract: Alpha (α)-asarone is a major effective compound isolated from the Chinese medicinal herb Acorus gramineus, which is widely used in clinical practice as an antiepileptic drug; however, its mechanism of action remains unclear. In this study, we have characterized the action of α-asarone on the excitability of rat hippocampal neurons in culture and on the epileptic activity induced by pentylenetetrazole or kainate injection in vivo. Under cell-attached configuration, the firing rate of spontaneous spiking was inhibited by application of α-asarone, which was maintained in the Mg2+-free solution. Under whole-cell configuration, α-asarone induced inward currents in a concentration-dependent manner with an EC50 of 248 ± 33 μM, which was inhibited by a GABAA receptor blocker picotoxin and a competitive GABAA receptor antagonist bicuculline but not a specific glycine receptor inhibitor strychnine. Measurement of tonic GABA currents and miniature spontaneous inhibitory postsynaptic currents indicated that α-asarone enhanced tonic GABAergic inhibition while left phasic GABAergic inhibition unaffected. In both pentylenetetrazole and kainate seizure models, α-asarone suppressed epileptic activity of mice by prolonging the latency to clonic and tonic seizures and reducing the mortality as well as the susceptibility to seizure in vivo presumably dependent on the activation of GABAA receptors. In summary, our results suggest that α-asarone inhibits the activity of hippocampal neurons and produces antiepileptic effect in central nervous system through enhancing tonic GABAergic inhibition. [Copyright &y& Elsevier]

This paper introduces a design methodology for a multi-tesla permanent magnet. Normally the permanent magnet is designed to provide the magnetic fields below 2 T. By employing high performance materials and the 3D magnetic circuit design method, a prototype magnet has been built and generates maximum 2.987 T field strength in 0.008 m air gap with less than 20 kg total weight. It is expected a practical, compact and light-weight high field source for NMR, MRI or other instruments. [ABSTRACT FROM PUBLISHER]

Abstract: Quinolin-8-ol p-[10′,15′,20′-triphenyl-5′-porphyrinyl]benzoate (1) was synthesized for the first time and developed as a ratiometric fluorescent chemosensor for recognition of Hg2+ ions in aqueous ethanol with high selectivity. The 1–Hg2+ complexation quenches the fluorescence of porphyrin at 646nm and induces a new fluorescent enhancement at 603nm. The fluorescent response of 1 towards Hg2+ seems to be caused by the binding of Hg2+ ion with the quinoline moiety, which was confirmed by the absorption spectra and 1H NMR spectrum. The fluorescence response fits a Hill coefficient of 1 (1.0308), indicating the formation of a 1:1 stoichiometry for the 1–Hg2+ complex. The analytical performance characteristics of the chemosensor were investigated. The sensor shows a linear response toward Hg2+ in the concentration range of 3×10−7 to 2×10−5 M with a limit of detection of 2.2×10−8 M. Chemosensor 1 shows excellent selectivity to Hg2+ over transition metal cations except Cu2+, which quenches the fluorescence of 1 to some extent when it exists at equal molar concentration. Moreover, the chemosensor are pH-independent in 5.0–9.0 and show excellent selectivity for Hg2+ over transition metal cations. [Copyright &y& Elsevier]

We developed a cyclic amplification method for an organic afterglow nanoreporter for the real‐time visualization of self‐generated reactive oxygen species (ROS). We promoted semiconducting polymer nanoparticles (PFODBT) as a candidate for emitting near‐infrared afterglow luminescence. Introduction of a chemiluminescent substrate (CPPO) into PFODBT (PFODBT@CPPO) resulted in a significant enhancement of afterglow intensity through the dual cyclic amplification pathway involving singlet oxygen (1O2). 1O2 produced by PFODBT@CPPO induced cancer cell necrosis and promoted the release of damage‐related molecular patterns, thereby evoking immunogenic cell death (ICD)‐associated immune responses through ROS‐based oxidative stress. The afterglow luminescent signals of the nanoreporter were well correlated with light‐driven 1O2 generation and anti‐cancer efficiency. This imaging strategy provides a non‐invasive tool for predicting the therapeutic outcome that occurs during ROS‐mediated cancer therapy. [ABSTRACT FROM AUTHOR]

We developed a cyclic amplification method for an organic afterglow nanoreporter for the real‐time visualization of self‐generated reactive oxygen species (ROS). We promoted semiconducting polymer nanoparticles (PFODBT) as a candidate for emitting near‐infrared afterglow luminescence. Introduction of a chemiluminescent substrate (CPPO) into PFODBT (PFODBT@CPPO) resulted in a significant enhancement of afterglow intensity through the dual cyclic amplification pathway involving singlet oxygen (1O2). 1O2 produced by PFODBT@CPPO induced cancer cell necrosis and promoted the release of damage‐related molecular patterns, thereby evoking immunogenic cell death (ICD)‐associated immune responses through ROS‐based oxidative stress. The afterglow luminescent signals of the nanoreporter were well correlated with light‐driven 1O2 generation and anti‐cancer efficiency. This imaging strategy provides a non‐invasive tool for predicting the therapeutic outcome that occurs during ROS‐mediated cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we rigorously establish an existence theorem of periodic solutions for the competition of Lotka–Volterra dynamic systems with a time delay and diffusion on time scales. It is shown that the existence of periodic solutions depend on the parameters of the model. It is also shown that a known result in the literature can can carry over quite easily to its discrete counterpart, and a much more accurate result can be obtained when studying the dynamic system on time scales. Moreover, one example is given to illustrate the result obtained. [Copyright &y& Elsevier]

Abstract: Salicylate is the major metabolite and active component of aspirin (acetylsalicylic acid), which is widely used in clinical medicine for treating inflammation, pain syndromes and cardiovascular disorders. The well-known mechanism underlying salicylate''s action mainly involves the inhibition of cyclooxygenase and subsequent decrease in prostaglandin production. Recent evidence suggests that salicylate also affects neuronal function through interaction with specific membrane channels/receptors. However, the effect of salicylate on synaptic and neural network function remains largely unknown. In this study, we investigated the effect of sodium salicylate on the synaptic transmission and neuronal excitation in the hippocampal CA1 area of rats, a key structure for many complex brain functions. With electrophysiological recordings in hippocampal slices, we found that sodium salicylate significantly enhanced neuronal excitation through reducing inhibitory GABAergic transmission without affecting the basal excitatory synaptic transmission. Salicylate significantly inhibited the amplitudes of both evoked and miniature inhibitory postsynaptic currents, and directly reduced γ-aminobutyric acid type A (GABAA) receptor-mediated responses in cultured rat hippocampal neurons. Together, our results suggest that the widely used aspirin might impair hippocampal synaptic and neural network functions through its actions on GABAergic neurotransmission. Given the capability of aspirin to penetrate the blood–brain barrier, the present data imply that aspirin intake may cause network hyperactivity and be potentially harmful in susceptible subpopulations. [Copyright &y& Elsevier]

The synthesis of a new compound, amide-linked diporphyrin xanthene(ADPX), and its application for preparation of lead(II) ion selective electrodes are described. The electrode was prepared with a PVC membrane combining ADPX as a neutral carrier, 2-nitrophenyl octyl ether (o-NPOE) as a plasticizer and sodium tetraphenylborate (NaTPB) as an additive in the percentage ratio of 3:3:65:32 (ADPX: NaTPB: o-NPOE: PVC, w:w). The electrode exhibited linear response with a near Nernstian slope of 28.2 mV per decade within the concentration range of 2.6×10-6 to 1.0×10-1 M lead ions, with a working pH range from 4.5 to 7.5, and a fast response time of less than 30 s. Selectivity coefficients for Pb(II) relative to a number of interfering ions were investigated. The electrode is highly selective for Pb2+ ions over a large number of cations. Several electroactive materials and solvent mediators have been compared and the experimental conditions were optimized. The sensor was applied as indicator electrode in titration of Pb(II) with potassium chromate solution with satisfied results. [ABSTRACT FROM AUTHOR]

Abstract: The design and synthesis of a porphyrin-appended terpyridine, 5-(4-([2,2′:6′,2″]-terpyridin-4-yl-carboxyamidyl)phenyl)-10,15,20-triphenylporphyrin (H2TPPTPy) and its application as potential fluoroionophore for recognition of metal ions are reported. For preparation of the fluoroionophore, a novel simple strategy with improved total yield has been applied for the synthesis of 2,2′:6′,2″-terpyridine-4′-carboxylic acid as a ligand. H2TPPTPy shows chelation-enhanced fluorescence effect with cadmium ion via the interruption of photoinduced electron transfer (PET) process, which has been utilized as the basis of the fabrication of the Cd(II)-sensitive fluorescent chemosensor. The analytical performance characteristics of the proposed Cd(II)-sensitive chemosensor were investigated. It shows a linear response toward Cd(II) in the concentration range of 3.2×10−6 to 3.2×10−4 M with a limit of detection of 1.2×10−6 M. The chemosensor shows good selectivity for Cd(II) over a large number of cations, such as alkali, alkali earth and transitional metal ions except Cu(II) and Zn(II). The sensor has been used for determination of Cd(II) in water samples with satisfactory recoveries. [Copyright &y& Elsevier]

Abstract: An electrochemical immunoassay technique has been developed based on the sensitive detection of the enzyme-generated product with a bi-electrode signal transduction system. The system uses two separate electrodes, an immunoelectrode and a detection electrode to form a galvanic cell to implement the redox reactions on two different electrodes, that is the enzyme-generated reductant in the anode region is electrochemically oxidized by an oxidant (silver ions) in the cathode apartment. Based on a sandwich procedure, after immunoelectrode with antibody immobilized on its surface bound with the corresponding antigen and alkaline phosphatase conjugated antibody successively, the immunoelectrode was placed in enzyme reaction solution and wired to the detection electrode which was immerged into a silver deposition solution. These two solutions are connected with a salt bridge. Thus a bi-electrode signal transduction system device is constructed in which the immunoelectrode acts as anode and the detection electrode serves as cathode. The enzyme bound on the anode surface initiates the hydrolysis of ascorbic acid 2-phosphate to produce ascorbic acid in the anode region. The ascorbic acid produced in the anodic apartment is electrochemically oxidized by silver ions coupled with the deposition of silver metal on the cathode. Via a period of 30min deposition, silver will deposited on the detection electrode in an amount corresponding to the quantity of ascorbic acid produced, leading to a great enhancement in the electrochemical stripping signal due to the accumulation of metallic silver by enzyme-generated product. Compared with the method using chemical deposition of silver, the electrochemical deposition of silver on a separate detection electrode apartment avoids the possible influence of silver deposition on the enzyme activity. [Copyright &y& Elsevier]

Abstract: A fluorescent chemical sensor for Hg(II) using 5,10,15-tris(pentafluorophenyl)corrole (H3(tpfc)) as fluorophore is described in this paper. The response of the sensor is based on the fluorescence quenching of H3(tpfc) by coordination with Hg(II). H3(tpfc) based sensor shows a linear response towards Hg(II) in the concentration range from 1.2×10−7 to 1.0×10−4 M, with a working pH range from 5.0 to 8.0. The response time for Hg(II) concentration ≤1.0×10−5 M is less than 5min. The sensor shows good selectivity for Hg(II) over alkali, and alkaline earth, and most of transition metal cations. The effect of the composition of the sensor membrane has been studied and the experimental conditions optimized. The corrole based sensor membrane can be easily regenerated just by washing with blank buffer solution after each measurement. The sensor has been used for determination of Hg(II) in water samples with satisfactory results. [Copyright &y& Elsevier]

The chitosan-supported iron(III) tetraphenylporphyrin was prepared and characterized structurally, and its ability to catalyse oxidation of cyclohexane into cyclohexanone and cyclohexanol with air in absence of any reductants and solvents was studied. The research results showed that the amino groups of the chitosan coordinated axially with the iron atoms of chloro[tetraphenylporphinatoiron(III)] to form chitosan-supported ironporphyrin, which has better catalytic power for cyclohexane oxidation with air than the corresponding unsupported ironporphyrin. Under reaction conditions of 418 K and 0.8 MPa, the cyclohexane oxidation catalyzed by chitosan-supported iron(III) tetraphenylporphyrin had 1.40×105 catalyst mole turnover (based on the iron atom), 10.48% cyclohexane conversion and the 79.20% cyclohexanone and cyclohexanol selectivity, respectively. The turnover in cyclohexane oxidation catalyzed by the supported ironporphyrin is about 22 times bigger than that by unsupported ironporphyrin and the conversion is about double. The values are also higher than 3.9% conversion and 78% selectivity catalyzed by soluble cobalt catalyst used in industry at present. This paper has also investigated the influences of reaction time, temperature and pressure on the catalyst turnover, cyclohexane conversion and ratio of cyclohexanol to cyclohexanone in the cyclohexane oxidation catalyzed by the chitosan-supported iron(III) tetraphenylporphyrin. [Copyright &y& Elsevier]

Phagosome maturation in macrophage is essential to the clearance of pathogenic materials in host defence but the dynamic features remain difficult to be measured in real time. Herein, we reported the multilayered Au@MnOx@SiO2 nanoparticle as a robust pH‐sensitive plasmonic nanosensor for monitoring the dynamic acidification features over the phagosome maturation process in macrophage under darkfield microscopy. For this multilayered nanosensor, the gold nanoparticle core plays a role of signal reporter, the MnOx shell and the outmost SiO2 act as the sensing layer and the protecting layer, respectively. After subject to the acidic buffer solution, the MnOx layer in the multilayered nanoprobe could be decomposed rapidly, resulting in a remarkable spectral shift and color change under darkfield microscopy. We demonstrated this nanosensor for the investigation of single phagosome acidification dynamics by monitoring the color changes of nanoprobes after phagocytosis over time. The nanoprobes after phagocytosized in macrophage displayed a slight color change within the first hour and then cost several minutes to change from red to green in the next stage, indicating the phagosome undergoes a slow first and then fast acidification feature as well as a slow‐to‐fast acidification translation over the phagosome maturation process. Moreover, we validated that the slow‐to‐fast acidification translation was dependent on the activation of V‐ATPase from the ATP depletion assay. We believed that this nanosensor is promising for studying the dynamic acidification features as well as disorders in phagosome maturation in phagocytic cells, which might provide valuable information for understanding the disease pathogenesis related to phagosome dysfunctions. [ABSTRACT FROM AUTHOR]

The sensitive and accurate detection of mature miRNA without the signal interference by pre-miRNAs is highly important. Herein, a size-selective DNA nanocage-based activatable CRISPR/Cas12a system was developed to achieve this goal. [ABSTRACT FROM AUTHOR]

Purpose: Biomechanical comparison of wedge and biconcave deformity of different height restoration after augmentation of osteoporotic vertebral compression fractures was analyzed by three-dimensional finite element analysis (FEA). Methods: Three-dimensional finite element model (FEM) of T11-L2 segment was constructed from CT scan of elderly osteoporosis patient. The von Mises stresses of vertebrae, intervertebral disc, facet joints, displacement, and range of motion (ROM) of wedge and biconcave deformity were compared at four different heights (Genant 0–3 grade) after T12 vertebral augmentation. Results: In wedge deformity, the stress of T12 decreased as the vertebral height in neutral position, flexion, extension, and left axial rotation, whereas increased sharply in bending at Genant 0; L1 and L2 decreased in all positions excluding flexion of L2, and T11 increased in neutral position, flexion, extension, and right axial rotation at Genant 0. No significant changes in biconcave deformity. The stress of T11-T12, T12-L1, and L1-L2 intervertebral disc gradually increased or decreased under other positions in wedge fracture, whereas L1-L2 no significant change in biconcave fracture. The utmost overall facet joint stress is at Genant 3, whereas there is no significant change under the same position in biconcave fracture. The displacement and ROM of the wedge fracture had ups and downs, while a decline in all positions excluding extension in biconcave fracture. Conclusions: The vertebral restoration height after augmentation to Genant 0 affects the von Mises stress, displacement, and ROM in wedge deformity, which may increase the risk of fracture, whereas restored or not in biconcave deformity. [ABSTRACT FROM AUTHOR]

Natural living systems are driven by delicate protein networks whose functions are precisely controlled by many parameters, such as number, distance, orientation, and position. Focusing on regulation rather than just imitation, the construction of artificial protein networks is important in many research areas, including biomedicine, synthetic biology and chemical biology. DNA origami, sophisticated nanostructures with rational design, can offer predictable, programmable, and addressable scaffolds for protein assembly with nanometer precision. Recently, many interdisciplinary efforts have achieved the precise construction of DNA origami-based protein networks, and their emerging application in many areas. To inspire more fantastic research and applications, herein we highlight the applicability and potentiality of DNA origami-based protein networks. After a brief introduction to the development and features of DNA origami, some important factors for the precise construction of DNA origami-based protein networks are discussed, including protein–DNA conjugation methods, networks with different patterns and the controllable parameters in the networks. The discussion then focuses on the emerging application of DNA origami-based protein networks in several areas, including enzymatic reaction regulation, sensing, bionics, biophysics, and biomedicine. Finally, current challenges and opportunities in this research field are discussed. [ABSTRACT FROM AUTHOR]

The construction of versatile functional hydrogel interfaces holds promising prospects in biosensing and bioengineering. Herein, we introduced a light-induced protein conjugation strategy for on-demand surface modification of hydrogel interface based on the photoclick cyclization between primary amine and o -nitrobenzyl alcohol. We achieved the on-demand protein conjugation by grafting the molecular plugin, 4-(hydroxymethyl)-3-nitrobenzoic acid (HNBA), onto the hydrogel surface, followed by the mask-aided photoclick reaction with the protein of interest. This method enables the creation of protein patterns on hydrogel interface with a lower limit of pattern width at ∼70 μm. With this method, we demonstrated the surface engineering of epidermal growth factor (EGF) on hydrogel interface for selective capture of EGF receptor-positive cancer cells with an efficiency over 80%. Moreover, we applied the mask-aided photoclick conjugation method for antigen capture and developed a photoclickable hydrogel interface-based dot blotting assay. Due to the high-efficient antigen capture of photoclick conjugation, the photoclickable hydrogel interface-based dot blotting assay shows improved sensitivity for antigen detection with a limit of detection as 0.065 ng. We believed that this light-induced protein conjugation method holds the potential as a robust strategy for the construction of bioactive hydrogel interfaces for various bio-related applications. A light-induced protein conjugation strategy was proposed for the on-demand surface modification of hydrogel interface, which relies on the photoclick cyclization between primary amine in protein of interest and 4-(hydroxymethyl)-3-nitrobenzoic acid grafted on the hydrogel interface. [Display omitted] • A photoclickable hydrogel interface was constructed by grafting a molecular plugin, 4-(hydroxymethyl)-3-nitrobenzoic acid. • With a mask-aided photoclick conjugation strategy, the on-demand surface modification of hydrogel interface with desirable patterns can be achieved with a lower limit of pattern width at ∼70 μm. • EGF-functionalized hydrogel interface was constructed with the light-induced protein conjugation strategy for selective capture of EGFR-positive cancer cells with an efficiency over 80%. • A photoclickable hydrogel interface-based dot blotting assay was developed for antigen detection with a limit of detection as 0.065 ng. [ABSTRACT FROM AUTHOR]

High-resolution imaging of dynamic molecular targets within living organisms is essential for comprehensive understanding of complex biological processes. DNA sensors have emerged as powerful tools for the sensing and imaging of a wide range of molecules. However, conventional DNA sensors are usually in an "always active" state, which may result in false positive signals and low temporal and spatial resolutions in complex cellular or in vivo environments. To meet these challenges, conditional DNA sensors are developed by integrating molecular switches into conventional DNA sensors, whose reactivity are shielded until being activated by certain stimulations. To better understand the development of conditional DNA sensors and accelerate their applications in bioimaging, we review the recent progress in the design of conditional DNA sensors for bioimaging, focusing on exogenous and endogenous stimulation strategies. Also, we discuss the challenges and opportunities of the construction and application of activating DNA fluorescence sensors under specific conditions. [Display omitted] • The conception of conditional nucleic acid sensors is proposed and defined. • The strategies for the fabrication of conditional nucleic acid sensors are summarized. • The applications of conditional nucleic acid sensors for bioimaging in vitro and in vivo was described. • The advantages of current conditional nucleic acid sensors as well as their limitation in bioimaging are discussed. [ABSTRACT FROM AUTHOR]

Organic dye based NIR‐II fluorescent probes, owing to their high signal‐to‐background ratio and deeper penetration, are highly useful for deep‐tissue high‐contrast imaging in vivo. However, it is still a challenge to design activatable NIR‐II fluorescent probes. Here, a novel class of polymethine dyes (NIRII‐RTs), with bright (quantum yield up to 2.03 %), stable, and anti‐solvent quenching NIR‐II emission, together with large Stokes shifts, was designed. Significantly, the novel NIR‐II dyes NIRII‐RT3 and NIRII‐RT4, equipped with a carboxylic acid group, can serve as effective NIR‐II platforms for the design of activatable bioimaging probes with high contrast. As a proof of concept, a series of target‐activatable NIRII‐RT probes (NIRII‐RT‐pH, NIRII‐RT‐ATP and NIRII‐RT‐Hg) for pH, adenosine triphosphate (ATP), and metal‐ion detection, were synthesized. By applying the NIRII‐RT probe, the real‐time monitoring of drug‐induced hepatotoxicity was realized. [ABSTRACT FROM AUTHOR]

Organic dye based NIR‐II fluorescent probes, owing to their high signal‐to‐background ratio and deeper penetration, are highly useful for deep‐tissue high‐contrast imaging in vivo. However, it is still a challenge to design activatable NIR‐II fluorescent probes. Here, a novel class of polymethine dyes (NIRII‐RTs), with bright (quantum yield up to 2.03 %), stable, and anti‐solvent quenching NIR‐II emission, together with large Stokes shifts, was designed. Significantly, the novel NIR‐II dyes NIRII‐RT3 and NIRII‐RT4, equipped with a carboxylic acid group, can serve as effective NIR‐II platforms for the design of activatable bioimaging probes with high contrast. As a proof of concept, a series of target‐activatable NIRII‐RT probes (NIRII‐RT‐pH, NIRII‐RT‐ATP and NIRII‐RT‐Hg) for pH, adenosine triphosphate (ATP), and metal‐ion detection, were synthesized. By applying the NIRII‐RT probe, the real‐time monitoring of drug‐induced hepatotoxicity was realized. [ABSTRACT FROM AUTHOR]

The in situ and real-time supervision of reactive oxygen species (ROS) generated during photodynamic therapy (PDT) is of great significance for lessening nonspecific damage and guiding personalized therapy. However, photosensitizers frequently fail to deliver successful treatment accompanying the ROS-related imaging signals produced, impeding simple treatment outcome predictions and therapeutic schedule adjustments. Here, we report a two-photon fluorescence self-reporting strategy for the in situ and real-time monitoring of treatment response via a novel black phosphorus-based two-photon nanoprobe (TPBP). TPBP effectively generated singlet oxygen (1O2) under near-infrared laser irradiation for PDT, and 1O2 stimulated a two-photon molecule to emit fluorescence signals for feedback of 1O2 generation, which facilitated the regulation of treatment parameters to achieve precise and personalized medicine in deep tissue. [ABSTRACT FROM AUTHOR]

Lysosomes contains numerous enzymes and proteins closely linked with cellular metabolism. The variation of lysosomal pH is closely related to cell homeostasis while hydrogen sulfide (H 2 S) has been regarded as an important gasotransmitter. Herein, via rational design, a high-sensitivity fluorescent probe ANp-Rh-Lys was synthesized for logical detection and bioimaging of H 2 S and pH in lysosomes of living cells. The probe showed different fluorescence signals towards H 2 S and lysosomal pH. Significantly, ANp-Rh-Lys is membrane-permeable and suitable for visualization of both pH variations and endogenous H 2 S in lysosomes. This logical design strategy may have great potential for detection of multiple analytes in complicated biological systems. A promising ratiometric fluorescent probe for logical imaging of H 2 S and pH in lysosomes was first proposed. Image 1 • As a proof-of-concept, to design the dual-sites for orthometric response by two species is of great challenge. • With different output fluorescence signals, a single fluorescent probe can realize logical imaging of pH and H 2 S in lysosome. • Our probe may serve as the basis for independently or concurrently detection of key biomolecules in the signal transduction and diseases formation. [ABSTRACT FROM AUTHOR]

A FRET-based probe for mapping the fluctuation of ONOO− in cisplatin-induced acute kidney injury was constructed. It exhibits ratiometric near infrared fluorescence and a dramatic decrease of its peak absorbance at 719 nm upon addition of ONOO− that is converted into remarkable signal changes in fluorescence and photoacoustic images respectively. [ABSTRACT FROM AUTHOR]

The Xihuashan and Tieshanlong tungsten deposit is an important large quartz vein‐type W‐polymetallic deposit in the southern Jiangxi Province, eastern Nanling Range. Zircon U–Pb analyses of representative ore‐forming granites from the Xihuashan and Tieshanlong tungsten deposit yield ages of 146.3 ± 2.9 Ma and 146.0 ± 3.8 Ma, respectively. According to the zircon Raman spectroscopy, these granitic rocks are disturbed by different degrees of hydrothermal alteration, whereas most zircons exhibit primary oscillatory zoning and Th/U ratios in the range of magmatic zircon, which means the analysis results represent the crystallization age of metallogenetic granitic assemblages. In combination with regional geological data, it is suggested that the Late Jurassic is probably another important episode of granitic magmatism and W‐Sn mineralization in southern Jiangxi Provinces, even South China. [ABSTRACT FROM AUTHOR]

The enzymatic-assisted signal amplification of DNA sensors is rarely applied in living cells due to the difficulties in protein delivery. In this study, we have proposed a biomineralization-based DNA nanoprobe to transport nucleases and DNA sensors for enzyme-assisted imaging of microRNA in living cells. [ABSTRACT FROM AUTHOR]

Herein, we report a pH stimulus-disaggregated BODIPY sensitizer (PTS) with low background-toxicity for achieving activated photodynamic/photothermal tumor therapy. Both the photodynamic and photothermal properties of PTS can be activated under acidic conditions, and PTS exhibits excellent antitumor properties, which is revealed by both in vitro and in vivo tests. [ABSTRACT FROM AUTHOR]

Genetically encoded fluorescent proteins (FPs) have been used for metal ion detection. However, their applications are restricted to a limited number of metal ions owing to the lack of available metal‐binding proteins or peptides that can be fused to FPs and the difficulty in transforming the binding of metal ions into a change of fluorescent signal. We report herein the use of Mg2+‐specific 10–23 or Zn2+‐specific 8–17 RNA‐cleaving DNAzymes to regulate the expression of FPs as a new class of ratiometric fluorescent sensors for metal ions. Specifically, we demonstrate the use of DNAzymes to suppress the expression of Clover2, a variant of the green FP (GFP), by cleaving the mRNA of Clover2, while the expression of Ruby2, a mutant of the red FP (RFP), is not affected. The Mg2+ or Zn2+ in HeLa cells can be detected using both confocal imaging and flow cytometry. Since a wide variety of metal‐specific DNAzymes can be obtained, this method can likely be applied to imaging many other metal ions, expanding the range of the current genetically encoded fluorescent protein‐based sensors. [ABSTRACT FROM AUTHOR]

Genetically encoded fluorescent proteins (FPs) have been used for metal ion detection. However, their applications are restricted to a limited number of metal ions owing to the lack of available metal‐binding proteins or peptides that can be fused to FPs and the difficulty in transforming the binding of metal ions into a change of fluorescent signal. We report herein the use of Mg2+‐specific 10–23 or Zn2+‐specific 8–17 RNA‐cleaving DNAzymes to regulate the expression of FPs as a new class of ratiometric fluorescent sensors for metal ions. Specifically, we demonstrate the use of DNAzymes to suppress the expression of Clover2, a variant of the green FP (GFP), by cleaving the mRNA of Clover2, while the expression of Ruby2, a mutant of the red FP (RFP), is not affected. The Mg2+ or Zn2+ in HeLa cells can be detected using both confocal imaging and flow cytometry. Since a wide variety of metal‐specific DNAzymes can be obtained, this method can likely be applied to imaging many other metal ions, expanding the range of the current genetically encoded fluorescent protein‐based sensors. [ABSTRACT FROM AUTHOR]

By assembling DNAzyme on DNA nanowires through DNA hybridization, we have developed a novel accelerated DNAzyme-based fluorescent nanoprobe for fast, sensitive and selective detection of miRNA. Moreover, the strategy was successfully applied for in situ imaging of miRNA-21 in different cell lines. [ABSTRACT FROM AUTHOR]

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]