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Hepatotoxicity is a serious problem faced by thousands of clinical drugs, and drug-induced liver injury (DILI) caused by chronic administration or overdose has become a major biosafety issue. However, the near-infrared (NIR) fluorescent probes currently used for liver injury detection still suffer from poor liver targeting ability and low sensitivity. Enzyme-activated fluorogenic probes with powerful in situ targeting ability are the key to improving the imaging effect of liver injury. Herein, we rationally designed a leucine aminopeptidase (LAP) activated fluorogenic probe hCy-CA-LAP, which greatly improved the hepatocyte-targeting capability by introducing a cholic acid group. The probe hCy-CA-LAP is converted into a high-emission hCy-CA fluorophore in the presence of LAP, showing high selectivity, high sensitivity and low detection limit (0.0067 U mL−1) for LAP, and successfully realizes the sensitive detection of small fluctuations of LAP in living cells. Moreover, the probe can achieve effective in situ accumulation in the liver, thereby achieving precise imaging and evaluation of two different types of drug-induced hepatotoxicity in vivo. Therefore, the probe hCy-CA-LAP may be a potential tool for exploring the roles of LAP and evaluating the degree of DILI., We rationally designed a leucine aminopeptidase (LAP) activated fluorogenic probe hCy-CA-LAP with high hepatocyte-targeting ability for accurate and sensitive imaging of DILI.

Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen (1O2), as well as the hypoxic microenvironment in the tumor tissue. Such problems have limited the application of PDT and appropriate solutions are highly demand. Methods: Herein, a programmatic treatment strategy is proposed for the development of a smart molecular prodrug (D-bpy), which comprise a two-photon photosensitizer and a hypoxia-activated chemotherapeutic prodrug. A rhodamine dye was designed to connect them and track the drug release by the fluorescent signal generated through azo bond cleavage. Results: The prodrug (D-bpy) can stay on the cell membrane and enrich at the tumor site. Upon light irradiation, the therapeutic effect was enhanced by a stepwise treatment: (i) direct generation of 1O2 on the cell membrane induced membrane destruction and promoted the D-bpy uptake; (ii) deep tumor hypoxia caused by two-photon PDT process further triggered the activation of the chemotherapy prodrug. Both in vitro and in vivo experiments, D-bpy have exhabited excellent tumor treatment effect. Conclusion: The innovative programmatic treatment strategy provides new strategy for the design of follow-up anticancer drugs.

Chemiluminescent probes based on 1,2-dioxetane scaffold are one of the most sensitive imaging modalities for detecting disease-related biomarkers and can obtain more accurate biological information in cells and in vivo. Due to the elimination of external light excitation, the background autofluorescence problem in fluorescence technology can be effectively avoided, providing ultrahigh sensitivity and signal-to-noise ratio for various applications. In this review, we highlight a comprehensive but concise overview of activatable 1,2-dioxetane-based chemiluminescent probes by reporting significant advances in accurate detection and bioimaging. The design principles and applications for reactive species, enzymes, and other disease-related biomarkers are systematically discussed and summarized. The challenges and potential prospects of chemiluminescent probes are also discussed to further promote the development of new chemiluminescence methods for biological analysis and diagnosis.

Accurate diagnosis of cancer at an early stage is the key to reduce cancer mortality and improve survival. PET imaging has high sensitivity but low spatial resolution, while CT imaging has good spatial location information. Therefore, the combination of PET and CT imaging can provide complementary advantages to achieve accurate early diagnosis of tumors. However, currently developed PET or CT imaging agents have only a single function. Here, we designed and constructed a self-assembled lipid nanocapsule encapsulated with iodixanol and labeled with self-chelated

A perspective on the development of peptide and protein modified metal clusters in cancer diagnostic applications., The biomedical features of metal clusters have been explored in tumor diagnostic applications in recent years. Peptide or protein protected metal clusters with low toxicity, ultra-small size and good biocompatibility are ideal bioanalytical tools, and exhibit better cancer diagnostic properties that have been attractive to oncologists. This perspective provides a rigorous but succinct overview of cancer diagnosis as a working concept for metal clusters by reporting the latest significant advances in the applications of metal clusters in tumor-related bioanalysis and diagnosis. The materials design principles, bioanalytical mechanisms and biomedical applications of metal clusters are described, and then the potential challenges and prospects of metal clusters in cancer diagnosis are discussed. A perspective addressing the role of metal clusters in this field is required to understand their effects and functions, as well as for the scientific community to further advance the development of metal clusters for broader diagnostic applications.

Organic phosphate biomolecules (OPBs) are indispensable components of eukaryotes and prokaryotes, such as acting as the fundamental components of cell membranes and important substrates for nucleic acids. They play pivotal roles in various biological processes, such as energy conservation, metabolism, and signal modulation. Due to the difficulty of detection caused by variety OPBs, investigation of their respective physiological effects in organisms has been restrained by the lack of efficient tools. Many small fluorescent probes have been employed for selective detection and monitoring of OPBs in vitro or in vivo due to the advantages of tailored properties, biodegradability and in situ high temporal and spatial resolution imaging. In this review, we summarize the recent advances in fluorescent probes for OPBs, such as nucleotides, NAD(P)H, FAD/FMN and PS. Importantly, we describe their identification mechanisms in detail and discuss the general strategies for these OPBs probe designs, which provide new insights and ideas for the future probe designs.

An efficient probe NB-NO2 for specific imaging of ulcerative colitis via hypoxia detection was developed.

FPGA-based acceleration has been emerged to avoid the cloud computing overload problem by accelerating the compute-intensive workload on edge networks. Though existing studies for FPGA-based edge acceleration have focused on optimizing the computing time, they did not address the burden of the FPGA-aided server under an enormous computing requests circumstance. The massive computing requests can cause delays in transmission and processing at the FPGA-aided server, leading to long response times and high system energy consumption. Therefore, we propose an emerging edge acceleration architecture based on FPGA cluster over the low-latency RDMA-based network. Preliminary simulation results demonstrate that our architecture is fast, scalable, and energy-efficient in comparison with the FPGA-aided servers cluster.

Thiophenols as high toxic environmental pollutants are poisonous for animals and aquatic organisms. Therefore, it is indispensable to monitor thiophenols in the environment. Herein, a novel near-infrared fluorescent probe was developed for the detection of thiophenols, which was easily prepared by one-step coupling of 2,4-dinitrobenzenesulfonyl chloride with Nile blue. The probe showed a significant near infrared (∼675 nm) fluorescence “turn-on” response to thiophenols with some good features including chromogenic reaction, high sensitivity and selectivity, fast response, near-infrared emission along with low detection limit (1.8 nM). The probe was employed to rapidly and visually determine thiophenols in several industrial wastewaters with good recoveries (90–110%). Moreover, this probe has been demonstrated good capability for imaging thiophenol in HeLa cells.

Microglia, the brain-resident macrophage, are involved in brain development and contribute to the progression of neural disorders. Despite the importance of microglia, imaging of live microglia at a cellular resolution has been limited to transgenic mice. Efforts have therefore been dedicated to developing new methods for microglia detection and imaging. Using a thorough structure-activity relationships study, we developed CDr20, a high-performance fluorogenic chemical probe that enables the visualization of microglia both in vitro and in vivo. Using a genome-scale CRISPR-Cas9 knockout screen, the UDP-glucuronosyltransferase Ugt1a7c was identified as the target of CDr20. The glucuronidation of CDr20 by Ugt1a7c in microglia produces fluorescence.

Sodium sulfite (Na2SO3) is widely used as a food additive, but the excessive residue of SO32− in food can cause irritative effects and damages to the human body. In this study, we reported a novel near-infrared (NIR) fluorescent probe (DCMQ) for visual detection of SO32− based on a chromogenic reaction. The probe can quantitatively determine SO32− with high specificity and sensitivity, fast response (

Hydrazine and bisulfite are poisonous to the environment and human health, hence it is necessary to monitor hydrazine and bisulfite in the environment and living cells. In this study, we reported a smart fluorescent probe (CMCA) for discriminative detection of hydrazine and bisulfite. The single fluorescent probe can respond to hydrazine and bisulfite with two different sets of colorimetric and ratiometric fluorescence signals together with high selectivity, fast response and low detection limit. The discriminative sensing behaviors of the probe for hydrazine and bisulfite were ascribed to different reaction mechanisms, which were confirmed by 1H NMR and HR-MS spectra. The probe has been successfully used to discriminatively determine hydrazine and bisulfite in industrial wastewater with good recoveries. Furthermore, the probe was employed to visualize hydrazine and bisulfite in live cells from different fluorescence channels with good performance. Therefore, this probe has great potential applications for discriminative detection of hydrazine and bisulfite in the environment and living cells.

To solve the problem of computing overload in cloud, we intend to design a trusted edge cloud computing model and method based on FPGA (Field Programmable Gate Array) clusters. Firstly, a device, named FPGA Box, with PCIe (Peripheral Component Interconnect Express) power supply capability is used to manage the FPGA accelerator in the model. Besides, the FPGA cluster provide heterogeneous accelerated computing services for the data center through the network. Furthermore, we proposed a trusted edge cloud computing method based on FPGA cluster. On the one hand, a bi-level encryption algorithm based on RSA is proposed to generate an authorized use code, which implied the FPGA accelerator IP (Internet Protocol) address and other information. On the other hand, based on the programmable features of the FPGA accelerators, we set FPGA registers as use status bits, which can control different working status of accelerator. Specifically, when the accelerators has been assigned, we also need upload the deadline of usage to it. Finally, the software activity process of the entire trusted edge cloud system is described in detail, including the process of generating authorized use code. Simulation results show that the edge cloud computing mechanism based on FPGA cluster is proved to be trusted and effective.

Towards the computing overload problem in cloud data center, we propose a computing offloading mechanism based on FPGA clusters for edge cloud. Firstly, the FPGA cluster we proposed is decoupled from traditional server, and FPGA BOX is used to power batch FPGA accelerators. The network-based FPGA cluster is deployed at the edge to undertake the computing tasks of the data center. On this basis, we propose an edge cloud network model based on FPGA clusters, and study the energy consumption minimization problem. Secondly, considering the diversity of computing tasks, the MapReduce algorithm based on the numbering mechanism proposed in this paper realizes the classification of computing tasks, and converts the energy consumption minimization problem into the energy consumption minimization problem when the user's computing tasks are determined. Based on the classification results, our improved Hungary algorithm can obtain the minimum energy consumption. Meantime, the computing task results can feedback to corresponding user according to the user information in classification results. Finally, numerical calculation results show that the computing offloading mechanism proposed in this paper shows good performance in terms of energy consumption.

With the rise of artificial intelligence and machine learning, many applications and services require FPGA support to speed up the training process and improve efficiency. FPGA has its unique advantages including inference; but now TensorFlow only supports CPU and GPU, TPU, does not support FPGA, cannot use FPGA to accelerate specific models, and cannot play the full role of FPGA in TensorFlow. Based on the above problems, this paper proposes a method for efficiently using FPGA in TensorFlow. This method uses TensorFlow's original device management mechanism, adds an abstract method for FPGA devices under the TensorFlow framework, and writes implementation specifications for FPGA operators. Finally, we used OpenCL to build kernels of FPGA devices, took full advantage of the parallel computing advantages of FPGA devices, and used the CNN LeNet5 model and MNIST dataset to conduct corresponding experiments. The experimental results show that the training accuracy of the two devices is basically the same. This paper provides a feasible solution for TensorFlow to use FPGA devices for neural network calculations.

Currently, TensorFlow architecture only supports CPU and GPU programming, and has not yet formed a unified support standard for FPGAs. To the best of our knowledge, when forward operators in TensorFlow specifies a new device, the backward gradient operator in the same neural network cannot use the same device, which does not comply with rules about node device allocation in TensorFlow. Therefore, we propose an improved algorithm for node device allocation based on placement mechanism and an optimization algorithm for conv2d operator based on OpenCL. The proposed improved algorithm for node device allocation makes forward and backward operators based on FPGA accelerator satisfy the node and device allocation requirements for all TensorFlow operators, and the conv2d operator optimization algorithm based on OpenCL takes full advantage of the parallel computing advantages of FPGA. Finally, this paper uses the CNN LeNet5 model and the MNIST dataset to conduct corresponding experiments. Referring to conv2d operator, based on FPGA accelerator, we implement both the forward and backward operators involved in the first four layers of the model. The experimental results show that the accuracy of the three methods is above 98%. Compared with CPU and GPU, the accuracy difference is only about five thousandths. In addition, in the case of different batch sizes, we tested the runtime of conv2d operator in the first layer of this model. The results show that when the input batch size increased to 10000, the FPGA runs 9 times faster than the CPU. It proved that we proposed an optimization solution for TensorFlow to use FPGA operators for neural network calculations.

Macrocyclic hexaoxazoles (6OTDs) are G-quadruplex (G4) ligands, and some derivatives, such as L2H2-6OTD (1a) bearing two aminobutyl side chains, show cytotoxicity towards cancer cells. To identify the cellular target of 1a, we employed a post-target-binding strategy utilizing click reaction (Huisgen cyclization) between the azide-conjugated ligand L2H2-6OTD-Az (1b) and the cell-permeable dye CO-1 bearing a strained alkyne moiety and the BODIPY fluorophore under Cu-free conditions. We confirmed that introduction of the small azide group did not alter the physical or biological properties, including anti-cancer activity, of 1a, and we also demonstrated bias-free localization of CO-1. The post-binding visualization strategy suggested that L2H2-6OTD (1a) colocalized with RNA G4 in living cells.

To investigate how electroacupuncture (EA) at Zusanli (ST 36) with varying intensities of stimulation affects dorsal root nerve signals in normal rats.Adult female Wistar rats were examined after drug-induced anesthesia and isolation of the L4 dorsal root associated with the Zusanli (ST 36) acupoint, using bipolar platinum electrodes. We applied EA at Zusanli (ST 36) with a continuous wave waveform for 1 min, and recorded action potentials in the L4 spinal cord dorsal root nerve with a frequency of 5 Hz and various current intensity levels (approximately 1-4 mA). In addition, we tested EA with a frequency of 15 Hz and current intensity of 1-4 mA. The L4 spinal cord dorsal nerve bundle action potentials were measured for 1 min of EA. To analyze the discharge frequency, we used the maximum Lyapunov exponent and Lempel-Ziv (LZ) complexity.At a fixed frequency, with increasing intensity of EA, dorsal root nerve filament discharge frequency revealed an initial increase, followed by a decreasing trend. A stimulation intensity of 3 mA induced a significantly greater discharge frequency, compared with stimulation intensities of 2 and 4 mA. EA stimulation evoked neuroelectric signals with chaotic characteristics. Increased intensity led to an initial increase in LZ complexity which then decreased, with a stimulation strength of 3 mA inducing the highest level of LZ complexity.EA of different intensities can induce nerve action potential encoding with different features.

Drug-induced acute kidney injury (AKI), caused by renal drug metabolism, has been regarded as a main problem in clinical pharmacology and practice., Drug-induced acute kidney injury (AKI), caused by renal drug metabolism, has been regarded as a main problem in clinical pharmacology and practice. However, due to the lack of effective biomarkers and noninvasive real-time tools, the early diagnosis of drug-induced AKI is still a crucial challenge. The superoxide anion (O2˙–), the preliminary reactive oxidative species, is closely related to drug-induced AKI. In this paper, we reported two new mitochondria-targeted fluorescent probes for investigating AKI via mapping the fluctuation of O2˙– with high sensitivity and selectivity by the combination of rational design and a probe-screening approach. Small-molecule fluorescent probes (Naph-O2˙– and NIR-O2˙–) with high accuracy and excellent selectivity were successfully applied to detect endogenously produced O2˙– in living cells and tissues by dual-model confocal imaging, and to trap the fluctuation of the O2˙– level during the drug-induced nephrotoxicity. Moreover, probe NIR-O2˙– was also used to elucidate the protective effects of l-carnitine (LC) against drug-induced nephrotoxicity for the first time. Therefore, these probes may be potential chemical tools for exploring the roles of O2˙– in complex nephrotoxicity disease systems.

A series of highly photostable, lysosome-targeted BODIPYs with tunable fluorescence from green to the near-infrared region was developed. The probes were found to show an accurate lysosome-targeting ability with high selectivity and high photostability under continuous excitation irradiation. The results show that these lysosome-targeted BODIPYs offer a simple and convenient tool for fluorescence imaging of lysosomes, which will be valuable for understanding the activity and function of lysosomes in related cells.

A cloud platform based on FPGA acceleration cards cluster and servers cluster is proposed in this paper. Multi-type boards in the cloud platform could provide multi-type application acceleration services to meet the needs of different tenants. Therefore, we propose to design an optimal task scheduling and service scheme to maximize tenants satisfaction and minimize operators benefits loss. Firstly, the problem of task scheduling is considered as a ‘max-min’ joint optimization problem. Then it is transformed into a bi-level optimization problem with the lower as tenants' satisfaction maximization problem and the upper as FPGA cloud platform operators benefits loss minimization problem. Finally, because the lower problem is convex, the MATSuMoTo algorithm is used to obtain the best task scheduling strategy of the cloud platform.

Summary Elastic fibers are present in a variety of tissues and are responsible for their resilience. Until now, no optical contrast agent in the near-infrared (NIR) wavelength range of 700–900 nm has been reported for the imaging of elastic fibers. Here, we report the discovery of a NIR zwitterionic elastin probe ElaNIR (elastin NIR) through fluorescent-image-based screening. The probe was successfully applied for in vitro , ex vivo , and in vivo imaging by various imaging modalities. Age-related elastin differences shown by in vivo fluorescent and photoacoustic imaging indicated that ElaNIR can be a potentially convenient tool for uncovering changes of elastin in live models.

Drug-induced acute kidney injury (AKI), caused by renal drug metabolism, has been regarded as a main problem in clinical pharmacology and practice. However, due to the lack of effective biomarkers and noninvasive real-time tools, the early diagnosis of drug-induced AKI is still a crucial challenge. The superoxide anion (O2˙-), the preliminary reactive oxidative species, is closely related to drug-induced AKI. In this paper, we reported two new mitochondria-targeted fluorescent probes for investigating AKI via mapping the fluctuation of O2˙- with high sensitivity and selectivity by the combination of rational design and a probe-screening approach. Small-molecule fluorescent probes (Naph-O2˙- and NIR-O2˙- ) with high accuracy and excellent selectivity were successfully applied to detect endogenously produced O2˙- in living cells and tissues by dual-model confocal imaging, and to trap the fluctuation of the O2˙- level during the drug-induced nephrotoxicity. Moreover, probe NIR-O2˙- was also used to elucidate the protective effects of l-carnitine (LC) against drug-induced nephrotoxicity for the first time. Therefore, these probes may be potential chemical tools for exploring the roles of O2˙- in complex nephrotoxicity disease systems.

A new strategy that integrates the targeting group and response moiety together for the preparation of mitochondrial probe was developed. Bioimaging studies have shown that for the first time, the newly designed probe HDFL-Cys can first accumulate in mitochondria and then react with the analyte., Mitochondria are vital organelles that not only produce cellular energy but also participate in many biological processes. Recently, various fluorescent probes have been developed for mitochondrial imaging. However, due to the lack of suitable dyes or strategies, it is difficult for most reported mitochondrial targeting probes to prove whether the analytes they detected are from mitochondria. In addition, positive charge on mitochondrial probes can seriously affect the mitochondrial environment. To address these issues, we herein put forward a novel strategy for probe design based on a smart NIR dye (HDFL) for mitochondrial targeting detection. Compared to general mitochondrial targeting probes that are modified with a target site and a reaction site, the new strategy is to combine the two sites together for a mitochondrial probe that would provide accurate detection of analytes in mitochondria without interference. As a proof of concept, we synthesized a mitochondrial-targetable probe HDFL-Cys for cysteine. Bioimaging studies have shown that the new type of probe HDFL-Cys can first accumulate in mitochondria and then react with the analyte (cysteine) accompanied by the departure of the targeting group (lipophilic cation moieties). Thus, it can specifically detect the analyte in mitochondria without interference from extra-mitochondrial analytes. We anticipate that the new strategy based on the novel NIR dye HDFL may be a potential platform for developing desirable ratiometric fluorescent probes for mitochondrial imaging.

A multi-color labelling technique for visualizing multiple intracellular apparatuses in their native environment using small fluorescent probes remains challenging. This approach requires both orthogonal and biocompatible coupling reactions in heterogeneous biological systems with minimum fluorescence background noise. Here, we present a palette of BODIPY probes containing azide and cyclooctyne moieties for copper-free click chemistry in living cells. The probes, referred to as ‘tame probes’, are highly permeable and specific in nature, leaving no background noise in cells. Such probes, which are rationally designed through optimized lipophilicity, water solubility and charged van der Waals surface area, allow us to demonstrate rapid and efficient concurrent multi-labelling of intracellular target components. We show that these probes are capable of not only labelling organelles and engineered proteins, but also showing the intracellular glycoconjugates’ dynamics, through the use of metabolic oligosaccharide engineering technology in various cell types. The results demonstrated in this study thus provide flexibility for multi-spectral labelling strategies in native systems in a high spatiotemporal manner.

We study the mobile data offloading problem in cooperative cellular networks, in which the cellular base station can offload a fraction of data traffic to its cooperative Wi-Fi networks. Both user satisfaction and benefit are important for the cellular network. Under the case that the cellular network cannot provide sufficient transmission resources, part of data traffic can be offloaded to its cooperative Wi-Fi networks to guarantee the user satisfaction, even though the benefit loss of the cellular network will be incurred. Meanwhile, considering the users are price sensitive, the operators, including cellular and Wi-Fi, can issue an appreciate unit price to attract more users and more traffic requirements to increase their total benefit. In this paper, we intend to design an optimal pricing scheme to maximize the user satisfaction and minimize the benefit losses of the operators simultaneously. First, we formulate the mobile data offloading problem as a joint optimization of “min–max” problem. Then, we convert the problem into a bi-level optimization problem, in which the lower level is to maximize the user satisfaction and the upper level is to minimize the benefit losses of the operators. Since the lower-level problem is convex, a centralized scheme based on the dynamic coordinate search-based method is employed to find the optimal solution of the bi-level problem. In addition, a distributed method is proposed to obtain the near-optimal solution quickly, where one-third-party agent is used to adjust the data traffic allocation. Simulation results show that the proposed method achieves the near-optimal solutions with limited iterations.

Drug toxicity is a long-standing concern of modern medicine. A typical anti-pain/fever drug paracetamol often causes hepatotoxicity due to peroxynitrite ONOO- . Conventional blood tests fail to offer real-time unambiguous visualization of such hepatotoxicity in vivo. Here we report a luminescent approach to evaluate acute hepatotoxicity in vivo by chromophore-conjugated upconversion nanoparticles. Upon injection, these nanoprobes mainly accumulate in the liver and the luminescence of nanoparticles remains suppressed owing to energy transfer to the chromophore. ONOO- can readily bleach the chromophore and thus recover the luminescence, the presence of ONOO- in the liver leads to fast restoring of the near-infrared emission. Taking advantages of the high tissue-penetration capability of near-infrared excitation/emission, these nanoprobes achieve real-time monitoring of hepatotoxicity in living animals, thereby providing a convenient screening strategy for assessing hepatotoxicity of synthetic drugs.

A novel design strategy for the fluorescence sensing of l-DOPA is reported. Resa-Sulf displays a significant turn-on fluorescence response to l-DOPA due to its reduction properties; this sensing mechanism was fully confirmed by mechanistic studies. Furthermore, Resa-Sulf was successfully utilized to quantitatively detect l-DOPA concentrations from a commercially available source.

The need for detecting and labelling environmentally and biologically important analytes has driven considerable research efforts in developing fluorescent probes. During the sensing process, molecular motions (i.e., molecular rotations or vibrations) of a flexible fluorescent probe can be significantly altered by its embedding micro-environment or analyte, thereby leading to substantial changes in readout signals. Motion-induced change in emission (MICE) can be utilized as an effective sensing mechanism. However, in comparison to the well-understood sensing mechanisms, such as photo-induced electron transfer (PET), intramolecular charge transfer (ICT), aggregation-induced emission (AIE) and disaggregation-induced emission (DIE), MICE has not been systematically discussed to date. In this tutorial review, we will summarize the concept and mechanisms of MICE for developing single-molecular fluorescent probes, present unique advantages of MICE based sensors, demonstrate their various applications, and discuss technical challenges in this field. We expect that this review will promote a deeper understanding of MICE and facilitate the development of novel MICE based probes.

Hydrogen sulfide (H2S) has been found to be an important biological regulator that plays important roles in many physiological and pathological processes. Near-infrared (NIR) fluorescent probes capable of selectively detecting H2S in vivo will be useful tools to understand its mechanisms in biological processes. Herein, we reported an easily synthesized and stimuli-responsive NIR fluorescent probe (QCy7-HS) for selective evaluation of endogenous H2S in the living cells and mice. In response to cellular H2S stimulus, QCy7-HS is converted to QCy7 and shows a unique off-on near-infrared fluorescence signal change. The results of selectivity and kinetic studies indicated that our probe has high H2S binding capacity. Therefore, this probe was used for the fluorescence detection of H2S in cells. Moreover, the probe was applied for study exogenous and endogenous H2S in live mice, indicating that the new probe can be used as an efficient tool on H2S related events in living animals.

Tumor initiating cells (TIC) are resistant to conventional anticancer therapy and associated with metastasis and relapse in cancer. Although various TIC markers and their antibodies have been proposed, it is limited to the use of antibodies for in vivo imaging or treatment of TIC. In this study, we discovered heme oxygenase 2 (HMOX2) as a novel biomarker for TIC and developed a selective small molecule probe TiNIR (tumor initiating cell probe with near infrared). TiNIR detects and enriches the functionally active TIC in human lung tumors, and through the photoacoustic property, TiNIR also visualizes lung TIC in the patient-derived xenograft (PDX) model. Furthermore, we demonstrate that TiNIR inhibits tumor growth by blocking the function of HMOX2, resulting in significantly increased survival rates of the cancer model mice. The novel therapeutic target HMOX2 and its fluorescent ligand TiNIR will open a new path for the molecular level of lung TIC diagnosis and treatment.

The novel ratiometric fluorescent probe HPQRB with an ESIPT effect based on Michael addition for highly sensitive and fast detection of sulfite in living HepG2 cells is reported. HPQRB can be easily synthesized by a two‐step condensation reaction. HPQRB has a large emission shift (Δλ=116 nm), which is beneficial for fluorescence imaging research, and its sulfite‐responsive site is based on a rhodamine‐like structure with the emission peak at 566 nm, which decreases with increasing sulfite concentration. and its HPQ structure always has an ESIPT effect throughout the reaction process, keeping the emission peak at 450 nm as a self‐reference. In particular, HPQRB has high selectivity for sulfite and responds quickly (within 30 s) with a low detection limit (44 nM). Furthermore, HPQRB has been successfully used for fluorescence imaging of sulfite in HepG2 cells, demonstrating the superior ability to detect sulfite under physiological conditions.

Near-infrared (NIR) fluorescence imaging technique is garnering increasing research attention due to various advantages. However, most NIR fluorescent probes still suffer from a false signals problem owing to their instability in real application. Especially in a pathological environment, many NIR probes can be easily destroyed due to the excessive generation of highly reactive species and causing a distorted false signal. Herein, we proposed an approach for developing a new stable NIR dye platform with an optically tunable group to eliminate false signals using the combination of dyes screening and rational design strategy. The conception is validated by the construction of two high-fidelity NIR fluorescent probes (NIR-LAP and NIR-ONOO–) sensing leucine aminopeptidase (LAP) and peroxynitrite (ONOO–), the markers of hepatotoxicity. These probes (NIR-LAP and NIR-ONOO–) were demonstrated to sensitively and accurately monitor LAP and ONOO– (detection limit: 80 mU/L for LAP and 90 nM for ONOO–), thereby allow...

NAD(P)H:quinone oxidoreductase-1 (NQO1) is attractive as a potential cancer biomarker because it is abnormally expressed in many solid tumors and is closely related to a variety of carcinogenic processes. Determining and evaluating the content/activity of NQO1 in tumors is of great significance for early cancer diagnosis and therapeutic effect evaluation. Enzyme-activated imaging probes with tailored properties, high selectivity and sensitivity, and high temporal and spatial resolution have become powerful tools for detecting and monitoring NQO1 activity. In this review, we aim to offer a rigorous but succinct overview of activatable imaging probes by reporting the significant progress made in accurately detecting and imaging NQO1 activity. The design strategies, mechanisms and applications of relevant probes are rationally analyzed and discussed. We also emphasized the potential challenges and prospects of NQO1-activated imaging probes to further advance the development of diagnosis and therapeutic methods for NQO1-related cancers.

Adenosine triphosphate (ATP), commonly produced in mitochondria, is required by almost all the living organisms; thus fluorescent probes for monitoring mitochondrial ATP levels fluctuation are essential and highly desired. Herein, we report a multisite-binding switchable fluorescent probe, ATP-Red 1, which selectively and rapidly responds to intracellular concentrations of ATP. Live-cell imaging indicated that ATP-Red 1 mainly localized to mitochondria with good biocompatibility and membrane penetration. In particular, with the help of ATP-Red 1, we successfully observed not only the decreased mitochondrial ATP levels in the presence of KCN and starvation state, but also the increased mitochondrial ATP levels in the early stage of cell apoptosis. These results indicate that ATP-Red 1 is a useful tool for investigating ATP-relevant biological processes.

Hydrogen sulfide (H2S) has been recognized as one of most important gaseous signaling molecules mediated by a variety of physiological and pathological processes. Yet, its functions remain largely elusive due to the lack of potent monitoring methods. Hereby this issue is addressed with a powerful new platform—dye-assembled upconversion nanoparticles (UCNPs). A series of chromophores with different absorption bands and fast responses towards H2S is combined with UCNPs and results in a library of H2S sensors with responsive emission signals ranging from the visible to the near-infrared (NIR) region. These nanoprobes demonstrate highly selective and rapid responses to H2S in vitro and in cells. Furthermore, H2S levels in blood can be detected using the developed nanoprobes. Hence the reported H2S sensing platform can serve as a powerful diagnostic tool to research H2S functions and to investigate H2S-related diseases.