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Fluorescence bioimaging through the second near-infrared window (NIR-II, 1000-1700 nm) has attracted much attention due to its deep penetration and high contrast. However, exploring new fluorescent materials, especially small molecular fluorophores with long wavelength and high brightness, is still quite challenging. By expanding π-conjugation and enhancing the intramolecular charge transfer effect, herein we report a series of new xanthene-based NIR-II dyes, named VIXs. Among these dyes, VIX-4 exhibits the best performance with fluorescence emission at 1210 nm and high brightness and has been used for dynamically imaging the blood flow of mice at 200 fps. By virtue of high spatiotemporal resolution of the dynamic imaging, we can distinguish directly the artery and vein through the blood flow direction and measure the blood flow volume by the videos. This study provides not only an effective tool for high spatial and temporal resolution bioimaging but also a new and promising conjugated skeleton for NIR-II dyes.

Metallic Na is a promising metal anode for large-scale energy storage. Nevertheless, unstable solid electrolyte interphase (SEI) and uncontrollable Na dendrite growth lead to disastrous short circuit and poor cycle life. Through phase field and ab initio molecular dynamics simulation, we first predict that the sodium bromide (NaBr) with the lowest Na ion diffusion energy barrier among sodium halogen compounds (NaX, X=F, Cl, Br, I) is the ideal SEI composition to induce the spherical Na deposition for suppressing dendrite growth. Then, 1,2-dibromobenzene (1,2-DBB) additive is introduced into the common fluoroethylene carbonate-based carbonate electrolyte (the corresponding SEI has high mechanical stability) to construct a desirable NaBr-rich stable SEI layer. When the Na||Na

Nitric oxide (NO) is a crucial neurotransmitter participating in many biological processes via nitrosylation reaction. NO produced in diverse subcellular regions also regulates the function of cells in different manners. A Golgi apparatus is rich in nitric oxide synthase and may serve as a potential therapeutic target for Alzheimer's disease (AD). However, due to the lack of an effective tool, it is difficult to reveal the relationship between Golgi-NO and AD. Herein, we report Golgi-NO as the first Golgi-targeted fluorescent probe for sensing and imaging NO in the Golgi apparatus. The probe is designed and synthesized by incorporating 4-sulfamoylphenylamide as a Golgi-targeted moiety to 6-carboxyrhodamine B, generating a fluorophore of Golgi-RhB with modifiable carboxyl, which is then combined with the NO recognition moiety of

Many fluorophores/probes suffer from the interference of albumin in biosystems. Herein, we propose an effective strategy to overcome this interference by virtue of both an albumin-insensitive fluorophore and its changeable π-conjugation, and demonstrate the strategy by designing an oxazine-based fluorogenic probe for aminopeptidase N (APN). The modification on the N atom in the oxazine fluorophore with alanine through a cleavable linker locks the resulting probe in a non-conjugated, colorless and non-fluorescent state, so the non-specific interaction of albumin produces no spectroscopic response. APN can selectively cleave the alanine moiety, restoring the large π-conjugation and strong fluorescence. The capability of the probe to eliminate the albumin influence has been demonstrated by imaging APN in different cell lines, and by quantitatively determining APN in human serum and mouse urine. The present strategy may be useful for developing more specific fluorogenic probes for other enzymes.

Drug-induced liver injury (DILI) is the most common reason for the post-marketing withdrawal of drugs. Poor understanding of the mechanisms of DILI presents a large challenge in clinical diagnosis. Previous evidences indicate a potential relationship between reactive nitrogen species (RNS) and DILI. Hence, we developed two specific probes, Golgi-HNO and Mito-HNO, for the multicolored and simultaneous in situ imaging of nitroxyl (HNO) in the Golgi apparatus and mitochondria, respectively. We discovered a significant rise in HNO levels in the livers of mice with DILI, which means that for the first time, we revealed a positive correlation between HNO levels and DILI. Based on changes in the HNO level, we also successfully explored the extent of liver damage induced by an anticarcinogen, bleomycin. In addition, we uncovered catalase was involved in HNO synthesis, which is the unprecedented function of catalase. These findings demonstrate that HNO is an ideal biomarker for DILI diagnosis, and Golgi-HNO and Mito-HNO are ideal fluorescent probes to study in situ HNO changes in various physiological and biochemical processes.

Objective. Nanodelivery is a modern technology involving improved delivery methods and drug formulations. The current development and initial applications of nanocarriers are pointing to new directions in the current development of nanomedicine. Researchers are increasingly applying nanodelivery to the delivery of therapeutic or diagnostic agents. This article discusses the preparation and application of nanocomplexes and nanoparticles, as well as their potential future value in clinical research. Through a review and analysis, it is hoped that this will serve as a guide for the future development of various nanodelivery technologies and help researchers learn more about these technologies. Materials and Methods. A literature search was conducted using the keywords “Nano drug delivery” or “Nanomedical materials” or “Nano”. A literature search was conducted in three major databases, PubMed, Web of Science, and Google Scholar, using the keywords such as “Nano drug delivery”, “Nanomedical materials”, or “Nanobubble drug delivery”. The initial search was screened by title and abstract. In the full-text review, the titles or abstracts were reviewed according to the selection criteria based on the inclusion criteria. The risk of bias and study quality was assessed according to the Cochrane guidelines, and possible biases such as selection bias and good selection bias were included in the review. Results. A total of 297 studies were included in this study, of which 219 were excluded based on the screening criteria, resulting in the inclusion of 78 studies, the majority of which were original studies and clinical trials, and a small number of which provided design and route of administration analysis of nanomaterial particles and effect fluorograms and were studied in more depth. This paper summarises and reviews the views and directions of the included articles. The main directions include cyclodextrin-based or grafted cyclodextrin nanomaterials, nanobubbles, and stimuli-sensitive and temperature-sensitive nanodelivery systems. Conclusion. The use of innovative, targeted drug delivery systems is effective in cancer drug delivery by summarising the previous studies. However, nanodelivery systems’ risks and therapeutic effects need to be evaluated before clinical application. Future research in the field of targeted drug delivery nanosystems should focus on the development of nanocarriers with high in vivo delivery capacity, good synergy with therapeutic agents, and milder short-term and long-term toxicological effects and conduct comprehensive preclinical trials on nanodrug delivery systems with high potential for clinical application as soon as possible, to find nanodrug delivery systems suitable for clinical use and put them into the clinical application as soon as possible.

Heat shock is a heat-related pathology characterized by a high body temperature and an obvious change of many enzymatic activities. Carboxylesterase (CE), as the major hydrolase in liver, is responsible for the hydrolysis of many drugs or the detoxification of various toxins from all organs. However, the correlation between heat shock and the CE activity in cells remains unknown, mainly due to the lack of a suitable research approach. Herein, a new water-soluble fluorescence probe, MYO-CE, with a specific bipiperidinyl recognition moiety has been developed for detecting the CE activity. MYO-CE reacted selectively with CE instead of other esterase, causing a large fluorescence off-on response at 560 nm with a detection limit of 0.39 U/mL. The applicability of MYO-CE for cell imaging was demonstrated by monitoring the alteration of the hepatocellular CE activity under inflammation. More importantly, we investigated the change of the CE activity during heat shock, uncovering a significant increase for the first time. This finding was further validated by a commercial colorimetric kit assay. The proposed probe shows a promising prospect for the CE study in cells under different pathological conditions.

Fluorescence bioimaging through the second near-infrared window (NIR-II, 1000-1700 nm) has attracted much attention due to its deep penetration and high contrast. However, exploring new fluorescent materials, especially small molecular fluorophores with long wavelength and high brightness, is still quite challenging. By expanding π-conjugation and enhancing the intramolecular charge transfer effect, herein we report a series of new xanthene-based NIR-II dyes, named VIXs. Among these dyes, VIX-4 exhibits the best performance with fluorescence emission at 1210 nm and high brightness and has been used for dynamically imaging the blood flow of mice at 200 fps. By virtue of high spatiotemporal resolution of the dynamic imaging, we can distinguish directly the artery and vein through the blood flow direction and measure the blood flow volume by the videos. This study provides not only an effective tool for high spatial and temporal resolution bioimaging but also a new and promising conjugated skeleton for NIR-II dyes.

Inflammation widely occurs in various tissues and organs in the human body. Rapid and accurate diagnosis of inflammation is essential to avoid severe complications. This study aims to obtain a non-destructive, fast, and comprehensive tool for the detection of pathogenic sites of inflammation in vivo. A fluorescence and photoacoustic dual-mode imaging probe, Cy-ASP, was first developed to detect inflammatory biomarker LTA4H with good sensitivity and selectivity in living small animal. Furthermore, the relationship between LTA4H and NF-κB in an LPS-induced cell was investigated. This work provides a new idea for the clinical diagnosis of pneumonia and hepatitis and revealing the upstream regulatory mechanism of LTA4H in the pneumonia model.

As an essential amino acid, cysteine is involved in various biosynthetic and metabolic processes, such as protein synthesis, hormone synthesis, and redox homeostatic maintenance. Inordinate cysteine levels are often associated with serious diseases. Thus, designing and synthesizing a novel fluorescent probe for determining the concentration of cellular cysteine, which could indirectly monitor the prevalence of these diseases, is essential. We developed a florescence probe P−Cy with good sensitivity for cysteine detection in vivo. P−Cy only exhibited good response toward cysteine but did not show response toward other biothiols, such as homocysteine (Hcy) and glutathione (GSH). In this study, we used P−Cy by successfully imaging cellular endogenous and exogenous cysteine levels. Furthermore, P−Cy was also performed in mice to detect cysteine level, indicating that P−Cy is a powerful tool for cysteine detection in situ.

We developed a photoacoustic and fluorescent dual-mode imaging probe, CCYS, for the detection of cysteine with high selectivity and sensitivity in a living system for the first time. By using CCYS, we found that the limited synthesis of glutathione in pulmonary fibrosis was not caused by cysteine deficiency.

Golgi oxidative stress is significantly associated with the occurrence and progression of hypertension. Notably, the concentration of hydrogen peroxide (H2O2) is directly proportional to the degree of Golgi oxidative stress. Therefore, based on a novel Golgi-targeting phenylsulfonamide group, we developed a two-photon (TP) fluorescent probe, Np-Golgi, for in situ H2O2 ratiometric imaging in living systems. The phenylsulfonamide moiety effectively assists Np-Golgi in the precise location of Golgi apparatus. In addition, the raw material of phenylsulfonamide is easily available, and chemical modification is easily implemented. By application of Np-Golgi, we explored the generation of H2O2 during Golgi oxidative stress, and also successfully revealed increases on the levels of Golgi H2O2 in the kidneys of mice with hypertension. This work provides an ideal tool to monitor Golgi oxidative stress for the first time and novel drug targets for the future treatment of hypertension.

Golgi pH homeostasis affects many different biological processes, including glycosylation. Recent studies have demonstrated that transmembrane protein 165 (TMEM165) deficiency leads to Golgi glycosylation abnormalities by disturbing Golgi pH homeostasis. However, due to the lack of specific tools to measure Golgi pH in situ, evidence for TMEM165 involvement in H+ transport in the Golgi apparatus is still absent. Herein, the photoacoustic and fluorescent dual-mode probe CPH was developed for ratiometric detection of Golgi pH. CPH was proved to accumulate in the Golgi apparatus and reversibly image Golgi pH in real-time with high sensitivity in cells. Furthermore, we found that the absence of TMEM165 influenced H+ equilibrium and caused Golgi apparatus acidification. Our work provides strong evidence that TMEM165 regulates Golgi pH homeostasis. Moreover, we believe that CPH has the potential to be a practical tool to monitor Golgi pH in various biological processes.

Severe atmospheric haze caused by industrial pollution has severely affected human health and led to the increasing incidence of cardiopulmonary diseases, including pneumonia. Conventional methods for diagnosis of pneumonia are complicated and tedious, and current clinical imaging techniques might cause organ injuries to some extent. Therefore, an accurate, fast, and intact imaging method must be developed to diagnose pneumonia in the early stages. In this study, we propose a new two-photon fluorescence probe, named as ASPC, for detection of the activity of the inflammatory biomarker LTA4H through specific recognition and cleavage of amides containing the unnatural amino acid l-AspBzl. The activity of LTA4H in the lung tissues of mice was rapidly and accurately monitored for the first time and could be an indicator for diagnosis of pneumonia. The severity of pneumonia in mice caused by haze particulate was determined through imaging the activity of LTA4H as biomarker and confirmed using a commercial ELISA...

Severe atmospheric haze caused by industrial pollution has severely affected human health and led to the increasing incidence of cardiopulmonary diseases, including pneumonia. Conventional methods for diagnosis of pneumonia are complicated and tedious, and current clinical imaging techniques might cause organ injuries to some extent. Therefore, an accurate, fast, and intact imaging method must be developed to diagnose pneumonia in the early stages. In this study, we propose a new two-photon fluorescence probe, named as ASPC, for detection of the activity of the inflammatory biomarker LTA

It is unclear whether green fluorescent protein (GFP) expression is maintained during the course of multilineage differentiation of muscle-derived stem cells (MDSCs). We isolated MDSCs from GFP-transgenic mice and transferred them to chondrogenic, neurogenic or myogenic media. Multilineage differentiation was examined by morphological observation, histological staining, immunocytochemical staining, real-time RT-PCR and Western blot. Both differentiated cells and non-differentiated cells maintained stable GFP expression until the cells exhibited a senescent phenotype. Thus, MDSCs from GFP-transgenic mice have multilineage potential in vitro and that GFP expression does not influence the multilineage potential of MDSCs (or vice versa).