Diagnosing Orthotopic Lung Tumor Using a NTR-Activatable Near-Infrared Fluorescent Probe by Tracheal Inhalation.

Nitroreductase (NTR) is an enzyme that is upregulated under tumor-depleted oxygen conditions. The majority of studies have been conducted on NTR, but many existing fluorescent imaging tools for monitoring NTR inevitably suffer from weak targeting, low sensitivity, and simple tumor models. Research on diagnosing lung tumors has been very popular in recent years, but targeting assays in orthotopic lung tumors is still of great research value, as such models better mimic the reality of cancer in the organism. Here, we developed a novel near-infrared (NIR) fluorescent probe IR-ABS that jointly targets NTR and carbonic anhydrase IX (CAIX). IR-ABS has excellent sensitivity and selectivity and shows exceptional NTR response in spectroscopic tests. The measurements ensured that this probe has good biosafety in both cells and mice. A better NTR response was found in hypoxic tumor cells at the cellular level, distinguishing tumor cells from normal cells. In vivo experiments demonstrated that IR-ABS achieves a hypoxic response at the zebrafish level and enables rapid and accurate tumor margin distinguishment in different mouse tumor models. More importantly, we successfully applied IR-ABS for NTR detection in orthotopic lung tumor models, further combined with tracheal inhalation drug delivery to improve targeting. To the best of our knowledge, we present for the first time a near-infrared imaging method for targeting lung cancerous tumor in situ via tracheal inhalation drug delivery, in contrast to the reported literature. This NIR fluorescence diagnostic strategy for targeting orthotopic lung cancer holds exciting potential for clinical aid in cancer diagnosis.

Developing a Two-Photon "AND" Logic Probe and Its Application in Alzheimer's Disease Differentiation.

In Alzheimer's disease, hypochlorous acid involved in the clearance of invading bacteria or pathogens and butyrylcholinesterase engaged in the hydrolysis of the neurotransmitter acetylcholine are relatively significantly altered. However, there are few dual detection probes for hypochlorous acid and butyrylcholinesterase. In addition, single-response probes suffer from serious off-target effects and near-infrared probes do not easily penetrate the blood-brain barrier due to their excessive molecular weight. In this work, we constructed a two-photon fluorescent probe that recognizes hypochlorous acid and butyrylcholinesterase based on a dual-lock strategy. The thiocarbonyl group is oxidized in the presence of hypochlorous acid, and the hydrolysis occurs at the 7-position ester bond in the existence of butyrylcholinesterase, releasing a strongly fluorescent fluorophore, 4-methylumbelliferone. Excellent imaging was performed in PC12 cells using this probe, and deep two-photon imaging was observed in the brains of AD mice after tail vein injection with this probe. It indicates that the probe can provide a promising tool for the more precise diagnosis of Alzheimer's disease.

A Bioresponsive Near-Infrared Fluorescent Probe for Facile and Persistent Live-Cell Tracking.

Molecular imaging significantly transforms the field of biomedical science and facilitates the visualization, characterization, and quantification of biologic processes. However, it is still challenging to monitor cell localization in vivo, which is essential to the study of tumor metastasis and in the development of cell-based therapies. While most conventional small-molecule fluorescent probes cannot afford durable cell labeling, transfection of cells with fluorescent proteins is limited by their fixed fluorescence, poor tissue penetration, and interference of autofluorescence background. Here, a bioresponsive near-infrared fluorescent probe is reported as facile and reliable tool for real-time cell tracking in vivo. The design of this probe relies on a new phenomenon observed upon fluorobenzene-conjugated fluorescent dyes, which can form complexes with cytosolic glutathione and actively translocates to lysosomes, exhibiting enhanced and stable cell labeling. Fluorobenzene-coupled hemicyanine, a near-infrared fluorophore manifests to efficiently staining tumor cells without affecting their invasive property and enables persistent monitoring of cell migration in metastatic tumor murine models at high resolution for one week. The method of fluorobenzene functionalization also provides a simple and universal "add-on" strategy to render ordinary fluorescent probes suitable for long-term live-cell tracking, for which currently there is a deficit of suitable molecular tools.

Application of Nitroimidazole-Carbobane-Modified Phenylalanine Derivatives as Dual-Target Boron Carriers in Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) has received extensive attention as noninvasive cell-level oncotherapy for treating solid cancer tumors. However, boron-containing drugs such as l-boronophenylalanine (BPA) and sodium borocaptate have low boron content and/or poor tumor-targeting ability, limiting their application. In this study, we designed and synthesized a series of nontoxic, dual-target boron carriers (B139, B142, and B151) with the ability to accumulate specifically in tumor cells. We found that the B139 uptake into hypoxic tumor regions was high, with a 70-fold boron content compared to BPA. In addition, in vivo observation showed that B139 can be trapped in tumor cells for a prolonged period and maintains an effective therapeutic concentration, with a peak boron concentration of 50.7 µg/g and a high tumor: blood boron ratio of >3, achieving ideal BNCT conditions. Cytotoxicity evaluation in mice further proved that B139 is safe and reliable. Therefore, B139 has great potential for BNCT application as a dual-target, safe, and efficient boron carrier.

Identification of Genes Associated With Hirschsprung Disease, Based on Whole-Genome Sequence Analysis, and Potential Effects on Enteric Nervous System Development.

BACKGROUND & AIMS: Hirschsprung disease, or congenital aganglionosis, is believed to be oligogenic-that is, caused by multiple genetic factors. We performed whole-genome sequence analyses of patients with Hirschsprung disease to identify genetic factors that contribute to disease development and analyzed the functional effects of these variants. METHODS: We performed whole-genome sequence analyses of 443 patients with short-segment disease, recruited from hospitals in China and Vietnam, and 493 ethnically matched individuals without Hirschsprung disease (controls). We performed genome-wide association analyses and gene-based rare-variant burden tests to identify rare and common disease-associated variants and study their interactions. We obtained induced pluripotent stem cell (iPSC) lines from 4 patients with Hirschsprung disease and 2 control individuals, and we used these to generate enteric neural crest cells for transcriptomic analyses. We assessed the neuronal lineage differentiation capability of iPSC-derived enteric neural crest cells using an in vitro differentiation assay. RESULTS: We identified 4 susceptibility loci, including 1 in the phospholipase D1 gene (PLD1) (P = 7.4 × 10-7). The patients had a significant excess of rare protein-altering variants in genes previously associated with Hirschsprung disease and in the ß-secretase 2 gene (BACE2) (P = 2.9 × 10-6). The epistatic effects of common and rare variants across these loci provided a sensitized background that increased risk for the disease. In studies of the iPSCs, we observed common and distinct pathways associated with variants in RET that affect risk. In functional assays, we found variants in BACE2 to protect enteric neurons from apoptosis. We propose that alterations in BACE1 signaling via amyloid ß precursor protein and BACE2 contribute to pathogenesis of Hirschsprung disease. CONCLUSIONS: In whole-genome sequence analyses of patients with Hirschsprung disease, we identified rare and common variants associated with disease risk. Using iPSC cells, we discovered some functional effects of these variants.

Methionine-Decorated Near Infrared Fluorescent Probe for Prolonged Tumor Imaging.

Methionine (Met) is one of the essential amino acids of which the transport system L is overexpressed in various tumor cells. In this study, a near-infrared fluorescent dye (IR-780) and methionine were conjugated through a piperazin-polyamines linker to form Cy-Met. The successful synthesis of Cy-Met was validated by optical characterization, NMR, and MS spectra. The absorption peak of Cy-Met was at 680 nm, and the fluorescence peak was at 790 nm. The cytotoxicity assay and cell imaging studies indicated that Cy-Met had good biocompatibility and specific affinity to tumor cells. The dynamic distribution and clearance investigations showed that Cy-Met was eliminated by the liver-intestine pathway. Notably, Cy-Met displayed tumor-targeting ability in U87, H22, and EAC tumor-bearing mice with an evident long circulation time. The results implied that Cy-Met could act as a promising fluorescence probe specialized for long-term tumor monitoring.

Hybrid profilometry using a single monochromatic multi-frequency pattern.

In this paper, we propose a novel profilometry scheme to acquire high quality depth, where only a single shot of a monochromatic pattern is utilized. We design a band-wise pattern consisting of fringe bands spatially modulated with coprime periods. After that, with the designed pattern, depth is obtained in a hybrid manner, where both phase-based profilometry and active stereo are incorporated. To be specific, pixels in smooth regions obtain their depth values through phases analysis. Especially, based on depth smooth property, we propose a novel phase unwrapping algorithm, which avoids the problem of error propagation and yields accurate unwrapping phases. On the other hand, for boundary regions, spatial stereo, which is more robust to depth discontinuities, is utilized to modify incorrect depth values. Both theoretical verification and experimental results demonstrate that the proposed scheme can generate high quality depth maps, even for complex scenes and isolated objects.

Discovery and optimization of new benzofuran derivatives against p53-independent malignant cancer cells through inhibition of HIF-1 pathway.

p53-independent malignant cancer is still severe health problem of human beings. HIF-1 pathway is believed to play an important role in the survival and developing progress of such cancers. In the present study, with the aim to inhibit the proliferation of p53-independent malignant cells, we disclose the optimization of 6a, the starting compound which is discovered in the screening of in-house compound collection. The structure-activity relationship (SAR) is summarized. The most potent derivative 8d, inhibits the proliferation of both p53-null and p53-mutated cells through inhibition of HIF-1 pathway. Our findings here provide a new chemotype in designing potent anticancer agent especially against those p53-independent malignant tumors.

Genome-wide copy number variation study in anorectal malformations.

Anorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10 000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology is unknown. To assess the genetic contribution to ARMs, we investigated single-nucleotide polymorphisms and copy number variations (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4006 Han Chinese controls were included. Overall, we detected a 1.3-fold significant excess of rare CNVs in patients. Stratification of patients by presence/absence of other congenital anomalies showed that while syndromic ARM patients carried significantly longer rare duplications than controls (P = 0.049), non-syndromic patients were enriched with both rare deletions and duplications when compared with controls (P = 0.00031). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls nor 11 943 healthy individuals from the Database of Genomic Variants. Importantly, these aberrations were observed in isolated ARM patients. Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication. DKK4 is a member of the WNT signaling pathway which is involved in the development of the anorectal region. In mice, Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provide a list of plausible candidate genes for the disorder.

Genome-wide copy number analysis uncovers a new HSCR gene: NRG3.

Hirschsprung disease (HSCR) is a congenital disorder characterized by aganglionosis of the distal intestine. To assess the contribution of copy number variants (CNVs) to HSCR, we analysed the data generated from our previous genome-wide association study on HSCR patients, whereby we identified NRG1 as a new HSCR susceptibility locus. Analysis of 129 Chinese patients and 331 ethnically matched controls showed that HSCR patients have a greater burden of rare CNVs (p = 1.50 × 10(-5)), particularly for those encompassing genes (p = 5.00 × 10(-6)). Our study identified 246 rare-genic CNVs exclusive to patients. Among those, we detected a NRG3 deletion (p = 1.64 × 10(-3)). Subsequent follow-up (96 additional patients and 220 controls) on NRG3 revealed 9 deletions (combined p = 3.36 × 10(-5)) and 2 de novo duplications among patients and two deletions among controls. Importantly, NRG3 is a paralog of NRG1. Stratification of patients by presence/absence of HSCR-associated syndromes showed that while syndromic-HSCR patients carried significantly longer CNVs than the non-syndromic or controls (p = 1.50 × 10(-5)), non-syndromic patients were enriched in CNV number when compared to controls (p = 4.00 × 10(-6)) or the syndromic counterpart. Our results suggest a role for NRG3 in HSCR etiology and provide insights into the relative contribution of structural variants in both syndromic and non-syndromic HSCR. This would be the first genome-wide catalog of copy number variants identified in HSCR.

2,2-Dichloroacetamide exposure induces behavior and memory disorders in mice: Detrimental effects of long-term dietary restriction on neurotoxicity.

2, 2-dichloroacetamide (DCAcAm), a nitrogen-containing disinfection byproduct (DBPs), is commonly found in potable water. This study aimed to compare the neurotoxicity of DCAcAm in C57/BL6 mice at both environmentally relevant and higher doses through oral exposure over a 28-day period. Furthermore, the potential effects of dietary restriction (DR) on the cerebral toxicity induced by 20 ppb DCAcAm were examined. The findings indicated that DCAcAm exposure and DR treatment resulted in reduced memory retention and cognitive adaptability in mice. Additionally, higher doses of DCAcAm exposure induced severe brain inflammation and oxidative stress. Metabolic profiling revealed disruptions in fatty acid, energy, and amino acid metabolism in the brain. Remarkably, the negative impacts of 20 ppb DCAcAm on the mice brain were worsened by DR treatment. Analysis of 16S rRNA sequencing revealed notable changes in the composition and structure of intestinal microorganisms after exposure to DCAcAm. This study discovered that DCAcAm has both direct effects on the brain and indirect effects through the microbial-brain-intestinal axis, which collectively result in neurotoxicity and dietary restriction exacerbates these effects. This study provides emerging views on the assessment of the toxicity of nitrogen containing DBPs.

Amine response smartphone-based portable and intelligent polyvinyl alcohol films for real-time detection of shrimp freshness.

Food freshness monitoring is an important component in ensuring food safety for consumers and the food industry. Therefore, there is an urgent need for a portable, low-cost, and efficient detection method to determine the freshness. In this study, polyvinyl alcohol (PVA) was used as polymer carrier to prepare electrospinning film containing curcumin (Cur) and gardenia blue (GB) as intelligent indicator label on food packaging for real-time nondestructive detection of freshness of shrimp. The detection limit of ammonia response is less than or equal to 20 ppm, and the detection time is about 1 min, indicating that it has a sensitive response effect. At the same time, a smartphone application that can identify amines in response to color changes has been developed, and consumers can understand freshness by scanning the label. This study demonstrates the huge potential of smart indicator labels for food freshness monitoring.

Screening and optimization of a water-soluble near-infrared fluorescent probe for drug-induced liver injury monitoring.

Peroxynitrite (ONOO-) is a potential biomarker of drug-induced liver injury (DILI) and is involved in the process of DILI. Therefore, developing a reliable detection method for ONOO- will greatly contribute to ensuring drug safety and improving treatment efficiency. Here, based on the previous work, two kinds of NIR fluorescence probes PN and SPN were developed with phenyl-hydrazine as the ONOO- recognition group, which based on two fluorophores RN and SRN that are stable to ONOO-. A sensitive NIR probe SPN with good water solubility, low detection limit and good biocompatibility was selected through in vitro spectral property screening. Further experimental results show that there is a good linear relationship between the response intensity of probe SPN to ONOO- and the concentration of ONOO-, and the detection limit can reach 19.7 nM. At the cellular level, probe SPN can achieve a good and specific response to endogenous and exogenous ONOO-. Also, the probe SPN can be used for imaging and detection of DILI in zebrafish level and small animal level, indicating that probe SPN can be used as a powerful tool for diagnosis of DILI and efficacy evaluation of therapeutic drugs.

Peroxynitrite/Lipid Droplet Sequence-Activated Dual-Lock Fluorescent Probes Enable Precise Intraoperative Imaging of Atherosclerotic Plaques.

The formation of atherosclerotic plaques is the root cause of various cardiovascular diseases (CVDs). Effective CVD interventions thus call for precise identification of the plaques to aid clinical assessment and treatment of such diseases. In this study, we introduced a dual-analyte sequentially activated logic fluorescence reporting system CNN2-B to precisely identify the atherosclerotic plaques in vivo. This probe was achieved by creating a dual-locked fluorescent sensor that permits highly specific and sensitive detection of peroxynitrite and lipid droplets─the two hallmarks of atherosclerosis (AS). The recognition group of the probe removed after reacting with ONOO- and intramolecular charge rearrangement occurred to generate a coumarin derivative structure. This structure had a strong solvent effect; it could recognize lipid droplets (LDs) in cells, thus exhibiting fluorescence without secondary molecular adjustment. The fluorescence was tremendously quenched by double locking; thus, an extreme fluorescence enhancement factor (F/F0) ratio of 365 for CNN2-B was obtained. Importantly, CNN2-B could move from the mitochondria to lipid droplets after being activated. CNN2-B exhibited higher selectivity and signal-to-noise (S/N) ratio than commercial probe hydroxyphenyl fluorescein (HPF). Therefore, atherosclerotic plaques in mouse models were delineated clearly by fluorescence imaging after in situ administration of CNN2-B.

Hypochlorite activatable ratiometric fluorescent probe based on endoplasmic reticulum stress for imaging of atherosclerosis.

Endoplasmic reticulum (ER) stress can induce reactive oxygen (ROS) generation which is directly associated with the emergence of atherosclerosis. Foam cells could promote atherogenesis by inducing ER stress. To understand hypochlorite (ClO-) levels in foam cells under ER stress, novel ER-targeted ClO- activatable ratiometric fluorescence probes Rx-NE and Rx-NCE were designed using a classical rhodamine dye and coumarin dye bridge moiety as the fluorescent skeleton. Both Rx-NE and Rx-NCE demonstrated ratiometric detection capabilities for ClO-, with Rx-NCE showing better sensitivity compared to Rx-NE. The probe Rx-NCE could detect the upregulation of ClO- in foam cells under ER stress and clearly outline delineation of the boundary of atherosclerotic plaques by dual-color imaging. Importantly, the hypochlorite-activated ratiometric probe Rx-NCE had been innovatively applied to the distinction of atherosclerotic blood vessels in atherosclerosis-bearing transgenic (tg) (flk1: eGFP) zebrafish. The probe Rx-NCE is of significant value for investigating the pathological role of ER stress and atherosclerotic diseases, as well as offering new insights into the identification of atherosclerosis.

Corynoxine B targets at HMGB1/2 to enhance autophagy for α-synuclein clearance in fly and rodent models of Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Acidic tumor microenvironment-activatable fluorescent diagnostic probe for the rapid identification and resection of human tumors via spraying.

A fluorescent diagnostic probe for real-time intraoperative image-guided tumor resection can significantly improve the efficiency and quality of oncological therapy, but their development is challenging. Herein, a novel fluorescent diagnostic probe called HLTC based on ß-carboline was designed and synthesized. HLTC was found to show a ∼10-fold enhancement of fluorescence quantum field with pH from 7.4 to 4.0, indicating its imaging potential in acid environment which is a typical hallmark of the tumor microenvironment (TME). Following fluorescence microscopy imaging showed HLTC could emit specific signals in cancer cells and sections, by both one-photon excitation and two-photon excitation. Importantly, HLTC enabled the precise and rapid delineation of both transplanted tumor and clinical tumor tissues within several minutes of simple topical spray. The tumor-to-background ratio (TBR) was up to 10.2 ± 1.0 at clinical liver cancer tissues and 9.9 ± 0.3 at clinical colon cancer tissues, allowing precise tumor margin identification and the effective guidance of surgical tumor resection. Furthermore, CCK8 assay, pharmacokinetic evaluation, blood analysis and H&E staining were performed, which verified high biocompatibility and biosafety of HLTC at working concentration. These results reveal the exciting potential of this small-molecule fluorescent diagnostic probe for real-time fluorescence-based navigation during surgical tumor resection.

Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease.

Hirschsprung's disease (HSCR), or aganglionic megacolon, is a congenital disorder characterized by the absence of enteric ganglia in variable portions of the distal intestine. RET is a well-established susceptibility locus, although existing evidence strongly suggests additional loci contributing to sporadic HSCR. To identify these additional genetic loci, we carried out a genome-wide association study using the Affymetrix 500K marker set. We successfully genotyped 293,836 SNPs in 181 Chinese subjects with sporadic HSCR and 346 ethnically matched control subjects. The SNPs most associated with HSCR were genotyped in an independent set of 190 HSCR and 510 control subjects. Aside from SNPs in RET, the strongest overall associations in plausible candidate genes were found for 2 SNPs located in intron 1 of the neuregulin1 gene (NRG1) on 8p12, with rs16879552 and rs7835688 yielding odds ratios of 1.68 [CI(95%):(1.40, 2.00), P = 1.80 x 10(-8)] and 1.98 [CI(95%):(1.59, 2.47), P = 1.12 x 10(-9)], respectively, for the heterozygous risk genotypes under an additive model. There was also a significant interaction between RET and NRG1 (P = 0.0095), increasing the odds ratio 2.3-fold to 19.53 for the RET rs2435357 risk genotype (TT) in the presence of the NRG1 rs7835688 heterozygote, indicating that NRG1 is a modifier of HSRC penetrance. Our highly significant association findings are backed-up by the important role of NRG1 as regulator of the development of the enteric ganglia precursors. The identification of NRG1 as an additional HSCR susceptibility locus not only opens unique fields of investigation into the mechanisms underlying the HSCR pathology, but also the mechanisms by which a discrete number of loci interact with each other to cause disease.

Summary of best evidence for enhanced recovery after surgery for patients undergoing lung cancer operations.

According to the cancer burden report released by the International Agency for Research on Cancer (IARC) in 2020, the mortality rate of lung cancer is 18%, ranking first in the world, and its morbidity and mortality rates are highest in China. Pneumonectomy is the preferred treatment for lung cancer patients, but surgery carries a significant risk of perioperative complications, which may affect the patient's functional recovery and quality of life. So, the rehabilitation of the large number of lung cancer patients in China requires greater attention. A number of studies have shown that the enhanced recovery after surgery (ERAS) protocol can reduce the risk of death, readmission rate, adjuvant chemotherapy time, postoperative pain level, anesthesia medication amount, length of stay, and hospitalization expenses. Foreign literature has successively issued guidelines to improve recovery among lung cancer patients, but Chinese-specific literature for patients undergoing lung cancer surgery or thoracic surgery remains inadequate. Some Chinese expert consensus have only considered part of the content of ERAS in thoracic surgery. To summary the evidence of the ERAS program for lung cancer surgery patients at home and abroad basing on evidence-based medicine is necessary. Therefore, this study used evidence-based practical thinking as a guide to (1) evaluate, integrate, and summarize relevant evidence guidelines and data resources at home and abroad so as to construct an enhanced recovery program for lung cancer patients suitable for Chinese national conditions and (2) provide a scientific basis for future research and practice in related fields.

Monitoring isoniazid metabolism in vivo using a near-infrared fluorescent probe.

As a strong nucleophilic substance, hydrazine is widely used in the fields of agriculture, industry, and medicine. Hydrazine compounds usually exist as intermediates of some drugs. Many drugs, such as isoniazid and carbidopa, produce hydrazine metabolites. Hydrazine is a genotoxic substance, which can cause DNA lesions and cancer via long-term exposure. Therefore, it is very important to monitor the level of hydrazine in the human body with high selectivity and sensitivity. Here, we synthesized a near-infrared (NIR) fluorescent probe Cy-HZ based on the hemicyanine skeleton to visualize the metabolism of the drug isoniazid in vivo. The ester group of the probe reacts with hydrazine to generate Cy-H, causing a change in fluorescence. Here, we studied its absorption and fluorescence spectra, the recognition response to hydrazine, the imaging of exogenous hydrazine in cells and the imaging in mice and further applied the probe to monitor the distribution and metabolism of isoniazid.