Corrigendum: Genetic overlap and causality between COVID-19 and multi-site chronic pain: the importance of immunity.

[This corrects the article DOI: 10.3389/fimmu.2024.1277720.].

Genetic overlap and causality between COVID-19 and multi-site chronic pain: the importance of immunity.

Background: The existence of chronic pain increases susceptibility to virus and is now widely acknowledged as a prominent feature recognized as a major manifestation of long-term coronavirus disease 2019 (COVID-19) infection. Given the ongoing COVID-19 pandemic, it is imperative to explore the genetic associations between chronic pain and predisposition to COVID-19. Methods: We conducted genetic analysis at the single nucleotide polymorphism (SNP), gene, and molecular levels using summary statistics of genome-wide association study (GWAS) and analyzed the drug targets by summary data-based Mendelian randomization analysis (SMR) to alleviate the multi-site chronic pain in COVID-19. Additionally, we performed a latent causal variable (LCV) method to investigate the causal relationship between chronic pain and susceptibility to COVID-19. Results: The cross-trait meta-analysis identified 19 significant SNPs shared between COVID-19 and chronic pain. Coloc analysis indicated that the posterior probability of association (PPH4) for three loci was above 70% in both critical COVID-19 and COVID-19, with the corresponding top three SNPs being rs13135092, rs7588831, and rs13135092. A total of 482 significant overlapped genes were detected from MAGMA and CPASSOC results. Additionally, the gene ANAPC4 was identified as a potential drug target for treating chronic pain (P=7.66E-05) in COVID-19 (P=8.23E-03). Tissue enrichment analysis highlighted that the amygdala (P=7.81E-04) and prefrontal cortex (P=8.19E-05) as pivotal in regulating chronic pain of critical COVID-19. KEGG pathway enrichment further revealed the enrichment of pleiotropic genes in both COVID-19 (P=3.20E-03,Padjust=4.77E-02,hsa05171) and neurotrophic pathways (P=9.03E-04,Padjust =2.55E-02,hsa04621). Finally, the latent causal variable (LCV) model was applied to find the genetic component of critical COVID-19 was causal for multi-site chronic pain (P=0.015), with a genetic causality proportion (GCP) of was 0.60. Conclusions: In this study, we identified several functional genes and underscored the pivotal role of the inflammatory system in the correlation between the paired traits. Notably, heat shock proteins emerged as potential objective biomarkers for chronic pain symptoms in individuals with COVID-19. Additionally, the ubiquitin system might play a role in mediating the impact of COVID-19 on chronic pain. These findings contribute to a more comprehensive understanding of the pleiotropy between COVID-19 and chronic pain, offering insights for therapeutic trials.

Investigating the shared genetic architecture between attention-deficit/hyperactivity disorder and risk taking behavior: A large-scale genomewide cross-trait analysis.

BACKGROUND: This study aims to explore the genetic architecture shared between Attention-Deficit/Hyperactivity Disorder (ADHD) and risk behavior. METHODS: Based on the latest large-scale Genome-wide association studies (GWAS), we firstly employed Linkage disequilibrium score regression (LDSC) and Local Analysis of Variant Association (LAVA) to investigate the genetic correlation between risk behavior and ADHD. Then, we conducted cross-trait analysis to identified the Pleiotropic loci. Finally, bidirectional Mendelian randomization analysis (MR) was applied to examine the causal relationship. RESULTS: We found a significant positive genetic correlation between ADHD and risk-taking behavior (rg = 0.351, p = 6.50E-37). The cross-trait meta-analysis identified 27 significant SNPs shared between ADHD and risk behavior. The most significant locus, located near the CADM2 gene on chromosome 3, had been identified associated with this two trait (pADHD = 3.07E-05 and prisk-taking behavior = 2.47E-30). The same situation can also be observed near the FOXP2 gene on chromosome 7 (rs8180817, pmeta = 5.72E-21). We found CCDC171 gene and other genes played a significant role in ADHD and risk behavior in mRNA level. Bidirectional MR analysis found a causal relationship between them. LIMITATION: The majority of our data sources were of European origin, which may limit the generalizability of our findings to other ethnic populations. CONCLUSION: This article reveals in depth the shared genetic structure between ADHD and risk-taking behavior, finding a significant positive genetic correlation between ADHD and risk-taking behavior. Providing insights for the future treatment and management of these two traits.

Ratiometric Near-Infrared Fluorescent Probe Monitors Ferroptosis in HCC Cells by Imaging HClO in Mitochondria.

Hypochlorous acid (HClO) is a typical endogenous ROS produced mainly in mitochondria, and it has strong oxidative properties. Abnormal HClO levels lead to mitochondrial dysfunction, strongly associated with various diseases. It has been shown that HClO shows traces of overexpression in cells of both ferroptosis and hepatocellular carcinoma (HCC). Therefore, visualization of HClO levels during ferroptosis of HCC is important to explore its physiological and pathological roles. So far, there has been no report on the visualization of HClO in ferroptosis of HCC. Thus, we present a ratiometric near-infrared (NIR) fluorescent probe Mito-Rh-S which visualized for the first time the fluctuation of HClO in mitochondria during ferroptosis of HCC. Mito-Rh-S has an ultrafast response rate (2 s) and large emission shift (115 nm). Mito-Rh-S was constructed based on the PET sensing mechanism and thus has a high signal-to-noise ratio. The cell experiments of Mito-Rh-S demonstrated that Fe2+- and erastin-induced ferroptosis in HepG2 cells resulted in elevated levels of mitochondrial HClO and that high concentration levels of Fe2+ and erastin cause severe mitochondrial damage and oxidative stress and had the potential to kill HepG2 cells. By regulating the erastin concentration, erastin induction time, and treatment of the ferroptosis model, Mito-Rh-S can accurately detect the fluctuation of mitochondrial HClO levels during ferroptosis in HCC.

Investigating the shared genetic architecture between COVID-19 and obesity: a large-scale genome wide cross-trait analysis.

Observational studies have reported high comorbidity between obesity and severe COVID-19. The aim of this study is to explore whether genetic factors are involved in the co-occurrence of the two traits. Based on the available genome-wide association studies (GWAS) summary statistics, we explored the genetic correlation and performed cross-trait meta-analysis (CPASSOC) and colocalization analysis (COLOC) to detect pleiotropic single nucleotide polymorphisms (SNPs). At the genetic level, we obtained genes detected by Functional mapping and annotation (FUMA) and the Multi-marker Analysis of GenoMic Annotation (MAGMA). Potential functional genes were further investigated by summary-data-based Mendelian randomization (SMR). Finally, the casualty was identiied using the latent causal variable model (LCV). A significant positive genetic correlation was revealed between obesity and COVID-19. We found 331 shared genetic SNPs by CPASSOC and 13 shared risk loci by COLOC. At the genetic level, We obtained 3546 pleiotropic genes, among which 107 genes were found to be significantly expressed by SMR. Lastly, we observed these genes were mainly enriched in immune pathways and signaling transduction. These indings could provide new insights into the etiology of comorbidity and have implications for future therapeutic trial.

Non-linear relationship between the body roundness index and metabolic syndrome: data from National Health and Nutrition Examination Survey (NHANES) 1999-2018.

Obesity is an important characteristic manifestation of metabolic syndrome (MetS), and body roundness index (BRI) is one of the anthropometric indicators associated with obesity. However, studies on the relationship between BRI and MetS risk are limited. We aimed to explore the relationship between baseline BRI and MetS in the USA population. Our study used data from the National Health and Nutrition Examination Survey from 1999 to 2018, ultimately enrolling and analysing 47 303 participants. Data-driven tertiles were used to categorise BRI levels, and multivariate logistic regression models were fitted to investigate the association of BRI with MetS in adults. In addition, receiver operating characteristic curve analysis was used to assess the ability of BRI to predict MetS. The distribution of BRI was different across ethnic groups with a gradual decrease in the proportion of non-Hispanic Whites and other races. In addition, BRI was significantly associated with traditional cardiovascular risk factors. Univariate regression analysis indicated BRI to be a moderate risk factor for MetS, and multivariate logistic regression analysis found that BRI remained an independent risk factor for MetS. After adjusting for confounding variables, a non-linear relationship was found between BRI levels and the prevalence of MetS. More importantly, BRI predicted MetS with the largest AUC among anthropometric measures. In summary, elevated baseline BRI levels are independently associated with the development of MetS, and baseline BRI may assist in identifying patients at risk for MetS, leading to early and optimal treatment to improve their outcomes.

Clinical manifestations and computed tomography angiography features of anomalous left coronary artery from the pulmonary artery syndrome. / å·¦å† çŠ¶åŠ¨è„‰å¼‚å¸¸èµ·æºäºŽè‚ºåŠ¨è„‰ç»¼åˆå¾ï¼šä¸´åºŠè¡¨çŽ°åŠCTA影像学特征.

OBJECTIVES: Anomalous left coronary artery from the pulmonary artery (ALCAPA) syndrome is a rare congenital coronary artery malformation with a high rate of clinical missed diagnosis and misdiagnosis. At present, there is a lack of reports on the clinical manifestations of ALCAPA and the imaging features of coronary computed tomography angiography (CTA). This study aims to summarize the clinical characteristics and coronary CTA imaging features of ALCAPA to improve the clinical diagnosis and treatment. METHODS: The clinical data of 24 ALCAPA syndrome patients were retrospectively collected, analyzed and summarized from January 1, 2013 to February 1, 2023 in the Second Xiangya Hospital of Central South University. According to the left and right coronary collateral circulation, the patients were classified into infantile type (7 cases) and adult type (17 cases). The differences of clinical manifestations and CTA imaging features were compared between the 2 types of patients. RESULTS: Of the 24 patients, a male-to-female ratio was at 1꞉5, and the median age of onset was 3.22 months for the infant type and 22.0 years for the adult type. The infantile type showed symptoms of left heart insufficiency at an early stage, while the adult type had a variety of clinical manifestations in 7 patients being asymptomatic and presented with a cardiac murmur on physical examination, 6 with symptoms of chronic myocardial ischemia, and 2 with malignant arrhythmias. CTA showed that 11 patients' the left coronary artery originated from the left posterior sinus of the pulmonary artery. All 7 infantile type patients had an enlarged left heart, left ventricular hypertrophy, reduced left heart function, lack of collateral circulation between the left and right coronary arteries, and normal coronary artery diameter. All 17 adult type patients showed dilated and tortuous coronary arteries with rich collateral circulation, and 7 adult type patients had preserved left heart function. CONCLUSIONS: The clinical manifestations and CTA imaging features of patients with the 2 types of ALCAPA are different, while CTA performance is characteristic and can be used as a means of definitive diagnosis, staging, surgical evaluation, and postoperative follow-up of ALCAPA syndrome.

A near-infrared fluorescent probe with remarkably large stokes shift for specifical imaging of peroxynitrite fluctuations in Hela cells.

Peroxynitrite (ONOO-), an endogenous reactive nitrogen species, plays an important role in maintaining intracellular homeostasis. Abnormal levels of ONOO- in cells could cause protein oxidation which is confirmed that related with Alzheimer's diseases, so accurate monitoring of ONOO- in cells is crucial. Herein, a novel fluorescent probe (XPC) based on dicyanomethylene-4H-benzothiopyran was developed by regulating its intramolecular charge transfer (ICT) effect to detect ONOO-. Once reaction with ONOO-, the fluorescence of XPC was turned on and the emission wavelength could reach up to 750 nm. Furthermore, XPC exhibited satisfactory performances for ONOO- such as large Stokes shift (200 nm), good sensitivity (Limit of detection = 13 nM), high selectivity to ONOO- over other a reactive nitrogen species (RNS)/reactive oxygen species (ROS). More importantly, XPC was successfully applied for monitoring the fluctuations of ONOO- in living cells.

Effects of biochar on runoff generation, soil and nutrient loss at the surface and underground on the soil-mantled karst slopes.

The effects of biochar (BC) on soil erosion and nutrient output have attracted widespread attention; however, the role of BC in soil and water conservation remains debated. In particular, the effect of BC on underground erosion and nutrient output in soil-mantled karst areas has not been clearly determined. The objective of this study was to investigate the effects of BC on soil and water conservation and nutrient output in surface-underground dual erosion structures in soil-mantled karst areas. Eighteen runoff plots (2 m × 1 m) were established at the Guizhou University research station. Two BC treatments (T1 = 30 t/ha; T2 = 60 t/ha) and a control treatment (CK = 0 t/ha) were used. The BC material was produced from corn straw. The experiment ran from January to December 2021 and a total of 1132.64 mm of rainfall was measured. Runoff and soil and nutrient loss at the surface and underground were collected during natural rainfall. The results showed that 1) compared to CK, the BC application significantly increased surface runoff (SR, P < 0.05) and reduced subsurface runoff (SF, P < 0.05), and underground fissure runoff (UFR) decreased in general but did not reach a significant level (P > 0.05). The total amount of SR collected in each treatment during the test period accounted for 51 %-63 % of the total amount of all collected outlet runoff (SR, SF and UFR); 2) total organic carbon (TOC), total nitrogen (TN) and total phosphorus (TP) were mainly exported through the UFR, and total potassium (TK) was mainly exported through the SR; and 3) compared to CK, the BC reduced TOC, TN and TP output through runoff but had no significant effect on TK output regardless of surface runoff or underground runoff. Thus, BC application reduces nonpoint source (NPS) pollution, and more importantly, it can inhibit TN and TP flow into groundwater through bedrock fissures. Our results provide further evidence for evaluating the soil and water conservation benefits of BC. Therefore, BC in soil-mantled karst agricultural areas can prevent groundwater pollution in karst regions. In general, BC enhances surface erosion and inhibits underground runoff and nutrients loss on soil-mantled karst slopes. This shows that the process through which BC application affects erosion in karst areas is complex, and further research is needed to investigate the long-term effects of BC application in this area.

Associations of metal mixtures in the meconium with birth outcomes in northern Taiwan.

Previous studies investigated prenatal exposure to neurotoxic metals in relation to birth anthropometrics. However, limited information has been developed on associations with birth outcomes of fetal exposure to metal mixtures using the meconium as a biomarker. The purpose of this study was to evaluate relationships of the combined effects of mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) concentrations in the meconium on birth outcomes (i.e., birth weight, birth length, and head circumference). This cross-sectional study was conducted in northern Taiwan between January 2007 and December 2009. We collected 526 meconium samples within the first 24 h after birth to measure the in utero mixed-metal exposure determined using inductively coupled plasma/mass spectrometry (ICP-MS). We used a multivariable regression and Bayesian kernel machine regression (BKMR) to estimate associations of the combined effects and identify important mixture components with growth impairments. Our results revealed Hg, Pb, Cd, and As concentrations in the meconium and enhanced the quantity of research on meconium analyses. The overall effects of Hg, Pb, Cd, and As concentrations in the meconium as prenatal exposure biomarkers were negatively associated with birth growth. Fetal exposure to Hg and Pb was correlated with decreased birth weights. Hg and Pb concentrations in the meconium were linearly inversely related to the birth weight, birth length, and head circumference. Effects of fetal exposure to As and Cd on birth outcomes were not obvious. A significant increasing relationship was detected between Hg concentrations in the meconium and maternal fish consumption during pregnancy. Higher Pb concentrations in the meconium were observed among infants of mothers who consumed Chinese herbal medicines. Reducing maternal fish consumption and Chinese herbal medicine consumption during pregnancy could limit infant exposure to metals.

Early warning model construction and validation for urinary tract infection in patients with neurogenic lower urinary tract dysfunction (NLUTD): a retrospective study.

Background: This study was performed to construct and validate an early risk warning model of urinary tract infection in patients with neurogenic lower urinary tract dysfunction (NLUTD). Methods: Eligible patients with NLUTD admitted to Shenzhen Longcheng hospital from January 2017 to June 2021 were recruited for model construction, internal validation and external validation. The first time point of data collection was within half a month of patients first diagnosed with NLUTD. The second time point was at the 6-month follow-up. The early warning model was constructed by logistic regression. The model prediction effects were validated using the area under the Receiver Operating Characteristic curve, the Boostrap experiment and the calibration plot of the combined data. The model was externally validated using sensitivity, specificity and accuracy. Results: Six predictors were identified in the model, namely patients ≥65 years old (OR = 2.478, 95%CI [1.215- 5.050]), female (OR = 2.552, 95%CI [1.286-5.065]), diabetes (OR = 2.364, 95%CI) [1.182-4.731]), combined with urinary calculi (OR = 2.948, 95%CI [1.387-6.265]), indwelling catheterization (OR = 1.988, 95%CI [1.003 -3.940]) and bladder behavior training intervention time ≥2 weeks (OR = 2.489, 95%CI [1.233-5.022]); and the early warning model formula was Y = 0.907 ×  age+ 0.937 × sex + 0.860 × diabetes +1.081 × combined with urinary calculi+ 0.687 × indwelling catheterization+ 0.912 × bladder behavior training intervention time-2.570. The results show that the area under the ROC curve is 0.832, which is close to that of 1,000 Bootstrap internal validation (0.828). The calibration plot shows that the early warning model has good discrimination ability and consistency. The external validation shows the sensitivity is 62.5%, the specificity is 100%, and the accuracy is 90%. Conclusion: The early warning model for urinary tract infection in patients with NLUTD is suitable for clinical practice, which can provide targeted guidance for the evaluation of urinary tract infection in patients with NLUTD.

Effect of Hydrophobic Treatments on Improving the Salt Frost Resistance of Concrete.

Hydrophobic treatment is an important method to improve the waterproof properties of concrete. To evaluate the effectiveness of hydrophobic treatments on improving the salt frost resistance of concrete, two representative commercial ordinary water repellent agents of silane and organosilicone emulsion were selected, and concrete specimens with three water/cement ratios were fabricated. After the application of repellent agents on concrete surfaces, accelerated saline (5% MgCl2) freeze-thaw cycles were conducted on the specimens. The mass losses and relative dynamic modulus of elasticity (RDME) of concrete were tested periodically. The contact angles and water absorption ratios of concrete with and without hydrophobic treatments were also tested. Results showed that the repellent agents could substantially enhance the hydrophobicity of concrete and greatly reduce its water absorption. Different repellent agents exerted diverse improvements on concrete hydrophobicity. Meanwhile, the repellent agents could improve concrete resistance against salt scaling and RDME losses to a certain degree, and concrete with strong hydrophobicity showed relatively high salt frost resistance. However, the ordinary water repellent agents cannot achieve the same enhancement on salt frost resistance of concrete as that on the water hydrophobicity of concrete. With saline freezing and thawing cycles, the hydrophobic layer formed by the repellent agents on superficial concrete was destroyed gradually. As a result, the salt frost resistance of concrete from the hydrophobic treatments was ultimately lost.

Rational design of a far-red fluorescent probe for endogenous biothiol imbalance induced by hydrogen peroxide in living cells and mice.

Intracellular biothiols are correlated with many diseases such as nerve disorder and Parkinson's disease likely due to a redox imbalance. In this work, we designed an ultrafast fluorescent probe (Cou-DNBS) for biothiols with a large Stokes shift (131 nm). The probe was constructed through linking the 2,4-dinitrobenzenesulfonyl moiety as the specially recognizing biothiols site to an iminocoumarin fluorophore Cou-NH obtained by fusing an additional benzene ring. The presence of biothiols could ultrafast perform a significant fluorescence emission at 617 nm upon the excitation of 480 with the low limits of detection (2.5 nM for Cys, 1.7 nM for Hcy and 0.84 nM for GSH). HRMS spectra as well as theoretical calculations further evidenced the rationale of recognition mechanism. Furthermore, the probe can successfully visualize endogenous biothiol recovery in living cells damaged by H2O2.

A dual-emission fluorescent probe for discriminating cysteine from homocysteine and glutathione in living cells and zebrafish models.

Cellular biothiols function crucially and differently in physiological and pathological processes. However, it is still challenging to detect and discriminate thiols within a single one molecule, especially for cysteine (Cys) and homocysteine (Hcy). In this study, a simple two-emission turn-on fluorescent biothiol probe (ICN-NBD) was rationally designed and synthesized through a facile ether bond linking 7-nitro-1,2,3-benzoxadiazole (NBD) and phenanthroimidazole containing a cyano tail. The probe in the presence of Cys elicited two fluorescence responses at 470 nm and 550 nm under excitation at 365 nm and 480 nm, respectively, because of the concomitant generation of both the fluorophore and NBD-N-Cys. In contrast, addition of Hcy and glutathione (GSH) could result in only a blue fluorescence enhancement at 470 nm. which was reasonably attributed to rearrangement from NBD-S-Hcy/GSH to NBD-N-Hcy/GSH as a result of geometrical constraints or solvent effects. Therefore, the fluorescent probe with the NBD scaffold could detect biothiols and simultaneously discriminate Cys from Hcy/GSH in both blue and green channels. The probe has been successfully applied for visualizing biothiols in living cells and zebrafish.

Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1.

Chronic kidney disease (CKD) is problem that has become one of the major issues affecting public health. Extensive clinical data suggests that the prevalence of hyperlipidemia in CKD patients is significantly higher than in the general population. Lipid metabolism disorders can damage the renal parenchyma and promote the occurrence of cardiovascular disease (CVD). Cyanate is a uremic toxin that has attracted widespread attention in recent years. Usually, 0.8% of the molar concentration of urea is converted into cyanate, while myeloperoxidase (MPO) catalyzes the oxidation of thiocyanate to produce cyanate at the site of inflammation during smoking, inflammation, or exposure to environmental pollution. One of the important physiological functions of cyanate is protein carbonylation, a non-enzymatic post-translational protein modification. Carbamylation reactions on proteins are capable of irreversibly changing protein structure and function, resulting in pathologic molecular and cellular responses. In addition, recent studies have shown that cyanate can directly damage vascular tissue by producing large amounts of reactive oxygen species (ROS). Oxidative stress leads to the disorder of liver lipid metabolism, which is also an important mechanism leading to cirrhosis and liver fibrosis. However, the influence of cyanate on liver has remained unclear. In this research, we explored the effects of cyanate on the oxidative stress injury and abnormal lipid metabolism in mice and HL-7702 cells. In results, cyanate induced hyperlipidemia and oxidative stress by influencing the content of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), catalase (CAT) in liver. Cyanate inhibited NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the phosphorylation of adenosine 5'monophosphate-activated protein kinase (AMPK), activated the mTOR pathway. Oxidative stress on the cells reduced significantly by treating with TBHQ, an antioxidant, which is also an activator of Nrf2. The activity of Nrf2 was rehabilitated and phosphorylation of mTOR decreased. In conclusion, cyanate could induce oxidative stress damage and lipid deposition by inhibiting Nrf2/HO-1 pathway, which was rescued by inhibitor of Nrf2.

Ultra-fast zinc ion detection in living cells and zebrafish by a light-up fluorescent probe.

As the second most abundant transition metal after iron in biological systems, Zn2+ takes part in various fundamental life processes such as cellular metabolism and apoptosis, neurotransmission. Thus, the development of analytical methods for fast detection of Zn2+ in biology and medicine has been attracting much attention but still remains a huge challenge. In this report, we develop a novel Zn2+-specific light-up fluorescent probe based on intramolecular charge transfer combined with chelation enhanced fluorescence induced by structural transformation. Addition of Zn2+ in vitro can induce a remarkable color change from colorless to green and a strong fluorescence enhancement with a red shift of 43 nm. Moreover, the probe shows an extremely low detection limit of 13 nM and ultra-fast response time of less than 1 s. The Zn2+ sensing mechanism was fully supported by TDDFT calculations as well as HRMS and 1H NMR titrations. The recognition of Zn2+ in living Hela cells as well as the MTT assay demonstrate that the probe can rapidly light-up detect Zn2+ in vivo with low cytotoxicity and good cell-permeability. Furthermore, the probe can also be successfully applied to bioimaging Zn2+ in living zebrafish.

A two-separated-emission fluorescent probe for simultaneous discrimination of Cys/Hcy and GSH upon excitation of two different wavelengths.

It is challenging to simultaneously discriminate two or three biothiols from each other due to their structural similarities as well as reactions sites. The development of multiple-signal fluorescent probes would be a promising way to overcome this issue. Herein, a two-separated-emission fluorescent probe for biothiols was developed based on the combination of nitrobenzofurazan (NBD) and phenanthroimidazole fluorophores linked by a facile ether bond. In the presence of Cys and Hcy, the probe in DMF-H2O demonstrates two separate fluorescence emissions at 480 and 550 nm upon excitation of two independent wavelengths. However, addition of GSH to the probe only leads to blue fluorescence at 480 nm. This difference can be reasonably ascribed to the fact that the NBD-GSH intermediate, unlike NBD-Cys/Hcy, cannot undergo an intramolecular cyclization-rearrangement reaction. The probe exhibits a rapid response with low limits of detection (14.7 nM for Cys, 14.4 nM for Hcy, and 13.4 nM for GSH) with large concentration ranges of 0-100 µM for Cys/Hcy and 0-200 µM for GSH. Furthermore, the probe is successfully applied to simultaneously distinguish endogenous Cys, Hcy, and GSH in living HeLa cells and zebrafish models.

A fast-response two-photon fluorescent probe for imaging endogenous H2O2 in living cells and tissues.

As a second messenger, hydrogen peroxide plays significant roles in numerous physiological and pathological processes and is related to various diseases including inflammatory disease, diabetes, neurodegenerative disorders, cardiovascular disease and Alzheimer's disease. Two-photon (TP) fluorescent probes reported for the detection of endogenous H2O2 are rare and most have drawbacks such as slow response and low sensitivity. In this report, we demonstrate a simple H2O2-specific TP fluorescent probe (TX-HP) containing a two-photon dye 6-hydroxy-2,3,4,4a-tetrahydro-1H-xanthen-1-one (TX) on the modulation of the ICT process. The probe exhibits a rapid fluorescent response to H2O2 in 9min with both high sensitivity and selectivity. The probe can detect exogenous H2O2 in living cells. Furthermore, the probe is successfully utilized for imaging H2O2 in liver tissues.

Two Distinctly Separated Emission Colorimetric NIR Fluorescent Probe for Fast Hydrazine Detection in Living Cells and Mice upon Independent Excitations.

Hydrazine is carcinogenic and highly toxic so that it can lead to serious environmental contamination and serious health risks although it has been extensively used as an effective propellant and an important reactive base in industry. Thus, the development of two-emission NIR fluorescent probes for rapid detection of hydrazine with high selectivity and sensitivity is of significance and of great challenge in both biological and environmental sciences. Here, we report a two-emission colorimetric fluorescent probe for the specific detection of hydrazine based on hydrazinolysis reaction under physiological conditions. In the presence of hydrazine, the probe showed an extremely remarkable fluorescence enhancement at 627 nm compared to the decrease at 814 nm excited at different wavelength in aqueous solution. This distinct difference of two emission intensities is suitable for detection of low concentration hydrazine with a detection limit of 0.38 ppb. Addition of hydrazine resulted in a remarkable color change from blue-green to red observed by the naked eye. Kinetic study indicated a fast response of the probe toward hydrazine in minutes. Furthermore, the probe can bioimage hydrazine in living HeLa cells and mice with low cytotoxicity and excellent biocompatibility.

A simple fluorescent probe for sensing cysteine over homocysteine and glutathione based on PET.

A big challenge is the discrimination of sulfhydryl-containing amino acids due to their structural similarity. We designed and synthesized a simple fluorescent probe 3 for specific detection of cysteine based on photo-induced electron transfer (PET). The acrylate and BODIPY moieties in probe 3 act as a reaction site and reporter group, respectively. So the synergistic effect of the substituent groups endows probe 3 very strong green fluorescence at 525nm (λex=500nm). The cleavage reaction induced by cysteine leads to acrylate hydrolysis, and thereby triggers PET on, which effectively quench the fluorescence of 3. Probe 3 exhibited a rapid response towards cysteine over homocysteine and glutathione. Probe 3 is successfully applied for sensing and imaging cysteine in vitro or in vivo cells with low cytotoxicity.