NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer.

BACKGROUND: Metabolic reprogramming plays a key role in cancer progression and clinical outcomes; however, the patterns and primary regulators of metabolic reprogramming in colorectal cancer (CRC) are not well understood. AIM: To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in promoting progression of CRC. METHODS: We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Consensus clustering was used to cluster CRC based on dysregulated metabolic genes. A prediction model was constructed based on survival-related metabolic genes. Sphere formation, migration, invasion, proliferation, apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC. mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells. In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth. RESULTS: We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes. Among these genes, NOX4 was highly expressed in tumor tissues and correlated with worse survival. In vitro, NOX4 overexpression induced clone formation, migration, invasion, and stemness in CRC cells. Furthermore, RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway. Trametinib, a MEK1/2 inhibitor, abolished the NOX4-mediated tumor progression. In vivo, NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis, whereas trametinib treatment can reversed the metastasis. CONCLUSION: Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis, suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.

Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer.

BACKGROUND: The efficacy of neoadjuvant chemotherapy (NAC) in advanced gastric cancer (GC) is still a controversial issue. AIM: To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC. METHODS: The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020. Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors. A nomogram model was employed to predict the response to NAC. RESULTS: In total 230 patients were finally included in this study, including 154 males (67.0%) and 76 females (33.0%). The mean age was (59.37 ± 10.60) years, ranging from 24 years to 80 years. According to the tumor regression grade standard, there were 95 cases in the obvious response group (grade 0 or grade 1) and 135 cases in the poor response group (grade 2 or grade 3). The obvious response rate was 41.3%. Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location (P < 0.001), histological differentiation (P = 0.001), clinical T stage (P = 0.008), and carbohydrate antigen 724 (P = 0.008). The C-index for the prediction nomogram was 0.806. The calibration curve revealed that the predicted value exhibited good agreement with the actual value. Decision curve analysis showed that the nomogram had a good value in clinical application. CONCLUSION: A nomogram combining tumor location, histological differentiation, clinical T stage, and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

The association between outdoor light at night exposure and adult obesity in Northeastern China.

Previous studies have linked exposure to light at night (LAN) with various health outcomes, but evidence is limited for the LAN-obesity association. Thestudy analysed data from 24,845 participants of the 33 Communities Chinese Health Study and obesity (BMI ≥28 kg/m2) was defined according to the Working Group on Obesity in China. The Global Radiance Calibrated Nighttime Lights data were used to estimate participants' LAN exposure. The mixed-effect regression models examined the LAN-BMI and LAN-obesity association. We found that higher LAN exposure was significantly associated with greater BMI and higher risk of obesity. Changes of BMI and the odds ratios (ORs) of obesity and 95% confidence intervals (CIs) for 2nd, 3rd, and 4th against the 1st quartile of LAN exposure were 0.363 (0.208, 0.519), 0.364 (0.211, 0.516) and 0.217 (0.051, 0.383); 1.228 (1.099, 1.371), 1.356 (1.196, 1.538) and 1.269 (1.124, 1.433), respectively. Age and regular exercise showed significant modification effects on the LAN-obesity association.

Fluorescence Enhancement of Adamantane-Modified Dyes in Aqueous Solution via Supramolecular Interaction with Methyl-ß-cyclodextrin and Their Application in Cell Imaging.

The fluorescence of functional dyes was generally quenched in aqueous solution, which hindered their application in water-bearing detections. In this work, a novel strategy based on host-guest interaction was provided for the purpose of fluorescence enhancement in aqueous solution and cell imaging. Three adamantane-modified fluorescent dyes (Coum-Ad, NP-Ad, NR-Ad) with coumarin, 1,8-naphthalimide and Nile Red as fluorophores were initially designed and prepared. The ((adamantan-1-yl)methyl)amino group, as the auxochrome of those dyes, complexed with methylated ß-cyclodextrin (M-ß-CD) via supramolecular interaction, and then fluorescent supramolecular nanoparticles (FSNPs) were formed by self-assembly in water. The inclusion equilibrium constant (K) could be as high as 3.94×104  M-1 . With the addition of M-ß-CD, fluorescence quantum yields of these dyes were separately improved to 69.8 %, 32.9 % and 41.3 %. Inspired by the above satisfactory results, six adamantane-modified probes organelle-NPAds with organelle-targeting capability were further obtained. As the formation of hydrogen bonds between organelle-NPAd2 and M-ß-CD verified by theoretical calculation, K of organelle-NPAd2 (5.13×104  M-1 ~4.53×105  M-1 ) with M-ß-CD was higher than that of organelle-NPAd1 (1.15×104  M-1 ~3.66×104  M-1 ) and their fluorescence quantum yields increased to 32.8 %~83.6 % in aqueous solution. In addition, fluorescence enhancement was realized in cell imaging with the addition of M-ß-CD.

Viscosity probes towards different organelles with red emission based on an identical hemicyanine structure.

A series of viscosity probes targeting different organelles were obtained using a single hemicyanine dye as the matrix structure. Specifically, probes 1a-d were obtained by introducing four amines (6-amino-2H-chromen-2-one, N-(2-aminoethyl)-4-methylbenzenesulfonamide, dodecan-1-amine and N,N diphenylbenzene-1,4-diamine) into the indole hemicyanine dye of the carboxylic acid with a D-π-A structure. Their maximum absorption wavelengths were in the range 570-586 nm and they had relatively large molar absorption coefficients, while their maximum emission wavelengths in the red light region were in the range 596-611 nm. Moreover, their fluorescence intensity in glycerol was 35-184 times higher than that in phosphate buffer solution (PBS). The lg(Fl) and lg η of probes 1a-d showed good linearity with high correlation coefficients according to the Förster-Hoffman equation. In addition, cell staining experiments demonstrated that 1a-c could target lysosomes, endoplasmic reticulum and mitochondria, respectively. They could also undergo viscosity-detectable changes in the corresponding organelles under the action of the corresponding ion carriers.

Multiple organelle-targeted 1,8-naphthyridine derivatives for detecting the polarity of organelles.

Four 1,8-naphthyridine derivatives (1a-1d) with different organelle targeting abilities were obtained using the Knoevenagel condensation reaction of 1,8-naphthyridine with 4-(N,N-diethylamino)benzaldehyde (2a), 4-(N,N-diphenylamino)benzaldehyde (2b), 4-(piperazin-1-yl)benzaldehyde (2c) and 4-(ethyl(4-formylphenyl)amino)-N-(2-((4-methylphenyl)sulfonamido)ethyl)butanamide (2d), respectively. The maximal absorption bands of dyes 1a-1d were observed at 375-447 nm, while their maximum emission peaks were situated at 495-605 nm. The optical properties showed that the fluorescence emission of dyes 1a-1d is shifted toward greater wavelengths as the system polarity (Δf) increased. Meanwhile, with increasing polarity of the mixed 1,4-dioxane/H2O system, the fluorescence intensity of dyes 1a-1d gradually decreased. Furthermore, the fluorescence intensity of 1a-1d enhanced by 12-239 fold as the polarity of 1,4-dioxane/H2O mixtures declined. 1a-1d had a large Stokes shift (up to 229 nm) in polar solvents in comparison to nonpolar solvents. The colocalization imaging experiments demonstrated that dyes 1a-1d (3-10 µM) were located in mitochondria, lipid droplets, lysosomes and the endoplasmic reticulum in living HeLa cells, respectively; and they could monitor the polarity fluctuation of the corresponding organelles. Consequently, this work proposes a molecular design idea with different organelle targeting capabilities based on the same new fluorophore, and this molecular design idea may provide more alternatives for polarity-sensitive fluorescent probes with organelle targeting.

A novel cuproptosis-related signature predicts prognosis and immunotherapy efficacy in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the leading histological subtype of lung cancer worldwide, causing high annual mortality. Tsvetkov et al. recently found a new form of regulated cell death, termed cuproptosis. The prognostic value of cuproptosis-related gene signature in LUAD remains uncertain. METHODS: A training cohort is identified by the TCGA-LUAD dataset, whereas validation cohorts one and two are identified by GSE72094 and GSE68465, respectively. GeneCard and GSEA were used to extract genes related to cuproptosis. Cox regression, Kaplan-Meier regression, and LASSO regression were used to construct a gene signature. The model's applicability was evaluated by Kaplan-Meier estimators, Cox models, ROC, and tAUC across two independent validation cohorts. We examined the model's connections with other forms of regulated cell death. The immunotherapy ability of the signature was demonstrated by applying TMB, immune relevant signatures, and TIDE. The GSEA and immune infiltration analysis offer a better understanding of how the signature functions and the role of immune cells in its prognostic power. RESULTS: A ten-gene signature was built and demonstrated owning prognostic power by being applied to the validation cohorts. The GSEA uncovered that the unfolded protein response, glycolysis/gluconeogenesis, and MYC were highly related to the gene signature. The ten-gene signature is closely related to related genes of apoptosis, necroptosis, pyroptosis, and ferroptosis. Our signature may have utility in predicting immunotherapy efficacy in LUADs. Mast cells were identified as key players that support the predicting capacity of the ten-gene signature through the immune infiltrating analysis. CONCLUSIONS: The novel ten-gene signature associated with apoptosis in cuproptosis that we obtained may contribute to improved LUAD management strategies and the ability to predict response to LUAD immunotherapy. It is suggested that mast cell infiltration might be related to the prognostic power of this signature.

ESIPT-based fluorescent enhanced probes prompted by methylated ß-cyclodextrin for the detection of thiophenols.

Thiophenol and its derivatives are compounds with high toxicity to organisms and environmental pollution, so it is necessary to detect the level of thiophenols in the environment and biological samples. The probes 1a-b were obtained by introducing the 2,4-dinitrophenyl ether group into diethylcoumarin-salicylaldehyde based compounds. And they can form host-guest compounds with methylated ß-cyclodextrin (M-ß-CD), the association constants of inclusion complexes are 49.2 M-1, 125 M-1 respectively. The fluorescence intensities of probes 1a-b at 600 nm (1a) and 670 nm (1b) increased significantly in thiophenols detection. Meanwhile, with the addition of M-ß-CD, the hydrophobic cavity of M-ß-CD significantly increased the fluorescence intensity of probes 1a-b, thus the detection limits of probes 1a-b to thiophenols were reduced from 410 nM, 365 nM to 62 nM, 33 nM respectively. Whereas, the good selectivity and short response time of probes 1a-b towards thiophenols was not affected in the presence of M-ß-CD. Moreover, probes 1a-b were used for further water sample detection and HeLa cell imaging experiments due to their good response to thiophenols and the results suggested that probes 1a-b had the potential to detect the content of thiophenols in water samples and living cells.

Diagnostic value of circular free DNA for colorectal cancer detection.

BACKGROUND: Minimally invasive or noninvasive, sensitive and accurate detection of colorectal cancer (CRC) is urgently needed in clinical practice. AIM: To identify a noninvasive, sensitive and accurate circular free DNA marker detected by digital polymerase chain reaction (dPCR) for the early diagnosis of clinical CRC. METHODS: A total of 195 healthy control (HC) individuals and 101 CRC patients (38 in the early CRC group and 63 in the advanced CRC group) were enrolled to establish the diagnostic model. In addition, 100 HC individuals and 62 patients with CRC (30 early CRC and 32 advanced CRC groups) were included separately to validate the model. CAMK1D was dPCR. Binary logistic regression analysis was used to establish a diagnostic model including CAMK1D and CEA. RESULTS: To differentiate between the 195 HCs and 101 CRC patients (38 early CRC and 63 advanced CRC patients), the common biomarkers CEA and CAMK1D were used alone or in combination to evaluate their diagnostic value. The area under the curves (AUCs) of CEA and CAMK1D were 0.773 (0.711, 0.834) and 0.935 (0.907, 0.964), respectively. When CEA and CAMK1D were analyzed together, the AUC was 0.964 (0.945, 0.982). In differentiating between the HC and early CRC groups, the AUC was 0.978 (0.960, 0.995), and the sensitivity and specificity were 88.90% and 90.80%, respectively. In differentiating between the HC and advanced CRC groups, the AUC was 0.956 (0.930, 0.981), and the sensitivity and specificity were 81.30% and 95.90%, respectively. After building the diagnostic model containing CEA and CAMK1D, the AUC of the CEA and CAMK1D joint model was 0.906 (0.858, 0.954) for the validation group. In differentiating between the HC and early CRC groups, the AUC was 0.909 (0.844, 0.973), and the sensitivity and specificity were 93.00% and 83.30%, respectively. In differentiating between the HC and advanced CRC groups, the AUC was 0.904 (0.849, 0.959), and the sensitivity and specificity were 93.00% and 75.00%, respectively. CONCLUSION: We built a diagnostic model including CEA and CAMK1D for differentiating between HC individuals and CRC patients. Compared with the common biomarker CEA alone, the diagnostic model exhibited significant improvement.

Efficient aerobic denitrification without nitrite accumulation by Pseudomonas mendocina HITSZ-D1 isolated from sewage sludge.

A highly efficient aerobic denitrifying microbe was isolated from sewage sludge by using a denitrifier enrichment strategy based on decreasing carbon content. The microbe was identified as Pseudomonas mendocina HITSZ-D1 (hereafter, D1). Investigation of the conditions under which D1 grew and denitrified revealed that it performed good growth and nitrate removal performance under a wide range of conditions. In particular, D1 rapidly removed all types of inorganic nitrogen without accumulation of the intermediate products nitrite and nitrous oxide. Overall, D1 showed a total nitrogen removal efficiency >96% at a C/N ratio of 8. The biotransformation modes and fates of three typical types of inorganic nitrogen were also assessed. Moreover, D1 had significantly higher denitrification efficiency and enzyme activities than other aerobic denitrifying microbes (Paracoccus denitrificans, Pseudomonas aeruginosa, and Pseudomonas putida). These results suggest that D1 has great potential for treating wastewater containing high concentrations of nitrogen.

Conjugated structures based on quinazolinones and their application in fluorescent labeling.

As an alkaloid, quinazolinone exhibits excellent biological properties; structurally, it also has the potential to construct fluorescent probes with conjugated structures. In this work, probes 5a-c and 6b were obtained by introducing quinazolone into aldehydes with different numbers of double bonds. Their absorption maxima were located at 420-540 nm and their emission maxima were at 500-600 nm in solvents of different polarities. In particular, probe 5c showed significant fluorescence enhancement with the increase in viscosity due to the limited intramolecular rotation, and its fluorescence intensity in glycerol was 37.8 times higher than that in water. Moreover, probes 5a-c and 6b containing the NH structure showed sensitive response to pH, and their fluorescence intensity in alkaline solution (pH 9-11) was suddenly enhanced, which was elucidated with the help of theoretical calculation. In addition, the cell experiments showed that probes 5a and 5b had the ability to target mitochondria and probes 5c and 6b targeted lysosomes in HeLa cells. Furthermore, the viscosity-sensitive probe 5c could be used for monitoring changes in lysosomal viscosity in HeLa cells, which had important guiding significance for designing multi-response fluorogenic probes and promoting the advancement of cancer diagnosis.

Biofilm inhibition based on controlling the transmembrane transport and extracellular accumulation of quorum sensing signals.

The regulation of bacterial quorum sensing (QS) has been used to inhibit biofouling in wastewater treatment plants and the formation of biofilms. In contrast to traditional QS regulation strategies, this study aimed to obstruct the transmembrane transport process of QS signals to decrease their extracellular accumulation. Three phytochemicals, astragaloside IV, eugenol, and baicalin were selected, their effects on biofilm formation by Pseudomonas aeruginosa PA14 were studied, and the mechanisms determined. The inhibition efficiency of biofilm formation by 50 mg/L astragaloside IV, 1 mg/L eugenol, and 1 mg/L baicalin were 37%, 26%, and 26%, respectively. Confocal laser scanning microscopy and analysis of extracellular polymeric substances indicated that the three inhibitors affected the structure and composition of the biofilms. Furthermore, bacterial motility and a variety of QS-related virulence factors were suppressed by the inhibitor treatment due to changes in bacterial QS. Notably, the three inhibitors all decreased the extracellular concentration of the QS signaling molecule 3-oxo-C12-homoseine lactone by affecting the function of efflux pump MexAB-OprM. This indirectly interfered with the bacterial QS system and thus inhibited biofilm formation. In conclusion, this study revealed the inhibitory effects and inhibition mechanism of three phytochemicals on efflux pump and QS of P. aeruginosa and realized the inhibition on biofilm formation. We update the efflux pump inhibitor library and provide a new way for biofilm contamination control.

Methylated Chromenoquinoline as a Novel Nucleus Fluorescent Probe for Nucleic Acid Imaging.

Two chromenoquinoline-based fluorescent probes 1a-b have been synthesized and investigated. Photofading behaviors of compounds 1a-b showed that at least 89% absorption remained after 6 h irradiating, meanwhile, many of ions and amino acids had negligible impacts on their fluorescence intensity, which meant they had excellent photostability and selectivity. Probes 1a-b exhibited strong absorption and emission in organic solvents with large fluorescence quantum yields, even in water probe 1a still had a relatively large fluorescence quantum yield (20%). Combined with DFT calculation, the influence of alkylation on optical properties of 1b was elucidated. In addition, the fluorescence intensity of probe 1b with red emission enhanced by 5.4-fold and 5.3-fold after DNA and RNA added, and the fluorescence quantum yield increased from 3% to 17% and 14%, respectively, but the neutral molecule 1a had no response to nucleic acid. Furthermore, confocal microscopy imaging of probes 1a-b showed that 1a targeted lipid droplets while the methylated probe 1b to nucleus in living HeLa cells. The results indicated that the subcellular targeting zone could be changed by alkylation of nitrogen atom on chromenoquinoline-based conveniently, which provided a new idea for designing and synthesizing new subcellular labeled probes.

Association between long-term ambient ozone exposure and attention-deficit/hyperactivity disorder symptoms among Chinese children.

BACKGROUND: Although ozone exposure has neurological toxicity, it remains unclear whether it was associated with an increased risk of attention-deficit/hyperactivity disorders (ADHD) among childhood. METHODS: We matched the four-year average ozone concentration with questionnaire data for 35,103 children aged 3-12 years from seven cities in Liaoning, China, 2012-2013. Using mixed-effect logistic regression models, we assessed the association of ozone concentration with multiple ADHD indicators using the Conners Abbreviated Symptom Questionnaire (C-ASQ), including explicit attention-deficit/hyperactivity symptoms (ADHD; score ≥15), attention-deficit/hyperactivity disorder tendencies (ADHD-T; 11 ≤ score ≤14), and attention-deficit/hyperactivity problems (ADHP; score ≥11). Results were also stratified by sociodemongraphics. RESULTS: After adjusting for covariates, we found that each interquartile range (IQR) increase in ozone concentration was associated with an increased risk of ADHD, ADHD-T, and ADHP (P < 0.001) with an odds ratio of 1.12 (95% confidence interval, 1.04-1.21), 1.08 (1.03-1.13), and 1.09 (1.05-1.14), respectively. Additionally, we found greater effect estimates in children who reported longer exercise time (vs those with limited exercise time) with odds ratio of 1.18 (1.07-1.31) vs 1.06 (0.96-1.17) for ADHD, 1.13 (1.06-1.21) vs 1.03 (0.96-1.10) for ADHD-T, and 1.15 (1.08-1.21) vs 1.04 (0.98-1.10) for ADHP. Non-breastfed children were also shown to be more vulnerable to ADHD with an odds ratio of 1.22 (1.09-1.36) compared with 1.06 (0.96-1.16) among the rest. CONCLUSIONS: Long-term ozone exposure may be associated with increased ADHD among children. Additional studies are needed to validate our findings and support policies and interventions to address this growing public health concern.

Exposure to ambient particulate matter and hyperuricemia: An eight-year prospective cohort study on male traffic officers in China.

BACKGROUND AND OBJECTIVES: Studies on the effects of airborne particulates of diameter ≤ 1 µm (PM1), airborne particulates of diameter ≤ 2.5 µm (PM2.5) and airborne particulates of diameter ranges from 1 to 2.5 µm (PM1-2.5) on incidence of hyperuricemia are limited. We aimed to investigate the associations between PM1, PM2.5, and PM1-2.5 and hyperuricemia among male traffic officers. METHODS: We conducted a prospective cohort study of 1460 traffic officers without hyperuricemia in Guangzhou, China from 2009 to 2016. Exposures of PM1 and PM2.5 were estimated with a spatiotemporal model. PM1-2.5 concentrations were calculated by subtracting PM1 from PM2.5 concentrations. Cox's proportional hazards regressions models were used to examine the association between PM1, PM2.5, and PM1-2.5 and hyperuricemia, adjusted for potential confounders. Associations between PM1, PM2.5, and PM1-2.5 and serum uric acid (SUA) levels were evaluated with multiple linear regression models. RESULTS: Hazard ratios (HRs) and 95% confidence intervals (CIs) of hyperuricemia associated with 10 µg/m3 increment in PM1, PM2.5, and PM1-2.5 were 1.67 (95% CI:1.30-2.36), 1.49 (95% CI: 1.27-1.75), and 2.18 (95% CI: 1.58-3.02), respectively. The SUA concentrations increased by 12.23 µmol/L (95% CI: 5.91-18.56), 6.93 µmol/L (95% CI: 3.02-10.84), and 8.72 µmol/L (95% CI: 0.76-16.68) per 10 µg/m3 increase in PM1, PM2.5, and PM1-2.5, respectively. Stratified analyses indicated the positive associations of PM2.5 and PM1-2.5 with SUA levels were stronger in non-smokers, and PM1, PM2.5, and PM1-2.5 with SUA levels were stronger in non-drinkers. CONCLUSION: Long-term PM1, PM2.5, and PM1-2.5 exposures may increase the risk of hyperuricemia and elevate SUA levels among male traffic officers, especially in non-smokers and non-drinkers.

Prospective association of family members' sugar-sweetened beverages intake with children's sugar-sweetened beverages consumption in China.

PURPOSE: We aimed to investigate whether parental and siblings' sugar-sweetened beverage (SSB) intake had prospective impact on children's SSB consumption, and the potential sex difference in these associations. METHODS: This study included a total of 904 children and their parents enrolled from 2004 to 2011 China Health and Nutrition Survey (CHNS) cohort study. SSB consumption information was estimated using a short dietary questionnaire and total energy intake was assessed with three-day 24-h dietary assessments at recruitment and follow-up surveys. Multivariate logistic or linear regression analyses were used to assess the association for SSB consumption between parents, siblings and children after adjusting for age, body mass index (BMI) z-score, household income and parental educational level. RESULTS: In this study, a majority (87.6%) of children consumed SSB. Among them, the median consumption of SSB was 70.3 ml/day per capita and 205.4 ml/day per consumer. Parental SSB consumption was relevant to children's SSB consumption, and this association was more pronounced in boys than in girls. Meanwhile, fathers seemed to have a stronger impact on whether children consume SSB than mothers which was reflected by lower P and higher OR. Additionally, children's SSB intake was prospectively associated with their older siblings' SSB consumption (P for trend < 0.03). CONCLUSIONS: Parental and older siblings' SSB consumption was relevant to children's SSB intake. Particularly, boys were more susceptible to parental impact than girls, and fathers seemed to have a greater influence on children than mothers.

Fluorescent probes based on acridine derivatives and their application in dynamic monitoring of cell polarity variation.

Polarity and viscosity, as important microenvironment parameters, play an essential role in cell metabolism. Therefore, 9-acridine carboxaldehyde reacted with cyano compounds to obtain polarity-sensitive probes 1a-b and viscosity-sensitive probes 1c-d. Among them, with the increase in solvent polarity, the maximum emission wavelength of acridine-dicyanoisophorone-based probe 1a red-shifted from 553 nm to 594 nm, the fluorescence quantum yield increased from 0.5% to 35.6%, and the fluorescence intensity enhanced 38 fold. The acridine-cyanofuranone based probe 1b also has a polarity response similar to 1a. Nevertheless, when the solution viscosity increased from 0.89 cP (100% water) to 856 cP (1% water), the fluorescence intensity of the acridine-tricyanodihydrofuran based probe 1c at 430 nm enhanced 5.6 times. The acridine-cyanobenzothiazole based probe 1d also had a viscosity response similar to 1c. In addition, probes 1a-b were used for further HeLa cell imaging experiments due to their good photostability and the results suggested that probe 1a could locate lipid droplets and probes 1b-c could stain lysosomes. Moreover, probes 1a-b could dynamically monitor the changes in intracellular polarity.

Distinguishing cancer cells from normal cells with an organelle-targeted fluorescent marker.

In this paper we report a hemicyanine dye that is used to distinguish cancer cells from normal cells with its ability to target different organelles. Probe 1, a red emission hemicyanine functional dye, was connected to oxazolo[4,5-b]pyridine and diethylaminobenzene with a double bond. The maximum absorption peaks of probe 1 were located in the 509-552 nm range in organic solvents. Meanwhile, the probe possessed a high molar extinction coefficient (5.50 × 104 M-1 cm-1 in DMSO) with high photostability. The maximum emission wavelength of the probe ranged from 572 nm to 644 nm, and it also had a large Stokes shift (126 nm in DMSO). In particular, the probe showed weak fluorescence in water (Φ = 0.016), whereas it displayed strong fluorescence at 595 nm in ß-cyclodextrin (ß-CD) solution (Φ = 0.13). In addition, cell colocalization experiments showed that probe 1 (3 µM) was located in the endoplasmic reticulum in cancer cells, while it could target lysosomes in normal cells. What's more, further cell imaging experiments demonstrated that the average fluorescence intensity of probe 1 (0.3 µM) in cancer cells increased with the addition of ß-CD, but it did not occur in normal cells. The study provides a convenient way to distinguish cancer cells from normal ones, which has potential for application in the early detection of cancer.

Preparation of Chromeno[b]quinoline Derivatives and Their Application for Lipid Droplets Markers.

Functional dyes with a chromeno[b]quinoline skeleton (3a-d) were synthesized by one-step cyclization between coumarin derivatives and aromatic amines under the promotion of anhydrous aluminum chloride in 41.2-45.8% yields. Their maximum absorption and emission wavelengths locate at 358-396 and 420-603 nm with large Stokes shifts (168-231 nm), and their intramolecular charge transfer has been corroborated by density functional theory calculations. Cell experiments have proved that the probes 3a-c possess the ability to target lipid droplets.

Near-infrared fluorescent probes based on a quinoxaline skeleton for imaging nucleic acids in mitochondria.

In this paper, two cationic probes 1a and 1b and a neutral dye 1c were successfully designed and synthesized according to the Knoevenagel condensation reaction, which combines the good optical properties of hemocyanine and the biocompatibility of nitrogen-containing heterocyclic rings based on a quinoxaline skeleton. Probes 1a and 1b showed an OFF-ON fluorescence response to nucleic acids with excellent selectivity. Specifically, the fluorescence intensity of probe 1a was enhanced by 18 and 133 times, respectively, along with the increase of DNA or RNA concentrations (0-600 µg mL-1). Furthermore, a good linear correlation between the fluorescence intensity of probes 1a and 1b and the concentrations of DNA or RNA (0-350 µg mL-1) was obtained. In particular, the maximum emission wavelengths of probes 1a and 1b reached the near-infrared region (660-664 nm) when DNA or RNA was detected, which might reduce the light damage to cells and facilitate cell experiments. Fluorescence imaging revealed that all three dyes could be localized in the mitochondria of HeLa cells. The difference was that probes 1a and 1b could stain the nucleic acid in the mitochondria, while dye 1c was only a neutral mitochondrial biomarker. The results indicated that probes 1a and 1b are promising in the development of low toxicity mitochondrial nucleic acid probes and are expected to be used in monitoring the normal state of mitochondrial nucleic acids for living cells, which will help improve the situation in that currently reported studies of fluorescent probes are mainly focused on the nucleic acids in the nucleus, but less so on DNA in the mitochondria.