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.

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.

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.

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.

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.

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.

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.

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.

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.

Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro.

BACKGROUND: The accumulation of single nucleotide variants (SNVs) and the emergence of neoantigens can affect tumour proliferation and the immune microenvironment. However, the SNV-related immune microenvironment characteristics and key genes involved in hepatocellular carcinoma (HCC) are still unclear. We aimed to evaluate differences in the SNV-related immune microenvironment, construct a prognostic model and validate the key genes in vitro. METHODS: The categories of samples were defined by the expression of SNV score-related genes to evaluate the differences in mutational features, immune environment and prognosis. The survival model was constructed with survival-associated genes and verified in two independent test datasets. RCAN2, the key gene screened out for biofunction, was validated in vitro. RESULTS: IC2, among the three integrated clusters (IC1, IC2, IC3) classified by the 82 SNV score-related genes, was distinct from the rest in SNV score and immune cell infiltration, showing a better prognosis. Seven prognostic markers, HTRA3, GGT5, RCAN2, LGALS3, CXCL1, CLEC3B, and CTHRC1, were screened to construct a prognostic model. The survival model distinguished high-risk patients with poor prognoses in three independent datasets (log-rank P < 0.0001, 0.011, and 0.0068, respectively) with acceptable sensitivity and specificity. RCAN2 was inversely correlated with NK cell infiltration, and knockdown of RCAN2 promoted proliferation in HCC. CONCLUSIONS: This study revealed the characteristics of the HCC SNV-associated subgroup and screened seven latent markers for their accuracy of prognosis. Additionally, RCAN2 was preliminarily proven to influence proliferation in HCC and it had a close relationship with NK cell infiltration in vitro. With the capability to predict HCC outcomes, the model constructed with seven key differentially expressed genes offers new insights into individual therapy.

Design and synthesis of a series of OFF-ON near infrared fluorescent probes for nucleic acid in aqueous solution.

Five cyanine dyes (6a-e) with aza units were prepared by the reaction of pyridinum or quinolinium with suitable aldehydes. They present several remarkable features including large Stokes shift (235-282 nm), long emission wavelength (640-698 nm) and excellent selectivity. Moreover, probes 6a-b display obvious and sensitive fluorescent response to DNA and RNA in aqueous solution, and the quantum yield of probe 6a response to RNA increases from 0 to 8.9%. More importantly, probes 6c and 6e can effectively avoid DNA interference and only respond to RNA in aqueous solution. In addition, laser confocal cell experiment has showed that probe 6b can image the nucleolus of nucleic acids in HeLa cells.

Series of Mitochondria/Lysosomes Self-Targetable Near-Infrared Hemicyanine Dyes for Viscosity Detection.

Six mitochondria/lysosomes self-targetable and viscosity-sensitive dyes (1a-1f) were developed via simple structure modification on cyanine-derived dyes. They all showed remarkable OFF-ON fluorescent response to viscosity in the near-infrared region (652-690 nm) and exhibited good linear relationship with solution viscosity. The transient absorption spectra were used to evaluate the excited-state lifetime of dye 1a in different viscosity environments. Furthermore, cellular imaging assays indicated that different derivatives (1a-1f) with the same chromophore core exhibited different organelle-targeting abilities. Among them, dyes 1a-1c could sense lysosomal viscosity fluctuations while dyes 1d-1f could be applied in mitochondrial viscosity detections.

The fluorescent markers based on oxazolopyridine unit for imaging organelles.

Bioactive oxazolopyridine unit was used in the synthesis of fluorescent markers for specific organelles in this paper. The compounds 1a-c are linked with double bond between oxazolopyridine ring and photogenic precursors (3a-c). Compound 1a showed higher fluorescence yield (0.86 in THF), compounds 1b-c showed larger stokes shifts in DMSO. In lipid vesicles environment, they also showed good optical properties. In addition, the three compounds are biomarkers with lower cytotoxicity. Among them, compound 1a based on oxazolopyridine and coumarin unit is a dual targetable fluorescent marker for mitochondria and lipid droplets; while the other two compounds 1b-c are only biomarkers for lipid droplets.

Tetradecanuclear and Octadecanuclear Gold(I) Sulfido Clusters: Synthesis, Structures, and Luminescent Selective Tracking of Lysosomes in Living Cells.

Reactions of the phosphanyl-gold(I) precursor [(AuCl)2(bdppmapy)] (1; bdppmapy = N,N-bis(diphenylphosphanylmethyl)-2-aminopyridine) with Na2S in a 1:1 or 1:2 molar ratio gave rise to one tetradecanuclear and one octanuclear Au(I) sulfido cluster, [Au14S6(bdppmapy)5]Cl2 (2) and [Au18S8(bdppmapy)6]Cl2 (3), respectively. The former displays a new structural framework in gold cluster chemistry. Compounds 2 and 3 showed strong green luminescence and were employed as excellent imaging probes to selectively light up the lysosomes of living cells. Their long-term tracking of lysosomes can be achieved for up to 36 h, while tracking with commercial Lyso-Tracker Red under the same conditions was limited to 3 h. Our work demonstrated the possibility of constructing novel gold(I) sulfido clusters supported by special P-N hybrid ligands and the potential application of these clusters as long-term selective trackers of lysosomes in bioimaging.

Rosamine with pyronine-pyridinium skeleton: unique mitochondrial targetable structure for fluorescent probes.

Two rosamine-based probes (1a-b) with pyronine-pyridinium skeleton were designed and prepared. Probe 1a bearing boron ester unit was oxidized and eliminated upon addition of hydrogen peroxide (H2O2), and the emission spectrum exhibited OFF-ON response accompanied by 33-fold fluorescent enhancement. In contrast, the fluorescence intensity of probe 1b enhanced 58 times after the dinitrophenyl ether part within the probe was removed by nucleophilic substitution with hydrosulfide (H2S). The design concept was based on the d-PET process in pyronine-pyridinium structures, and free 4-pyridinyl-substituted pyronine dye showing strong fluorescence was released followed by elimination. Furthermore, as biocompatible molecules, probes 1a-b have been successfully applied for imaging in live HeLa and Ges-1 cells, and all of them can serve as mitochondrial targetable probes in red channel for detecting independent species.

The improvement of lysosome targetability with oligoethyleneoxy chains linked benzo[a]phenoxazine.

In order to improve lysosome targetability of probes, fluorescent probes based on benzo[a]phenoxazine attaching different length oligoethyleneoxy chains were designed and prepared. Probes 2a-c containing N-pyridineium-3-yl exhibited almost ON-OFF near-infrared emission responses at 697-701 nm from pH 2.8 to 7.2, and the calculated pKa values of 2a-c were 4.90, 4.92 and 5.03 respectively. More importantly, fluorescent imaging experiments indicated that probes 2a-c were all lysosome biomarkers for Ges-1 and HeLa cells, which was because the introduction of oligoethyleneoxy groups improved the biocompatibility of probes, so that the probes 2a-c were better transported to lysosomes via the endocytosis pathway of the cells. Moreover, the probe 2a was selected as a representative, which not only showed good reversibility and selectivity, but used to successfully image lysosomal pH increases induced by chloroquine.

The fluorescent biomarkers for lipid droplets with quinolone-coumarin unit.

Two quinolone-coumarin skeleton derivatives (1a, 1b) have been prepared by Friedländer synthesis with 2-aminoaryl ketone and 3-acetyl-7-diethylaminocoumarin. The dyes showed excellent photo stability. Their optical properties in five organic solvents have been measured, and the wavelength range of the maximum fluorescence emission peaks was from 469 nm to 509 nm. Besides, both of them exhibited high fluorescence quantum yields (0.79-0.96) in these organic solvents. The pH influenced optical properties tests indicated dyes 1a-b have strong fluorescence in sub acid (pH = 6.0) to alkaline environment (pH = 9.0). Their fluorescence quantum yields in neutral aqueous solution (pH = 7.0) were 0.82 (1a) and 0.78 (1b) respectively. In addition, dyes 1a-b exhibited stable fluorescence intensity in the presence of some metal cations and biomolecules in neutral solution (pH = 7.0). Subsequently, confocal microscopy imaging indicated that dyes 1a-b could be used as biomarkers for lipid droplets in living and fixed cells (I929 and HeLa cells).