[Application of precision-cut lung slice technology to study the role of DDR2 in pulmonary fibrosis].

Pulmonary fibrosis is a severe lung interstitial disease characterized by the destruction of lung tissue structure, excessive activation and proliferation of fibroblasts, secretion and accumulation of a large amount of extracellular matrix (ECM), and impaired lung function. Due to the complexity of the disease, a suitable animal model to mimic human pulmonary fibrosis has not yet been established. Precision-cut lung slice (PCLS) has been a widely used in vitro method to study lung physiology and pathogenesis in recent years. This method is an in vitro culture technology at the level between organs and cells, because it can preserve the lung tissue structure and various types of airway cells in the lung tissue, simulate the in vivo lung environment, and conduct the observation of various interactions between cells and ECM. Therefore, PCLS can compensate for the limitations of other models such as cell culture. In order to explore the role of discoidin domain receptor 2 (DDR2) in pulmonary fibrosis, Ddr2flox/flox mice were successfully constructed. The Cre-LoxP system and PCLS technology were used to verify the deletion or knockdown of DDR2 in mouse PCLS. Transforming growth factor ß1 (TGF-ß1) can induce fibrosis of mouse PCLS in vitro, which can simulate the in vivo environment of pulmonary fibrosis. In the DDR2 knock down-PCLS in vitro model, the expression of various fibrosis-related factors induced by TGF-ß1 was significantly reduced, suggesting that knocking down DDR2 can inhibit the formation of pulmonary fibrosis. The results provide a new perspective for the clinical study of DDR2 as a therapeutic target in pulmonary fibrosis.

Epidemiological trends and sociodemographic factors associated with acute hemorrhagic conjunctivitis in mainland China from 2004 to 2018.

BACKGROUND: Acute hemorrhagic conjunctivitis (AHC) is classified as a class C notifiable infectious disease in China and poses a great threat to public health. This study aimed to investigate the epidemiological trends and hotspots of AHC in mainland China. Sociodemographic factors that could contribute to early warning of AHC were further explored. METHODS: Yearly and monthly incidences of acute hemorrhagic conjunctivitis by date and region from 2004 to 2018 were extracted from the Data Center of China Public Health Science. Joinpoint regression and spatial autocorrelation analysis were performed to explore the epidemiological trends and hotspots of AHC. A generalized linear model was then applied to explore the relationship between sociodemographic factors and AHC incidence. RESULTS: The average annual AHC incidence was 3.58/100,000 in mainland China. The first-level spatial and temporal aggregation areas were distributed in Guangxi, Hainan, Guangdong, Guizhou, Hunan, Jiangxi, Fujian, Chongqing, Hubei, Anhui, and Zhejiang, with gathering times from 2010/1/1 to 2010/12/31 (RR = 20.13, LLR = 474,522.89, P < 0.01). After 2010, the AHC incidence was stable (APC = - 8.37, 95% CI: - 23.02-9.06). However, it was significantly increased in low- and middle-income provinces (AAPC = 10.65, 95% CI: 0.62-21.68, AAPC = 11.94, 95% CI: 0.62-24.53). The peak of AHC occurred during the August to October period. Children who age 0-3 years are identified as high-risk group with AHC incidence significantly increased (APC = 31.54, 95% CI: 0.27-72.56). Birth rate, population ages 0-14 (% of total population), passenger traffic, and urban population (% of total population) were positively associated with the AHC incidence, while per capita gross domestic product was negatively associated with the AHC incidence. CONCLUSION: Overall, the AHC incidence was stable after 2010 in China, but it was significantly increased in low- and middle-income provinces. Regions with a high birth rate, population ages 0-14 (% of the total population), passenger traffic, urban population (% of the total population) and low per capita gross domestic product are at high risk of incidences of AHC. In the future, public health policy and resource priority for AHC in regions with these characteristics are necessary.

Simultaneous determination of 44 pharmaceutically active compounds in water samples using solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry.

This study examines an improved and simplified method for solid-phase extraction (SPE), which offers rapid and accurate determination and identification of 44 pharmaceutically active compounds using ultra-performance liquid chromatography (UPLC) and tandem mass spectrometry (MS/MS). The common active compounds include four macrolides, seventeen sulfonamides, four quinolones, chloramphenicol, eight ß-lactams, four tetracyclines, lincomycin, amantadine, 4-acetamidophenol, phenylbutazone, trimethoprim, clenbuterol, and hydrocortisone in water samples. We optimized crucial parameters of MS/MS, UPLC, and SPE and studied the matrix effect related to the modified analytical process from water samples. The matrix-matched calibration curves were accomplished at seven concentration levels and a satisfactory linear relationship (r2 > 0.994) was observed within the range of 0.1-500 ng/mL. Results show varying limits of detection (0.0111-0.966 ng/L for different analytes based on signal-to-noise (S/N) = 3) and limits of quantitation (0.0382-3.26 ng/L). Recoveries of the spiked samples ranged from 75.7 to 108% with relative standard deviation lower than 9.6%. The proposed method was successfully applied to the analysis of real samples.

Determination of a broad spectrum of endocrine-disrupting pesticides in fish samples by UHPLC-MS/MS using the pass-through cleanup approach.

We describe a new methodology for the simultaneous determination of the endocrine-disrupting herbicides (acetochlor, alachlor, amitrole, and atrazine), fungicides (carbendazim, triadimefon, penconazole, and propiconazole), and insecticides (carbaryl and carbofuran) in fish samples followed by high-performance liquid chromatography with tandem mass spectrometry. Samples were extracted and purified using the pass-through cleanup approach. The recoveries of the pesticides were in the range 71.8-116.5%, with relative standard deviations lower than 15.28%. Limits of quantitation were in the range of 0.03-2.50 µg/kg. Validation results on linearity, accuracy, and precision, as well as on application to the analysis of the endocrine-disrupting pesticides in 20 fish samples, demonstrated the applicability to screen the presence of pesticides in fish.

Comparison of extraction solvents and sorbents in the quick, easy, cheap, effective, rugged, and safe method for the determination of pesticide multiresidue in fruits by ultra high performance liquid chromatography with tandem mass spectrometry.

An improved analytical method was developed for the simultaneous quantification of several plant growth regulators and fungicides (carbendazim, pyrimethanil, metalaxyl, triadimefon, paclobutrazol, thiophanate, prochloraz, dimethomorph, difenoconazole, (4-chlorophenoxy)-acetic acid, (2,4-dichlorophenoxy)-acetic acid, thiadiazuron, forchlorfenuron and gibberellins) in fruits followed by ultra high performance liquid chromatography with tandem mass spectrometry. Samples were extracted and purified using a modified QuEChERS method. Different extraction solvents and sorbents in the QuEChERS method were compared. Optimum results were followed by the addition of 1% acetic acid in acetonitrile; C18 sorbent was added due to the acidic nature of several pesticides. The recoveries of the pesticides were in the range 73.7-118.4%, with relative standard deviations lower than 16.63%. Limits of detection ranged from 0.1-1.0 µg/kg. The method presented here is simple, rapid, sensitive and can be applied to large-scale monitoring programs to screen the presences of pesticides in fruits.

Rapid determination of quinolones in cosmetic products by ultra high performance liquid chromatography with tandem mass spectrometry.

This study developed an improved analytical method for the simultaneous quantification of 13 quinolones in cosmetics by ultra high performance liquid chromatography combined with ESI triple quadrupole MS/MS under the multiple reaction monitoring mode. The analytes were extracted and purified by using an SPE cartridge. The limits of quantification ranged from 0.03 to 3.02 µg/kg. The precision for determining the quinolones was <19.39%. The proposed method was successfully developed for the determination of quinolones in real cosmetic samples.

Simultaneous determination of 20 phthalate esters in oil-free food by UPLC/MS/MS.

A quantitative method was established for the determination of 20 phthalate esters (PAEs) in oil-free food by ultra-performance LC/MS/MS and was used to evaluate the PAEs of 111 oil-free samples from supermarkets in Hangzhou City. By quantification with the internal standard D4-bis(2-ethylexyl) phthalate, linearity ranges of the 20 PAEs were observed with correlation coefficients of 0.9990-0.9999. For liquid and solid sample, the spiking recoveries were 65.5-129.9% with RSD of 2.7-9.7% and 70.9-126.9% with RSD of 1.6-9.8% (n = 6), and the method LODs were 0.05-7.4 microg/L and 0.6-14.4 microg/kg, respectively. Most of the 111 oil-free samples had detectable PAEs; the detection rate was 23.0-42.0%, and the concentration of PAEs was in the range of 1.0-38 610.9 microg/kg. The detection rate in the drink packaged in a glass bottle was the highest, next was laver, and the detection rate in the drink packaged in a plastic bottle was the lowest.

Therapeutic effects of fatty acid binding protein 1 in mice with pulmonary fibrosis by regulating alveolar epithelial regeneration.

INTRODUCTION: Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease with limited therapeutic options and high lethality, related to alveolar type II epithelial (ATII) cell dysregulation, the abnormal repair of alveolar epithelial cells and activation of fibroblasts promote the development of pulmonary fibrosis. Fatty acid binding protein 1 (FABP1) was significantly downregulated in the fibrotic state by proteomics screening in our previous date, and the ATII cell dysregulation can be mediated by FABP1 via regulating fatty acid metabolism and intracellular transport. The aim of this study was to evaluate the role and potential mechanism of FABP1 in the development of pulmonary fibrosis. METHODS: Proteomics screening was used to detect changes of the protein profiles in two different types (induced by bleomycin and silica, respectively) of pulmonary fibrosis models. The localisation of FABP1 in mouse lung was detected by Immunofluorescence and immunohistochemistry. Experimental methods such as lung pathology, micro-CT, western blotting, small animal imaging in vivo, EdU, etc were used to verify the role of FABP1 in pulmonary fibrosis. RESULTS: The expression of FABP1 in the mouse lung was significantly reduced in the model of pulmonary fibrosis from our proteomic analysis and immunological methods, the double immunofluorescence staining showed that FABP1 was mainly localised in type II alveolar epithelial cells. Additionally, the expression of FABP1 was negatively correlated with the progression of pulmonary fibrosis. Further in vivo and in vitro experiments showed that overexpression of FABP1 alleviated pulmonary fibrosis by protecting alveolar epithelium from injury and promoting cell survival. CONCLUSION: Our findings provide a proof-of-principle that FABP1 may represent an effective treatment for pulmonary fibrosis by regulating alveolar epithelial regeneration, which may be associated with the fatty acid metabolism in ATII cells.

Associations between Temperature and Influenza Activity: A National Time Series Study in China.

Previous studies have reported that temperature is the main meteorological factor associated with influenza activity. This study used generalized additive models (GAMs) to explore the relationship between temperature and influenza activity in China. From the national perspective, the average temperature (AT) had an approximately negative linear correlation with the incidence of influenza, as well as a positive rate of influenza H1N1 virus (A/H1N1). Every degree that the monthly AT rose, the influenza cases decreased by 2.49% (95%CI: 1.24%-3.72%). The risk of influenza cases reached a peak at -5.35 °C with RRs of 2.14 (95%CI: 1.38-3.33) and the monthly AT in the range of -5.35 °C to 18.31 °C had significant effects on the incidence of influenza. Every degree that the weekly AT rose, the positive rate of A/H1N1 decreased by 5.28% (95%CI: 0.35%-9.96%). The risk of A/H1N1 reached a peak at -3.14 °C with RRs of 4.88 (95%CI: 1.01-23.75) and the weekly AT in the range of -3.14 °C to 17.25 °C had significant effects on the incidence of influenza. Our study found that AT is negatively associated with influenza activity, especially for A/H1N1. These findings indicate that temperature could be integrated into the current influenza surveillance system to develop early warning systems to better predict and prepare for the risks of influenza.

Development of a Multiresidue Method for Endocrine-Disrupting Pesticides by Solid Phase Extraction and Determination by UHPLC-MS/MS from Drinking Water Samples.

A rapid and efficient method based on solid phase extraction and liquid chromatography-tandem mass spectrometry was validated, allowing the determination of the endocrine-disrupting herbicides (acetochlor, alachlor, amitrole and atrazine), fungicides (carbendazim, triadimefon, penconazole and propiconazole), and insecticides (carbaryl and carbofuran) in drinking water. Low method detection limits (0.01-0.64 ng/L) and method quantification limits (0.03-2.13 ng/L) were obtained with satisfactory recoveries and precision for the endocrine-disrupting pesticides. The method was applied for real drinking water samples collected in the area of the city of Hangzhou (Zhejiang, China); the results showed that carbendazim, atrazine and acetochlor were detected in the drinking water samples and acetochlor was the most detected analyte.

Determination of Sterigmatocystin in Infant Cereals from Hangzhou, China.

A simple method was developed for the determination of sterigmatocystin in infant cereals. The method consists of a quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction approach and cleanup with an SPE HLB cartridge. After purification for separation and quantification of sterigmatocystin, HPLC with UV detection and diode-array detection (DAD) was used at sterigmatocystin levels >10 µg/kg, whereas ultra-performance LC with electrospray ionization (ESI) and tandem MS (MS/MS) was used at levels <10 µg/kg. The compound was determined by UV-DAD at 325 nm and by ESI-MS/MS in the positive ionization mode. Good r(2) values (≥0.99) were found with both UV-DAD and ESI-MS/MS, and satisfactory recoveries (84.8-96.2%) of sterigmatocystin in infant cereals were demonstrated, with RSD values ≤11.43%. The developed analytical method was used for the determination of sterigmatocystin in infant cereals from Hangzhou, China.

Disruption of zebrafish (Danio rerio) sexual development after full life-cycle exposure to environmental levels of triadimefon.

In this study, zebrafish was exposed to environmental levels of triadimefon (0.125, 0.25, 0.5 µg/mL) from 24 h post fertilization to 120 days post fertilization. Several endpoints that related to reproductive function were evaluated. It was found that the body length, body weight and vitellogenin transcription were significantly reduced for fish exposed to triadimefon. Histological examination showed that the sex ratio of fish skewed to male and female exposed to 0.5 µg/mL triadimefon had immature ovary. The breeding success, as determined from data on egg production and spawning, was reduced in fish exposed to 0.25 µg/mL triadimefon. In the offspring, the reduced egg fertility, hatching rate and survival were observed in eggs exposed to 0.5 µg/mL triadimefon. These findings indicated that triadimefon had the potential to adversely affect the sexual development and breeding success through the multiple endocrine actions.