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The relations of polycyclic aromatic hydrocarbons (PAHs) exposure with platelet indices remain unclear. Based on the baseline data from the Wuhan-Zhuhai Cohort Study, we used generalized linear model, multivariate logistic regression analysis and restricted cubic splines (RCS) to assess linear and nonlinear relationship of PAHs exposure with platelet indices. The results showed that among Wuhan individuals, there were the non-linear relations between total hydroxynaphthalene (ΣOHNa) and mean platelet volume (MPV) or ratio of mean platelet volume to platelet count (MPVP), total hydrophenanthrene (ΣOHPh) and MPV or platelet distribution width (PDW), the sum concentration of urinary monohydroxylated metabolites of PAHs (ΣOH-PAHs) and ratio of platelet count to lymphocyte count (PLR) or MPVP, 1-hydropyrene (1-OHP) and PLR or PDW. But among Zhuhai individuals, neither linear nor non-linear relations were found between each of OH-PAHs or ΣOH-PAHs and platelet indices. The findings indicate that serum MPV and MPVP may be independent biomarkers of effects of exposing to environmental PAHs on human bodies.

Diabetes mellitus (DM) has recently become one of the major diseases that have received attention. Cordycepin (molecular formula: C

Quantitative PCR (qPCR) assay using TaqMan™ probe was widely used in the detection of different nucleic acids. However, this technology has several drawbacks, including false negative results caused by primer-dimer (PD) and false positive issues due to primer-probe aggregations. Here, we designed a modified TaqMan™-Molecular Beacon probe by adding an antisense base and a new type of primer pair named central-homo primer pairs bearing 5-10 bases homologous sequence on the 3' end. Using the HBV qPCR assay as a proof of concept, the new design significantly improved the accuracy of the TaqMan™ qPCR assay for HBV detection. Application of the central-homo primer pair led to significantly delayed Ct values by 5-10 cycles compared with conventional primer design. The modified probe containing an antisense base did not produce any detectable signal in repeating primer-probe aggregation experiments. Furthermore, the use of the central-homo primer pair and the non-competitive internal control could solve the false negative problem caused by PD formation. We validated this customized duplex qPCR system using 208 clinical samples collected from patients in clinic showing accuracy was higher than that of the conventional qPCR method.

Exposure to Polycyclic aromatic hydrocarbons (PAHs) has been associated with inflammatory responses. Fractional exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) are both important inflammatory mediators especially in airways. However, few studies have investigated associations of PAH exposures with FeNO or eCO. Therefore, we aimed to quantify the associations of urinary PAH metabolites with FeNO and eCO levels, and investigate their potential effect modifiers by linear mixed models among 4133 participants from the Wuhan-Zhuhai cohort in China. We further performed stratified analyses to estimate effect modification. We found significant associations of increased urinary PAH metabolites with elevated eCO and FeNO. Among all participants, each 1% increase of 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 3-hydroxyphenanthrene, and total PAH metabolites was significantly associated with a 12.6% (95% confidence interval: 9.3%, 15.9%), 9.7% (6.5%, 12.9%), 7.5% (4.1%, 10.9%), 3.2% (0.2%, 6.2%), 2.7% (0.1%, 5.3%), and 6.5% (2.7%, 10.4%) increased eCO level, respectively; while each 1% increase of urinary 1-hydroxynaphthalene, 9-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 2-hydroxyphenanthrene was associated with a -3.0% (-5.8%, -0.2%), 2.9% (0.3%, 5.6%), 3.2% (1.0%, 5.4%), and 4.5% (2.2%, 6.9%) change of FeNO level, respectively. Positive associations between certain urinary PAH metabolites and eCO were observed among both ever-smokers and non-smokers, and the associations were stronger among ever-smokers than that among non-smokers. Increased urinary PAH metabolites were associated with decreased FeNO among ever-smokers and elevated FeNO levels among non-smokers. Our findings suggest that PAH exposures may impair airway through inducing inflammatory response, especially among ever-smokers.

Background Inflammation may play an important role in the association between exposure to polycyclic aromatic hydrocarbons (PAHs) and atherosclerotic cardiovascular disease (ASCVD) risk. However, the underlying mechanisms remain unclear. Objectives To investigate the association of PAHs exposure with ASCVD risk and effects of mean platelet volume (MPV) or Club cell secretory protein (CC16) on the association. Methods A total of 2022 subjects (689 men and 1333 women) were drawn from the baseline Wuhan residents of the Wuhan-Zhuhai Cohort study. Data on demography and the physical examination were obtained from each participant. Urinary monohydroxy PAH metabolites (OH-PAHs) levels were measured by a gas chromatography-mass spectrometry. We estimated the association between each OH-PAHs and the 10-year ASCVD risk or coronary heart disease (CHD) risk using logistic regression models, and further analyze the mediating effect of MPV or plasma CC16 on the association by using structural equation modeling. Results The results of multiple logistic regression models showed that some OH-PAHs were positively associated with ASCVD risk but not CHD risk, including 2-hydroxyfluoren (β = 1.761; 95% CI: 1.194–2.597), 9-hydroxyfluoren (β = 1.470; 95% CI: 1.139–1.898), 1-hydroxyphenanthrene (β = 1.480; 95% CI: 1.008–2.175) and ΣOH-PAHs levels (β = 1.699; 95% CI: 1.151–2.507). The analysis of structural equation modeling shows that increased MPV and increased plasma CC16 levels contributed 13.6% and 15.1%, respectively, to the association between PAHs exposure and the 10-year ASCVD risk (p Conclusions Exposure to PAHs may increase the risk of atherosclerosis, which was partially mediated by MPV or CC16.

Association of exposure to polycyclic aromatic hydrocarbons (PAHs) with increased urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation has been reported in occupational population and children. However, studies on the association between them in general population are limited. A total of 1864 eligible subjects from the baseline Wuhan participants of the Wuhan-Zhuhai Cohort Study (n = 3053) were included in this study, after excluding individuals with certain disease and missing data on urinary monohydroxy PAHs (OH-PAHs) and 8-OHdG levels. Urinary monohydroxy PAHs and 8-OHdG levels were measured by gas chromatography-mass spectrometry and high performance liquid chromatography-electrochemical detection, respectively. Association of urinary OH-PAHs with urinary 8-OHdG was analyzed by multiple linear regression analysis. We found a dose-dependent relationship between urinary PAHs metabolites and urinary 8-OHdG (p 0.05 for all). Furthermore, more evidence for the association of total concentrations of urinary OH-PAHs with 8-OHdG levels were observed in individuals with normal body mass index or central obesity (p 0.01 for all). There was a dose-dependent relationship between urinary OH-PAHs levels and urinary 8-OHdG levels among a general Chinese population. Exposure to background PAHs may have a greater influence on urinary 8-OHdG levels in individuals with central obesity.

Neurensin-2 (NRSN2) is a 24KD protein, which is reported located in the membrane, while its biological functions remain unknown, not to mention in the field of tumor biology. In current study, we aimed to analyze the functions of NRSN2 in ovarian cancer. We screened TCGA database and surprisingly found that its copy number and mRNA level are gained and heightened respectively in parts of serous ovarian cancer patients. In current study, both loss- and gain- function assays found that NRSN2 is associated with the malignant phenotype in ovarian cancer cells, because NRSN2 plays a remarkable role in anchorage-independent colony formation, subcutaneous tumor formation, cell invasion, and chemoresistance. Furthermore, we found that the level of NRSN2 was positively correlated with the expression of stem cell marker CD133. In addition, Wnt canonical signaling and Twist/Akt/Erk axis were also regulated by NRSN2. In conclusion, we found that a poorly studied protein, NRSN2, which is associated with the malignant phenotype of serous ovarian cancer and as a membrane protein; it could be a target for serous ovarian cancer treatment.

Lung function is related to socioeconomic status (SES) and exposure to polycyclic aromatic hydrocarbons (PAHs). However, joint effect of SES and exposure to PAHs on lung function has been largely unknown. We aimed to investigate joint effects of SES and urinary OH-PAHs levels on lung function parameters. This study included 2739 Wuhan participants from the baseline survey of the Wuhan-Zhuhai (WHZH) Cohort Study (n=3053). They completed the questionnaire, physical examination and provided blood and urine samples. Twelve urinary monohydroxy-PAHs metabolites (OH-PAHs) and lung function were measured by gas chromatography-mass spectrometry and digital spirometers, respectively. Individuals with low educational levels and low or high levels of urinary ΣOH-PAHs had a 3.5% (95% CI: -5.4, -1.6%) or 4.2% (95% CI: -6.1, -2.3%) reduction in the ratio of forced expiratory volume in 1s to forced vital capacity (FEV1/FVC), respectively, and those with middle levels of education and high levels of urinary ΣOH-PAHs had a 2.1% (95% CI: -5.4, -1.6%) reduction in the FEV1/FVC ratio, rather than those with high levels of education and low levels of urinary ΣOH-PAHs. Individuals with low levels of education had a -3.0% (95% CI: -4.4, -1.6%) reduction in FEV1/FVC compared with individuals with high levels of education. Urinary OH-PAHs levels were marginally negatively related to FEV1 in all participants (p=0.073). The results indicated that there was a prominent effect of low levels of education and higher exposure to PAHs on lung function decline, indicating that it is a necessary to take measures to promote the education level and reduce exposure to environmental PAHs.

Background The high prevalence of hepatitis C virus (HCV) infection and the resulting burden of the disease are significant issues to public health worldwide. Although direct-acting antiviral drugs (DAAs) with good tolerance and bioavailability are available, resistance-associated substitutions (RASs) often jeopardize the successful sustainment of virological responses in HCV treatment. High-frequency baseline RASs in treatment-naive patients can lead to failures in DAA treatment. Clinical data on HCV RASs in patients from China are limited and require investigations. Methods 262 HCV RNA positive plasma from Chinese blood donors were genotyped and amplified with subtype-specific primers for NS3 and NS5A regions. RASs were analyzed using Geno2pheno. The codon usage of each resistance-associated substitution was calculated for genetic barrier analysis. Results The two main subtypes in mainland China were 1b and 2a, followed by subtype 6a, 3b, 3a, and 1a. In NS3 region of 1b subtype, substitutions (T54S, V55A, Y56F, Q80 K/L, S122 G/T, R117 H/C, V170I and S174A) were present in 89.7% (96/107) of the samples. Other RASs (M28L, R30Q, P58 L/S and Y93H) were observed in 22.1% (25/113) of the samples in NS5A region. A crucial RAS, Q80K, and two other mutations (S122G + V170I) was identified in the same sequence, which reduced its susceptibility to protease inhibitor ASV and resulted in resistance to SMV. In NS5A, Y93H was detected in 9.7% (11/113) of the 1b samples, leading to medium-to-high level resistance to all six commercialized NS5A inhibitors. S122G-NS3 and Y93H-NS5A occurred simultaneously in 38.1% (7/22) of the samples with mutations in both two regions. Moreover, codon usage of S122G-NS3 and Y93H-NS5A revealed that both variants had the lowest genetic barrier and required only one transition to confer resistance. Conclusions Low genetic barriers facilitated the generation of resistance mutants and threated the efficacy of DAA regimens. The baseline RASs posed a great challenge to real-world DAA application.

Properties of gelatin composite films（with 4% glycerol as plasticizer）with different mass concentrations of microfibrillated cellulose (MFC) (0.2-1.0%) were investigated. The prepared composite films with 1.0 % MFC showed the highest tensile strength (12.32 MPa) with the lowest water absorption rate (391.1 %). The composite films can be dissolved in hot water of 95°C in less than 5 minutes. However, the addition of MFC had insignificant effect on the heat shrinkage and light transmittance of the resultant composite films.

Stellera chamaejasme ，widely distributed on the Qinghai-Tibet Plateau， is a poisonous plant causing serious harm to grassland. Activated carbons have been prepared from the roots of Stellera chamaejasme via phosphoric acid and zinc chloride activation at500 °C for 60 min with an impregnation ratio of 3:1. Yield (25.1% -27.6%), ash (4.5%-4.9%), methylene blue ( 195.0 mg/g-254.5 mg/g), iodine value (720.4 mg/g- 810.5 mg/g), specific surface area (1023.3 m 2 /g-1216.7 m 2 /g), specific pore volume (2.13 cm 3 /g-2.26 cm 3 /g), mesopore volume (1.30 cm 3 /g-1.59 cm 3 /g) and average pore size (5.88nm-7.45 nm) of the products were determined. The results from both the zinc chloride and phosphoric acid activation processes showed that the activated carbons of S. chamaejasme roots exhibit a characterization of natural developed mesopores.

Cellulosic pulps were prepared from Achnatherum inebrians straw using soda, soda anthraquinone (soda-AQ), and Kraft pulping processes. The main chemical compositions in A. inebrians straw are 70.5% holocellulose, 41.6% alpha-cellulose, and 18.2% lignin, similar to those in other non-wood materials. The conditions of a liquid/solid ratio of 4.5:1, a time-to-maximum temperature of 100 min, a maximum temperature of 165 °C and a time-at-maximum temperature of 40 min were used in all pulping processes. The results showed that the pulp yield was 35.12–37.01%, the kappa number was 13.23–17.67, drainage index was 19–21 °SR and the viscosity of pulps was 846–898 mL/g. Tear index, tensile index, burst index and brightness of the paper were 5.27–5.83 mN m2/g, 16.58–18.11 mN/g, 1.76–2.37 kPa m2/g and 40.7–43.1% ISO respectively. It is indicated that A. inebrians straw can be used as an alternative raw material for pulping.

The incidence of diabetes is increasing rapidly in Chinese population, and it has been postulated that environmental factors may play a role in the etiology of diabetes. Therefore, we aimed to investigate the association between PAHs exposure and risk of diabetes in a community-based population of 2824 participants with completed questionnaires, measurements of biochemical indices, and urinary PAHs metabolites. We found that elevated urinary PAHs metabolites were associated, in a dose-dependent manner, with increased risk of diabetes. Particularly, these associations were more evident in subjects who were female, less than 55 years old, nonsmokers, and normal weight. In addition, there was a modest improvement in diabetes discrimination of prediction models when incorporating certain PAHs metabolites into conventional risk factors (CRF). Overall, our data suggested that there may be a dose-dependent relationship between PAHs metabolites and risk of diabetes among general Chinese population.

High expression of Aurora kinase A (Aurora-A) has been found to confer cancer cell radio- and chemoresistance, however, the underlying mechanism is unclear. In this study, by using Aurora-A cDNA/shRNA or the specific inhibitor VX680, we show that Aurora-A upregulates cell proliferation, cell cycle progression, and anchorage-independent growth to enhance cell resistance to cisplatin and X-ray irradiation through dysregulation of DNA damage repair networks. Mechanistic studies showed that Aurora-A promoted the expression of ATM/Chk2, but suppressed the expression of BRCA1/2, ATR/Chk1, p53, pp53 (Ser15), H2AX, γH2AX (Ser319), and RAD51. Aurora-A inhibited the focus formation of γH2AX in response to ionizing irradiation. Treatment of cells overexpressing Aurora-A and ATM/Chk2 with the ATM specific inhibitor KU-55933 increased the cell sensitivity to cisplatin and irradiation through increasing the phosphorylation of p53 at Ser15 and inhibiting the expression of Chk2, γH2AX (Ser319), and RAD51. Further study revealed that BRCA1/2 counteracted the function of Aurora-A to suppress the expression of ATM/Chk2, but to activate the expression of ATR/Chk1, pp53, γH2AX, and RAD51, leading to the enhanced cell sensitivity to irradiation and cisplatin, which was also supported by the results from animal assays. Thus, our data provide strong evidences that Aurora-A and BRCA1/2 inversely control the sensitivity of cancer cells to radio- and chemotherapy through the ATM/Chk2-mediated DNA repair networks, indicating that the DNA repair molecules including ATM/Chk2 may be considered for the targeted therapy against cancers with overexpression of Aurora-A.

Background Ageing is related to the risk of many diseases and is affected by genetic, epigenetic, and environmental factors. Exposure to the ubiquitous pollutant polycyclic aromatic hydrocarbons (PAHs) is known to cause health damage, but the relation between such exposure with methylation ageing has not been studied. We undertook an association analysis of exposure to PAHs and DNA methylation ageing, a novel and promising ageing marker. Methods We built a model of methylation age and defined two ageing indicators (ageing rate, calculated as ratio of methylation to chronological age; and Δage, calculated as methylation minus chronological age) on the basis of genome-wide methylation data of blood in five panels of Chinese individuals (N=596). Participants included 137 coke oven workers (aged 26–60 years) who were chronically and occupationally exposed to high levels of PAHs; 101 patients with acute coronary syndrome (aged 40–86 years) from Wuhan, China; 97 patients with this syndrome (aged 38–83 years) from Guangdong, China; 162 healthy individuals (aged 26–79 years) from Wuhan; and 99 healthy individuals (aged 37–80 years) from Zhuhai, China. Exposure to individual PAHs was assessed by ten urinary PAH metabolites. We examined the relations between PAH exposure and the two ageing indicators, and investigated the potential CpGs mediating the association. Written informed consent was obtained from all participants. Our study was approved by the ethics committee of Tongji Medical College, Wuhan, China. No study subjects were from clinical trials. Findings Coke oven workers, who were exposed to high levels of PAHs at work (mean nature-log-transformed total urinary PAHs −1·909 [SD 0·461]), had significant age acceleration (2·7% increase in ageing rate [p=0·002] and 1·218-year increase in Δage [p=0·01] compared with all other panels). Urinary 3-OH-phenanthrene and 9-OH-phenanthrene were independently and significantly associated with the two ageing indicators in our non-disease panels. One unit increase of nature-log-transformed 9-OH-phenanthrene was associated with a 1·8% increase (p=0·0029) in ageing rate and a 1·1-year increase (p=0·0002) in Δage, whereas for 3-OH-phenanthrene the increase was 1·3% (p=0·0050) for ageing rate and 0·57 year (p=0·0109) for Δage. Methylation at several ageing-related and PAH-related CpGs (annotated on ELOVL2 , KLHL35 , FHL2 , BOK , PDP1 , and OTUD7A ) was reported to mediate the effect of PAH exposure on methylation ageing. Interpretation Our study revealed a significant association between PAH exposure and accelerated methylation ageing. The importance of exposure-related ageing needs to be further investigated. Funding National Key Basic Research and Development Program, Natural National Scientific Foundation, the 111 Project, the Program for Changjiang Scholars, and Innovative Research Team Scholars.