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Purification of antibodies has become a critical factor in antibody production. A high-purity specific antibody against antigens, especially small molecules, seems to be difficult to obtain, even with the help of a protein A affinity column, which is a conventional and broadly used ligand for the separation of antibody and non-antibody proteins. Therefore, it is urgent to develop a cheap, simple, efficient, and stable method to separate the specific antibody from other antibodies. In this study, to improve the sensitivity and accuracy of immunoassay results, enrofloxacin (ENR) was grafted onto polyethylenimine (PEI) by the abundant amino groups and then the whole ligand (ENR-PEI) was conjugated to CNBr-Sepharose 4B to prepare the affinity column for the purification of the specific antibody against ENR from polyclonal antibodies. Scanning electron microscopy and Fourier transform infrared spectroscopy verification showed that Sepharose 4B was successfully modified by ENR-PEI with excellent uniformity. The capacity of the prepared column could reach to 6.15 mg of specific antibody with high purity per milliliter resin due to the high coupling ratio (49.3:1) of ENR on PEI, and the IC50 value of the antibody after purification was 47.58 ng/mL with a lowest limit of detection (IC10) of 1.099 ng/mL-18 times lower than those of the antibody purified through the protein A column. All the results showed that this new kind of resin could be used as the potential ligand in the purification of the trace-specific antibody against antigens in complex mixtures with high efficiency and specificity.

Background Obesity is reported to be associated with oxidative stress which can cause lipid peroxidation. However, the effects of gain in various weight-related anthropometric indices on lipid peroxidation remain unclear. We aimed to examine the cross-sectional and longitudinal associations between altered weight-related anthropometric indices and a marker of lipid peroxidation among urban adults in China. Methods A total of 3762 participants from the Wuhan-Zhuhai cohort were included in the present study, with a follow-up of 3 years. Six weight-related anthropometric indicators were measured and calculated, including waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), and body adiposity index (BAI). Individual urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) was determined via enzyme-linked immunosorbent assay to evaluate lipid peroxidation. We used generalized linear models to analyze the cross-sectional and longitudinal associations of weight-related anthropometric indices with a marker of lipid peroxidation and stratified analyses to estimate effect modification. Results We found significant relationships between WHR, WHtR, ABSI, and urinary 8-iso-PGF2α at baseline. Each 1% increase in WHR, WHtR, and ABSI was significantly associated with a 0.007, 0.004, and 0.104 increase in log-transformed 8-iso-PGF2α concentration, respectively (P

Background Cancer-associated fibroblasts (CAFs) are an essential component of tumor microenvironment. They are attracting increasing attentions due to their crucial role in tumor growth, drug-resistance and metastasis. Cisplatin is a first-line chemotherapy drug applying in various types of cancer. There are intensive studies on cisplatin's effect on tumor cells, however, its effect on CAFs remains poorly understood. In the present study, we investigated the effect of cisplatin on CAFs. Methods Cell migration was detected by wound healing assay. Cell invasion was performed by the transwell assay. mRNA expression was detected by quantitative PCR, and protein expression was detected by Western blotting. Tumor growth was measured using BALB/c nude mice tumor models. Results Cisplatin attenuated the promoting capacity of CAFs on lung cancer cell migration and invasion, via suppressing CAFs' effect on metastasis-related genes including Twist1, vascular endothelial growth factor receptor (VEGFR), MMP2, and AKT signaling pathway. Keratin 8 (KRT8) was identified as a target of cisplatin. KRT8 upregulation in CAFs is responsible for the inhibitory effect of cisplatin on lung cancer cells metastasis potential through AKT pathway suppression. The stimulation of AKT by AKT activator SC79 reversed KRT8's effect on cell migration. Importantly, in vivo study also showed that CAFs enhanced tumor growth significantly, and cisplatin effectively abrogated the promoting effect of CAFs on tumor growth. Conclusion Our results revealed a novel mechanism that cisplatin attenuated the metastasis promoting effect of CAFs via KRT8/AKT signaling pathway. This finding highlights KRT8 in CAFs as a potential therapeutic candidate for metastasis treatment.

BACKGROUND There is now increasing demand for the immunoassay of procymidone residue in foodstuffs. However, the matrix interference could significantly affect the analysis. Till now there is no detailed information on the source of the interference and the mechanism involved, which greatly limits the real application of these techniques. RESULTS Significant matrix effect was observed in the ELISA of procymidone in negative vegetable samples (leek, broccoli and cucumber). By the investigation with both vegetable extracts and standard solutions, the chlorophyll was confirmed as an important source of the matrix effect. Therefore, a new strategy was proposed for the pretreatment based on the exploitation of 5-sulfosalicylic acid. It was demonstrated to effectively eliminate chlorophyll and exhibited little affluence on procymidone and the competitive indirect ELISA (ci-ELISA) performance. The established technique was validated with different vegetables. With the spiking concentration of procymidone investigated, the recovery rate of ci-ELISA was 71.52% ~ 120.37%, and the relative standard deviation was 4.05% ~ 17.61%. CONCLUSION The chlorophyll was for the first time illuminated as an important source of matrix interference to the immunoassay of procymidone in vegetables. A new pretreatment based on 5-sulfosalicylic acid was established to remove chlorophyll and therefore eliminate the matrix effect. Validated with different vegetable samples, the new technique was demonstrated much better efficiency in comparison to conventional methods, which indicated its promising application for the development of immunoassays of herb-origin samples. This article is protected by copyright. All rights reserved.

Purpose: This study aimed to determine the longitudinal association between hand grip strength (HGS) and the development of non-alcoholic fatty liver disease (NAFLD) in adults.Design: A cohort study.Methods: This study was conducted in a general Chinese population (n = 14,154) from 2013–2018. NAFLD was diagnosed by liver ultrasonography during evaluating alcohol consumption. The associations between the HGS and NAFLD were assessed using a multivariable Cox proportional hazards regression model.Results: During the study period with a mean follow-up duration of 3.20 years, 2,452 participants developed NAFLD. The risk of NAFLD decreased progressively with increasing HGS in both men and women (P for trend CI) for NAFLD incidence across the quartiles of HGS were 1 (reference), 0.90 (0.79, 1.02), 0.69 (0.60, 0.79), and 0.44 (0.37, 0.52) for men and 1 (reference), 0.82 (0.69, 0.96), 0.54 (0.45, 0.66), and 0.41 (0.33, 0.52) for women, respectively. The interaction terms for body mass index (BMI)-HGS and waist-HGS were significant in men and women (all P < 0.0001). The participants with normal BMIs and waist circumferences had the lowest hazard ratios on the subgroup analyses. The sensitivity analysis that defined NAFLD using the hepatic steatosis and fatty liver indices revealed results that were similar to the main analyses.Conclusion: The present study indicates that the HGS is inversely associated with the incidence of NAFLD.

Tumor progression requires the communication between tumor cells and tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are major components of stromal cells. CAFs contribute to metastasis process through direct or indirect interaction with tumor cells; however, the underlying mechanism is largely unknown. Here, we reported that autophagy was upregulated in lung cancer-associated CAFs compared to normal fibroblasts (NFs), and autophagy was responsible for the promoting effect of CAFs on non-small cell lung cancer (NSCLC) cell migration and invasion. Inhibition of CAFs autophagy attenuated their regulation on epithelial–mesenchymal transition (EMT) and metastasis-related genes of NSCLC cells. High mobility group box 1 (HMGB1) secreted by CAFs mediated CAFs’ effect on lung cancer cell invasion, demonstrated by using recombinant HMGB1, HMGB1 neutralizing antibody, and HMGB1 inhibitor glycyrrhizin (GA). Importantly, the autophagy blockade of CAFs revealed that HMGB1 release was dependent on autophagy. We also found HMGB1 was responsible, at least in part, for autophagy activation of CAFs, suggesting CAFs remain active through an autocrine HMGB1 loop. Further study demonstrated that HMGB1 facilitated lung cancer cell invasion by activating the NFκB pathway. In a mouse xenograft model, the autophagy specific inhibitor chloroquine abolished the stimulating effect of CAFs on tumor growth. These results elucidated an oncogenic function for secretory autophagy in lung cancer-associated CAFs that promotes metastasis potential, and suggested HMGB1 as a novel therapeutic target.

Background Previous studies reported that obesity indices were inversely associated with lung function. However, the underlying mechanisms remain unclear. We aimed to assess the potential mediating effect of systemic inflammation in the associations between obesity indices and lung function decline among a general population. Methods We conducted a cross-sectional study among 3442 participants from the Wuhan-Zhuhai cohort. Plasma C-reactive protein (CRP) was assayed as a marker of systemic inflammation. The relationships among several obesity indices (body mass index, BMI; waist circumference, WC; waist-to-hip ratio, WHR; waist-to-height ratio, WHtR), plasma CRP and lung function were assessed by generalized linear models. The role of CRP in the associations between obesity indices and lung function was analyzed using mediation analysis. Results We observed inverse associations between abdominal obesity indices (WC, WHR and WHtR) and lung function parameters, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) (all P

Background With the rapid development of the socioeconomic status, the mortality of several cancers has been changed in China during the past 30 years. We aimed to estimate the trends of mortality and years of life lost (YLLs) of various cancers in urban and rural areas of China from 1990 to 2017. Methods The mortality data were collected from Chinese yearbooks and the age structure of population from the Chinese sixth population census were used as reference to calculate age‐standardized mortality rates (ASMRs) and YLLs rates. Joinpoint regression analysis was implemented to calculate the annual percent change (APC) of mortality rates and YLL rates for cancers. YLLs owing to premature death were calculated as age‐specific cancer deaths multiplied by the reference life expectancy at birth of 80 years for male and 82.5 years for female. Results The ASMRs of all cancers showed significant decreasing trends for urban residents from 1990 to 2017, such downward trend without significance was also observed among rural residents. Interestingly, ASMRs of lung cancer and breast cancer have raised continuously in rural areas since 1990. The age‐standardized YYL rates for urban and rural residents decreased with 1.02% and 0.85% per year, respectively. YLLs in rural areas were higher than those in urban areas, whereas YLLs of urban outstripped those of rural finally with the increasing in YLLs of urban areas (216.71% for men and 207.87% for women). Conclusion The ASMRs and YLL rates of all cancers have declined in urban and rural areas from 1990 to 2017. YLLs increased in urban areas and remained higher level in rural areas after 2014 year. Preventive measures should be strengthened to against cancer, especially for lung cancer., Mortality rate and YLL rate of cancer were analyzed by joinpoint regression. The ASMRs of cancer in both urban and rural areas in China declined from 1990 to 2017. YLLs increased in urban areas and remained higher levels in rural areas from 1990 to 2017.

Detection of pathogenic bacteria by polymerase chain reaction (PCR) is progressively emerging, although it is still hindered by a complex matrix, long-term bacterial enrichment and low bacterial abundance. Here, we report a novel material based on boronate affinity for recognition and enrichment of bacteria using a pre-PCR method. After optimization, the material exhibited high boronate affinity toward bacteria, with adsorption capacities of S. aureus and Salmonella spp. incubated in 0.01 M PBS (pH 7.4) at 37 °C for 15 min calculated as (906.60 ± 15.73) × 107 cfu/g and (582.59 ± 13.19) × 107 cfu/g, respectively, without any bacterial death during the binding process. The material was then applied to enrich S. aureus and Salmonella spp. from the spiked water and 25% cow milk samples followed by mPCR, which resulted in high bacterial enrichment and demonstrated great potential for selective enrichment of bacteria in food samples.

Background Central obesity and polycyclic aromatic hydrocarbons (PAHs) exposure were reported as independent risk factors for lung function decline. However, the interaction between central obesity and PAHs exposure on lung function is still unclear. Objectives To evaluate the impact of central obesity, urinary polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and their combined effects on lung function in general population. Methods Lung function and urinary OH-PAHs were measured for 3,749 participants from the Wuhan-Zhuhai cohort. Central obesity was evaluated by waist-to-hip ratio. Generalized linear regression was used to estimate combined effect of central obesity and OH-PAHs on lung function. Results Compared with participants without central obesity and with low urinary total OH-PAHs (∑OH-PAHs) level, those with central obesity and high urinary ∑OH-PAHs level had 59.4 mL and 61.0 mL reductions for forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1), respectively (P Conclusion Polycyclic aromatic hydrocarbons exposure has combined effect with central obesity on lung function parameters.

Background Heavy metals were related to increased risk of atherosclerotic cardiovascular disease (ASCVD). However, potential mechanisms under such associations remain unclear. We aimed to investigate the mediating role of mean platelet volume in the associations between heavy metals exposure and 10-year ASCVD risk. Method Urinary heavy metals and mean platelet volume were measured in 3081 adults from the Wuhan-Zhuhai cohort in China. The associations between urinary heavy metals, mean platelet volume and 10-year ASCVD risk were separately analyzed through generalized linear models and logistic regression models. Mediation analyses were conducted to assess the role of mean platelet volume in the associations between urinary heavy metals and 10-year ASCVD risk. Results After adjusting for potential confounders, 10-year ASCVD risk was positively associated with urinary iron (odds ratio (OR) = 1.142, 95% confidence interval (1.038–1.256)), copper (OR = 1.384 (1.197–1.601)), zinc (OR = 1.520 (1.296–1.783)), cadmium (OR = 1.153 (0.990, 1.342)) and antimony (OR = 1.452 (1.237–1.704)), and negatively related with urinary barium (OR = 0.905 (0.831–0.985)). Also, we found significant dose–response relationships between urinary iron, zinc, antimony and mean platelet volume, as well as between mean platelet volume and 10-year ASCVD risk (all pfor trends Conclusions Elevated concentrations of urinary iron, copper, zinc, cadmium and antimony were associated with increased risk of 10-year ASCVD. Mean platelet volume partially mediated the associations of urinary iron, zinc and antimony with 10-year ASCVD risk.

Lung cancer is one of the most prevalent cancers in China, and its incidence and morbidity remain high due to various independent factors. Lung adenocarcinoma (ADC) is the most common type of non-small cell lung carcinoma. Circular RNA plasmacytoma variant translocation 1 (circ-PVT1) plays an oncogenic role in various types of cancer, but the specific role of circ-PVT1 in lung ADC has not yet been reported. In the present study, circ-PVT1 was knocked down in A549 cells and the cell viability, proliferation, migration and invasion were measured via MTT, colony formation, wound healing and Transwell assays, respectively. Then, the cell viability of A549 cells with circ-PVT1-knockdown or -overexpression was detected after exposure to cisplatin (DDP). After confirming the associations among circ-PVT1, microRNA (miR)-429 and forkhead box k1 (FOXK1) using various tools and assays, the cellular functions of A549 cells treated with combined short hairpin (sh)RNA-circ-PVT1 and miR-429 inhibitor/pcDNA3.1-FOXK1 were tested again. The expression of circ-PVT1 was found to be increased in lung ADC cells, and shRNA-circ-PVT1 led to decreased cell viability, proliferation, migration and invasion. The expression of circ-PVT1 was higher in A549/DDP cells than that in A549 cells, and the activity of caspase-3 was also activated by DDP in A549/DDP cells transfected with shRNA-circ-PVT1, whereas it was inactivated by DDP in A549 cells transfected with circ-PVT1 overexpression plasmid. Furthermore, the decreased cell viability, proliferation, invasion and migration induced by shRNA-circ-PVT1 could be abated by transfection with miR-429 inhibitor and pcDNA3.1-FOXK1. In conclusion, interference of circ-PVT1 inhibits the progression of lung ADC and enhances its sensitivity to DDP via miR-429/FOXK1, which may provide a theoretical basis for the use of novel targets in the treatment of lung ADC.

Background Previous studies have suggested that ambient air pollution negatively affects frailty, but whether indoor air pollution exposure affects frailty is unknown. Method This study was conducted on 4946 older adults (≥60 years) followed from baseline to 4 years in the Chinese Longitudinal Healthy Longevity Survey. Household fuel types and frailty were assessed with self-rated questionnaires and physical examination. The relationships between indoor air pollution and frailty via phenotypic frailty and a frailty index were explored with logistic regression models and Cox proportional hazard regression models in both a cross-sectional and follow-up design. Additionally, the effects of indoor air pollution on phenotypic frailty together with mild cognitive impairment (MCI) were further investigated. Results In the cross-sectional study, the adjusted ORs (95% CIs) for frailty assessment with the frailty index and phenotypic frailty were 1.28 (1.12, 1.46) and 1.36 (1.18, 1.57), respectively. Solid fuel use was a risk factor in prefrail/frail patients with [OR and 95% CI, 1.88 (1.41, 2.50)], or without MCI [OR and 95% CI, 1.37 (1.17, 1.61)], as compared with the groups with no phenotypic prefrailty/frailty and no MCI. Moreover, solid cooking fuel use was positively associated with the incidence of phenotypic prefrailty and frailty. The adjusted HRs (95% CIs) for phenotypic prefrailty and frailty were 1.26 (1.03, 1.55). Conclusions Solid cooking fuels can be regarded as a risk factor for frailty. Moreover, our findings suggest that more attention should be paid to solid cooking fuel using as it relates to phenotypic frailty together with MCI.

Background Physical limitation, which has been linked to outdoor air pollution exposure in previous studies, is a risk factor for disability and even for premature death. Although people often spend more time indoors, the relationship between indoor air pollution and physical function has not been fully explored. Methods The associations of household fuel types with self-reported and performance-based physical functioning were tested on a total of 12,458 participants in the China Health and Retirement Longitudinal Study (CHARL), using generalized linear models and logistic regression models. Additionally, subgroup analyses according to smoking status and number of chronic diseases, were performed regarding these associations. Results Our results revealed that after adjusting for potential confounds, solid fuel use in cooking showed −0.08 (−0.13, −0.04) and −0.15 (−0.23, −0.06) declines in self-reported and performance-based physical functioning scores (higher scores means fewer physical limitations), when compared with cleaner groups, respectively. Considering these outcomes as binary variables, the ORs (95% CIs) for abnormal self-reported and performance-based physical functioning in the solid fuel cooking group were 1.226 (1.053–1.427) and 1.194 (1.072–1.330), respectively. No significant association between heating fuel use and physical functioning was observed. Additionally, no modification effect of smoking status and the number of chronic diseases on the association between cooking fuel use and performance-based physical functioning was observed (P > 0.05). Conclusion Our findings suggested that solid cooking fuel use may be associated with self-reported and performance-based physical functioning decline of middle-aged and elder Chinese populations.

Rapid detection of pathogenic bacteria particularly in food samples demands efficient separation and enrichment strategies. Here, hydrophilic temperature-responsive boronate affinity magnetic nanocomposites were established for selective enrichment of bacteria. The thermo-responsive polymer brushes were developed by surface-initiated atom transfer radical polymerization of N-isopropylacrylamide (NIPAm) and allyl glycidyl ether (AGE), followed by a reaction of epoxy groups, and incorporation of fluorophenylboronic acid. The physical and chemical characteristics of the magnetic nanocomposites were analyzed systematically. After optimization, S. aureus and Salmonella spp. showed high binding capacities of 32.14 × 106 CFU/mg and 50.98 × 106 CFU/mg in 0.01 M PBS (pH 7.4) without bacteria death. Bacterial bindings can be controlled by altering temperature and the application of competing monosaccharides. The nanocomposite was then utilized to enrich S. aureus and Salmonella spp. from the spiked tap water, 25% milk, and turbot extraction samples followed by multiplex polymerase chain reaction (mPCR), which resulted in high bacteria enrichment, and demonstrated great potential in separation of bacteria from food samples.

Background: To date, few studies have focused on the influence of indoor air pollution on cognitive impairment. Thus, we aimed to explore the association of household fuel use, the major cause of household air pollution, with cognitive functioning among a sample of middle-aged and older Chinese individuals. Methods: A total of 10,372 and 8,397 participants from the China Health and Retirement Longitudinal Study (CHARLS) were enrolled in the cross-sectional and follow-up analyses, respectively. Cognitive functioning was evaluated via a structured questionnaire in three dimensions: orientation and attention, episodic memory, and visuo-construction. The associations between household solid fuel use (for cooking and heating) and cognitive functioning were elucidated by generalized linear models. Furthermore, we explored the combined effect of solid fuel use in cooking and heating and examined the effects of switching cooking fuel types on a 4-year change in cognitive functioning. Results: In the cross-sectional study, solid fuel use for cooking or heating, separately or simultaneously, was positively associated with cognitive impairment, after adjusting for potential confounders. Similarly, in the follow-up study, solid cooking fuel use was associated with a greater decline in cognitive score overall (β = −0.24, 95% confidence interval [CI]: −0.45, −0.04), mostly in the episodic memory (β = −0.19, 95% CI: −0.34, −0.03) and visuo-construction (β = −0.03, 95% CI: −0.05, −0.01) dimensions; solid heating fuel use was associated only with a greater decrease in the orientation and attention dimension (β = −0.13, 95% CI: −0.25, −0.01). A combined effect of household fuel use was also observed (P

To investigate the associations between sleep duration and atherosclerotic cardiovascular disease (ASCVD) risk and the potential mechanism. Overall, 24,471 subjects without ASCVD were included from Dongfeng-Tongji (DFTJ) cohort. Data collection included questionnaires and general medical examinations. We used logistic regression models and generalized linear models to examine the associations between sleep duration, peripheral white blood cell (WBC) counts, and 10-year ASCVD risk. Mediation analyses were further performed to assess the potential role of peripheral WBC counts in the associations between sleep duration and 10-year ASCVD risk. Increased risk of 10-year ASCVD was observed as sleep duration extended. After adjusting for potential confounders, the odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of 10-year ASCVD were 1.24 (1.11–1.38), 1.12 (1.03–1.22), and 1.21(1.08–1.36) for individuals with nighttime sleeping duration of ≥ 9 h, daytime napping duration of > 30 min, and daily sleep duration of ≥ 9 h, respectively. Peripheral WBC counts mediated 14.1%, 14.5%, and 12.6% in the associations of nighttime sleep duration of ≥ 9 h, daytime napping duration of > 30 min and daily sleep duration of ≥ 9 h with 10-year ASCVD risk, respectively. Extended sleep durations are associated with the increased 10-year ASCVD risk, and the associations are partially mediated by peripheral WBC counts.

Indoor air pollution caused by solid fuel use in cooking and heating in China is common. The relationship between household solid fuel use and peak expiratory flow (PEF) in middle-aged and older adults in China has not been clarified. The aim of this study was to assess the relationship between long-term household solid fuel use (clean for both cooking and heating, solid for either cooking or heating, and solid for both cooking and heating) and PEF changes in middle-aged and older adults using a nationally representative prospective cohort. Covariance analysis was used to compare PEF changes in different indoor air pollution exposure groups. Separate analysis of cooking and heating as well as sub-group analyses by age, sex and smoking status were conducted, linear mixed growth model analysis was used to evaluate the association between cooking fuel type and PEF. A total of 6818 participants were enrolled in the cohort analysis. Results revealed that solid fuel use in cooking and heating separately or conjointly were associated with reduced PEF (solid fuel use in cooking: least square mean [LSM] = 19.9, 95% confidence interval [CI]: 11.5-28.2, P = 0.03; solid fuel use in heating: LSM = 19.4, 95% CI:11.2-27.5, P = 0.04; both solid fuel use: LSM = 17.6, 95% CI: 9.3-25.9, P for trend0.0001), especially in participants aged65 years (LSM = -9.22, 95% CI: 27.9-69.52, P for trend0.0001), females (LSM = -6.41, 95% CI: 19.12-6.30, P for trend0.0001) and current or former smokers (LSM = -21.55, 95% CI: 36.14 to -6.97, P 0.02). Compared to that of participants using clean fuels for cooking, PEF of participants using solid fuels were decreased by 3.5 l/min per 2 years over a 4-year follow-up. This cohort study highlights the adverse effects of indoor air pollution on lung function in middle aged and older adults in China.

The recently identified anion channel LRRC8 volume-regulated anion channels (VRACs) are heteromeric hexamers constituted with the obligate LRRC8A subunit paired with at least one of the accessory LRRC8B to LRRC8E subunits. In addition to transport chloride, taurine, and glutamate, LRRC8 VRACs also transport the anticancer agent cisplatin and STING agonists 2′3′-cyclic GMP–AMP (cGAMP) and cyclic dinucleotides; hence, they are implicated in a variety of physiological and pathological processes, such as cell swelling, stroke, cancer, and viral infection. Although the subunit composition largely determines VRAC substrate specificity, the opening of various VRAC pores under physiological and pathological settings remains enigmatic. In this study, we demonstrated that VRACs comprising LRRC8A and LRRC8E (LRRC8A/E–containing VRACs), specialized in cGAMP transport, can be opened by a protein component present in serum under resting condition. Serum depletion ablated the tonic activity of LRRC8A/E–containing VRACs, decreasing cGAMP transport in various human and murine cells. Also, heating or proteinase K treatment abolished the ability of serum to activate VRAC. Genetic analyses revealed a crucial role for cGAMP synthase (cGAS) in serum/TNF–promoted VRAC activation. Notably, the presence of cGAS on the plasma membrane, rather than its DNA-binding or enzymatic activity, enabled VRAC activation. Moreover, phospholipid PIP2 seemed to be instrumental in the membrane localization of cGAS and its association with VRACs. Corroborating a role for LRRC8A/D–containing VRACs in cisplatin transport, serum and TNF markedly potentiated cisplatin uptake and killing of cancer cells derived from human or mouse. Together, these observations provide new insights into the complex regulation of VRAC activation and suggest a novel approach to enhance the efficacy of cGAMP and cisplatin in treating infection and cancer.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is related to decreased lung function. However, whether oxidative damage is involved in this relationship remains unclear. This study was aimed to explore the potential mediating role of oxidative DNA or lipid damage in the association between PAH exposure and lung function. Methods The urinary levels of monohydroxy polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and lung function parameters were measured among 3367 participants from the baseline of the Wuhan-Zhuhai cohort. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostane (8-iso-PGF2α) were determined to evaluate the individuals’ oxidative DNA and lipid damage degrees, respectively. Linear mixed models were used to investigate the associations of urinary OH-PAHs, 8-OHdG and 8-iso-PGF2α with lung function parameters. Mediation analysis was further conducted to assess the potential role of oxidative damage in the association between urinary OH-PAHs and lung function. Results Each one-percentage increase in the sum of urinary OH-PAHs, high-molecular-weight or low-molecular-weight OH-PAHs (ƩOH-PAHs, ƩHMW OH-PAH or ƩLMW OH-PAHs, respectively) was associated with a 0.2152-, 0.2076- or 0.1985- ml decrease in FEV1, and a 0.1891-, 0.2195- or 0.1634- ml decrease in FVC, respectively. Additionally, significantly positive dose-response relationships of ƩOH-PAHs, ƩHMW OH-PAH and ƩLMW OH-PAHs with urinary 8-OHdG or 8-iso-PGF2α, as well as an inverse dose-response relationship between urinary 8-OHdG and FVC, were observed (all P for trend

OBJECTIVE Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation, and fasting plasma glucose (FPG) alteration and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG. RESEARCH DESIGN AND METHODS FPG and urinary biomarkers of oxidative DNA damage (8-hydroxy-deoxyguanosine [8-OHdG]), lipid peroxidation (8-iso-prostaglandin-F2α [8-iso-PGF2α]), and acrylamide exposure (N-acetyl-S-[2-carbamoylethyl]-l-cysteine [AAMA], N-acetyl-S-[2-carbamoyl-2-hydroxyethyl]-l-cysteine [GAMA]) were measured for 3,270 general adults from the Wuhan-Zhuhai cohort. The associations of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG were assessed by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis. RESULTS We found significant linear positive dose-response relationships of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG (except GAMA with FPG) and 8-iso-PGF2α with FPG. Each 1-unit increase in log-transformed level of AAMA, AAMA + GAMA (ΣUAAM), or 8-iso-PGF2α was associated with a 0.17, 0.15, or 0.23 mmol/L increase in FPG, respectively (P and/or P trend < 0.05). Each 1% increase in AAMA, GAMA, or ΣUAAM was associated with a 0.19%, 0.27%, or 0.22% increase in 8-OHdG, respectively, and a 0.40%, 0.48%, or 0.44% increase in 8-iso-PGF2α, respectively (P and P trend < 0.05). Increased 8-iso-PGF2α rather than 8-OHdG significantly mediated 64.29% and 76.92% of the AAMA- and ΣUAAM-associated FPG increases, respectively. CONCLUSIONS Exposure of the general adult population to acrylamide was associated with FPG elevation, oxidative DNA damage, and lipid peroxidation, which in turn partly mediated acrylamide-associated FPG elevation.

Background Disease caused by SARS-CoV-2 broke out in Wuhan in December 2019. We utilized confirmed cases outside Hubei Province to analyze epidemiologic characteristics and evaluate the effect of traffic restrictions implemented in Hubei beginning on 23 January 2020. Methods Information on 7015 confirmed cases from 19 January to 8 February 2020 in all provinces outside Hubei was collected from the national and local health commissions in China. Incubation period and interval times were calculated using dates of the following events: contact with an infected person, onset, first visit, and diagnosis. We evaluated changes in incubation period and interval times. Results The average age of all cases was 44.24 years. The median incubation period was 5 days and extended from 2 days on 23 January to 15 days on 8 February. The proportion of imported cases decreased from 85.71% to 33.19% after 23 January. In addition, lengths of intervals between onset and diagnosis, onset and first visit, and first visit and diagnosis decreased over time. Conclusions Rapidly transmitting COVID-19 has a short incubation period. The onset mainly occurred among young to middle-aged adults. Traffic restrictions played an important role in the decreased number of imported cases outside Hubei.

Polycyclic aromatic hydrocarbon (PAH) exposure has been considered a risk factor for cardiovascular diseases (CVD), whereas possible mechanisms for this association have not been fully understood. This study focused on exploring the potential effect of oxidatively damaged DNA on the relationships between PAH exposure and the 10-year atherosclerotic CVD (ASCVD) risk. Urinary levels of monohydroxy PAH metabolites (OH-PAHs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG, the typical biomarker for oxidatively damaged DNA) were measured among 3052 subjects in the baseline of the Wuhan-Zhuhai cohort. The relationships between urinary OH-PAHs, 8-oxodG and 10-year risk of ASCVD were analyzed by linear mixed models and logistic regression models, respectively. The mediation analysis was further applied to explore the role of 8-oxodG in the relationship between urinary OH-PAHs and 10-year ASCVD risk. After controlling for potential confounders, the log-transformed level of total urinary low molecular weight OH-PAHs (∑LMW OH-PAHs) was significantly associated with an elevated risk of 10-year ASCVD [odds ratio (OR) = 1.222, 95% confidence interval (CI): 1.065-1.402]. More specifically, significantly positive dose-response relationships between total urinary hydroxynaphthalene (∑OHNa), hydroxyfluorene (∑OHFlu), hydroxyphenanthrene (∑OHPh) and 10-year ASCVD risk were observed (all P for trend0.05). We also found positive relationships between urinary OH-PAH levels and 8-oxodG, as well as between urinary 8-oxodG levels and 10-year risk of ASCVD. Moreover, mediation analyses indicated that urinary 8-oxodG mediated 14.49%, 12.62% and 10.55% of the associations between urinary ∑LMW OH-PAHs, ∑OHNa, ∑OHFlu and 10-year ASCVD risk, respectively. These findings suggest that the oxidatively damaged DNA pathway may be a possible mechanism underlying PAH-associated ASCVD risk elevation.

Polycyclic Aromatic Hydrocarbons (PAHs) exposure was related with metabolic syndrome (MetS) and heart rate variability (HRV) reduction, and HRV was also affected by cardiometabolic traits. However, the role of cardiometabolic traits in the associations from PAHs exposures to HRV was largely unknown. We conducted this study to investigate whether the relationship between PAHs exposure and HRV reduction was mediated by cardiometabolic traits. Levels of urinary polycyclic aromatic hydrocarbons metabolites (OH-PAHs), 10min-HRV, and metabolic traits were accurately measured for 2476 participants from Wuhan-Zhuhai (WHZH) cohort. Single mediator and multiple mediator models were used to evaluate the mediation effects of cadiometabolic traits. The concentrations of ΣOH-PAHs ranged from 4.20 to 8.63 mg/mmol Cr. When compared with the lowest tertile, ΣOH-PAHs in the highest tertile were significantly related with 20% (95% confidence interval [95%CI]:1%, 40%), 35% (95%CI: 14%, 56%), 22% (95%CI: 1%, 44%), and 38% (95%CI: 9%, 68%) decreases in very low frequency (VLF), low frequency (LF), high frequency (HF), and total power (TP) for participants with MetS, respectively. No statistically significant associations between ΣOH-PAHs and HRV indices were observed for participants without MetS. Similar results were found when we investigated the relationships between OH-PAHs and HRV indices by three groups of OH-PAHs (including total hydroxynaphthalene [ΣOHNa], total hydroxy fluorene [ΣOHFlu], and total hydroxyphenanthrene [ΣOHPh] metabolites). Further, mediation analysis suggested that cardiometabolic traits, including fasting glucose (GLU), high density lipoprotein (HDL), and blood pressure partially mediated the relationship from ΣOH-PAHs to HRV reduction. GLU was the strongest mediator, with mediation percentages of 15.70% for VLF, 14.70% for LF, 43.03% for HF, and 5.61% for TP. Our study found that the relationships between OH-PAHs and HRV reduction differed among participants with and without MetS, and these relationships were found to be partially mediated by cardiometabolic traits, especially fasting glucose. Further studies are encouraged to validate our findings and investigate potential mechanisms.

Most lung cancer patients die of metastasis. Recent studies have indicated that dysregulated microRNAs (miRNAs) are involved not only in tumorigenesis, but also in metastasis. In the present study, we found that over-expression of miR-26a-5p potentiated the migration and invasion of lung cancer cells evidenced by wound healing assay and transwell assay, and metastasis-related genes MMP-9 and CD44 were up-regulated. We identified integrin-beta8 (ITGβ8) as a novel target of miR-26a, and ITGβ8 expression was negatively correlated with miR-26a-5p expression in lung cancer specimens. Mechanism study showed that miR-26a-5p enhanced lung cancer cell metastasis via activation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, and ITGβ8 mediated the activation of JAK2/STAT3 pathway by miR-26a-5p. By using in vivo imaging technology, we found that miR-26a-5p enhanced both tumor growth and metastasis in vivo; and activated JAK2/STAT3 pathway. Taken together, our results demonstrated that miR-26a-5p potentiated lung cancer cell metastasis via JAK2/STAT3 pathway by targeting ITGβ8. This finding provides insights into the mechanism underlying miRNAs regulation on lung cancer metastasis; and suggests miR-26a-5p as a therapeutic target for lung cancer treatment.

Previous publications have indicated that some metals are associated with an increased prevalence of type 2 diabetes mellitus (T2DM); however, the mechanisms remain largely unknown. This study aimed to quantify the associations of oxidative DNA damage with urinary metals and prevalence of T2DM among the general population, and further to assess the role of oxidative DNA damage in mediating the association of urinary metals with prevalence of T2DM. Diagnoses of T2DM were performed clinically or by measuring fasting levels of plasma glucose ≥7.0mmol/L. Concentrations of urinary metals and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in 2127 participants were measured using inductively coupled plasma-mass spectrometry and high-performance liquid chromatography. Relationships among urinary metals, 8-OHdG (a biomarker for oxidative DNA damage), and prevalence of T2DM were analyzed using mediation analysis. After adjusting for covariates, we found that the log-transformed levels of urinary copper, arsenic, selenium, molybdenum, and antimony were positively associated with prevalence of T2DM. Urinary 8-OHdG was not only positively correlated with copper, arsenic, selenium, and antimony in an upwardly trending, dose-responsive manner but was also positively associated with prevalence of T2DM (odds ratio (OR): 1.95; 95% CI: 1.17-3.24). Mediation analysis estimated that urinary 8-OHdG mediated 13.22% and 8.84% of associations between prevalence of T2DM and concentrations of urinary arsenic and antimony, respectively (all P value

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.

Depression is one of the most common mental disorders. Effects of air pollution from outdoor and indoor on depression were inconsistent. We assessed 30,139 participants from Northeast China to explore the associations between long term exposures of outdoor and indoor solid fuel use and depressive symptoms. Multiple logistic regressions models as well as multiplicative interaction and additive interaction analysis were used. Outdoor exposures to air pollutants of particulate matter (with an aerodynamic diameter

Phenethyl isothiocyanate (PEITC) is a natural compound abundant in cruciferous vegetables. PEITC possesses anti-tumor effect in various human malignances. Our previous study has shown that benzyl isothiocyanates (BITC) induce autophagy in lung cancer cells. However, whether autophagy play a role in the inhibitory effect of PEITC on lung cancer metastasis is unclear. In this study, we found that PEITC suppressed migration and invasion of lung cancer cells by regulating MMP2. It also induced autophagy, evidenced by the formation of acidic vesicular organelles (AVOs), the punctate pattern of LC3, the accumulation of LC3-II, and the expression of Beclin-1. Inhibition of autophagy by 3-MA and chloroquine (CQ) or knock down of Beclin-1 enhanced PEITC-caused metastasis inhibition. JAK2/STAT3 pathway was suppressed by PEITC, and further inhibited by 3-MA and CQ or Beclin-1 knock down, as a result of decreased expression of p-JAK2 and p-STAT3. Blocking JAK2/STAT3 pathway by inhibitor AG490 and Stattic suppressed cell migration and decreased the expression of MMP2, MMP9, Twist, and c-Myc. Further in vivo study showed that PEITC inhibited tumor growth, induced autophagy and suppressed JAK2/STAT3 pathway, and inhibitor CQ enhanced this effect. Taken together, our results demonstrate that PEITC inhibits metastasis potential of lung cancer cells, and induces autophagy. The autophagy induced by PEITC preserves metastasis potential of lung cancer cells, via activation of JAK2/STAT3 pathway. Inhibition of autophagy enhanced the inhibitory effect of PEITC on metastasis potential of lung cancer cells. Our finding suggests that targeting autophagy could be a promising strategy for anti-metastasis therapies.

// Limin Wang 1, * , Limin Cao 1, * , Huimin Wang 1, * , Boning Liu 1 , Qicheng Zhang 1 , Zhaowei Meng 2 , Xiang Wu 3 , Qinghua Zhou 1 and Ke Xu 1 1 Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China 2 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China 3 Core Facility Center, Tianjin Medical University General Hospital, Tianjin 300052, China * These authors have contributed equally to this work Correspondence to: Ke Xu, email: ke_xu@hotmail.com Keywords: lung cancer, cancer-associated fibroblasts, metastasis, EMT, IL-6 Received: December 08, 2016 Accepted: June 02, 2017 Published: June 28, 2017 ABSTRACT Recent studies indicate that cancer-associated fibroblasts (CAFs) are involved in tumor growth, invasion and metastasis, however, the underling mechanisms remain unclear. In the present study, we investigated the role of CAFs on the metastatic potential of lung cancer cells. The stromal fibroblasts we isolated from lung cancer tissues presented CAFs characteristics with high levels of α-smooth muscle actin (α-SMA) and fibroblast-activating protein (FAP). Our data showed that the conditioned medium from cultured CAFs (CAF-CM) dramatically enhanced migration and invasion of lung cancer cells. CAF-CM induced epithelial-mesenchymal transition (EMT) by regulating the expression of EMT-associated markers E-cadherin and vimentin, and also modulated metastasis-related genes MMP-2 and VEGF both in vitro and in vivo . Further mechanistic studies demonstrated that CAFs enhanced the metastatic potential of lung cancer cells by secreting IL-6, subsequently activating of JAK2/STAT3 signaling pathway. Additionally, the inhibition of IL-6/STAT3 signaling pathway by IL-6 neutralizing antibody or specific inhibitors of JAK2/STAT3 reversed CAF-CM induced EMT and migration of lung cancer cells. Taken together, these findings revealed a novel mechanism that CAFs induced EMT and promoted metastasis of lung cancer cells through the IL-6/STAT3 signaling pathway.

Isothiocyanates (ITCs) are natural compounds abundant in cruciferous vegetables. Numerous studies have shown that ITCs exhibit anticancer activity by affecting multiple pathways including apoptosis and oxidative stress, and are expected to be developed into novel anticancer drugs. In our previous studies, we demonstrated that ITCs effectively inhibit the proliferation of non-small cell lung cancer (NSCLC) cells, also induce apoptosis and autophagy. In the present study, we found that phenethyl isothiocyanate (PEITC) had significant synergistic effects with epidermal growth factor receptor tyrosine kinase inhibitor Gefitinib in NSCLC cell lines NCI-H1299 and SK-MES-1; and the degradation of antiapoptotic factor myeloid cell leukemia 1 (Mcl-1) caused by PEITC treatment played key roles in the sensitivity of NSCLC cells to Gefitinib. We further illustrated that PEITC regulated the expression of Mcl-1 through protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic translation initiation factor 2α-CHOP-Noxa pathway by a posttranscriptional modulation. Pretreatment with endoplasmic reticulum stress (ER stress) inhibitor tauroursodeoxycholic acid and knockdown of PERK expression attenuated the degradation of Mcl-1 caused by PEITC. In in vivo study, nude mice bearing NCI-H1299 xenograft were administrated with PEITC (50 mg/kg, ip) and Gefitinib (50 mg/kg, ig) for 15 days, the PEITC-Gefitinib combination treatment resulted in a significant synergistic reduction in tumor growth, and significantly induced both ER stress and Mcl-1 degradation in tumor tissues. In conclusion, we explored the prospect of PEITC in improving the efficacy of targeted drug therapy and demonstrated the synergistic effects and underlined mechanisms of PEITC combined with Gefitinib in NSCLC cells treatment. This study provided useful information for developing novel therapy strategies by combination treatment of PEITC with targeted drugs.

OBJECTIVES: Shift work is associated with metabolic disorders as it disturbs circadian rhythms. However, the potential association of shift work with knee osteoarthritis (KOA), a metabolic-related disease, has not been confirmed. The objective of this study was to quantify the association of shift work with the risk of KOA. METHODS: This retrospective cohort study comprising 13 741 retired workers from the Dongfeng Motor Corporation. KOA was defined by knee pain and clinical X-ray radiographs. Occupational history, including job description and shift work, was collected from face-to-face interviews using questionnaires. Cox proportional hazards regression models were used to estimate exposure–response relationships. RESULTS: During the 590 085 person-years of follow-up, a total of 847 cases of KOA (incidence of KOA was 143.5 per 100 000 person-years) were identified. After adjusting for potential confounders, shift work was independently associated with an elevated risk of KOA [hazard ratio (HR) 1.19, 95% confidence interval 1.03–1.36]. Compared with daytime workers, the risk of KOA increased with prolonged periods of shift work; the HR of KOA for participants with 1–9 years, 10–19 years, and ≥20 years shift work were 1.03 (95% CI 0.84–1.26), 1.19 (95% CI 0.98–1.46), and 1.42 (95% CI 1.15–1.76), respectively. The HR for KOA associated with shift work gradually decreased as the period after finishing shift work increased. CONCLUSION: Our results indicated that shift work could be an independent risk factor for KOA.

Lambda-cyhalothrin is a pyrethroid widely used in crop, fruit and vegetable production, but has potential health threats to human. Immunoassay is a cheap, rapid and facile method to detect lambda-cyhalothrin, yet wide application of this method still requires improvement in the construction of antigen. In this study, we developed a one-step lambda-cyhalothrin hapten synthesis that transformed the cyanide group in lambda-cyhalothrin to amide. Complete antigen was assembled by coupling the amide with succinic-anhydride-activated carrier proteins, and corresponding polyclonal antibodies were generated using Balb/c mice. Using antibody generated by the method in this paper, the competitive ELISA demonstrated the lowest detection limit of 3.772 μg/L for lambda-cyhalothrin, and no significant cross-reactivity for other pyrethroid pesticides was observed. All the results suggested we have established a more efficient technique of generating lambda-cyhalothrin antibody. Furthermore, since the activated proteins used in this study are highly controllable, we believe these proteins could potentially be the prototype of a series of standardized carrier proteins for the synthesis of complete antigens.

[Su(var)3‑9, enhancer of zeste, Trithorax] domain‑​containing protein 7 (SETD7) is a protein lysine methyltransferase that methylates both histone H3K4 and non‑histone proteins, such as transcription factors. The methylation on proteins alters their activity and affects a series of biological processes. Recent studies have demonstrated that SETD7 contributes to tumor progression and may play different roles in tumor development. However, the effect of SETD7 on lung cancer cell migration and invasion has not been fully elucidated. The present study demonstrated that the expression of SETD7 was significantly downregulated in lung cancer tissues in comparison with that in matched non‑cancer tissues, and lung cancer cell lines also exhibited lower SETD7 levels compared with normal human bronchial epithelial cells. Overexpression of SETD7 inhibited the migration and invasion of lung cancer cells, whereas decreased SETD7 expression promoted cell migration and invasion. Further study revealed that SETD7 regulated the expression of the metastasis‑related genes metalloproteinase 2, Twist1 and vascular endothelial growth factor. Furthermore, SETD7 knockdown activated the Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling pathway and enhanced lung cancer cell migration, whereas the STAT3‑specific inhibitor Stattic abrogated the effect of SETD7 on cell migration. Taken together, these data indicated that SETD7 acts as a tumor suppressor, and the reduced expression of SETD7 may contribute to lung cancer progression. The findings of the present study suggest that SETD7 may be a novel candidate for the treatment of metastatic lung cancer.

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites, biomarkers of internal PAH exposure, are commonly used to explore the effects of PAH on human health. However, the correlation between environmental PAH exposure and the species or levels of urinary PAH metabolites remains unclear. We collected detailed information on PAH exposure sources, including cigarette smoking, cooking, traffic and diet habits via structured questionnaires, and determined 12 urinary monohydroxylated PAH metabolites (OH-PAHs) among 4092 participants from the Wuhan-Zhuhai cohort. Linear mixed models and generalized linear models were conducted to explore the associations of urinary metabolite levels with single or multiple PAH exposure sources. We also calculated the standardized regression coefficients to further compare the contributions of different sources to urinary OH-PAH levels. Our results showed that increasing levels of urinary 1-, 2-hydroxynaphthalene (1-, 2- OHNa) and 2-hydroxyfluorene (2-OHFlu) were significantly correlated with tobacco smoking (all P 0.01). The concentrations of 1-, 2- OHNa and 9-hydroxyfluorene (9-OHFlu) were positively correlated with dietary intake (all P 0.05). Individuals who spent a long time in traffic showed elevated levels of 9-OHFlu and 1-hydroxyphenanthrene (1-OHPh) compared with individuals who spent a short time in traffic (all P 0.05). Self-cooking was associated only with elevated 1-hydroxypyrene (1-OHP) levels. Moreover, good kitchen ventilation resulted in significantly decreased urinary low-molecular-weight OH-PAH levels. These findings suggested that cigarette smoking, self-cooking, high dietary PAH intake and a long time spent in traffic were associated with increased levels of specific urinary PAH metabolites, and good kitchen ventilation effectively reduced the exposure to low-molecular-weight PAHs in self-cooking participants.

Objective: The aim of this study was to investigate and analyze the prognostic factors affecting lymph node (LN) metastasis and postoperative recurrence in patients with primary small cell...

Acrylamide exposure along with resultant potential adverse health effects have attracted global concern, and the World Health Organization calls for more and urgent studies on the health risks from acrylamide. However, the association and mechanism between acrylamide exposure and pulmonary dysfunction remain unclear. Our goals were to investigate the relationship of internal acrylamide exposure with lung function reduction, and the potential mediating role of systematic inflammation in that relationship. Our study was conducted within the Wuhan-Zhuhai cohort. Urinary biomarkers of acrylamide exposure (N-acetyl-S-(2-carbamoylethyl)-l-cysteine, AAMA; N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine, GAMA) and lung function were determined among 3271 general adults, of whom 2595 had test results of systemic inflammatory marker plasma C-reactive protein (CRP). We employed linear mixed models to assess the relations among urinary acrylamide metabolites, pulmonary function and plasma CRP, and PRODCLIN program to evaluate the mediating role of CRP. We observed that urinary acrylamide metabolites were inversely and dose-dependently related to lung function (P trend0.05). Each 1-unit increment in log-transformed level of AAMA, GAMA, or AAMA+GAMA (ΣUAAM) was significantly (P 0.05) related to a 59.9-, 64.2-, or 64.3-mL reduction in FVC, and a 53.9-, 59.7-, or 58.5-mL reduction in FEV

Carbon disulfide (CS2) has been reported to induce disorder of glucose metabolism. However, the associations of CS2 exposure with plasma glucose levels and risk of diabetes have not been explored in general population, and the underlying mechanisms remain unclear. We aim to examine the relationships between CS2 exposure and fasting plasma glucose (FPG) levels, as well as diabetes, and assess the potential role of oxidative stress among the abovementioned relationships in Chinese general adults. The concentrations of urinary biomarkers of CS2 exposure (2-thiothiazolidin-4-carboxylic acid, TTCA), and biomarkers for lipid peroxidation (8-isoprostane, 8-iso-PGF2α) and DNA oxidative damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) were measured among 3338 urban adults from the Wuhan-Zhuhai cohort. Additionally, FPG levels were tested promptly. Generalized linear models and logistic regression models were used to quantify the associations among urinary TTCA, oxidative damage markers, FPG levels and diabetes risk. Mediation analysis was employed to estimate the role of oxidative damage markers in the association between urinary TTCA and FPG levels. We discovered a significant relationship between urinary TTCA and FPG levels with regression coefficient of 0.080 (95% CI: 0.002,0.157). Besides, the risk of diabetes was positively related to urinary TTCA (OR:1.282, 95% CI: 1.055,1.558), particularly among those who did not exercise regularly. Each 1% increase of urinary TTCA concentration was associated with a 0.096% and 0.037% increase in urinary 8-iso-PGF2α and 8-OHdG, respectively. Moreover, we found an upward trend of FPG level as urinary 8-iso-PGF2α gradually increased (Ptrend

The interaction between some proteins and immune globulin has been confirmed as an important source of matrix interference with the immunoassay of fishery products, but detailed biochemical properties of these proteins have not been indicated. Two interference-inducing proteins (42 and 36 kD) in flounder were isolated, characterized, and identified. Their influences on the immunoassay of norfloxacin were confirmed by western blotting and enzyme-linked immunosorbent assay. The pI value and pH stability of the two proteins were also investigated. Using LC-MS/MS, the two proteins were identified as fructose-bisphosphate aldolase, and such results were partly verified by the aldolase activity of the 42 and 36 kD isolates. Considering the prevalence of these proteins (as multi-functional aldolase of muscles) in foods, these results would help to further understand the matrix effects in various immunoassays as well as the development of effective techniques to improve the efficiency of immunoassays.

Neomycin is widely used in veterinary medicine, while the confirmatory analysis of neomycin residues in aquatic samples has not been well identified. Here, in this study, an immunoaffinity chromatography (IAC) for determination of neomycin residues in aquatic sample was developed and optimized. The average maximum reserved content of neomycin (MRC) was calculated as 1611 ng, and by the simple regeneration with phosphate buffer saline, the recovery value maintained above 75 % even at the 32nd reusage (at the loading amount of 1200 ng). With the combination of IAC and high-performance liquid chromatography (HPLC), a new strategy for the analysis of neomycin was proposed and validated with different aquatic products. With the spiking concentration from 400 to 1200 ng/Kg, the recovery value was observed in the range of 75.58–117.80 %, and the CV was lower than 11 %. All these results suggested that the IAC-HPLC is a new and promising technique for the routine monitoring of neomycin residue in aquatic products.

A capillary immunochromatographic assay (CICA) using colloidal gold-labeled monoclonal antibodies was developed for semi-quantitative detection of clenbuterol (CLE) in this paper. This novel system fabricated in a competitive format was supported by glass capillary because of its easily modified, low cost, favorable optical properties. Here, two different-sized gold nanoparticles (13 and 26 nm) were prepared and corresponding assay conditions were optimized. By comparing the results between the two different-sized AuNPs, the 26-nm-AuNPs manifested higher sensitivities which the detection limit was estimated to be 0.35 ng/ml and the cut-off level with the naked eye of 2.5 ng/ml was observed. Using the optimized parameters, the intra-assay and inter-assay coefficients of variation (CVs) were ≤10.2 % and the recovery reached 70.8–115.5 % in pig urine, pork, beef, pork sausage and luncheon meat. The performance, including sample preparation, could be accomplished within 24 min. These results suggest that CICA holds promising use for sensitive, simple and low-cost on-site detection of CLE.

Effective removal of cadmium (Cd) from Chlamys farreri by introducing ZnSO4, EDTA-Na2, and sodium citrate into seawater has previously been reported. However, some mechanisms underlying this removal are not clear. To address this lack of clarity, the present study aimed to investigate the changes of Cd forms in Chlamys farreri from treatment of these additives and analyze the physiological and biochemical responses by comparing the changes over treatment time in Catalase (CAT), Superoxide dismutase (SOD), and Glutathione s-transferase (GST) activity, as well as Malonaldehyde (MDA) concentration and glycogen level. Three forms of Cd, including protein -Cd, liberated Cd, and amino acid/peptide -Cd, were found, and they were sorted according to their Cd content into the following groups: protein -Cd > liberated Cd > amino acid/peptide-Cd. The removal rates of the three forms of Cd were 43.2%, 59.5%, and 59.0%, respectively, using ZnSO4 and EDTA-Na2. Additionally, a significant increase in Zn content was observed, which may suggest that reduction of bound Cd was partly due to the displacement of Cd by Zn. Moreover, Cd depuration using the additives can mitigate oxidative stress only in the first 12 h. Glycogen content continued to reduce over time, inferring that the healthy status of Chlamys farreri under treatment of the additives containing Zn can only be maintained within 12 h for excreting Cd when linking these physiological responses with the ability of the additives to remove Cd only in a short time, i.e. 12 h. The results indicated that Cd should be removed from Chlamys farreri for practical reasons.

Previous studies found that exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with type 2 diabetes (T2D) prevalence. However, the potential mechanism is still unclear. In this study, we investigated 3031 Chinese urban adults to discover the relationship between PAH exposure and plasma Interleukin-22 (IL-22) and potential role of IL-22 in the association between PAH and fasting plasma glucose (FPG) or risk of T2D. After adjustment for potential confounders, significant dose-response relationships were observed between several urinary PAH metabolites with FPG and the prevalence of T2D. Each 1-U increase in ln-transformed value of 2-hydroxynaphthalene (2-OHNa), 2-hydroxyphenanthrene (2-OHPh), 3-hydroxyphenanthrene (3-OHPh), 4-hydroxyphenanthrene (4-OHPh), 9-hydroxyphenanthrene (9-OHPh), 1-hydroxypyrene (1-OHP) or total PAH metabolites was significantly associated with a 0.053, 0.026, 0.037, 0.045, 0.051, 0.041 or 0.047 unit decrease in IL-22 level, respectively. In addition, plasma IL-22 level was negatively associated with FPG and prevalence of T2D in a dose-dependent manner. Mediation analysis showed that IL-22 mediated 8.48 %, 3.87 %, 6.64 %, 6.47 %, and 8.67 % of the associations between urinary 2-OHNa, 1-OHPh, 3-OHPh, 4-OHPh, and 9-OHPh with the prevalence of T2D, respectively. These results indicated that urinary PAHs metabolites were inversely associated with plasma levels of IL-22, but positively related to FPG and the T2D prevalence. Downregulation of IL-22 might play a significant role in mediating PAHs exposure-associated risk increasement of T2D.

Copper have been reported to be associated with metabolic diseases. However, results on copper exposure with blood lipid profiles are inconsistent, and the underlying mechanisms of this association remain unclear. This study focused on investigating associations between urinary copper and blood lipid profiles; and exploring the potential role of systemic inflammation in such relationships. Concentrations of urinary copper, plasma C-reactive protein (CRP), and four blood lipid parameters (e.g., Total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) were measured in the adult participants from Wuhan-Zhuhai cohort. The associations between copper, CRP, and four blood lipids were assessed by the multivariable linear regression models, and the 3D mesh graphs was used to examine the joint effects of copper exposure and CRP on four blood lipid parameters. In addition, we used mediation analysis to investigate the mediated effects of CRP in the relationships between copper exposure and blood lipid profiles. Each 1% increase in urinary copper was statistically significantly associated with a 5.32% (95% CI: 2.48%, 8.24%) increase in TG after adjusting for the confounders (P 0.05). No significant associations were observed between urinary copper and the other three blood lipid parameters (all P 0.05). In addition, urinary copper increased monotonically with plasma CRP elevation, which in turn, was positively associated with TC, TG, and LDL-C and negatively related to HDL-C (all P 0.05). Results from 3D mesh graphs demonstrated that increased levels of plasma CRP with higher urinary copper corresponded to higher TC, TG, LDL-C, and lower HDL-C concentrations. Mediation analysis observed that CRP mediated 6.27% in the relationships of urinary copper and TG. These findings suggest that systemic inflammation partly mediated the association between copper exposure and abnormal blood lipid, and may contribute to the development of dyslipidemias.