Publications by authors named "Linling Yu"

39 Publications

Associations of polychlorinated biphenyls exposure with plasma glucose and diabetes in general Chinese population: The mediating effect of lipid peroxidation.

Environ Pollut 2022 Jun 20;308:119660. Epub 2022 Jun 20.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address:

Polychlorinated biphenyls (PCBs) exposure has been related to the abnormal glucose metabolism and the risk of diabetes. However, the joint effects of various PCBs are uncertain and the potential mechanisms remain unclear. Our objectives were to evaluate the associations of serum PCBs with fasting plasma glucose (FPG) and the risk of diabetes among a general Chinese population, and to estimate the mediating effects of oxidative stress in the above associations. Serum levels of seven indicator-PCBs (PCB-28, 52, 101, 118, 138, 153, and 180) and FPG values were determined among 4498 subjects from the Wuhan-Zhuhai cohort. Oxidative DNA damage biomarker (urinary 8-hydroxy-2'-deoxyguanosine, 8-OHdG) and lipid peroxidation biomarker (urinary 8-isoprostane, 8-iso-PGF) were also measured. Positive relationships of serum PCBs with FPG values as well as the risk of diabetes were observed. With each 1% increment in the natural log-transformed values of wet weight serum PCBs, FPG levels increased a 0.125% for PCB-52, 0.168% for PCB-118, 0.221% for PCB-138, 0.273% for PCB-153, and 0.379% for ΣPCB (the sum of seven PCBs). The adjusted odds ratios of diabetes associated with wet weight PCBs were 1.186 for PCB-52, 1.373 for PCB-118, 1.635 for PCB-153, and 1.456 for ΣPCB. The seven serum PCBs showed positive overall effect on the risk of diabetes. Elevated PCB-28, PCB-52, PCB-118, PCB-138, PCB-153, and ΣPCB were associated with the increased urinary 8-iso-PGF, which was positively related with FPG values. Furthermore, urinary 8-iso-PGF partially mediated the positive associations between PCBs and FPG values, with the mediated proportions ranged from 3.20 to 12.93%. In conclusion, our results suggested that serum PCBs were positively related with increased oxidative stress, FPG values, and the risk of diabetes among a general Chinese population. Serum PCBs mixture had positive overall effect on the risk of diabetes. Lipid peroxidation partly mediated the FPG elevation induced by PCB exposure.
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http://dx.doi.org/10.1016/j.envpol.2022.119660DOI Listing
June 2022

A review of practical statistical methods used in epidemiological studies to estimate the health effects of multi-pollutant mixture.

Environ Pollut 2022 Aug 27;306:119356. Epub 2022 Apr 27.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address:

Environmental risk factors have been implicated in adverse health effects. Previous epidemiological studies on environmental risk factors mainly analyzed the impact of single pollutant exposure on health, while in fact, humans are constantly exposed to a complex mixture consisted of multiple pollutants/chemicals. In recent years, environmental epidemiologists have sought to assess adverse health effects of exposure to multi-pollutant mixtures based on the diversity of real-world environmental pollutants. However, the statistical challenges are considerable, for instance, multicollinearity and interaction among components of the mixture complicate the statistical analysis. There is currently no consensus on appropriate statistical methods. Here we summarized the practical statistical methods used in environmental epidemiology to estimate health effects of exposure to multi-pollutant mixture, such as Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regressions, shrinkage methods (least absolute shrinkage and selection operator, elastic network model, adaptive elastic-net model, and principal component analysis), environment-wide association study (EWAS), etc. We sought to review these statistical methods and determine the application conditions, strengths, weaknesses, and result interpretability of each method, providing crucial insight and assistance for addressing epidemiological statistical issues regarding health effects from multi-pollutant mixture.
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http://dx.doi.org/10.1016/j.envpol.2022.119356DOI Listing
August 2022

Acrylamide exposure increases cardiovascular risk of general adult population probably by inducing oxidative stress, inflammation, and TGF-β1: A prospective cohort study.

Environ Int 2022 Jun 25;164:107261. Epub 2022 Apr 25.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address:

Acrylamide (ACR) exposure and consequent health hazards are alarming public health issues that attract worldwide concern. The World Health Organization urges more researches into health hazards from ACR exposure. However, whether and how ACR exposure increases cardiovascular risk remain unclear, and we sought to address these issues in this prospective cohort study conducted on 3024 general adults with 3-year follow-up (N = 871 at follow-up). Individual urinary ACR metabolites (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine [AAMA] and N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine [GAMA]) as credible biomarkers of ACR exposure were detected to assess their cross-sectional and longitudinal relationships with 10-year cardiovascular disease (CVD) risk, a well measure of overall cardiovascular risk. Besides, biomarkers of oxidative stress (urinary 8-hydroxy-deoxyguanosine [8-OHdG] and 8-iso-prostaglandin-F2α [8-iso-PGF2α]) and inflammation (circulating mean platelet volume [MPV] and plasma C-reactive protein [CRP]) as well as plasma transforming growth factor-β1 (TGF-β1) were measured to assess their mediating/mechanistic roles in the relationships of ACR metabolites with 10-year CVD risk. We found AAMA, GAMA, and ΣUAAM (AAMA + GAMA) were cross-sectionally and longitudinally related to increased 10-year CVD risk with odds ratios (95% confidence intervals [CIs]) of 1.32 (1.04, 1.70), 1.81 (1.36, 2.40), and 1.40 (1.07, 1.82), respectively, and risk ratios (95% CIs) of 1.99 (1.10, 3.60), 2.48 (1.27, 4.86), and 2.13 (1.15, 3.94), respectively. Furthermore, 8-OHdG, 8-iso-PGF2α, MPV, CRP, and TGF-β1 were found to significantly mediate 8.06-48.92% of the ACR metabolites-associated 10-year CVD risk increment. In summary, daily ACR exposure of general adults was cross-sectionally and longitudinally associated with increased cardiovascular risk, which was partly mediated by oxidative stress, inflammation, and TGF-β1, suggesting for the first time that ACR exposure may well increase cardiovascular risk of general adult population partly by mechanisms of inducing oxidative stress, inflammation, and TGF-β1. Our findings have important public health implications that provide potent epidemiological evidence and vital mechanistic insight into cardiovascular risk increment from ACR exposure.
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http://dx.doi.org/10.1016/j.envint.2022.107261DOI Listing
June 2022

Characterization of a heptapeptide-modified microsphere for oriented antibody immobilization.

J Pept Sci 2022 Apr 12:e3411. Epub 2022 Apr 12.

Department of Biochemical Engineering, School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin, China.

Oriented immobilization of antibodies is important for the effective recognition of target antigens. In this paper, a heptapeptide ligand, HWRGWVC (HC7), was modified onto non-porous monosized poly(glyceryl methacrylate) (pGMA) microspheres (named pGMA-HC7) to explore the antibody immobilization behaviors. Characterization of the microspheres by particle size analyzer, scanning electron microscopy, Fourier transform infrared spectroscopy, and reversed-phase chromatography proved the success of each fabrication step. The capacity and activity of antibody immobilization through HC7 were studied using immunoglobulin G (IgG) as a model antibody and horseradish peroxidase (HRP) as a model antigen. Additionally, IgG immobilizations on pGMA microspheres by nonspecific adsorption and covalent coupling through carbodiimide chemistry were conducted for comparison. pGMA-HC7 exhibited an IgG adsorption capacity of 3-4 mg/g in 10 min by the specific binding of HC7 without nonspecific interactions. Notably, the ligand HC7 showed a by two orders of magnitude stronger affinity for IgG than its original hexapeptide ligand HWRGWV. Moreover, the capacity and activity of the immobilized anti-HRP antibody on pGMA-HC7 were 1.6-fold and 3-fold higher than those of the covalent coupling, respectively. The results proved the superior role of HWRGWVC in the affinity binding of antibody and the potential of pGMA-HC7-25 in immunoassay and immunodiagnostic applications.
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http://dx.doi.org/10.1002/psc.3411DOI Listing
April 2022

Association of caffeine and caffeine metabolites with obesity among children and adolescents: National Health and Nutrition Examination Survey (NHANES) 2009-2014.

Environ Sci Pollut Res Int 2022 Mar 30. Epub 2022 Mar 30.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

The effect of caffeine exposure on children's health remains poorly understood. We aimed to characterize the associations of caffeine and caffeine metabolites with adiposity outcomes among children and adolescents. We performed cross-sectional analyses of 1,447 children and adolescents aged 6-19 years from the 2009-2014 National Health and Nutrition Examination Survey. The linear regression and weighted quantile sum (WQS) regression were used to explore the associations of urinary caffeine and 14 caffeine metabolites with adiposity outcomes, including body mass index (BMI) z-score, waist circumference (WC), obesity, and overweight. In linear regression models, compared with the participants who consumed low caffeine, higher BMI z-score, WC, and risks of obesity and overweight were more likely among those who consumed high caffeine (P < 0.05). In WQS regression models, an interquartile range increase in the weighted caffeine index was significantly associated with increased BMI z-score (β = 0.10, 95% CI = 0.01, 0.17) and WC (β = 1.20, 95% CI = 0.31, 2.09), and risks of obesity (OR = 1.09, 95% CI = 1.02, 1.17). Totally, no modification effect of age or gender was observed in the linear regression model. Nonetheless, in WQS models, the positive associations of caffeine exposure with WC and risks of obesity and overweight were significant in children aged 6-11 years rather than 12-19 years. When stratified by gender, caffeine exposure was significantly associated with BMI z-score and WC in both boys and girls. These results add novel evidence that caffeine exposure might be associated with adverse adiposity outcomes among children and adolescents.
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http://dx.doi.org/10.1007/s11356-022-19836-1DOI Listing
March 2022

Evi1 involved in benzene-induced haematotoxicity via modulation of PI3K/mTOR pathway and negative regulation Serpinb2.

Chem Biol Interact 2022 Feb 26;354:109836. Epub 2022 Jan 26.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China. Electronic address:

Benzene is a widely used chemical and an environmental pollutant. Exposure to benzene can cause blood diseases, but the mechanisms underlying benzene haematotoxicity have not been fully clarified. Ecotropic virus integration site-1 (Evi1), a transcription factor, plays important roles in normal haematopoiesis and haematological diseases. In this study, we investigated the role and mechanism of Evi1 in benzene-induced haematotoxicity. We found that benzene exposure significantly increased Evi1 level in white blood cells (WBCs) in occupational benzene workers as well as mouse bone marrow cells. Further in vitro results demonstrated that compared with control cells exposed to same 1,4-benzoquinone (1,4-BQ, an important active metabolite of benzene) concentration, Evi1 downregulation significantly reduced cell proliferation, and disrupted cell viability, apoptosis, erythroid and megakaryotic cell differentiation and cell cycle. Additionally, down-regulation of Evi1 suppressed phosphoinositide 3-kinase (PI3K)/mTOR signalling pathway and elevated its target gene Serpinb2 following 1,4-BQ exposure. Moreover, the PI3K activator could partially relieve the inhibitory effect of down-regulation of Evi1 on cell proliferation and increase cell arrest in in G2/M phase. What's more, downregulation of Serpinb2 could partially alleviate proliferation inhibition and reverse cell cycle changes in G0/G1 phase and S phase induced by Evi1 inhibition. In conclusion, our data revealed that Evi1 downregulation aggravated the inhibition of cell proliferation and arrested cells in the G0/G1 phase when exposed to 1,4-BQ, potentially by inactivating the PI3K/mTOR pathway and upregulating downstream target gene Serpinb2. Our study provides novel insights on mechanism by which Evi1 participates in benzene-induced haematotoxicity.
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http://dx.doi.org/10.1016/j.cbi.2022.109836DOI Listing
February 2022

The influence of social network on COVID-19 vaccine hesitancy among healthcare workers: a cross-sectional survey in Chongqing, China.

Hum Vaccin Immunother 2021 12 4;17(12):5048-5062. Epub 2022 Jan 4.

EPI Department, Chongqing Municipal Center for Disease Control and Prevention, Chongqing, China.

The factors that lead to coronavirus disease 2019 (COVID-19) vaccine hesitancy among health-care workers (HCWs) are unclear. We aimed to identify the factors that influence HCWs' hesitancy, especially the influence of their social network. Using an online platform, we surveyed HCWs in Chongqing, China, in January 2021 to understand the factors that influence the COVID-19 vaccine hesitancy among HCWs. Proportional allocation stratified sampling method was used to recruit respondents. Multivariable logistic regression and social network analysis (SNA) were used to analyze the influence factors. A total of 5247 HCWs were included and 23.3% of them were vaccine-hesitant. Participants were more hesitant if they had chronic diseases ( = 1.411, 95% : 1.146-1.738), worked in tertiary hospitals ( = 1.546, 95% : 1.231-1.942), and reported a history of vaccine hesitancy ( = 1.637, 95% : 1.395-1.920) and refusal toward other vaccines ( = 2.433, 95% : 2.067-2.863). The participants with a social network to communicate COVID-19 immunization were less hesitant ( = 0.850, 95% : 0.728-0.993). Several influential members with social networks were found in SNA. Most of these influential members in the networks were department leaders who were willing to get COVID-19 vaccines ( < .05). Hesitant subgroups among Chinese HCWs were linked to the lack of a social network to communicate COVID-19 immunization. Our findings may lead to tailored interventions to enhance COVID-19 vaccine uptake among HCWs by targeting key members in social network.
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http://dx.doi.org/10.1080/21645515.2021.2004837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903998PMC
December 2021

Role of MRI in characterizing serous borderline ovarian tumor and its subtypes: Correlation of MRI features with clinicopathological characteristics.

Eur J Radiol 2022 Feb 21;147:110112. Epub 2021 Dec 21.

Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, 1# Xueshi Road, Hangzhou, Zhejiang 310006, China. Electronic address:

Purpose: This study aimed to investigate the diagnostic value of MRI in serous borderline ovarian tumor (SBOT), and to determine the MRI features of SBOT and their correlations with clinicopathological characteristics.

Materials And Methods: A total of 121 patients suspected of SBOT by preoperative MRI and then underwent surgery at our hospital were retrospectively reviewed. The accuracy of MRI in diagnosing SBOT was assessed. MRI features of the SBOT subtypes were compared and their correlations with clinicopathological characteristics were evaluated.

Results: SBOT was confirmed by postoperative pathology in 95 patients, including 77 patients with conventional SBOT (SBOT-C) and 18 patients with micropapillary SBOT (SBOT-MP). The accuracy of MRI in diagnosing SBOT was 87.6%. Three MRI morphological patterns of SBOT were identified: (i) mainly solid, (ii) mainly cystic, and (iii) mixed. Branching papillary architecture and internal branching (PA&IB) structures corresponding to multiple branching papillary projections and internal fibrous stalks in tumors were observed in 69.7% of SBOTs on T2-weighted images. MRI findings were consistent with postoperative pathology. Compared with SBOT-C, patients with SBOT-MP were more likely to display elevated cancer antigen 125, bilateral tumors, peritoneal implantation, lymph node metastasis, and advanced tumor staging. No significant differences were observed in MRI features between SBOT-C and SBOT-MP groups.

Conclusion: MRI has good performance in diagnosing SBOT. MRI findings of SBOT are consistent with clinicopathological characteristics. The PA&IB structure is the characteristic MRI finding of SBOT. Compared to SBOT-C, SBOT-MP tends to display more aggressive clinical behavior, but their MRI features are similar.
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http://dx.doi.org/10.1016/j.ejrad.2021.110112DOI Listing
February 2022

Benzo(a)pyrene induces airway epithelial injury through Wnt5a-mediated non-canonical Wnt-YAP/TAZ signaling.

Sci Total Environ 2022 Apr 25;815:151965. Epub 2021 Nov 25.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Wnt5a is a key mediator of non-canonical Wnt signaling, and an early indicator of epithelial injury and lung dysfunction. Polycyclic aromatic hydrocarbons (PAHs) could induce acute pulmonary pathogenesis, of which the underlying mechanism remains unclear. To elucidate the potential role of Wnt5a-mediated non-canonical Wnt-YAP/TAZ signaling in the lung injury induced by short-term exposure of benzo(a)pyrene (BaP, a representative PAHs), intratracheally instilled mouse model was used and further interfered with its Wnt5a level by small molecule antagonists and agonists. Our data revealed that BaP exposure induced the lung inflammatory response and reduced the expression of Clara cell secretory protein (CC16) in a dose-dependent manner. More importantly, the activation of Wnt5a and downstream YAP/TAZ were accompanied with the enhanced release of epithelial-derived thymic stromal lymphopoietin and interleukin-33, which acted as pro-inflammatory cytokines. Functionally, inhibition of Wnt5a attenuated the BaP-induced inflammation and recuperated CC16 expression, as well as suppressed the epithelial cytokines release. Whereas promoting Wnt5a expression affected the toxic effects of BaP oppositely. Our findings together suggest that Wnt5a is a potential endogenous regulator in lung inflammation and airway epithelial injury, and Wnt5a-YAP/TAZ signaling contributes to lung dysfunction in acute exposure to BaP.
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http://dx.doi.org/10.1016/j.scitotenv.2021.151965DOI Listing
April 2022

Associations of propylene oxide exposure with fasting plasma glucose and diabetes: Roles of oxidative DNA damage and lipid peroxidation.

Environ Pollut 2022 Jan 1;292(Pt B):118453. Epub 2021 Nov 1.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, And State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address:

Whether propylene oxide (PO) exposure is associated with hyperglycemia were rarely explored. We aimed to determine the relationship between PO exposure and glucose metabolism, and potential role of oxidative stress. Among 3294 Chinese urban adults, urinary PO metabolite (N-Acetyl-S-(2-hydroxypropyl)-L-cysteine, 2HPMA), biomarkers of oxidative DNA damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) and lipid peroxidation (8-isoprostane, 8-iso-PGF) in urine were determined. The associations of 2HPMA with 8-OHdG, 8-iso-PGF, fasting plasma glucose (FPG), and risk of diabetes were explored. The roles of 8-OHdG and 8-iso-PGF on association of 2HPMA with FPG and risk of diabetes were detected. After adjusted for potential confounders, each 1-unit increase in log-transformed concentration of 2HPMA was associated with a 0.15-mmol/L increase in FPG level, and the adjusted OR (95% CI) of diabetes by the associations of log-transformed urinary 2HPMA concentrations was 1.47 (95% CI: 1.03-2.11). Combination effects of 2HPMA with 8-OHdG or 8-iso-PGF on risk of diabetes were detected, and elevated 8-iso-PGF significantly mediated 34.5% of the urinary 2HPMA-associated FPG elevation. PO exposure was positively associated with FPG levels and risk of diabetes. PO exposure combined with DNA oxidative damage or lipid peroxidation may increase the risk of diabetes, and lipid peroxidation may partially mediate the PO exposure-induced FPG elevation.
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http://dx.doi.org/10.1016/j.envpol.2021.118453DOI Listing
January 2022

Immunosuppression characterized by increased Treg cell and IL-10 levels in benzene-induced hematopoietic toxicity mouse model.

Toxicology 2021 12 18;464:152990. Epub 2021 Oct 18.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. Electronic address:

Benzene is a typical hematopoietic toxic substance, that can cause serious blood and circulatory system diseases such as aplastic anemia, myelodysplastic syndrome and acute myeloid leukemia, but the immunological mechanism by which this occurs is not clear. T helper cells play a key role in regulating the immune balance in the body. In this study, benzene-induced hematopoietic toxicity BALB/c mice model was established, and changes in immune organs and T helper cell subsets (Th1, Th2, Th17 and Treg cells) were explored. At 28 days after subcutaneous injection of 150 mg/kg benzene, mice showed pancytopenia and obvious pathological damage to the bone marrow, spleen, and thymus. Flow cytometry revealed that the number of CD4CD25Foxp3 Treg cells in the spleen increased significantly. The level of IL-10 in the spleen, serum, and bone marrow increased, while the levels of IL-17 in the spleen and serum decreased. Furthermore, the levels of CD4 and CD8 proteins in the spleen decreased. Immunofluorescence results showed that levels of Foxp3, a specific transcription factor that induced the differentiation of Treg cells, increased after exposure to benzene. Our results demonstrate that immunosuppression occurred in the benzene-induced hematopoietic toxicity model mice, and Treg cells and secreted IL-10 may play a key role in the process.
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http://dx.doi.org/10.1016/j.tox.2021.152990DOI Listing
December 2021

Incidence and disease burden of coal workers' pneumoconiosis worldwide, 1990-2019: evidence from the Global Burden of Disease Study 2019.

Eur Respir J 2021 11 25;58(5). Epub 2021 Nov 25.

Dept of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

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http://dx.doi.org/10.1183/13993003.01669-2021DOI Listing
November 2021

Lipidomic analysis reveals disturbances in glycerophospholipid and sphingolipid metabolic pathways in benzene-exposed mice.

Toxicol Res (Camb) 2021 Aug 15;10(4):706-718. Epub 2021 Jun 15.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China.

Benzene, a known occupational and environmental contaminant, has been recognized as the hematotoxin and human carcinogen. Lipids have a variety of important physiological functions and the abnormal lipid metabolism has been reported to be closely related to the occurrence and development of many diseases. In the present study, we aim to utilize LC-MS/MS lipidomic platform to identify novel biomarkers and provide scientific clues for mechanism study of benzene hematotoxicity. Results showed that a total of 294 differential metabolites were obtained from the comparison of benzene-treated group and control group. The glycerophospholipid pathway was altered involving the down-regulation of the levels of phosphatidylcholine and phosphatidylserine. In addition, phosphatidylethanolamine (PE) and 1-Acyl-sn-glycero-3-phosphocholine levels were increased in benzene-treated group. Based on the relationship between PE and autophagy, we then found that effective biomarker of autophagy, Beclin1 and LC3B, were increased remarkably. Furthermore, following benzene treatment, significant decreases in glucosylceramide (GlcCer) and phytosphingosine (PHS) levels in sphingolipid pathway were observed. Simultaneously, the levels of proliferation marker (PCNA and Ki67) and apoptosis regulator (Bax and Caspase-3) showed clear increases in benzene-exposed group. Based on our results, we speculate that disturbances in glycerophospholipid pathway play an important role in the process of benzene-induced hematopoietic toxicity by affecting autophagy, while sphingolipid pathway may also serve as a vital role in benzene-caused toxicity by regulating proliferation and apoptosis. Our study provides basic study information for the future biomarker and mechanism research underlying the development of benzene-induced blood toxicity.
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http://dx.doi.org/10.1093/toxres/tfab053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403594PMC
August 2021

Systemic inflammation mediates the association of heavy metal exposures with liver injury: A study in general Chinese urban adults.

J Hazard Mater 2021 10 29;419:126497. Epub 2021 Jun 29.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address:

Heavy metal exposures have been reported to be associated with increased risk for liver injury. However, the potential mechanisms of the association remain unclear. A repeated-measure study of 9367 observations was conducted to quantify the associations of urinary heavy metals with serum alanine aminotransferase (ALT), a biomarker for liver injury, and assess the mediating role of systemic inflammation in such associations among general Chinese adults. In single-metal models, positive dose-response relationships between urinary vanadium (V), chromium (Cr), copper (Cu), arsenic (As), cadmium (Cd), tungsten (W), and lead (Pb) and serum ALT were observed. In the multiple-metal model containing the seven metals mentioned above, V and Cu remained positively associated with ALT. In longitudinal analyses of 3-6 years, each 1-unit increase in log-transformed levels of V and Cu was associated with an additional rate of annual ALT increase (95% CI) for 1.3% (0.7-1.8%) and 1.3% (0.7-2.0%), respectively. Plasma CRP concentrations were not only positively associated with urinary Cu and Cd, but also positively related with ALT. Furthermore, mediation analyses showed that CRP mediated 4.70% and 7.03% of urinary Cu- and Cd-associated ALT elevations. Our study provides clues for the prevention of heavy metal-induced liver injury.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126497DOI Listing
October 2021

Spatiotemporal analysis of COVID-19 outbreaks in Wuhan, China.

Sci Rep 2021 07 1;11(1):13648. Epub 2021 Jul 1.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Few study has revealed spatial transmission characteristics of COVID-19 in Wuhan, China. We aimed to analyze the spatiotemporal spread of COVID-19 in Wuhan and its influence factors. Information of 32,682 COVID-19 cases reported through March 18 were extracted from the national infectious disease surveillance system. Geographic information system methods were applied to analysis transmission of COVID-19 and its influence factors in different periods. We found decrease in effective reproduction number (Rt) and COVID-19 related indicators through taking a series of effective public health measures including restricting traffic, centralized quarantine and strict stay-at home policy. The distribution of COVID-19 cases number in Wuhan showed obvious global aggregation and local aggregation. In addition, the analysis at streets-level suggested population density and the number of hospitals were associated with COVID-19 cases number. The epidemic situation showed obvious global and local spatial aggregations. High population density with larger number of hospitals may account for the aggregations. The epidemic in Wuhan was under control in a short time after strong quarantine measures and restrictions on movement of residents were implanted.
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http://dx.doi.org/10.1038/s41598-021-93020-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249501PMC
July 2021

Triiodothyronine ameliorates silica-induced pulmonary inflammation and fibrosis in mice.

Sci Total Environ 2021 Oct 26;790:148041. Epub 2021 May 26.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Environmental exposure to silica or particles is very common in natural, agricultural and industrial activities. Chronic silica exposure can lead to silicosis, which remains one of the most serious interstitial lung diseases all through the world, while viable therapeutic choices are restricted. Triiodothyronine (T3) has been shown to exert a defensive role in many pulmonary diseases, however, rare data are available regarding the role of T3 on silica-induced injury. We constructed an experimental silicosis mouse model and T3 was intraperitoneally administrated after instillation of silica to observe the effect of T3 on silica-induced lung inflammation and fibrosis. Our results showed that the silicosis mouse model was accompanied by changes in thyroid morphology and function, and T3 supplement reduced silica-induced lung damage, inflammation and collagen deposition. The protective properties of T3 on silica-induced lung injury could be partially mediated through thyroid hormone receptors. And the mechanism by which T3 treatment ameliorated silica-induced fibrosis appeared to be via the reduction of glycolysis. Also, T3 could sufficiently postpone the progression of pulmonary fibrosis in established silicosis. Our findings reveal that administration of T3 could down-regulate the inflammatory response, pulmonary fibrosis and other lung damage caused by silica. The reduction of glycolysis may be one of the mechanisms.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148041DOI Listing
October 2021

Associations between urinary phthalate metabolite concentrations and markers of liver injury in the US adult population.

Environ Int 2021 10 6;155:106608. Epub 2021 May 6.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address:

Background: Phthalates have been largely used for years in varieties of products worldwide. However, research on the joint toxic effect of various phthalates exposure on the liver is lacking.

Objectives: We aimed to assess exposure to phthalates on liver function tests (LFTs).

Methods: This analysis included data on 6046 adults (≥20 years old) who participated in a National Health and Nutrition Examination Survey (NHANES) in 2007-2016. We employed linear regression and Bayesian kernel machine regression (BKMR), to explore the associations of urinary phthalate metabolites with 8 indicators of LFTs.

Results: Di(2-ethylhexyl) phthalate (ΣDEHP) was found to be positively associated with serum alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) (all P  < 0.05). We found significant positive associations of ∑DEHP, mono-ethyl phthalate (MEP) and mono-(carboxyisononyl) phthalate (MCNP) with total bilirubin (TBIL) (all P  < 0.05). ΣDEHP, mono-n-butyl phthalate (MBP), mono-(3-carboxypropyl) phthalate (MCPP) and mono-benzyl phthalate (MBzP) were negatively associated with serum ALB (all P  < 0.05). The BKMR analyses showed a significantly positive overall effect on ALT, AST, ALP and TBIL levels with high concentrations of phthalate metabolites and a significantly negative overall effect on ALB and TP, when all the chemicals at low concentrations.

Conclusions: Our results add novel evidence that exposures to phthalates might be adversely associated with the indicators of LTFs, indicating the potential toxic effect of phthalate exposures on the human liver.
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http://dx.doi.org/10.1016/j.envint.2021.106608DOI Listing
October 2021

Preliminary study on impacts of polystyrene microplastics on the hematological system and gene expression in bone marrow cells of mice.

Ecotoxicol Environ Saf 2021 May 4;218:112296. Epub 2021 May 4.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China. Electronic address:

Microplastics (MPs) are currently a global environmental pollutants and health hazards that caused by MPs cannot be ignored. However, studies on MP toxicity in mammals are scare. Here, we investigated the effects of two doses (0.1 mg and 0.5 mg) of 5 µm polystyrene microplastic (PS-MP) particles on the hematological system of mice through traditional toxicology experiments and assessed the related potential biological mechanisms using transcriptome sequencing analysis. The toxicological examinations showed that the 0.5 mg dose significantly decreased white blood cell count, increased Pit count, and inhibited the growth of colony-forming unit CFU-G, CFU-M and CFU-GM. Compared with the control group, there were 41 differentially expressed genes (DEGs) in the 0.1 mg-treated group and 32 significantly changed genes in 0.5 mg-treated group. Of note, eight genes were found to be significantly altered in both the PS-MP-treated groups. Gene ontology analysis showed that DEGs were mainly involved in T cell homeostasis, response to osmotic stress, extracellular matrix and structure organization, and metabolic process of NADP and nucleotides. In addition, pathway analysis revealed that the Jak/Stat pathway, pentose and glucuronate interconversions, nicotinate and nicotinamide metabolism, biosynthesis of unsaturated fatty acids, and the pentose phosphate pathway were involved in PS-MP-induced toxicity in mice. These results indicated that PS-MP exposure can cause hematotoxicity to some extent, impact gene expression, and disturb related molecular and biological pathways in mouse bone marrow cells. Our study provides fundamental data on the hematotoxicity of PS-MPs in terrestrial mammals that will help to further assess the corresponding health risks in these mammals.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112296DOI Listing
May 2021

Recent advances in protein chromatography with polymer-grafted media.

Authors:
Linling Yu Yan Sun

J Chromatogr A 2021 Feb 5;1638:461865. Epub 2021 Jan 5.

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China. Electronic address:

The strategy of using polymer-grafted media is effective to create protein chromatography of high capacity and uptake rate, giving rise to an excellent performance in high-throughput protein separation due to its high dynamic binding capacity. Taking the scientific development and technological innovation of protein chromatography as the objective, this review is devoted to an overview of polymer-grafted media reported in the last five years, including their fabrication routes, protein adsorption and chromatography, mechanisms behind the adsorption behaviors, limitations of polymer-grafted media and chromatographic operation strategies. Particular emphasis is placed on the elaboration and discussion on the behaviors of ion-exchange chromatography (IEC) with polymer-grafted media because IEC is the most suitable chromatographic mode for this kind of media. Recent advances in both the theoretical and experimental investigations on polymer-grafted media are discussed by focusing on their implications to the rational design of novel chromatographic media and mobile phase conditions for the development of high-performance protein chromatography. It is concluded that polymer-grafted media are suitable for development of IEC and mixed-mode chromatography with charged and low hydrophobic ligands, but not for hydrophobic interaction chromatography with high hydrophobic ligands and affinity chromatography with ligands that have single binding site on the protein.
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http://dx.doi.org/10.1016/j.chroma.2020.461865DOI Listing
February 2021

Protein adsorption to poly(2-aminoethyl methacrylate)-grafted Sepharose gel: Effects of chain length and charge density.

J Chromatogr A 2021 Feb 31;1638:461869. Epub 2020 Dec 31.

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China. Electronic address:

Grafting functional polymer chains onto porous resins has been found to drastically increase both adsorption capacity and uptake rate in protein chromatography. In this work, 2-aminoethyl methacrylate (AEM) was used for grafting onto Sepharose FF gel, and six anion-exchangers of different polyAEM (pAEM) chain lengths (ionic capacities, ICs), FF-pAEM, were obtained for protein adsorption and chromatography. It was found that protein adsorption capacity (q) increased with increasing pAEM chain length, but the uptake rate, represented by the ratio of effective pore diffusivity to the free solution diffusivity (D/D), showed an up-down trend, reaching a peak value (D/D=0.55) at an IC of 313 mmol/L. Partial charge neutralization of the AEM-grafted resin of the highest IC (513 mmol/L) by reaction with sodium acetate produced three charge-reduced resins, FF-pAEM513-R. With reducing the charge density, the adsorption capacity kept unchanged and then decreased, but the uptake rate monotonically increased, reaching a maximum (about 2-fold increase) at a residual IC of 263 mmol/L. It is notable that, at the same IC, the charge-reduced resin (FF-pAEM513-R) presented similar or even higher values of q and D/D than its FF-pAEM counterpart. Particularly, at the same IC of 263 mmol/L, a ~50% enhancement of D/D was observed. Both adsorption capacity and uptake rate in the charge-reduced resin with a residual IC of 339 mmo/L (FF-pAEM513-R339) decreased more sharply with increasing NaCl concentration by comparison with FF-pAEM513, indicating its increased salt-sensitivity than FF-pAEM513. That is, charge reduction on the AEM-grafted resin could accelerate protein uptake at 0 mmol/L NaCl but decrease salt tolerance. Column breakthrough experiments showed that FF-pAEM513-R339 was favorable for high flow rate protein chromatography at low NaCl concentration (0 mmol/L), whereas FF-pAEM513 was a good choice in a wide range of salt concentrations at low flow rate. This research proved the excellent protein chromatography performance of the AEM-based anion-exchangers.
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http://dx.doi.org/10.1016/j.chroma.2020.461869DOI Listing
February 2021

Associations of urinary carbon disulfide metabolite with oxidative stress, plasma glucose and risk of diabetes among urban adults in China.

Environ Pollut 2021 Mar 29;272:115959. Epub 2020 Oct 29.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, And State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address:

Carbon disulfide (CS) has been reported to induce disorder of glucose metabolism. However, the associations of CS 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 CS 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 CS exposure (2-thiothiazolidin-4-carboxylic acid, TTCA), and biomarkers for lipid peroxidation (8-isoprostane, 8-iso-PGF) 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-PGF and 8-OHdG, respectively. Moreover, we found an upward trend of FPG level as urinary 8-iso-PGF gradually increased (P<0.05), and urinary 8-iso-PGF mediated 21.12% of the urinary TTCA-associated FPG increment. Our findings indicated that urinary CS metabolite was associated with increased FPG levels and diabetes risk in general population. Lipid peroxidation partly mediated the association of urinary CS metabolite with FPG levels.
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http://dx.doi.org/10.1016/j.envpol.2020.115959DOI Listing
March 2021

Toxicity in hematopoietic stem cells from bone marrow and peripheral blood in mice after benzene exposure: Single-cell transcriptome sequencing analysis.

Ecotoxicol Environ Saf 2021 Jan 26;207:111490. Epub 2020 Oct 26.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China. Electronic address:

Benzene is a ubiquitous, occupational, and environmental hematotoxic and leukemogen. Damage to hematopoietic stem cells (HSCs) induced by benzene and its metabolites is a key event in bone marrow (BM) depression and leukemogenesis. There are no reports on transcriptome profiles of HSCs following benzene exposure. Here, Smart-seq2 single-cell transcriptome sequencing was used to detect transcriptomic alternations in BM HSCs and peripheral blood HSCs (PBSCs) in male C57B/6 mice exposed to benzene. We found that benzene caused hematotoxicity which was confirmed by routine blood test, pathological examination, and HSCs percentage analysis. A total of 1514 differentially expressed genes (DEGs) in BM HSCs and 1703 DEGs in PBSCs were screened after treatment with benzene. Weighted gene correlation network analysis revealed that pathways in cancer, transcriptional misregulation in cancer, and hematopoietic cell lineage are vital pathways involved in benzene-induced toxicity in BM HSCs, whereas hematopoietic cell lineage and leukocyte transendothelial migration are critical pathways in PBSCs. Of note, there were 164 common DEGs in both HSCs, out of which 53 genes were co-regulated in both types of HSCs. Subsequent pathway analysis of these 53 genes indicated that the most relevant pathways involved neutrophil degranulation and CD93 localized in the core of the network of the 53 genes, which are known to regulate leukemia stem cell self-renewal and quiescence. Our results could enhance our understanding of HSC responses to benzene, facilitate the identification of potential molecular biomarkers and future studies on its mechanism of toxicity toward HSCs.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111490DOI Listing
January 2021

Epidemiological characteristics and the entire evolution of coronavirus disease 2019 in Wuhan, China.

Respir Res 2020 Oct 8;21(1):257. Epub 2020 Oct 8.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Background: Coronavirus Disease 2019 (COVID-19) spread rapidly around the world. We aimed to describe the epidemiological characteristics and the entire evolution of COVID-19 in Wuhan, and to evaluate the effect of non-pharmaceutical intervention by the government.

Methods: The information of COVID-19 cases until Mar 18, 2020 in Wuhan were collected from the national infectious disease surveillance system in Hubei province.

Results: A total of 49,973 confirmed cases were reported until Mar 18, 2020 in Wuhan. Among whom, 2496 cases died and the overall mortality was 5.0%. Most confirmed cases (25,619, 51.3%) occurred during Jan 23 to Feb 4, with a spike on Feb 1 (new cases, 3374). The number of daily new cases started to decrease steadily on Feb 19 (new cases, 301) and decreased greatly on Mar 1 (new cases, 57). However, the mortality and the proportion of severe and critical cases has been decreasing over time, with the lowest of 2.0 and 10.1% during Feb 16 to Mar 18, 2020, respectively. The percentage of severe and critical cases among all cases was 19.6%, and the percentage of critical and dead cases aged over 60 was 70.1 and 82.0%, respectively.

Conclusion: The number of new cases has dropped significantly after the government taking the isolation of four types of personnel and the community containment for 14 days. Our results indicate that the mortality and proportion of severe and critical cases gradually decreased over time, and critical and dead cases are more incline to be older individuals.
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http://dx.doi.org/10.1186/s12931-020-01525-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542568PMC
October 2020

Protein adsorption to (3-acrylamido propyl) trimethyl ammonium chloride-grafted Sepharose gel: Charge density reduction via copolymerizing with electroneutral monomer drastically increases uptake rate.

J Chromatogr A 2020 Oct 18;1629:461483. Epub 2020 Aug 18.

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China. Electronic address:

Polymer-grafting to porous materials is an effective way to create protein ion-exchangers of high capacity and uptake rate because the 3D architecture of the polymeric ion exchange groups provides high binding space and facilitated transport of the bound protein. Herein, a new anion exchanger was fabricated by grafting (3-acrylamide propyl) trimethyl ammonium chloride (APTAC) onto Sepharose FF gel for protein adsorption and chromatography. The ion exchanger, denoted as FF-pAPTAC, presented high capacity but limited uptake rate in bovine serum albumin (BSA) adsorption due to the high charge density of the cationic polymer chains. To solve the problem, we proposed to copolymerize APTAC with an electroneutral monomer, acrylamide (AM), onto Sepharose FF to modulate the charge density of the grafted polymer chains. By decreasing the feeding molar ratio of APTAC to AM, the ionic capacity (IC) of the copolymerized resins, FF-p(AM-APTAC)n (n denotes IC in mmol/L), decreased, but the chain length could be remained almost unchanged due to the similar reactivity ratios of the two monomers. With decreasing IC, the static adsorption capacity (q) of FF-p(AM-APTAC)n decreased gradually because of the decline of protein binding sites. The uptake rate, however, represented by the ratio of effective pore diffusivity to the free solution diffusivity (D/D), exhibited a strong uptrend with decreasing IC, reaching ~2.5-fold of the maximum observed with FF-pAPTACn. It is considered that the decrease of charge density weakened protein binding strength to the chains and increased the chain flexibility, which consequently facilitated the transport of bound proteins on the chains. Moreover, at the same IC, each FF-p(AM-APTAC)n displayed similar adsorption capacity but high uptake rate as compared with its FF-pAPTACn counterpart mainly due to the longer chain length of the copolymer. Particularly, ~6.5-fold enhancement of D/D was observed at IC = 50 ± 2 mmol/L. Both high adsorption capacity and uptake rate made FF-p(AM-APTAC)n exhibit superior dynamic binding performance. The findings proved that reducing chain charge density by copolymerizing an electroneutral monomer was promising for fabrication of high-performance protein ion exchangers.
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http://dx.doi.org/10.1016/j.chroma.2020.461483DOI Listing
October 2020

l-Carnitine protects against 1,4-benzoquinone-induced apoptosis and DNA damage by suppressing oxidative stress and promoting fatty acid oxidation in K562 cells.

Environ Toxicol 2020 Oct 1;35(10):1033-1042. Epub 2020 Jun 1.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing, China.

Widespread occupational and environmental exposure to benzene is unavoidable and poses a public health threat. Studies of potential interventions to prevent or relieve benzene toxicity are, thus, essential. Research has shown l-carnitine (LC) has beneficial effects against various pathological processes and diseases. LC possesses antioxidant activities and participates in fatty acid oxidation (FAO). In this study, we investigated whether 1,4-benzoquinone (1,4-BQ) affects LC levels and the FAO pathway, as well as analyzed the influence of LC on the cytotoxic effects of 1,4-BQ. We found that 1,4-BQ significantly decreased LC levels and downregulated Cpt1a, Cpt2, Crat, Hadha, Acaa2, and Acadvl mRNA expression in K562 cells. Subsequent assays confirmed that 1,4-BQ decreased cell viability and increased apoptosis and caspase-3, -8, and -9 activities. It also induced obvious oxidative stress and DNA damage, including an increase in the levels of reactive oxygen species and malondialdehyde, tail DNA%, and olive tail moment. Additionally, the mitochondrial membrane potential was significantly reduced. Cotreatment with LC (500 μmol/L) relieved these alterations by reducing oxidative stress and increasing the protein expression levels of Cpt1a and Hadha, particularly in the 20 μmol/L 1,4-BQ group. Thus, our results demonstrate that 1,4-BQ causes cytotoxicity, reduces LC levels, and downregulates the FAO genes. In contrast, LC exhibits protective effects against 1,4-BQ-induced apoptosis and DNA damage by decreasing oxidative stress and promoting the FAO pathway.
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http://dx.doi.org/10.1002/tox.22939DOI Listing
October 2020

Increasing incidence of asbestosis worldwide, 1990-2017: results from the Global Burden of Disease study 2017.

Thorax 2020 09 28;75(9):798-800. Epub 2020 May 28.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Global incidence and temporal trends of asbestosis are rarely explored. Using the detailed information on asbestosis from the Global Burden of Disease (GBD) 2017, we described the age-standardised incidence rate (ASIR) and its average annual percentage change. A Joinpoint Regression model was applied to identify varying temporal trends over time. Although the use of asbestos has been completely banned in many countries, the ASIR of asbestosis increased globally from 1990 to 2017. Furthermore, the most pronounced increases in ASIR of asbestosis were detected in high-income North America and Australasia. These findings indicate that efforts to change the asbestos regulation policy are urgently needed.
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http://dx.doi.org/10.1136/thoraxjnl-2020-214822DOI Listing
September 2020

Triiodothyronine Attenuates Silica-Induced Oxidative Stress, Inflammation, and Apoptosis via Thyroid Hormone Receptor α in Differentiated THP-1 Macrophages.

Chem Res Toxicol 2020 05 3;33(5):1256-1265. Epub 2020 Apr 3.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Alveolar macrophage (AM) injury and inflammatory response are key processes in pathological damage caused by silica. However, the role of triiodothyronine (T3) in silica-induced AM oxidative stress, inflammation, and mitochondrial apoptosis remained unknown. To investigate the possible effects and underlying mechanism of T3 in silica-induced macrophage damage, differentiated human acute monocytic leukemia cells (THP-1) were exposed to different silica concentrations (0, 50, 100, 200, and 400 μg/mL) for 24 h. Additionally, silica-activated THP-1 macrophages were treated with gradient-dose T3 (0, 5, 10, 20, and 40 nM) for 24 h. To illuminate the potential mechanism, we used short hairpin RNA to knock down the thyroid hormone receptor α (TRα) in the differentiated THP-1 macrophages. The results showed that T3 decreased lactate dehydrogenase and reactive oxygen species levels, while increasing cell viability and superoxide dismutase in silica-induced THP-1 macrophages. In addition, silica increased the expression of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), and T3 treatment reduced those pro-inflammatory cytokines secretion. Compared with silica-alone treated groups, cells treated with silica and T3 restored the mitochondrial membrane potential loss and had reduced levels of cytochrome and cleaved caspase-3 expressions. Lastly, we observed that TRα-knockdown inhibited the protective effects of T3 silica-induced THP-1 macrophages. Together, these findings revealed that T3 could serve as a potential therapeutic target for protection against silica-induced oxidative stress, inflammatory response, and mitochondrial apoptosis, which are mediated by the activation of the T3/TRα signal pathway.
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http://dx.doi.org/10.1021/acs.chemrestox.0c00018DOI Listing
May 2020

Association between indoor formaldehyde exposure and asthma: A systematic review and meta-analysis of observational studies.

Indoor Air 2020 07 19;30(4):682-690. Epub 2020 Mar 19.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

About 339 million people worldwide are suffering from asthma. We aimed to investigate whether exposure to formaldehyde (FA) is associated with asthma, which could provide clues for preventive and mitigation actions. This article provides a systematic review and meta-analysis of observational studies to assess the association between indoor FA exposure and the risk of asthma in children and adults. An electronic search of PubMed, Embase, and Web of Science was performed to collect all relevant studies published before January 1, 2020, and a total of 13 papers were included in this meta-analysis. A random-effect model was conducted to calculate the pooled odds ratio (OR) between FA exposure and asthma. We found that each 10 µg/m increase in FA exposure was significantly associated with a 10% increase in the risk of asthma in children (OR = 1.10, 95% confidence interval = 1.00-1.21). We sorted the FA concentrations reported in the selected articles and categorized exposure variables into low (FA ≤ 22.5 µg/m ) and high exposure (FA > 22.5 µg/m ) according to the median concentration of FA. In the high-exposure adult group, FA exposure may also be associated with an increased risk of asthma (OR = 1.81, 95% CI = 1.18-2.78).
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http://dx.doi.org/10.1111/ina.12657DOI Listing
July 2020

Protein adsorption to poly(ethylenimine)-modified Sepharose FF: VIII: Impacts of surface ion-exchange groups at different polymer grafting densities.

J Chromatogr A 2020 Jan 10;1610:460538. Epub 2019 Sep 10.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Our previous studies on protein adsorption to the anion-exchangers of poly(ethylenimine) (PEI)-grafted Sepharose FF found that both adsorption capacity and uptake rate of bovine serum albumin (BSA) increased greatly when the PEI grafting density reached over a critical ionic capacity (cIC) due to the 3D protein binding and occurrence of "chain delivery" of bound proteins. Moreover, by the investigation on the anion-exchangers of diethylaminoethyl (DEAE)-modified and DEAE-dextran-grafted Sepharose FF, we found the unique role of surface ligand in facilitating protein uptake kinetics on dextran-functionalized anion exchangers as the "transfer station" for the "chain delivery" of bound proteins. However, what would be the contribution of surface ligands on the transport of bound proteins on PEI chains at a wide range across cIC, particularly at the lower IC range where no "chain delivery" was present? We have thus designed this research to answer the question. To this purpose, we fabricated three series of PEI-Sepharose FF resins, one without surface ligand (i.e., FF-PEI) and two with surface DEAE modifications at DEAE coupling densities of 60 and 90 mmol/L (i.e., FF-D60-PEI and FF-D90-PEI), and focused on the role of surface DEAE at different PEI densities in BSA adsorption equilibrium and uptake kinetics in a wide IC range of PEI across cIC (∼600 mmol/L for BSA). It was found that, at low grafting-ligand densities (IC cIC, however, both adsorption capacity and uptake rate changed only slightly (<5% and <10%, respectively) by the addition of surface DEAE groups. The results revealed that at IC < cIC, the surface DEAE groups provided the supplement of available binding sites and facilitated the happenings of the "chain delivery" of bound proteins as the "transfer station", both of which were limited at the low IC range. However, at IC > cIC, the extended flexible PEI chains have already afforded 3D binding space with high accessibility and easy happening of "chain delivery" of bound proteins, so the surface DEAE groups between neighboring PEI chains did not work in assisting the transport of bound proteins. Moreover, when the IC was lower but close to the cIC, the FF-D-PEI resins exhibited higher uptake rates than FF-PEI resins at a similar or even lower IC values. These findings indicate that surface modification of charged groups in PEI-based anion exchangers of low grafting density would be an efficient strategy to fabricate high performance protein ion exchangers.
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http://dx.doi.org/10.1016/j.chroma.2019.460538DOI Listing
January 2020

Protein adsorption to poly(ethylenimine)-modified sepharose FF: VII. Complicated effects of pH.

J Chromatogr A 2018 Dec 22;1580:72-79. Epub 2018 Oct 22.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Previously, we have studied protein adsorption behaviors on a series of poly(ethylenimine) (PEI)-grafted Sepharose FF, and a critical ionic capacity of PEI-grafted resins was observed, above which both protein adsorption capacity (q) and effective pore diffusivity (D) increased drastically. Moreover, reducing the charge density of the PEI-grafted resins from an ionic capacity of 740 mmol/L (FF-PEI-L740) to 440 mmol/L (FF-PEI-R440) by neutralization of the amino groups of PEI chains with sodium acetate brought out a three-fold increase of D value at pH 8. In this work, FF-PEI-L740 and FF-PEI-R440 were selected to investigate the complicated effects of pH on protein adsorption behavior using bovine serum albumin (BSA) as the model protein. It was found that, for FF-PEI-L740, both the q and D values decreased significantly when pH decreased from 9 to 5.5, and then increased dramatically at pH 5, and finally decreased remarkably at pH 4.5. The results were considered due to the following causes: The decrease of pH from 9 to 5.5 led to a greatly increased electrostatic repulsion between the PEI chains due to the increased dissociation degree of PEI, which caused the increase in steric hindrance effects and decrease in the bound protein transport by chain delivery. At pH 5, which was near the pI of BSA (∼4.9), the presence of few protein charges greatly decreased the electrostatic hindrance effect on protein transport and the high charge density of FF-PEI-L740 provided extensively accessible binding sites and facilitated the happening of chain delivery as well. At pH 4.5, the net charge of BSA shifted to positive, likely charged with PEI, so the overall electrostatic repulsion greatly hindered protein uptake. For FF-PEI-R440, whose charge density was much lower than FF-PEI-L740, its q and D values even increased mildly when pH decreased from 8 to 5.5, because its slightly-increased charge density did not cause much increased electrostatic and steric hindrance effects but provided more binding sites for protein adsorption. At pH 5, the few charges of BSA and the low charge density of FF-PEI-R440 could not afford enough electrostatic interaction for protein binding, resulting in significantly decreased q and D values. Besides, column breakthrough experiments revealed that FF-PEI-R440 kept high dynamic binding capacity (DBC) (>120 mg/mL) at pH 5.5-8, while FF-PEI-L740 offered high DBC (>80 mg/mL) at pH 5, 7 and 8 with a higher salt concentration (100 mmol/L NaCl). These findings demonstrated the excellence of FF-PEI-L740 and FF-PEI-R440 in different conditions, and would help in the design and selection of suitable resins for high-performance protein chromatography.
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http://dx.doi.org/10.1016/j.chroma.2018.10.033DOI Listing
December 2018
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