Publications by authors named "Man Cheng"

55 Publications

Acrylamide exposure and pulmonary function reduction in general population: The mediating effect of systemic inflammation.

Sci Total Environ 2021 Jul 9;778:146304. Epub 2021 Mar 9.

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

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 trend<0.05). 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, respectively. Such relationships were independent of smoking, and were significant in physically inactive rather than physically active participants. AAMA (β = 0.10), GAMA (β = 0.16) and ΣUAAM (β = 0.12) were significantly (P < 0.05) related to increased CRP, which was significantly (P < 0.05) related to reduced FVC (β = -55.3) and FEV (β = -40.6). We further found that increased CRP significantly (P < 0.05) mediated 6.34-11.1% of the urinary acrylamide metabolites-associated lung function reductions. For the first time, our findings suggested that exposure to acrylamide in daily life was related to reduced lung function and increased systemic inflammation in general population, and systemic inflammation further mediated acrylamide-associated lung function reduction, indicating a potential mechanistic role of systemic inflammation underlying pulmonary dysfunction from acrylamide exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146304DOI Listing
July 2021

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

Environ Int 2021 May 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
May 2021

Rashba valleys and quantum Hall states in few-layer black arsenic.

Nature 2021 May 5;593(7857):56-60. Epub 2021 May 5.

Zhejiang Province Key Laboratory of Quantum Technology and Device, Department of Physics, Zhejiang University, Hangzhou, People's Republic of China.

Exciting phenomena may emerge in non-centrosymmetric two-dimensional electronic systems when spin-orbit coupling (SOC) interplays dynamically with Coulomb interactions, band topology and external modulating forces. Here we report synergetic effects between SOC and the Stark effect in centrosymmetric few-layer black arsenic, which manifest as particle-hole asymmetric Rashba valley formation and exotic quantum Hall states that are reversibly controlled by electrostatic gating. The unusual findings are rooted in the puckering square lattice of black arsenic, in which heavy 4p orbitals form a Brillouin zone-centred Γ valley with p symmetry, coexisting with doubly degenerate D valleys of p origin near the time-reversal-invariant momenta of the X points. When a perpendicular electric field breaks the structure inversion symmetry, strong Rashba SOC is activated for the p bands, which produces spin-valley-flavoured D valleys paired by time-reversal symmetry, whereas Rashba splitting of the Γ valley is constrained by the p symmetry. Intriguingly, the giant Stark effect shows the same p-orbital selectiveness, collectively shifting the valence band maximum of the D Rashba valleys to exceed the Γ Rashba top. Such an orchestrating effect allows us to realize gate-tunable Rashba valley manipulations for two-dimensional hole gases, hallmarked by unconventional even-to-odd transitions in quantum Hall states due to the formation of a flavour-dependent Landau level spectrum. For two-dimensional electron gases, the quantization of the Γ Rashba valley is characterized by peculiar density-dependent transitions in the band topology from trivial parabolic pockets to helical Dirac fermions.
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http://dx.doi.org/10.1038/s41586-021-03449-8DOI Listing
May 2021

Association of shift work with cardiovascular disease risk among Chinese workers.

Chronobiol Int 2021 Apr 28:1-9. Epub 2021 Apr 28.

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

To evaluate the association of shift work with 10-year cardiovascular disease (CVD) risk among Chinese workers. We included 23,064 workers in the first follow-up of the Dongfeng-Tongji cohort study. Questionnaires and physical examinations were conducted to collect data for all participants. Framingham Risk Score was calculated according to the multivariable risk algorithms, and used to evaluate 10-year CVD risk. Logistic regression models were used to assess the relationship between shift work and 10-year CVD risk. Among 23,064 individuals, 51.92% of workers suffered shift work, and the proportions of shift work duration of 1-<10, 10-<20, and ≥20 years were 17.29%, 17.35% and 17.30%, respectively. Compared with individuals without a shift work history, the odds ratios (ORs) and 95% confidence intervals (CIs) of 10-year CVD were 1.027 (0.900-1.173), 1.058 (0.927-1.206) and 1.191 (1.036-1.368) for individuals with shift work duration of 1-<10 years, 10-<20 years, and ≥20 years, respectively, after adjusting for potential confounders. And the association was more obvious in males. When shift work and obesity were combined, the OR (95%CI) of high 10-year CVD risk (3.373, 2.390-4.761) was significantly increased for obese individuals with shift work of ≥20 years. Besides, the OR (95%CI) for higher 10-year CVD risk associated with shift work decreased as the leaving shift work duration prolonged. Shift work is associated with a higher 10-year CVD risk, especially among males. Obesity has a synergistic effect on such association while leaving shift work reduces such association.
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http://dx.doi.org/10.1080/07420528.2021.1917593DOI Listing
April 2021

Peripheral white blood cell counts mediated the associations of sleep duration with atherosclerotic cardiovascular disease risk: a cross-sectional study of middle-aged and older Chinese.

Sleep Breath 2021 Mar 18. Epub 2021 Mar 18.

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

Purpose: To investigate the associations between sleep duration and atherosclerotic cardiovascular disease (ASCVD) risk and the potential mechanism.

Methods: 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.

Results: 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.

Conclusions: Extended sleep durations are associated with the increased 10-year ASCVD risk, and the associations are partially mediated by peripheral WBC counts.
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http://dx.doi.org/10.1007/s11325-021-02338-8DOI Listing
March 2021

Ectopic CD137 expression by rhabdomyosarcoma provides selection advantages but allows immunotherapeutic targeting.

Oncoimmunology 2021 02 4;10(1):1877459. Epub 2021 Feb 4.

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Rhabdomyosarcoma (RMS) is a heterogeneous soft tissue neoplasm most frequently found in children and adolescents. As the prognosis for recurrent and metastatic RMS remains poor, immunotherapies are hoped to improve quality of life and survival. CD137 is a member of tumor necrosis factor receptor family and a T cell costimulatory molecule which induces potent cellular immune responses that are able to eliminate malignant cells. Therefore, it was puzzling to find expression of CD137 on an RMS tissue microarray by multiplex staining. CD137 is not only expressed by infiltrating T cells but also by malignant RMS cells. Functional in vitro experiments demonstrate that CD137 on RMS cells is being transferred to adjacent antigen-presenting cells by trogocytosis, where it downregulates CD137 ligand, and thereby reduces T cell costimulation which results in reduced killing of RMS cells. The transfer of CD137 and the subsequent downregulation of CD137 ligand is a physiological negative feedback mechanism that is likely usurped by RMS, and may facilitate its escape from immune surveillance. In addition, CD137 signals into RMS cells and induces IL-6 and IL-8 secretion, which are linked to RMS metastasis and poor prognosis. However, the ectopic expression of CD137 on RMS cells is an Achilles' heel that may be utilized for immunotherapy. Natural killer cells expressing an anti-CD137 chimeric antigen receptor specifically kill CD137-expressing RMS cells. Our study implicates ectopic CD137 expression as a pathogenesis mechanism in RMS, and it demonstrates that CD137 may be a novel target for immunotherapy of RMS.
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http://dx.doi.org/10.1080/2162402X.2021.1877459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872024PMC
February 2021

Effects of exogenous nerve growth factor on the expression of BMP-9 and VEGF in the healing of rabbit mandible fracture with local nerve injury.

J Orthop Surg Res 2021 Jan 21;16(1):74. Epub 2021 Jan 21.

Oral Maxillofacial Trauma and Orthognathic Surgery, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Background: Mandibular fracture healing is a complex process involving nerves and growth factors. Nerve growth factor (NGF) not only facilitates the maintenance of sympathetic neurite growth but also stimulates other growth factors that can promote the essential osteogenesis and angiogenesis for fracture healing. Therefore, it is necessary to analyze the combined effects of NGF, bone morphogenic protein-9 (BMP-9), and vascular endothelial growth factor (VEGF) to accelerate the healing of mandible fractures.

Methods: The models of mandible fracture with local nerve injury established in 48 rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group, and intact group. The recovery of nerve reflex was assessed by observing the number of rabbits with lower lip responses to acupuncture. The fracture healing was observed with visual and CBCT, and then callus tissues from the mandibular fracture area were collected for hematoxylin and eosin (HE) staining observation, and the expression of BMP-9 and VEGF in callus at different stages was detected by quantitative real-time PCR (qRT-PCR).

Results: Needling reaction in the lower lip showed the number of animals with nerve reflex recovery was significantly higher in the NGF group than that in the GS and blank groups at the 2nd and 4th weeks after the operation. The combined results of macroscopic observation, CBCT examination, and histological analysis showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in the NGF group and the amount of callus formation and reconstruction was better than that in the GS group at the 2nd week after the operation. The qRT-PCR results indicated that the expression levels of BMP-9 and VEGF in the four groups reached the highest values at the 2nd week, while the expression levels of both in the NGF group were significantly higher than that in the GS group.

Conclusion: The exogenous NGF could accelerate the healing of mandible fractures. This work will provide a new foundation and theoretical basis for clarifying the mechanism of fracture healing, thereby promoting fracture healing and reducing the disability rate of patients.
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http://dx.doi.org/10.1186/s13018-021-02220-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818757PMC
January 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

Gas6 or Mer deficiency ameliorates silica-induced autophagosomes accumulation in mice lung.

Toxicol Lett 2021 Feb 21;337:28-37. Epub 2020 Nov 21.

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 and Ministry of Environmental Protection, 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:

Published evidences have shown that autophagy plays an important role in silica-induced lung inflammation and collagen deposition. Our previous study found that the level of growth arrest-specific protein 6 (Gas6) in bronchoalveolar lavage fluid was increased after silica exposure. However, it is unclear whether Gas6 is involved in the regulation of silica-induced autophagy dysfunction. In this study, we observed an autophagosomes accumulation in wild-type C57BL/6 (WT) mice lung after silica intratracheal instillation and then investigated whether genetic loss of Gas6 (Gas6) could ameliorate it. Our data showed that Gas6 mice exhibited a limited autophagosomes accumulation from days 7-84 after silica exposure, revealed by reduced induction and increased degradation of autophagosomes in mice lung tissue. Interestingly, silica particles could elevate the expression of Mer receptor, which was significantly decreased in Gas6 mice (P < 0.05). Furthermore, we found that Mer deficiency (Mer) could also reduce the formation of autophagosomes and restore the function of impaired lysosomes in silica-treated mice. Taken together, our results indicate that genetic loss of Gas6 attenuates silica-induced autophagosomes accumulation partly through down-regulating the expression of Mer receptor. Targeting Gas6/Mer-mediated autophagy pathway may provide a novel insight into the prevention and therapy of silica-induced pulmonary fibrosis.
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http://dx.doi.org/10.1016/j.toxlet.2020.11.013DOI Listing
February 2021

Active RNA interference in mitochondria.

Cell Res 2021 Feb 17;31(2):219-228. Epub 2020 Aug 17.

Key Laboratory for RNA Biology, Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China.

RNA interference (RNAi) has been thought to be a gene-silencing pathway present in most eukaryotic cells to safeguard the genome against retrotransposition. Small interfering RNAs (siRNAs) have also become a powerful tool for studying gene functions. Given the endosymbiotic hypothesis that mitochondria originated from prokaryotes, mitochondria have been generally assumed to lack active RNAi; however, certain bacteria have Argonaute homologs and various reports suggest the presence of specific microRNAs and nuclear genome (nDNA)-encoded Ago2 in the mitochondria. Here we report that transfected siRNAs are not only able to enter the matrix of mitochondria, but also function there to specifically silence targeted mitochondrial transcripts. The mitoRNAi effect is readily detectable at the mRNA level, but only recordable on relatively unstable proteins, such as the mtDNA-encoded complex IV subunits. We also apply mitoRNAi to directly determine the postulated crosstalk between individual respiratory chain complexes, and our result suggests that the controversial observations previously made in patient-derived cells might result from differential adaptation in different cell lines. Our findings bring a new tool to study mitochondrial biology.
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http://dx.doi.org/10.1038/s41422-020-00394-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027830PMC
February 2021

Iron promotes breast cancer cell migration via IL-6/JAK2/STAT3 signaling pathways in a paracrine or autocrine IL-6-rich inflammatory environment.

J Inorg Biochem 2020 09 24;210:111159. Epub 2020 Jun 24.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

Iron overload can act as catalyst for the formation of free radicals, which may promote oxidant-mediated breast carcinogenesis. However, the association between iron and breast cancer has not been comprehensively elucidated. In this study, we found that iron overload upregulated the inflammatory cytokine interleukin-6 (IL-6) expression to activate Janus Kinases 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) signaling in triple negative breast cancer (TNBC) MDA-MB-231 cell lines, resulting in epithelial-mesenchymal transition (EMT) and cancer cell migration, but it had no effects on the estrogen receptor (ER)-positive breast cancer MCF-7 cells. However, in the presence of exogenous IL-6, iron overload could also dramatically induce an autocrine IL-6 loop in ER-positive MCF-7 cells to active IL-6/JAK2/STAT3 signaling, resulting in enhanced EMT and cell motility. In vivo animal studies also identified that iron overload promoted the progression of low metastatic breast cancer tumorigenicity and lung metastasis following the addition of exogenous IL-6. This study suggested that iron overload could result in inducible IL-6 expression leading to promote malignant transformation of breast cancer cells in an paracrine or autocrine IL-6-rich inflammatory environment. Anti-inflammation and iron depletion therapy would be an effective therapeutic/preventive strategy for suppressing breast cancer progression.
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http://dx.doi.org/10.1016/j.jinorgbio.2020.111159DOI Listing
September 2020

IL-22: A potential mediator of associations between urinary polycyclic aromatic hydrocarbon metabolites with fasting plasma glucose and type 2 diabetes.

J Hazard Mater 2021 01 23;401:123278. Epub 2020 Jun 23.

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

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.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123278DOI Listing
January 2021

Magnetic Structure and Metamagnetic Transitions in the van der Waals Antiferromagnet CrPS.

Adv Mater 2020 Jul 5;32(28):e2001200. Epub 2020 Jun 5.

State Key Laboratory for Artificial Microstructure & Mesoscopic Physics, School of Physics, Peking University, Beijing, 100871, P. R. China.

In 2D magnets, interlayer exchange coupling is generally weak due to the van der Waals layered structure but it still plays a vital role in stabilizing the long-range magnetic ordering and determining the magnetic properties. Using complementary neutron diffraction, magnetic, and torque measurements, the complete magnetic phase diagram of CrPS crystals is determined. CrPS shows an antiferromagnetic ground state (A-type) formed by out-of-plane ferromagnetic monolayers with interlayer antiferromagnetic coupling along the c axis below T = 38 K. Due to small magnetic anisotropy energy and weak interlayer coupling, the low-field metamagnetic transitions in CrPS that is, a spin-flop transition at ≈0.7 T and a spin-flip transition from antiferromagnetic to ferromagnetic under a relatively low field of 8 T, can be realized for H∥c. Intriguingly, with an inherent in-plane lattice anisotropy, spin-flop-induced moment realignment in CrPS for H∥c is parallel to the quasi-1D chains of CrS octahedra. The peculiar metamagnetic transitions and in-plane anisotropy make few-layer CrPS flakes a fascinating platform for studying 2D magnetism and for exploring prototype device applications in spintronics and optoelectronics.
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http://dx.doi.org/10.1002/adma.202001200DOI Listing
July 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

Acrylamide Exposure and Oxidative DNA Damage, Lipid Peroxidation, and Fasting Plasma Glucose Alteration: Association and Mediation Analyses in Chinese Urban Adults.

Diabetes Care 2020 07 28;43(7):1479-1486. Epub 2020 Apr 28.

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

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 ( and/or 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 ( and 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.
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http://dx.doi.org/10.2337/dc19-2603DOI Listing
July 2020

Exposure to acrylamide and reduced heart rate variability: The mediating role of transforming growth factor-β.

J Hazard Mater 2020 08 15;395:122677. Epub 2020 Apr 15.

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:

The potential adverse health effects of acrylamide have drawn worldwide attention and the World Health Organization has urged further urgent studies on its health threat. Herein we explored the exposure-response relationship and underlying mechanism between internal acrylamide exposure and heart rate variability (HRV) alteration, a marker of cardiac autonomic dysfunction. We measured six HRV indices and two urinary acrylamide metabolites (N-Acetyl-S-(2-carbamoylethyl)-l-cysteine, AAMA; N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine, GAMA) for 2997 general Chinese adults from the Wuhan-Zhuhai cohort, of whom 2414 had data on plasma transforming growth factor-β1 (TGF-β1). The associations among urinary acrylamide metabolites, HRV and TGF-β1 were evaluated by linear mixed models and restricted cubic spline models. The mediating role of TGF-β1 was investigated by conducting mediation analysis. We found significantly negative dose-response relationships of all urinary acrylamide metabolites and TGF-β1 with all six HRV indices after adjusting for potential confounders (all P < 0.05). Urinary GAMA (β=0.074, P < 0.05) rather than AAMA (β=0.024, P > 0.05) was positively and dose-dependently associated with TGF-β1, which in turn significantly mediated 5.71-7.41 % of the GAMA-associated HRV reduction. Our findings suggest for the first time that daily exposure of general population to acrylamide is associated with cardiac autonomic dysfunction, where a mechanism involving TGF-β pathway may be involved.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122677DOI Listing
August 2020

Association of urinary dimethylformamide metabolite with lung function decline: The potential mediating role of systematic inflammation estimated by C-reactive protein.

Sci Total Environ 2020 Jul 10;726:138604. Epub 2020 Apr 10.

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:

Dimethylformamide (DMF) is a volatile organic compound listed as one of the four toxicants with the highest priority for human field study. However, the effect of DMF exposure on lung function and the underlying mechanisms remain unknown. We aimed to investigate the exposure-response relationship and possible mechanism between internal DMF exposure and lung function alteration. We studied 3701 Chinese adults from the Wuhan-Zhuhai cohort with a 3-year follow-up. The cross-sectional relationship between urinary biomarker of DMF exposure (N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine, AMCC) and lung function, and the mediating role of plasma C-reactive protein (CRP) were assessed. We also convened a sub-cohort (N = 138) to assess the stability of AMCC in repeated urine samples collected for continuous 3 days and intervals of 1, 2 and 3 years. The longitudinal association between AMCC and lung function change in 3 years was further assessed. We found a dose-response relationship between AMCC and lung function reduction. Each 2-fold increase in AMCC was cross-sectionally associated with a 23.12-mL (95% CI: -36.68, -9.55) decrease in FVC and a 19.01-mL (95% CI: -31.08, -6.93) decrease in FEV. Increased CRP significantly mediated 5.39% and 5.87% of the AMCC-associated FVC and FEV reductions, respectively. With 3-year follow-up, AMCC showed a fair to excellent stability (intra-class correlation coefficients were 0.88, 0.55, 0.60 and 0.50 for continuous 3 days, intervals of 1, 2 and 3 years, respectively) and was dose-dependently associated with longitudinal lung function decline. Compared with those with persistent low AMCC levels, participants with persistent high AMCC levels had a 101.09-mL/year (95% CI: -167.40, -34.77) decline in FVC and a 66.27-mL/year (95% CI: -114.14, -18.41) decline in FEV in the sub-cohort. Similar results were found in the full-cohort. Our findings suggest that exposure of general population to environmental DMF may impair lung function, and systematic inflammation may be an underlying mechanism.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138604DOI Listing
July 2020

Simultaneous tracking of two motor domains reveals near simultaneous steps and stutter steps of myosin 10 on actin filament bundles.

Biochem Biophys Res Commun 2020 Feb 17. Epub 2020 Feb 17.

Department of Physics, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong; Division of Life Science, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong; State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong. Electronic address:

Myosin X (Myo10) has several unique design features including dimerization via an anti-parallel coiled coil and a long lever arm, which allow it to preferentially move on actin bundles. To understand the stepping behavior of single Myo10 on actin bundles, we labeled two heads of Myo10 dimers with different fluorophores. Unlike previously described for myosin V (Myo5) and VI (Myo6), which display alternating hand-over-hand stepping, Myo10 frequently took near simultaneous steps of both heads, and less frequently, 2-3 steps of one head before the other head stepped. We suggest that this behavior results from the unusual kinetic features of Myo10, in conjunction with the structural properties of the motor domain/lever arm, which will favor movement on actin bundles rather than on single filaments.
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http://dx.doi.org/10.1016/j.bbrc.2020.02.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429334PMC
February 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

On the Relationship Between General Auditory Sensitivity and Speech Perception: An Examination of Pitch and Lexical Tone Perception in 4- to 6-Year-Old Children.

J Speech Lang Hear Res 2020 02 11;63(2):487-498. Epub 2020 Feb 11.

Faculty of Education, Division of Speech and Hearing Sciences, The University of Hong Kong, Pokfulam.

Purpose Theoretical models and substantial research have proposed that general auditory sensitivity is a developmental foundation for speech perception and language acquisition. Nonetheless, controversies exist about the effectiveness of general auditory training in improving speech and language skills. This research investigated the relationships among general auditory sensitivity, phonemic speech perception, and word-level speech perception via the examination of pitch and lexical tone perception in children. Method Forty-eight typically developing 4- to 6-year-old Cantonese-speaking children were tested on the discrimination of the pitch patterns of lexical tones in synthetic stimuli, discrimination of naturally produced lexical tones, and identification of lexical tone in familiar words. Results The findings revealed that accurate lexical tone discrimination and identification did not necessarily entail the accurate discrimination of nonlinguistic stimuli that followed the pitch levels and pitch shapes of lexical tones. Although pitch discrimination and tone discrimination abilities were strongly correlated, accuracy in pitch discrimination was lower than that in tone discrimination, and nonspeech pitch discrimination ability did not precede linguistic tone discrimination in the developmental trajectory. Conclusions Contradicting the theoretical models, the findings of this study suggest that general auditory sensitivity and speech perception may not be causally or hierarchically related. The finding that accuracy in pitch discrimination is lower than that in tone discrimination suggests that comparable nonlinguistic auditory perceptual ability may not be necessary for accurate speech perception and language learning. The results cast doubt on the use of nonlinguistic auditory perceptual training to improve children's speech, language, and literacy abilities.
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http://dx.doi.org/10.1044/2019_JSLHR-19-00104DOI Listing
February 2020

JAK2/STAT3 involves oxidative stress-induced cell injury in N2a cells and a rat MCAO model.

Int J Neurosci 2020 Nov 24;130(11):1142-1150. Epub 2020 Feb 24.

Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.

In this study, we sought to test the hypothesis that oxidative stress injury in ischemic brains and HO-treated mouse neuroblastoma Neuro-2a cells (N2a) was related to STAT3 activation. Rat middle cerebral artery occlusion (MCAO) model and HO-treated mouse neuroblastoma Neuro-2a cells (N2a) were used to investigate the relationship between oxidative stress injury and STAT3 activation. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) content and STAT3 protein phosphorylation level were significantly increased after cerebral ischemia-reperfusion. HO treatment inhibited the cell viability, induced the apoptosis, and further raised pSTAT3 protein level in N2a cells. Moreover, the addition of AG490, the protein inhibitor of JAK2, significantly alleviated cerebral ischemic damage in vivo and HO-induced injury , and JAK2 siRNA also alleviated HO-induced injury in N2a cell. JAK2/STAT3 pathway may play a crucial role in mediating reactive oxidative species (ROS)-induced cell injury in rat middle cerebral artery occlusion (MCAO) model and N2a cells. ROS scavenging and down-regulation of STAT3 activation might be a candidate design of therapeutic strategies against oxidative stress-related neurological diseases.
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http://dx.doi.org/10.1080/00207454.2020.1730829DOI Listing
November 2020

Reply.

Occup Med (Lond) 2019 12;69(8-9):637-638

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http://dx.doi.org/10.1093/occmed/kqz138DOI Listing
December 2019

microRNAs expression in relation to particulate matter exposure: A systematic review.

Environ Pollut 2020 May 21;260:113961. Epub 2020 Jan 21.

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

MicroRNAs (miRNAs) are a class of small, non-coding RNAs with a post-transcriptional regulatory function on gene expression and cell processes, including proliferation, apoptosis and differentiation. In recent decades, miRNAs have attracted increasing interest to explore the role of epigenetics in response to air pollution. Air pollution, which always contains kinds of particulate matters, are able to reach respiratory tract and blood circulation and then causing epigenetics changes. In addition, extensive studies have illustrated that miRNAs serve as a bridge between particulate matter exposure and health-related effects, like inflammatory cytokines, blood pressure, vascular condition and lung function. The purpose of this review is to summarize the present knowledge about the expression of miRNAs in response to particulate matter exposure. Epidemiological and experimental studies were reviewed in two parts according to the size and source of particles. In this review, we also discussed various functions of the altered miRNAs and predicted potential biological mechanism participated in particulate matter-induced health effects. More rigorous studies are worth conducting to understand contribution of particulate matter on miRNAs alteration and the etiology between environmental exposure and disease development.
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http://dx.doi.org/10.1016/j.envpol.2020.113961DOI Listing
May 2020

Development of a Bispecific Antibody Targeting CD30 and CD137 on Hodgkin and Reed-Sternberg Cells.

Front Oncol 2019 24;9:945. Epub 2019 Sep 24.

Department of Physiology, National University of Singapore, Singapore, Singapore.

Hodgkin Lymphoma (HL) is a malignancy that frequently affects young adults. Although, there are effective treatments not every patient responds, necessitating the development of novel therapeutic approaches, especially for relapsed and refractory cases. The two TNF receptor family members CD30 and CD137 are expressed on Hodgkin and Reed Sternberg (HRS) cells, the malignant cells in HL. We found that this co-expression is specific for HRS cells. Based on this discovery we developed a bispecific antibody that binds preferentially to the CD30, CD137-double positive HRS cells. The CD30, CD137 bispecific antibody gets internalized into HRS cells opening up the possibility to use it as a carrier for a toxin. This antibody also induces antibody-dependent, cell-mediated cytotoxicity in CD30, CD137-double positive HRS cells. The enhances specificity of the CD30, CD137 bispecific antibody to HRS cells makes it a promising candidate for development as a novel HL treatment.
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http://dx.doi.org/10.3389/fonc.2019.00945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768943PMC
September 2019

Homocysteine enhances neural stem cell autophagy in in vivo and in vitro model of ischemic stroke.

Cell Death Dis 2019 07 22;10(8):561. Epub 2019 Jul 22.

Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.

The elevated level of the amino acid metabolite homocysteine (Hcy) is known as a risk factor for ischemic stroke. The molecular mechanisms responsible for neurotoxicity of Hcy remain largely unknown in ischemic brains. The previous studies have shown that Hcy decreases the proliferation and viability of neural stem cells (NSCs) in vivo and in vitro. Autophagy is required for the maintenance of NSCs homeostasis. In the current study, we hypothesized that the toxic effect of Hcy on NSCs may involve the changes in autophagy level following cerebral ischemia/reperfusion injury. The results showed that Hcy reduced cell viability, increased LDH release, and induced nonapoptotic cell death in primary NSCs exposed to oxygen-glucose deprivation)/reoxygenation (OGD/R). Treatment with autophagy inhibitor 3-methyladenine (3MA) partly reversed the decrease in the viability and prevented LDH release triggered by Hcy combined with OGD/R. Increased punctate LC3 dots co-localizing with Nestin-stained NSCs were also observed in the subventricular zone of Hcy-treated MCAO animals, which were partially blocked by 3MA. In vitro studies further revealed that Hcy induced the formation of autophagosomes, markedly increased the expression of the autophagic markers and decreased p-ERK, p-PI3K, p-AKT, and p-mTOR levels. In addition, MHY1485, an activator of mTOR, reduced Hcy-induced increase in LC3 and Beclin 1 protein levels, meanwhile ERK and PI3K activators (TPA, curcumin for ERK and IGF-1 for PI3K, respectively) enhanced Hcy-triggered mTOR inhibition in OGD/R NSCs. Our findings suggest that Hcy may cause excessive autophagy by downregulation of both PI3K-AKT- and ERK- dependent mTOR signaling, thereby facilitates the toxicity of Hcy on NSCs in ischemic brains.
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http://dx.doi.org/10.1038/s41419-019-1798-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646339PMC
July 2019

Prevention of Morbidity in Sickle Cell Disease (POMS2a)-overnight auto-adjusting continuous positive airway pressure compared with nocturnal oxygen therapy: a randomised crossover pilot study examining patient preference and safety in adults and children.

Trials 2019 Jul 18;20(1):442. Epub 2019 Jul 18.

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

Design: This randomised crossover trial compared nocturnal auto-adjusting continuous positive airway pressure (APAP) and nocturnal oxygen therapy (NOT) in adults and children with sickle cell anaemia, with patient acceptability as the primary outcome. Secondary outcomes included pulmonary physiology (adults), safety, and daily pain during interventions and washout documented using tablet technology.

Methods: Inclusion criteria were age > 8 years and the ability to use an iPad to collect daily pain data. Trial participation was 4 weeks; week 1 involved baseline data collection and week 3 was a washout between interventions, which were administered for 7 days each during weeks 2 and 4 in a randomised order. Qualitative interviews were transcribed verbatim and analysed for content using a funnelling technique, starting generally and then gaining more detailed information on the experience of both interventions. Safety data included routine haematology and median pain days between each period. Missing pain day values were replaced using multiple imputation.

Results: Ten adults (three female, median age 30.2 years, range 18-51.5 years) and eleven children (five female, median age 12 years, range 8.7-16.9 years) enrolled. Nine adults and seven children completed interviews. Qualitative data revealed that the APAP machine was smaller, easier to handle, and less noisy. Of 16 participants, 10 preferred APAP (62.5%, 95% confidence interval (CI) 38.6-81.5%). Haemoglobin decreased from baseline on APAP and NOT (mean difference -3.2 g/L (95% CI -6.0 to -0.2 g/L) and -2.5 g/L (95% CI -4.6 to 0.3 g/L), respectively), but there was no significant difference between interventions (NOT versus APAP, 1.1 (-1.2 to 3.6)). Pulmonary function changed little. Compared with baseline, there were significant decreases in the median number of pain days (1.58 for APAP and 1.71 for NOT) but no significant difference comparing washout with baseline. After adjustment for carry-over and period effects, there was a non-significant median difference of 0.143 (95% CI -0.116 to 0.401) days additional pain with APAP compared with NOT.

Conclusion: In view of the point estimate of patient preference for APAP, and no difference in haematology or pulmonary function or evidence that pain was worse during or in washout after APAP, it was decided to proceed with a Phase II trial of 6 months APAP versus standard care with further safety monitoring for bone marrow suppression and pain.

Trial Registration: ISRCTN46078697 . Registered on 18 July 2014.
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http://dx.doi.org/10.1186/s13063-019-3461-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637584PMC
July 2019

Deferoxamine-induced high expression of TfR1 and DMT1 enhanced iron uptake in triple-negative breast cancer cells by activating IL-6/PI3K/AKT pathway.

Onco Targets Ther 2019 31;12:4359-4377. Epub 2019 May 31.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

Deferoxamine (DFO) is a commonly used iron chelator, which can reduce the iron levels in cells. DFO is normally used to treat iron-overload disease, including some types of cancer. However, our previous studies revealed that DFO treatment significantly increased the iron concentrations in triple-negative breast cancer cells (TNBCs) resulting in enhanced cell migration. But the mechanism of DFO-induced increasing iron uptake in aggressive TNBCs still remained unclear. Iron metabolism-related proteins in aggressive breast cancer MDA-MB-231, HS578T and BT549 cells and nonaggressive breast cancer MCF-7 and T47D cells were examined by immunofluorescence and Western blotting. The possible regulatory mechanism was explored by Western blotting, co-incubation with neutralizing antibodies or inhibitors, and transwell assay. In this study, we found that DFO treatment significantly increased the levels of iron uptake proteins, DMT1 and TfR1, in aggressive TNBCs. Moreover, both TfR1 and DMT1 expressed on cell membrane were involved in high iron uptake in TNBCs under DFO-induced iron deficient condition. For the possible regulatory mechanism, we found that DFO treatment could promote a high expression level of IL-6 in aggressive MDA-MB-231 cells. The activated IL-6/PI3K/AKT pathway upregulated the expression of iron-uptake related proteins, TfR1 and DMT1, leading to increased iron uptakes. We demonstrated that DFO could upregulate expression of TfR1 and DMT1 , which enhanced iron uptake via activating IL-6/PI3K/AKT signaling pathway in aggressive TNBCs.
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http://dx.doi.org/10.2147/OTT.S193507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549404PMC
May 2019

Folic acid deficiency enhanced microglial immune response via the Notch1/nuclear factor kappa B p65 pathway in hippocampus following rat brain I/R injury and BV2 cells.

J Cell Mol Med 2019 07 13;23(7):4795-4807. Epub 2019 May 13.

Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.

Recent studies revealed that folic acid deficiency (FD) increased the likelihood of stroke and aggravated brain injury after focal cerebral ischaemia. The microglia-mediated inflammatory response plays a crucial role in the complicated pathologies that lead to ischaemic brain injury. However, whether FD is involved in the activation of microglia and the neuroinflammation after experimental stroke and the underlying mechanism is still unclear. The aim of the present study was to assess whether FD modulates the Notch1/nuclear factor kappa B (NF-κB) pathway and enhances microglial immune response in a rat middle cerebral artery occlusion-reperfusion (MCAO) model and oxygen-glucose deprivation (OGD)-treated BV-2 cells. Our results exhibited that FD worsened neuronal cell death and exaggerated microglia activation in the hippocampal CA1, CA3 and Dentate gyrus (DG) subregions after cerebral ischaemia/reperfusion. The hippocampal CA1 region was more sensitive to ischaemic injury and FD treatment. The protein expressions of proinflammatory cytokines such as tumour necrosis factor-α, interleukin-1β and interleukin-6 were also augmented by FD treatment in microglial cells of the post-ischaemic hippocampus and in vitro OGD-stressed microglia model. Moreover, FD not only dramatically enhanced the protein expression levels of Notch1 and NF-κB p65 but also promoted the phosphorylation of pIkBα and the nuclear translocation of NF-κB p65. Blocking of Notch1 with N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester partly attenuated the nuclear translocation of NF-κB p65 and the protein expression of neuroinflammatory cytokines in FD-treated hypoxic BV-2 microglia. These results suggested that Notch1/NF-κB p65 pathway-mediated microglial immune response may be a molecular mechanism underlying cerebral ischaemia-reperfusion injury worsened by FD treatment.
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http://dx.doi.org/10.1111/jcmm.14368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584545PMC
July 2019

Shift work and ischaemic heart disease: meta-analysis and dose-response relationship.

Occup Med (Lond) 2019 May;69(3):182-188

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

Background: Shift work is common in many industries. The potential association between shift work and ischaemic heart disease (IHD) remains controversial.

Aims: To conduct a systematic review and meta-analysis of epidemiological evidence and summarize the potential relationship between shift work and IHD.

Methods: We searched all relevant case-control and cohort studies that were published from January 1970 to October 2017 on PubMed, Web of Science and Embase. The random-effects model and the generalized least-squares trend model were, respectively, used to evaluate the pooled relative risk and dose-response relationship between shift work and IHD. Two different authors extracted data and assessed the quality of each study independently.

Results: Twenty-one articles with 31 independent results of 19 782 IHD cases in 320 002 participants were included. The pooled relative risk for the association between shift work and risk of IHD was 1.13 (95% CI 1.08-1.20, I2 = 53%, P < 0.001). Further evaluation of dose-response relationship indicated that each 1-year increase in shift work was associated with 0.9% (RR = 1.009; 95% CI 1.006-1.012) increase of the risk of IHD.

Conclusions: This meta-analysis updated the evidence that shift work was associated with the risk of IHD and supported a positive dose-response relationship between the risk of IHD and increasing duration of shift work.
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http://dx.doi.org/10.1093/occmed/kqz020DOI Listing
May 2019

Changes of Soil Microbiological Properties during Grass Litter Decomposition in Loess Hilly Region, China.

Int J Environ Res Public Health 2018 08 21;15(9). Epub 2018 Aug 21.

Shanxi Research Academy of Environment Sciences, Taiyuan 030000, Shanxi, China.

Litter, the link between soil and plant, is an important part of nutrient return to soil. Deeply understanding the effect of litter decomposition on soil microbiological properties is important for the sustainable development of grasslands. Three plants ( Celak., Trin. and ledeb.) leaf litter were selected. A simulation experiment using the nylon bag method was conducted to measure the soil microbial biomass carbon and nitrogen, and soil enzyme activity during litter decomposition. The results showed that the decomposition of three leaf litter enhanced soil microbial carbon and nitrogen. The change rate of soil microbial carbon and nitrogen decreased as Ar.S > St.B > Th.Q. The activities of soil invertase, soil urease, and soil nitrate reductase were significantly improved by the coverage of leaf litter. After 741-day litter decomposition, the change rate of soil invertase was from 16.7% to 33.2%. The change rate of soil urease was highest in the Th.Q treatment; St.B treatment and Ar.S treatment followed, and lowest in the control. The change rates of soil nitrate reductase in the St.B and Ar.S treatment were >1000% higher than those of other treatments. The response of soil enzyme activity to litter decomposition "lagged" behind the change of soil microbial biomass. The significant increase of soil microbial biomass and enzyme activity demonstrated that litter decomposition played an important role in maintaining soil ecological function.
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http://dx.doi.org/10.3390/ijerph15091797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164776PMC
August 2018