| 1. |
- Liu, Jian, et al.
(författare)
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Quantitative proteomics approach reveals novel biomarkers and pathological mechanism of keloid
- 2022
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Ingår i: PROTEOMICS - Clinical Applications. - : John Wiley & Sons. - 1862-8346 .- 1862-8354. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- Background Keloid is a pathological skin scar formation with complex and unclear molecular pathology mechanism. Novel biomarkers and associated mechanisms are needed to improve current therapies.Objectives To identify novel biomarkers and underlying pathological mechanisms of keloids.MethodsSix pairs of keloid scar tissues and corresponding normal skin tissues were quantitatively analyzed by a high-resolution label-free mass spectrometry-based proteomics approach. Differential protein expression data was further analyzed by a comprehensive bioinformatics approach to identify novel biomarkers and mechanistic pathways for keloid formation. Candidate biomarkers were validated experimentally.Results In total, 1359 proteins were identified by proteomic analysis. Of these, 206 proteins exhibited a significant difference in expression between keloid scar and normal skin tissues. RCN3 and CALU were significantly upregulated in keloids. RCN1 and PDGFRL were uniquely expressed in keloids. Pathway analysis suggested that the XBP1-mediated unfolded protein response (UPR) pathway was involved in keloid formation. Moreover, a PDGFRL centric gene coexpression network was constructed to illustrate its function in skin.Conclusions and Clinical Relevance Our study proposed four novel biomarkers and highlighted the role of XBP1-mediated UPR pathway in the pathology of keloids. It provided novel biological insights that contribute to develop novel therapeutic strategies for keloids.
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| 2. |
- Bergman, Susanna L., et al.
(författare)
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In-situ studies of oxidation/reduction of copper in Cu-CHA SCR catalysts: Comparison of fresh and SO2-poisoned catalysts
- 2020
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Ingår i: Applied Catalysis B: Environmental. - : Elsevier BV. - 0926-3373 .- 1873-3883. ; 269
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Tidskriftsartikel (refereegranskat)abstract
- SO2-poisoning results in deactivation of Cu-CHA SCR under standard SCR conditions; however regeneration at 700 °C completely restores the SCR performance. To understand the nature of these effects, Cu-species in the fresh and poisoned catalysts were characterized by in-situ temperature-dependent time-resolved Cu K-edge X-ray absorption spectroscopy using the multivariate curve resolution alternating least squares (MCR-ALS) approach and continuous Cauchy wavelet transforms. The extracted chemically-meaningful reference spectra of Cu-species were analyzed by DFT-assisted XANES calculations. Cu-bisulfates were found as the most energetically favorable poisoned Cu-species. The response of Cu-species to a reducing environment differs in the fresh and SO2-poisoned catalysts. Differences in reducibility are related to the formation of quasi-linear Cu-complexes in the SO2-poisoned catalyst formed during heating in H2/He. Heating in H2/He leads to partial desulfurization of the poisoned catalyst. Cooling in H2/He after heating results in more facile formation of Cu-metal clusters in fresh catalyst than in SO2-poisoned.
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| 3. |
- Deng, Tingzhi, et al.
(författare)
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Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice
- 2021
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Age-related hearing loss (ARHL) is associated with cognitive dysfunction; however, the detailed underlying mechanisms remain unclear. The aim of this study is to investigate the potential underlying mechanism with a system genetics approach. A transcriptome-wide association study was performed on aged (12-32 months old) BXD mice strains. The hippocampus gene expression was obtained from 56 BXD strains, and the hearing acuity was assessed from 54 BXD strains. Further correlation analysis identified a total of 1,435 hearing-related genes in the hippocampus (p < 0.05). Pathway analysis of these genes indicated that the impaired glutamatergic synapse pathway is involved in ARHL (p = 0.0038). Further gene co-expression analysis showed that the expression level of glutamine synthetase (Gls), which is significantly correlated with ARHL (n = 26, r = -0.46, p = 0.0193), is a crucial regulator in glutamatergic synapse pathway and associated with learning and memory behavior. In this study, we present the first systematic evaluation of hippocampus gene expression pattern associated with ARHL, learning, and memory behavior. Our results provide novel potential molecular mechanisms involved in ARHL and cognitive dysfunction association.
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| 4. |
- Guo, Jianqiu, et al.
(författare)
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Associations of melamine and cyanuric acid exposure with markers of kidney function in adults : Results from NHANES 2003-2004
- 2020
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- Higher melamine exposure may increase the risk of kidney stone formation and kidney injury in infants, but little is known about the potential nephrotoxic effects of environmental low-dose melamine and its derivative exposure on kidney function of adults in the general population. Our objective was to assess associations between urinary concentrations of melamine and its derivative, cyanuric acid, and kidney function through analyzing the data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. Information on 298 participants aged ≥20 years was utilized. Urinary melamine and cyanuric acid levels were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were calculated to reflect kidney function. Covariate-adjusted creatinine standardization concentrations accounting for sex, race, age, race/ethically, and body mass index, was employed to control potential confounding of kidney function. Multivariable linear regression models were conducted to estimate associations of covariate-adjusted creatinine standardization urinary melamine and cyanuric acid concentrations with eGFR and UACR. Log-binomial regression models were performed to estimate risks of impaired kidney function and hypertension associated with urinary melamine and cyanuric acid levels. The geometric mean values of urinary melamine and cyanuric acid concentrations were 1.51 μg/L [95% confidence interval (CI): 1.21 μg/L, 1.89 μg/L] and 5.86 μg/L (95% CI: 5.34 μg/L, 6.44 μg/L), respectively. The median value of estimated daily intake (EDI) for melamine was 0.06 (ranging from undetectable to 1.11) μg/kg body weight/day calculated by urinary concentration and creatinine excretion accounting for sex and body weight. Adults in the fourth quartile of melamine and cyanuric acid exposure had 0.142 mL/min/1.73 m2 (95% CI: -0.271, -0.014) and 0.106 mL/min/1.73 m2 (95% CI: -0.020, 0.006) lower eGFR for melamine and cyanuric acid, respectively, compared to participants in the first quartile of exposure with adjustment for potential confounders. To our best knowledge, this is the first study to report associations between melamine and its derivative and kidney function of the U.S. adults from NHANES 2003-2004. The suggestive evidence revealed that individuals with high melamine exposure had lower eGFR than those with low melamine exposure, although no significant association between melamine and cyanuric acid exposure and markers of kidney function was observed. These findings should be interpreted with caution regarding the possible reverse causality.
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| 5. |
- Guo, Jianqiu, et al.
(författare)
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Early life triclosan exposure and neurodevelopment of children at 3 years in a prospective birth cohort
- 2020
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Ingår i: International journal of hygiene and environmental health. - : Urban & Fischer. - 1438-4639 .- 1618-131X. ; 224
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early life exposure to triclosan, an emerging endocrine disrupting chemical, may adversely impact childhood neurodevelopment, but limited epidemiologic studies have examined the associations.OBJECTIVE: We evaluated the associations between prenatal and postnatal triclosan exposure and child neurodevelopment at 3 years.METHODS: The study included 377 mother-child pairs who participated in Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. Triclosan concentrations in maternal and 3-year-old child urine samples were quantified using gas chromatography-tandem mass spectrometry (GC-MS/MS). Gesell Developmental Schedules (GDS) were used to assess child neurodevelopment at 3 years of age. Multivariate linear regression models were applied to estimate associations of prenatal and postnatal urinary triclosan concentrations with children's developmental quotients (DQs).RESULTS: Detection frequencies of triclosan in maternal and childhood urine samples were 100% and 99.5%, respectively. The median values of prenatal and postnatal urinary triclosan levels were 0.65 and 0.44 μg/L, respectively. One ln-unit increase of maternal urinary triclosan concentration was associated with increase of DQ scores in motor area of children (regression coefficient, β = 0.28, 95% confidence interval, CI: 0.03, 0.54; p = 0.03). In sex-stratified analyses, maternal urinary triclosan levels were significantly related to increases in DQ scores in motor area among boys (β = 0.25, 95%CI: 0.01, 0.50; p = 0.04), while postnatal urinary triclosan concentrations were inversely associated with DQ scores in social area in boys (β = -0.37, 95%CI: -0.72, -0.03; p = 0.03).CONCLUSIONS: The findings suggested that prenatal triclosan exposure predicted increases in motor scores, while postnatal triclosan exposure was related to reductions in social scores of 3-year-old children. These associations were only observed in boys. The biological mechanisms linking triclosan exposure to neurodevelopment await further studies.
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| 6. |
- Guo, Jianqiu, et al.
(författare)
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Maternal and childhood urinary phenol concentrations, neonatal thyroid function, and behavioral problems at 10 years of age : The SMBCS study
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 743
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Environmental phenols, bisphenol A (BPA), triclosan (TCS), and benzophenone-3 (BP-3), are known as emerging endocrine-disrupting chemicals; however, their impacts on thyroid hormones and children's neurobehaviors are still unclear.OBJECTIVES: We aimed to examine the associations of prenatal and childhood exposure to phenols with neonatal thyroid function and childhood behavioral problems aged 10 years.METHODS: A total of 386 mother-singleton pairs were included from Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. We quantified urinary BPA, TCS and BP-3 concentrations in maternal and 10-year-old children's urine samples using gas chromatography tandem mass spectrometry and thyroid function parameters in cord serum samples. Caregivers completed the Strength and Difficulties Questionnaire (SDQ) for their children at 10 years of age. Multivariable linear regression models and logistic regression models were applied to estimate associations of urinary phenol concentrations with thyroid hormones and risks of children's behavioral problems, respectively.RESULTS: The median values of urinary BPA, TCS and BP-3 concentrations for pregnant women were 1.75 μg/L, 0.54 μg/L and 0.37 μg/L, while 1.29 μg/L, 6.64 μg/L and 1.39 μg/L for children, respectively. Maternal urinary BPA concentrations were in associations with 1.00% [95% confidence interval (CI): 0.20%, 1.92%] increases in cord serum FT4 concentrations and significantly associated with increased risks of total difficulties [odds ratio (OR): 1.45, 95% CI: 1.07, 1.97], while maternal urinary levels of BP-3 were significantly related to poorer prosocial behaviors (OR: 1.58, 95% CI: 1.04, 2.39) of children at 10 years of age. In sex-stratified analyses, maternal urinary BPA concentrations were related to increased total difficulty subscales only in boys.CONCLUSIONS: The findings indicated that higher prenatal urinary BPA concentrations were associated with increased risks of total difficulties, especially in boys and maternal urinary BP-3 concentrations were related to poorer prosocial behaviors at 10 years.
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| 7. |
- Guo, Jianqiu, et al.
(författare)
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Prenatal exposure to multiple phenolic compounds, fetal reproductive hormones, and the second to fourth digit ratio of children aged 10 years in a prospective birth cohort
- 2021
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Ingår i: Chemosphere. - : Pergamon Press. - 0045-6535 .- 1879-1298. ; 263
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Tidskriftsartikel (refereegranskat)abstract
- Select phenols are known to possess hormone-disrupting properties, but no previous study has addressed the potential effects of prenatal exposure to phenol mixtures on fetal reproductive hormones and children's second to fourth digit (2D: 4D) ratio, a marker for in utero testosterone (T) exposure. We aimed to explore interrelations of prenatal phenol exposures individually and in mixtures, cord serum reproductive hormones, and 2D: 4D ratio of children aged 10 years. Urinary 11 phenol concentrations were determined from 392 pregnant women participating in a longitudinal birth cohort. We estimated associations of prenatal phenol exposures individually and in mixtures with cord reproductive hormones and children's 2D:4D ratio using three statistical approaches, including generalized linear models (GLMs), elastic net regression (ENR) models and Bayesian kernel machine regression (BKMR) models. In female newborns, the three models showed that maternal triclosan (TCS) concentrations were significantly negatively associated with cord serum T levels [regression coefficient (β) = -0.076, 95% confidence interval (CI): 0.138, -0.013; p = 0.018]. Additionally, maternal urinary bisphenol A (BPA) levels were related to decreases in 2D:4D ratio of the left hand in girls by GLMs (β = -0.003, 95% CI: 0.007, -0.001; p = 0.024) and ENR models, but not BKMR models. We provided evidence that prenatal TCS exposure predicted lower cord serum T levels, and maternal BPA exposure was related to decreased 2D:4D ratio of the left hand in females.
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| 8. |
- He, Wei, et al.
(författare)
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China's Terrestrial Carbon Sink Over 2010–2015 Constrained by Satellite Observations of Atmospheric CO2 and Land Surface Variables
- 2022
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Ingår i: Journal of Geophysical Research: Biogeosciences. - 2169-8953. ; 127:2
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Tidskriftsartikel (refereegranskat)abstract
- The magnitude and distribution of China's terrestrial carbon sink remain uncertain due to insufficient constraints at large scales, whereby satellite data offer great potential for reducing the uncertainty. Here, we present two carbon sink estimates for China constrained either by satellite CO2 column concentrations (XCO2) within the Global Carbon Assimilation System or by remotely sensed soil moisture and Fraction of Absorbed Photosynthetically Active Radiation (FAPAR) in addition to in situ CO2 observations within the Carbon Cycle Data Assimilation System. They point to a moderate size of carbon sinks of 0.34 ± 0.14 (mean ± unc.) and 0.43 ± 0.09 PgC/yr during 2010–2015, which are supported by an inventory-based estimate for forest and soil carbon sink (0.26 PgC/yr) and fall in the range of contemporary ensemble atmospheric inversions (0.25–0.48 PgC/yr). They also agree reasonably well on interannual variations, which reflect the carbon sink anomalies induced by regional droughts in southwest China. Furthermore, their spatial distributions are broadly consistent that of the forest inventory-based estimate, indicating that the largest carbon sinks locate in central and eastern China. Their estimates for forest carbon sink coincide fairly well with the inventory-based estimate across different regions, especially when aggregated to the north and south of China. Although enhanced recently by afforestation, China's carbon sink was also significantly weakened by regional droughts, which were often not fully represented in previous in situ CO2-based inversions due to insufficient observations. Our results suggest that satellite-based atmospheric CO2 and land surface observations are vital in characterizing terrestrial net carbon fluxes at regional scales.
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| 9. |
- Hu, Wei, et al.
(författare)
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Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrin beta 6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.
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| 10. |
- Li, Wenting, et al.
(författare)
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Effects of prenatal exposure to five parabens on neonatal thyroid function and birth weight : Evidence from SMBCS study
- 2020
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Ingår i: Environmental Research. - : Academic Press. - 0013-9351 .- 1096-0953. ; 188
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parabens, suspected as endocrine-disrupting chemicals, are nearly ubiquitous in the human body and exposure to these chemicals during pregnancy may disrupt thyroid hormones homeostasis and even affect fetal growth, although the impacts are still unclear.OBJECTIVES: We aimed to estimate associations of maternal urinary paraben concentrations with cord serum thyroid hormones and birth weight.METHODS: A subset of 437 mother-newborn pairs were included from a prospective birth cohort with five parabens quantified in maternal urine and seven thyroid function indicators measured in cord serum samples. Multivariable linear regression models and elastic net regression (ENR) models were applied to explore associations between individual and mixtures of prenatal urinary paraben concentrations and thyroid hormones and birth weight, respectively.RESULTS: Maternal urinary ethyl-paraben (EtP) concentrations were associated with increased cord serum total triiodothyronine levels (TT3) [percent change: 1.51%; 95% confidence interval (CI): 0.20%, 2.74%; p=0.017]. Urinary propyl-paraben (PrP) levels predicted higher thyroid peroxidase antibodies (percent change: 4.19%, 95% CI: 0.20%, 8.44%; p=0.041). Maternal urinary EtP and butyl-paraben (BuP) concentrations were significantly positively associated with birth weight [regression coefficient, (β)=40.9g, 95% CI: 3.99, 76.6; p=0.030; β=62.1g, 95% CI: 8.70, 115; p=0.023, for EtP and BuP, respectively]. In sex-stratified analyses, positive relationship between EtP levels and birth weight was observed in boys. Urinary EtP concentrations predicted higher TT3 levels in cord serum samples, assessing parabens as a chemical mixture with ENR models.CONCLUSIONS: Prenatal exposure to parabens may affect thyroid hormone indicators with increased serum TT3 levels and associate with higher birth weight, especially in boys. The underlying biological mechanisms and effects of prenatal paraben exposures on disruption of thyroid function homeostasis and potential impacts of childhood growth and development needed to be further investigated.
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