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Adequate dietary intake of amino acids is imperative for normal animal growth. Our previous work using rat hepatocarcinoma Fao cells demonstrated that growth hormone (GH) resistance, coupled with a concurrent reduction in insulin-like growth factor 1 (Igf1) mRNA levels, may underlie the growth retardation associated with a low-protein diet (LPD). In this study, we investigated whether FGF21 contributes to liver GH resistance in Fao rat hepatoma cells under amino acid deprivation conditions. Mice subjected to an LPD exhibited growth retardation, compromised GH signaling in the liver, and decreased blood IGF-1 levels compared with those on a control diet. To assess the potential involvement of fibroblast growth factor (FGF) 21, produced in response to amino acid deficiency, in the development of GH resistance, we examined GH signaling and Igf1 mRNA levels in Fao cells cultured in amino acid-deprived medium. Despite the inhibition of Fgf21 expression by the integrated stress response inhibitor, an inhibitor of the eukaryotic initiation factor 2-activating transcription factor 4 pathway, GH resistance persisted in response to amino acid deprivation. Additionally, the introduction of FGF21 into the control medium did not impair either GH signaling or GH-induced Igf1 transcription. These data suggest that, in Fao cells, amino acid deprivation induces GH resistance independently of FGF21 activity. By shedding light on the mechanisms behind growth retardation-associated GH resistance linked to amino acid deficiencies, our findings provide valuable insights for clinicians in formulating effective treatment strategies for individuals facing these challenges., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Bioaccessibility of halogenated flame retardants (HFRs) and organophosphorus esters (OPEs) is necessarily investigated to provide more accurate risk assessment and information about absorption behavior of these pollutants. In this study, total and bioaccessible concentrations of HFRs (including legacy and alternative substances) and OPEs were determined in settled dust samples collected from Vietnamese e-waste and end-of-life vehicle (ELV) processing areas. Concentrations of both HFRs and OPEs were significantly higher in the e-waste dust than ELV dust. Bioavailability of HFRs and OPEs in dust was determined by using an in vitro assay with human-simulated digestive fluids, dialysis membrane, and Tenax® TA sorptive sink. Bioaccessibility of HFRs was markedly lower than that of OPEs, which could be largely due to higher hydrophobicity of HFRs compared to OPEs. Bioaccessibility of almost hydrophobic compounds were markedly lower in the e-waste dust (containing micronized plastic debris) than in the ELV dust (containing oily materials), suggesting the influence of specific dust matrices on pollutant bioaccessibility. Although the daily uptake doses of selected HFRs and OPEs from dust were markedly higher in the e-waste sites compared to the ELV sites, the direct exposure risk was not significant. Our results suggest that bioaccessibility can partly explain the differences between dust and uptake profiles, which may relate to accumulation profiles of HFRs and OPEs in human samples., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Neither TP53 mutation nor DNA methylation status has been established as a biomarker alone of metastatic colorectal cancer. We analyzed the association between TP53 mutation functional subtypes and genome-wide DNA methylation status (GWMS) as combined prognostic markers., Methods: Patient clinical data were obtained from the TRICOLORE study, a randomized phase III trial. The TP53 mutations were classified into wild-type, gain-of-function (GOF) mutations, and non-gain-of-function (non-GOF) mutations. GWMS of the tumor tissues classified them into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). Overall survival (OS) was compared based on these subgroups., Results: Of the 209 patients, 60 (28.7%) were HMCC and 149 (71.3%) were LMCC, 35 (16.7%) were TP53 wild-type and 174 (83.3%) were TP53 mutants including 79 (45.4%) GOF mutations and 95 (54.6%) non-GOF mutations. The OS of the HMCC group was shorter than that of the LMCC group (median 25.3 vs. 40.3 months, P < .001, hazard ratio 1.87) in the total cohort. The combined subgroup analyses of GWMS and TP53 mutation subtypes showed that the HMCC/GOF group had significantly shorter OS than the HMCC/non-GOF group, the LMCC/GOF group, and the LMCC/non-GOF group (median 17.7; 35.3, 40.3, and 41.2 months, P = .007, P < .001, and P < .001, respectively), regardless of the primary tumor location. By the multivariate analysis, only HMCC (P = .009) was a poor prognostic factor in the GOF mutation group., Conclusions: TP53 GOF with HMCC is a newly identified poorest prognostic molecular subset in metastatic colorectal cancer., Competing Interests: Disclosure Dr. Kota Ouchi reports honoraria from Taiho, Lilly, Asahi Kasei, and Merck, outside the submitted work; Dr. Shin Takahashi reports honoraria from Taiho, Asahi Kasei, Daiichi Sankyo, Chugai Pharma, Yakult, Merck, Ono, and Bristol-Myers Squibb, and research funding from Merck and Ono, outside the submitted work; Prof. Yasuhide Yamada reports honoraria from Taiho, Ono, and Boehringer Ingelheim, and research funding from Chugai, outside the submitted work; Prof. Yoshito Komatsu reports honoraria from Lilly, Taiho, Chugai Pharma, Takeda, Bayer, Bristol-Myers Squibb, Sanofi, Merck, Yakult, Ono, Nipro Corporation, Moroo Co, Asahi Kasei, Mitsubishi Tanabe Pharma, Otsuka, Medical Review Co, and Daiichi Sankyo, and research funding from Merck Sharp & Dohme, Taiho, Yakult, Bayer, Daiichi Sankyo, Ono, NanoCarrier, Sanofi, Sysmex, Shionogi, IQVIA, PAREXEL, Astellas, Mediscience Planning, Sumitomo Dainippon Pharma, A2 Healthcare, Incyte, Lilly, Nipro Corporation, and BeiGene, outside the submitted work; Dr. Ken Shimada reports research funding from Taiho and Chugai Pharma, outside the submitted work; Dr. Tatsuro Yamaguchi reports honoraria from Chugai Pharma, outside the submitted work; Dr. Masanobu Takahashi reports speaker's bureau from Taiho, Bristol-Myers Squibb, and Ono, and research funding from Chugai Pharma and Ono, outside the submitted work; Prof. Ishioka reports honoraria from Daiichi Sankyo, Ono, Taiho, Chugai Pharma, Sanofi, Nippon Kayaku, Takeda, Kyowa Kirin International, Asahi Kasei, Shionogi, Lilly, Otsuka, Yakult, and Tsumura & Co, and research funding from Chugai Pharma, Taiho, Takeda, Yakult, Daiichi Sankyo, Asahi Kasei, Nippon Kayaku, Ono, Kyowa Kirin, Tsumura & Co, Bayer, Shionogi, Otsuka, Sanofi, Lilly, Hitachi and Riken Genesis, outside the submitted work. All remaining authors have declared no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Short-finned pilot whales (SFPW) are a group of cetaceans found globally in tropical and temperate seas and are commonly stranded in the group, but the reason behind their stranding is still unknown. No detailed information on the contamination status and bioaccumulation of halogenated organic compounds, including polychlorinated biphenyls (PCBs), in the SFPW from Indonesian waters has been reported. Therefore, we analyzed all 209 PCB congeners in the blubber of 20 SFPW specimens stranded along the coast of Savu Island, East Nusa Tenggara, Indonesia, in October 2012 to explain the status of contamination, congener profiles, potential risk of PCBs to cetaceans, and the determination of unintentionally produced PCBs (u-PCBs) in the blubber of SFPW. Concentrations of Σ209PCBs, Σ7in-PCBs, Σ12dl-PCBs, and Σ21u-PCBs were between 48 and 490 (mean:240 ± 140), 22-230 (110 ± 60), 2.6-38 (17 ± 10), and 1.0-13 (6.3 ± 3.7) ng g -1 lipid weight (lw), respectively. Congener-specific profiles of PCBs among sex and estimated age groups were observed; relatively high proportions of tri-to penta-CBs in juveniles and highly chlorinated recalcitrant congeners in structure-activity groups (SAGs) in sub-adult females were noted. The estimated toxic equivalency (TEQs) value for dl-PCBs ranged from 2.2 to 60 TEQ WHO pg/g lw, with juveniles containing high TEQ values than sub-adults and adults. Although the TEQs and concentrations of PCBs in SFPW stranded along Indonesian coasts were lower than those reported for similar whale species from other North Pacific regions, further research is needed to assess the long-term impact of halogenated organic pollutants on their survival and health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Measuring personal exposure to flame retardants (FRs) is crucial for assessing and controlling human health risks posed by FRs during the recycling of electronic waste (e-waste) and end-of-life vehicles (ELVs). Here, we examined the use of handwipes and silicone wristbands to measure personal FR exposure for e-waste and ELV recycling workers and their children in Vietnam. On the handwipes from the e-waste recycling workers, the predominant five FRs detected were TBBPA (median concentration: 3700 ng/wipe), BDE-209 (1700 ng/wipe), TPHP (500 ng/wipe), DBDPE (410 ng/wipe), and BPA-BDPP (360 ng/wipe). On the handwipes from ELV recycling workers, TPHP (60 ng/wipe), IPPDPP (47 ng/wipe), BIPPPP/DIPPDPP (33 ng/wipe), BDE-209 (26 ng/wipe), and TCIPP (23 ng/wipe) were detected as the five predominant FRs. On the wristbands from the e-waste recycling workers, the five predominant FRs detected were TBBPA (median concentration: 340 ng/g), BDE-209 (330 ng/g), DBDPE (65 ng/g), TPHP (50 ng/g), and TMPP (34 ng/g). On the wristbands from the ELV recycling workers, TPHP (34 ng/g), IPPDPP (18 ng/g), TCIPP (14 ng/g), TDMPP (13 ng/g), BIPPPP/DIPPDPP (9.3 ng/g) and TMPP (9.3 ng/g) were detected as the predominant FRs. The data obtained with the wristbands were comparable to those obtained with the handwipes. Similar FR profiles were found in between the workers and their children. The profiles indicate that the informal e-waste and ELV recycling caused FR exposure not only for workers but also for their children who live in the workshops. By using the handwipe and wristband sampling approaches, we determined types and concentrations of FRs to which the workers and their children were dominantly exposed. Silicone wristband- and handwipe-based assessment is expected to be effective means of measuring personal FR exposure for the informal e-waste and ELV recycling workers and their children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The occurrence of 209 PCB congeners was determined in a sediment core dated between 1930 and 2019 from Lake Biwa, a typical temperate monomictic lake in Japan. Concentrations of total PCBs ranged from 5.3 to 48 ng/g dry weight (dw), showing a highest peak at the 1960s to 1970s. The temporal trend of total PCBs in this sediment core generally matched with Japanese PCB production and emission pattern (i.e., increasing from the 1950s, peaking at 1970, and gradually decreasing since 1972). The vertical PCB profiles in our core were affected by physical mixing and bioturbation. By using a detailed and comprehensive analytical method, we have found elevated concentrations and special historical profiles of several congeners such as CB-7, -11, -47/48/75, -51, -68, and -209, which are still rarely included in routine PCB analysis. Some tetra-CB congeners like CB-47/48/75, -51, and -68 showed their concentration peaks at the early 2010s, which may be unintentionally produced during polymer manufacturing processes. PCB homolog- and congener-specific profiles in our sediment core samples have experienced weathering with higher proportions of penta- and hexa-CBs as compared to the Kanechlor usage pattern (i.e., dominated by tri- and tetra-CBs). Both intentional (i.e., technical mixtures) and unintentional (e.g., PCB-containing polymers and pigments) sources of PCBs were suggested from congener-specific analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Concentrations of 34 unsubstituted and methylated polycyclic aromatic hydrocarbons (PAHs and Me-PAHs) and AhR-mediated activities in settled dust samples were determined by a combination of gas chromatography-mass spectrometry and an in vitro reporter gene assay (PAH-CALUX). The levels of Σ34PAHs and bioassay-derived benzo[a]pyrene equivalents (CALUX BaP-EQs) were significantly higher in workplace dust from informal end-of-life vehicle dismantling workshops than in common house dust and road dust. In all the samples, the theoretical BaP-EQs of PAHs (calculated using PAH-CALUX relative potencies) accounted for 28 ± 19% of the CALUX BaP-EQs, suggesting significant contribution of aryl hydrocarbon receptor (AhR) agonists and/or mixture effects. Interestingly, the bioassay-derived BaP-EQs in these samples were significantly correlated with not only unsubstituted PAHs with known carcinogenic potencies but also many Me-PAHs, which should be included in future monitoring and toxicity tests. The bioassay responses of many sample extracts were substantially reduced but not suppressed with sulfuric acid treatment, indicating contribution of persistent AhR agonists. Cancer risk assessment based on the CALUX BaP-EQs has revealed unacceptable level of risk in many cases. The application of bioassay-derived BaP-EQs may reduce underestimation in environmental management and risk evaluation regarding PAHs and their derivatives (notably Me-PAHs), suggesting a consideration of using in vitro toxic activity instead of conventional chemical-specific approach in such assessment practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The supply of Rashkind balloon atrial septostomy (BAS) catheters (Medtronic, Minneapolis, MN, USA) has suddenly been discontinued in the world due to its recall. Consequently, Japan fell into a critical shortage of standard BAS catheters. Although the use of static BAS is off-label in Japan, its importance is increasing in such a situation. A nationwide survey of static BAS is needed in such a critical period., Methods: A questionnaire survey was conducted among centers in Japan regarding BAS performed between October 1, 2020, and December 15, 2020, while the supply of Rashkind BAS catheter was discontinued., Results: We received answers from 70 of the 90 centers, for a response rate of 78%. In this survey, 25 patients who underwent static BAS were enrolled, and a total of 47 BAS procedures were performed. Median age and weight at static BAS were 10 days of life and 3001 g, respectively. The most common diagnosis was transposition of the great arteries without pulmonary stenosis and hypoplastic left heart syndrome and its variants, with 8 cases each. The most frequently used balloon diameter was 10 mm (13 balloons), followed by 12 mm (10 balloons), and 3 cases required double-balloon techniques. The 3-point scale of the efficacy of static BAS rated by physicians were 10 excellent, 15 good, and 0 poor, respectively. Complications included cardiac tamponade during the procedure in 1 patient and the need for Rashkind BAS later in 2 patients. Comparing the share of static BAS in all transcatheter atrial septostomy, its share in the current survey (28/53) is significantly higher compared to the annual registry data in 2018 (86/304) (p < 0.01)., Conclusions: This survey shows that static BAS is widely performed in Japan and is effective and safe. Static BAS cases have increased significantly due to a shortage of standard BAS catheters., (Copyright © 2021. Published by Elsevier Ltd.)

Comprehensive and updated information about polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) in surface sediments from Hanoi, the capital city of Vietnam, is rather scarce. In this study, concentrations and profiles of 209 PCBs, 41 polybrominated diphenyl ethers (PBDEs), 2,2',4,4',5,5'-hexabromobiphenyl (BB-153), hexabromocyclododecane (HBCD), pentabromoethylbenzene (PBEB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), and decabromodiphenyl ethane (DBDPE) were determined in sediment samples collected from the Red River and some inner-city rivers of Hanoi. Concentrations (ng/g dry weight, median and range) of pollutants decreased in the order: DBDPE (28; not detected ND - 59) ≈ PCBs (27; 1.7-50) > PBDEs (23; 0.20-61) > HBCD (1.2; ND - 5.2) > BTBPE (0.46; ND - 3.6) > BB-153 (0.004; ND - 0.014) > PBEB (ND). Pollutant levels in the inner-city river sediments were about one to two orders of magnitude higher than those measured in the Red River main stream sediments. Tri-to hexa-CBs are major homologs but detailed profiles vary between individual samples, reflecting source and/or seasonal variations. CB-11 and CB-209 were found at higher proportions in sediments than in technical PCB mixtures, suggesting their novel sources from pigments. Deca-BDE and DBDPE are the most predominant BFRs with an increasing trend predicted for DBDPE. A preliminary ecological risk assessment was conducted for these pollutants in sediments. Total PCBs and deca-BDE in a few inner-city river sediments may exhibit adverse effects on benthic organisms, but no serious risk was estimated in general., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Monitoring data on organic pollutants published between the late 1960s and 2020 are reviewed to provide comprehensive and updated insights into their bioaccumulation characteristics, sources, and fate in snakes. Multiple organic pollutant classes including pesticides, polychlorinated biphenyls, chlorinated paraffins, dioxin-related compounds, alkanes, polycyclic aromatic hydrocarbons, flame retardants, plasticizers, etc., were detected in various aquatic and terrestrial snake species with concentrations and patterns varying between species and locations. In general, higher concentrations of organic pollutants were found in snakes collected from contaminated sites (e.g., densely populated, pesticide-treated, and waste processing areas), suggesting that snakes can serve as good biomonitors of environmental pollution caused by organic contaminants. Factors influencing concentrations and patterns of organic pollutants in snakes are discussed, providing an overview of current understanding about their accumulation, transformation, and elimination processes. Potential negative effects associated with organic pollutants in snakes and their predators are also considered. Based on such discussions, research gaps and future perspectives on the utilization of snake biomonitoring studies are addressed, heading towards an effective monitoring and assessment scheme for a variety of legacy and emerging organic pollutants in the environment., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This review provides focused insights into the contamination status, sources, and ecological risks associated with multiple classes of antibiotics in surface water from the East and Southeast Asia based on publications over the period 2007 to 2020. Antibiotics are ubiquitous in surface water of these countries with concentrations ranging from <1 ng/L to hundreds μg/L and median values from 10 to 100 ng/L. Wider ranges and higher maximum concentrations of certain antibiotics were found in surface water of the East Asian countries like China and South Korea than in the Southeast Asian nations. Environmental behavior and fate of antibiotics in surface water is discussed. The reviewed occurrence of antibiotics in their sources suggests that effluent from wastewater treatment plants, wastewater from aquaculture and livestock production activities, and untreated urban sewage are principal sources of antibiotics in surface water. Ecological risks associated with antibiotic residues were estimated for aquatic organisms and the prevalence of antibiotic resistance genes and antibiotic-resistant bacteria were reviewed. Such findings underline the need for synergistic efforts from scientists, engineers, policy makers, government managers, entrepreneurs, and communities to manage and reduce the burden of antibiotics and antibiotic resistance in water bodies of East and Southeast Asian countries., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Although bioaccessibility testing is applied worldwide for appropriate chemical risk assessment, few studies have focused on the bioaccessibility of flame retardants (FRs), especially inhalation exposure. This study assessed inhalation exposure to FRs in indoor dust by workers at e-waste-dismantling workshops in northern Vietnam, by using modified simulated epithelial lung fluid (SELF) and artificial lysosomal fluid (ALF). The average mass concentrations of FRs were 130,000 ng/g for workplace dust (n = 3), 140,000 ng/g for floor dust (n = 3), and 74,000 ng/g for settled dust (n = 2), whereas the average bioaccessible concentrations of FRs were 1900, 1400, and 270 ng/g in the SELF condition and 2600, 770, and 490 ng/g in the ALF condition, respectively. Results clearly indicate that the bioaccessible concentrations of FRs are markedly lower than their mass concentrations. Tris(2-chloroethyl) phosphate (TCEP, ~19%), tris(2-chloroisopropyl) phosphate (TCIPP, ~35%), and tris(1,3-dichloroisopropyl) phosphate (TDCIPP, ~22%) showed comparably high bioaccessibility in both SELF and ALF conditions. In contrast, the bioaccessibility of tetrabromobisphenol A (TBBPA, ~20%) was high in the SELF condition, but not in the ALF condition. With regard to the test compounds' physicochemical properties, the inhalation bioaccessibility of FRs in both conditions increased as molecular weight or octanol-water partition coefficient decreased, and it decreased as water solubility decreased. Health risk assessment clearly indicated that the hazard quotient of FRs via inhalation exposure for workers in the e-waste-dismantling workshops was less than 1, suggesting that the inhalation exposure to FRs during indoor dismantling of e-waste at this site was negligible based on the current methodology of non-cancer health risk assessment used in this study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Previous studies have suggested that unidentified compounds constitute a large proportion of extractable organochlorine (EOCl) and extractable organobromine (EOBr) in the crude extracts without fractionation; however, the proportion of unidentified EOX (X = chlorine, bromine) associated with high-/low-molecular-weight compounds is still unknown. In this study, we applied gel permeation chromatography to fractionate extracts from archived liver samples of high-trophic marine and terrestrial mammals (striped dolphins, cats, and raccoon dogs), for which concentrations of legacy organohalogen contaminants (polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers [PBDEs]) had been previously reported. EOX in high- (>1000 g/mol) and low- (≤1000 g/mol) molecular-weight fractions (EOX-H and EOX-L) were determined by neutron activation analysis. Comparison of EOCl and EOBr enabled the characterization among species. Despite small differences in the concentrations and molecular-weight profiles of EOCl among species, the contribution of chlorine in identified compounds to EOCl-L varied from 1.5% (cats) to 79% (striped dolphins). Considerable species-specific variations were observed in the concentrations of EOBr: striped dolphins exhibited significantly greater concentrations of both EOBr-H and EOBr-L than cats and/or raccoon dogs. Moreover, the contribution of bromine in PBDEs to EOBr-L was >50% in two cats, while it was <6% in other specimens. This is the first report on EOBr mass balance in cetaceans and on EOX mass balance in terrestrial mammals living close to humans. These results suggest the need for analysis of unidentified chlorinated compounds in terrestrial mammals and unidentified brominated compounds in marine mammals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The formation, emission, environmental occurrence, and potential adverse effects of unintentionally produced polychlorinated biphenyls (PCBs) in pigments are reviewed, providing a comprehensive and up-to-date picture on these pollutants. PCBs are typically formed during manufacturing of organic pigments that involve chlorinated intermediates and reaction solvents, rather than those of inorganic pigments. Concentrations and profiles of PCBs vary greatly among pigment types and producers, with total PCB levels ranging from lower than detection limits to several hundred ppm; major components can be low-chlorinated (e.g., CB-11) or high-chlorinated congeners (e.g., CB-209). Pigment-derived PCBs can be released into the environment through different steps including pigment production, application, and disposal. They can contaminate atmospheric, terrestrial, and aquatic ecosystems, and then affect organisms living there. This situation garners scientific and public attention to nonlegacy emissions of PCBs and suggests the need for appropriate monitoring, management, and abatement strategies regarding these pollutants., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Contamination levels and profiles of mono- to deca-chlorinated biphenyls (PCBs) were characterized in a sediment core dated in 1954-2011 from Beppu Bay, southwestern Japan, providing a comprehensive and detailed picture on the environmental occurrence, temporal trends, and emission sources of these pollutants in the study area. Concentrations of total PCBs in the core ranged from 3.5 to 150 (median 15) ng g -1 dry weight and exhibited depth profile matching with Japanese PCB production and emission patterns (i.e., drastically increasing from the early 1960s, peaking in 1970, and then rapidly decreasing). Origin of PCBs in the studied samples largely associated with Kanechlor mixtures (e.g., KC-300 and KC-400), especially for sediment layers dated between the mid-1960s and early 1970s (i.e., the intensive PCB production period in Japan). In addition, dechlorination and weathering signals and emerging inputs of PCBs were also observed in deeper and shallower sediment segments with notable proportions of some unique congeners such as CB-47/48/51 and CB-11, respectively. Historical fluxes of PCBs in our samples showed quite similar vertical shape as concentrations. In the context of national implementation for complete treatment of PCB-containing waste until 2024, further investigations on spatiotemporal trends and environmental loads of PCBs in Japan are necessary., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Concentrations and congener-specific profiles of total 209 polychlorinated biphenyls (PCBs) were investigated in settled dust samples collected from end-of-life vehicle (ELV) processing, urban, and rural areas in northern Vietnam. Concentrations of total 209 PCBs, seven indicator congeners, and twelve dioxin-like PCBs decreased in the order: ELV working > ELV living ≈ urban > rural dusts. Penta- and hexa-CBs dominated the homolog patterns in all the samples with higher proportions in the ELV dusts compared to the urban and rural house dusts. The abundance and pattern of PCBs in the ELV dusts suggest on-going emissions of these compounds related to processing of vehicular oils and lubricants containing PCBs, whereas the presence of PCBs in the urban and rural house dusts indicate long-time releases. However, levels of some PCBs identified as by-products of pigment manufacturing (e.g., PCB-11 and PCB-209) were higher in the urban house dusts than those from other locations, resulting from human activities utilizing paints and pigments. Daily intake doses (ID), non-carcinogenic hazard quotient (HQ), and lifetime cancer risk (CR) of PCBs through dust ingestion were estimated for ELV workers and residents in the studied areas. The workers and children in the ELV sites were estimated to be at higher risk of PCB exposure, however almost all of the HQ < 1 and CR < 10 -4 indicate no serious risk related to dust-bound PCBs., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Improper processing activities of e-waste are potential sources of polycylic aromatic hydrocarbons (PAHs) and their derivatives, however, information about the environmental occurrence and adverse impacts of these toxic substances is still limited for informal e-waste recycling areas in Vietnam and Southeast Asia. In this study, unsubstituted and methylated PAHs were determined in surface soil and river sediment samples collected from a rural village with informal e-waste recycling activities in northern Vietnam. Total levels of PAHs and MePAHs decreased in the order: workshop soil (median 2900; range 870-42,000 ng g -1 ) > open burning soil (2400; 840-4200 ng g -1 ) > paddy field soil (1200; range 530-6700 ng g -1 ) > river sediment samples (750; 370-2500 ng g -1 ). About 60% of the soil samples examined in this study were heavily contaminated with PAHs. Fingerprint profiles of PAHs and MePAHs in the soil and sediment samples indicated that these pollutants were mainly released from pyrogenic sources rather than petrogenic sources. The emissions of PAHs and MePAHs in this area were probably attributed to uncontrolled burning of e-waste and agricultural by-products, domestic coal and biomass combustion, and traffic activities. Carcinogenicity and mutagenicity of PAHs in the e-waste workshop soils were significantly higher than those of the field soils; however, the incremental lifetime cancer risk of PAH-contaminated soils in this study ranged from 5.5 × 10 -9 to 4.6 × 10 -6 , implying acceptable levels of human health risk. Meanwhile, concentrations of some compounds such as phenanthrene, anthracene, fluoranthene, benz[a]anthracene, and benzo[a]pyrene in several soil samples exceeded the maximum permissible concentrations, indicating the risk of ecotoxicological effects., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019. Published by Elsevier B.V.)

This article is based on my presentation at the 9th International Congress of the Growth Hormone Research and Insulin-like Growth Factor (IGF) Societies at Seattle, USA on 17th, September 2018. In the article, after a general introduction to IGF research, I briefly review the IGF research being published from 2016 to 2018, focusing on what I believe represent the most interesting areas of progress. These areas include ligands of the IGF-I receptor, ligand binding to the IGF-I receptor, long-term signaling through the IGF-I receptor, intracellular organelles where IGF signals are transmitted, and novel functions of the IGFBPs. Lastly, I discuss future directions of IGF research from my point of view., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The occurrence and profiles of 19 polycyclic aromatic hydrocarbons (PAHs) and 15 methylated derivatives (Me-PAHs) were examined in settled dust samples collected from workplaces and living areas of an informal end-of-life vehicle (ELV) processing village, and house dusts from urban and rural areas in northern Vietnam. Concentrations of total PAHs and Me-PAHs decreased in the order: ELV workplace (median 5700, range 900-18,000 ng g -1 ) > rural house (3700, 1800-6200 ng g -1 ) > urban house (1800, 620-3100 ng g -1 ) ≈ ELV living dusts (1000, 600-3900 ng g -1 ). PAHs with 4 rings or more dominated in almost all the samples, indicating the abundance of pyrogenic sources (e.g., vehicular emissions and domestic thermal processes). Levels of Me-PAHs were exceeded those of PAHs in several ELV samples, revealing specific petrogenic sources derived from vehicle processing activities. Results from source apportionment analysis have partially identified traffic emission, biomass and coal combustion, and mixed petrogenic-pyrogenic sources related to ELV waste as the major sources of PAHs and Me-PAHs in the urban, rural, and ELV areas, respectively. Daily intake doses and health risk related to PAHs and Me-PAHs in settled dusts were estimated for ELV workers and residents living in the study areas. The worst exposure scenario of dust-bound PAHs showed a potential cancer risk for the ELV workers, meanwhile, no significant non-cancer and cancer risk was expected for other exposed groups. A more comprehensive and accurate risk assessment of PAHs and related compounds should be conducted in Vietnam., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The environmental contamination by benzotriazole ultraviolet stabilizers (BUVSs) has received consider attention due to their long-term and widespread usage in various consumer and industrial products in accordance with solar UV radiation increase. The present study shows the baseline data of BUVSs in human breast milk from several areas in Japan, the Philippines, and Vietnam. Total concentrations of the 8 BUVSs in breast milk ranged from

A full congener-specific determination of polychlorinated biphenyls (PCBs) was conducted for street dusts in some areas in northern Vietnam. Total 209 PCB concentrations (median and range) of 14 (2.2-120), 11 (6.6-32), and 0.25 (0.10-0.97) ng g -1 were measured in the street dusts from an industrial park, an urban area, and a rural commune, respectively, suggesting environmental loads of PCBs related to industrialization and urbanization in northern Vietnam. PCB patterns of street dusts from the industrial park were dominated by lightly chlorinated homologs (tri- and tetra-CBs), while more highly chlorinated homologs (penta- and hexa-CBs) were the major contributors to total PCBs in the urban samples, indicating different emission sources. Linear correlations of log-transformed sum of 7 indicator congeners with total PCBs and sum of dioxin-like PCBs were observed. PCB-11, an inadvertently produced congener of pigment manufacturing processes, was detected in all the samples with more elevated proportions in the urban and rural areas than industrial park. Our results have revealed complex emission sources of PCBs in the study areas, including both historical (e.g., the past usage of imported PCB-containing oils and old electric equipment) and current sources such as releases from industrial activities and increasing use of new consumer products. Occupationally exposed persons (e.g., street sweepers, street vendors, and traffic policemen) and children in the urban and industrial areas were estimated to receive much higher doses of dust-bound PCBs than general population, suggesting the need for appropriate protection conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Past studies have reported several persistent organic pollutants (POPs) in different environmental matrices from a tropical coastal site, Parangipettai (PI), located along the bank of the Vellar River in Tamil Nadu, south India. Hence to fill the data gap after the strict ban on several POPs, high volume air sampling was conducted in PI to study the variability of atmospheric organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs) during summer, pre-monsoon and monsoon seasons. Emission source regions were tracked by using five days back trajectory analysis. Range of air concentrations in pg/m 3 were: dichlorodiphenyltrichloroethane (DDT), 13 - 1976; hexachlorocyclohexane (HCH), 260-1135, hexachlorocyclobenzene (HCB), 52-135, chlordanes, 36-135 and endosulfans, 66-1013. Six PBDE congeners ranged between 25 and 155 pg/m 3 with the highest concentration in summer followed by pre-monsoon and monsoon. Atmospheric DDT and HCH in PI have drastically reduced from the past report thereby showing the strict ban on agricultural use of these compounds. During monsoon, fresh source of o,p'-DDT, trans-chlordane and α-endosulfan was evident. Higher level of endosulphan sulfate in PI seems to be likely affected by the air mass, originating from a neighbouring state Kerela, where endosulfan has been extensively used for cashew plantations. Similarly in summer, the day recorded with the highest level of PBDEs, the sample was concurrently impacted by air parcel comprised of two major clusters, 1 (25%) and 2 (49%) that traversed through the metropolitan cities like Bangalore and Chennai. Dominance of BDE-99 over BDE-47 in PI is in line with the PBDE profile reported from Chennai city during similar time frame. Average concentration of tetra and penta BDE congeners in summer samples were nearly 2-3 folds higher than pre-monsoon or monsoon. Given the fact that strong localised sources for heavier BDE congeners are lacking in PI, regional atmospheric transport from the strong emission source regions in Chennai might have impacted PBDE concentration in PI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Of 942 organic micro-pollutants screened, 167 compounds were detected at least once in the atmosphere in some primitive waste processing sites and an urban area in northern Vietnam by using a polyurethane foam-based passive air sampling (PUF-PAS) method and an Automated Identification and Quantification System with a Database (AIQS-DB) for GC-MS. Total concentrations of organic pollutants were higher in samples collected from an urban area of Hanoi city (2300-2600 ng m -3 ) as compared with those from an end-of-life vehicle (ELV) dismantling area in Bac Giang (900-1700 ng m -3 ) and a waste recycling cooperative in Thai Nguyen (870-1300 ng m -3 ). Domestic chemicals (e.g., n-alkanes, phthalate ester plasticizers, and synthetic phenolic antioxidants) dominated the organic pollutant patterns in all the samples, especially in the urban area. Pesticides (e.g., permethrins, chlorpyrifos, and propiconazole) were found in the atmosphere around the ELV sites at more elevated concentrations than the other areas. Levels of polycyclic aromatic hydrocarbons and their derivatives in the Bac Giang and Thai Nguyen facilities were significantly higher than those measured in Hanoi urban houses, probably due to the waste processing activities. Daily intake doses of organic pollutants via inhalation were estimated for waste processing workers and urban residents. This study shall provide preliminary data on the environmental occurrence, potential emission sources, and effects of multiple classes of organic pollutants in urban and waste processing areas in northern Vietnam., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In developing countries, inappropriate recycling of e-waste has resulted in the environmental release of toxicants, including heavy metals, that may have deleterious health effects. In this study, we estimated daily metal intakes in five households in a Vietnamese village located in an e-waste processing area and assessed the health risk posed by exposure to the metals. Garden soil, floor dust, 24-h duplicate diet, and ambient air samples were collected from five households in northern Vietnam in January 2014. All samples were acid-digested, and contents of Cd, Cu, Mn, Pb, Sb, and Zn were measured by using ICP mass spectrometry and ICP atomic emission spectroscopy. In addition, the soil, dust, and diet samples were subjected to an bioaccessibility extraction test to determine bioaccessible metal concentrations. Hazard quotients were estimated from bioaccessible metal concentrations, provisional tolerable weekly intakes, and reference doses. Garden soil and floor dust were estimated to be mainly contributors to daily Pb intake, as indicated by calculations using bioaccessible metal concentrations and the U.S. Environmental Protection Agency soil plus dust ingestion rate. Diet was suggested to contribute significantly to daily Cd, Cu, Mn, Sb, and Zn intake. Estimated metal exposures via inhalation were negligible, as indicated by calculations using International Atomic Energy Agency reference inhalation rates. The maximum hazard quotients were calculated as 0.2 (Cd), 0.09 (Cu), 0.3 (Mn), 0.6 (Pb), 0.2 (Sb), and 0.5 (Zn), on the basis of bioaccessible metal concentrations. The contributions of Cd, Cu, Mn, Sb, and Zn except Pb to potential noncancer risk for adult residents of the five households in the e-waste processing area may be low., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The present study examined the occurrence and potential sources of mono- to octa-brominated dibenzo-p-dioxins/dibenzofurans (Mo-OBDD/Fs) in Tokyo Bay, Japan, using surface sediments and 210 Pb-dated sediment cores (covering the period 1895-2000) collected in 2002. The results showed a clear difference in the spatio-temporal trend between PBDFs and PBDDs. The spatial distribution of PBDF concentrations in the surface sediments showed a decreasing trend from the head to the mouth of the bay, which was similar to that of polybrominated diphenyl ethers (PBDEs) reported previously for the same sediment samples. In the sediment cores, PBDF and PBDE concentrations increased drastically after the 1960s and reached the highest levels in the late 1990s. In addition, a significant positive correlation was observed between the concentrations of their predominant congeners, 1,2,3,4,6,7,8-HpBDF and BDE-209. These results indicate that main contamination sources of PBDFs were technical PBDE formulations, especially DecaBDE. In contrast, total PBDDs in the surface sediments were rather uniform in the whole area of the bay. Furthermore, in the sediment cores, PBDD levels showed marginal fluctuation over the past century, with the predominance of 2,7-/2,8-DiBDDs and 1,3,7-/1,3,8-TrBDDs in all the sediment layers. It is noteworthy that these PBDD congeners were also found in the sediment layers corresponding to the pre-industrial era, supporting their natural formation in the coastal environment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

It is known that protein malnutrition develops fatty liver in rats. However, the mechanisms by which protein malnutrition enhances lipid accumulation in the liver are not fully understood. Our previous studies have demonstrated that protein malnutrition upregulates insulin signaling with an increase in TG levels in rat livers. Here, we examined whether the upregulated insulin signaling contributes to an enhancement of TG accumulation under protein malnutrition. As it is difficult to analyze insulin-induced hepatic TG synthesis in vivo, the isolated hepatocytes derived from rats fed a low-protein diet were used. The hepatocytes were isolated from rats fed a 15% casein diet (15C) as a control diet or a 5% casein diet (5C) as a low-protein diet and then treated with insulin. As shown in vivo, insulin signaling was upregulated in isolated hepatocytes from 5C-fed rats (5C hepatocytes). However, the insulin-induced increase in the mRNA levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS), was similar in both groups. The amounts of TG synthesized from both glucose and palmitate, as well as ACC1 and FAS protein levels, were increased at the basal state in 5C hepatocytes, but were not further increased by insulin. These results indicate that TG synthesis via both de novo fatty acid synthesis and esterification is enhanced in 5C hepatocytes, which is independent of the upregulation of insulin signaling., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Insulin receptor substrates (IRSs) are phosphorylated by IGF-I receptor tyrosine kinase in a ligand-dependent manner. In turn, they bind to and activate effector proteins such as PI3K, leading to various cell responses including cell proliferation. We had reported that ubiquitin ligase Nedd4 induces mono-ubiquitination of IRS-2, thereby enhancing IRS-2 tyrosine phosphorylation, leading to increased IGF signaling and mitogenic activity. Here we show that ubiquitin-specific protease 15 (USP15) antagonizes the effect of Nedd4 on IRS-2. We identified USP15 as a protein that preferentially bound to IRS-2 when IRS-2 was conjugated with ubiquitin. In HEK293 cells, Nedd4 overexpression induced IRS-2 ubiquitination, which was decreased by USP15 co-expression while increased by USP15 knockdown. Nedd4 overexpression enhanced IGF-I-dependent IRS-2 tyrosine phosphorylation, and USP15 co-expression suppressed it. Conversely, USP15 knockdown increased IRS-2 tyrosine phosphorylation and downstream signaling in prostate cancer PC-3 cells. We concluded that USP15 attenuates IGF-I signaling by antagonizing Nedd4-induced IRS-2 ubiquitination., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Organotin compounds (OTs) are ubiquitous contaminants with a broad range of applications ranging from biocides and pesticides to catalysts for the production of polyurethane foams and silicones. The deleterious effects of some OTs (particularly tributyltin - TBT) upon wildlife and experimental animals are well documented and include endocrine disruption, immunotoxicity, neurotoxicity, genotoxicity and metabolic dysfunction in which obesity is included. However, virtually no data on the current human exposure levels is available. In order to bridge this gap, we quantified for the first time the levels of OTs in duplicate diet samples from members of the University of Aveiro in Portugal. OTs were detected in 32% of the 28 diet samples analyzed, at relatively low levels. TBT and monobutyltin were detected only in two samples and dibutyltin was detectable in three samples. Dioctyltin was quantified in four samples and monooctyltin in three samples. Phenyltins were below the detection limit in all the diet samples analyzed. Overall, for the vast majority of the samples (89%), the estimated daily intakes (EDI) of organotins through food were much lower than the established tolerable daily intakes (TDI). Hence, for the majority of the participants the risk associated with food ingestion is low., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The long-distance transport potential of toxic lead (Pb) by plastic marine debris was examined by pure water leaching experiments using plastic fishery floats containing high level of additive-Pb such as 5100±74.3mgkg(-1). The leaching of Pb ended after sequential 480-h leaching experiments, and the total leaching amount is equivalent to approximately 0.1% of total Pb in a float. But it recovered when the float was scratched using sandpaper. We propose that a "low-Pb layer," in which Pb concentration is negligibly small, be generated on the float surface by the initial leaching process. Thickness of the layer is estimated at 2.5±1.2μm, much shallower than flaws on floats scratched by sandpaper and floats littering beaches. The result suggests that the low-Pb layer is broken by physical abrasion when floats are washed ashore, and that Pb inside the floats can thereafter leach into beaches., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Although complex mixtures of dioxin-related compounds (DRCs) can be released from informal e-waste recycling, DRC contamination in African e-waste recycling sites has not been investigated. This study examined the concentrations of DRCs including chlorinated, brominated, mixed halogenated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs, PBDD/Fs, PXDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in surface soil samples from the Agbogbloshie e-waste recycling site in Ghana. PCDD/F and PBDD/F concentrations in open burning areas (18-520 and 83-3800 ng/g dry, respectively) were among the highest reported in soils from informal e-waste sites. The concentrations of PCDFs and PBDFs were higher than those of the respective dibenzo-p-dioxins, suggesting combustion and PBDE-containing plastics as principal sources. PXDFs were found as more abundant than PCDFs, and higher brominated analogues occurred at higher concentrations. The median total WHO toxic equivalent (TEQ) concentration in open burning soils was 7 times higher than the U.S. action level (1000 pg/g), with TEQ contributors in the order of PBDFs>>PCDD/Fs>PXDFs. DRC emission to soils over the e-waste site as of 2010 was estimated, from surface soil lightness based on the correlations between concentrations and lightness, at 200mg (95% confidence interval 93-540 mg) WHO-TEQ over three years. People living in Agbogbloshie are potentially exposed to high levels of not only chlorinated but also brominated DRCs, and human health implications need to be assessed in future studies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Three oligomeric organophosphorus flame retardants (o-PFRs), eight monomeric PFRs (m-PFRs), tetrabromobisphenol A (TBBPA), and polybrominated diphenyl ethers (PBDEs) were identified and quantified in surface soils and river sediments around the e-waste recycling area in Bui Dau, northern Vietnam. Around the e-waste recycling workshops, 1,3-phenylene bis(diphenyl phosphate) (PBDPP), bisphenol A bis(diphenyl phosphate) (BPA-BDPP), triphenyl phosphate (TPHP), TBBPA, and PBDEs were dominant among the investigated flame retardants (FRs). The respective concentrations of PBDPP, BPA-BDPP, TPHP, TBBPA and the total PBDEs were 6.6-14000 ng/g-dry, <2-1500 ng/g-dry, 11-3300 ng/g-dry, <5-2900 ng/g-dry, and 67-9200 ng/g-dry in surface soils, and 4.4-78 ng/g-dry, <2-20 ng/g-dry, 7.3-38 ng/g-dry, 6.0-44 ng/g-dry and 100-350 ng/g-dry in river sediments. Near the open burning site of e-waste, tris(methylphenyl) phosphate (TMPP), (2-ethylhexyl)diphenyl phosphate (EHDPP), TPHP, and the total PBDEs were abundantly with respective concentrations of <2-190 ng/g-dry, <2-69 ng/g-dry, <3-51 ng/g-dry and 1.7-67 ng/g-dry in surface soils. Open storage and burning of e-waste have been determined to be important factors contributing to the emissions of FRs. The environmental occurrence of emerging FRs, especially o-PFRs, indicates that the alternation of FRs addition in electronic products is shifting in response to domestic and international regulations of PBDEs. The emissions of alternatives from open storage and burning of e-waste might become greater than those of PBDEs in the following years. The presence and environmental effects of alternatives should be regarded as a risk factor along with e-waste recycling., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This study demonstrated the contamination levels of polychlorinated biphenyls (PCBs), hydroxylated PCBs (OH-PCBs), polybrominated diphenyl ethers (PBDEs), methoxylated PBDEs (MeO-PBDEs), hydroxylated PBDEs (OH-PBDEs), and bromophenols (BPhs), and their relationships with thyroid hormones (THs), in the serum of human donors from an e-waste recycling site and a rural site in Hung Yen province, Vietnam. Occupationally related exposure was indicated by significantly higher residue levels of PCBs, OH-PCBs, PBDEs, and BPhs in the serum of donors from the e-waste recycling site (median: 420, 160, 290, and 300pgg(-1) wet wt, respectively) than those in the serum of donors from the rural site (median: 290, 82, 230, and 200pgg(-)(1) wet wt, respectively). On the other hand, levels of OH-/MeO-PBDEs were significantly higher in serum of donors from the reference site (median: 160 and 20pgg(-1) wet wt, respectively) than in those from the e-waste recycling site (median: 43 and 0.52pgg(-1) wet wt, respectively). In addition, we implemented stepwise generalized linear models to assess the association between the levels of TH and PCBs, PBDEs, and their related compounds. In females, we found positive associations of PCBs and OH-PCB concentrations with total thyroxine, free thyroxine, total triiodothyronine, and free triiodothyronine, and a negative association with thyroid-stimulating hormone concentrations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We report a case of aortic regurgitation (AR), coronary artery-to-pulmonary artery (CAPA) fistula, pulmonary atresia with ventricular septal defect (PA/VSD), and major aortopulmonary collateral arteries (MAPCAS). As a result of coronary steal and AR, myocardial ischemia and ventricular dysfunction occurred. When the patient was 2 months old with a body weight of 2.7 kg, we performed fistula ligation, aortic valvuloplasty, unifocalization of the MAPCAS, and right ventricle-to-pulmonary artery shunting. After the operation, the AR volume reduced, and the patient was scheduled for repair., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Dioxin-Responsive Chemical-Activated LUciferase gene eXpression assay (DR-CALUX) was applied to assess the total toxic activity of the mixture of PAHs and related compounds as well as dioxin-related compounds in road dust from urban areas of Hanoi, Vietnam. Road dust from Hanoi contained significantly higher DR-CALUX activities (3 to 39, mean 20 ng CALUX-TEQ/g dw) than those from a rural site (2 to 13, mean 5 ng CALUX-TEQ/g dw). The total concentrations of 24 major PAHs (Σ24PAHs) in urban road dust (0.1 to 5.5, mean 2.5 μg/g dw) were also 6 times higher than those in rural road dust (0.08 to 1.5, mean 0.4 μg/g dw). Diagnostic ratios of PAHs indicated vehicular engine combustion as the major PAH emission source in both sites. PAHs accounted for 0.8 to 60% (mean 10%) and 2 to 76% (mean 20%) of the measured CALUX-TEQs in road dust for Hanoi the rural site, respectively. Benzo[b]-/benzo[k]fluoranthenes were the major TEQ contributors among PAHs, whereas DRCs contributed <0.1% to CALUX-TEQs for both rural and urban sites. These results suggest TEQ contribution of other aryl hydrocarbon receptor agonists in road dust. Significant PAH concentrations in urban dust indicated high mutagenic and carcinogenic potencies. Estimated results of incremental life time cancer risk (ILCR) indicated that Vietnamese populations, especially those in urban areas such as Hanoi, are potentially exposed to high cancer risk via both dust ingestion and dermal contact. This is the first study on the exposure risk of AhR agonists, including PAHs and DRCs, in urban road dust from a developing country using a combined bio-chemical analytical approach., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Although informal e-waste recycling sites (EWRSs) are hotspots of both polychlorinated and polybrominated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs and PBDD/Fs), human exposure to the latter has not been studied in details. This study investigated the accumulation levels and profiles of dioxin-related compounds (DRCs) in breast milk samples from women living in two Vietnamese EWRSs and estimated the intake contribution from e-waste-related exposure. Screening results using Dioxin-Responsive Chemically Activated LUciferase gene eXpression assay (DR-CALUX) showed higher dioxin-like (DL) activities in samples from the EWRS Bui Dau than in those from the EWRS Trang Minh and a reference site (2.3-10 vs 1.7-4.8 and 0.60-5.7 pg CALUX-TEQ/g lipid, n=10, 6 and 9, respectively). Chemical analysis results of selected samples show that the WHO-TEQ levels of PCDD/Fs, DL-PCBs and PBDD/Fs in EWRS samples were not significantly higher than in those from the reference site (0.22-7.4 vs 1.1-3.0 pg/g lipid) and within the Vietnamese background range, but women involved in recycling accumulated higher concentrations of PCDFs (13-15 vs 2.3-8.8 pg/g lipid) and PBDFs (1.1-1.5 vs <1.1 pg/g lipid). By comparing the DRC profile in milk of these women with the reported profile in house dust from the same site, dust ingestion was estimated to contribute most of the intake for tetraBDF, 37 per cent to 55 per cent for penta-octaCDFs, but less than twenty per cent for PCDDs and DL-PCBs, and 26 per cent for total WHO-TEQs. The DL activities in some EWRS milk samples were not fully explained by chemical data, suggesting contribution from unidentified compounds. The estimated WHO-TEQ intake doses for breastfed infants (1.3-33 pg/kg/d) mostly exceeded the tolerable value, especially for those living in the EWRSs; and unidentified DRCs might increase further the dioxin-related health risk., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Tributyltin (TBT) is a biocide extremely toxic to a wide range of organisms, which has been used for decades in antifouling paints. Despite its global ban in 2008, TBT is still a problem of great concern due to the high levels trapped in sediments. Aeromonas molluscorum Av27 is a TBT degrading bacterium that was isolated from an estuarine system. We investigated the ability and the role of this bacterium on TBT degradation in this estuarine system, using a microcosm approach in order to mimic environmental conditions. The experiment was established and followed for 150 days. Simultaneously, changes in the indigenous bacterial community structure were also investigated. The results revealed a maximum TBT degradation rate of 28% accompanied by the detection of the degradation products over time. Additionally, it was observed that TBT degradation was significantly enhanced by the presence of Av27. In addition a significantly higher TBT degradation occurred when the concentration of Av27 was higher. TBT degradation affected the bacterial community composition as revealed by the changes in the prevalence of Proteobacteria subdivisions, namely the increase of Deltaproteobacteria and the onset of Epsilonproteobacteria. However, the addition of Av27 strain did not affect the dominant phylotypes. Total bacterial number, bacterial biomass productivity, 16S rRNA gene and denaturing gradient gel electrophoresis (DGGE) analyses also indicated alterations on the bacterial community structure over time, with bacteria non-tolerant to pollutants increasing their representativeness, as, for instance, the increase of the number of Alphaproteobacteria clones from 6% in the beginning to 12% at the end of the experiment. The work herein presented confirms the potential of Av27 strain to be used in the decontamination of TBT-polluted environments., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Nucleoside transport is important for nucleic acid synthesis in cells that cannot synthesize nucleosides de novo, and for entry of many cytotoxic nucleoside analog drugs used in chemotherapy. This study demonstrates that various steroid hormones induce inhibition of nucleoside transport in mammalian cells. We analyzed the inhibitory effects of estradiol (E2) on nucleoside transport using SH-SY5Y human neuroblastoma cells. We observed inhibitory effects after acute treatment with E2, which lasted in the presence of E2. However, when E2 was removed, the effect immediately disappeared, suggesting that E2 effects are not mediated through the canonical regulatory pathway of steroid hormones, such as transcriptional regulation. We also discovered that E2 could competitively inhibit thymidine uptake and binding of the labeled nucleoside transporter inhibitor, S-[4-nitrobenzyl]-6-thioinosine (NBTI), indicating that E2 binds to endogenous nucleoside transporters, leading to inhibition of nucleoside transport. We then tested the effects of various steroids on nucleoside uptake in NBTI-sensitive cells, SH-SY5Y and NBTI-insensitive cells H9c2 rat cardiomyoblasts. We found E2 and progesterone clearly inhibited both NBTI-sensitive and insensitive uptake at micromolar concentrations. Taken together, we concluded that steroid hormones function as novel nucleoside transport inhibitors by competition with nucleosides for their transporters., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Fish consumption is known to have several health benefits for humans. However, the accumulation of toxic contaminants, such as PCBs, PBDEs and HBCDs in fish could pose health hazards. These contaminants were measured in tilapia fish species collected from Ghana. Mean levels were PCBs (62 ng/g lw), PBDEs (7.3 ng/g lw) and HBCDs (1.2 ng/g lw) and the predominance of CB-153, CB-138, CB-180, BDE-47 and α-HBCD is in concordance with scientific literature. The congener profiles of PBDEs and PCBs in the fish suggest that sources of Penta- and Deca-BDE technical mixtures as well as technical PCB mixture (Clophen A60) exist in Ghana, while textile operations and associated release of untreated wastewater are likely to be significant sources of HBCDs. Comparison of the results with some reported studies showed moderate contamination in Ghana although Ghana is a developing country in Africa. Concentrations of PCBs measured in all the specimens in this study were below the food safety guidelines issued by the Food and Drug Administration, USA and the European Commission. The calculated hazard index levels of the target contaminants were below the threshold value of one, indicating that the levels of the target contaminants do not seem to constitute a health risk via fish consumption, with regard to PCBs, PBDEs and HBCDs, based on the limited number of samples that was accounted for in this study. However, due to the continuous discharge of untreated effluents, follow up studies are warranted as the consumption of fish is the primary route of human exposure to PCBs. This maiden report on the status of PBDEs and HBCDs in fish from Ghana will contribute to the knowledge about environmental contamination by POPs in a less industrialized region of the world so far sparsely covered in the literature., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The dynamic process of adipose differentiation involves stepwise expressions of transcription factors and proteins specific to the mature fat cell phenotype. In this study, it was revealed that expression levels of IntS6 and IntS11, subunits of the Integrator complex, were increased in 3T3-L1 cells in the period when the cells reached confluence and differentiated into adipocytes, while being reduced to basal levels after the completion of differentiation. Suppression of IntS6 or IntS11 expression using siRNAs in 3T3-L1 preadipocytes markedly inhibited differentiation into mature adipocytes, based on morphological findings as well as mRNA analysis of adipocyte-specific genes such as Glut4, perilipin and Fabp4. Although Pparγ2 protein expression was suppressed in IntS6 or IntS11-siRNA treated cells, adenoviral forced expression of Pparγ2 failed to restore the capacity for differentiation into mature adipocytes. Taken together, these findings demonstrate that increased expression of Integrator complex subunits is an indispensable event in adipose differentiation. Although further study is necessary to elucidate the underlying mechanism, the processing of U1, U2 small nuclear RNAs may be involved in cell differentiation steps., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The management of congenitally corrected transposition of the great arteries and associated lesions is frequently challenging. Restrictive ventricular septal defect and mild pulmonary stenosis are contraindications to the double switch procedure, including the atrial-Rastelli switch procedure, due to the production of postoperative left ventricular outflow tract obstruction. We describe a case of aortic translocation using the hemi-Mustard procedure after left ventricular training in order to prevent postoperative left ventricular outflow obstruction., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Summary: LST8 is a component of both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Herein, to examine the role of LST8, a common component of mTOR complexes, in the regulation of mTORC1 and mTORC2, first, we showed over-expression of LST8 in HepG2 to markedly enhance basal phosphorylation levels of not only p70 S6 kinase but also Akt. In contrast, LST8 knockdown by siRNA in HepG2 decreased phosphorylation levels of both p70 S6 kinase and Akt. These results indicate the LST8 expression level to determine basal mTORC1 and mTORC2 activities, since LST8 appears to be the component present at the lowest level in both mTORC1 and mTORC2 complexes. Previously, we reported S6 kinase phosphorylation to be reduced by over-expression of the Cterminally deleted Raptor mutant (Raptor-ΔCT) not binding to mTOR or LST8, while phosphorylation levels of Akt were markedly enhanced with no alteration in IRS-1 phosphorylation or PI 3-kinase activity. Using Raptor-ΔCT, we investigated the competition for association with LST8 between mTORC1 and mTORC2. Over-expression of Raptor-ΔCT abolished formation of the Raptor, S6 kinase, mTOR and LST8 complex, while the amount of LST8 in the Rictor-mTOR complex was increased. Therefore, it is likely that Raptor-mTOR and Rictor-mTOR complexes compete for association with LST8, and this mechanism may contribute to the reciprocal negative regulations of mTORC1 and mTORC2 activities, in terms of their LST8 components.:, (© 2012 Asian Oceanian Association for the Study of Obesity . All rights reserved.)

Insulin receptor substrates (IRSs) play central roles in insulin/insulin-like growth factor (IGF) signaling and mediate a variety of their bioactivities. IRSs are tyrosine-phosphorylated by activated insulin receptor/IGF-I receptor tyrosine kinase in response to insulin/IGF, and are recognized by signaling molecules possessing the SH2 domain such as phosphatidylinositol 3-kinase (PI3K), leading to the activation of downstream pathways. Recent studies have suggested that degradation of IRSs by the ubiquitin-proteasome pathway leads to impaired insulin/IGF signaling, but the precise mechanism underlying the process is still unclear. In this study, we identified deubiquitinating enzyme ubiquitin specific protease 7 (USP7) as an IRS-2-interacting protein and demonstrated that deubiquitinase activity of USP7 plays important roles in IRS-2 stabilization through the ubiquitin-proteasome pathway. In addition, insulin treatment dissociated USP7 from IRS-2, leading to degradation of IRS-2. This dissociation was prevented by treatment with LY294002, a PI3K inhibitor, indicating that insulin activation of the PI3K pathway leads to dissociation of IRS-2 from USP7 and IRS-2 degradation. We obtained similar results for IRS-1 in cells treated with insulin and for IRS-2 in cells treated with IGF-I. Taken together, this is the first report demonstrating that USP7 is an IRS-1/2 deubiquitinating enzyme forming a negative feedback loop in insulin/IGF signaling., (Copyright © 2012 Elsevier Inc. All rights reserved.)

To understand human contamination by multi-trace elements (TEs) in electrical and electronic waste (e-waste) recycling site at Agbogbloshie, Accra in Ghana, this study analyzed TEs and As speciation in urine of e-waste recycling workers. Concentrations of Fe, Sb, and Pb in urine of e-waste recycling workers were significantly higher than those of reference sites after consideration of interaction by age, indicating that the recycling workers are exposed to these TEs through the recycling activity. Urinary As concentration was relatively high, although the level in drinking water was quite low. Speciation analysis of As in human urine revealed that arsenobetaine and dimethylarsinic acid were the predominant As species and concentrations of both species were positively correlated with total As concentration as well as between each other. These results suggest that such compounds may be derived from the same source, probably fish and shellfish and greatly influence As exposure levels. To our knowledge, this is the first study on human contamination resulting from the primitive recycling of e-waste in Ghana. This study will contribute to the knowledge about human exposure to trace elements from an e-waste site in a less industrialized region so far scantly covered in the literature., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The growth of thyroid cells is tightly regulated by thyroid stimulating hormone (TSH) through the cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathway by potentiating the mitogenic activity of insulin and insulin-like growth factors (IGFs). However, we recently reported that thyroglobulin (Tg), a major product of the thyroid, also induces the growth of thyroid cells cultured in 0.2% serum in the absence of TSH and insulin. In this report, we demonstrate that Tg induced phosphorylation of molecules of the c-Raf/MEK/ERK pathway of the mitogen-activated protein kinase (MAPK). The MEK-1/2 inhibitor PD98059 suppressed Tg-induced phosphorylation of ERK1/2 and reduced bromodeoxyuridine (BrdU) incorporation. Tg also induced expression of the essential transcriptional factors c-Myc, c-Fos and c-Jun and phosphorylation of the retinoblastoma (Rb) protein. The present results, together with the previous report, suggest that Tg utilizes multiple signaling cascades to induce thyroid cell growth independent of TSH/cAMP stimulation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Excessive oxidative stress plays a causal role in various diseases such as diabetes, hypertension, atherosclerosis, and heart failure. Acromegaly is a pathological condition associated with excess growth hormone (GH) and insulin-like growth factor-I (IGF-I) and a high prevalence of diabetes, hypertension, atherosclerosis, and heart failure; resulting in premature death. We hypothesized that these conditions may be associated with increased oxidative stress., Objective and Methods: We explored the oxidative stress levels in the serum and tissues of GH-transgenic rats as an animal model for acromegaly. We also measured the oxidative stress levels in the serum of patients with acromegaly and age-, sex-, and BMI-matched control subjects. We examined the effects of GH and IGF-I on reactive oxygen species (ROS) production in C2C12 myocytes., Results: The levels of an oxidative stress marker, serum thiobarbituric acid reactive substances (TBARS) were increased in the GH-transgenic rats. Further, tissue oxidative stress damage was enhanced in the cardiomyocytes and vascular smooth muscle cells in the aorta of the GH-transgenic rats. In addition, serum TBARS levels and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were increased in acromegaly in humans. IGF-I but not GH induced ROS production in C2C12 myocytes in vitro., Conclusions: These data indicate that the increased levels of IGF-I are associated with enhanced oxidative stress in rats and humans. In addition, increased ROS may play an important role in the complications and premature death in acromegaly., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Organotin compounds (OTs) are ubiquitous in the marine environment and high concentrations (μg g(-1) range) in sediments from different coastal areas around the world have been reported. However, few reports have described the OTs contamination status in the offshore and deep sea environment. This work investigated organotin levels in Nazaré canyon for the first time. Levels of monobutyltin (MBT), dibutyltin (DBT), tributyltin (TBT), diphenyltin (DPT), triphenyltin (TPT), dioctyltin (DOT) and trioctyltin (TOT) were quantified in sediment samples from the upper flanks of the canyon and from the adjacent coastal area. TBT levels detected in the canyon flanks are about two to three orders of magnitude lower than those found in the coastal area. Nevertheless, when quantifiable, TBT levels in the canyon samples were higher than the Environmental Assessment Criteria set for TBT in sediments by the OSPAR Commission indicating that at those locations negative ecological impacts are likely to occur., (Copyright © 2011. Published by Elsevier Ltd.)

Insulin receptor substrates (IRSs) are phosphorylated by activated insulin/insulin-like growth factor (IGF)-I receptor tyrosine kinases. Phosphotyrosyl IRSs are recognized by signaling molecules possessing src homology region 2 (SH2) domains, which mediate various insulin/IGF bioactivities. However, we have shown that IRSs are also associated with other proteins by a phosphotyrosine-independent mechanism. Here, we demonstrated that IRSs form high-molecular-mass complexes (we named these complexes IRSomes) with various proteins and we elucidated their possible roles. Blue native-polyacrylamide gel electrophoresis of cell lysates revealed IRSome formation. Some proteins associated with IRSs in IRS-isoform-, cell-type-, or stimulus-specific manners. Results of the in vitro tyrosine phosphorylation assay indicated that tyrosine phosphorylation of IRS-1 by insulin receptor was decreased when IRS-1 was contained in IRSomes prepared from 3T3-L1 adipocytes treated with TNF-α. Also, tyrosine phosphorylation of IRS-2 by IGF-I receptor was increased when IRS-2 was contained in IRSomes prepared from FRTL-5 thyrocytes treated with dibutyryl cAMP. These results demonstrated that cytokine/hormone-induced formation of IRSomes modulates availability of IRSs to receptor tyrosine kinases., (Copyright © 2010 Elsevier Inc. All rights reserved.)