Search

2,4-Di-tert-butylphenol (2,4-DTBP) is an important commercial antioxidant and a toxic natural secondary metabolite that has been detected in humans. However, there is scant information regarding its toxicological effects. We asked whether 2,4-DTBP is a potential obesogen. Using a human mesenchymal stem cell adipogenesis assay, we found that exposure to 2,4-DTBP led to increased lipid accumulation and expression of adipogenic marker genes. Antagonist assays revealed that 2,4-DTBP increased lipid accumulation by activating the peroxisome proliferator-activated receptor (PPAR) γ-retinoid X receptor (RXR) heterodimer. 2,4-DTBP likely activated the PPARγ/RXRα heterodimer by activating RXRα but not directly binding to PPARγ. We confirmed that 2,4-DTBP directly bound to RXRα by solving the crystal structure of this complex, then predicted and demonstrated that related compounds could also activate RXRα. Our study demonstrated that 2,4-DTBP and related chemicals could act as obesogens and endocrine disruptors via RXRs. These data showed that 2,4-DTBP belongs to a family of compounds whose endocrine-disrupting and obesogenic effects can be strongly modulated by their chemical composition. Structure–activity studies such as the present one could help guide the rational development of safer antioxidants that do not interact with important nuclear receptors having broad effects on human development and physiology. [ABSTRACT FROM AUTHOR]

The threading dislocations (TDs) in GaAs/Si epitaxial layers due to the lattice mismatch seriously degrade the performance of the lasers grown on silicon. The insertion of InAs quantum dots (QDs) acting as dislocation filters is a pretty good alternative to solving this problem. In this paper, a finite element method (FEM) is proposed to calculate the critical condition for InAs/GaAs QDs bending TDs into interfacial misfit dislocations (MDs). Making a comparison of elastic strain energy between the two isolated systems, a reasonable result is obtained. The effect of the cap layer thickness and the base width of QDs on TD bending are studied, and the results show that the bending area ratio of single QD (the bending area divided by the area of the QD base) is evidently affected by the two factors. Moreover, we present a method to evaluate the bending capability of single-layer QDs and multi-layer QDs. For the QD with 24-nm base width and 5-nm cap layer thickness, taking the QD density of 1011 cmâˆ'2 into account, the bending area ratio of single-layer QDs (the area of bending TD divided by the area of QD layer) is about 38.71%. With inserting five-layer InAs QDs, the TD density decreases by 91.35%. The results offer the guidelines for designing the QD dislocation filters and provide an important step towards realizing the photonic integration circuits on silicon. [ABSTRACT FROM AUTHOR]

We investigate the thermal stresses for GaAs layers grown on V-groove patterned Si substrates by the finite-element method. The results show that the thermal stress distribution near the interface in a patterned substrate is nonuniform, which is far different from that in a planar substrate. Comparing with the planar substrate, the thermal stress is significantly reduced for the GaAs layer on the patterned substrate. The effects of the width of the V-groove, the thickness, and the width of the SiO2 mask on the thermal stress are studied. It is found that the SiO2 mask and V-groove play a crucial role in the stress of the GaAs layer on Si substrate. The results indicate that when the width of V-groove is 50 nm, the width and the thickness of the SiO2 mask are both 100 nm, the GaAs layer is subjected to the minimum stress. Furthermore, Comparing with the planar substrate, the average stress of the GaAs epitaxial layer in the growth window region of the patterned substrate is reduced by 90%. These findings are useful in the optimal designing of growing high-quality GaAs films on patterned Si substrates. [ABSTRACT FROM AUTHOR]

BACKGROUND: Numerous studies have indicated the estrogenic effects of polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs (OH-PBDEs). However, the previous mechanistic studies focused on their estrogenic effects through genomic transcriptional activation of estrogen receptors. OBJECTIVE: The present study aimed to investigate the estrogenic effects of PBDEs and OH-PBDEs via nongenomic G protein-coupled estrogen receptor (GPER) pathways. METHODS: The binding affinities of 12 PBDEs and 18 OH-PBDEs with GPER were determined by a fluorescence competitive binding assay in a human breast cancer cell line (SKBR3). Molecular docking was performed to simulate the interactions. Their activities on GPER pathways were investigated by detecting calcium mobilization and cyclic adenosine monophosphate (cAMP) accumulation in SKBR3 cells. The effects on SKBR3 cell migration were investigated using Boyden chamber and wound-healing assays. RESULTS: Our results showed that 11 of the OH-PBDEs but none of the PBDEs bound to GPER directly. Relative binding affinities ranged from 1.3% to 20.0% compared to 17[beta]-estradiol. Docking results suggested that the hydroxyl group played an essential role in the binding of OH-PBDEs to GPER by forming hydrogen bond interactions. Most of the OH-PBDEs activated subsequent GPER signaling pathways. Among them, 4'-OH-BDE-049, 5'-OH-BDE-099, and 3'-OH-BDE-154 displayed the highest activity with lowest effective concentrations (LOECs) of 10-100 nM. These three OH-PBDEs also promoted SKBR3 cell migration via GPER pathways with LOECs of 0.1- 1 [micro]M. CONCLUSION: OH-PBDEs could bind to GPER, activate the subsequent signaling pathways, and promote SKBR3 cell migration via GPER pathways. OH-PBDEs might exert estrogenic effects by a novel nongenomic mechanism involving the activation of GPER at nanomolar concentrations. https:// doi.org/10.1289/EHP2387, Introduction Polybrominated diphenyl ethers (PBDEs) have been and are currently used as flame retardant additives in a variety of industrial and consumer products such as plastic materials and textile fabrics [...]

Previously, perfluoroalkyl substances (PFASs) have been found to be associated with many adverse effects mediated by the peroxisome proliferator-activated receptor α (PPARα) and PPARγ. Here, we found another subtype of the peroxisome proliferator-activated receptors (PPARs); the PPARβ/δ mediated pathway might also be a potential adverse outcome pathway for PFASs. We investigated the direct binding and transcriptional activity of PFASs toward human PPARβ/δ, and further revealed the structure-binding and structure–activity relationship between PFASs and PPARβ/δ. The receptor binding experiment showed that their binding potency was dependent on the carbon chain length and the terminal functional group. For twelve perfluoroalkyl carboxylic acids (PFCAs), an inverted U-shaped relationship existed between the PPARβ/δ binding potency and the carbon chain length, with perfluorododecanoc acid (C12) showing the highest binding potency. The three perfluoroalkane sulfonic acids (PFSAs) exhibited a stronger binding potency than their PFCA counterparts. The two fluorotelomer alcohols (FTOHs) showed no binding potency. In receptor transcriptional activity assays, they enhanced the PPARβ/δ transcriptional activity. Their transcriptional activity was also related to the carbon chain length and the terminal functional group. Molecular docking analysis showed the PFASs fitted into the ligand binding pocket of PPARβ/δ with a binding geometry similar to a fatty acid. [ABSTRACT FROM AUTHOR]

There has been long-standing evidence that the lower-chlorinated polychlorinated biphenyls (LC-PCBs) can be metabolized to hydroxylated metabolites (OH-PCBs), which play important roles in the LC-PCBs induced toxicity. Recently, multiple studies have demonstrated the further metabolic transformation of OH-PCBs to LC-PCB sulfates in vitro and in vivo. Several studies found LC-PCB sulfates could bind with thyroid hormone (TH) transport proteins in the serum, indicating the potential relevance of these metabolites in the TH system disruption effects. However, the interaction of LC-PCB sulfates with the TH nuclear receptor (TR), another kind of important functional protein in the TH system, has not been explored. Here, by using a fluorescence competitive binding assay, we demonstrated that LC-PCB sulfates could bind with TRα. Moreover, the LC-PCB sulfates had higher binding potency than their corresponding OH-PCB precursors. By using a luciferase reporter gene assay, we found the LC-PCB sulfates showed agonistic activity towards the TRα signaling pathway. Molecular docking simulation showed all the tested LC-PCB sulfates could fit into the ligand binding pocket of the TRα. The LC-PCB sulfates formed hydrogen bond interaction with arginine 228 residue of TRα by their sulfate groups, which might facilitate the TR binding and agonistic activity. The present study suggests that interaction with the TR might be another possible mechanism by which LC-PCB sulfate induce TH system disruption effects. Image 1 • LC-PCB sulfates may contribute to LC-PCBs induced TH system disruption effects. • LC-PCB sulfates bound to TRα directly. • LC-PCB sulfates showed higher TRα binding affinity than their OH-PCBs precursors. • LC-PCB sulfates showed agonistic activity towards TRα signaling pathway. • LC-PCB sulfates could form hydrogen bond interaction with arginine 228 residue. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) can be metabolized to hydroxylated PBDEs (OH-PBDEs), which play important roles in their disruption effects on the thyroid hormone (TH) system. Recently, multiple in vitro studies suggested that OH-PBDEs might be further metabolically transformed to PBDE sulfates. However, information about the bioactivity of PBDE sulfate metabolites is limited. In the present study, we explored the possible disruption effects of PBDE sulfates to the TH system by studying their binding and activity towards TH transport proteins and nuclear receptors. We found PBDE sulfates could bind to two major TH transport proteins (thyroxine-binding globulin and transthyretin). Besides, PBDE sulfates could also bind to two subtypes of TH nuclear receptors (TRα and TRβ) and showed agonistic activity towards the subsequent signaling pathway. Moreover, the PBDE sulfates showed higher binding potency to TH transport proteins and TRs compared with their corresponding OH-PBDE precursors. Molecular docking results showed that replacement of hydroxyl groups with sulfate groups might lead to more hydrogen bond interactions with these proteins. Overall, our study suggested that PBDE sulfates might disturb the TH system by binding to TH transport proteins or TRs. Our finding indicated a possible mechanism for the TH system disruption effects of PBDEs through their sulfate metabolites. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that exogenous hydrogen sulfide can alleviate the development of diabetic cardiomyopathy (DCM) by inhibiting oxidative stress, inflammation, and apoptosis. However, the underlying mechanism is not fully understood. Nuclear expression and function of the transcription factor Forkhead box protein O (FoxO1) have been associated with cardiovascular diseases, and thus, the importance of FoxO1 in DCM has gained increasing attention. This study was designed to investigate the interactions between hydrogen sulfide (H2S) and nuclear FoxO1 in DCM. Methods: Diabetes was induced in adult male C57BL/6J mice by intraperitoneal injection of streptozotocin and was treated with H2S donor sodium hydrosulfide for 12 weeks. The H9C2 cardiomyoblast cell line and neonatal rat cardiomyocytes (NRCMs) were treated with the slow‐releasing H2S donor GYY4137 before high‐glucose (HG) exposure with or without pretreatment with the Akt inhibitor MK‐2206 2HCl. Changes in FoxO1 protein phosphorylation and subcellular localization were determined in H9C2 cells, NRCMs, and cardiac tissues from normal and diabetic mice. Cardiac structure and function in the diabetic mice were evaluated by echocardiography and histological analysis and compared with those in control animals. Results: The echocardiographic and histopathological data indicated that exogenous H2S improved cardiac function and attenuated cardiac hypertrophy and myocardial fibrosis in diabetic mice. H2S also improved HG‐induced oxidative stress and apoptosis in cardiac tissue and NRCMs. In addition, H2S induced FoxO1 phosphorylation and nuclear exclusion in vitro and in vivo, and this function was not inhibited by MK‐2206 2HCl. Alanine substitution mutation of three sites in FoxO1‐enhanced FoxO1 transcriptional activity, and subsequent treatment with exogenous H2S could not prevent HG‐induced nuclear retention. Conclusions: Our data indicate that H2S is a novel regulator of FoxO1 in cardiac cells and provide evidence supporting the potential of H2S in inhibiting the progression of DCM. Our data indicate that hydrogen sulfide (H2S) is a novel regulator of Forkhead box protein O in cardiac cells and provide evidence supporting the potential of H2S in inhibiting the progression of diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

The wide use of the alternatives to bisphenol A (BPA) has raised concerns about their potential toxicities. Considering the disrupting activity of BPA on thyroid hormone (TH) signaling, we investigated whether bisphenol S (BPS) and bisphenol F (BPF), two leading alternatives, could interfere with TH signaling pathway using a series of assays in vitro and in vivo . In the fluorescence competitive binding assay, we found BPS and BPF, like BPA, bound to TH receptors (TRα and TRβ), with the binding potencies an order of magnitude lower than BPA (BPA > BPF > BPS). Molecular docking data also show their binding potencies to TRs. In the coactivator recruitment assay, BPS and BPF recruited coactivator to TRβ but not TRα, with weaker potencies than BPA. Correspondingly, agonistic actions of the three bisphenols in the absence or presence of T3 were observed in the TR-mediated reporter gene transcription assay. Also, all the three bisphenols induced TH-dependent GH3 cell proliferation, whereas BPA and BPF inhibited T3 induction in the presence of T3. As for in vivo assay, the three bisphenols like T3 induced TH-response gene transcription in Pelophylax nigromaculatus tadpoles, but in the presence of T3 altered T3-induced gene transcription in a biphasic concentration-response manner. These results for the first time demonstrate that BPS and BPF, like BPA, have potential to interfere with TH signaling pathway, i.e., they generally activate TH signaling in the absence of T3, but in the presence of TH, display agonistic or/and antagonistic actions under certain condition. Our study highlights the potential risks of BPS and BPF as BPA alternatives. [ABSTRACT FROM AUTHOR]

Recent studies reported that atorvastatin (ATOR) alleviated progression of experimental diabetic cardiomyopathy (DCM), possibly by protecting against apoptosis. However, the underlying mechanisms of this protective effect remain unclear. Therefore, our study investigated the role of the glycogen synthase kinase (GSK)-3β-protein phosphatase 2A(PP2A)-NF-κB signaling pathway in the anti-apoptotic and cardioprotective effects of ATOR on cardiomyocytes cultured in high glucose (HG) and in DCM. Our results showed that, in HG-cultured cardiomyocytes, phosphorylation of GSK-3β was decreased, while that of the PP2A catalytic subunit C (PP2Ac) and IKK/IкBα was increased, followed by NF-кB nuclear translocation and apoptosis. IKK/IкBα phosphorylation and NF-кB nuclear translocation were also increased by treatment of cells with okadaic acid (OA), a selective PP2A inhibitor, or by silencing PP2Ac expression. The opposite results were obtained by silencing GSK-3β expression, which resulted in PP2Ac activation. Furthermore, IKK/IкBα phosphorylation and NF-кB nuclear translocation were markedly inhibited and apoptosis attenuated in cells treated with ATOR. These effects occurred through inactivation of GSK-3β and subsequent activation of PP2Ac. They were abolished by treatment of cells with OA or PP2Ac siRNA. In mice with type 1 diabetes mellitus, treatment with ATOR, at 10 mg-kg−1-d−1, significantly suppressed GSK-3β activation, IKK/IкBα phosphorylation, NF-кB nuclear translocation and caspase-3 activation, while also activating PP2Ac. Finally, improvements in histological abnormalities, fibrosis, apoptosis and cardiac dysfunction were observed in diabetic mice treated with ATOR. These findings demonstrated that ATOR protected against HG-induced apoptosis in cardiomyocytes and alleviated experimental DCM by regulating the GSK-3β-PP2A-NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Biotransformation of 8:2 fluorotelomer alcohol (8:2 FTOH) can form potentially more toxic metabolites. However, the responsible cytochrome P450 (CYP) isoform(s) and phase II metabolism have not been studied in humans. Here, we characterized the in vitro metabolism of 8:2 FTOH by recombinant human CYPs, human liver microsomes, and human liver cytosol. The results showed that among the 11 isoforms investigated, CYP2C19 was the only enzyme capable of catalyzing 8:2 FTOH with Km and Vmax values of 18.8 μM and 8.52 pmol min−1 pmol−1 P450, respectively. The phase I metabolite was identified as 8:2 fluorotelomer aldehyde (8:2 FTAL). HLMs also catalyzed 8:2 FTOH transformation, with the Vmax and intrinsic clearance (CLint) values similar to those of CYP2C19 after the protein content is taken into account. Molecular docking showed that the hydroxyl group of 8:2 FTOH accesses the heme iron-oxo of CYP2C19 in an energetically favored orientation. 8:2 FTOH was also transformed by phase II enzymes to form O-glucuronide and O-sulfate conjugates. The CLint values follow the order of sulfation ＞ oxidation ＞ glucuronidation, suggesting that conjugation is the major metabolic pathway, which explains the low yield of perfluoroalkyl acids (PFCAs). These results provide new insight into fluorotelomer alcohol biotransformation and indirect human exposure to PFCAs. [ABSTRACT FROM AUTHOR]

In this paper, we proposed our recent works on inductively coupled plasma (ICP) etching of GaAs in Cl 2 /Ar and Cl 2 /Ar/O 2 chemistry for pattern structure transferring and analyzed their etching mechanism. It is proposed that the etching rate reduction due to introduction of extra Cl 2 and additional O 2 in the plasma chemistry is resulted from their influences on all ICP etching process aspects. Moreover, with results presented here, it shows that by introducing O 2 into plasma chemistry, the etched GaAs surface roughness will be optimized and the etching ratio of photoresist to GaAs will be tuned. [ABSTRACT FROM AUTHOR]

Vertical InAs/GaAs nanowire (NW) heterostructures with a straight InAs segment have been successfully fabricated on Si (111) substrate by using AlGaAs/GaAs buffer layers coupled with a composition grading InGaAs segment. Both the GaAs and InAs segments are not limited by the misfit strain induced critical diameter. The low growth rate of InAs NWs is attributed to the AlGaAs/GaAs buffer layers which dramatically decrease the adatom diffusion contribution to the InAs NW growth. The crystal structure of InAs NW can be tuned from zincblende to wurtzite by controlling its diameter as well as the length of GaAs NWs. This work helps to open up a road for the integration of high-quality III-V NW heterostructures with Si. [ABSTRACT FROM AUTHOR]

We report on the Au-assisted vapour--liquid--solid (VLS) growth of GaAs/InxGa1-xAs/GaAs (0.2 ≤ x ≤ 1) axial double-heterostructure nanowires on GaAs (111) B substrates via the metal--organic chemical vapor deposition (MOCVD) technique. The influence of the indium (In) content in an Au particle on the morphology of nanowires is investigated systematically. A short period of pre-introduced In precursor before the growth of InxGa1-x As segment, coupled with a group III precursor interruption, is conducive to obtaining symmetrical heterointerfaces as well as the desired In/Ga ratio in the InxGa1-x As section. The nanowire morphology, such as kinking and tapering, are thought to be related to the In composition in the catalyst alloy as well as the VLS growth mechanism. [ABSTRACT FROM AUTHOR]

Nonlinear optical property of semiconductor nanowires plays a key role in nanoscale optoelectronics. In this paper, we demonstrate an excellent frequency converter based on GaAs nanowires (NWs), in which second harmonic generation (SHG) is excited by femtosecond lasers from 800 nm to 1800 nm. Simultaneous SHG with a bandwidth of 300-nm is excited by a super-continuum source at 1000-1600 nm. Broadband SHG can also be acquired from an isolated single NW and the process is coherent. The experimental results suggest that GaAs NWs are potential broadband optical nonlinear converters in nanoscale optoelectronics. [ABSTRACT FROM AUTHOR]

Obesity has become a very large concern worldwide, reaching pandemic proportions over the past several decades. Lifestyle factors, such as excess caloric intake and decreased physical activity, together with genetic predispositions, are well-known factors related to obesity. There is accumulating evidence suggesting that exposure to some environmental chemicals during critical windows of development may contribute to the rapid increase in the incidence of obesity. Agrochemicals are a class of chemicals extensively used in agriculture, which have been widely detected in human. There is now considerable evidence linking human exposure to agrochemicals with obesity. This review summarizes human epidemiological evidence and experimental animal studies supporting the association between agrochemical exposure and obesity and outlines possible mechanistic underpinnings for this link. • Positive associations exist between agrochemical exposures and adult obesity. • Prenatal exposure to agrochemicals could lead to childhood obesity. • Numerous possible mechanisms underlie the obesogenic effects of agrochemicals. • Nuclear receptors likely mediate many obesogenic effects of agrochemicals. • Epigenetics and the gut microbiome likely play key roles in the obesogenic effect of agrochemicals. [ABSTRACT FROM AUTHOR]

As a class of widely used ultraviolet filters, hydroxylated benzophenones (BPs) have been detected in various environmental and human samples, raising concerns about their ecological and health effects. BPs were found to impair reproductive functions, and their disruption effects on estrogen receptor, G protein-coupled estrogen receptor, and androgen receptor were investigated as possible mechanisms of action. In the present study, we investigated the binding and activation of estrogen related receptor γ (ERRγ) as an alternative mechanism of BPs reproductive toxicity. In competitive fluorescence binding assays, all of the 8 tested BPs were found to bind to the ligand-binding domain of ERRγ but with varying binding affinity. Molecular dock analysis indicated that binding of BPs to ERRγ in the agonistic conformation is preferred. In luciferase reporter gene assays in HepG2 cells, all the 8 BPs activated the transcription of ΕRRγ in a concentration-dependent manner in the range of 3–100 μM,consistent with the docking result. Hazard quotient calculation revealed a high risk on the BP-type personal care products users. The combined in vitro and in silico results suggest that binding and activation of ERRγ might be the molecular initiating events of an alternative mechanism of BPs endocrine disruption toxicity. Image 1 • Hydroxylated benzophenones (BPs) interact directly with estrogen related receptor γ (ERRγ) in vitro and in silico. • ERRγ transcriptional activity is enhanced by BPs which might lead to their endocrine disruption toxicity. • Exposure level of BP-type personal care product users is at high health risk. [ABSTRACT FROM AUTHOR]

Airborne lower-chlorinated PCBs are vulnerable to metabolization to PCB sulfates through further sulfation of the hydroxylated metabolites (OH-PCBs). However, studies on the toxic effects and mechanisms of PCB sulfates are still very limited. Here, we investigated for the first time the potential endocrine disruption effects of PCB sulfates through estrogen-related receptor γ (ERRγ) in comparison with their OH-PCBs precursors and PCB parent compounds. The binding affinity of thirteen PCBs/OH-PCBs/PCB sulfates was measured by using fluorescence competitive binding assays based on fluorescence polarization (FP). All of the tested chemicals could bind to ERRγ with the K d (dissociation constant) values ranging from not available (NA) to 3.2 μM 4′–OH–PCB 12 showed the highest binding affinity with K d value of 3.2 μM, which was comparable to that of a synthetic ERRγ agonist GSK4716. The effects of the thirteen chemicals on the ERRγ transcriptional activity were determined by using the luciferase reporter gene assay. We found the PCBs/OH-PCBs/PCB sulfates acted as agonists for ERRγ, with the lowest observed effective concentration reaching 3 μM. The binding affinity and agonistic activity of PCBs towards ERRγ were both enhanced after hydroxylation, while further sulfation of OH-PCBs decreased the activity instead. Molecular docking simulation showed that OH-PCBs had lower binding energy than the corresponding PCBs and PCB sulfates, indicating that OH-PCBs had higher binding affinity theoretically. In addition, OH-PCBs could form hydrogen bonds with amino acids Glu316 and Arg247 while PCBs and PCB sulfates could not, which might be the main factor impacting the binding affinity and agonistic activity. Overall, ERRγ is a novel target for lower-chlorinated PCBs and their metabolites. Image 1 • Lower-Chlorinated Polychlorinated Biphenyls and their metabolites can bind to and activate ERRγ. • The OH-PCBs had higher binding affinity with ERRγ than parent PCBs and PCB sulfates. • The OH-PCBs had higher agonistic activity on ERRγ than parent PCBs and PCB sulfates. • Molecular simulation explained well the differences of binding and agonistic activity. • The forming of hydrogen bonds play essential roles in binding and activity. This study provided a new possible mechanism for the endocrine disruption effects of PCBs and their metabolites through activation of ERRγ mediated signal pathways. [ABSTRACT FROM AUTHOR]