Binding and Activation of Estrogen-Related Receptor γ: A Novel Molecular Mechanism for the Estrogenic Disruption Effects of DDT and Its Metabolites.

DDT and its metabolites (DDTs) can induce estrogenic effects. Previous mechanistic investigations mainly concentrated on activating the genomic transcription of estrogen receptor (ER) pathways. Here, we identified whether estrogen-related receptor γ (ERRγ), an orphan nuclear receptor, is a potential target of DDTs by receptor binding, transcriptional activity, and receptor-mediated pathway assays. Fluorescence polarization-based binding assays showed that all eight DDTs bound to ERRγ directly, with Kd values ranging from 0.73-168.82 µM. Among them, 2,2-bis(4-chlorophenyl)ethanol (4,4'-DDOH) exhibited the highest binding affinity, which was 2.5-fold stronger than GSK4716, a well-known ERRγ agonist. Eight DDTs exhibited agonistic activity toward the ERRγ pathway, with 4,4'-DDOH showing the strongest potency. In silico studies revealed that DDTs tended to bind with ERRγ in the agonistic conformation. Using a SKBR3 breast cancer cell model, we further found that nanomolar or micromolar levels of DDTs significantly activated the ERRγ pathway in cells and induced cell proliferation through the ERRγ-modulated cell cycle. These results indicated that the binding and activation of DDTs to ERRγ might serve as molecular initiating events for subsequent ERRγ-mediated signaling pathways and adverse outcomes. Overall, our results demonstrated that ERRγ might be a crucial pathway involved in the estrogenic disruption effects of DDTs.

A High-Throughput Platform for the Rapid Quantification of Phosphorylated Histone H2AX in Cell Lysates Based on Microplate Electrochemiluminescence Immunosensor Array.

Sensitive detection of phosphorylated histone H2AX (γH2AX) in cells as a biomarker of DNA double-strand breaks has great significance in the field of molecular toxicology and life science research. However, current γH2AX detection methods require labor- and time-consuming steps. Here, for the first time, we designed a simple electrochemiluminescence (ECL) immunoassay integrated with a microplate-based sensor array to realize sensitive and high-throughput detection of γH2AX in cell lysates. Under the optimized conditions, this ECL immunosensor array could linearly respond to γH2AX concentrations in the range from 2 × 102 to 1 × 105 pg/mL. In addition, our approach possessed excellent specificity and satisfactory reproducibility, and its practicality was verified in real cell lysates. The whole process including instrumental and manual operation was completed in no more than 3 h. This study provides a convenient and rapid alternative method for the sensitive quantification of γH2AX, which shows promising application in high-throughput screening of genotoxic chemicals and drug candidates.

Environmental Estrogens and Their Biological Effects through GPER Mediated Signal Pathways.

Many environmental chemicals have been found to exert estrogenic effects in cells and experimental animals by activating nuclear receptors such as estrogen receptors and estrogen-related receptors. These compounds include bisphenols, pesticides, polybrominated diphenyl ethers (PBDEs), organophosphate flame retardants, phthalates and metalloestrogens. G protein-coupled estrogen receptor (GPER) exists widely in numerous cells/tissues of human and other vertebrates. A number of studies have demonstrated that GPER plays a vital role in mediating the estrogenic effects of environmental pollutants. Even at very low concentrations, these chemicals may activate GPER pathways, thus affect many aspects of cellular functions including proliferation, metastasis and apoptosis, resulting in cancer progression, cardiovascular disorders, and reproductive dysfunction. This review summarized the environmental occurrence and human exposure levels of these pollutants, and integrated current experimental evidence toward revealing the underlying mechanisms of pollutant-induced cellular dysfunction via GPER. The GPER mediated rapid non-genomic actions play an important role in the process leading to the adverse effects observed in experimental animals and even in human beings.

B4 Cluster-Based 3D Porous Topological Metal as an Anode Material for Both Li- and Na-Ion Batteries with a Superhigh Capacity.

The high rate performance of a battery requires the anode to be conductive not just ionically but also electronically. This criterion has significantly stimulated the study on 3D porous topological metals composed of nonmetal atoms with a light mass. Many carbon-based 3D topological metals for batteries have been reported, while similar work for 3D boron remains missing. Here, we report the first study of a 3D boron topological metal as an anode material for Li or Na ions. Based on systematic calculations, we found that the reported 3D topological metal H-boron composed of B4 cluster shows a low mass density (0.91 g/cm3) with multiple adsorption sites for Li and Na ions due to the electron-deficient feature of boron, leading to an ultrahigh specific capacity of 930 mAh/g for Li and Na ions with a small migration barrier of 0.15 and 0.22 eV, respectively, and small volume changes of 0.6% and 9.8%. These intriguing features demonstrate that B-based 3D topological quantum porous materials are worthy of further study for batteries.

Yttrium-Sodium Halides as Promising Solid-State Electrolytes with High Ionic Conductivity and Stability for Na-Ion Batteries.

All-solid-state sodium-ion batteries (ASIBs) are promising candidates for large-scale energy storage applications. To build such a battery system, efficient solid-state electrolytes (SSEs) with high sodium ionic conductivity at room temperature and good electrochemical stability as well as interface compatibility are required. In this work, using density functional theory combined with molecular dynamics simulation and a phase diagram, we have studied the potential of yttrium halide-based materials (Na3YX6, where X = Cl or Br) with inherent cation vacancies as diffusion carriers for solid electrolytes in ASIBs. A great balance between electrochemical stability and ionic conductivity found in these two systems overcomes the shortcomings of sulfide- and oxide-based SSEs. In particular, these two materials show Na+ conductivities of 0.77 and 0.44 mS cm-1 at 300 K and wide electrochemical windows of 0.51-3.75 and 0.57-3.36 V, and good interfacial stability with Na metal anode and high-potential polyanion (fluoro)phosphate cathode materials, respectively. These features make halide-based materials promising efficient solid-state electrolytes for Na-ion batteries.

2D CrCl2(pyrazine)2 monolayer: high-temperature ferromagnetism and half-metallicity.

The ferromagnetism in Cr-based monolayers is of current interest (2019 Nat. Nanotechnol. 14 408), however, the Curie temperature is low. How can we enhance the thermal stability of ferromagnetism? Motivated by the recent synthesis of the layered conductive magnet CrCl2(pyrazine)2 (2018 Nat. Chem. 10 1056), we perform first-principles calculations and Monte Carlo simulations to demonstrate that the exfoliated 2D CrCl2(pyrazine)2 monolayer is stable dynamically and thermally, and it is a ferromagnetic half-metal with a sizeable band gap of 2.8 eV in the semiconducting channel, and the strong in-plane Cr-Cr interaction results in a large magnetic anisotropy energy. Moreover, the sheet exhibits a high Curie temperature of 350 K due to the enhanced magnetic exchange interaction resulting from the aromatic property of pyrazine. All of these intriguing features endow 2D CrCl2(pyrazine)2 sheet with good potentials for applications in nanoscale spintronics devices.

A BN analog of two-dimensional triphenylene-graphdiyne: stability and properties.

Motivated by the feasibility of hybridizing C- and BN-units as well as the recent synthesis of a triphenylene-graphdiyne (TpG) monolayer, for the first time we explore the stability and electronic band structure of the Tp-BNyne monolayer composed of C-chains and the BN analog of triphenylene (Tp-BNyne) by using density functional theory. We find that the single layer Tp-BNyne is stable and exhibits a semiconducting character with a direct band gap of 3.78 eV. The band gap of Tp-BNyne can be flexibly tuned in a wide range by applying uniaxial straining in different directions, or by changing the length of the carbon chain, or by stacking in multilayers with different configurations, while the feature of a direct band gap can be well maintained. These intriguing characteristics endow the Tp-BNyne monolayer with additional advantages over the pristine TpG monolayer, which would stimulate more effort on the design and synthesis of novel 2D materials with high stability, tunable porosity, and controllable functionality for nanoelectronic and optoelectronic applications.

Predicting criteria continuous concentrations of metals or metalloids for protecting marine life by use of quantitative ion characteristic-activity relationships-species sensitivity distributions (QICAR-SSD).

Marine pollution by metals has been a major challenge for ecological systems; however, water quality criteria (WQC) for metals in saltwater is still lacking. Especially from a regulatory perspective, chronic effects of metals on marine organisms should receive more attention. A quantitative ion characteristic-activity relationships-species sensitivity distributions (QICAR-SSD) model, based on chronic toxicities for eight marine organisms, was established to predict the criteria continuous concentrations (CCCs) of 21 metals. The results showed that the chronic toxicities of various metals had good relationships with their physicochemical properties. Predicted CCCs of six metals (Hg2+, Cu2+, Pb2+, Cd2+, Ni2+ and Zn2+) were in accordance with the values recommended by the U.S. EPA, with prediction errors being less than an order of magnitude. The QICAR-SSD approach provides an alternative tool to empirical methods and can be useful for deriving scientifically defensible WQC for metals for marine organisms and conducting ecological risk assessments.

Predicting toxic potencies of metal oxide nanoparticles by means of nano-QSARs.

BACKGROUND: The enormous physicochemical and structural diversity of metal oxide nanoparticles (MeONPs) poses significant challenges to the testing of their biological uptake, biodistribution, and effects that can be used to develop understanding of key nano-bio modes of action. This has generated considerable uncertainties in the assessment of their human health and environmental risks and has raised concerns about the adequacy of their regulation. In order to surpass the extremely resource intensive case-by-case testing, intelligent strategies combining testing methods and non-testing predictive modeling should be developed. METHODS: The quantitative structure-activity relationship (QSARs) in silico tools can be instrumental in understanding properties that affect the potencies of MeONPs and in predicting toxic responses and thresholds of effects. RESULTS: The present study proposes a predictive nano-QSAR model for predicting the cytotoxicity of MeONPs. The model was applied to test the relationships between 26 physicochemical properties of 51 MeONPs and their cytotoxic effects in Escherichia coli. The two parameters, enthalpy of formation of a gaseous cation (▵Hme+) and polarization force (Z/r), were elucidated to make a significant contribution for the toxic effect of these MeONPs. The study also proposed the mechanisms of toxic potency in E. coli through the model, which indicated that the MeONPs as well as their released metal ions could collectively induce DNA damage and cell apoptosis. SIGNIFICANCE: These findings may provide an alternative method for prioritizing current and future MeONPs for potential in vivo testing, virtual prescreening and for designing environmentally benign nanomaterials.

[Observation on therapeutic effect of acupuncture and moxibustion combined with cupping on senile psychophysiologic disorders].

OBJECTIVE: To probe into the feasibility of acupuncture and moxibustion combined with rapid and repeated cupping at points on the back for treatment of senile psychophysiologic disorders. METHODS: Sixty cases of clinically commonly-seen senile psychophysiologic disorders were randomly divided into the treatment group treated by acupuncture and moxibustion combined with rapid and repeated cupping at points on the back and the control group treated by oral administration of small dose of medicine for expectant treatment. Their therapeutic effects were compared. RESULTS: The therapeutic effect of the treatment group was better than that of the control group (P < 0.01). CONCLUSION: Acupuncture and moxibustion combined with rapid and repeated cupping at points on the back can more rapidly alleviate the psychotic symptoms of thinking more and misgivings, gloominess, desire to cry, restlessness due to deficiency, anger, impatient for senile psychophysiologic disorders.