Development of a compact helicon plasma source with two sets of ring array permanent magnets for the study of blue core plasma.

A compact helicon plasma source for the study of helicon plasma, especially for the study of blue core plasma, is designed and developed with permanent magnets (PMs). The structure of the PMs consists of two sets of ring array magnets with opposite magnetization. This structure can provide a higher magnetic field with fewer PMs, which is helpful for controlling the device's mass. A quartz tube with 50 cm in length, 5 cm in outer diameter, and 0.3 cm in thickness is used. Argon helicon plasma is produced at ∼38 sccm (3.4 Pa inlet chamber and 0.122 Pa diffusion chamber) by a radio frequency (RF) power of ∼13.56 MHz using a helical antenna under a high magnetic field (∼1600 G). Preliminary results measured by the Langmuir probe, photomultiplier tube (PMT), CCD, and Hall coil are applied to characterize the helicon plasma in this source, such as the mode transition and the formation of the blue core with the RF power variation. The device generates the blue core (W mode) plasma at a lower power of about 200 W, and the energy coupling efficiency is as high as 65%.

Experimental Determination of Hydrogen Isotope Transport Parameters in Vanadium.

Deuterium permeation through vanadium membranes in a wide range of pressures and the temperature range ~250-550 °C was experimentally investigated. Measurements on the same material were carried out in three laboratories with different features for an extended characterization and for cross-check validation. A unified equation for deuterium permeability in pure vanadium (99%) was provided as Φ=1.27×10-4·e-8667/T mol m-1 s-1 Pa-0.5, which represents a significant progress for the characterization of the transport properties in this material, given the spread of data, which can currently be found in the literature. Adsorption and recombination rate constants were also measured for hydrogen and deuterium at low pressure for the same range of temperatures. Finally, the influence of the surface roughness was examined by measuring samples with different surface finish.

[Removal of Nitrate Nitrogen by Microbial Photoelectrochemical Cell: PANI/TiO2-NTs as a Photoanode].

The use of microbial photoelectrochemical cells (MPECs) for the removal of contaminants is a cost-effective and environment-friendly method. Based on the preparation of polyaniline/titanium dioxide nanotube array (PANI/TiO2-NTs) composite photoelectrodes, an MPEC system comprising PANI/TiO2-NTs photoanode and biocathode was constructed and the removal performance of nitrate nitrogen (NO3--N) was studied. The experimental results showed that the PANI/TiO2-NT electrode exhibited the best photoelectric performance when the PANI loading time was 80 s. Compared with the TiO2-NTs electrode, the photocurrent density doubled. The light-driven MPEC system could realize autotrophic denitrification without an external voltage. The biodegradation of NO3--N conformed to the pseudo first-order kinetics. The higher the photoresponse current density, the better the denitrification performance of the system. When the initial concentration of NO3--N was 25 mg·L-1 and the photoresponse current density increased from 0.17 mA·cm-2 to 0.67 mA·cm-2, the average denitrification rate increased from 0.83 mg·(L·h)-1 to 2.83 mg·(L·h)-1. High-throughput sequencing of the biocathode microbial membranes revealed that Pseudomonas (27.37%) was the dominant bacteria. It was considered that the photogenerated electrons generated by the PANI/TiO2-NTs photoanode were transmitted to the cathode through an external circuit. Pseudomonas and other microorganisms with autotrophic denitrification and electrochemical activity directly used the electrons on the electrode as the sole electron donors for autotrophic denitrification reaction.

Design, Synthesis, and Structure-Activity Relationships of Indoline-Based Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-Like 2 (Keap1-Nrf2) Protein-Protein Interaction Inhibitors.

The Keap1 (Kelch-like ECH-associated protein 1)-Nrf2 (nuclear factor erythroid 2-related factor 2)-ARE (antioxidant response element) pathway is the major defending mechanism against oxidative stresses, and directly disrupting the Keap1-Nrf2 protein-protein interaction (PPI) has been an attractive strategy to target oxidative stress-related diseases, including cardiovascular diseases. Here, we describe the design, synthesis, and structure-activity relationships (SARs) of indoline-based compounds as potent Keap1-Nrf2 PPI inhibitors. Comprehensive SAR analysis and thermodynamics-guided optimization identified 19a as the most potent inhibitor in this series, with an IC50 of 22 nM in a competitive fluorescence polarization assay. Further evaluation indicated the proper drug-like properties of 19a. Compound 19a dose-dependently upregulated genes and protein level of Nrf2 as well as its downstream markers and showed protective effects against lipopolysaccharide-induced injury in both H9c2 cardiac cells and mouse models. Collectively, we reported here a novel indoline-based Keap1-Nrf2 PPI inhibitor as a potential cardioprotective agent.

Discovery of a head-to-tail cyclic peptide as the Keap1-Nrf2 protein-protein interaction inhibitor with high cell potency.

Directly disrupting Keap1-Nrf2 protein-protein interaction (PPI) has emerged as a novel way to activate Nrf2. Peptide Keap1-Nrf2 PPI inhibitors have been reported with high Keap1 binding affinity. However, these peptide inhibitors show weak activity in cells. In this study, the head-to-tail cyclic strategy was applied in the development of peptide inhibitors. The privileged residue sequence with minimal acidic residues was used as the template for the cyclic peptide, and the appropriate conjugation method was designed based on the peptide-Keap1 binding mode. The glycine was introduced as the linker to connect both sides, which can avoid the terminal charge, enhance the peptide stability and constrain the binding conformation simultaneously. The obtained novel cyclic peptide 3 showed high binding affinity with Keap1 and possessed high potency in Nrf2 activation at cellular level. We also showed that peptide 3 exhibited effective anti-inflammatory effects in mouse RAW 264.7 cells by activating the Nrf2-regulated defense system and enhancing the antioxidant capacity. This study proved that the head-to-tail cyclic strategy is quite useful in improving the cell potency of peptide Keap1-Nrf2 inhibitors and provided a possible way to develop drug-like peptides as therapeutic Nrf2 activators.

Design, Synthesis, and Initial Evaluation of Affinity-Based Small-Molecule Probes for Fluorescent Visualization and Specific Detection of Keap1.

Keap1 is a pluripotent protein which plays a predominant role in cellular homeostasis and stress responses. Given that the cellular environment is quite dynamic and versatile, further investigation of the function of Keap1 depends on tools for specific and real-time detection of Keap1. Herein, we report the development of functional affinity-based small-molecule probes which can overcome some shortcomings of current methods and be applied in further studying the function of Keap1.

NRF2 promotes breast cancer cell proliferation and metastasis by increasing RhoA/ROCK pathway signal transduction.

Nuclear factor erythroid 2-related factor (NRF2) is an important transcription factor in oxidative stress regulation. Overexpression of NRF2 is associated with human breast carcinogenesis, and increased NRF2 mRNA levels predict poor patient outcome for breast cancer. However, the mechanisms linking gain of NRF2 expression and poor prognosis in breast cancer are still unclear. Here, we provide evidence that NRF2 deletion inhibits proliferation and metastasis of breast cancer cells by down-regulating RhoA. Restoration of RhoA in MCF7 and MDA-MB-231 cells induced NRF2 knockdown-suppressed cell growth and metastasis in vitro, and NRF2 silencing suppressed stress fiber and focal adhesion formation leading to decreased cell migration and invasion. Mechanistic studies showed that NRF2 binds to the promoter region of estrogen-related receptor α (ERR1) and may function as a silencer. This may enhance RhoA protein stability and lead to RhoA overexpression in breast cancer cell. Our findings indicate that NRF2 silencing-mediated reduction of RhoA expression contributes, at least in part, to the poor outcome of breast cancer patients with high NRF2 expression.