Nuclear factor E2-related factor 2 (NRF2) plays an important role in redox metabolism and antioxidant defense. Under normal conditions, NRF2 proteins are maintained at very low levels because of their ubiquitination and proteasomal degradation via binding to the kelch-like ECH associated protein 1 (KEAP1)-E3 ubiquitin ligase complex. However, oxidative and/or electrophilic stresses disrupt the KEAP1-NRF2 interaction, which leads to the accumulation and transactivation of NRF2. During recent decades, a growing body of evidence suggests that NRF2 is frequently activated in many types of cancer by multiple mechanisms, including the genetic mutations in the KEAP1-NRF2 pathway. This suggested that NRF2 inhibition is a promising strategy for cancer therapy. Recently, several NRF2 inhibitors have been reported with anti-tumor efficacy. Here, we review the mechanisms whereby NRF2 is dysregulated in cancer and its contribution to the tumor development and radiochemoresistance. In addition, among the NRF2 inhibitors reported so far, we summarize and discuss repurposed NRF2 inhibitors with their potential mechanisms and provide new insights to develop selective NRF2 inhibitors.

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The ubiquitous field-effect transistor (FET) is widely used in modern digital integrated circuits, computers, communications, sensors, and other applications. However, reliable biological FET (bio-FET) is not available in real life due to the rigorous requirement for highly sensitive and selective bio-FET fabrication, which remains a challenging task. Here, we report an ultrasensitive and selective bio-FET created by the nanorings of molybdenum disulfide (MoS 2 ) nanopores inspired by nuclear pore complexes. We characterize the nanoring of MoS 2 nanopores by scanning transmission electron microscopy, Raman, and X-ray photoelectron spectroscopy spectra. After fabricating MoS 2 nanopore rings-based bio-FET, we confirm edge-selective functionalization by the gold nanoparticle tethering test and the change of electrical signal of the bio-FET. Ultrahigh sensitivity of the MoS 2 nanopore edge rings-based bio-FET (limit of detection of 1 ag/mL) and high selectivity are accomplished by effective coupling of the aptamers on the nanorings of the MoS 2 nanopore edge for cortisol detection. We believe that MoS 2 nanopore edge rings-based bio-FET would provide platforms for everyday biosensors with ultrahigh sensitivity and selectivity.

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residence time on CH4 and C2H4 yields indicates that the cracking reactions of the volatiles (which generate more hydrocarbon gases) begin at an earlier stage during pyrolysis as pressure increases from 100 to 309 psig, consistent with both the weight loss and the tar yield decreasing more rapidly during the early stage of pyrolysis at 309 psig than at 100 psig.The apparent first-order rate constants for devolatilization were dependent on the extent of devolatilization and on the applied pressure. The devolatilization rate decreased significantly with increasing pressure. At each pressure, rate constants decreased as pyrolysis proceeded to greater extents of devolatilization. The first-order rate constants for swelling were similarly dependent on extent of swelling and applied pressure. Swelling rates reached a maximum at 100 psig and decreased as pressure was increased further. At each applied pressure, swelling rate constants decreased as swelling proceeded. The different effects of pressure on devolatilization rate and swelling rate provide evidence that two different mass-transfer mechanisms are operative, depending on applied pressure. At 100 psig or higher, the reduction in both devolatilization and swelling rates suggests that bubble transport was the main mass-transfer mechanism. At atmospheric pressure the devolatilization rate is higher but the swelling rate is lower than those observed at elevated pressures, indicating that a diffusional mechanism is predominant.Richard Hogg for assistance in using the optical image analysis system. Mohammad Fatemi developed the computer models of particle residence time and temperature used in this study, and Carl Martin and Ronald Wincek assisted in maintaining the high-pressure entrained-flow reactor system.

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