KEAP1-NRF2 Pathway as a Novel Therapeutic Target for EGFR-Mutant Non-small Cell Lung Cancer.

Background: Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer.

Prognostic Impact of Reactive Oxygen Species Modulator 1 in Surgically Resected Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinomas.

Introduction: Reactive oxygen species modulator 1 (Romo1) is a novel protein that is critically involved in the intracellular production of reactive oxygen species. Evidence has revealed that Romo1 is associated with treatment outcomes of various human malignancies, including lung cancer. However, the clinical implications of this protein in surgically resected lung cancers harboring epidermal growth factor receptor (EGFR) mutations have not been investigated.

Implantable Electroceutical Approach Improves Myelination by Restoring Membrane Integrity in a Mouse Model of Peripheral Demyelinating Neuropathy.

Although many efforts are undertaken to treat peripheral demyelinating neuropathies based on biochemical interventions, unfortunately, there is no approved treatment yet. Furthermore, previous studies have not shown improvement of the myelin membrane at the biomolecular level. Here, an electroceutical treatment is introduced as a biophysical intervention to treat Charcot-Marie-Tooth (CMT) disease-the most prevalent peripheral demyelinating neuropathy worldwide-using a mouse model.

An electroceutical approach enhances myelination via upregulation of lipid biosynthesis in the dorsal root ganglion.

As the myelin sheath is crucial for neuronal saltatory conduction, loss of myelin in the peripheral nervous system (PNS) leads to demyelinating neuropathies causing muscular atrophy, numbness, foot deformities and paralysis. Unfortunately, few interventions are available for such neuropathies, because previous pharmaceuticals have shown severe side effects and failed in clinical trials. Therefore, exploring new strategies to enhance PNS myelination is critical to provide solution for such intractable diseases.

Ambient Mass Spectrometry Imaging of Small Molecules from Cells and Tissues.

New methods to analyze cells and tissues in ambient condition without any harsh chemical fixation or physical freezing and drying are summarized in this report. The first approach, an atmospheric pressure mass spectrometry imaging method, is based on laser ablation in atmospheric pressure assisted by atmospheric plasma and nanomaterials such as nanoparticles and graphene to enhance laser ablation. The second one is based on secondary ion mass spectrometry (SIMS) imaging of live cells in solution capped with single-layer graphene to preserve intact and hydrated biological samples even under ultrahigh vacuum for SIMS bio-imaging in solution.

APOE4-carrying human astrocytes oversupply cholesterol to promote neuronal lipid raft expansion and Aβ generation.

The ε4 allele of APOE-encoding apolipoprotein (ApoE) is one of the strongest genetic risk factors for Alzheimer's disease (AD). One of the overarching questions is whether and how this astrocyte-enriched risk factor initiates AD-associated pathology in neurons such as amyloid-β (Aβ) accumulation. Here, we generate neurons and astrocytes from isogenic human induced pluripotent stem cells (hiPSCs) carrying either APOE ε3 or APOE ε4 allele and investigate the effect of astrocytic ApoE4 on neuronal Aβ production.

TGF-β Increases MFGE8 Production in Myeloid-Derived Suppressor Cells to Promote B16F10 Melanoma Metastasis.

There is growing evidence that myeloid-derived suppressor cells (MDSCs) are directly involved in all stages leading to metastasis. Many mechanisms for this effect have been proposed, but mechanisms of coregulation between tumor cells and MDSCs remain poorly understood. In this study, we demonstrate that MDSCs are a source of milk fat globule-epidermal growth factor (EGF) factor 8 (MFGE8), which is known to be involved in tumor metastasis.

Mass spectrometry imaging of untreated wet cell membranes in solution using single-layer graphene.

We report a means by which atomic and molecular secondary ions, including cholesterol and fatty acids, can be sputtered through single-layer graphene to enable secondary ion mass spectrometry (SIMS) imaging of untreated wet cell membranes in solution at subcellular spatial resolution. We can observe the intrinsic molecular distribution of lipids, such as cholesterol, phosphoethanolamine and various fatty acids, in untreated wet cell membranes without any labeling. We show that graphene-covered cells prepared on a wet substrate with a cell culture medium reservoir are alive and that their cellular membranes do not disintegrate during SIMS imaging in an ultra-high-vacuum environment.

Microscopic and nanoscopic protein imaging by SIMS and helium ion microscopy.

Single protein imaging and understanding their interactions are of paramount importance to understand the life phenomena. Recently reported multiplex protein SIMS imaging methodology using metal-oxide nanoparticle conjugated antibodies can be extended to a single protein imaging methodology using He ion microscopy (HIM). It is proposed here that single protein can be imaged in the microscale and the nanoscale by the complementary use of SIMS and HIM.

Anti-Biofouling Features of Eco-Friendly Oleamide-PDMS Copolymers.

The biofouling of marine organisms on a surface induces serious economic damage. One of the conventional anti-biofouling strategies is the use of toxic chemicals. In this study, a new eco-friendly oleamide-PDMS copolymer (OPC) is proposed for sustainable anti-biofouling and effective drag reduction.

Improved ion imaging of slowly dried neurons and skin cells by graphene cover in time-of-flight secondary ion mass spectrometry.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a powerful tool to obtain both chemical information and spatial distribution of specific molecules of interest on a specimen surface. However, since the focused ion beam requires ultrahigh vacuum conditions for desorption and ionization of analytes, proper specimen preparation, such as drying, freeze-drying, and frozen dehydration, is required for ToF-SIMS analysis. In particular, biological specimens with high moisture content generally have a problem of specimen deformation during the normal drying process for a vacuum environment.

Preparation of cellular samples using graphene cover and air-plasma treatment for time-of-flight secondary ion mass spectrometry imaging.

We report on sample preparation methods based on plasma treatment for an improvement of multiple molecular ion images of cellular membranes in the ToF-SIMS method. The air-plasma treatment of fixed cellular samples efficiently removed the organic residues of any solutions used during sample preparation and improved the quality of ToF-SIMS images due to the resulting clean surface. We also studied cell preparation methods that combine single-layer graphene covering with air-plasma treatment to achieve a synergistic effect that eliminates background spectra by organic impurities while minimizing morphological cell deformation in a vacuum environmental analysis.

Graphene-Coated Glass Substrate for Continuous Wave Laser Desorption and Atmospheric Pressure Mass Spectrometric Imaging of a Live Hippocampal Tissue.

The atmospheric pressure mass spectrometric (AP-MS) imaging technology combined with an inverted optical microscopic system is a powerful tool for determining the presence and spatial distributions of specific biomolecules of interest in live tissues. Efficient desorption and ionization are essential to acquire mass spectrometric (MS) information in an ambient environment. In this study, we demonstrate a new and efficient desorption process using a graphene-coated glass substrate and a continuous wave (CW) laser for high-resolution AP-MS imaging of a live hippocampal tissue.

Quantitative Analysis of Calcium Phosphate Nanocluster Growth Using Time-of-Flight Medium-Energy-Ion-Scattering Spectroscopy.

One of the remaining challenges in material chemistry is to unveil the quantitative compositional/structural information and thermodynamic nature of inorganic materials especially in the initial nucleation and growth step. In this report, we adopted newly developed time-of-flight medium-energy-ion-scattering (TOF-MEIS) spectroscopy to address this challenge and explored heterogeneously grown nanometer-sized calcium phosphate as a model system. With TOF-MEIS, we discovered the existence of calcium-rich nanoclusters (Ca/P ∼ 3) in the presence of the non-collagenous-protein-mimicking passivating ligands.

Immunomodulatory Function of Myeloid-Derived Suppressor Cells during B Cell-Mediated Immune Responses.

Myeloid-derived suppressor cells (MDSCs) play roles in immune regulation during neoplastic and non-neoplastic inflammatory responses. This immune regulatory function is directed mainly toward T cells. However, MDSCs also regulate other cell populations, including B cells, during inflammatory responses.

BAFF-neutralizing interaction of belimumab related to its therapeutic efficacy for treating systemic lupus erythematosus.

BAFF, a member of the TNF superfamily, has been recognized as a good target for autoimmune diseases. Belimumab, an anti-BAFF monoclonal antibody, was approved by the FDA for use in treating systemic lupus erythematosus. However, the molecular basis of BAFF neutralization by belimumab remains unclear.

AuAg Bimetallic Non-Alloyed Nanoparticles on SiO₂ Spacer Layer for Improved Light Absorption in Thin-Film -Si Solar Cells.

We present a light trapping structure consisting of gold and silver (AuAg) bimetallic non-alloyed nanoparticles (BNNPs) on a silicon dioxide (SiO2) spacer layer over crystalline silicon (c-Si) film, designed to improve the absorption of thin-film c-Si solar cells. Prior to fabrication of the AuAg BNNPs on the SiO2 spacer layer, numerical investigations were carried out using electromagnetic field simulation following the finite-difference time-domain method. The hemispherical Au8Ag8 BNNPs were fabricated and deposited on a 15 nm-thick SiO2 spacer layer, which enhanced light trapping in the c-Si film over a broad wavelength range (450-1100 nm).