Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma

Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPK, AKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, the cancer progresses. These activating gene mutations for the EGFR are present in 10–20% of lung adenocarcinomas. Approximately 3–7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway, stimulates the proliferation of tumor cells, and inhibits apoptosis. A new group of drugs—small-molecule tyrosine kinase inhibitors—has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases.     

Extracellular Vesicles and Asthma—More Than Just a Co-Existence

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.     

Phosphorylated chitosan/poly(vinyl alcohol) based proton exchange membranes modified with propylammonium nitrate ionic liquid and silica filler for fuel cell applications

In our previous work, phosphorylated chitosan was modified through polymer blending with poly(vinyl alcohol) (PVA) polymer to produce N-methylene phosphonic chitosan/poly(vinyl alcohol) (NMPC/PVA) composite membranes. The aim of this work is to further investigate the effects of a propylammonium nitrate (PAN) ionic liquid and/or silicon dioxide (SiO₂) filler on the morphology and physical properties of NMPC/PVA composite membranes. The temperature-dependent ionic conductivity of the composite membranes with various ionic liquid and filler compositions was studied by varying the loading of PAN ionic liquid and SiO₂-PAN filler in the range of 5–20 wt%. As the loading of PAN ionic liquid increased in the NMPC/PVA membrane matrix, the ionic conductivity value also increased with the highest value of 0.53 × 10^?3 S cm^?1 at 25 °C and increased to 1.54 × 10^?3 S cm^?1 at 100 °C with 20 wt% PAN. The NMPC/PVA-PAN (20 wt%) composite membrane also exhibited the highest water uptake and ion exchange capacity, with values of 60.5% and 0.60 mequiv g^?1, respectively. In addition, in the single-cell performance test, the NMPC/PVA-PAN (20 wt%) composite membrane displayed a maximum power density, which was increased by approximately 14% compared to the NMPC/PVA composite membrane with 5 wt% SiO₂-PAN. This work demonstrated that modified NMPC/PVA composite membranes with ionic liquid PAN and/or SiO₂ filler showed enhanced performance compared with unmodified NMPC/PVA composite membranes for proton exchange membrane fuel cells.     

Blends of Bio-Based Poly(Limonene Carbonate) with Commodity Polymers

In this study, blends of the bio-based poly(limonene carbonate) (PLimC) with different commodity polymers are investigated in order to explore the potential of PLimC toward generating more sustainable polymer materials by reducing the amount of petro- or food-based polymers. PLimC is employed as minority component in the blends. Next to the morphology and thermal properties of the blends the impact of PLimC on the mechanical properties of the matrix polymers is studied. The interplay of incompatibility and zero-shear melt viscosity contrast determines the blend morphology, leading for all blends to a dispersed droplet morphology for PLimC. Blends with polymers of similar structure to PLimC (i.e., aliphatic/aromatic polyester) show the best performance with respect to mechanical properties, whereas blends with polystyrene or poly(methyl methacrylate) are too brittle and polyamide 12 blends show very low elongations at break. In blends with Ecoflex (poly(butylene adipate-co-terephthalate)) and Arnitel EM400 (copoly(ether ester)) with poly(butylene terephthalate) hard and polytetrahydrofuran soft segments) a threefold increase in E-modulus can be achieved, while keeping the elongation at break at reasonable high values of ≈200%, making these blends highly interesting for applications.     

Revealing the high sensitivity in the metal toinsulator transition properties of the pulsed laser deposited VO2 thin films

Vanadium dioxide (VO₂) is known as a typical 3d-orbital transition metal oxide exhibiting the metal-to-insulator-transition (MIT) property near room temperature. However, their electronic applications have been challenged by the quality and uniformity of VO₂ thin films. In this work, we demonstrate the high sensitivity in the valence charge of vanadium and the MIT properties of the VO₂ thin films to the deposition temperature. This observation indicates the necessity to eliminate the inhomogeneity in the temperature distribution of substrate during the vacuum-deposition process of VO₂. In addition, a high thermoelectric power factor (PF, e.g., exceeding 1 μWcm⁻¹K⁻²) was achieved in the metallic phase of the VO₂ thin films and this value is comparable to typical organic or oxide thermoelectric materials. We believe this high PF enriches the potential functionality in thermoelectric energy conversions beyond the existing electronic applications of the current vacuum-grown VO₂ thin films.     

A thermal perspective of flash sintering: The effect of AC current ramp rate on microstructure evolution

In flash sintering experiments, the thermal history of the sample is key to understanding the mechanisms underlying densification rate and final properties. By combining robust temperature measurements with current-ramp-rate control, this study examined the effects of the thermal profile on the flash sintering of yttria-stabilized zirconia, with experiments ranging from a few seconds to several hours. The final density was maximized at slower heating rates, although processes slower than a certain threshold led to grain growth. The amount of grain growth observed was comparable to a similar conventional thermal process. The bulk electrical conductivity correlated with the maximum temperature and cooling rate. The only property that exhibited behavior that could not be attributed to solely the thermal profile was the grain boundary conductivity, which was consistently higher than conventional in flash sintered samples. These results suggest that, during flash sintering, athermal electric field effects are relegated to the grain boundary.     

Nitrogen-doped cobalt sulfide as an efficient electrocatalyst for hydrogen evolution reaction in alkaline and acidic media

The enhancement in intrinsic catalytic activity and material conductivity of an electrocatalyst can leads to promoting HER activity. Herein, a successful nitrogenation of CoS₂ (N–CoS₂) catalyst has been investigated through the facile hydrothermal process followed by N₂ annealing treatment. An optimized N–CoS₂ catalyst reveals an outstanding hydrogen evolution reaction (HER) performance in alkaline as well as acidic electrolyte media, exhibiting an infinitesimal overpotential of ?0.137 and ?0.097 V at a current density of ?10 mA/cm² (?0.309 and ?0.275 V at ?300 mA/cm²), corresponding respectively, with a modest Tafel slope of 117 and 101 mV/dec. Moreover, a static voltage response was observed at low and high current rates (?10 to ?100 mA/cm²) along with an excellent endurance up to 50 h even at ?100 mA/cm². The excellent catalytic HER performance is ascribed to improved electronic conductivity and enhanced electrochemically active sites, which is aroused from the synergy and mutual interaction between heteroatoms that might have varied the surface chemistry of an active catalyst.     

Manufacturing catalyst-coated membranes by ultrasonic spray deposition for PEMFC: Identification of key parameters and their impact on PEMFC performance

This study deals with the manufacturing of catalyst-coated membranes (CCMs) for newcomers in the field of coating. Although there are many studies on electrode ink composition for improving the performance of proton-exchange membrane fuel cells (PEMFCs), there are few papers dealing with electrode coating itself. Usually, it is a know-how that often remains secret and constitutes the added value of scientific teams or the business of industrialists. In this paper, we identify and clarify the role of key parameters to improve coating quality and also to correlate coating quality with fuel cell performance via polarization curves and electrochemical active surface area measurements. We found that the coating configurations can affect the performance of lab-made CCMs in PEMFCs. After the repeatability of the performance obtained by our coating method has been proved, we show that: (i) edge effects, due to mask shadowing - cannot be neglected when the active surface area is low, (ii) a heterogeneous thickness electrode produces performance lower than a homogeneous thickness electrode, and (iii) the origin and storage of platinum on carbon powders are a very important source of variability in the obtained results.     

Grain orientation evolution and multi-scale interfaces enhanced thermoelectric properties of textured Sr0.9La0.1TiO3 based ceramics

Sr_0.9La_0.1TiO₃ based textured ceramics (SLTT-S3T) with a texture fraction of 0.81 are successfully fabricated by the reactive template grain growth method, in which Sr_0.9La_0.1TiO₃/20 wt%Ti was used as matrix and 10 wt% plate-like Sr₃Ti₂O₇ template seeds were used as templates. The phase transition, microstructure evolution, and the anisotropic thermoelectric properties of SLTT-S3T ceramics were investigated. The results show that the ceramics are mainly composed of Sr_0.9La_0.1TiO₃ and rutile TiO₂ phases. Grains grow with a preferred orientation along (h00). A maximum ZT of 0.26 at 1073 K was achieved in the direction perpendicular to the tape casting direction. The low lattice thermal conductivity of 1.9 W/(m K) at 1073 K was obtained decreased by 34%, 40%, and 38% compared with non-textured, SrTiO₃ and Sr_0.9La_0.1TiO₃ ceramics prepared by the same process, can be attributed to the enhanced phonon scattering by the complex multi-scale boundaries and interfaces. This work provides a strategy of microstructural design for thermoelectric oxides to decrease intrinsic lattice thermal conductivity and further regulate thermoelectric properties via texture engineering.