Overall signature of acquired KRAS gene changes in advanced non-small cell lung cancer patient with EGFR-TKI resistance.

OBJECTIVE: Numerous scattered case studies continue to demonstrate a strong correlation between acquired KRAS mutations and epidermal growth factor receptor-tyrosine kinase inhibitor resistance in non-small cell lung cancer. However, the comprehensive understanding of the KRAS pathway following the failure of epidermal growth factor receptor-tyrosine kinase inhibitor therapy remains limited. METHODS: We conducted a retrospective evaluation of the next generation sequencing data from 323 patients with advanced non-small cell lung cancer and EGFR-activating mutations after experiencing progression with epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Our analysis specifically focused on the acquired changes to the KRAS gene. RESULTS: Among the 323 patients with advanced non-small cell lung cancer and EGFR-activating mutations who experienced resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy, 14 individuals (4.3%) developed resistance due to acquired KRAS alterations. Of these 14 patients, 10 cases (71.4%) were due to KRAS missense mutations, 1 case (7.2%) was due to KRAS gene fusion and 3 cases (21.4%) were due to KRAS amplification. Notably, we identified one newly demonstrated KRAS gene fusion (KRAS and LMNTD1), one KRAS G13D and one KRAS K117N. The emergence of acquired KRAS alterations was often accompanied by novel mutations and high tumor mutation burden, with TP53, CNKN2A, PIK3CA, MYC, STK11, CDK4, BRCA2 and ERBB2 being the most frequently observed concurrent mutations. The median progression-free survival and overall survival for the 14 patients were 5.2 and 7.3 months, respectively. Acquired KRAS missense variants were associated with significantly worse progression-free survival compared with other KRAS variant subtypes (P < 0.028). CONCLUSIONS: This study provides significant evidence of the role of acquired KRAS variants in the development of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Our results contribute to the growing body of knowledge on the mutational profiles associated with resistance to epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Furthermore, our study highlights the KRAS gene change as a significant mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy.

A Low-Cost AI Buoy System for Monitoring Water Quality at Offshore Aquaculture Cages.

The ocean resources have been rapidly depleted in the recent decade, and the complementary role of aquaculture to food security has become more critical than ever before. Water quality is one of the key factors in determining the success of aquaculture and real-time water quality monitoring is an important process for aquaculture. This paper proposes a low-cost and easy-to-build artificial intelligence (AI) buoy system that autonomously measures the related water quality data and instantly forwards them via wireless channels to the shore server. Furthermore, the data provide aquaculture staff with real-time water quality information and also assists server-side AI programs in implementing machine learning techniques to further provide short-term water quality predictions. In particular, we aim to provide a low-cost design by combining simple electronic devices and server-side AI programs for the proposed buoy system to measure water velocity. As a result, the cost for the practical implementation is approximately USD 2015 only to facilitate the proposed AI buoy system to measure the real-time data of dissolved oxygen, salinity, water temperature, and velocity. In addition, the AI buoy system also offers short-term estimations of water temperature and velocity, with mean square errors of 0.021 °C and 0.92 cm/s, respectively. Furthermore, we replaced the use of expensive current meters with a flow sensor tube of only USD 100 to measure water velocity.

Percolation of Ion-Irradiation-Induced Disorder in Complex Oxide Interfaces.

Mastery of order-disorder processes in highly nonequilibrium nanostructured oxides has significant implications for the development of emerging energy technologies. However, we are presently limited in our ability to quantify and harness these processes at high spatial, chemical, and temporal resolution, particularly in extreme environments. Here, we describe the percolation of disorder at the model oxide interface LaMnO3/SrTiO3, which we visualize during in situ ion irradiation in the transmission electron microscope. We observe the formation of a network of disorder during the initial stages of ion irradiation and track the global progression of the system to full disorder. We couple these measurements with detailed structural and chemical probes, examining possible underlying defect mechanisms responsible for this unique percolative behavior.

Phytophthora capsici PcFtsZ2 Is Required for Asexual Development and Plant Infection.

In bacteria, FtsZ proteins form a Z ring that is the initial step preceding septal fission. FtsZ proteins enable the division of mitochondria in early eukaryotes and are present in some kingdoms but have been lost in animals, fungi, and plants. Here, we have identified two Phytophthora capsici ortholog genes of Escherichia coli FtsZs, designated PcFtsZ1 and PcFtsZ2. Overexpression of PcFtsZ2 in E. coli fully complemented the overexpression phenotype of EcFtsZ. In contrast, overexpression of PcFtsZ1 in E. coli had minimal impact on cell division and separation. Thus, we focused on evaluating the impact of altered expression of PcFtsZ2 in P. capsici, as it exhibited the strongest phenotype. PcFtsZ2 was expressed at the highest levels in mycelia, sporangia, and germinating cysts, as well as in late infection. PcFtsZ2 mis-expression lines showed aberrant asexual growth and development of P. capsici. Alterations in the expression of PcFtsZ2 changed the distribution of mitochondria in hyphae and sporangia and, also, affected the number, size, and shape of actin plaques. Silencing of PcFtsZ2 restrained growth and development of invasive structures, especially cysts and sporangia, substantially inhibiting the ability of transformants to cause blight lesions. In overexpressed transformant lines, cyst and sporangial germination rates were only half that of controls, but hyphal growth from direct germination of sporangia was more rapid than controls. These transformant lines were only slightly impaired in virulence relative to controls. This study emphasizes the essential role of the evolutionarily conserved FtsZ2 proteins in affecting cytoskeleton dynamics.

Molecular dynamics simulations of displacement cascades in LiAlO2 and LiAl5O8 ceramics.

Molecular dynamics was employed to investigate the radiation damage due to collision cascades in LiAlO2 and LiAl5O8, the latter being a secondary phase formed in the former during irradiation. Atomic displacement cascades were simulated by initiating primary knock-on atoms (PKA) with energy values = 5, 10 and 15 keV and the damage was quantified by the number of Frenkel pairs formed for each species: Li, Al and O. The primary challenges of modeling an ionic system with and without a core-shell model for oxygen atoms were addressed and new findings on the radiation resistance of these ceramics are presented. The working of a variable timestep function and the kinetics in the background of the simulations have been elaborated to highlight the novelty of the simulation approach. More importantly, the key results indicated that LiAlO2 experiences much more radiation damage than LiAl5O8, where the number of Li Frenkel pairs in LiAlO2 was 3-5 times higher than in LiAl5O8 while the number of Frenkel pairs for Al and O in LiAlO2 are ~ 2 times higher than in LiAl5O8. The primary reason is high displacement threshold energies (Ed) in LiAl5O8 for Li cations. The greater Ed for Li imparts higher resistance to damage during the collision cascade and thus inhibits amorphization in LiAl5O8. The presented results suggest that LiAl5O8 is likely to maintain structural integrity better than LiAlO2 in the irradiation conditions studied in this work.

ZEB1-AS1 mediates bone metastasis through targeting miR-320b/BMPR1A axis in lung cancer.

OBJECTIVE: This study aimed to explore the role and regulatory mechanism of lncRNA ZEB1-AS1 in lung cancer. METHODS: The expression of ZEB1-AS1 and miR-320b was determined by qRT-PCR. Cell viability, proliferation migration, and invasion were assessed using the CCK-8, colony-forming, and Transwell assay. EMT markers were quantified using western blot. The growth of subcutaneous tumor growth and metastatic bone tumors was evaluated in mouse model of lung cancer. Additionally, metastatic bone tumors were examined using H&E staining. RESULTS: ZEB1-AS1 expression was upregulated, while miR-320b levels were downregulated in lung cancer. Knockdown of ZEB1-AS1 resulted in a significant suppression of cell viability, proliferation, migration, invasion, and EMT in A549 cells. Furthermore, we confirmed the targeting relationship between ZEB1-AS1 and miR-320b, as well as between miR-320b and BMPR1A. Our findings suggested that ZEB1-AS1 regulated cell viability, proliferation, migration, and invasion, as well as EMT, in lung cancer cells by targeting the miR-320b/BMPR1A axis. Moreover, our in vivo experiments confirmed that ZEB1-AS1 mediated bone metastasis through targeting miR-320b/BMPR1A axis in mice with lung cancer. CONCLUSION: ZEB1-AS1 mediated bone metastasis through targeting miR-320b/BMPR1A axis in lung cancer.

Selective plasmonic gas sensing: H2, NO2, and CO spectral discrimination by a single Au-CeO2 nanocomposite film.

A Au-CeO(2) nanocomposite film has been investigated as a potential sensing element for high-temperature plasmonic sensing of H(2), CO, and NO(2) in an oxygen containing environment. The CeO(2) thin film was deposited by molecular beam epitaxy (MBE), and Au was implanted into the as-grown film at an elevated temperature followed by high temperature annealing to form well-defined Au nanoclusters. The Au-CeO(2) nanocomposite film was characterized by X-ray diffraction (XRD) and Rutherford backscattering spectrometry (RBS). For the gas sensing experiments, separate exposures to varying concentrations of H(2), CO, and NO(2) were performed at a temperature of 500 °C in oxygen backgrounds of 5.0, 10, and ∼21% O(2). Changes in the localized surface plasmon resonance (LSPR) absorption peak were monitored during gas exposures and are believed to be the result of oxidation-reduction processes that fill or create oxygen vacancies in the CeO(2). This process affects the LSPR peak position either by charge exchange with the Au nanoparticles (AuNPs) or by changes in the dielectric constant surrounding the particles. Spectral multivariate analysis was used to gauge the inherent selectivity of the film between the separate analytes. From principal component analysis (PCA), unique and identifiable responses were seen for each of the analytes. Linear discriminant analysis (LDA) was also used and showed separation between analytes as well as trends in gas concentration. Results indicate that the Au-CeO(2) thin film is selective to O(2), H(2), CO, and NO(2) in separate exposures. This, combined with the observed stability over long exposure periods, shows the Au-CeO(2) film has good potential as an optical sensing element for harsh environmental conditions.

Flexible pillared graphene-paper electrodes for high-performance electrochemical supercapacitors.

Flexible graphene paper (GP) pillared by carbon black (CB) nanoparticles using a simple vacuum filtration method is developed as a high-performance electrode material for supercapacitors. Through the introduction of CB nanoparticles as spacers, the self-restacking of graphene sheets during the filtration process is mitigated to a great extent. The pillared GP-based supercapacitors exhibit excellent electrochemical performances and cyclic stabilities compared with GP without the addition of CB nanoparticles. At a scan rate of 10 mV s(-1) , the specific capacitance of the pillared GP is 138 F g(-1) and 83.2 F g(-1) with negligible 3.85% and 4.35% capacitance degradation after 2000 cycles in aqueous and organic electrolytes, respectively. At an extremely fast scan rate of 500 mV s (-1) , the specific capacitance can reach 80 F g(-1) in aqueous electrolyte. No binder is needed for assembling the supercapacitor cells and the pillared GP itself may serve as a current collector due to its intrinsic high electrical conductivity. The pillared GP has great potential in the development of promising flexible and ultralight-weight supercapacitors for electrochemical energy storage.

USP47 stabilizes BACH1 to promote the Warburg effect and non-small cell lung cancer development via stimulating Hk2 and Gapdh transcription.

Increasing studies demonstrated that ubiquitination plays a crucial part in the pathogenesis of non-small cell lung cancer (NSCLC), and targeted adjustment of the deubiquitination enzymes is a potential means for cancer treatment. However, the role of ubiquitin carboxyl-terminal hydrolase 47 (USP47) in NSCLC is still unclear. Here, we show that USP47 was upregulated in NSCLC clinical tissues and greatly related to advanced tumor stages and survival rate. Functional experimental results showed that USP47 promoted the cell proliferation in vitro and tumor growth in vivo. And the overexpression of USP47 promoted the glycolysis capacity of lung cancer cells. Mechanistic investigations showed that USP47 promoted NSCLC development, which depends a lot on directly binding to and deubiquitination of the basic leucine zipper transcription factor 1 (BACH1, BTB and CNC homology 1). BACH1 was also significantly overexpressed in primary NSCLC tissues and positively correlated with the expression of USP47. The promotion of USP47 on the Warburg effect and NSCLC progression was mediated by the deubiquitination of BACH1 and the downstream transcriptional regulation of hexokinase 2 (Hk2) and glyceraldehyde-phosphate dehydrogenase (Gapdh). Therefore, targeting USP47/BACH1 axis might offer a new way to inhibit the progression of NSCLC.

Energy-dispersive X-ray spectroscopy and atom-probe tomography data quantifying component-ratios of multicomponent nano-precipitates in ion-irradiated ceria.

Samples of ∼1 µm films of CeO2 doped with 2 wt% Mo, 1.5 wt% Ru, 0.75 wt% Pd, 0.5 wt% Re and 0.25 wt% Rh grown with pulsed laser deposition were irradiated with I2+ ions (610 °C and 730 °C, 1016 and 5 × 1016 I2+/cm2). For selected samples post-irradiation heat treatment was conducted (900 °C, 1100 °C). The specimens were sectioned with focused ion beam milling and characterized in a transmission electron microscope with energy-dispersive x-ray spectroscopy, and with atom-probe tomography. Energy-dispersive x-ray spectroscopy was used to obtain elemental maps showing the distribution of dopants in the specimen after exposure. Some of these maps are discussed in detail in our companion article "Formation of multicomponent alloy particles in doped ceria under I2+ ion irradiation and thermal annealing" in the Journal of Nuclear Materials [1]. Advanced computational analysis could be used to more accurately quantify local compositions. Data is provided for additional regions of interest and one additional irradiation condition. The doped ceria film that was heat treated at 1100 °C delaminated from the substrate in most places. Samples were extracted from the underside of a delaminated piece and analyzed with atom-probe tomography. The resulting data show ceria and a Mo-rich particle and demonstrate that this approach is feasable in principle to study local compositions in a sample exposed to such extreme conditions.