EGFR exon 19-deletion aberrantly regulate ERCC1 expression that may partly impaired DNA damage repair ability in non-small cell lung cancer

Background Epidermal growth factor receptor (EGFR) activating mutations are usually associated with DNA damage repair (DDR) deficiency. However, the precise mechanism has remained elusive. In this study, we aimed to investigate whether EGFR exon 19 deletion mutation downstream signals contributed to DDR deficiency by downregulation of excision repair cross-complementation group-1 (ERCC1), a key factor in DDR, expression and function. Methods We first measured cell survival, DNA damage (gamma-H2AX foci formation) and damage repair (ERCC1 and RAD51 foci formation) ability in response to DNA cross-linking drug in EGFR exon 19 deletion and EGFR wild-type cells separately. We then investigated the involvement of EGFR downstream signals in regulating ERCC1 expression and function in EGFR exon 19 deletion cells as compared with EGFR wild-type ones. Results We observed increased gamma-H2AX, but impaired ERCC1 and RAD51 nuclear foci formation in EGFR exon 19 deletion cells as compared with EGFR wild-type ones treated with DNA cross-linker. In addition, we identified that inhibition of EGFR exon 19 deletion signals increased ERCC1 expression, whereas blocked wild-type EGFR signals decreased ERCC1 expression, on both mRNA and protein levels. Furthermore, EGFR exon 19 deletion downstream signals not only inhibited ERCC1 expression but also influenced ERCC1 foci formation in response to DNA cross-linker. Conclusion Our findings indicated that the aberrant EGFR exon 19 deletion signals were not only associated with decreased expression of ERCC1 but were also involved in impaired ERCC1 recruitment in response to DNA cross-link damage, thereby providing us with more evidence for exploring the mechanism of DDR deficiency in EGFR mutant NSCLC.Peer reviewe

Next-generation sequencing of homologous recombination genes could predict efficacy of platinum-based chemotherapy in non-small cell lung cancer

BackgroundWith the widespread use of next-generation sequencing (NGS) in clinical practice, an increasing number of biomarkers that predict a response to anti-tumor therapy in non-small cell lung cancer (NSCLC) has been identified. However, validated biomarkers that can be used to detect a response to platinum-based chemotherapy remain unavailable. Several studies have suggested that homologous recombination deficiency (HRD) may occur in response to platinum-based chemotherapy in ovarian cancer and breast cancer. However, currently there is a lack of proven and reliable HRD markers that can be used to screen for patients who may benefit from platinum-based chemotherapy, especially in NSCLC.MethodsNGS was used to screen for gene mutations, including homologous recombination (HR) genes and common driver gene mutations in NSCLC. Cox regression analysis was performed to identify potential clinicopathological or gene mutation factors associated with survival in patients receiving platinum-based chemotherapy, while Kaplan–Meier analysis with the log-rank test was performed to assess the effect of HR gene mutations on progression-free survival (PFS).ResultsIn a retrospective cohort of 129 patients with advanced NSCLC, 54 who received platinum-based chemotherapy with or without anti-angiogenic therapy were included in the analysis. Univariate and multivariate Cox proportional hazard regression analyses showed that HR gene mutations were associated with platinum-based chemotherapy sensitivity. Efficacy results indicated that the objective response rates (ORR) for patients with BRCA1/2 mutations and BRCA1/2 wild type were 75% and 30.4% (p=0.041), while the median PFS was 7.5 and 5.5 months (hazard ratio [HR], 0.52; 95% CI, 0.27–1.00; p=0.084), respectively. The ORRs of patients with HR gene mutations and HR gene wild type were 60% and 23.6% (p=0.01), and the median PFS was 7.5 and 5.2 months (HR, 0.56; 95% CI, 0.32–0.97; p=0.033), respectively.ConclusionsHR gene mutations show potential as promising biomarkers that may predict sensitivity to platinum-based chemotherapy in advanced and metastatic NSCLC

Facet-dependent growth of InAsP quantum wells in InP nanowire and nanomembrane arrays

Selective area epitaxy is a powerful growth technique that has been used to produce III-V semiconductor nanowire and nanomembrane arrays for photonic and electronic applications. The incorporation of a heterostructure such as quantum wells (QWs) brings new functionality and further broadens their applications. Using InP nanowires and nanomembranes as templates, we investigate the growth of InAsP QWs on these pure wurtzite nanostructures. InAsP QWs grow both axially and laterally on the nanowires and nanomembranes, forming a zinc blende phase axially and wurtzite phase on the sidewalls. On the non-polar {1100} sidewalls, the radial QW selectively grows on one sidewall which is located at the semi-polar 〈112〉 A side of the axial QW, causing the shape evolution of the nanowires from hexagonal to triangular cross section. For nanomembranes with {1100} sidewalls, the radial QW grows asymmetrically on the {1100} facet, destroying their symmetry. In comparison, nanomembranes with {1120} sidewalls are shown to be an ideal template for the growth of InAsP QWs, thanks to the uniform QW formation. These QWs emit strongly in the near IR region at room temperature and their emission can be tuned by changing their thickness or composition. These findings enrich our understanding of the QW growth, which provides new insights for heterostructure design in other III-V nanostructures.National Natural Science Foundation of China (No. 61974166, 51702368 and 61874141); Hunan Provincial Natural Science Foundation of China (2018JJ3684); Open Project of the State Key Laboratory of Luminescence and Applications (SKLA-2018-07); and The Australian Research Council (ARC) are acknowledged for financial support

2023 roadmap for potassium-ion batteries

The heavy reliance of lithium-ion batteries (LIBs) has caused rising concerns on the sustainability of lithium and transition metal and the ethic issue around mining practice. Developing alternative energy storage technologies beyond lithium has become a prominent slice of global energy research portfolio. The alternative technologies play a vital role in shaping the future landscape of energy storage, from electrified mobility to the efficient utilization of renewable energies and further to large-scale stationary energy storage. Potassium-ion batteries (PIBs) are a promising alternative given its chemical and economic benefits, making a strong competitor to LIBs and sodium-ion batteries for different applications. However, many are unknown regarding potassium storage processes in materials and how it differs from lithium and sodium and understanding of solid–liquid interfacial chemistry is massively insufficient in PIBs. Therefore, there remain outstanding issues to advance the commercial prospects of the PIB technology. This Roadmap highlights the up-to-date scientific and technological advances and the insights into solving challenging issues to accelerate the development of PIBs. We hope this Roadmap aids the wider PIB research community and provides a cross-referencing to other beyond lithium energy storage technologies in the fast-pacing research landscape

STRN-ALK Fusion in Lung Adenocarcinoma with Brain Metastasis Responded Well to Ensartinib: A Case Report

STRN-ALK fusion is a rare ALK rearrangement identified in non-small cell lung cancer (NSCLC) patients. Here, we reported a case of lung adenocarcinomas with brain metastasis, harboring STRN-ALK fusion, responded well to ensartinib. This case report could provide more information for the therapeutic strategy selecting of NSCLC patients harboring STRN-ALK fusion

A Frame Theory of Energetic Life: A Twisting Energy Solidified on the Holographic Fractal Structure

Life, as the most mysterious and unique phenomenon on the Earth, has confused humans since time began. Why does life exist as it does and how has the diversity of life developed? We, herein, propose a new theory of energetic life, based on existing energy laws, to interpret the evolution and categorization of physical life forms, from microscopic life to macroscopic life. According to this theory, life is a process in which a mass of energy flows and diffuses in the environment. This energy takes DNA as the three-dimensional blueprint, protein as the basic material unit, and fractal network structure as the framework, so as to solidify from energy and form a semi-solid structure. DNA base pairs simultaneously have dual properties as protein pointers and spatial coordinates, and the multi-level self-similar fractal helix structure ultimately guides the formation of different levels of the fractal structure of organisms. This theory organically links the life phenomenon from microscopic to macroscopic levels, from gene, cell and organ to organism, and it provides a new perspective on life, which may inspire biologists to better reveal the mystery of life

A Frame Theory of Energetic Life: A Twisting Energy Solidified on the Holographic Fractal Structure

Life, as the most mysterious and unique phenomenon on the Earth, has confused humans since time began. Why does life exist as it does and how has the diversity of life developed? We, herein, propose a new theory of energetic life, based on existing energy laws, to interpret the evolution and categorization of physical life forms, from microscopic life to macroscopic life. According to this theory, life is a process in which a mass of energy flows and diffuses in the environment. This energy takes DNA as the three-dimensional blueprint, protein as the basic material unit, and fractal network structure as the framework, so as to solidify from energy and form a semi-solid structure. DNA base pairs simultaneously have dual properties as protein pointers and spatial coordinates, and the multi-level self-similar fractal helix structure ultimately guides the formation of different levels of the fractal structure of organisms. This theory organically links the life phenomenon from microscopic to macroscopic levels, from gene, cell and organ to organism, and it provides a new perspective on life, which may inspire biologists to better reveal the mystery of life

Effects of addition of ultrafine WC and fine WC/Co on microstructure and mechanical properties of WC-10Co cemented carbides

The ultrafine WC powders with particle size of 0.5 μm were coated by nano Co particles for preparation of the fine WC/Co powder. Then it was mixed with the coarse WC and Co powders, following compacted and sintered in vacuum at 1420 ℃ for 1 h for obtaining the WC-10Co cemented carbides. The morphology, the grain structure, hardness, bending strength and fracture toughness of WC-10Co cemented carbides with the fine WC/Co and ultrafine WC for comparison were investigated by scanning electron microscopy, transmission electron microscope, universal testing machine, etc. The results reveal that the addition of the fine WC/Co has greater influence on the densification of WC-10Co cemented carbides than the ultrafine WC, and can form the dual-grained structure with a mean WC grain size of 2.18 μm, and the WC-10Co with ultrafine WC has a mean WC grain size of 3.57 μm. The WC-10Co with fine WC/Co can reduce grain growth rate and hinder dissolution of the fine grains, resulting in generation of coarse grains with truncated triangular prism and stepped surface by defect-assisted and dissolution-precipitation mechanism. The WC-10Co with fine WC/Co can improve both hardness and fracture toughness, 1131HV30 and 22.1 MPa·m1/2, respectively. Furthermore, with the same hardness of 1131HV30, its fracture toughness is 27.7% higher than linear fitted fracture. The mechanism analysis shows that the addition of ultrafine WC will lead to the formation of abnormal grains, which is not conductive to the performance; while the addition of fine WC/Co simultaneously forms the dual-grained structure and uniform Co distribution structure and reduces the defects in the grains, improves the comprehensive properties

Observation of Erlotinib in the Treatment of Elderly Patients with Advanced Non-small Cell Lung Cancer and COPD

Background and objective To evaluate the clinical efficacy and the security of erlotinib in the treatment of elderly patients with advanced non-small cell lung cancer and COPD. Methods Fifteen patients with advanced non-small cell lung cancer and COPD were treated with erlotinib 150 mg/d, and then the adverse reactions and clinical effects were recorded. Results The effective rate was 20%. We analyzed the effective rate of stage III and IV, and there were no significant difference between the two (P=0.569). KPS was increased in 40% patients. Mild or moderate rash, diarrhea, nausea and vomiting were the main adverse reactions. Conclusion For elderly patients with advanced non-small cell lung cancer and COPD, the use of erlotinib might achieve better security and effectiveness

DataSheet_1_Next-generation sequencing of homologous recombination genes could predict efficacy of platinum-based chemotherapy in non-small cell lung cancer.xlsx

BackgroundWith the widespread use of next-generation sequencing (NGS) in clinical practice, an increasing number of biomarkers that predict a response to anti-tumor therapy in non-small cell lung cancer (NSCLC) has been identified. However, validated biomarkers that can be used to detect a response to platinum-based chemotherapy remain unavailable. Several studies have suggested that homologous recombination deficiency (HRD) may occur in response to platinum-based chemotherapy in ovarian cancer and breast cancer. However, currently there is a lack of proven and reliable HRD markers that can be used to screen for patients who may benefit from platinum-based chemotherapy, especially in NSCLC.MethodsNGS was used to screen for gene mutations, including homologous recombination (HR) genes and common driver gene mutations in NSCLC. Cox regression analysis was performed to identify potential clinicopathological or gene mutation factors associated with survival in patients receiving platinum-based chemotherapy, while Kaplan–Meier analysis with the log-rank test was performed to assess the effect of HR gene mutations on progression-free survival (PFS).ResultsIn a retrospective cohort of 129 patients with advanced NSCLC, 54 who received platinum-based chemotherapy with or without anti-angiogenic therapy were included in the analysis. Univariate and multivariate Cox proportional hazard regression analyses showed that HR gene mutations were associated with platinum-based chemotherapy sensitivity. Efficacy results indicated that the objective response rates (ORR) for patients with BRCA1/2 mutations and BRCA1/2 wild type were 75% and 30.4% (p=0.041), while the median PFS was 7.5 and 5.5 months (hazard ratio [HR], 0.52; 95% CI, 0.27–1.00; p=0.084), respectively. The ORRs of patients with HR gene mutations and HR gene wild type were 60% and 23.6% (p=0.01), and the median PFS was 7.5 and 5.2 months (HR, 0.56; 95% CI, 0.32–0.97; p=0.033), respectively.ConclusionsHR gene mutations show potential as promising biomarkers that may predict sensitivity to platinum-based chemotherapy in advanced and metastatic NSCLC.</p