Identification of Enriched Driver Gene Alterations in Subgroups of Non-Small Cell Lung Cancer Patients Based on Histology and Smoking Status

BACKGROUND: Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with non-small cell lung cancer. METHODS: Patients with primary lung cancer who underwent clinical genetic tests at Guangdong General Hospital were enrolled. Driver genes were detected by sequencing, high-resolution melt analysis, qPCR, or multiple PCR and RACE methods. RESULTS: 524 patients were enrolled in this study, and the differences in driver gene alterations among subgroups were analyzed based on histology and smoking status. In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%), PTEN (9.1%), PIK3CA (5.2%), c-Met (4.8%), KRAS (4.5%), STK11 (2.7%), and BRAF (1.9%). The three most frequently altered genes in a subgroup of smokers with adenocarcinoma were EGFR (22.0%), STK11 (19.0%), and KRAS (12.0%). We only found EGFR (8.0%), c-Met (2.8%), and PIK3CA (2.6%) alterations in the non-smoker with squamous cell carcinoma (SCC) subgroup. PTEN (16.1%), STK11 (8.3%), and PIK3CA (7.2%) were the three most frequently enriched genes in smokers with SCC. DDR2 and FGFR2 only presented in smokers with SCC (4.4% and 2.2%, respectively). Among these four subgroups, the differences in EGFR, KRAS, and PTEN mutations were statistically significant. CONCLUSION: The distinct features of driver gene alterations in different subgroups based on histology and smoking status were helpful in defining patients for future clinical trials that target these genes. This study also suggests that we may consider patients with infrequent alterations of driver genes as having rare or orphan diseases that should be managed with special molecularly targeted therapies

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью

A'- B Intersite Cooperation-Enhanced Water Splitting in Quadruple Perovskite Oxide CaCu₃Ir₄O₁₂

Developing highly efficient electrochemical catalysts and exploring the basic mechanisms for the oxygen evolution reaction (OER) are key issues for the large-scale commercialization of environmentally friendly electrolytic hydrogen energy. Compared with a simple ABO3 perovskite, the A-site-ordered quadruple structure AA'3B4O12 shows enhanced OER activity, but the underlying mechanisms remain unknown. Herein, we find that the quadruple perovskite oxide CaCu3Ir4O12 has stable and superior electrochemical activity with a very low overpotential of 252 mV to achieve the current density of 10 mA·cm-2 in alkaline solution. Operando X-ray absorption spectroscopy reveals that the B-site Ir is an OER active site with a variable valence state from the initial Ir4+ approach to Ir5+, while the A'-site Cu is inactive with a constant valence state during the OER process. Density functional theory calculations demonstrate that the A'-B intersite cooperation synergistically enhances OER activity via the corner-sharing Cu-O-Ir framework owing to the strong 3d-2p-5d orbital hybridizations, regardless of the inactive Cu site. In the structural constitution of CaCu3Ir4O12, a small Cu-O-Ir bond angle (110.7°) forms. The special orbital symmetry as well as the delicate 3d-5d levels enhance the orbital overlap and therefore promote the charge transfer, favoring the superior OER activity of CaCu3Ir4O12.

The Asia Oceania Human Proteome Organisation Membrane Proteomics Initiative. Preparation and characterisation of the carbonate-washed membrane standard

The Asia Oceania Human Proteome Organisation (AOHUPO) has embarked on a Membrane Proteomics Initiative with goals of systematic comparison of strategies for analysis of membrane proteomes and discovery of membrane proteins. This multilaboratory project is based on the analysis of a subcellular fraction from mouse liver that contains endoplasmic reticulum and other organelles. In this study, we present the strategy used for the preparation and initial characterization of the membrane sample, including validation that the carbonate-washing step enriches for integral and lipid-anchored membrane proteins. Analysis of 17 independent data sets from five types of proteomic workflows is in progress.7 page(s