Clinicopathological Characteristics and Therapeutic Effect of Patients with Non-small Cell Lung Cancer and Uncommon EGFR Mutations

Objective To investigate the clinicopathological characteristics and treatment effect of patients with non-small cell lung cancer (NSCLC) and uncommon epidermal growth factor receptor (EGFR) gene mutations. Methods Real-time fluorescence quantitative PCR was used to detect the mutation of EGFR in 674 samples of patients with NSCLC.The correlation between uncommon EGFR mutations and clinicopathological characteristics was analyzed. Results The EGFR mutation rate was 47.92%, of which the incidence of uncommon EGFR mutations was 5.19%, showed the presence of ex18 G719 A/S/C (G719X)(1.63%), ex20ins (1.04%), ex21 L861Q (0.74%), and compound mutations (1.78%).Correlation analysis showed that uncommon EGFR mutations were more common in women, non-smokers, patients with high-medium differentiation and adenocarcinoma, and patients were more prone to brain and bone metastasis (all P 0.05).Follow-up information was available on 31 patients, with a median follow-up time of 10 months, of which 23 were in advanced stage.Among eight patients with G719X mutation in late stage, seven patients used EGFR tyrosine kinase inhibitor (EGFR TKIs)(five of them used afatinib) in the first line and had a median PFS of 12 months; one patient received chemotherapy with pemetrexed and carboplatin and had PFS of seven months, which was lower than that of the TKI group.Among four patients with L861Q mutation in late stage, one patient was untreated and the three remaining were treated with TKI in the first line and had a median PFS of eight months.The patient who was treated with afatinib and bevacizumab was still stable after 11 months of follow-up.Two patients with EGFR ex20ins in advanced stage were treated with chemotherapy and bevacizumab.Nine patients with compound mutations in advanced stage were treated with TKI; among which, five patients harboring T790M compound mutations were treated with third-generation TKI and had a median PFS of more than 10 months. Conclusion The correlation between specific uncommon EGFR mutation and clinical pathological characteristics varies.For advanced patients with uncommon EGFR mutations (except for ex20ins), TKI is generally chosen as the first-line clinical treatment.Afatinib is recommended for advanced NSCLC patients with G719X and L861Q mutations.Third-generation TKI has significant efficacy in patients with complex mutations containing T790M

DBS: a fast and informative segmentation algorithm for DNA copy number analysis

Abstract Background Genome-wide DNA copy number changes are the hallmark events in the initiation and progression of cancers. Quantitative analysis of somatic copy number alterations (CNAs) has broad applications in cancer research. With the increasing capacity of high-throughput sequencing technologies, fast and efficient segmentation algorithms are required when characterizing high density CNAs data. Results A fast and informative segmentation algorithm, DBS (Deviation Binary Segmentation), is developed and discussed. The DBS method is based on the least absolute error principles and is inspired by the segmentation method rooted in the circular binary segmentation procedure. DBS uses point-by-point model calculation to ensure the accuracy of segmentation and combines a binary search algorithm with heuristics derived from the Central Limit Theorem. The DBS algorithm is very efficient requiring a computational complexity of O(n*log n), and is faster than its predecessors. Moreover, DBS measures the change-point amplitude of mean values of two adjacent segments at a breakpoint, where the significant degree of change-point amplitude is determined by the weighted average deviation at breakpoints. Accordingly, using the constructed binary tree of significant degree, DBS informs whether the results of segmentation are over- or under-segmented. Conclusion DBS is implemented in a platform-independent and open-source Java application (ToolSeg), including a graphical user interface and simulation data generation, as well as various segmentation methods in the native Java language

Substrate Effect on Band Bending of MoSe2 Monolayer Near Mirror‐Twin Domain Boundaries

Abstract Band bending near mirror twin domain boundaries (MTBs) in a MoSe2 monolayer grown on different substrates, i.e., highly oriented pyrolytic graphite (HOPG), graphene‐on‐SiC, and crystalline Au(110), is investigated by low temperature scanning tunneling microscopy/spectroscopy. Upshift bending of the valence band edge near MTB is observed on both graphene and HOPG substrates, whereas a downshift bending is found on Au(110). For the former, the magnitudes of bending are different. This is explained based on the static charge model, where an accumulative charge exists at MTBs due to both the electrical dipole discontinuity across the MTB as well as charge transfer between the substrate and MoSe2 epilayer. The relevance of the static electric model is further affirmed by noting a geometric effect on the band bending, where it is asymmetric across the vertex of an MTB loop

Supramolecular Polymer Nanocomposites for Biomedical Applications

Polymer nanocomposites, a class of innovative materials formed by polymer matrixes and nanoscaled fillers (e.g., carbon-based nanomaterials, inorganic/semiconductor nanoparticles, metal/metal-oxide nanoparticles, polymeric nanostructures, etc.), display enhanced mechanical, optoelectrical, magnetic, catalytic, and bio-related characteristics, thereby finding a wide range of applications in the biomedical field. In particular, the concept of supramolecular chemistry has been introduced into polymer nanocomposites, which creates myriad “smart” biomedical materials with unique physicochemical properties and dynamic tunable structures in response to diverse external stimuli. This review aims to provide an overview of the chemical composition, morphological structures, biological functionalities, and reinforced performances of supramolecular polymer nanocomposites. Additionally, recent advances in biomedical applications such as therapeutic delivery, bioimaging, and tissue engineering are also discussed, especially their excellent properties leveraged in the development of multifunctional intelligent biomedical materials

Potent Antimicrobial and Antibiofilm Activities of Feleucin-K3 Analogs Modified by α-(4-Pentenyl)-Ala against Multidrug-Resistant Bacteria

The dramatic increase in antimicrobial resistance (AMR) highlights an urgent need to develop new antimicrobial therapies. Thus, antimicrobial peptides (AMPs) have emerged as promising novel antibiotic alternatives. Feleucin-K3 is an amphiphilic α-helical nonapeptide that has powerful antimicrobial activity. In our previous study, it was found that the fourth residue of Feleucin-K3 is important for antimicrobial activity. After α-(4-pentenyl)-Ala was introduced into this position, both the antimicrobial activity and stability were greatly improved. Herein, to improve the limitations of Feleucin-K3, this unnatural amino acid was further introduced into different positions of Feleucin-K3. Among these synthetic Feleucin-K3 analogs, the N-terminal-substituted analog Feleucin-K65 (K65) and C-terminal-substituted analog Feleucin-K70 (K70) had preferable antimicrobial activity. In particular, their antimicrobial activities against multidrug-resistant bacteria were more potent than that of antibiotics. The stabilities of these peptides in salt and serum environments were improved compared with those of Feleucin-K3. In addition, these analogs had low hemolytic activity and AMR. More importantly, they effectively inhibited biofilm formation and exhibited considerable efficacy compared with traditional antibiotics against biofilm infection caused by methicillin-resistant Staphylococcus aureus (MRSA). In antimicrobial mechanism studies, K65 and K70 mainly permeated the outer membrane and depolarized the cytoplasmic membrane, resulting in cellular component leakage and cell death. In summary, analogs K65 and K70 are potential antimicrobial alternatives to solve the antibiotic crisis

A robust anticorrosive coating derived from superhydrophobic, superoleophobic, and antibacterial SiO2@POS/N+ composite materials

Traditional coatings are easily susceptible by the contamination of organic pollutants and parasitism of bacterium, resulting in severe corrosion damage to the protected substrates. The coating with superhydrophobic, superoleophobic and antibacterial properties would not only spontaneously form an air layer when it is immersed into corrosive medium and effectively obstruct corrosive medium to devastate metal matrix, but also be beneficial to improve the coating's anti-fouling performance along with its antibacterial functionality. However, traditional anticorrosive methods are problematic with low anticorrosion efficiency and single function. Herein, a robust anticorrosive coating stemmed from superhydrophobic, superoleophobic, and antibacterial SiO2 @POS/N+5 composite was prepared by sol-gel and spray method, with water contact angle and water sliding angle up to 160.8 ± 3.1° and 3.0° and oil contact angle and oil sliding angle up to 152.5 ± 3.0° and 3.0° were achieved, respectively. The SiO2@POS/N+5 coating has excellent protection performance (99.98 %), mechanical properties and corrosion durability (21 d). Notably, the SiO2@POS/N+5 composite material has excellent antibacterial effect against Staphylococcus aureus (S. aureus) (100 %) as well. The superamphiphobic coating proposed in this study affords a feasible strategy for bacterial contamination of metal surfaces in marine industries

Domain generalization enables general cancer cell annotation in single-cell and spatial transcriptomics

Abstract Single-cell and spatial transcriptome sequencing, two recently optimized transcriptome sequencing methods, are increasingly used to study cancer and related diseases. Cell annotation, particularly for malignant cell annotation, is essential and crucial for in-depth analyses in these studies. However, current algorithms lack accuracy and generalization, making it difficult to consistently and rapidly infer malignant cells from pan-cancer data. To address this issue, we present Cancer-Finder, a domain generalization-based deep-learning algorithm that can rapidly identify malignant cells in single-cell data with an average accuracy of 95.16%. More importantly, by replacing the single-cell training data with spatial transcriptomic datasets, Cancer-Finder can accurately identify malignant spots on spatial slides. Applying Cancer-Finder to 5 clear cell renal cell carcinoma spatial transcriptomic samples, Cancer-Finder demonstrates a good ability to identify malignant spots and identifies a gene signature consisting of 10 genes that are significantly co-localized and enriched at the tumor-normal interface and have a strong correlation with the prognosis of clear cell renal cell carcinoma patients. In conclusion, Cancer-Finder is an efficient and extensible tool for malignant cell annotation

SATB2 is a sensitive marker for lower gastrointestinal well-differentiated neuroendocrine tumors

Special AT-rich sequence binding protein-2 (SATB2) is selectively expressed in the lower gastrointestinal tract mucosa and has been identified as a sensitive marker for colorectal adenocarcinomas. The goal of this study was to investigate the expression of SATB2 in well-differentiated neuroendocrine tumors to explore its potential as a diagnostic marker for hindgut well-differentiated neuroendocrine tumors. Immunohistochemical staining with a monoclonal antibody to SATB2 was performed on full tissue blocks in 167 well-differentiated neuroendocrine tumors of various origins. The staining was semi-quantitatively scored as 0 (no tumor cell staining), 1+ (1-25%), 2+ (26-50%), 3+ (51-75%) and 4+ (76-100%). Positive SATB2 staining was seen in 17% foregut (14/84, 12/66 primary and 2/18 metastatic), 12% midgut (3/22, 3/18 primary and 0/7 metastatic), and 90% hindgut (52/58, 44/49 primary and 8/9 metastatic) well differentiated neuroendocrine tumors. Most hindgut well-differentiated neuroendocrine tumors (41/58) showed 4+ staining. The specificity of SATB2 for foregut, midgut and hindgut well-differentiated neuroendocrine tumors was 34%, 54% and 84%, respectively. Our results indicate that SATB2 is a sensitive marker for hindgut well-differentiated neuroendocrine tumors though it is not entirely specific. SATB2 should be included in the immunohistochemical panel in working out metastatic well-differentiated neuroendocrine tumor of an unknown origin.Peking University Cancer Hospital Institute [12-01]; Beijing Health and Family Planning Commission; Clinical Science Fund of the Chinese PLA General Hospital [2012-FC-TSYS-3050]; Beijing Municipal Science and Technology Commission NOVA Program Fund [2012B033]SCI(E)[email protected]