The brush materials modified with organosilicon were prepared by the powder metallurgy method, and their current-carrying friction and wear properties were compared with those of brush materials ...modified with SiO2. The materials were characterized by SEM, XRD, XPS, deep etching, and roughness. The results showed that, compared with the SiO2, organosilicon can significantly reduce the wear rate of brush materials by 67–88%, because the SiOC fiber produced by pyrolysis of organosilicon could control the graphite content on the friction surface by reducing abrasive wear. In the aspect of wear mechanism, organosilicon could greatly reduce the abrasive wear of the materials and the mated materials, but aggravated the adhesive wear of the materials.
•Novel KMT2C mutations in Chinese breast cancer patients were identified.•The clinical relevance of KMT2C mutations in patients with breast cancer was revealed.•KMT2C is a potential susceptibility ...gene of Asian breast cancer patients with ILC.
As an important regulator of epigenetics, histone lysine methyltransferase 2C (KMT2C), is frequently mutated in multiple human cancers and is considered to be crucial for the occurrence and development of numerous cancers. However, the relationship between KMT2C mutation and clinicopathological characteristics in patients with breast cancer is unclear. In the present study, we performed next-generation sequencing to investigate the mutation status of KMT2C in 411 treatment-naive Chinese patients with breast cancer at Guangdong Provincial People's Hospital (GDPH), and further compared the results to those of patients with breast cancer from The Cancer Genome Atlas (TCGA, n = 981) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1454) cohorts. The KMT2C mutation rate was 8.0% (33/411) in the GDPH cohort, whereas that in the TCGA and the METABRIC cohorts was 7.0% (69/981) and 14.5% (211/1454), respectively. Nineteen novel mutations were observed in the GDPH cohort. KMT2C mutations were found to be significantly associated with patients older than 50 years (GDPH: p = 0.007; TCGA: p = 0.005; METABRIC: p = 0.015). The KMT2C mutation rate in HR+/HER2- breast cancer patients was higher than that in the other subtypes (GDPH: p = 0.047; TCGA: p = 0.032; METABRIC: p = 0.046). In addition, KMT2C mutations in the GDPH cohort were observed in invasive lobular breast cancer (ILC) at 30.8% (4/13). Further, KMT2C mutation was not found to be an independent risk factor in the prognosis of patients with breast cancer TCGA: hazard ratio (HR), 1.71; 95% confidence interval (CI), 0.88–3.31; p = 0.111; METABRIC: HR, 2.03; 95% CI, 0.45–3.08; p = 0.419. This is the first study to preliminarily elucidate the role of KMT2C mutations in Chinese patients with breast cancer and further identified significant KMT2C mutation differences according to race and ethnicity. KMT2C might be a susceptibility gene of Chinese patients with ILC that would help define high-risk groups that could benefit from adapted, personalized screening strategies.
HER2-positive breast cancer is a biologically and clinically heterogeneous disease. Based on the expression of hormone receptors (HR), breast tumors can be further categorized into HR positive and HR ...negative. Here, we elucidated the comprehensive somatic mutation profile of HR+ and HR− HER2-positive breast tumors to understand their molecular heterogeneity. In this study, 64 HR+/HER2+ and 43 HR-/HER2+ stage I-III breast cancer patients were included. Capture-based targeted sequencing was performed using a panel consisting of 520 cancer-related genes, spanning 1.64 megabases of the human genome. A total of 1119 mutations were detected among the 107 HER2-positive patients. TP53, CDK12 and PIK3CA were the most frequently mutated, with mutation rates of 76, 61 and 49, respectively. HR+/HER2+ tumors had more gene amplification, splice site and frameshift mutations and a smaller number of missense, nonsense and insertion-deletion mutations than HR-/HER2+ tumors. In KEGG analysis, HR+/HER2+ tumors had more mutations in genes involved in homologous recombination (P = 0.004), TGF-beta (P = 0.007) and WNT (P = 0.002) signaling pathways than HR-/HER2+ tumors. Moreover, comparative analysis of our cohort with datasets from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium revealed the distinct somatic mutation profile of Chinese HER2-positive breast cancer patients. Our study revealed the heterogeneity of somatic mutations between HR+/HER2+ and HR-/HER2+ in Chinese breast cancer patients. The distinct mutation profile and related pathways are potentially relevant in the development of optimal treatment strategies for this subset of patients.
Reducing the impact of artificial neural networks (ANN) affected by sources of uncertainty is crucial to improving the reliability of the flood prediction model. This study proposes an ensemble ...artificial neural network (EANN) model to predict the degree of flooding in coastal cities. Combined methods are used to reduce the model’s uncertainty, heuristic neural pathway strength feature selection is used to select inputs, the coupling method is used to optimize network architecture and parameters, and the integration method which paralleling three ANN models with different predicted lead periods ensemble together is used to capture output uncertainty. The EANN model has successfully predicted flooding in the Chinese coastal city of Macao during a typhoon, with convincing accuracy. The study also analyzed the impacts of both long and short training datasets with appropriate time intervals on ANN modeling performance. It was found that the performance of short training datasets, with appropriate time intervals, was similar to or better than models with long training datasets.
The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual ...HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32-0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30-0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.
•An in vitro fermentation of FCS-pg by human gut microflora was investigated.•FCS-pg can be digested by gut microflora from partial human fecal samples.•FCS-pg was mainly fermented by Bacteroides, ...Bifidobacterium and Clostridium.•It increased the content of probiotics bacteria in achieving health-enhancing effect.
A fucosylated chondroitin sulfate (FCS-pg) with highly repeated structure from Pearsonothuria graeffei was subjected to a in vitro fermentation model to investigate its fermentability and effects on human gut microflora. High performance liquid chromatography (HPLC) measurement found FCS-pg can be fermented to short chain fatty acids (SCFAs) by gut microflora from partial human fecal samples. 16S rRNA gene-based polymerase chain reaction-based denaturing gradient gel electrophoresis (PCR-DGGE) profiling and real-time quantitative PCR analysis showed that FCS-pg mainly increased the proportions of Clostridium cluster XI, Bacteriodes prevotella group, Bifidobacterium genus, Clostridium cluster I and Clostridium cluster XIVab, whereas the numbers of the Enterobacteriaceae and Lactobacillus decreased. These results indicated that FCS-pg was mainly fermented by Bacteroides, Bifidobacterium and Clostridium. It increased the content of probiotics bacteria in achieving health-enhancing effect, was slightly different than most sulfated polysaccharides from marine animals. The current study provides useful new information on the mechanism of absorption and functional activity on FCS-pg within the gastrointestinal tract of the human body.
Bulk Si
2
BC
3
N ceramics were reinforced with SiC coated multi-walled carbon nanotubes (MWCNTs). The phase compositions, mechanical properties, and thermal shock resistance, as well as the oxidation ...resistance of the designed Si
2
BC
3
N ceramics were comparatively investigated. The results show that nano SiC coating can be formed on MWCNTs through pyrolyzing polysilazane, which improves the oxidation resistance of MWCNTs. A stronger chemical bonding is formed between the SiC coated MWCNTs and SiC particles, contributing to improved flexural strength (532.1 MPa) and fracture toughness (6.66 MPa·m
1/2
). Besides, the 2 vol% SiC coated MWCNTs reinforced Si
2
BC
3
N ceramics maintains much higher residual strength (193.0 MPa) after thermal shock test at 1000 °C. The enhanced properties should be attributed to: (1) the breaking of MWCNTs and the debonding between MWCNTs and SiC interfaces, which leads to more energy dissipation; (2) the rough surfaces of SiC coated MWCNTs increase the adhesion strength during the “pull out” of MWCNTs.
Bacterial communities are important components of reservoir ecosystems, participating in and determining the material–energy transformations within reservoirs. The intense material–energy transport ...during the flood season can cause perturbations to the stratified environment and material distribution within the reservoir, with the bacterial community being the most sensitive indicator of these changes. In this study, we analyzed sediments from four representative sampling sites before and after the flood season in a seasonally stratified reservoir and compared the diversity and composition of bacterial communities before and after the flood season using 16S rRNA high-throughput sequencing technology. The results showed that the bacterial community structure was different before and after flood season, and the bacterial abundance and α diversity were slightly higher before flood season than after flood season, and the relative abundance of bacteria was relatively low, and the dominant genera were not obvious. After flood season, the dominant genera were mainly Acinetobacter, Flavobacterium, Pseudomonas, Arthrobacter, and Massilia, all of which were aerobic denitrifying bacteria with strong denitrification ability. It is clear that the reservoir bacterial community structure changes significantly between flood seasons and plays a key role in later stages of aquatic ecology restoration. These results provide a new way of interpreting the dynamic changes in reservoir aquatic ecology.
In synthetic aperture radar (SAR) image classification applications, there are three categories of data, including training and benchmark data with fixed classes, as well as actual data in practical ...applications. A real problem comes that there exist unknown classes not included in training and benchmark data, which is defined as the open set condition. However, little work on recognizing unknown classes and analyzing the separability of SAR datasets has been developed. Motivated by this observation, this article demonstrates the difficulty of practical classification and analyzes SAR dataset separability in open set conditions. In this article, the SAR separability analyzer (SAR-SA) is proposed to model each known class as a multivariate Gaussian distribution. SAR-SA can classify the known classes and recognize the samples locating in each known distribution with low probabilities as unknown. Besides, SAR datasetwise separability index (DSI) and classwise separability index (CSI) are defined to quantify the separability in open set conditions at the dataset level and class level. DSI and CSI are effective indicators of the difficulty of SAR classification datasets. Extensive experimental results demonstrate that the DSI in open set conditions is nearly half of that in supervised conditions. Dataset with low DSI is hard to realize accurate classification in open set conditions. At the class level, even though the SAR image classes are semantically different from each other, there exists more or less overlap between the distributions of supervised known classes and unknown classes. Classes with low CSI are harder to be correctly classified and recognized.
Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency ...of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next‐generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non‐BRCA1/2 gene. Major mutant non‐BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non‐BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER‐2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non‐BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non‐BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.
What's new?
The prevalence of mutations in breast cancer predisposition genesare not well investigated in Asia. We assessed germline mutations of 40 cancer susceptibility genes in 937 consecutive selected breast cancer patients from 26 centers of China, and discovered 23.8% of participates carried the pathogenic mutation, including 6.8% with mutations in non‐BRCA1/2 genes, while TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%).There was no factors predicted for detrimental mutations in non‐BRCA1/2 genes when treated as a whole.
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