Biofilms contribute to bacterial infection and drug resistance and are a serious threat to global human health. Antibacterial nanomaterials have attracted considerable attention, but the inhibition of biofilms remains a major challenge. Herein, we propose a nanohole-boosted electron transport (NBET) antibiofilm concept. Unlike known antibacterial mechanisms (e.g., reactive oxygen species production and cell membrane damage), nanoholes with atomic vacancies and biofilms serve as electronic donors and receptors, respectively, and thus boost the high electron transport capacity between nanomaterials and biofilms. Electron transport effectively destroys the critical components (proteins, intercellularly adhered polysaccharides and extracellular DNA) of biofilms, and the nanoholes also significantly downregulate the expression of genes related to biofilm formation. The anti-infection capacity is thoroughly verified both in vitro (human cells) and in vivo (rat ocular and mouse intestinal infection models), and the nanohole-enabled nanomaterials are found to be highly biocompatible. Importantly, compared with typical antibiotics, nanomaterials are nonresistant and thereby exhibit high potential for use in various applications. As a proof-of-principle demonstration, these findings hold promise for the use of NBET in treatments for pathogenic bacterial infection and antibiotic drug resistance.
The development of machine learning provides solutions for predicting the complicated immune responses and pharmacokinetics of nanoparticles (NPs) in vivo. However, highly heterogeneous data in NP studies remain challenging because of the low interpretability of machine learning. Here, we propose a tree-based random forest feature importance and feature interaction network analysis framework (TBRFA) and accurately predict the pulmonary immune responses and lung burden of NPs, with the correlation coefficient of all training sets >0.9 and half of the test sets >0.75. This framework overcomes the feature importance bias brought by small datasets through a multiway importance analysis. TBRFA also builds feature interaction networks, boosts model interpretability, and reveals hidden interactional factors (e.g., various NP properties and exposure conditions). TBRFA provides guidance for the design and application of ideal NPs and discovers the feature interaction networks that contribute to complex systems with small-size data in various fields.
An association between epidermal growth factor receptor (EGFR) and clinical characteristics of non-small cell lung cancer (NSCLC) was reported ten years ago. In addition, a different type of relationship was seen in different ethic races. However, the relationship between these factors is not well understood in the Guangxi province. Up to now, there are only very limited data on the association of TTF1/EGFR protein positivity and EGFR mutation status in NSCLC. This study aims to investigate the role of EGFR gene mutation status on the clinical characteristics and the relationship with TTF-1/EGFR protein positivity of patients with NSCLC in Guangxi, China. 1506 samples from different patients with NSCLC were detected by amplification refractory mutation system for 29 hotspot mutations. Analysis of the relationship between clinical characteristics and EGFR mutation status was performed by using the crosstabs Chi-square and SPSS 21.0 software. Of 1506 samples, 537 (35.7%) revealed tyrosine kinase inhibitor (TKI) sensitive EGFR mutations with 27 (1.8%) cases harboring TKI resistant EGFR mutations or union co-existing EGFR-TKIs sensitive mutations. EGFR-TKIs sensitive mutations were not significantly associated with age and TNM-M stage (P = 0.863; P = 0.572, respectively). However, they were significantly associated with p-stage, TNM-T stage and TNM-N stage (P = 0.011, P < 0.001, P = 0.036, respectively). Immunohistochemical studies revealed that TTF-1 and EGFR protein expression level were all associated with EGFR mutation status (P < 0.001, P = 0.002, respectively). Of the 537 EGFR-TKIs sensitive mutation cases, the rates of exon 19-del, 18 G719X point, exon 21 L858R and L861Q points were 54.6, 0.9, 42.3 and 0.9%, respectively. EGFR TKI-sensitive mutations commonly occur in female, non-smoking and adenocarcinoma patients. The p-stage, TNM-T stage, TNM-N stage, EGFR and TTF-1 protein expression levels have close relationships with EGFR mutation status.
The way of cell death can be roughly divided into two categories: cell necrosis and PCD(programmed cell death). Pyroptosis is a kind of PCD, its occurrence depends on the gasdermin protein family and it will produce inflammatory response. With constant research in recent years, more and more evidences show that pyroptosis is closely related to the occurrence and development of tumors. The treatment of tumors is a big problem worldwide. We focus on whether we can discover new potential tumor markers and new therapeutic targets from the mechanism. If we can understand the mechanism of pyroptosis and clear the relationship between pyroptosis and the development of tumors, this may provide a new reference for clinical cancer treatment.
Background: Perineural invasion (PNI) is closely associated with poor survival in several types of malignant tumours, but whether this is true in vulvar squamous cell carcinoma (VSCC) is unclear. The aims of this study were to determine the prognostic significance of PNI in patients with VSCC. Patients and methods: We retrospectively analysed clinico-pathological data on 105 patients with VSCC (stages IB-IV) treated surgically at our medical center between 2005 and 2015. Results: PNI was detected in 30 (28.6%) patients, and it was significantly associated with well-known clinical risk factors: large tumour size, depth of invasion, lymphatic vascular space invasion (LVSI), and intra- or extra-nodal spread. Significantly greater proportions of patients with PNI received adjuvant therapy after surgery ( P =0.001) or showed local recurrence ( P =0.002). Multivariable analysis indicated that risk factors for disease-free survival were tumour size (HR 3.02, 95%CI 1.75–7.75), LVSI (HR 4.82, 95%CI 1.36–17.07), depth of invasion (HR 3.11, 95%CI 1.50–6.44), lymph node metastasis (HR 3.15, 95%CI 1.14–8.96) and positive or close surgical margins (HR 4.86, 95%CI 1.67–14.19). The latter three variables were also risk factors for overall survival. PNI was associated with significantly shorter disease-free survival (DFS) ( P =0.020) and overall survival (OS) ( P =0.017) based on the log-rank test. Among patients who received adjuvant treatment, Kaplan-Meier curves indicated no significant differences between PNI-positive or -negative subgroups in disease-free survival ( P =0.085) or overall survival ( P =0.061). Based on multivariable analysis of all patients, PNI was not a significant risk factor for either type of survival . Conclusion: PNI in VSCC is associated with significantly shorter disease-free and overall survival, though it appears to be a weak independent predictor of worse prognosis. Combining PNI with other risk factors may be useful for predicting whether postoperative adjuvant therapy will be needed.
To further understand the bias combustion behavior of new coal used for horizontal bias combustion and obtain its characteristic parameters, combustion experiments were conducted in a 250-kW pilot-scale bias combustion simulator; multiple research measurements of flame spectra, combustion temperatures, and burnout rates of residual solids were used. Bituminous coal from Australia, sub-bituminous coal from Indonesia, and a blend of these coals were tested. The effects of the raw-coal equivalent moisture (RCEM), pulverized-coal fineness (PCF), and coal type on the ignition characteristics of parallelbias pulverized-coal jets in a reducing atmosphere were investigated. The results indicate that, with decreasing RCEM and PCF, the standoff distance gradually decreased, the flame stability gradually increased, the burnout rate gradually increased, and the ignition characteristics gradually improved. The RCEM had negative effects on ignition in the early stage but positive effects during subsequent combustion. Sub-bituminous coal exhibited a homogeneous−heterogeneous combined ignition mode as the RCEM increased. Bituminous coal changed to homogeneous ignition from homogeneous−heterogeneous combined ignition as the PCF increased. For the sequence bituminous coal, blended coal, sub-bituminous coal, the standoff distance gradually increased, the flame stability gradually decreased, the burnout rate gradually decreased, and the ignition characteristics gradually worsened. When the RCEM of the primary air/pulverized-coal jets reached the moisture content of each raw coal sample, the ignition mode was homogeneous for bituminous coal and a homogeneous−heterogeneous combination for sub-bituminous and blended coals. The ignition characteristics of the blended coal resembled those of sub-bituminous coal, and the burnout characteristics of blended coal resembled those of bituminous coal.
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