The Pressure Relief and Permeability Increase Mechanism of Crossing-Layers Directional Hydraulic Fracturing and Its Application

AbstractIn order to reduce roof-floor blind area of hydrofracture in underground mines, expand influenced range of fracturing, improve the effect of hydrofracture, a pressure relief and permeability increase model of hydraulic fracturing was built on the basis of analysing the mechanism of crack initiation and the characteristics of fracture development. After discussing the mechanism of directional hydraulic fracturing and carrying out related numerical simulation, a directional hydraulic fracturing technique was proposed. The coal fracture development distribution rule in the process of directional hydraulic fracturing was analysed, and the directional hydraulic fracturing technique was applied in the F15-31010 mining workface of The Twelfth Coal of Pingdingshan Coal Mining Group. The results show that single-drill hole fracturing effective radius rise to 6m under the pressure of 27Mpa, which is 3-5 times more than before, and the average concentration of single-drill hole gas drainage promote to 87.5%, average flow up 55.6% than no-directional hydraulic fracturing. All these suggest that the technology obtains remarkable effect, and has a high application value

ATP6L promotes metastasis of colorectal cancer by inducing epithelial-mesenchymal transition

ATP6L, the C subunit of the V-ATPase V0 domain, is involved in regulating the acidic tumor micro-environment and may promote tumor progression. However, the expression and functional role of ATP6L in tumors have not yet been well explored. In this study, we found that ATP6L protein overexpression was related to colorectal cancer histological differentiation (P <0.001), presence of metastasis (P <0.001) and recurrence (P = 0.02). ATP6L expression in the liver metastatic foci was higher than in the primary foci (P = 0.04). ATP6L expression was notably concomitant with epithelial-mesenchymal transition (EMT) immunohistochemical features, such as reduced expression of the epithelial marker E-cadherin (P = 0.021) and increased expression of the mesenchymal marker vimentin (P = 0.004). Results of in vitro and in vivo experiments showed that ATP6L expression could alter cell morphology, regulate EMT-associated protein expression, and enhance migration and invasion. The effect of ATP6L on metastasis was further demonstrated in a tail vein injection mice model. In addition, the mouse xenograft model showed that ATP6L-overexpressing HCT116 cells grew into larger tumor masses, showed less necrosis and formed more micro-vessels than the control cells. Taken together, our results suggest that ATP6L promotes metastasis of colorectal cancer by inducing EMT and angiogenesis, and is a potential target for tumor therapy

Epileptic seizure prediction based on EEG using pseudo-three-dimensional CNN

Epileptic seizures are characterized by their sudden and unpredictable nature, posing significant risks to a patient’s daily life. Accurate and reliable seizure prediction systems can provide alerts before a seizure occurs, as well as give the patient and caregivers provider enough time to take appropriate measure. This study presents an effective seizure prediction method based on deep learning that combine with handcrafted features. The handcrafted features were selected by Max-Relevance and Min-Redundancy (mRMR) to obtain the optimal set of features. To extract the epileptic features from the fused multidimensional structure, we designed a P3D-BiConvLstm3D model, which is a combination of pseudo-3D convolutional neural network (P3DCNN) and bidirectional convolutional long short-term memory 3D (BiConvLstm3D). We also converted EEG signals into a multidimensional structure that fused spatial, manual features, and temporal information. The multidimensional structure is then fed into a P3DCNN to extract spatial and manual features and feature-to-feature dependencies, followed by a BiConvLstm3D input to explore temporal dependencies while preserving the spatial features, and finally, a channel attention mechanism is implemented to emphasize the more representative information in the multichannel output. The proposed has an average accuracy of 98.13%, an average sensitivity of 98.03%, an average precision of 98.30% and an average specificity of 98.23% for the CHB-MIT scalp EEG database. A comparison of the proposed model with other baseline methods was done to confirm the better performance of features through time–space nonlinear feature fusion. The results show that the proposed P3DCNN-BiConvLstm3D-Attention3D method for epilepsy prediction by time–space nonlinear feature fusion is effective

Toxin-Encoding Genes and Drug Susceptibility of Staphylococcus aureus from Vegetables Consumed Raw

Objective: To investigate the toxin-encoding genes and antibiotic susceptibility of Staphylococcus aureus isolates from retail vegetables consumed raw. Methods: The 27 S. aureus isolates from tomato, lettuce, spinach and cabbage collected from supermarkets, farmers’ markets and vendors in Xi’an, Baoji, Hanzhong and Yan’an of Shaanxi province were identified by PCR amplification of the nuc gene, the prevalence of 19 toxin-encoding genes and 12 antibiotic resistance encoding genes in these isolates was evaluated, and the antibiotic susceptibility to 14 antibiotics was determined by the agar dilution method. Results: Seventeen of these isolates were identified as methicillin-susceptible S. aureus (MSSA) and the remaining 10 isolates were identified as oxacillin-susceptible methicillin-resistant S. aureus (OS-MRSA). A total of eight toxin-encoding genes were detected in the 27 isolates, and the detection rate (29.6%, 8/27) of sec was highest. In addition, 51.9% (14/27) of these isolates carried at least one toxin-encoding gene, and nine toxin-encoding gene profiles were totally identified. Seven antibiotic resistance genes including blaZ, mecA, ermC, tetK, dfrG, dfrK, and aac(6’)/aph(2”) were detected. The isolates were all susceptible to oxacillin, rifampicin and vancomycin. Resistance to amoxicillin/clavulanate was most commonly detected, followed by trimethoprim/sulfamethoxazole, ampicillin, erythromycin, cefoxitin, ciprofloxacin, ceftriaxone, gentamicin, amikacin, tetracycline and chloramphenicol. Twenty-four (88.9%) isolates were resistant to three or more antibiotics. Conclusion: OS-MRSA is prevalent in vegetables consumed raw in Shaanxi province, and it has multiple antibiotic resistances and carries multiple toxin-encoding gens, posing a potential food safety hazard

Pathomic Features Reveal Immune and Molecular Evolution From Lung Preneoplasia to Invasive Adenocarcinoma

Recent statistics on lung cancer, including the steady decline of advanced diseases and the dramatically increasing detection of early-stage diseases and indeterminate pulmonary nodules, mark the significance of a comprehensive understanding of early lung carcinogenesis. Lung adenocarcinoma (ADC) is the most common histologic subtype of lung cancer, and atypical adenomatous hyperplasia is the only recognized preneoplasia to ADC, which may progress to adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and eventually to invasive ADC. Although molecular evolution during early lung carcinogenesis has been explored in recent years, the progress has been significantly hindered, largely due to insufficient materials from ADC precursors. Here, we employed state-of-the-art deep learning and artificial intelligence techniques to robustly segment and recognize cells on routinely used hematoxylin and eosin histopathology images and extracted 9 biology-relevant pathomic features to decode lung preneoplasia evolution. We analyzed 3 distinct cohorts (Japan, China, and United States) covering 98 patients, 162 slides, and 669 regions of interest, including 143 normal, 129 atypical adenomatous hyperplasia, 94 AIS, 98 MIA, and 205 ADC. Extracted pathomic features revealed progressive increase of atypical epithelial cells and progressive decrease of lymphocytic cells from normal to AAH, AIS, MIA, and ADC, consistent with the results from tissue-consuming and expensive molecular/immune profiling. Furthermore, pathomics analysis manifested progressively increasing cellular intratumor heterogeneity along with the evolution from normal lung to invasive ADC. These findings demonstrated the feasibility and substantial potential of pathomics in studying lung cancer carcinogenesis directly from the low-cost routine hematoxylin and eosin staining

Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas

The evolution of DNA methylome and methylation intra-tumor heterogeneity (ITH) during early carcinogenesis of lung adenocarcinoma has not been systematically studied. We perform reduced representation bisulfite sequencing of invasive lung adenocarcinoma and its precursors, atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma. We observe gradual increase of methylation aberrations and significantly higher level of methylation ITH in later-stage lesions. The phylogenetic patterns inferred from methylation aberrations resemble those based on somatic mutations suggesting parallel methylation and genetic evolution. De-convolution reveal higher ratio of T regulatory cells (Tregs) versus CD8 + T cells in later-stage diseases, implying progressive immunosuppression with neoplastic progression. Furthermore, increased global hypomethylation is associated with higher mutation burden, copy number variation burden and AI burden as well as higher Treg/CD8 ratio, highlighting the potential impact of methylation on chromosomal instability, mutagenesis and tumor immune microenvironment during early carcinogenesis of lung adenocarcinomas

Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC

Proteomic Analysis of Rhesus Macaque Brain Explants Treated With Borrelia burgdorferi Identifies Host GAP-43 as a Potential Factor Associated With Lyme Neuroborreliosis

BackgroundLyme neuroborreliosis (LNB) is one of the most dangerous manifestations of Lyme disease, but the pathogenesis and inflammatory mechanisms are not fully understood.MethodsCultured explants from the frontal cortex of rhesus monkey brain (n=3) were treated with live Borrelia burgdorferi (Bb) or phosphate-buffered saline (PBS) for 6, 12, and 24 h. Total protein was collected for sequencing and bioinformatics analysis. In addition, changes in protein expression in the explants over time following Bb treatment were screened.ResultsWe identified 1237 differentially expressed proteins (DEPs; fold change ≥1.5 or ≤0.67, P-value ≤0.05). One of these, growth-associated protein 43 (GAP-43), was highly expressed at all time points in the explants. The results of the protein-protein interaction network analysis of DEPs suggested that GAP-43 plays a role in the neuroinflammation associated with LNB. In HMC3 cells incubated with live Bb or PBS for 6, 12, and 24 h, real-time PCR and western blot analyses confirmed the increase of GAP-43 mRNA and protein, respectively.ConclusionsElevated GAP-43 expression is a potential marker for LNB that may be useful for diagnosis or treatment