Effect of Al Content on Microstructure and Properties of AlxCr0.2NbTiV Refractory High-Entropy Alloys.

High-temperature creep refers to the slow and continuous plastic deformation of materials under the effects of high temperatures and mechanical stress over extended periods, which can lead to the degradation or even failure of the components' functionality. AlxCr0.2NbTiV (x = 0.2, 0.5, or 0.8) refractory high-entropy alloys were fabricated by arc melting. The effects of Al content on the microstructure of AlxCr0.2NbTiV alloys were studied using X-ray diffraction, scanning electron microscopy, and electron backscatter diffraction. The microhardness, compression properties, and nanoindentation creep properties of AlxCr0.2NbTiV alloys were also tested. The results show that the AlxCr0.2NbTiV series exhibits a BCC single-phase structure. As the Al content increases, the lattice constant of the alloys gradually decreases, and the intensity of the (110) crystal plane diffraction peak increases. Adding aluminum enhances the effect of solution strengthening; however, due to grain coarsening, the microhardness and room temperature compressive strength of the alloy are only slightly improved. Additionally, because the effect of solution strengthening is diminished at high temperatures, the compressive strength of the alloy at 1000 °C is significantly reduced. The creep mechanism of the alloys is predominantly governed by dislocation creep. Moreover, increasing the Al content helps to reduce the sensitivity of the alloy to the loading rate during the creep process. At a loading rate of 2.5 mN/s, the Al0.8Cr0.2NbTiV alloy exhibits the lowest creep strain rate sensitivity index (m), which is 0.0758.

SAFER: sub-hypergraph attention-based neural network for predicting effective responses to dose combinations.

Background: The potential benefits of drug combination synergy in cancer medicine are significant, yet the risks must be carefully managed due to the possibility of increased toxicity. Although artificial intelligence applications have demonstrated notable success in predicting drug combination synergy, several key challenges persist: (1) Existing models often predict average synergy values across a restricted range of testing dosages, neglecting crucial dose amounts and the mechanisms of action of the drugs involved. (2) Many graph-based models rely on static protein-protein interactions, failing to adapt to dynamic and context-dependent networks. This limitation constrains the applicability of current methods. Results: We introduced SAFER, a Sub-hypergraph Attention-based graph model, addressing these issues by incorporating complex relationships among biological knowledge networks and considering dosing effects on subject-specific networks. SAFER outperformed previous models on the benchmark and the independent test set. The analysis of subgraph attention weight for the lung cancer cell line highlighted JAK-STAT signaling pathway, PRDM12, ZNF781, and CDC5L that have been implicated in lung fibrosis. Conclusions: SAFER presents an interpretable framework designed to identify drug-responsive signals. Tailored for comprehending dose effects on subject-specific molecular contexts, our model uniquely captures dose-level drug combination responses. This capability unlocks previously inaccessible avenues of investigation compared to earlier models. Finally, the SAFER framework can be leveraged by future inquiries to investigate molecular networks that uniquely characterize individual patients.

Systematic characterization of protein structural features of alternative splicing isoforms using AlphaFold 2.

Alternative splicing is an important cellular process in eukaryotes, altering pre-mRNA to yield multiple protein isoforms from a single gene. However, our understanding of the impact of alternative splicing events on protein structures is currently constrained by a lack of sufficient protein structural data. To address this limitation, we employed AlphaFold 2, a cutting-edge protein structure prediction tool, to conduct a comprehensive analysis of alternative splicing for approximately 3,000 human genes, providing valuable insights into its impact on the protein structural. Our investigation employed state of the art high-performance computing infrastructure to systematically characterize structural features in alternatively spliced regions and identified changes in protein structure following alternative splicing events. Notably, we found that alternative splicing tends to alter the structure of residues primarily located in coils and beta-sheets. Our research highlighted a significant enrichment of loops and highly exposed residues within human alternatively spliced regions. Specifically, our examination of the Septin-9 protein revealed potential associations between loops and alternative splicing, providing insights into its evolutionary role. Furthermore, our analysis uncovered two missense mutations in the Tau protein that could influence alternative splicing, potentially contributing to the pathogenesis of Alzheimer's disease. In summary, our work, through a thorough statistical analysis of extensive protein structural data, sheds new light on the intricate relationship between alternative splicing, evolution, and human disease.

Extracting Drug-Protein Relation from Literature Using Ensembles of Biomedical Transformers.

Automatic extraction of relations between drugs/chemicals and proteins from ever-growing biomedical literature is required to build up-to-date knowledge bases in biomedicine. To promote the development of automated methods, BioCreative-VII organized a shared task - the DrugProt track, to recognize drug-protein entity relations from PubMed abstracts. We participated in the shared task and leveraged deep learning-based transformer models pre-trained on biomedical data to build ensemble approaches to automatically extract drug-protein relation from biomedical literature. On the main corpora of 10,750 abstracts, our best system obtained an F1-score of 77.60% (ranked 4th among 30 participating teams), and on the large-scale corpus of 2.4M documents, our system achieved micro-averaged F1-score of 77.32% (ranked 2nd among 9 system submissions). This demonstrates the effectiveness of domain-specific transformer models and ensemble approaches for automatic relation extraction from biomedical literature.

Double-single-atom MoCu-embedded porous carbons boost the electrocatalytic N2 reduction reaction.

NH3 is an essential ingredient of chemical, fertilizer, and energy storage products. Industrial nitrogen fixation consumes an enormous amount of energy, which is counter to the concept of carbon neutrality, hence eNRR ought to be implemented as a clean alternative. Herein, we propose a double-single-atom MoCu-embedded porous carbon material derived from uio-66 (MoCu@C) by plasma-enhanced chemical vapor deposition (PECVD) to boost eNRR capabilities, with an NH3 yield rate of 52.4 µg h-1 gcat.-1 and a faradaic efficiency (FE) of 27.4%. Advanced XANES shows that the Mo active site receives electrons from Cu, modifies the electronic structure of the Mo active site and enhances N2 adsorption activation. The invention of rational MoCu double-single-atom materials and the utilization of effective eNRR approaches furnish the necessary building blocks for the fundamental study and practical application of Mo-based materials.

Evaluation of Ultra-High-Pressure Sterilization in Terms of Bactericidal Effect, Qualities, and Shelf Life of 'Xinli No. 7' (Pyrus sinkiangensis) Pear Juice.

In this study, ultra-high-pressure sterilization (UHPS) of Xinli No. 7 juice (XL7) was explored and optimized. A challenge to implement UHPS in juice as a full alternative to thermal treatment could be represented by the adoption of a pressure level of up to 500 MPa for 20 min at one cycle followed by the packaging in aseptic conditions. It was found that UHPS and HS treatments could effectively kill the microorganisms in XL7 juice but HS treatment would inevitably lose the nutritional quality in the juice, while UHPS treatment could better maintain the glyconic acid content, functional components, and antioxidant activity and reduce Browning degree and improve the stability of XL7 juice. The deterioration rate of UHPS and HS-treated XL7 juice increased with the increased storage temperature. The predicted shelf life of UHPS and HS-treated XL7 juice was 68 and 41 days at 4 °C, respectively. Collectively, UHPS treatment combined with low-temperature storage might be an effective way to prolong the shelf life of XL7 juice.

Detection rate and shunt grading with synchronous testing of contrast transcranial Doppler and contrast transthoracic echocardiography: Preliminary findings.

Patent foramen ovale, a common congenital atrial septal defect, may lead to cardiac right-to-left shunting (RLS), which has been associated with various diseases. Reliable techniques for detecting RLS are essential for diagnosis and assist with treatment decision-making. Contrast transcranial Doppler (c-TCD), contrast transthoracic echocardiography (c-TTE), and contrast transesophageal echocardiography can be used to detect RLS. However, it is still unclear which ultrasound modalities are the most practical and cost-effective. To evaluate the efficacy of synchronous c-TCD and c-TTE in detecting cardiac RLS. We prospectively designed and continuously recruited 100 patients with cryptogenic stroke, migraines, transient ischemic attack, unexplained syncope, or dizziness admitted at the First Affiliated Hospital of Shenzhen University between February 2020 and August 2020. Ninety-five patients underwent synchronous c-TCD and c-TTE (during a single contrast-enhanced ultrasound session). We compared synchronous test results with the results of c-TCD alone and c-TTE alone. Ninety-five patients successfully underwent synchronous c-TCD and c-TTE, with the data analyzed for each individual. The positive detection rates of Grade I, II, and III shunts with synchronous c-TCD and c-TTE were higher than those with c-TTE or c-TCD alone (P = .047, P = .002, and P = .024, respectively). Overall, the positive detection rates of synchronous tests, c-TCD alone, and c-TTE were 69.5%, 51.6%, and 31.6%, respectively (P = .000, and P = .012). Among the 66 patients who were double-RLS-positive (both c-TTE and c-TCD showed positive results), as detected by the synchronous test, 26 (39.3%) patients who underwent c-TTE alone had higher shunt grades detected than those who underwent c-TCD alone. Conversely, 5 (7.6%) patients who underwent c-TCD alone had higher shunt grades detected than those who underwent c-TTE alone (P = .000). Synchronous c-TCD and c-TTE testing can significantly improve the detection rate, accuracy, and test process efficacy for quantifying RLS, and reduce the testing risk, workload, and medical costs.

Prediction of Brain Metastases Development in Patients With Lung Cancer by Explainable Artificial Intelligence From Electronic Health Records.

PURPOSE: Early detection of brain metastases (BMs) is critical for prompt treatment and optimal control of the disease. In this study, we seek to predict the risk of developing BM among patients diagnosed with lung cancer on the basis of electronic health record (EHR) data and to understand what factors are important for the model to predict BM development through explainable artificial intelligence approaches accurately. MATERIALS AND METHODS: We trained a recurrent neural network model, REverse Time AttentIoN (RETAIN), to predict the risk of developing BM using structured EHR data. To interpret the model's decision process, we analyzed the attention weights in the RETAIN model and the SHAP values from a feature attribution method, Kernel SHAP, to identify the factors contributing to BM prediction. RESULTS: We developed a high-quality cohort with 4,466 patients with BM from the Cerner Health Fact database, which contains over 70 million patients from more than 600 hospitals. RETAIN uses this data set to achieve the best area under the receiver operating characteristic curve at 0.825, a significant improvement over the baseline model. We also extended a feature attribution method, Kernel SHAP, to structured EHR data for model interpretation. Both RETAIN and Kernel SHAP can identify important features related to BM prediction. CONCLUSION: To the best of our knowledge, this is the first study to predict BM using structured EHR data. We achieved decent prediction performance for BM prediction and identified factors highly relevant to BM development. The sensitivity analysis demonstrated that both RETAIN and Kernel SHAP could discriminate unrelated features and put more weight on the features important to BM. Our study explored the potential of applying explainable artificial intelligence for future clinical applications.

miR-508-5p serves as an anti-oncogene by targeting S100A16 to regulate AKT signaling and epithelial-mesenchymal transition process in lung adenocarcinoma cells.

BACKGROUND: Our aim was to expose the effect of miR-508-5p on the developmental and biological behaviour of lung adenocarcinoma (LUAC). METHODS: The KM plotter was used to analyze the survival significance of miR-508-5p and S100A16 expression in LUAC patients. qRT-PCR was performed to detect the expression of miR-508-5p and S100A16 in LUAC tissue and LUAC cell lines. CCK8, colony formation and Transwell were performed to evaluate the effects of miR-508-5p and S100A16 on cell proliferation and metastasis. Dual luciferase reporter assay was used to verify that S100A16 were targets of miR-508-5p. Western blot analysis was performed to analyze protein expression. RESULTS: Results showed that low miR-508-5p expression in LUAC tissues indicated poorer overall survival of LUAC patients and miR-508-5p was downregulated in LUAC cell lines compared to the normal human lung epithelial cell line. miR-508-5p mimics could inhibit A549 cell proliferation and metastasis abilities, while miR-508-5p Antagomir showed the opposite effect. We identified S100A16 as one direct target of miR-508-5p, and rescuing S100A16 expression could reverse the effect of miR-508-5p mimics on A549 cell proliferation and metastasis. miR-508-5p could involve the coordination of AKT signaling and epithelial-mesenchymal transition (EMT) progress using western-blot assays and rescuing S100A16 expression could reverse the inhibited AKT signaling and EMT progress induced by miR-508-5p mimics. CONCLUSIONS: We found that miR-508-5p targeted S100A16 to regulate AKT signaling and EMT progress in A549 cells, resulting in impaired cell proliferation and metastasis activity, suggesting that miR-508-5p might be a promising therapeutic target and an important diagnostic and prognostic marker for improved LUAC therapeutic schedule.

Efficacy and safety of intensified antithrombotic therapy followed by stenting in treatment of highly severe stenosis accompanied by thrombosis in carotid atherosclerosis.

OBJECTIVE: This study explored the efficacy and safety of intensified antithrombotic therapy followed by stenting in treatment of highly severe stenosis accompanied by thrombosis in patients with carotid atherosclerosis (CAS). METHODS: This study recruited a total of 24 CAS patients between June 2016 and November 2020 in the research group, who had highly severe stenosis accompanied by in situ thrombosis and were treated with intensified antithrombotic treatment followed by stenting. The control group included 17 patients treated with stent angioplasty immediately after diagnosis with stenosis and thrombosis between January 2012 and May 2016. The efficacy and safety of treatment were compared between these two groups. RESULTS: The thrombus completely disappeared in 22 out of 24 patients (91.67%) in the research group after intensified antithrombotic treatment followed by stenting. Two patients still had the thrombus, but the volume was significantly reduced compared to that pre-treatment. The incidence of clinical events and new infarctions in the research group was significantly lower than that in the control group. In addition, the research group had significantly lower incidence of embolus antedisplacement and blocking the emboshield during the operation than the control group. There were no significant differences in the incidence of long-term complications and mortality between these two groups. The clinical prognosis of patients in the research group was significantly better than that of those in the control group within 3 months after treatment. CONCLUSION: Intensified antithrombotic therapy followed by stenting can effectively reduce the risk of perioperative complications in CAS patients with highly severe stenosis accompanied by thrombosis and improve the long-term clinical prognosis of patients without increasing the risk of bleeding.

Microstructure and Mechanical Properties of AlN/Al Joints Brazing by a Sputtering Al/Cu Bilayer Film Solder.

This paper presents a magnetron sputtering Al/Cu bilayer film solder to realize the brazing of AlN ceramic and Al metal. The effect of different temperatures on the structure and mechanical properties of brazed joints is studied. The results show that the sputtered Al particles have a sputtering wetting effect on AlN ceramic. The contact angle of molten Al on AlN ceramic with Al film deposited at 700 °C is as low as about 30°. While the contact angle of molten Al on AlN ceramic without Al film deposited at 1000 °C is about 89°. There is a large amount of Cu enrichment in brazed joints at 600 °C. The weld structure is a mixture of Al solid solution and AlCu compound. The shear strength of the brazed joint is only 70.6 MPa, and the joint fracture shows a large number of brittle fracture morphologies. With the increase of brazing temperature, the phenomenon of Cu enrichment in the joint gradually weakens, and the weld structure gradually transforms into a solid solution of Cu in Al. The shear strength of the brazed joint continues to increase, and the joint fracture morphology gradually changes from brittle fracture to furrow-like plastic fracture morphology. When the brazing temperature is increased to 660 °C, the distribution of Cu in the joint is evenly dispersed, and the shear strength of the brazed joint reaches the highest value of 107.8 MPa. The joint fracture is completely furrow-like plastic fracture morphological composition.

Characterizing spatial variations of city-wide elevated PM10 and PM2.5 concentrations using taxi-based mobile monitoring.

The spatial distribution of elevated particulate matter (PM) concentrations represents a public health concern due to its association with adverse health effects. In this study, a city-wide spatial variability of PM (PM10 and PM2.5) concentrations in Jinan, China is evaluated using a combination of measurements from 1700 fixed sites and taxi-based mobile monitoring (300 taxis recruited). The taxi fleet provides high spatial resolution and minimizes temporal sampling uncertainties that a single mobile platform cannot address. A big dataset of PM concentrations covering three land-use domains (roadway, community and open-field) and pollution episodes is derived from the taxi-based mobile monitoring (~3 × 107 pairs of PM10 and PM2.5). The ability of taxi-based mobile monitoring to characterize location-specific concentrations is assessed. We applied an "elevation ratio" to identify the elevated PM concentrations and quantified the ratios at 30-m road segments. Higher PM concentrations occurred during haze episode with lower elevation ratios in all land-use domains compares to non-haze episode. Different characteristics (distribution and range) of the elevation ratios are shown in different land-use domains which highlight the potential local emission hotspots and could have transformative implications for environmental management, thus, contribute to the effectiveness of pollution control strategy.

Nonlinearity in mass spectrometry for quantitative multi-component gas analysis in reaction processes.

Quantitative mass spectrometry analysis for multi-component gas phase reaction processes is a typical multi-input and multi-output (MIMO) nonlinear problem. Conventional calibration and analytical methods that are based on the common hypothesis of linearity of the detected signal and gas parameters, could result in misjudgment of the reaction mechanism and inaccuracy in the determination of the reaction kinetics. In the present work, theoretical derivations based on equivalent characteristic spectrum analysis (ECSA®), discrete mode experiments and continuous mode experiments were performed, and the nonlinearity of mass spectrometry was confirmed. It is only possible to determine the physical parameters such as flow rate and/or concentrations of gases by properly handling the nonlinearity of mass spectrometry. In such case comprehensive reaction mechanisms and even the kinetics of the process can be accurately characterized. Well-handled nonlinear mass spectrometry analysis ensures a reliable and highly accurate identification for the multi-component gas phase reaction processes, and ensures high signal-to-noise ratio for detecting the small-flow gases at a wide range of carrier gas flow.

CEP120-mediated KIAA0753 recruitment onto centrioles is required for timely neuronal differentiation and germinal zone exit in the developing cerebellum.

Joubert syndrome (JS) is a recessive ciliopathy in which all affected individuals have congenital cerebellar vermis hypoplasia. Here, we report that CEP120, a JS-associated protein involved in centriole biogenesis and cilia assembly, regulates timely neuronal differentiation and the departure of granule neuron progenitors (GNPs) from their germinal zone during cerebellar development. Our results show that depletion of Cep120 perturbs GNP cell cycle progression, resulting in a delay of cell cycle exit in vivo. To dissect the potential mechanism, we investigated the association between CEP120 interactome and the JS database and identified KIAA0753 (a JS-associated protein) as a CEP120-interacting protein. Surprisingly, we found that CEP120 recruits KIAA0753 to centrioles, and that loss of this interaction induces accumulation of GNPs in the germinal zone and impairs neuronal differentiation. Importantly, the replenishment of wild-type CEP120 rescues the above defects, whereas expression of JS-associated CEP120 mutants, which hinder KIAA0753 recruitment, does not. Together, our data reveal a close interplay between CEP120 and KIAA0753 for the germinal zone exit and timely neuronal differentiation of GNPs during cerebellar development, and mutations in CEP120 and KIAA0753 may participate in the heterotopia and cerebellar hypoplasia observed in JS patients.

Investigation on Low-Temperature Thermoelectric Properties of Ag2Se Polycrystal Fabricated by Using Zone-Melting Method.

Silver selenide, Ag2Se, is a promising low-temperature thermoelectric material which can be used to harvest the low-quality waste heat for electrical power generation or cool the microelectronics. Currently, the investigation on Ag2Se and its derivatives has become a hot topic in the thermoelectric community, but the thermoelectric properties of Ag2Se below 300 K have been rarely investigated. In this study, we prepared Ag2Se by using the zone-melting method. The electrical and thermal transport properties of zone-melted Ag2Se from 5 to 380 K were systematically investigated and compared with the previously reported data of Ag2Se and other typical low-temperature thermoelectric materials, such as Mg3Bi2, Bi2Te3, and BiSb. Ag2Se shows intrinsic semiconductor features, ultrahigh carrier mobility, small density-of-state effective mass, and ultralow lattice thermal conductivity. At 300 K, the zT of zone-melted Ag2Se is 0.75. This study will shed light on the further investigation of Ag2Se.

Iguratimod promotes transformation of mononuclear macrophages in elderly patients with rheumatoid arthritis by nuclear factor-κB pathway.

BACKGROUND: The role of macrophages in rheumatoid arthritis (RA) and its mechanism have attracted much attention in RA pathogenesis. Macrophages accumulate in the synoviums of RA, and the proportion of M1 type pro-inflammatory macrophages is higher than that of M2 type anti-inflammatory macrophages, leading to the secretion of inflammatory molecules and the aggravation of inflammatory reaction, which has made macrophages a potential target of RA drugs. Iguratimod is a kind of cyclo-oxygenase-2 inhibitor that affects macrophage polarity. It is speculated that its anti-inflammatory and anti-rheumatic effects may be related to the regulation of macrophage M1/M2 ratio. AIM: To investigate the effects of Iguratimod on the polarity of mononuclear macrophages in elderly patients with RA. METHODS: Elderly patients with RA and joint effusion were selected, including 10 men and 25 women, with an average age of 66.37 ± 4.42 years. Patients were treated with oral administration of 25 mg Iguratimod (Iremod, State Food and Drug Administration Approval No. H20110084) twice daily for 12 wk. Disease Activity Score 28 and Health Assessment Questionnaire score were collected according to the disease severity before and after treatment. Venous blood and joint effusion fluid were collected, mononuclear macrophages were extracted and expression of cell surface markers CD86, CD64, CD163, and CD206 was analyzed by flow cytometry. The concentration of inflammatory factors interleukin (IL)-6, IL-1ß, transforming growth factor-ß, and IL-4 in the joint effusion fluid was analyzed by enzyme-linked immunosorbent assay. Expression of mononuclear cells inhibitor of nuclear factor-κB (IκB) and phosphorylated IκB in peripheral blood was analyzed by western blotting. RESULTS: Disease Activity Score 28 score and Health Assessment Questionnaire score of patients treated with Iguratimod decreased significantly. The percentage of cell surface markers CD86 and CD64 decreased significantly, and the percentage of CD163 and CD206 increased significantly (P < 0.05). The inflammatory factors IL-6 and IL-1ß decreased significantly, and transforming growth factor-ß and IL-4 increased significantly. Western blot analysis showed that mononuclear cell inhibitor of nuclear factor-κB in peripheral blood was significantly increased after treatment, and its phosphorylation level was significantly decreased (P < 0.05). CONCLUSION: Iguratimod can promote the transformation of mononuclear macrophages from M1 to M2 in elderly patients with RA by inhibiting the nuclear factor-κB pathway, thus improving symptoms of RA.

The Effect of Temperature and Sputtered Particles on the Wettability of Al/Al2O3.

Two kinds of Al2O3 ceramic samples with and without Al film deposited were designed respectively. The influences of temperature and high kinetic energy sputtering particles on the wettability and interface strength of Al/Al2O3 were studied by comparing the wetting behavior of molten aluminum on two samples. The results show that molten aluminum does not wet the Al2O3 sample without Al film deposited at 700 °C, the contact angle is 165°, and the interfacial shear strength is 28 MPa. With the increase of temperature, the contact angle decreases continuously, and the interface shear strength gradually increases. The fracture of the brazed joint is transferred from the interface to the brazing seam. In comparison, the sample deposited with Al film is wetted by molten aluminum at 700 °C, and the contact angle is only 12°. The interface shear strength is about 120 MPa and is less affected by temperature. The shear fracture of the joint occurs in the brazed seam of Al metal. Therefore, the high energy generated by either the temperature increase or the particle sputtering enable the Al atoms to overcome the energy barrier to form Al-O bonds with the O atoms on the Al2O3 ceramic surface, thereby improving the wettability of Al/Al2O3.

LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most common malignancies with the highest morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) are recently recognized as noteworthy regulators of different tumors, counting NSCLC. However, the biological functions and regulatory mechanism of lncRNA WT1-AS in NSCLC progression still stay uninvestigated. METHODS: WT1-AS and miR-494-3p levels in NSCLC cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR). In the current study, the regulatory effects of WT1-AS/miR-494-3p axis on cellular behaviors of NSCLC cell lines (A549 and NCI-H1975) were evaluated by a variety of methods. Cell counting kit-8 (CCK-8) and EDU assays were adopted to assess NSCLC cell proliferation. Tunnel staining and flow cytometry assay were applied to determine cell apoptosis and cell cycle distribution. Besides, cell migration and invasion abilities were analyzed by performing wound healing and transwell assays. Meanwhile, the levels of key proteins related to NSCLC cell apoptosis and PTEN/PI3K/AKT pathway were examined using Western blot assay. In addition, luciferase reporter assays were used to determine the interaction between WT1-AS and miR-494-3p or miR-494-3p and PTEN. RESULTS: Visibly downregulated WT1-AS in NSCLC cell lines was obtained from Broad Institute Cancer Cell Line Encyclopedia (CCLE) database and further verified by performing RT-qPCR. Besides, miR-494-3p was the downstream target gene of WT1-AS and obviously upregulated miR-494-3p in NSCLC cell lines was confirmed. WT1-AS overexpression suppressed cell proliferation, migration and invasion abilities while enhanced cell apoptosis of A549 and NCI-H1975 cells. Furthermore, upregulation of miR-494-3p distinctly reversed these inhibitory effects of WT1-AS overexpression on the tumorigenesis and progression of NSCLC. In addition, WT1-AS promoted PTEN expression and thereby inhibited activation of PI3K/AKT pathway by sponging miR-494-3p. CONCLUSION: To conclude, lncRNA WT1-AS impeded cell proliferation, migration, invasion but accelerated cell apoptosis via negatively regulating miR-494-3p to mediate PTEN/PI3K/AKT pathway in NSCLC.

Segmenting Thoracic Cavities with Neoplastic Lesions: A Head-to-head Benchmark with Fully Convolutional Neural Networks.

Automatic segmentation of thoracic cavity structures in computer tomography (CT) is a key step for applications ranging from radiotherapy planning to imaging biomarker discovery with radiomics approaches. State-of-the-art segmentation can be provided by fully convolutional neural networks such as the U-Net or V-Net. However, there is a very limited body of work on a comparative analysis of the performance of these architectures for chest CTs with significant neoplastic disease. In this work, we compared four different types of fully convolutional architectures using the same pre-processing and post-processing pipelines. These methods were evaluated using a dataset of CT images and thoracic cavity segmentations from 402 cancer patients. We found that these methods achieved very high segmentation performance by benchmarks of three evaluation criteria, i.e. Dice coefficient, average symmetric surface distance and 95% Hausdorff distance. Overall, the two-stage 3D U-Net model performed slightly better than other models, with Dice coefficients for left and right lung reaching 0.947 and 0.952, respectively. However, 3D U-Net model achieved the best performance under the evaluation of HD95 for right lung and ASSD for both left and right lung. These results demonstrate that the current state-of-art deep learning models can work very well for segmenting not only healthy lungs but also the lung containing different stages of cancerous lesions. The comprehensive types of lung masks from these evaluated methods enabled the creation of imaging-based biomarkers representing both healthy lung parenchyma and neoplastic lesions, allowing us to utilize these segmented areas for the downstream analysis, e.g. treatment planning, prognosis and survival prediction.

Diffusion Barrier Performance of AlCrTaTiZr/AlCrTaTiZr-N High-Entropy Alloy Films for Cu/Si Connect System.

In this study, high-entropy alloy films, namely, AlCrTaTiZr/AlCrTaTiZr-N, were deposited on the n-type (100) silicon substrate. Then, a copper film was deposited on the high-entropy alloy films. The diffusion barrier performance of AlCrTaTiZr/AlCrTaTiZr-N for Cu/Si connect system was investigated after thermal annealing for an hour at 600 °C, 700 °C, 800 °C, and 900 °C. There were no Cu-Si intermetallic compounds generated in the Cu/AlCrTaTiZr/AlCrTaTiZr-N/Si film stacks after annealing even at 900 °C through transmission electron microscopy (TEM) and atomic probe tomography (APT) analysis. The results indicated that AlCrTaTiZr/AlCrTaTiZr-N alloy films can prevent copper diffusion at 900 °C. The reason was investigated in this work. The amorphous structure of the AlCrTaTiZr layer has lower driving force to form intermetallic compounds; the lattice mismatch between the AlCrTaTiZr and AlCrTaTiZ-rN layers increased the diffusion distance of the Cu atoms and the difficulty of the Cu atom diffusion to the Si substrate.