Zinc-finger protein 331 (ZNF331), a Kruppel-associated box zinc-finger protein gene, was identified as a putative tumor suppressor in our previous study. However, the role of ZNF331 in tumorigenesis ...remains elusive. We aimed to clarify its epigenetic regulation and biological functions in gastric cancer. ZNF331 was silenced or downregulated in 71% (12/17) gastric cancer cell lines. A significant downregulation was also detected in paired gastric tumors compared with adjacent non-cancer tissues. In contrast, ZNF331 was readily expressed in various normal adult tissues. The downregulation of ZNF331 was closely linked to the promoter hypermethylation as evidenced by methylation-specific PCR, bisulfite genomic sequencing and reexpression by demethylation agent treatment. DNA sequencing showed no genetic mutation/deletion of ZNF331 in gastric cancer cell lines. Ectopic expression of ZNF331 in the silenced cancer cell lines MKN28 and HCT116 significantly reduced colony formation and cell viability, induced cell cycle arrests and repressed cell migration and invasive ability. Concordantly, knockdown of ZNF331 increased cell viability and colony formation ability of gastric cancer cell line MKN45. Two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomic approach were applied to analyze the molecular basis of the biological functions of ZNF331. In all, 10 downstream targets of ZNF331 were identified to be associated with regulation of cell growth and metastasis. The tumor-suppressive effect of ZNF331 is mediated at least by downregulation of genes involved in cell growth promotion (DSTN, EIF5A, GARS, DDX5, STAM, UQCRFS1 and SET) and migration/invasion (DSTN and ACTR3), and upregulation of genome-stability gene (SSBP1) and cellular senescence gene (PNPT1). A novel target of ZNF331 (DSTN) was functionally validated. Overexpression of DSTN in BGC-823 cells increased colony formation and migration ability. In conclusion, our results suggest that ZNF331 possesses important functions for the suppression of gastric carcinogenesis as a novel functional tumor-suppressor gene.
Summary
Background
Pioneering effort has been made to facilitate the recognition of pathology in malignancies based on whole‐slide images (WSIs) through deep learning approaches. It remains unclear ...whether we can accurately detect and locate basal cell carcinoma (BCC) using smartphone‐captured images.
Objectives
To develop deep neural network frameworks for accurate BCC recognition and segmentation based on smartphone‐captured microscopic ocular images (MOIs).
Methods
We collected a total of 8046 MOIs, 6610 of which had binary classification labels and the other 1436 had pixelwise annotations. Meanwhile, 128 WSIs were collected for comparison. Two deep learning frameworks were created. The ‘cascade’ framework had a classification model for identifying hard cases (images with low prediction confidence) and a segmentation model for further in‐depth analysis of the hard cases. The ‘segmentation’ framework directly segmented and classified all images. Sensitivity, specificity and area under the curve (AUC) were used to evaluate the overall performance of BCC recognition.
Results
The MOI‐ and WSI‐based models achieved comparable AUCs around 0·95. The ‘cascade’ framework achieved 0·93 sensitivity and 0·91 specificity. The ‘segmentation’ framework was more accurate but required more computational resources, achieving 0·97 sensitivity, 0·94 specificity and 0·987 AUC. The runtime of the ‘segmentation’ framework was 15·3 ± 3·9 s per image, whereas the ‘cascade’ framework took 4·1 ± 1·4 s. Additionally, the ‘segmentation’ framework achieved 0·863 mean intersection over union.
Conclusions
Based on the accessible MOIs via smartphone photography, we developed two deep learning frameworks for recognizing BCC pathology with high sensitivity and specificity. This work opens a new avenue for automatic BCC diagnosis in different clinical scenarios.
What's already known about this topic?
The diagnosis of basal cell carcinoma (BCC) is labour intensive due to the large number of images to be examined, especially when consecutive slide reading is needed in Mohs surgery.
Deep learning approaches have demonstrated promising results on pathological image‐related diagnostic tasks.
Previous studies have focused on whole‐slide images (WSIs) and leveraged classification on image patches for detecting and localizing breast cancer metastases.
What does this study add?
Instead of WSIs, microscopic ocular images (MOIs) photographed from microscope eyepieces using smartphone cameras were used to develop neural network models for recognizing BCC automatically.
The MOI‐ and WSI‐based models achieved comparable areas under the curve around 0·95.
Two deep learning frameworks for recognizing BCC pathology were developed with high sensitivity and specificity.
Recognizing BCC through a smartphone could be considered a future clinical choice.
Linked Comment: Lee and Soyer. Br J Dermatol 2020; 182:540–541.
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Observation shows that eastern China experienced an interdecadal shift in the summer precipitation during the second half of the 20th century. The summer precipitation increased in the middle and ...lower reaches of the Yangtze River valley, whereas it decreased in northern China. Here we use a coupled ocean-atmosphere general circulation model and multi-ensemble simulations to show that the interdecadal shift is mainly caused by the anthropogenic forcing. The rapidly increasing greenhouse gases induce a notable Indian Ocean warming, causing a westward shift of the western Pacific subtropical high (WPSH) and a southward displacement of the East Asia westerly jet (EAJ) on an interdecadal timescale, leading to more precipitation in Yangtze River valley. At the same time the surface cooling effects from the stronger convection, higher precipitation and rapidly increasing anthropogenic aerosols contribute to a reduced summer land-sea thermal contrast. Due to the changes in the WPSH, the EAJ and the land-sea thermal contrast, the East Asian summer monsoon weakened resulting in drought in northern China. Consequently, an anomalous precipitation pattern started to emerge over eastern China in the late 1970s. According to the model, the natural forcing played an opposite role in regulating the changes in WPSH and EAJ, and postponed the anthropogenically forced climate changes in eastern China. The Indian Ocean sea surface temperature is crucial to the response, and acts as a bridge to link the external forcings and East Asian summer climate together on a decadal and longer timescales. Our results further highlight the dominant roles of anthropogenic forcing agents in shaping interdecadal changes of the East Asian climate during the second half of the 20th century.
Recently a new diluted magnetic semiconductor, (Ba,K)(Zn,Mn)2As2 (BZA), with high Curie temperature was discovered, showing an independent spin and charge-doping mechanism. This makes BZA a promising ...material for spintronics devices. We report the successful growth of a BZA single crystal for the first time in this study. An Andreev reflection junction, which can be used to evaluate spin polarization, was fabricated based on the BZA single crystal. A 66% spin polarization of the BZA single crystal was obtained by Andreev reflection spectroscopy analysis.
Discrete particle simulation has been recognized as a useful numerical technique for elucidating the fundamentals of granular matter. For gas−solid two-phase flow in fluidization, such simulations ...are achieved by combining the discrete flow of the particle phase with the continuum flow of the gas phase. However, differences exist in the actual implementation of this idea in the literature. This paper attempts to rationalize this matter by discussing important aspects including the governing equations in relation to the so-called models A and B, which use different treatments of pressure drop in the well-established two-fluid model, different coupling schemes between the gas and solid phases, and different equations for quantifying the particle−fluid interaction. For the purpose of quantitative analysis, gas fluidization of binary mixtures of particles is simulated with different model formulations, and a comparison of the results in terms of flow pattern and mixing/segregation kinetics shows a significant difference. Physical experiments are then conducted under similar conditions to assess the two model formulations, and the results suggest that the model B treatment is favored. The reason for the difference is also discussed in terms of the particle−fluid interaction force. On this basis, a method to reduce the difference between the two model formulations is proposed and tested.
•Study the thermosolutal convection in a porous cubic cavity filled in power-law fluids.•Simulate the 3D convection with the compact high order finite volume method.•Reveal the shear-thinning fluids ...is more effective on the change of irreversibilities, heat and mass transfer.•Find the effect of heterogeneity level on fluid flow and entropy generation.
The article reports a numerical study of entropy generation due to the double-diffusive natural convection in a 3D heterogeneous porous cubic saturated with power-law fluids and submitted to horizontal thermal and concentration gradients. The governing equations based on a generalized non-Darcy model are solved by using the compact high order finite volume method. This approach is devised to detect the effects of the heterogeneity level, the buoyancy ratio and the porous thermal Rayleigh number on the fluid flow and its associated irreversibility characteristics. The results show that the mean Nusselt and Sherwood number reduce, while the total entropy generation increases, as the level of heterogeneity increases by the exponential distribution of the permeability; the mean Nusselt, Sherwood number and total entropy generation increases as the porous thermal Rayleigh number increases or the buoyancy ratio increases (decreases) for the thermal dominated flow (solutal dominated flow) by the heat and mass transfer performance. Apart from that, our numerical tests of the approach on the shear-thinning, the Newtonian and shear-thickening fluids show that the impacts of different power-law indexes on the entropy generation due to fluid friction, heat and mass transfer are mainly manifested in rheological properties, which elucidate that the shear-thinning fluids is more effective than shear-thickening fluids. The studies may help us establish a physically reasonable methodology to systemically assess fluid flow and energy consumption in heterogeneous porous media in the real world.
Aim To evaluate the feasibility of determining the chemical composition of urinary stones using computed tomography (CT) spectral imaging (SI) Materials and methods Two hundred and ten urinary stones ...were scanned in vitro using the SI mode and conventional polychromatic imaging (CPI; 120 kVp) mode. The radiodensity at 50 keV and 120 kVp, the mean calcium density (CD), and the water density (WD) were measured using the 50 keV images, 120 kVp images, calcium-based images, and water-based images, respectively. These parameters and the calcium–water ratio (CWR) were compared between different types of stones. CWR was defined as: CWR = calcium density/water density. Results According to the results determined by infrared spectroscopy, 116 pure urinary stones were divided into five groups: uric acid (UA, n = 16), struvite (STR, n = 23), cystine (CYS, n = 10), calcium phosphate (CaP, n = 29), and calcium oxalate (COX, n = 38). CD, CWR, and the radiodensity of stones at 50 keV CT imaging of each group were as follows: UA (−3.55 ± 10.85 mg/ml, 0.03 ± 0.05, 510.08 ± 157.29 HU); STR (224.99 ± 64.28 mg/ml, 0.19 ± 0.07, 1058.58 ± 260.13 HU); CYS (139.67 ± 34.66 mg/ml, 0.13 ± 0.03, 725.75 ± 142.35 HU); CaP (619.39 ± 26.13 mg/ml, 0.69 ± 0.11, 2617.46 ± 186.22 HU); COX (518.61 ± 95.5 mg/ml, 0.58 ± 0.1, 2247.47 ± 379.51 HU). The differences in the CD, CRW, and radiodensity of stones at 50 keV CT imaging among the groups were statistically significant by binary comparison ( p < 0.05). There were no significant differences in the radiodensity of stones at 120 keV CT imaging between UA and CYS ( p = 0.267), CaP and COX ( p = 0.065), and in the WD between STR and CYS ( p = 0.108). Conclusion SI provides a novel method to better characterize pure urinary stones using the mean CD, CWR, and the radiodensity of stones at 50 keV CT imaging.
We compare the evolution of microstructure and mechanical properties of Ag/Ni multilayers of varying layer thickness (1–200nm) subjected to helium ion and proton irradiation at room temperature to ...similar dose, ∼2 displacements-per-atom on average. Layer structure remained intact after both types of irradiation although defects accumulated in the layers are different. Helium bubbles were the major defects in helium ion irradiated films, while dislocation loops were ubiquitous in proton irradiated multilayers. In He ion irradiated multilayers, radiation hardening was greater than that in proton irradiated specimens, and the magnitude of hardening decreased with decreasing individual layer thickness. In comparison no size dependent hardening was observed in proton irradiated films. Mechanisms of irradiation induced hardening were discussed.
Early diagnosis of atrial fibrillation is important as it is crucial for improving patient outcomes. Fibroblast growth factor-2 (FGF2) may serve as a diagnostic biomarker for heart failure due to its ...ability to promote cardiac fibrosis and hypertrophy; however, the relationship between FGF2 concentration and heart failure is unclear. Therefore, this study aimed to explore whether FGF2 could aid in distinguishing patients with heart failure from healthy controls and those with dyspnea without heart failure. Additionally, to evaluate the possible correlation between serum FGF2 levels and its diagnostic parameters in patients with heart failure.
Plasma FGF2 concentration was measured in 114 patients with a complaint of dyspnea (enrolled in the study between January 2022 and August 2022). Based on heart failure diagnosis, the patients were assigned to three groups, as follows: heart failure (n = 80), non-heart-failure dyspnea (n = 34), and healthy controls (n = 36), following physical examination. Possible correlations between serum FGF2 levels and other prognostic parameters in patients with heart failure were analyzed.
Serum FGF2 levels were higher in patients with heart failure (125.60 88.95, 183.40 pg/mL) than in those with non-heart-failure dyspnea (65.30 28.85, 78.95 pg/mL) and healthy controls (78.90 60.80, 87.20 pg/mL) (p < 0.001). Receiver operating characteristic curve analysis identified FGF2 concentration as a significant predictor in heart failure diagnosis, with an area under the curve of 0.8693 (p < 0.0001). Importantly, in the heart failure group, serum FGF2 concentrations correlated with key prognostic parameters for heart failure, such as reduced left ventricular ejection fraction and elevated serum levels of N-terminal pro-B-type natriuretic peptide.
Elevated serum FGF2 level is strongly associated with an increased risk of heart failure and could serve as a useful biomarker to complement vital diagnostic parameters for heart failure.
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