Circular RNAs (circRNAs) have received increasing attention in human tumor research. However, there are still a large number of unknown circRNAs that need to be deciphered. The aim of this study is ...to unearth novel circRNAs as well as their action mechanisms in hepatocellular carcinoma (HCC).
A combinative strategy of big data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology was employed to dig HCC-related circRNAs and to explore their potential action mechanisms. A connectivity map (CMap) analysis was conducted to identify potential therapeutic agents for HCC.
Six differently expressed circRNAs were obtained from three Gene Expression Omnibus microarray datasets (GSE78520, GSE94508 and GSE97332) using the RobustRankAggreg method. Following the RT-qPCR corroboration, three circRNAs (hsa_circRNA_102166, hsa_circRNA_100291 and hsa_circRNA_104515) were selected for further analysis. miRNA response elements of the three circRNAs were predicted. Five circRNA-miRNA interactions including two circRNAs (hsa_circRNA_104515 and hsa_circRNA_100291) and five miRNAs (hsa-miR-1303, hsa-miR-142-5p, hsa-miR-877-5p, hsa-miR-583 and hsa-miR-1276) were identified. Then, 1424 target genes of the above five miRNAs and 3278 differently expressed genes (DEGs) on HCC were collected. By intersecting the miRNA target genes and the DEGs, we acquired 172 overlapped genes. A protein-protein interaction network based on the 172 genes was established, with seven hubgenes (JUN, MYCN, AR, ESR1, FOXO1, IGF1 and CD34) determined from the network. The Gene Oncology, Kyoto Encyclopedia of Genes and Genomes and Reactome enrichment analyses revealed that the seven hubgenes were linked with some cancer-related biological functions and pathways. Additionally, three bioactive chemicals (decitabine, BW-B70C and gefitinib) based on the seven hubgenes were identified as therapeutic options for HCC by the CMap analysis.
Our study provides a novel insight into the pathogenesis and therapy of HCC from the circRNA-miRNA-mRNA network view.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary
Background
Liver fibrosis is the strongest histological risk factor for liver‐related complications and mortality in metabolic dysfunction‐associated fatty liver disease (MAFLD). Second ...harmonic generation/two‐photon excitation fluorescence (SHG/TPEF) is a powerful tool for label‐free two‐dimensional and three‐dimensional tissue visualisation that shows promise in liver fibrosis assessment.
Aim
To investigate combining multi‐photon microscopy (MPM) and deep learning techniques to develop and validate a new automated quantitative histological classification tool, named AutoFibroNet (Automated Liver Fibrosis Grading Network), for accurately staging liver fibrosis in MAFLD.
Methods
AutoFibroNet was developed in a training cohort that consisted of 203 Chinese adults with biopsy‐confirmed MAFLD. Three deep learning models (VGG16, ResNet34, and MobileNet V3) were used to train pre‐processed images and test data sets. Multi‐layer perceptrons were used to fuse data (deep learning features, clinical features, and manual features) to build a joint model. This model was then validated in two further independent cohorts.
Results
AutoFibroNet showed good discrimination in the training set. For F0, F1, F2 and F3‐4 fibrosis stages, the area under the receiver operating characteristic curves (AUROC) of AutoFibroNet were 1.00, 0.99, 0.98 and 0.98. The AUROCs of F0, F1, F2 and F3‐4 fibrosis stages for AutoFibroNet in the two validation cohorts were 0.99, 0.83, 0.80 and 0.90 and 1.00, 0.83, 0.80 and 0.94, respectively, showing a good discriminatory ability in different cohorts.
Conclusion
AutoFibroNet is an automated quantitative tool that accurately identifies histological stages of liver fibrosis in Chinese individuals with MAFLD.
Deep learning (DL) model and joint model (AutoFibroNet). Both deep learning models are used for automated classification and quantification of liver fibrosis stages, in which the AutoFibroNet uses multi‐layer perceptron (MLP) to integrate clinical features, manual features and DL features before classification.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Intrinsic polar metals are rare, especially in oxides, because free electrons screen electric fields in a metal and eliminate the internal dipoles that are needed to break inversion symmetry. Here we ...use first-principles high-throughput structure screening to predict a new polar metal in bulk and thin film forms. After screening more than 1000 different crystal structures, we find that ordered BiPbTi
2
O
6
can crystallize in three polar and metallic structures, which can be transformed between via pressure or strain. In a heterostructure of layered BiPbTi
2
O
6
and PbTiO
3
, multiple states with different relative orientations of BiPbTi
2
O
6
polar displacements, and PbTiO
3
polarization, can be stabilized. At room temperature, the interfacial coupling enables electric fields to first switch PbTiO
3
polarization and subsequently drive 180° change of BiPbTi
2
O
6
polar displacements. At low temperatures, the heterostructure provides a tunable tunnelling barrier and might be used in multi-state memory devices.
Polar metal oxides are not frequently observed, yet offer attractive properties for functional devices. Now, high-throughput structure screening of a thousand crystal structures reveals that BiPbTi
2
O
6
can form both polar and metallic structures.
Artificial intelligence in ultrasound Shen, Yu-Ting; Chen, Liang; Yue, Wen-Wen ...
European journal of radiology,
June 2021, 2021-Jun, 2021-06-00, 20210601, Volume:
139
Journal Article
Peer reviewed
•The quantification of image pixel values makes AI technology suitable for this field.•AI technology in US can deliver effective, efficient and equitable benefits.•Radiologists can gain greater ...diagnostic confidence with the aid of AI technology.
Ultrasound (US), a flexible green imaging modality, is expanding globally as a first-line imaging technique in various clinical fields following with the continual emergence of advanced ultrasonic technologies and the well-established US-based digital health system. Actually, in US practice, qualified physicians should manually collect and visually evaluate images for the detection, identification and monitoring of diseases. The diagnostic performance is inevitably reduced due to the intrinsic property of high operator-dependence from US. In contrast, artificial intelligence (AI) excels at automatically recognizing complex patterns and providing quantitative assessment for imaging data, showing high potential to assist physicians in acquiring more accurate and reproducible results. In this article, we will provide a general understanding of AI, machine learning (ML) and deep learning (DL) technologies; We then review the rapidly growing applications of AI-especially DL technology in the field of US-based on the following anatomical regions: thyroid, breast, abdomen and pelvis, obstetrics heart and blood vessels, musculoskeletal system and other organs by covering image quality control, anatomy localization, object detection, lesion segmentation, and computer-aided diagnosis and prognosis evaluation; Finally, we offer our perspective on the challenges and opportunities for the clinical practice of biomedical AI systems in US.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC ...cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized mutated genes such as FAT1, FAT2, ZNF750 and KMT2D, in addition to those already known (TP53, PIK3CA and NOTCH1). Further SCNV evaluation, immunohistochemistry and biological analysis suggested their functional relevance in ESCC. Notably, RTK-MAPK-PI3K pathways, cell cycle and epigenetic regulation are frequently dysregulated by multiple molecular mechanisms in this cancer. Our approaches also uncovered many druggable candidates, and XPO1 was further explored as a therapeutic target because it showed both gene mutation and protein overexpression. Our integrated study unmasks a number of novel genetic lesions in ESCC and provides an important molecular foundation for understanding esophageal tumors and developing therapeutic targets.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Ferroelectricity in layered bismuth oxide down to 1 nanometer Yang, Qianqian; Hu, Jingcong; Fang, Yue-Wen ...
Science (American Association for the Advancement of Science),
2023-Mar-24, 2023-03-24, 20230324, Volume:
379, Issue:
6638
Journal Article
Peer reviewed
Open access
Atomic-scale ferroelectrics are of great interest for high-density electronics, particularly field-effect transistors, low-power logic, and nonvolatile memories. We devised a film with a layered ...structure of bismuth oxide that can stabilize the ferroelectric state down to 1 nanometer through samarium bondage. This film can be grown on a variety of substrates with a cost-effective chemical solution deposition. We observed a standard ferroelectric hysteresis loop down to a thickness of ~1 nanometer. The thin films with thicknesses that range from 1 to 4.56 nanometers possess a relatively large remanent polarization from 17 to 50 microcoulombs per square centimeter. We verified the structure with first-principles calculations, which also pointed to the material being a lone pair-driven ferroelectric material. The structure design of the ultrathin ferroelectric films has great potential for the manufacturing of atomic-scale electronic devices.
Size-selected negatively-charged boron clusters (Bn−) have been found to be planar or quasi-planar in a wide size range. Even though cage structures emerged as the global minimum at B39−, the global ...minimum of B40− was in fact planar. Only in the neutral form did the B40 borospherene become the global minimum. How the structures of larger boron clusters evolve is of immense interest. Here we report the observation of a bilayer B48− cluster using photoelectron spectroscopy and first-principles calculations. The photoelectron spectra of B48− exhibit two well-resolved features at low binding energies, which are used as electronic signatures to compare with theoretical calculations. Global minimum searches and theoretical calculations indicate that both the B48− anion and the B48 neutral possess a bilayer-type structure with D2h symmetry. The simulated spectrum of the D2h B48− agrees well with the experimental spectral features, confirming the bilayer global minimum structure. The bilayer B48−/0 clusters are found to be highly stable with strong interlayer covalent bonding, revealing a new structural type for size-selected boron clusters. The current study shows the structural diversity of boron nanoclusters and provides experimental evidence for the viability of bilayer borophenes.
Objectives
Transient elastography (TE), as a non‐invasive method, has been studied for evaluation of portal hypertension in patients with chronic liver diseases (CLD) with variable results. We ...studied the performance of TE for detection of significant portal hypertension, oesophageal varices and large oesophageal varices using meta‐analysis.
Methods
PubMed, the Cochrane Library, EMBASE and ISI web of Knowledge were searched. The studies published in English relating to the diagnostic value of TE for significant portal hypertension, oesophageal varices and large oesophageal varices in patients with CLD were collected.
Results
A total of 18 studies, which included 3644 patients were analysed. Summary sensitivity and specificity were 0.90 (95% confidence interval (CI), 0.81–0.95) and 0.79 (95% CI, 0.58–0.91) for significant portal hypertension, and 0.87 (95% CI, 0.80–0.92) and 0.53 (95% CI, 0.36–0.69) for oesophageal varices and 0.86 (95% CI, 0.71–0.94) and 0.59 (95% CI, 0.45–0.72) for large oesophageal varices respectively. The HSROCs were 0.93 for significant portal hypertension, 0.84 for oesophageal varices and 0.78 for large oesophageal varices respectively. TE was very informative with 81% probability of correctly detection significant portal hypertension following a ‘positive’ measurement (over the threshold value) and lowering the probability of disease to as low as 11% when ‘negative’ measurement (below the threshold value) when pre‐test probability was 50% whereas, for oesophageal varices or large oesophageal varices, the probability of a correct diagnosis following a ‘positive’ measurement did not exceeded 70%.
Conclusions
TE could be used as a good screening tool for significant portal hypertension, but only moderate diagnostic utility for the prediction of oesophageal varices or large oesophageal varices.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background and aims
Treatment of non‐alcoholic steatohepatitis (NASH) is challenging, because suppressing fibrotic progression has not been achieved consistently by drug candidates currently in ...clinical trials. The aim of this study was to investigate the molecular interplays underlying NASH‐associated fibrosis in a mouse NASH model and human specimens.
Methods
Mice were divided into 4 groups: Controls; NASH (high fat/Calorie diet plus high fructose and glucose in drinking water, HFCD‐HF/G) for 16 weeks; HFCD‐HF/G plus docosahexaenoic acid (DHA) for 16 or 8 weeks.
Results
Along with NASH progression, fibrotic deposition was documented in HFCD‐HF/G‐fed mice. Liver succinate content was significantly increased along with decreased expression of succinate dehydrogenase‐A (SDH‐A) in these mice; whereas, GPR‐91 receptor expression was much enhanced in histology compared to control mice, and co‐localized histologically with hepatic stellate cells (HSCs). Succinate content was increased in fatty acid‐overloaded primary hepatocytes with significant oxidant stress and lipotoxicity. Exposure to succinate led to up‐regulation of GPR‐91 receptor in primary and immortalized HSCs. In contrast, suppression of GPR‐91 receptor expression abolished succinate stimulatory role in GPR‐91 expression and extracellular matrix production in HSCs. All these changes were minimized or abrogated by DHA supplementation in vivo or in vitro. Moreover, GPR‐91 receptor expression correlates with severity of fibrosis in human NASH biopsy specimens.
Conclusion
Succinate accumulation in steatotoic hepatocytes may result in HSC activation through GPR‐91 receptor signalling in NASH progression, and the cross‐talk between hepatocytes and HSC through GPR‐91 signalling is most likely to be the molecular basis of fibrogenesis in NASH.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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