Nucleotide-level prediction of CircRNA-protein binding based on fully convolutional neural network.

Introduction: CircRNA-protein binding plays a critical role in complex biological activity and disease. Various deep learning-based algorithms have been proposed to identify CircRNA-protein binding sites. These methods predict whether the CircRNA sequence includes protein binding sites from the sequence level, and primarily concentrate on analysing the sequence specificity of CircRNA-protein binding. For model performance, these methods are unsatisfactory in accurately predicting motif sites that have special functions in gene expression. Methods: In this study, based on the deep learning models that implement pixel-level binary classification prediction in computer vision, we viewed the CircRNA-protein binding sites prediction as a nucleotide-level binary classification task, and use a fully convolutional neural networks to identify CircRNA-protein binding motif sites (CPBFCN). Results: CPBFCN provides a new path to predict CircRNA motifs. Based on the MEME tool, the existing CircRNA-related and protein-related database, we analysed the motif functions discovered by CPBFCN. We also investigated the correlation between CircRNA sponge and motif distribution. Furthermore, by comparing the motif distribution with different input sequence lengths, we found that some motifs in the flanking sequences of CircRNA-protein binding region may contribute to CircRNA-protein binding. Conclusion: This study contributes to identify circRNA-protein binding and provides help in understanding the role of circRNA-protein binding in gene expression regulation.

Effect of inoculating thermophilic bacterial consortia on compost efficiency and quality.

The objective of this study was to investigate the potential effects of thermophilic bacterial consortia on compost efficiency and quality. The application of bacterial consortia resulted in an earlier onset of the thermophilic period (THP), an increased upper temperature limit, and an extended duration of the THP by 3-5 days compared to the control group (CK). Microbial inoculation significantly improved the efficiency of organic matter degradation, as well as the content of water-soluble nitrogen (WSN) and humic acid-carbon (HAC). In the case of consortium Ⅱ inoculation (T2), the activities of cellobiohydrolase, ß-glucosidase, and protease were increased by 81.81 %, 70.13 %, and 74.09 % at the THP respectively compared to CK. During the maturation stage, T2 also exhibited the highest PV, n/PIII, n value (1.33) and HAC content (39.53 mg·g-1), indicating that inoculation of consortium Ⅱ effectively promoted substrate maturity and product quality. Moreover, this inoculation effectively optimized the bacterial communities, particularly the growth of Planococcus, Chelatococcus, and Chelativorans during the composting, which were involved in carbon and nitrogen conversion or HAC synthesis. Carbohydrate and amino acid metabolism, and membrane transport were predominant in the consortia-inoculated samples, with an increased gene abundance, suggesting that inoculation contributed to promoting the biodegradation of lignocellulose and the exchange of favorable factors. In conclusion, this study demonstrates that inoculating thermophilic bacterial consortia has a positive impact on enhancing the resource utilization efficiency of agricultural waste and improving the quality of compost products.

Dopaminergic damage pattern predicts phenoconversion time in isolated rapid eye movement sleep behavior disorder.

PURPOSE: The exact phenoconversion time from isolated rapid eye movement (REM) sleep behavior disorder (iRBD) to synucleinopathies remains unpredictable. This study investigated whole-brain dopaminergic damage pattern (DDP) with disease progression and predicted phenoconversion time in individual patients. METHODS: Age-matched 33 iRBD patients and 20 healthy controls with 11C-CFT-PET scans were enrolled. The patients were followed up 2-10 (6.7 ± 2.0) years. The phenoconversion year was defined as the base year, and every 2 years before conversion was defined as a stage. Support vector machine with leave-one-out cross-validation strategy was used to perform prediction. RESULTS: Dopaminergic degeneration of iRBD was found to occur about 6 years before conversion and then abnormal brain regions gradually expanded. Using DDP, area under curve (AUC) was 0.879 (90% sensitivity and 88.3% specificity) for predicting conversion in 0-2 years, 0.807 (72.7% sensitivity and 83.3% specificity) in 2-4 years, 0.940 (100% sensitivity and 84.6% specificity) in 4-6 years, and 0.879 (100% sensitivity and 80.7% specificity) over 6 years. In individual patients, predicted stages correlated with whole-brain dopaminergic levels (r = - 0.740, p < 0.001). CONCLUSION: Our findings suggest that DDP could accurately predict phenoconversion time of individual iRBD patients, which may help to screen patients for early intervention.

A facile and scalable strategy for constructing Janus cotton fabric with persistent antibacterial activity.

Natural cotton fibers have attached considerable attention due to their excellent wearing comfort, breathability and warmth. However, it remains a challenge to devise a scalable and facile strategy to retrofit natural cotton fibers. Here, the cotton fiber surface was oxidized by sodium periodate with a mist process, then [2-(methacryloyloxy) ethyl] trimethylammonium chloride (DMC) was co-polymerized with hydroxyethyl acrylate (HA) to obtain an antibacterial cationic polymer (DMC-co-HA). The self-synthesized polymer was covalently grafted onto the aldehyde-functionalized cotton fibers via an acetal reaction between hydroxyl groups of the polymer and aldehyde groups of the oxidized cotton surface. Finally, the resulted Janus functionalized cotton fabric (JanCF) revealed robust and persistent antimicrobial activity. The antibacterial test showed that when the molar ratio of DMC/HA was 50: 1, JanCF possessed the best BR (bacterial reduction) values of 100 % against Escherichia coli and Staphylococcus aureus. Furthermore, the BR values could be maintained over 95 % even after the durability test. In addition, JanCF exhibited excellent antifungal activity against Candida albicans. The cytotoxicity assessment confirmed that JanCF exhibited a reliable safety effect on human skin. Particularly, the intrinsic outstanding characteristics (strength, flexibility, etc.) of the cotton fabric were not considerably deteriorated compared to the control samples.

Influence of Light-EmittingDiode-Derived Blue Light Overexposure on Rat Ocular Surface.

We aim to investigate the effect of overexposure to blue light on the rat ocular surface and explore the potential mechanisms. 450 nm light-emitting diode (LED) derived light at 1000 lux was used to irradiate SD rats, 12 hours a day, for consecutive 28 days. Rats in the control group were exposed to 400 lux white light at the same time (in an indoor environment). Tear film breakup time (TBUT), tear volume, and corneal fluorescein staining scores were used to measure the changes to the ocular surface. Expressions of nuclear factor-κB (NF-κB), inhibitor-κB (I-κB), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by real-time PCR, and the activation of the NF-κB pathway was detected by Western blotting, respectively. Cornea ultrastructure was examined by TEM and optical microscope on day 28. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB signaling pathway, was used to measure the inhibition of blue light injury. The above indexes were detected again when compared with the solvent-treated group. On day 28, compared with day 0, the TBUT of the blue light group was significantly shorter, and the score was significantly higher. The amount of tear secretion changed slightly with time. HE and PAS staining revealed significantly decreased corneal epithelial cell layers and increased goblet cells after 28-day irradiation of blue light. Disarranged stromal cells, vacuoles in the basal nuclei, and decreased desmosomes were also found in the blue light group. Significantly increased levels of NF-κB, IL-6, TNF-α, and the ratio of phosphorylated NF-κB p65 (pNF-κB p65) to total NF-κB p65 implied blue light-induced damage and pathway activation. In addition, PDTC significantly reduced the phosphorylation of NF-κB activated in blue light-treated corneas and alleviated the ocular surface changes caused by blue light. Finally, our results demonstrated that long-term blue light exposure in rats could cause ocular surface changes and manifest as dry eye. Inflammation and activation of the NF-κB pathway may play a role in the pathogenesis.

Facile Strategy for Constructing Highly Thermally Conductive Epoxy Composites Based on a Salt Template-Assisted 3D Carbonization Nanohybrid Network.

The construction of an interconnected nanofiller network is critical for the preparation of highly effective thermal management composites, though it remains a challenge to eliminate the anisotropic thermal conductivity of the nanofiller-induced defective interfacial heat-flow efficiency. In this work, a facile and novel approach is proposed to optimize phonon transport by building a salt template-assisted three-dimensional (3D) carbonization nanohybrid network in an epoxy system. The advantage of the salt template relied on green and scalable merits to construct a 3D nanofiller network and supporting abundant holes for the introduction of a polymer matrix after washing. Meanwhile, the contained carbonization materials contributed to reducing the interfacial phonon scattering issues of the filler/filler and filler/polymer for an efficient heat-flow pathway. As a result of this effect, the prepared epoxy nano-composites presented a high thermal conductivity of 4.27 W/m K, resulting in a 1841% increase compared to the thermal conductivity of the pure epoxy resin. In addition, the epoxy composites exhibited good mechanical properties and thermal conductive performance during heating and cooling. Therefore, this study may provide new insights into the design and preparation of thermal management polymers to meet the applicational requirements of electronics.

Association of Plasma and Electroencephalography Markers With Motor Subtypes of Parkinson's Disease.

Objective: The aim of this study was to investigate the correlations of plasma neurodegenerative proteins and electroencephalography (EEG) dynamic functional network (DFN) parameters with disease progression in early Parkinson's disease (PD) with different motor subtypes, including tremor-dominant (TD) and postural instability and gait disorder (PIGD). Methods: In our study, 33 patients with PD (21 TD and 12 PIGD) and 33 healthy controls (HCs) were enrolled. Plasma neurofilament light chain (NfL), α-synuclein (α-syn), total-tau (t-tau), ß-amyloid 42 (Aß42), and ß-amyloid 40 (Aß40) levels were measured using an ultrasensitive single-molecule array (Simoa) immunoassay. All the patients with PD underwent EEG quantified by DFN analysis. The motor and non-motor performances were evaluated by a series of clinical assessments. Subsequently, a correlation analysis of plasma biomarkers and EEG measures with clinical scales was conducted. Results: In the TD group, plasma NfL exhibited a significant association with MDS-UPDRS III and Montreal Cognitive Assessment (MoCA). A higher Aß42/40 level was significantly related to a decrease in Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) in the PIGD group. In terms of the correlation between EEG characteristic parameters and clinical outcomes, trapping time (TT) delta was positively correlated with MDS-UPDRS III and MoCA scores in the TD group, especially in the prefrontal and frontal regions. For other non-motor symptoms, there were significant direct associations of k PLI theta with HAMD and HAMA, especially in the prefrontal region, and k PLI gamma was particularly correlated with Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores in the prefrontal, frontal, and parietal regions in the TD group. Furthermore, there was a significant positive correlation between plasma t-tau and k PLI , and pairwise correlations were found among plasma NfL, theta TT, and MoCA scores in the TD group. Conclusion: These results provide evidence that plasma neurodegenerative proteins and EEG measures have great potential in predicting the disease progression of PD subtypes, especially for the TD subtype. A combination of these two kinds of markers may have a superposition effect on monitoring and estimating the prognosis of PD subtypes and deserves further research in larger, follow-up PD cohorts.

Prolyl Isomerization-Mediated Conformational Changes Define ATR Subcellular Compartment-Specific Functions.

ATR is a PI3K-like kinase protein, regulating checkpoint responses to DNA damage and replication stress. Apart from its checkpoint function in the nucleus, ATR actively engages in an antiapoptotic role at mitochondria following DNA damage. The different functions of ATR in the nucleus and cytoplasm are carried out by two prolyl isomeric forms of ATR: trans- and cis-ATR, respectively. The isomerization occurs at the Pin1 Ser428-Pro429 motif of ATR. Here, we investigated the structural basis of the subcellular location-specific functions of human ATR. Using a mass spectrometry-based footprinting approach, the surface accessibility of ATR lysine residues to sulfo-NHS-LC-biotin modification was monitored and compared between the cis- and the trans-isomers. We have identified two biotin-modified lysine residues, K459 and K469, within the BH3-like domain of cis-ATR that were not accessible in trans-ATR, indicating a conformational change around the BH3 domain between cis- and trans-ATR. The conformational alteration also involved the N-terminal domain and the middle HEAT domain. Moreover, experimental results from an array of complementary assays show that cis-ATR with the accessible BH3 domain was able to bind to tBid while trans-ATR could not. In addition, both cis- and trans-ATR can directly form homodimers via their C-terminal domains without ATRIP, while nuclear (trans-ATR) in the presence of ATRIP forms dimer-dimer complexes involving both N- and C-termini of ATR and ATRIP after UV. Structural characteristics around the Ser428-Pro429 motif and the BH3 domain region are also analyzed by molecular modeling and dynamics simulation. In support, cis conformation was found to be significantly more energetically favorable than trans at the Ser428-Pro429 bond in a 20-aa wild-type ATR peptide. Taken together, our results suggest that the isomerization-induced structural changes of ATR define both its subcellular location and compartment-specific functions and play an essential role in promoting cell survival and DNA damage responses.

Expression and clinical significance of CXCL17 and GPR35 in endometrial carcinoma.

Endometrial carcinoma is one of the most common gynecologic malignancies. CXCL17-CXCR8 (GPR35) axis is reported to play an indispensability role in tumors. Our purpose is to screen possible prognostic and immune-related factors in endometrial carcinoma by detecting the mRNA and protein expression of CXCL17 and CXCR8. We use the qRT-PCR method to test the mRNA expression of CXCL17 and CXCR8 in 35 pairs of endometrial carcinoma and adjacent tissue. The protein expression of CXCL17 and CXCR8 in 30 cases of normal proliferative endometrium, 30 cases of endometrial atypical hyperplasia and 50 cases of endometrial carcinoma was detected by tissue microarray immunohistochemistry. There was no significant difference in the positive expression rate between endometrial adenocarcinoma tissue and endometrial atypical hyperplasia tissue (P > 0.05). But significantly better than normal proliferative tissue (P < 0.001). Correlation analysis of CXCR8 and CXCL17 in endometrial carcinoma showed a positive correlation (r = 0.9123, P < 0.0001). For patients with endometrial cancer, the overall survival (OS) of patients with high CXCL17 expression was significantly higher than that low CXCL17 expression (log-rank test, P < 0.0001), whereas CXCR8 had no statistical significance. But the expression of CXCR8 is an independent prognostic factor of OS in endometrial carcinoma patients. Our study showed that CXCL17 and CXCR8 may be involved in the occurrence and development of endometrial cancer. High expression of CXCL17 may be used as a biomarker for predicting survival. Because CXCL17 and CXCL18 are related to lymphocytes and immune regulation, they are expected to become potential targets for immunotherapy.

CKMT1A is a novel potential prognostic biomarker in patients with endometrial cancer.

PURPOSE: The International Federation of Gynecology and Obstetrics (FIGO) stage remains the standard staging system for the assessment of endometrial cancer (EC) prognosis. Thus, we aim to identify the significant genes or biomarkers associated with the stage of endometrial cancer, which may also help reveal the mechanism of EC progression and assess the prognosis of patients with EC. MATERIALS AND METHODS: We compared the mRNA expression levels of EC patients with stages I and II as well as stages III and IV in the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) of EC patients at different stages were selected by volcano plot and Venn analysis. Gene Ontology (GO) and Pathways were applied to analyze the identified genes. Protein protein interaction (PPI) network was employed to identify the correlation. The survival analyses based on TCGA database were conducted for further screening. The Human Protein Atlas, quantitative PCR and immunohistochemistry were utilized to confirm the differences in expression of DEGs in endometrial cancer samples at different FIGO stages. RESULTS: CKMT1A was identified as a candidate gene. Through survival analyses, we found that CKMT1A may be a poor prognostic factor in the overall survival of endometrial cancer patients. GO and Pathways revealed that CKMT1A is closely associated with the metabolic process. More importantly, Human Protein Atlas and quantitative PCR confirmed the differences in expression of CKMT1A in endometrial cancer samples at different FIGO stages. CONCLUSION: In summary, this study shows that CKMT1A is a newly identified essential tumor progression regulator of endometrial cancer, which may give rise to novel therapeutic strategies in the management of endometrial cancer patients to prolong its prognosis and prevent tumor progression.

Differentiation of paediatric posterior fossa tumours by the multiregional and multiparametric MRI radiomics approach: a study on the selection of optimal multiple sequences and multiregions.

OBJECTIVE: To evaluate the diagnostic performance of a radiomics model based on multiregional and multiparametric MRI to classify paediatric posterior fossa tumours (PPFTs), explore the contribution of different MR sequences and tumour subregions in tumour classification, and examine whether contrast-enhanced T1 weighted (T1C) images have irreplaceable added value. METHODS: This retrospective study of 136 PPFTs extracted 11,958 multiregional (enhanced, non-enhanced, and total tumour) features from multiparametric MRI (T1- and T2 weighted, T1C, fluid-attenuated inversion recovery, and diffusion-weighted images). These features were subjected to fast correlation-based feature selection and classified by a support vector machine based on different tasks. Diagnostic performances of multiregional and multiparametric MRI features, different sequences, and different tumoral regions were evaluated using multiclass and one-vs-rest strategies. RESULTS: The established model achieved an overall area under the curve (AUC) of 0.977 in the validation cohort. The performance of PPFTs significantly improved after replacing T1C with apparent diffusion coefficient maps added into the plain scan sequences (AUC from 0.812 to 0.917). When oedema features were added to contrast-enhancing tumour volume, the performance did not significantly improve. CONCLUSION: The radiomics model built by multiregional and multiparametric MRI features allows for the excellent distinction of different PPFTs and provides valuable references for the rational adoption of MR sequences. ADVANCES IN KNOWLEDGE: This study emphasized that T1C has limited added value in predicting PPFTs and should be cautiously adopted. Selecting optimal MR sequences may help guide clinicians to better allocate acquisition sequences and reduce medical costs.

Effective degradation of VOCs from wood by Fe2+ chelate activated dual oxidant (H2O2-PS).

Wood is rich in extractives and volatile oils that emit unpleasant odors and some harmful volatile organic compounds (VOCs). Chemical oxidation technologies processes high efficiency on the destruction of aqueous organic components via oxidation by radicals, however, wood block treatment scenarios suffer from the low availability of radicals in aqueous conditions owing to the special structure of the wood blocks, limitations of mass transfer and the short life of free radicals. Herein, ethylenediaminetetraacetic acid (EDTA) is selected as a chelating agent to synthesize EDTA-Fe2+ chelate, thus introducing Fe2+ into the wood by vacuum impregnation. The Fe2+ is evenly distributed and immobilized in the wood to form a chemical oxidation system via in-situ activation of the dual oxidant (H2O2-PS), which truncates the contact distance between free radicals and extractives/volatile oils thus enhancing the removal efficiency. Various controlling factors, including EDTA/Fe2+ molar ratio, Fe2+dosage, PS/H2O2 molar ratio, and persulfate (PS) dosage are evaluated. The degradation products of VOCs by headspace solid-phase micro-extraction combined with gas chromatography-mass spectrometry (HS-SPME/GC-MS) indicate that the wood VOC removal rate is ∼80%. The Electron paramagnetic resonance (EPR) analysis further reveals that SO4-· and ·OH are the primary reactive species. The characterization of wood properties illustrates that the process has no destructive effect. The results of this work may provide a theoretical basis for feasibility of the practical application of the EDTA-Fe2+/H2O2-PS system.

Factors Correlated with the Accuracy of Colposcopy-Directed Biopsy: A Systematic Review and Meta-Analysis.

PURPOSE/AIM OF THE STUDY: Colposcopy-directed cervical biopsy has played a major role in diagnosing cervical lesions. The precision of colposcopy-guided biopsy has been questioned. We analyzed several factors that may be correlated with the accuracy of biopsy. METHODS: PubMed, EMBASE were searched from January 1, 1998 to March 1, 2020. Odds ratio with 95% confidence intervals (CIs) were calculated. SELECTION CRITERIA: Included studies evaluated factors correlated with the accuracy of biopsy and patients' final diagnosis was established by histological examination of the specimen obtained by conization, loop electrosurgical excision procedure (LEEP), or colpohysterectomy. RESULTS: A total of 10 studies were selected for the systematic review and meta-analysis. The pooled analysis indicated that the diagnostic inaccuracies of colposcopy-directed cervical biopsy were magnified in women who were 50 years of age or older. Postmenopausal status and transformation zone 3 type were also associated with the diagnostic inaccuracies of colposcopy-directed biopsy. High-grade squamous intraepithelial lesions had better concordance rates than low-grade squamous intraepithelial lesions. The number of vaginal deliveries, number of biopsies, and HPV type were associated with biopsy underdiagnosis and biopsy overestimation. CONCLUSIONS: This meta-analysis found that the correlation between the histological findings at biopsy and after surgical treatment was influenced by women's age, menopausal status, and the transformation zone type. The diagnostic efficacy was also better for high-grade squamous intraepithelial lesions than for low-grade squamous intraepithelial lesions. Further large-scale randomized clinical trials are required to analyze the factors correlated with biopsy underdiagnosis and biopsy overestimation.

Effect of Tai Chi on cardiac function in patients with myocardial infarction: A protocol for a randomized controlled trial.

BACKGROUND: Myocardial infarction is 1 of the most serious cardiovascular diseases. Early interventional therapy preserves the cardiac function of patients with myocardial infarction to the greatest extent, but it is far from meeting people's need only limited to cardiac revascularization. It is also necessary to help patients improve their quality of life, exercise tolerance, and reduce the incidence of acute cardiac recurrence as much as possible. All these depend on cardiac rehabilitation (CR) are based on exercise. Early and correct CR helps to improve the patient's heart function and improve living standards. Traditional Chinese exercise Tai Chi as an alternative form of CR has gradually become popular, but it lacks large samples and high-quality clinical studies to verify it. This study aims to explore the effect of Tai Chi on the cardiac function of patients with myocardial infarction, and to provide a strong basis for patients to choose which CR exercise. METHODS: This is a prospective randomized controlled trial. 272 patients with myocardial infarction will be randomly divided into an experimental group and a control group according to 1:1, with 136 cases in each group. The control group: conventional treatment; the experimental group: increase Tai Chi exercise on the basis of the control group. Both groups will receive standard treatment for 24 weeks and will be followed up for 3 months. Observation indicators include: total effective rate, 6 minutes walking test, brain natriuretic peptide, left ventricular ejection fraction, the adverse reaction rate, etc. The data will be analyzed by using SPSS 25.0 software. DISCUSSION: This study will evaluate the effect of Tai Chi on the cardiac function of patients with myocardial infarction. The results of this test will provide clinical evidence for patients to choose which CR exercise. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/QKWDP.

Accurate segmentation for different types of lung nodules on CT images using improved U-Net convolutional network.

ABSTRACT: Since lung nodules on computed tomography images can have different shapes, contours, textures or locations and may be attached to neighboring blood vessels or pleural surfaces, accurate segmentation is still challenging. In this study, we propose an accurate segmentation method based on an improved U-Net convolutional network for different types of lung nodules on computed tomography images.The first phase is to segment lung parenchyma and correct the lung contour by applying α-hull algorithm. The second phase is to extract image pairs of patches containing lung nodules in the center and the corresponding ground truth and build an improved U-Net network with introduction of batch normalization.A large number of experiments manifest that segmentation performance of Dice loss has superior results than mean square error and Binary_crossentropy loss. The α-hull algorithm and batch normalization can improve the segmentation performance effectively. Our best result for Dice similar coefficient (0.8623) is also more competitive than other state-of-the-art segmentation algorithms.In order to segment different types of lung nodules accurately, we propose an improved U-Net network, which can improve the segmentation accuracy effectively. Moreover, this work also has practical value in helping radiologists segment lung nodules and diagnose lung cancer.

Low expression of developing brain homeobox 2 (Dbx2) may serve as a biomarker to predict poor prognosis in endometrial cancer.

OBJECTIVE: For investigating Dbx2's expression in endometrial cancer (EC) and its effect on prognosis of patients with EC. METHODS: A comparison was performed in the Cancer Genome Atlas (TCGA) database in terms of the expression profiling of EC and the survival data. To obtain differential expression genes (DEGs), Volcano plot and Venn analysis were adopted. DEGs function was performed by carrying out the GO annotation analysis (GO) and gene set enrichment analysis (GSEA). In clinical EC samples, PCR was applied to the verification of Dbx2's expression. RESULTS: Dbx2 was a downregulated expression in tumor tissues. Dbx2 can have a poor prognosis role in EC by regulating the apoptotic signaling pathway and the immune pathway. Lower expression of Dbx2 was related to lymph node metastasis and FIGO stage. CONCLUSION: Dbx2 is downregulated in endometrial cancer, which serves as a biomarker to predict poor prognosis.

miR-140-5p Aggravates Insulin Resistance via Directly Targeting GYS1 and PPP1CC in Insulin-Resistant HepG2 Cells.

BACKGROUND: Much attention has been paid to the regulatory role of microRNA (miRNA) in insulin resistance. Nevertheless, how miR-140-5p regulates insulin resistance remains unclear. In this research, we aim to investigate the roles of miR-140-5p in insulin resistance. METHODS: qRT-PCR is used to analyze the expression level of miR-140-5p in insulin-resistant HepG2 cells. Glucose consumption and glucose uptake are detected to study the effect of miR-140-5p knockdown in insulin-resistant HepG2 cells and miR-140-5p overexpression in HepG2 cells. Bioinformatic analysis, luciferase reporter assay and confirmatory experiments are applied to identify the target gene bound with miR-140-5p and study the effect of miR-140-5p on the downstream substrates of target genes. Rescue experiments have verified the roles of miR-140-5p and target gene in glucose metabolism. RESULTS: The expression level of miR-140-5p was upregulated in insulin-resistant HepG2 cells and was significantly correlated with cellular glucose metabolism. Functionally, miR-140-5p overexpression induced impairment of glucose consumption and glucose uptake. Besides, bioinformatics analysis indicated that glycogen synthetase (GYS1) and protein phosphatase 1 catalytic subunit gamma (PPP1CC) were the target genes of miR-140-5p. Western blotting and qRT-PCR results revealed a negative correlation between GYS1, PPP1CC and miR-140-5p. The glycogen detection results showed that miR140-5p inhibited the production of the downstream substrates of the target gene. Rescue experiments showed that inhibition of GYS1 or PPP1CC partially enhanced the insulin-resistant effects of miR-140-5p knockdown in insulin-resistant HepG2 cells. CONCLUSION: miR-140-5p overexpression augments the development of insulin resistance and miR-140-5p may be served as a therapeutic target of metabolic diseases.

Direct and indirect parameter imaging methods for dynamic PET.

The method of reconstructing parametric images from dynamic positron emission tomography (PET) data with the linear Patlak model has been widely used in scientific research and clinical practice. Whether for direct or indirect image reconstruction, researchers have deeply investigated the associated methods and effects. Among the existing methods, the traditional maximum likelihood expectation maximization (MLEM) reconstruction algorithm is fast but produces a substantial amount of noise. If the parameter images obtained by the MLEM algorithm are postfiltered, a large amount of image edge information is lost. Additionally, although the kernel method has a better noise reduction effect, its calculation costs are very high due to the complexity of the algorithm. Therefore, to obtain parametric images with a high signal-to-noise ratio (SNR) and good retention of detailed information, here, we use guided kernel means (GKM) and dynamic PET image information to conduct guided filtering and perform parametric image reconstruction. We apply this method to direct and indirect reconstruction, and through computer simulations, we show that our proposed method has higher identifiability and a greater SNR than conventional direct and indirect reconstruction methods. We also show that our method produces better images with direct than with indirect reconstruction.

Magnetic resonance imaging reconstruction algorithm under complex convolutional neural network in diagnosis and prognosis of cerebral infarction.

This study was to explore the application value of magnetic resonance imaging (MRI) image reconstruction model based on complex convolutional neural network (CCNN) in the diagnosis and prognosis of cerebral infarction. Two image reconstruction methods, frequency domain reconstruction network (FDRN) and image domain reconstruction network (IDRN), were introduced based on the CCNN algorithm. In addition, they were integrated to form two new MRI image reconstruction models, namely D-FDRN and D-IDRN. The peak signal to noise ratio (PSNR) value and structural similarity index measure (SSIM) value of the image were compared and analyzed before and after the integration. The MRI images of patients with cerebral infarction in the dataset were undertaken as the data source, the average diffusion coefficient (DCavg) and apparent diffusion coefficient (ADC) values of different parts of the MRI image were measured, respectively. The correlation of the vein abnormality grading (VABG) to the infarct size and the degree of stenosis of the responsible vessel was analyzed in this study. The results showed that the PSNR and SSIM values of the MRI reconstructed image of the D-IDRN algorithm based on the CCNN algorithm in this study were higher than those of other algorithms. There was a positive correlation between the VABG and the infarct size (r = 0.48 and P = 0.002), and there was a positive correlation between the VABG the degree of stenosis of the responsible vessel (r = 0.58 and P < 0.0001). The ADC value of the central area of the infarct on the affected side was significantly greatly lower than that of the normal side (P < 0.01), and the DCavg value of the central area of the infarct was much lower in contrast to the normal side (P < 0.05). It indicated that an image reconstruction algorithm constructed in this study could improve the quality of MRI images. The ADC value and DCavg value changed in the infarct central area could be used as the basis for the diagnosis of cerebral infarction. If the vein was abnormal, the patient suffered from severe vascular stenosis, large infarction area, and poorer prognosis.