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OBJECTIVE: This study aims to analyze the molecular characteristics of the novel coronavirus (SARS-CoV-2) Omicron variant BA.2.76 in Jining City, China. METHODS: Whole-genome sequencing was performed on 87 cases of SARS-CoV-2 infection. Evolutionary trees were constructed using bioinformatics software to analyze sequence homology, variant sites, N-glycosylation sites, and phosphorylation sites. RESULTS: All 87 SARS-CoV-2 whole-genome sequences were classified under the evolutionary branch of the Omicron variant BA.2.76. Their similarity to the reference strain Wuhan-Hu-1 ranged from 99.72 to 99.74%. In comparison to the reference strain Wuhan-Hu-1, the 87 sequences exhibited 77-84 nucleotide differences and 27 nucleotide deletions. A total of 69 amino acid variant sites, 9 amino acid deletions, and 1 stop codon mutation were identified across 18 proteins. Among them, the spike (S) protein exhibited the highest number of variant sites, and the ORF8 protein showed a Q27 stop mutation. Multiple proteins displayed variations in glycosylation and phosphorylation sites. CONCLUSION: SARS-CoV-2 continues to evolve, giving rise to new strains with enhanced transmission, stronger immune evasion capabilities, and reduced pathogenicity. The application of high-throughput sequencing technologies in the epidemic prevention and control of COVID-19 provides crucial insights into the evolutionary and variant characteristics of the virus at the genomic level, thereby holding significant implications for the prevention and control of the COVID-19 pandemic.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pandemics , Genomics , China , Amino Acids , NucleotidesABSTRACT
Hepatoblastoma (HB) is a common primary liver malignant tumor in children. Long non-coding RNAs (lncRNAs) are closely engaged in HB progression. The role and regulatory molecule mechanism of lncRNA small nucleolar RNA host gene 1 (SNHG1) in HB remain unclear. Through qRT-PCR or western blot, we found that SNHG1 and proviral integration site for moloney murine leukemia virus 3 (PIM3) were elevated but miR-6838-5p was decreased in HB cells. Cell biology experiments revealed that SNHG1 depletion or miR-6838-5p upregulation suppressed cell proliferation, migration, and invasion of HB cells. Mechanistically, luciferase activity assay validated that miR-6838-5p could interact with SNHG1 or PIM3. SNHG1 up-regulated PIM3 expression via sponging miR-6838-5p. Moreover, miR-6838-5p inhibitor abolished SNHG1 depletion-mediated suppression of malignant behaviors in HB cells. PIM3 overexpression neutralized miR-6838-5p mimics-mediated repression of malignant phenotypes in HB cells. Furthermore, miR-6838-5p overexpression suppressed RhoA activation, which was restored by PIM3 upregulation. What's more, the results at the cellular level were further verified by nude mice tumor formation experiment. In conclusion, SNHG1 regulated miR-6838-5p/PIM3/RhoA axis to promote malignant phenotypes of HB, which might provide novel therapeutic target for HB treatment.
Subject(s)
Hepatoblastoma , MicroRNAs , RNA, Long Noncoding , Animals , Mice , Child , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Hepatoblastoma/genetics , Mice, Nude , Cell Proliferation/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , Proto-Oncogene Proteins/genetics , Protein Serine-Threonine Kinases/geneticsABSTRACT
Vascular diseases, such as vascular malformations and hemangiomas, are often classified into "fast-flow" and "slow-flow" based on their internal blood velocity. Fast-flow vascular diseases of maxillofacial regions are a kind of complicated and dangerous pathological changes originating from or containing arteries, their treatment is often complex and different from disease to disease, and large amounts of intraoperative blood loss and poor operation field may cause side injury or other problems without a detailed map of the lesion. The authors use the combination of color Doppler ultrasound and three-dimensional computed tomography angiography to diagnose and classify 36 cases of maxillofacial fast-flow vascular diseases, from January 2018 to December 2022 presented in the authors' department. Three-dimensional computed tomography angiography can display the location, type, and blood supply of lesions, whereas color Doppler ultrasound has unique advantages in identifying some special lesions (such as the colorful images of orificium fistulaes and the "Yin-yang sign" of pseudoaneurysms), then projecting and marking them on the body surface, which greatly facilitate the surgical procedure. This cost-effective and noninvasive combination shows significant clinical application value.
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We aimed to examine impacts and functional mechanism of circular RNA forkhead box N2 (FOXN2) in tacrolimus (TAC)- and dexamethasone (Dex)-induced lipid metabolism disorders. RNA level and protein contents in TAC, Dex, or combined TAC- plus Dex-treated patients and Huh-7 cells were measured utilizing quantitative real-time (qRT)-PCR and western blotting assays measured the formation of lipid droplet. Total cholesterol (TC) and triglyceride (TG) levels were determined using corresponding commercial kits and Oil red O staining. RNA immunoprecipitation and RNA pull-down verified the binding relationship among circFOXN2, polypyrimidine tract binding protein 1 (PTBP1) and fatty acid synthase (FASN). Male C57BL/6 mice were used to establish a dyslipidemia mouse model to validate the discoveries at the cellular level. Dex treatment significantly promoted TAC-mediated increase of TC and TG in serum samples and Huh-7 cells. Moreover, circFOXN2 was reduced but FASN was elevated in TAC-treated Huh-7 cells, and these expression trends were markedly enhanced by Dex cotreatment. Overexpression of circFOXN2 could reverse the accumulation of TC and TG and the upregulation of FASN and sterol regulatory element binding transcription factor 2 (SREBP2) mediated by Dex and TAC cotreatment. Mechanistically, circFOXN2 reduced FASN mRNA stability by recruiting PTBP1. The protective roles of circFOXN2 overexpression on lipid metabolism disorders were weakened by FASN overexpression. In vivo finding also disclosed that circFOXN2 greatly alleviated the dysregulation of lipid metabolism triggered by TAC plus Dex. CircFOXN2 alleviated the dysregulation of lipid metabolism induced by the combination of TAC and Dex by modulating the PTBP1/FASN axis.NEW & NOTEWORTHY Collectively, our experiments revealed for the first time that circFOXN2 alleviated the Dex- and TAC-induced dysregulation of lipid metabolism by regulating the PTBP1/FASN axis. These findings suggested that circFOXN2 and FASN might be candidate targets for the treatment of Dex- and TAC-induced metabolic disorders.
Subject(s)
Dyslipidemias , Liver Transplantation , Mice , Animals , Male , Glucocorticoids , Tacrolimus/metabolism , Mice, Inbred C57BL , Fatty Acid Synthases , Dyslipidemias/chemically induced , Dyslipidemias/drug therapy , Dyslipidemias/genetics , RNA/metabolism , RNA Stability , Liver/metabolismABSTRACT
Hepatitis B virus (HBV) infection and type-2 diabetes mellitus (T2DM) affect millions of individuals worldwide, whereas their interplay remains largely unclear. Here, we analyzed a large cohort of 330 HBV-infected inpatients with T2DM (so-called HBV + T2DM patients) and 330 T2DM inpatients without HBV infection (T2DM patients). Poor glycemic control was defined by glycated hemoglobin (HbA1c) ≥ 7%. Among 330 HBV + T2DM patients, 252 (76%) aged ≥ 50 years, 223 (68%) were males, 205 (62%) experienced poor glycemic control. The propensity-score matching approach was applied to match patient age, gender, comorbidities, and antidiabetic treatment between T2DM + HBV and T2DM patients. Compared with T2DM patients, HBV + T2DM patients had poorer glycemic control, longer hospitalization length, and higher alanine aminotransferase (p < 0.05). HBV + T2DM patients with HBV DNA ≥ 100 IU/mL or HBsAg ≥ 0.05 IU/mL had worse HbA1c control than T2DM patients without HBV infection (p < 0.05). HBV + T2DM patients who received no anti-HBV therapy had worse HbA1c control than HBV + T2DM patients receiving anti-HBV therapy (p < 0.05). Both insulin and anti-HBV therapy were significant factors associated with glycemic control in HBV + T2DM patients. Overall, HBV + T2DM patients exhibited poorer glycemic control than T2DM patients, but their clinical outcomes were likely improved by insulin plus anti-HBV treatment. Early management of HBV infection likely contributes to better clinical outcomes in HBV-infected patients with T2DM.
Subject(s)
Diabetes Mellitus, Type 2 , Hepatitis B , Male , Humans , Female , Retrospective Studies , Glycated Hemoglobin , Glycemic Control , Blood Glucose , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Hepatitis B/complications , Hepatitis B/drug therapy , Insulin/therapeutic use , Hepatitis B virus/geneticsABSTRACT
The unique magnetic field environment during electromagnetic launch imposes higher requirements on the design and protection of the internal electronic system within the launch load. This low-frequency, Tesla-level extreme magnetic field environment is fundamentally distinct from the Earth's geomagnetic field. The excessive change rate of magnetic flux can readily induce voltage within the circuit, thus disrupting the normal operation of intelligent microchips. Existing simulation methods primarily focus on the physical environments of rails and armatures, making it challenging to precisely compute the magnetic field environment at the load's location. In this paper, we propose a computational rail model based on the magneto-mechanical coupling model of a railgun. This model accounts for the dynamic current distribution during the launch process and simulates the magnetic flux density distribution at the load location. To validate the model's accuracy, three-axis magnetic sensors were placed in front of the armature, and the dynamic magnetic field distribution during the launch process was obtained using the projectile-borne-storage testing method. The results indicate that compared to the previous literature methods, the approach proposed in this paper achieves higher accuracy and is closer to experimental results, providing valuable support for the design and optimization of the launch load.
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For many years, Shiliu Buxue Syrup (SLBXS) has been used in the treatment of anemia in Xinjiang, China. However, the potential therapeutic mechanism of SLBXS in the treatment of anemia remains unclear. We qualitatively analyzed the ingredients of SLBXS and predicted the underlying mechanisms by network pharmacology. A mice model of anemia was established by subcutaneous injection of 1-Acetyl-2-phenylhydrazine (APH). Spleen metabolomics was performed to screen potential biomarkers and pathways related to anemia. Furthermore, core targets of crucial pathways were experimentally validated. Finally, molecular docking was used for predicting interactions between compositions and targets. Network pharmacology indicated that the 230 SLBXS ingredients may affect 141 target proteins to regulate the PI3K/AKT and HIF-1 signaling pathways. Metabolomics revealed that SLBXS could mediate 30 biomarkers, such as phosphoric acid, l-pyroglutamic acid, alpha-Tocopherol, 1-stearoyl-rac-glycerol, and dihydroxyacetone phosphate, to regulate drug metabolism-other enzymes, glutathione metabolism, glycolysis or gluconeogenesis, nicotinate and nicotinamide metabolism, nitrogen metabolism, and purine metabolism. Western blot indicated that SLBXS can regulate the protein expression levels of AKT1, Bcl2, Caspase3, HIF-1α, VEGF-A, and NOS2. The molecular docking revealed that most of the compositions had a good binding ability to the core targets. Based on these findings, we speculate that SLBXS treats anemia mainly by modulating the PI3K/AKT and HIF-1 pathways and glutathione and glycolytic metabolisms.
Subject(s)
Anemia , Drugs, Chinese Herbal , Anemia/drug therapy , Animals , Biomarkers , Drugs, Chinese Herbal/pharmacology , Glutathione , Metabolomics , Mice , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-aktABSTRACT
Ferroelectric materials have aroused the researchers' great interest due to their wide applications. Here, a displacement-type ferroelectric-ferroelectric phase transition material [(NH3)(CH2)3(NH3)]2[InBr6]Br·H2O (1) with Tc = 143 K was successfully prepared. The ferroelectric phase transition is verified by the characterization techniques such as differential scanning calorimetry, single-crystal structure elucidation, dielectric and ferroelectric measurements. The single-crystal structure elucidation reveals that the displacement and distortion of [(NH3)(CH2)3(NH3)]2+ cations lead to the phase transition from Cmc21 to Pca21. The spontaneous polarizations at 293 and 133 K are 0.15 and 0.12 µC·cm-2, respectively. We expect that this work will help in further exploration of some new ferroelectric materials.
ABSTRACT
The in vitro experiments of TGF-ß1 and the results of RT-PCR could not be repeated. In order not to affect others, the authors have asked for a retraction. Reference: Qiang Yin, Shan Liu, Anbing Dong, Xiufang Mi, Fengyun Hao, Kejun Zhang. Targeting Transforming Growth Factor-Beta1 (TGF-ß1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFkappakB-PUMA Signaling. Med Sci Monit 2016; 22: 2267-2277. DOI: 10.12659/MSM.898702.
ABSTRACT
Aiming at the application of laser active imaging detection technology, this paper studied the beam homogenization system of a semiconductor laser based on a homogenizing pipe. Firstly, the principle of the homogenizing pipe was introduced. Secondly, the homogenization effect, which was influenced by several geometric parameters (aperture size, length, and taper) of the homogenizing pipe using the optical design software, was simulated for the fiber-coupled semiconductor laser. Finally, according to the simulated results, a laser illumination system composed of a fiber-coupled semiconductor laser, a homogenizing pipe, and an aspheric lens was designed, which can obtain a rectangular uniform light spot in a long distance. The effectiveness of the illumination system was verified by simulation and experiment, respectively. Simulation results suggested that the uniformity of the spot at a distance of 20 m was 85.6%, while divergence angle was 10 mrad. The uniformity of the spot at a distance of 120 m was 91.5%, while divergence angle was 10 mrad. Experimental results showed that the uniformity of the spot at a distance of 20 m was 87.7%, while divergence angle was 13 mrad. The uniformity of the spot at a distance of 120 m was 93.3%, while divergence angle was 15 mrad. The laser illumination system designed in this paper was simple and easy to assemble, and has strong practicability. The results in this paper have certain reference value and guiding significance for the homogenization design of semiconductor lasers.
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This work aimed to develop and evaluate a post-acquisition data processing strategy, referred to as a mass defect filter (MDF), for rapid target the resin glycosides in root of Convolvulus scammonia by setting mass rang and mass defect range from high-resolution MS data. The full-scan mass data were acquired by high-performance liquid chromatography coupled with Q Exactive Plus hybrid quadrupole-orbitrap mass spectrometer that featured high resolution, mass accuracy, and sensitivity. To screen resin glycosides, three parent filter m/z 871, m/z 853, and m/z 869 combined with diagnostic fragment ions (DFIs) approach were applied to remove the interference from complex herbal extract. The targeted components were characterized based on detailed fragment ions. Using this approach, 80 targeted components, including 22 glycosidic acids and 58 resin glycosides were tentatively identified. The present results suggested that the proposed MDF strategy would be adaptable to the analysis of complex system in relevant filed.
Subject(s)
Convolvulus , Glycosides , Chromatography, High Pressure Liquid/methods , Glycosides/chemistry , Ions , Mass Spectrometry/methods , Resins, PlantABSTRACT
BACKGROUND: This study aimed to probe and verify aberrantly methylated and expressed genes in hepatoblastoma and to analyze their interactions with tumor immune microenvironment. METHODS: Aberrantly methylated and expressed genes were obtained by comprehensively analyzing gene expression and DNA methylation profiles from GSE81928, GSE75271 and GSE78732 datasets. Their biological functions were predicted by the STRING and Metascape databases. CIBERSORT was utilized for inferring the compositions of tumor-infiltrating immune cells (TIICs) in each sample. Correlation between hub genes and immune cells was then analyzed. Hub genes were validated in hepatoblastoma tissues via western blot or immunohistochemistry. After transfection with sh-NOTUM, migration and invasion of HuH-6 and HepG2 cells were investigated. The nude mouse tumorigenesis model was constructed. RESULTS: Totally, 83 aberrantly methylated and expressed genes were determined in hepatoblastoma, which were mainly involved in metabolic and cancer-related pathways. Moreover, their expression was liver-specific. 13 hub genes were screened, which were closely related to immune cells in hepatoblastoma tissues. Among them, it was confirmed that AXIN2, LAMB1 and NOTUM were up-regulated and SERPINC1 was down-regulated in hepatoblastoma than normal tissues. NOTUM knockdown distinctly weakened migration and invasion of HuH-6 and HepG2 cells and tumor growth in vivo. CONCLUSIONS: This study identified aberrantly methylated and expressed signatures that were in relation to immune microenvironment in hepatoblastoma. Targeting NOTUM hub gene could suppress migration and invasion of hepatoblastoma cells. Thus, these aberrantly methylated and expressed genes might act as therapeutic agents in hepatoblastoma therapy.
Subject(s)
Gene Expression , Hepatoblastoma/genetics , Liver Neoplasms/genetics , Tumor Microenvironment/genetics , Animals , Antithrombin III/genetics , Axin Protein/genetics , Cell Line, Tumor , Cell Movement/genetics , DNA Methylation , Databases, Genetic , Down-Regulation , Epigenesis, Genetic , Epigenomics , Esterases/genetics , Hep G2 Cells , Hepatoblastoma/immunology , Humans , Laminin/genetics , Liver Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating , Male , Mice , Mice, Nude , Neoplasm Invasiveness/genetics , Protein Interaction Maps , Tumor Microenvironment/immunology , Up-RegulationABSTRACT
The influence of multiple dimensional carbon nanomaterials, such as graphene quantum dots (GQD), multi-walled carbon nanotubes (MWCNT), and graphene sheets (GNS) of the thermoelectric properties in poly(3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT: PSS)-based hybrids have been investigated. PEDOT: PSS matrix was successfully used to prepare PEDOT: PSS/GQDs (PGQD), PEDOT: PSS/MWCNT (PCNT) and PEDOT: PSS/GNS (PGNS) composite films. According to structural characteristics, strongπ-πinteractions existed between carbon materials and PEDOT: PSS, and PEDOT: PSS layers with organized and arranged morphology were easier templated by GNS than GQD or MWCNT. It was found that besides energy filtering effect, hole-phonon interaction occurred with further addition of GNS and GQDs in PGNS and PGQD composite films. The optimal power factor (PF) of approximately 580 and 103µW m-1K-2at 363 K were acquired in PGNS composite films at 5 wt% GNS and PGQD films with 1 wt% GQD filling, respectively. Unlike PGNS and PGQD films, electrical conductivity of PCNT reduced upon the addition of MWCNT, while the Seebeck coefficient decreased firstly, and then increased and reached to the highest value at 10 wt% MWCNT. The optimal PF of 381.8µW m-1K-2at 363 K was obtained with weight fraction of 0.1 wt% in PCNT films.
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It is of great significance to circumvent the inherent trade-off between strength and extensibility for epoxy resins. Herein dynamic Cu-benzotriazole cross-links are incorporated, as the appropriate intermolecular coordination interaction, into high performance epoxy networks, and the resulting epoxy resins exhibits outstanding thermal stability and mechanical properties, their strength and extensibility are simultaneously improved. Additionally, local manipulation of coordination crosslinking confers the film with anti-counterfeiting function.
Subject(s)
Epoxy Resins , Polymers , TriazolesABSTRACT
In recent decades, little progress of objective evaluation of pain and noxious stimulation has been achieved under anesthesia. Some researches based on medical signals have failed to provide a general understanding of this problem. This paper presents a feature extraction method for heart rate variability signals, aiming at further improving the evaluation of noxious stimulation. In the process of data processing, the empirical mode decomposition is used to decompose and recombine heart rate variability signals, and the sliding time window approach is used to extract the signal features of noxious stimulation, respectively. The influence of window size on feature extraction is studied by changing the window size. By comparing the results, the feature extraction in the process of data processing is valuable, and the selection of window size has a significant impact. With the increase of selected window sizes, we can get better detection results. But for the best choice of window size, to ensure the accuracy of the results and to make it easy to use, then, we need to get just a suitable window size.
Subject(s)
Anesthesia, General , Heart Rate/physiology , Monitoring, Physiologic/methods , Noxae , Adolescent , Adult , Electrocardiography , Female , Humans , Male , Middle Aged , Signal Processing, Computer-Assisted , Time Factors , Young AdultABSTRACT
Here, we report a case of postoperative recurrence of gallbladder carcinoma (GBC) in a patient who declined systemic chemotherapy. ATM S1905Ifs*25 and STK11 K262Sfs*25 mutations were detected by next-generation sequencing. Oral administration of olaparib was initiated. One month later, the patient experienced relief of clinical symptoms, a decrease in CA19-9 level, and a reduction in abnormal signal in the subcapsular region. The tumor response remained stable for approximately 13 months. This is the first case to demonstrate the clinical benefits of olaparib treatment in a patient with GBC harboring an ATM-inactivating mutation. This observation helps to better inform treatment options to enhance the care of patients with advanced GBC. KEY POINTS: A patient with gallbladder carcinoma harboring an ATM-inactivating mutation responded to olaparib with a progression-free survival of 13 months. This is the first report that demonstrates the clinical benefits of olaparib treatment in a patient with gallbladder carcinoma with an ATM-inactivating mutation. It also highlights the importance of next-generation sequencing, which can provide valuable information for planning effective targeted therapies for gallbladder carcinoma. Evidence-based decisions help determine the best choice of treatment for individualized patient care.
Subject(s)
Gallbladder Neoplasms , Ataxia Telangiectasia Mutated Proteins/genetics , Gallbladder Neoplasms/drug therapy , Gallbladder Neoplasms/genetics , Humans , Mutation , Neoplasm Recurrence, Local , Phthalazines , Piperazines , Treatment OutcomeABSTRACT
OBJECTIVE: This study is performed to explore the role of transcription factor FOXM1 in promoting the self-renewal and proliferation of liver cancer stem cells (LCSCs) by regulating the expression of acetaldehyde dehydrogenase-2 (ALDH2). METHODS: CD133+ CD24+ LCSCs were sorted and identified. A series of experiments were carried out to determine the proliferation, colony formation rate, migration, invasion, and apoptosis of LCSCs after interfering with FOXM1. Proliferation-, epithelial-mesenchymal transition (EMT)-, apoptosis-, and stemness-related factors were then detected by western blot analysis. Tumor xenograft in nude mice was used to figure out the role of FOXM1 in tumorigenesis in vivo by regulating ALDH2 expression. Luciferase activity assay was conducted to determine whether FOXM1 could target ALDH2 promoter region and thereby affecting ALDH2 expression. RESULTS: The sorted CD133+ CD24+ Huh-7 cells had the characteristic of stem cells. FOXM1 was highly expressed in CD133+ CD24+ Huh-7 cells. Silencing FOXM1 inhibited the proliferation and colony formation of LCSCs and decreased the expression of proliferating cell nuclear antigen and Ki-67 protein; inhibited the migration, invasion, and EMT of LCSCs while promoting the apoptosis of LCSCs, as well as promoted the expression of Bax and cleaved-caspase-3, and inhibited the expression of Bcl-2. Silencing FOXM1 inhibited the expression of Nanog, Oct4, and Sox2 in LCSCs by decreasing the expression of ALDH2. in vivo experiment, silencing FOXM1 suppressed tumorigenesis of LCSCs by decreasing the expression of ALDH2. CONCLUSION: Our study provides evidence that silencing FOXM1 inhibits stemness of LCSCs by decreasing the expression of ALDH2, and represses the proliferation, migration, invasion, and tumorigenesis while inducing the apoptosis of LCSCs.
Subject(s)
Aldehyde Dehydrogenase, Mitochondrial/metabolism , Carcinoma, Hepatocellular/pathology , Cell Movement , Cell Proliferation , Forkhead Box Protein M1/metabolism , Gene Expression Regulation, Neoplastic , Neoplastic Stem Cells/pathology , Aldehyde Dehydrogenase, Mitochondrial/genetics , Animals , Apoptosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Transformation, Neoplastic , Epithelial-Mesenchymal Transition , Forkhead Box Protein M1/genetics , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice , Neoplasm Invasiveness , Neoplastic Stem Cells/metabolism , Signal Transduction , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: MiR-203 has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB. METHODS: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3'UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively. RESULTS: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression. CONCLUSION: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy.
Subject(s)
Hepatoblastoma/genetics , Liver Neoplasms/genetics , MicroRNAs/genetics , Neovascularization, Pathologic/genetics , RNA, Long Noncoding/genetics , Vascular Endothelial Growth Factor A/genetics , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/metabolism , Up-Regulation , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Ventricular septal defect is the most common type of CHD, and transcatheter ventricular septal defect closure has been shown to be an alternative to surgical closure with acceptable mortality and morbidity as well as encouraging results. Short-term and mid-term follow-ups have indicated the safety and efficacy of transcatheter closure, but long-term follow-up results were rare. In this report, we first found that aortic regurgitation occurred in patients 9-12 years following transcatheter closure and regurgitation were gradually increased. The findings indicate that the long-term outcome of transcatheter closure of ventricular septal defect may not be as satisfied as expected.
Subject(s)
Aortic Valve Insufficiency/etiology , Cardiac Catheterization/adverse effects , Cardiac Surgical Procedures/adverse effects , Heart Septal Defects, Ventricular/surgery , Postoperative Complications , Septal Occluder Device/adverse effects , Aortic Valve Insufficiency/diagnosis , Cardiac Catheterization/methods , Child , Child, Preschool , Female , Follow-Up Studies , Heart Septal Defects, Ventricular/diagnosis , Humans , Male , Time FactorsABSTRACT
The high density, large capacity, and long-term stability of DNA molecules make them an emerging storage medium that is especially suitable for the long-term storage of large datasets. The DNA sequences used in storage need to consider relevant constraints to avoid nonspecific hybridization reactions, such as the No-runlength constraint, GC-content, and the Hamming distance. In this work, a new nonlinear control parameter strategy and a random opposition-based learning strategy were used to improve the Harris hawks optimization algorithm (for the improved algorithm NOL-HHO) in order to prevent it from falling into local optima. Experimental testing was performed on 23 widely used benchmark functions, and the proposed algorithm was used to obtain better coding lower bounds for DNA storage. The results show that our algorithm can better maintain a smooth transition between exploration and exploitation and has stronger global exploration capabilities as compared with other algorithms. At the same time, the improvement of the lower bound directly affects the storage capacity and code rate, which promotes the further development of DNA storage technology.