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PURPOSE: To compare clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) created with the single covered-uncovered stent (Viatorr TIPS Endoprosthesis) versus covered stent (Fluency) versus a combination of covered and uncovered stent. MATERIALS AND METHODS: From May 2016 and July 2019, a total of 180 liver cirrhosis patients with recurrent variceal bleeding underwent TIPS creation with single covered-uncovered stent (n = 63) or covered stent (n = 41) or a covered and uncovered stent combination (n = 76). Shunt dysfunction, rebleeding, overt hepatic encephalopathy and mortality was estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The difference of baseline characteristics among these three groups were not significant. The included patients had a median age of 51 years (IQR 43-61), and 101 (56.1%) were men. The 1-year and 2-year shunt dysfunction rates were 1.6% and 3.2% in the single covered-uncovered stent group, 7.3% and 7.3% in the covered stent group and 5.3% and 6.6% in the combination group, respectively. There was no significant difference among groups [Hazard Ratio (HR) (95%CI): 1 vs 2.29 (0.38 - 13.72) vs 2.10 (0.41 - 10.83); P = 0.913]. No significant differences in the incidence of all-cause rebleeding were observed between the groups at 1 year (Viatorr vs Fluency vs combination: 11.1% vs 17.1% vs 10.5%) as well as 2 years (15.9% vs 17.1% vs 11.8%), with the HR (95%CI) being 1 vs 1.27 (0.5-3.21) vs 0.74 (0.30-1.82); P = 0.475). The 1-year and 2-year incidence of overt hepatic encephalopathy were 30.2% and 30.2% in the single covered-uncovered stent group, 22.0% and 22.0% in the covered stent group and 25.0% and 25.0% in the combination group, respectively. However, there was no significant difference among these three groups (P = 0.402). In addition, there was no significant difference in the 1-year and 2-year mortality (6.3% and 7.9% vs. 4.9% and 9.8% vs. 6.6% and 9.2%, P = 0.606). CONCLUSION: No significant difference was observed among different stent groups. Fluency covered stent and the generic bare stent/Fluency covered stent was not an unreasonable alternative to the Viatorr stent for TIPS creation.
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Ti3 C2 Tx Quantum dots (QDs)/L-Ti3 C2 Tx fiber electrode (Q3 M7 ) with high capacitance and excellent flexibility is prepared by a wet spinning method. The assembled units Ti3 C2 Tx nanosheets (NSs) with large size (denoted as L-Ti3 C2 Tx ) is obtained by natural sedimentation screen raw Ti3 AlC2 , etching, and mechanical delamination. The pillar agent Ti3 C2 Tx QDs is fabricated by an ultrasound method. Q3 M7 fiber electrode gave a specific capacitance of 1560 F cm-3 , with a capacity retention rate of 79% at 20 A cm-3 , and excellent mechanical strength of 130 Mpa. A wide temperature all-solid-state the delaminated montmorillonite (F-MMT)/Polyvinyl alcohol (PVA) dimethyl sulfoxide (DMSO) flexible hydrogel (DHGE) (F-MMT/PVA DHGE) Q3 M7 fiber supercapacitor is assembled by using Q3 M7 fiber as electrodes and F-MMT/PVA DHGE as electrolyte and separator. It showed a volume specific capacitance of 413 F cm-3 at 0.5 A cm-3 , a capacity retention of 97% after 10 000 cycles, an energy density of 36.7 mWh cm-3 at a power density of 311 mW cm-3 , and impressive capacitance and flexibility over a wide temperature range of -40 to 60 °C. This work provides an effective strategy for designing and assembling wide temperature all-solid-state fiber supercapacitors with optimal balance of capacitive performance and flexibility.
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Primary liver cancer (PLC) that originates in the liver is a malignant tumor with the worst prognosis. Hepatocellular carcinoma (HCC) is the most common type of PLC. Most PLC cases are diagnosed at advanced stages mainly due to their insidious onset and rapid progression. Patients with PLC undergo surgical intervention or localized treatment, but their survival is often affected by its high relapse rate. Medical treatment is the primary option for patients with liver cancer, especially with advanced extrahepatic metastases. Molecular targeted therapy exerts an anti-tumor effect by acting on various signaling pathways involved in molecular pathogenesis; however, high drug resistance and low therapeutic responsiveness of PLC to molecular targets challenge the treatment option. In recent years, after surgical intervention, radiotherapy, chemotherapy, and/or molecular targeted therapy, autologous cell immunotherapy has been adopted for PLC. As a typical autologous cell immunotherapy, CAR T-cell therapy uses genetically modified T cells to express tumor-specific chimeric antigen receptors (CARs). Its targeting ability, persistent nature, and tumor-killing function result in a significant impact on the treatment of hematological tumors. However, no breakthrough has happened in the research specific to the curation of lung cancer, liver cancer, breast cancer, and other common solid tumors. In this context, a combination of molecular targeted therapy and CAR T-cell therapy was used to treat a patient with advanced HCC to achieve a partial remission(PR) and facilitate further liver transplantation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patologia , Imunoterapia Adotiva , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas/metabolismo , Linfócitos T , Receptores de Antígenos de Linfócitos T , Recidiva Local de Neoplasia/metabolismoRESUMO
Photo-assisted Li-O2 batteries are introduced as a promising strategy for reducing severe overpotential by directly employing photocathodes. Herein, a series of size-controlled single-element boron photocatalysts are prepared by the meticulous liquid phase thinning methods by combining probe and water bath sonication, and their bifunctional photocathodes in the photo-assisted Li-O2 batteries are systematically investigated. The boron-based Li-O2 batteries have shown incremental round-trip efficiencies as the sized reduction of boron under illumination. It is noteworthy that the completely amorphous boron nanosheets (B4 ) photocathode not only delivers an optimizing round-trip efficiency of 190% on the basis of the ultra-high discharge voltage (3.55 V) and ultra-low charge voltage (1.87 V) but also gives a high rate performance and ultralong durability with a round-trip efficiency of 133% after 100 cycles (200 h) compared with the other-sized boron photocathodes. This remarkable photoelectric performance of the B4 sample can be attracted to the synergistic effect on the suitable semiconductor property, high conductivity, and strengthened catalytic ability of boron nanosheets coated with ultrathin amorphous boron-oxides overlayer. This research can open a new avenue to facilitate the rapid development of high-efficiency photo-assisted Li-O2 batteries.
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All-solid-state Ti3C2Tx neutral symmetric fiber supercapacitors (PVA EGHG Ti3C2Tx FSCs) with high energy density and wide temperature range are constructed by using polyvinyl alcohol (PVA)-ethylene glycol hydrogel (EGHG)-sodium perchlorate (NaClO4) as electrolyte and separator, and Ti3C2Tx fiber as electrodes. Ti3C2Tx fiber is prepared using 130 mg mL-1 Ti3C2Tx nanosheet ink as an assembly unit in a coagulation bath of isopropyl alcohol (IPA) and distilled water with 5 wt% CaCl2 by a wet spinning method. The prepared Ti3C2Tx fiber exhibits a specific capacity of 385 F cm-3 and a capacitance retention of 94 % after 10,000 cycles in 1 M NaClO4 electrolyte. The assembled PVA EGHG Ti3C2Tx FSCs deliver a specific capacitance of 41 F cm-3, a volumetric energy density of 5 mWh cm-3, and a capacitance retention of 92 % after 500 times continuous bending. Furthermore, it shows good flexibility and excellent capacitance over a wide temperature range of -40 to 40 °C and maintains its electrochemical performance under varying degrees of bending. This study provides a viable strategy for designing and assembling all-solid-state neutral symmetric fiber supercapacitors with high energy density and wide temperature range.
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Due to the lack of high-quality Sika Deer (Cervus nippon) transcriptome and sRNAome across multiple organs or development stages, it is impossible to comprehensively analyze the mRNA and miRNA regulatory networks related to growth, development and immunity response. In this study, we used single molecule-real time sequencing (SMRT-seq) and Illumina sequencing methods to generate transcriptome and sRNAome from ten tissues and four age groups of Sika Deer to help us understand molecular characteristics and global miRNA expression profiles. The results showed that a total of 240,846 consensus transcripts were generated with an average length of 2,784 bp. 4,329 Transcription factors (TFs), 109,000 Simple Sequence Repeats (SSRs) and 18,987 Long non-coding RNAs (LncRNAs) were identified. Meanwhile, 306 known miRNAs and 143 novel miRNAs were obtained. A large number of miRNAs showed organ-specific and age-specific differential expression patterns. In particular, we found that the organ-specific miRNAs were enriched in the brain, some of which shared only between the brain and adrenal. These miRNAs were involved in maintaining specific functions within the brain and adrenal. By constructing miRNA96mRNA interaction networks associated with Sika Deer immunity, we found that miRNAs (miR-148a, miR-26a, miR-214, let-7b, etc.) and mRNAs (CD6, TRIM38, C3, CD163, etc.) might play an important role in the immune response of Sika Deer spleen. Together, our study generated an improved transcript annotation for Sika Deer by SMRT-seq and revealed the role of miRNA in regulating the growth, development and immunity response of Sika Deer.
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Background: Hepatocellular carcinoma (HCC) remains a worldwide burden. However, the mechanisms behind the malignant biological behavior of HCC remain unclear. The homeobox (HOX) family could act as either promoters or suppressors in different kinds of malignancies. Our study discovered the role of HOXB5 in regulating HCC progression. Methods: The HOXB5 expression was assessed by RT-PCR analysis in human HCC samples and cell lines. HOXB5 transcriptional regulation of the EGFR was verified by the luciferase reporter assay and chromatin immunoprecipitation experiment. The oncogenic role of HOXB5 in HCC progression was analyzed by CCK8, colony-forming, and transwell assays. Results: Upregulation of HOXB5 was found in human HCC, and was strongly correlated with HCC tumor size, tumor-nodule metastasis, TNM stage, and relatively unfavorable OS and DFS. Ectopic expression of HOXB5 promoted the capacity of cell growth and clonogenicity, while the inhibition of HOXB5 decreased the proliferation and clonogenicity potential in vitro by CCK8 and colony-forming assays. In addition, HOXB5 also promoted cell migration by transwell experiment. Mechanism studies elucidated that HOXB5 triggers HCC progression via direct transcriptional activation of EGFR. The upregulation of HOXB5 is regulated by miR-200a-3p and miR-181-5p. Transfection of miR-200a-3p and miR-181-5p mimics blocked the cell proliferation and migration regulated by HOXB5, while overexpression of the 3'-UTR mutant HOXB5 abolished the suppressive effect of miR-200a-3p and miR-181-5p, but not the wild-type HOXB5. Conclusion: HOXB5 is a promising prognostic factor in human HCC. Targeting miR-200a-3p and the miR-181-5p/HOXB5/EGFR signaling pathway may provide new options for the treatment strategies of HCC.
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To elucidate the complex physiological process of testis development and spermatogenesis in Sika deer, this study evaluated the changes of miRNA and mRNA profiles in the four developmental stages of testis in the juvenile (1-year-old), adolescence (3-year-old), adult (5-year-old), and aged (10-year-old) stages. The results showed that a total of 198 mature, 66 novel miRNAs, and 23,558 differentially expressed (DE) unigenes were obtained; 14,918 (8,413 up and 6,505 down), 4,988 (2,453 up and 2,535 down), and 5,681 (2,929 up and 2,752 down) DE unigenes, as well as 88 (43 up and 45 down), 102 (44 up and 58 down), and 54 (18 up and 36 down) DE miRNAs were identified in 3- vs. 1-, 5- vs. 3-, and 10- vs. 5-year-old testes, respectively. By integrating miRNA and mRNA expression profiles, we predicted 10,790 mRNA-mRNA and 69,883 miRNA-mRNA interaction sites. The target genes were enriched by GO and KEGG pathways to obtain DE mRNA (IGF1R, ALKBH5, Piwil, HIF1A, BRDT, etc.) and DE miRNA (miR-140, miR-145, miR-7, miR-26a, etc.), which play an important role in testis development and spermatogenesis. The data show that DE miRNAs could regulate testis developmental and spermatogenesis through signaling pathways, including the MAPK signaling pathway, p53 signaling pathway, PI3K-Akt signaling pathway, Hippo signaling pathway, etc. miR-140 was confirmed to directly target mutant IGF1R-3'UTR by the Luciferase reporter assays. This study provides a useful resource for future studies on the role of miRNA regulation in testis development and spermatogenesis.
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Hepatocellular carcinoma (HCC) is one of the most common cancers. MicroRNA has been studied more and more deeply and may become a new target for the treatment of HCC. Here, we investigated the role of miR-455-3p in HCC progression. Compared with non-tumor tissues and normal human hepatic cells, miR-455-3p expression was significantly downregulated in HCC tissues and cell lines. And overexpression of miR-455-3p inhibited cell proliferation and migration but promoted cell apoptosis in HCC cell lines HepG2 and Huh7. Mechanism studies displayed that miR-455-3p targeted HDAC2 and negatively regulated HDAC2 expression. Moreover, HDAC2 was highly expressed in HCC tissues and cell lines. Overexpression of HDAC2 reversed the inhibitory effects of miR-455-3p on cell proliferation, migration and cell cycle protein (CDK6 and cyclin D1) expression, and neutralized the promotion effects of miR-455-3p on cell apoptosis and the activation of p53 pathway. Furthermore, a p53 inhibitor Pifithrin-α (PFT-α) effectively abolished the effects of miR-455-3p on HCC cell behaviors. Additionally, the role of miR-455-3p in tumorigenesis was evaluated by using a mouse xenograft model, and the data showed that miR-455-3p suppressed tumor growth in vivo. In summary, our results suggested that miR-455-3p targeted HDAC2 to inhibit cell proliferation, migration and promote cell apoptosis via the activation of p53 pathway.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Histona Desacetilase 2/genética , Histona Desacetilase 2/metabolismo , Humanos , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Developing and designing bifunctional electrocatalysts are very important for the production of hydrogen from water electrolysis. The reasonable interface modulation can effectively lead to the optimization of electronic configuration through the interface electron transfer in the heterostructures and thus resulting in the enhanced efficiency. In this work, self-supported and heterogeneous interface-rich Ni3S2@FeNi2S4@NF electrocatalyst for overall water splitting was designed and prepared through a controllable step-wise hydrothermal process. Density functional theory calculations suggest that heterogeneous interface formed between Ni3S2 and FeNi2S4 can optimize the Gibbs free energy for H* adsorption (ΔGH*). Benefiting from the open structure of the nanosheet arrays, the abundant heterogeneous interfaces in Ni3S2@FeNi2S4@NF composite, the positive synergistic effect between Ni3S2 and FeNi2S4, and the good conductivity of foamed nickel (NF) substrate, the optimized Ni3S2@FeNi2S4@NF nanoarray catalyst displayed excellent electrocatalytic activities, the overpotential is only 83 mV and 235 mV for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) at 10 mA cm-2, respectively. Importantly, an alkaline electrolyser directly using the Ni3S2@FeNi2S4@NF as both the anode and cathode achieved an ultralow cell voltage of 1.46 V, accompanied by outstanding stability. The performance is better than that of most other transition-metal sulfides electrocatalysts. This work may provide a useful strategy for reasonably regulating heterogeneous interfaces to effectively improve the performance of materials, thus accelerating the practical application of transition-metal sulfides electrocatalysts for overall water splitting.
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BACKGROUND: Upregulation of circHIPK3 has been observed in several kinds of malignancies. However, the mechanisms of circHIPK3 in HCC metastases remains unclear. We investigated the role and the mechanisms of circHIPK3 in the development of HCC. METHODS: HCC tissues and paired adjacent non-tumor tissues of surgical patients were used to evaluate circHIPK3 expression. A series of biological experiments had been taken to evaluate the pro-metastatic ability of circHIPK3 during HCC development in vitro and in vivo. The potential mechanisms of circHIPK3 in HCC development were identified by RT-qPCR, Western blot, RIP, and luciferase reporter assays. RESULTS: CircHIPK3 expression is significantly upregulated during HCC development. Overexpression of circHIPK3 promotes cell migration, invasion, and metastases in vitro and in vivo. CircHIPK3 promoted HCC metastases by sponging miR-338-3p to regulate EMT-associated proteins E-cadherin, vimentin, and ZEB2 expression. CONCLUSION: CircHIPK3 plays a regulatory role in metastatic HCC by sponging miR-338-3p to induce ZEB2 expression, thus promoting EMT procession.
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Carcinoma Hepatocelular/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , RNA Circular/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias Experimentais , Proteínas Serina-Treonina Quinases/genética , RNA Circular/genética , Regulação para Cima , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genéticaRESUMO
Duodenal varices are an uncommon presentation of portal hypertension and can result in significant gastrointestinal bleeding with a high mortality. Diagnosis can be difficult and therapeutic options limited. We present a case of upper gastrointestinal bleeding in a woman aged 54 years with primary biliary cholangitis who was ultimately diagnosed with ectopic duodenal variceal bleed, which was successfully treated with transjugular intrahepatic portosystemic shunt. Transjugular intrahepatic portosystemic shunt provide an effective treatment for ectopic duodenal variceal bleed caused by liver cirrhosis, though interventional radiologists need to remain aware of and vigilant for the complications and risks of this treatment option.
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Ovarian tumour domain containing 6B antisense RNA1 (OTUD6B-AS1), a newly identified long noncoding RNA (lncRNA), has been reported as a key cancer-related lncRNA. However, the detailed relevance of OTUD6B-AS1 in hepatocellular carcinoma (HCC) remains undetermined. This study was designed to determine the functional significance and regulatory mechanism of OTUD6B-AS1 in HCC. We found that the expression of OTUD6B-AS1 was up-regulated in HCC tissues, and patients with high levels of OTUD6B-AS1 expression had shorter survival rates than those with low OTUD6B-AS1 expression. Elevated expression of the lncRNA was also found in multiple HCC cell lines and the silencing of OTUD6B-AS1 significantly decreased proliferation, colony formation and invasion. Correspondingly, OTUD6B-AS1 overexpression had the opposite effect on HCC cell invasion, colony formation and proliferation. Notably, OTUD6B-AS1 was identified as a molecular sponge of microRNA-664b-3p (miR-664b-3p). The down-regulation of miR-664b-3p was detected in HCC tissues and cell lines, and the up-regulation of miR-664b-3p repressed proliferation and invasion in HCC cells by targeting the glycogen synthase kinase-3ß interaction protein (GSKIP). Moreover, OTUD6B-AS1 knockdown or miR-664b-3p up-regulation exerted a suppressive effect on Wnt/ß-catenin signalling via the down-regulation of GSKIP. In addition, GSKIP overexpression markedly reversed OTUD6B-AS1 knockdown- or miR-664b-3p overexpression-induced antitumour effects in HCC. Further data confirmed that OTUD6B-AS1 knockdown exerted a tumour-inhibition role in HCC in vivo. Overall, these findings indicate that the lncRNA OTUD6B-AS1 accelerates the proliferation and invasion of HCC cells by enhancing GSKIP/Wnt/ß-catenin signalling via the sequestration of miR-664b-3p. Our study reveals a novel molecular mechanism, mediated by lncRNA OTUD6B-AS1, which may play a key role in regulating the progression of HCC.
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Carcinoma Hepatocelular/genética , MicroRNAs/genética , Neoplasias Ovarianas/genética , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Endopeptidases/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Via de Sinalização Wnt/genética , beta Catenina/metabolismoRESUMO
The recovery property of asphalt binders plays an important role in the performance and service life of asphalt pavements. Since the internal stress is the driving force for the recovery of asphalt binders, the accurate measurement of the internal stress is full of significance. Based on this rationale, this paper aims to measure the internal stress of asphalt binders using a creep and step-loading recovery (CSR) test and characterizing the recovery behaviors by the internal stress. One base asphalt binder and one styrene-butadiene-styrene (SBS)-modified binder are selected in this study. The key elements of the CSR test are carefully designed and its accuracy is verified in three aspects, including the loading conditions, the effect of disturbance by step-loads, and accuracy of measured internal stress. Then, a kinetics-based recovery model is proposed to evaluate and predict the recovery properties of asphalt binders from its causal relationship. The constant-rate recovery activation energy indicates a major difference with nondestructive and destructive loading conditions, while the fast-rate recovery activation energy keeps almost constant regardless of the loading conditions. After that, the healing activation energy is calculated by using the kinetics-based recovery model and the results indicate that SBS modified asphalt binder shows better healing abilities than a base binder.
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With increased awareness of environmental protection, the output of traditional curing agents such as cement and lime is less and less, so it is urgent to develop new curing agents with high efficiency and environmental benefits. Thus, this study aims at investigating the application of rice husk ash (RHA) from agricultural waste to the soft soil stabilization. A series of tests are conducted to analyze the strength development process and soil-water characteristics of rice husk ash-lime (RHA-lime) stabilized soils. The results of the strength tests showed that by increasing the content of RHA, the unconfined compressive strength (UCS) and splitting strength of stabilized soils increased first and then decreased. The effective shear strength indexes of the three soil types (soft soil, lime-stabilized soil, and RHA-lime soil) are measured and compared. It is found that RHA can effectively improve the shear resistance and water resistance of stabilized soil. The results of methylene blue test demonstrated that RHA can also promote the reduction of the specific surface area and swelling potential energy of lime-stabilized soil. In addition, the influence of RHA on mineral composition and morphology change in stabilized soils is studied at the microscopic level. The X-ray diffraction tests and scanning electron microscope (SEM) tests showed that strength development and change of soil-water properties of RHA-lime stabilized soil are attributed to enhanced cohesion by cementation and pores filling with agglomerated mineral.
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Green and renewable organic redox molecules are greatly advantageous over conventional inorganic intercalation electrode materials in terms of electrochemical reversibility and cycling stability. However, their electrical insulation prevents them from being used alone as electrode materials for supercapacitors. Herein, 2-amino-3-chloro-1,4-naphthoquinone (ACNQ) molecules were covalently grafted onto graphene nanosheets (GNS) via diazotization. The ACNQ-functionalized GNS (CNQ-GNS) electrode material exhibited a high specific capacitance of 364.2 ± 10 F g-1 at a current density of 1 A g-1, which is much larger than that of bare GNS (190 ± 6 F g-1). Moreover, the electrode exhibited an outstanding rate capability (capacitance retention of 76.8% at 100 A g-1). Finally, an asymmetric supercapacitor device was fabricated using graphene nanosheets as the positive electrode and the optimized CNQ-GNS as the negative electrode, which displayed a high energy density of 19.1 W h kg-1 at a power density of 0.8 kW kg-1 with a long cycling life span (nearly no loss after 10 000 cycles at 5 A g-1) in 1 M H2SO4 electrolyte. Briefly, the highly conductive GNS scaffold delivers a high electrical double-layer capacitance, while the organic functional groups covalently bonded on the GNS contribute additional faradaic pseudocapacitance, resulting in outstanding electrochemical energy storage.
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Accumulating evidence has suggested that the ataxia telangiectasia group D complementing (ATDC) gene is an emerging cancer-related gene in multiple human cancer types. However, little is known about the role of ATDC in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the expression level, biological function and underlying mechanism of ATDC in HCC. The expression of ATDC in HCC cells was detected by quantitative real-time polymerase chain reaction and western blot analysis. Cell growth was determined by cell counting kit-8 assay and colony formation assay. Cell invasion was assessed by Transwell invasion assay. The activation status of Wnt/ß-catenin signalling was evaluated by the luciferase reporter assay. Functional experiments showed that the silencing of ATDC expression significantly suppressed the growth and invasion of HCC cells, whereas the overexpression of ATDC promoted the growth and invasion of HCC cells in vitro. Moreover, we showed that ATDC overexpression promoted the phosphorylation of glycogen synthase kinase (GSK)-3ß and resulted in the activation of Wnt/ß-catenin signalling. Notably, the inhibition of GSK-3ß activity significantly abrogated the tumour suppressive effect of ATDC silencing, while the silencing of ß-catenin partially reversed the oncogenic effect of ATDC overexpression. Taken together, these findings reveal an oncogenic role of ATDC in HCC and show that the suppression of ATDC impedes the growth and invasion of HCC cells associated with the inactivation of Wnt/ß-catenin signalling. Our study suggests that ATDC may serve as a potential therapeutic target for HCC.
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Carcinoma Hepatocelular/patologia , Proteínas de Ligação a DNA/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Hepáticas/patologia , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Invasividade Neoplásica , Fosforilação , Fator de Transcrição 4/metabolismo , Fatores de Transcrição/deficiência , Fatores de Transcrição/genéticaRESUMO
OBJECTIVES: Early placement of transjugular intrahepatic portosystemic shunt (TIPS) has been shown to improve survival in high-risk patients (Child-Pugh B plus active bleeding at endoscopy or Child-Pugh C 10-13) with cirrhosis and acute variceal bleeding (AVB). However, early TIPS criteria may overestimate the mortality risk in a significant proportion of patients, and the survival benefit conferred by early TIPS in such patients has been questioned. Alternative criteria have been proposed to refine the criteria used to identify candidates for early TIPS. Nevertheless, the true survival benefit provided (or not) by early TIPS compared with standard treatment in the different risk categories has not been investigated in specifically designed comparative studies. DESIGN: We collected data on 1425 consecutive patients with cirrhosis and AVB who were admitted to 12 university hospitals in China between December 2010 and June 2016. Of these, 206 patients received early TIPS, and 1219 patients received standard treatment. The Fine and Gray competing risk regression model was used to compare the outcomes between the two groups that were stratified based on the currently available risk stratification systems after adjusting for liver disease severity and other potential confounders. RESULTS: Overall, early TIPS was associated with an 80% relative risk reduction (RRR) in mortality at 6 weeks (adjusted HR=0.20; 95% CI: 0.10 to 044; p<0.001) and 51% RRR at 1 year (adjusted HR=0.49, 95% CI: 0.32 to 0.73; p<0.001) compared with standard treatment. In stratification analyses, the RRRs in mortality did not significantly differ among the risk categories. However, the absolute risk reductions (ARRs) of mortality were more pronounced in high-risk patients. The ARRs at 6 weeks were -2.1%, -10.2% and -32.4% in Model for End-stage Liver Disease (MELD) ≤11, 12-18 and ≥19 patients and were -1.5%, -9.1% and -23.2% in Child-Pugh A, B and C patients, respectively (interaction tests, p<0.001 for both criteria). The ARRs for mortality at 1 year were -1.7%, -5.4% and -32.7% in MELD ≤11, 12-18 and ≥19 patients, respectively, and -3.6%, -5.2% and -20.3% in Child-Pugh A, B and C patients, respectively (interaction tests, p<0.001 for both criteria). After adjusting for liver disease severity and other potential confounders, a survival benefit was observed in MELD ≥19 or Child-Pugh C patients but not in MELD ≤11 or Child-Pugh A patients. In MELD 12-18 patients, a survival benefit was observed within 6 weeks but not at 1 year. In Child-Pugh B patients, a survival benefit was observed in those with active bleeding but not those without active bleeding. However, the evaluation of active bleeding was associated with a high interobserver variability. Furthermore, early TIPS was associated with a significantly reduced incidence of failure to control bleeding or rebleeding and new or worsening ascites, without increasing the risk of overt hepatic encephalopathy. CONCLUSIONS: Early TIPS was associated with improved survival in patients with MELD ≥19 or Child-Pugh C cirrhosis but not in patients with MELD ≤11 or Child-Pugh A cirrhosis. For MELD 12-18 or Child-Pugh B patients, future studies addressing optimal selection criteria for early TIPS remain highly warranted.
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Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Cirrose Hepática/terapia , Derivação Portossistêmica Transjugular Intra-Hepática , Adulto , Idoso , China , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/mortalidade , Feminino , Hemorragia Gastrointestinal/complicações , Hemorragia Gastrointestinal/mortalidade , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Tempo para o Tratamento , Resultado do TratamentoRESUMO
Herein, the mechanical properties and carbonation durability of engineered cementitious composites (ECC) were studied. For the cost-efficient utilization of ECC materials, different types of specimens were cast with polypropylene (PP) and hydrophilic polyvinyl alcohol (HPVA) fibers. The compressive strength, Poisson’s ratio, strength-deflection curves, cracking/post-cracking strength, impact index, and tensile strain-stress curves of two types of ECC materials, with differing fiber contents of 0 vol %, 1 vol %, 1.5 vol %, and 2 vol %, were investigated with the use of compressive tests, four-point bending tests, drop-weight tests, and uniaxial tensile tests. In addition, the matrix microstructure and failure morphology of the fiber in the ECC materials were studied by scanning electron microscopy (SEM) analysis. Furthermore, carbonation tests and characterization of steel corrosion after carbonization were employed to study durability resistance. The results indicated that for both PP fiber- and HPVA fiber-reinforced ECCs, the compressive strength first increases and then decreases as fiber content increases from 0 vol % to 2 vol %, reaching a maximum at 1 vol % fiber content. The bending strength, deformation capacity, and impact resistance show significant improvement with increasing fiber content. The ECC material reinforced with 2 vol % PP fiber shows superior carbonized durability with a maximum carbonation depth of only 0.8 mm.