97 research outputs found

    CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma

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    BackgroundThe physiological regulatory functions of circRNAs have become a topic of intensive research in recent years. Increasing evidence supports a significant role of circRNAs during cancer initiation and progression, including hepatocellular carcinoma (HCC).Materials and MethodsA bioinformatics analysis from three independent Gene Expression Omnibus (GEO) databases was performed to profile and screen the dysregulated circRNAs in HCC. RT-qPCR was used to examine the expression level of circUBAP2 in HCC and adjacent non-tumor tissues. Then, proliferation assays (CCK8 and colony formation) and migration assays (transwell and wound healing) were performed to examine effect of circUBAP2 in vitro. Immunoprecipitation, RNA pulldown, FISH, and dual-luciferase reporter assay was conducted to explore the circUBAP2-related mechanism for regulating HCC progression. Moreover, a mouse xenograft model and a mouse lung metastasis model confirmed the effect of circUBAP2 in vivo.ResultsIn this study, we found a novel circRNA: circUBAP2, which was identified by bioinformatics analysis. Among 91 HCC patients, circUBAP2 was significantly upregulated in HCC tissues, and negatively correlated with aggressive clinical characteristics and prognosis. Functional assays demonstrated that circUBAP2 promoted cell proliferation, colony formation, migration, and invasion in vitro. Moreover, circUBAP2 enhanced tumor growth and pulmonary metastasis in vivo. Mechanistically, circUBAP2 acts as a competing endogenous RNA (ceRNA) for miR-194-3p, a tumor suppressor in HCC. We confirmed that MMP9 was direct target for miR-194-3p, which was regulated by circUBAP2.ConclusionCircUBAP2 plays a significant role in promoting HCC via the miR-194-3p/MMP9 pathway and could serve as a promising prognostic biomarker and novel therapeutic target for HCC patients

    Sphingosine kinase 1–mediated inhibition of Fas death signaling in rheumatoid arthritis B lymphoblastoid cells

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    Objective It is becoming increasingly apparent that B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). Due to the scarcity of B cells in RA, it has been technically difficult to functionally characterize B cell apoptosis in this disease. As a necessary first step to identify candidate aberrations, we investigated Fas-mediated signaling events in immortalized peripheral blood B lymphoblastoid cell lines (LCLs) from patients with RA and controls. Methods Cell death was determined by the MTS assay, and apoptosis was detected by the TUNEL assay and DNA laddering. Proteolytic activation of caspase 3 was determined by immunoblotting, and its enzymatic activity was determined by a fluorometric technique. Messenger RNA (mRNA) expression was quantified by real-time polymerase chain reaction (PCR) analysis. The functional role of sphingosine kinase (SPHK) was determined by measuring its enzymatic activity, by quantifying the levels of its product, sphingosine 1-phosphate (S1P), and by investigating the ability of the SPHK inhibitor N , N -dimethylsphingosine and isozyme-specific small interfering RNA (siRNA) oligonucleotides to reverse signaling aberrations. Results LCLs from patients with RA displayed disease-specific Fas-mediated signal transduction impairment with consequent resistance to cell death. RA LCLs displayed high constitutive SPHK activity and increased levels of S1P. Real-time PCR analysis showed higher SPHK-1 mRNA expression levels in RA patients compared with paired controls. Increased SPHK-1 (but not SPHK-2) mRNA levels were observed in synovial tissue from RA patients. Competitive inhibitors of SPHK reversed the resistance of RA LCLs to Fas-induced apoptosis. Additionally, resistance to Fas-mediated signaling was reversed by siRNA oligonucleotides specific for SPHK-1 but not by oligonucleotides specific for SPHK-2. Conclusion These findings demonstrate disease-specific resistance to Fas-mediated death signaling in patients with RA and implicate increased SPHK-1 activity as the cause of this aberration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49513/1/21635_ftp.pd

    Automated Mapping of Ms 7.0 Jiuzhaigou Earthquake (China) Post-Disaster Landslides Based on High-Resolution UAV Imagery

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    The Ms 7.0 Jiuzhaigou earthquake that occurred on 8 August 2017 triggered hundreds of landslides in the Jiuzhaigou valley scenic and historic-interest area in Sichuan, China, causing heavy casualties and serious property losses. Quick and accurate mapping of post-disaster landslide distribution is of paramount importance for earthquake emergency rescue and the analysis of post-seismic landslides distribution characteristics. The automatic identification of landslides is mostly based on medium- and low-resolution satellite-borne optical remote-sensing imageries, and the high-accuracy interpretation of earthquake-triggered landslides still relies on time-consuming manual interpretation. This paper describes a methodology based on the use of 1 m high-resolution unmanned aerial vehicle (UAV) imagery acquired after the earthquake, and proposes a support vector machine (SVM) classification method combining the roads and villages mask from pre-seismic remote sensing imagery to accurately and automatically map the landslide inventory. Compared with the results of manual visual interpretation, the automatic recognition accuracy could reach 99.89%, and the Kappa coefficient was higher than 0.9, suggesting that the proposed method and 1 m high-resolution UAV imagery greatly improved the mapping accuracy of the landslide area. We also analyzed the spatial-distribution characteristics of earthquake-triggered landslides with the influenced factors of altitude, slope gradient, slope aspect, and the nearest faults, which provided important support for the further study of post-disaster landslide distribution characteristics, susceptibility prediction, and risk assessment.This work was funded by the National Key Research and Development Program of China (Project No. 2018YFC1505202), the National Natural Science Foundation of China (41941019), the State Key Laboratory of Geohazard Prevention and Geoenvironment Protection Independent Research Project (SKLGP2020Z012), the project on identification and monitoring of potential geological hazards with remote sensing in Sichuan Province (510201202076888) and the Everest Scientific Project at Chengdu University of Technology (2020ZF114103)

    Defect-enriched iron fluoride-oxide nanoporous thin films bifunctional catalyst for water splitting

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    Developing cost-effective electrocatalysts operated in the same electrolyte for water splitting, including oxygen and hydrogen evolution reactions, is important for clean energy technology and devices. Defects in electrocatalysts strongly influence their chemical properties and electronic structures, and can dramatically improve electrocatalytic performance. However, the development of defect-activated electrocatalyst with an efficient and stable water electrolysis activity in alkaline medium remains a challenge, and the understanding of catalytic origin is still limited. Here, we highlight defect-enriched bifunctional eletrocatalyst, namely, three-dimensional iron fluoride-oxide nanoporous films, fabricated by anodization/fluorination process. The heterogeneous films with high electrical conductivity possess embedded disorder phases in crystalline lattices, and contain numerous scattered defects, including interphase boundaries, stacking faults, oxygen vacancies, and dislocations on the surfaces/interface. The heterocatalysts efficiently catalyze water splitting in basic electrolyte with remarkable stability. Experimental studies and first-principle calculations suggest that the surface/edge defects contribute significantly to their high performance

    UV RESISTANCE LOCUS 8 From Chrysanthemum morifolium Ramat (CmUVR8) Plays Important Roles in UV-B Signal Transduction and UV-B-Induced Accumulation of Flavonoids

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    UV Resistance Locus 8 (UVR8), an ultraviolet-B (UV-B; 280–315 nm) photoreceptor, participates in the regulation of various plant growth and developmental processes. UV-B radiation is an important factor enhancing the production of active components in medicinal plants. To-date, however, studies on UV-B photoreceptors have largely focused on Arabidopsis, and the functions of UVR8 in medicinal plants are still largely unknown. In the present study, a homolog of Arabidopsis UVR8, CmUVR8, was isolated from Chrysanthemum morifolium Ramat, and its structure and function were analyzed in detail. Protein sequence analysis showed that CmUVR8 contained nine conserved regulators of chromosome condensation 1 repeats, seven conserved bladed propellers, one C27 region, three “GWRHT” motifs and several crucial amino acid residues (such as 14 Trps and 2 Args), similar to AtUVR8. 3-D structural analysis of CmUVR8 indicated that its structure was similar to AtUVR8. Heterologous expression of CmUVR8 could rescued the deficient phenotype of uvr8-6, a mutant of UVR8 in Arabidopsis, indicating the role of CmUVR8 in the regulation of hypocotyl elongation and HY5 gene expression under UV-B irradiation. Moreover, CmUVR8 regulates UV-B-induced expression of four flavonoids biosynthesis-related genes and the UV-B-induced accumulation of flavonoids. Furthermore, the interaction between CmUVR8 and CmCOP1 were confirmed using a yeast two-hybrid assay. These results indicated that CmUVR8 plays important roles in UV-B signal transduction and the UV-B-induced accumulation of flavonoids, as a counterpart of AtUVR8

    Regulatory Mechanisms of the Wnt/β-Catenin Pathway in Diabetic Cutaneous Ulcers

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    Skin ulcers are a serious complication of diabetes. Diabetic patients suffer from vascular lesions and complications such as peripheral neuritis, peripheral vascular lesions, and collagen abnormalities, which result in skin wounds that are refractory and often develop into chronic ulcers. The healing of skin ulcers requires an inflammatory reaction, wound proliferation, remodeling regulation, and control of stem cells. Studies investigating diabetic cutaneous ulcers have focused on cellular and molecular levels. Diabetes can cause nerve and blood vessel damage, and persistent high blood sugar levels can cause systemic multisite nerve damage based on peripheral neuropathy. The long-term hyperglycemia state enables the polyol glucose metabolism pathway to be activated, increasing the accumulation of toxic substances in the vascular injured nerve tissue cells. Sustained hyperglycemia leads to dysfunction of epithelial cells, leading to a decrease in pro-angiogenic signaling and nitric oxide production. In addition, due to impaired leukocyte function in hyperglycemia, immune function is impaired and the immune response at relevant sites is insufficient, making diabetic foot more difficult to heal. The Wnt/β-catenin pathway is a highly conserved signal transduction pathway involved in a variety of biological processes, such as cell proliferation, apoptosis, and differentiation. It is considered an important pathway involved in the healing of skin wounds. This article summarizes the mechanism of action of the Wnt/β-catenin pathway involved in the inflammatory responses to diabetic ulcers, wound proliferation, wound remodeling, and stem cells. The interactions between the Wnt signal pathway and other metabolic pathways are also discussed

    Direct observation of layer-stacking and oriented wrinkles in multilayer hexagonal boron nitride

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    Hexagonal boron nitride (h-BN) has long been recognized as an ideal substrate for electronic devices due to its dangling-bond-free surface, insulating nature and thermal/chemical stability. Therefore, to analyse the lattice structure and orientation of h-BN crystals becomes important. Here, the stacking order and wrinkles of h-BN are investigated by transmission electron microscopy (TEM). It is experimentally confirmed that the layers in the h-BN flakes are arranged in the AA' stacking. The wrinkles in a form of threefold network throughout the h-BN crystal are oriented along the armchair direction, and their formation mechanism was further explored by molecular dynamics simulations. Our findings provide a deep insight about the microstructure of h-BN and shed light on the structural design/electronic modulations of two-dimensional crystals.Comment: 7 pages, 5 figure

    Analysis on contamination of Bacillus cereus in foodstuff in Jilin Province from 2011 to 2019

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    Objective To understand the contamination of Bacillus cereus in foodstuff of Jilin Province from 2011 to 2019, and to provide theoretical basis for food safety monitoring and prevention of foodborne diseases. Methods Totally 3 173 samples were collected from the catering service and circulation of nine prefecture (city) levels in Jilin Province from 2011 to 2019. Bacillus cereus in food was detected according to the method of GB 4789.14-2014 national food safety standard microbiological examination of food. The detection rate was analyzed by rate, composition ratio and χ2 test. Results Among 3 173 food samples from 2011 to 2019 in Jilin Province, the total detection rate of Bacillus cereus was 23.6% (750/3 173), the highest was in 2015 (38.5%, 62/161), and the lowest was in 2017 (11.8%, 20/170). Baishan City had the highest detection rate (35.8%, 139/388), followed by Yanbian Prefecture (31.4%, 97/309), and Siping City had the lowest detection rate (15.3%, 76/496). The detection rate of egg and egg products was the highest (60.0%, 3/5), followed by milk and dairy products (39.3%, 114/290) and infant food (31.1%, 185/595). Contamination of Bacillus cereus was the highest in department stores (32.4%, 22/68), followed by snack bars and beverage stores (30.9%, 43/139), and fast food stores (29.1%, 25/86). The median (interquartile interval) of the detection result of Bacillus cereus by colony forming units method was 5.8 (2.9, 8.7) CFU/g (mL), and the median (interquartile interval) of that by most probable number method was 6.4 (3.2, 9.6) MPN/g (mL). Conclusion There were different degrees of Bacillus cereus contamination in foodstuff in Jilin Province. Among the different cities, foodstuff samples collected from Baishan City was much more serious. Eggs and egg products, milk and dairy products were the main contaminated food. Safety monitoring and management of the snack bar, beverage shop and places in department store should be strengthen

    Minimizing the programming power of phase change memory by using graphene nanoribbon edge-contact

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    Nonvolatile phase change random access memory (PCRAM) is regarded as one of promising candidates for emerging mass storage in the era of Big Data. However, relatively high programming energy hurdles the further reduction of power consumption in PCRAM. Utilizing narrow edge-contact of graphene can effectively reduce the active volume of phase change material in each cell, and therefore realize low-power operation. Here, we demonstrate that a write energy can be reduced to about ~53.7 fJ in a cell with ~3 nm-wide graphene nanoribbon (GNR) as edge-contact, whose cross-sectional area is only ~1 nm2. It is found that the cycle endurance exhibits an obvious dependence on the bias polarity in the cell with structure asymmetry. If a positive bias was applied to graphene electrode, the endurance can be extended at least one order longer than the case with reversal of polarity. The work represents a great technological advance for the low power PCRAM and could benefit for in-memory computing in future.Comment: 14 pages, 4 figure
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