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        Linking transcriptional and genetic tumor heterogeneity through allele analysis of single-cell RNA-seq data

        Fan, Jean,Lee, Hae-Ock,Lee, Soohyun,Ryu, Da-eun,Lee, Semin,Xue, Catherine,Kim, Seok Jin,Kim, Kihyun,Barkas, Nikolaos,Park, Peter J.,Park, Woong-Yang,Kharchenko, Peter V. Cold Spring Harbor Laboratory Press 2018 Genome research Vol.28 No.8

        <P>Characterization of intratumoral heterogeneity is critical to cancer therapy, as the presence of phenotypically diverse cell populations commonly fuels relapse and resistance to treatment. Although genetic variation is a well-studied source of intratumoral heterogeneity, the functional impact of most genetic alterations remains unclear. Even less understood is the relative importance of other factors influencing heterogeneity, such as epigenetic state or tumor microenvironment. To investigate the relationship between genetic and transcriptional heterogeneity in a context of cancer progression, we devised a computational approach called HoneyBADGER to identify copy number variation and loss of heterozygosity in individual cells from single-cell RNA-sequencing data. By integrating allele and normalized expression information, HoneyBADGER is able to identify and infer the presence of subclone-specific alterations in individual cells and reconstruct the underlying subclonal architecture. By examining several tumor types, we show that HoneyBADGER is effective at identifying deletions, amplifications, and copy-neutral loss-of-heterozygosity events and is capable of robustly identifying subclonal focal alterations as small as 10 megabases. We further apply HoneyBADGER to analyze single cells from a progressive multiple myeloma patient to identify major genetic subclones that exhibit distinct transcriptional signatures relevant to cancer progression. Other prominent transcriptional subpopulations within these tumors did not line up with the genetic subclonal structure and were likely driven by alternative, nonclonal mechanisms. These results highlight the need for integrative analysis to understand the molecular and phenotypic heterogeneity in cancer.</P>

      • KCI등재

        Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression

        Da Zhou,Yuan-Wen Chen,Ze-Hua Zhao,Rui-Xu Yang,Feng-Zhi Xin,Xiao-Lin Liu,Qin Pan,Huiping Zhou,Jian-Gao Fan 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

        Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is wellknown that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/ insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

      • KCI등재

        In Vivo Biocompatibility and Improved Compression Strength of Reinforced Keratin/Hydroxyapatite Scaffold

        Jie Fan,Meng-Yan Yu,Tong-da Lei,Yong-Heng Wang,Fu-Yuan Cao,Xiao Qin,Yong Liu 한국조직공학과 재생의학회 2018 조직공학과 재생의학 Vol.15 No.2

        A rapid freezing/lyophilizing/reinforcing process is suggested to fabricate reinforced keratin/hydroxyapatite (HA) scaffold with improved mechanical property and biocompatibility for tissue engineering. The keratin, extracted from human hair, and HA mixture were rapidly frozen with liquid nitrogen and then lyophilized to prepare keratin/HA laminar scaffold. The scaffold was then immersed in PBS for reinforcement treatment, and followed by a second lyophilization to prepare the reinforced keratin/HA scaffold. The morphology, mechanical, chemical, crystal and thermal property of the keratin/HA scaffold were investigated by SEM, FTIR, XRD, DSC, respectively. The results showed that the keratin/HA scaffold had a high porosity of 76.17 ± 3%. The maximum compressive strength and compressive modulus of the reinforced scaffold is 0.778 and 3.3 MPa respectively. Subcutaneous implantation studies in mice showed that in vivo the scaffold was biocompatible since the foreign body reaction seen around the implanted scaffold samples was moderate and became minimal upon increasing implantation time. These results demonstrate that the keratin/HA reinforced scaffold prepared here is promising for biomedical utilization.

      • KCI등재

        Keratin/PEO/hydroxyapatite Nanofiber Membrane with Improved Mechanical Property for Potential Burn Dressing Application

        Jie Fan,Tong-da Lei,Meng-Yan Yu,Yong-Heng Wang,Fu-Yuan Cao,Qingqi Yang,Faming Tian,Yong Liu 한국섬유공학회 2020 Fibers and polymers Vol.21 No.2

        Keratin, as a promising substitute for tissue engineering due to its excellent biocompatibility and bioactivity, is used to combine one or more other polymers together. However, compound nanofibers with high keratin content (normally>90 wt.%) may result in the poor elongation of nanofiber membranes such as wound dressing. In this work, different ratios of hydroxyapatites (HA) modified by sodium hexametaphosphate were blended with keratin/polyethylene oxide (PEO) spinning solution to produce reinforced keratin blend nanofiber nonwoven membranes as a potential candidate wound dressing. The tensile strength of keratin blend nanofiber membrane with 15 % modified HA addition was two times higher than that without HA. The morphologies and chemical structure of keratin/PEO/HA nanofiber membranes were investigated using SEM, FTIR, and TG. The biocompatibility and the burn repairing performance of keratin/PEO/HA nanofiber mat were also investigated by cell culture and animal burn model. The results showed that the Keratin/PEO/HA nanofiber membranewas beneficial to enhance the proliferation of L929 cell, exhibiting an advantages in reducing inflammatory response in the infective stage and enhancing skin repairing process in the following recover stages. Our data suggested that keratin/PEO/HA nanofiber membrane could serve as a promising burn dressing for treatment of the skin burn.

      • KCI등재

        Facile Synthesis of Graphene–Enwrapped Ag3PO4 Composites with Highly Efficient Visible Light Photocatalytic Performance

        Shi Lei,Da Chen,Wenting Xie,Jing Zhang,Guangxing Ping,Meiqiang Fan,Laishun Qin,Liqun Bai,Zhi Chen,Chunju Lv,Kangying Shu 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2016 NANO Vol.11 No.1

        In this work, thermally exfoliated graphene nanosheets (GNS) were employed to prepare novel Ag3PO4–GNS composite photocatalysts by a facile chemical precipitation approach. The asprepared Ag3PO4–GNS composite photocatalysts were characterized by X-ray diffraction (XRD) pattern, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), Raman spectroscopy, thermogravimetric (TG) analysis, ultraviolet-visible diffuse re-flectance spectroscopy (DRS) and photoluminescence (PL) spectra. It was found that the Ag3PO4 particles were well deposited on the surfaces of GNS. Compared with bare Ag3PO4 and Ag3PO4–rGO composite, the Ag3PO4–GNS composite exhibited enhanced photocatalytic activity for the photodegradation of rhodamine B (RhB) under visible light irradiation. The photocatalytic degradation rate of Ag3PO4–GNS composite was 1.7 times that of bare Ag3PO4 and about 1.3 times that of Ag3PO4–rGO for the degradation of RhB. Furthermore, the photocatalytic stability of Ag3PO4–GNS composite was also greatly enhanced. This enhanced photocatalytic activity and stability could be ascribed to the positive synergetic effects between the Ag3PO4 particles and GNS sheets, which could provide a greater number of active adsorption sites, suppress charge recombination and reduce the serious photocorrosion of Ag3PO4. Moreover, the photocatalytic degradation of RhB over Ag3PO4–GNS composites was also optimized, suggesting that the optimal amount of GNS in the composites was 11.4 wt.%. This work shows a great potential of Ag3PO4–GNS composite for environmental treatment of organic pollutants.

      • KCI등재

        Toward Understanding the Adsorption And Inhibition Mechanism of Cu‑MBTA Passivation Film on Copper Surface: A Combined Experimental and DFT Investigation

        Mengrui Liu,Da Yin,Baimei Tan,Fan Yang,Xiaoqin Sun,Pengcheng Gao,Shihao Zhang,Yazhen Wang 대한금속·재료학회 2021 ELECTRONIC MATERIALS LETTERS Vol.17 No.1

        The adsorption and passivation reactions of 5-methyl benzotriazole (MBTA) with different copper samples (as received, citricacid treated and citric acid and KIO4treated) were studied. The experiments were characterized by contact angle measurement,potentiodynamic polarization curve, electrochemical impedance spectroscopy and X-ray photoelectron spectroscopy. The results showed that the adsorption behavior of MBTA on different treated surfaces was different and MBTA was preferentiallyadsorbed on the surface of citric acid treated copper. Based on the density functional theory, quantum chemicaldescriptors such as the frontier molecular orbital energies EHOMO,ELUMOand the energy gap between them, molecularelectrostatic potential, and Fukui function had been calculated and discussed. The adsorption mechanism of MBTA andcopper surface was further revealed, which had positive significance for the corrosion inhibition of copper surface in copperinterconnection CMP.

      • KCI등재

        Risk Factors of Unsatisfactory Robot-Assisted Pedicle Screw Placement: A Case-Control Study

        Qi Zhang,Ming-Xing Fan,Xiao-Guang Han,Ya-Jun Liu,Da He,Bo Liu,Wei Tian 대한척추신경외과학회 2021 Neurospine Vol.18 No.4

        Objective: To identify potential risk factors of unsatisfactory screw position during robot-assisted pedicle screw fixation. Methods: A retrospective analysis of robot-assisted pedicle screw fixation performed in Beijing Jishuitan Hospital from March 2018 to March 2019 was conducted. Research data was collected from the medical record and imaging systems. Univariate tests were performed on the potential risk factors (patient’s characteristics and surgical factors) of unsatisfactory screw position during robot-assisted pedicle screw fixation. For statistically significant variables in univariate tests, a logistic regression test was used to identify independent risk factors for unsatisfactory screw position. Results: A total of 780 pedicle screws placed in 163 robot-assisted surgeries were analyzed. The rate of perfect screw positions was 93.08%, and the unsatisfactory rate was 6.92%. In patients with severe obesity (body mass index≥30 kg/m2) (odds ratio [OR], 2.459; 95% confidence interval [CI], 1.199–5.044; p=0.014), osteoporosis (T≤-2.5) (OR, 1.857; 95% CI, 1.046–3.295; p=0.034), and the segments 3 levels away from the tracker (OR, 2.216; 95% CI, 1.119–4.387; p=0.022), robot-assisted pedicle screw placement has a higher risk of screw malposition. Conclusion: During robot-assisted pedicle screw placement for patients with severe obesity, osteoporosis, and segments 3 levels away from the tracker, vigilance should be maintained during surgery to avoid postoperative complications due to unsatisfactory screw position.

      • KCI등재

        Telerobotic Spinal Surgery Based on 5G Network: The First 12 Cases

        Wei Tian,Mingxing Fan,Cheng Zeng,Yajun Liu,Da He,Qi Zhang 대한척추신경외과학회 2020 Neurospine Vol.17 No.1

        Objective: The purpose of this study was to determine the efficacy and feasibility of 5th generation wireless systems (5G) telerobotic spinal surgery in our first 12 cases. Methods: A total of 12 patients (5 males, 7 females; age, 23–71 years) with spinal disorders (4 thoracolumbar fractures, 6 lumbar spondylolisthesis, 2 lumbar stenosis) were treated with 5G telerobotic spinal surgery. Sixty-two pedicle screws were implanted. Results: All patients had substantial relief from their symptoms. Screw placements were classified using Gertzbein-Robbins criteria. There were 59 grade A, 3 grade B. Mean operation time was 142.5±46.7 minutes. Mean guiding wire insertion time was 41.3±9.8 minutes. The deviation between the planned and actual positions was 0.76±0.49 mm. No intraoperative adverse event was found. Conclusion: 5G remote robot-assisted spinal surgery is accurate and reliable. We conclude that 5G telerobotic spinal surgery is both efficacious and feasible for the management of spinal diseases with safety.

      • Quantifying and monitoring functional photosystem II and the stoichiometry of the two photosystems in leaf segments: approaches and approximations.

        Chow, Wah Soon,Fan, Da-Yong,Oguchi, Riichi,Jia, Husen,Losciale, Pasquale,Park, Youn-Il,He, Jie,Oquist, Gunnar,Shen, Yun-Gang,Anderson, Jan M W. Junk ; Kluwer Academic Publishers 2012 Photosynthesis research Vol.113 No.1

        <P>Given its unique function in light-induced water oxidation and its susceptibility to photoinactivation during photosynthesis, photosystem II (PS II) is often the focus of studies of photosynthetic structure and function, particularly in environmental stress conditions. Here we review four approaches for quantifying or monitoring PS II functionality or the stoichiometry of the two photosystems in leaf segments, scrutinizing the approximations in each approach. (1) Chlorophyll fluorescence parameters are convenient to derive, but the information-rich signal suffers from the localized nature of its detection in leaf tissue. (2) The gross O(2) yield per single-turnover flash in CO(2)-enriched air is a more direct measurement of the functional content, assuming that each functional PS II evolves one O(2) molecule after four flashes. However, the gross O(2) yield per single-turnover flash (multiplied by four) could over-estimate the content of functional PS II if mitochondrial respiration is lower in flash illumination than in darkness. (3) The cumulative delivery of electrons from PS II to P700(+) (oxidized primary donor in PS I) after a flash is added to steady background far-red light is a whole-tissue measurement, such that a single linear correlation with functional PS II applies to leaves of all plant species investigated so far. However, the magnitude obtained in a simple analysis (with the signal normalized to the maximum photo-oxidizable P700 signal), which should equal the ratio of PS II to PS I centers, was too small to match the independently-obtained photosystem stoichiometry. Further, an under-estimation of functional PS II content could occur if some electrons were intercepted before reaching PS I. (4) The electrochromic signal from leaf segments appears to reliably quantify the photosystem stoichiometry, either by progressively photoinactivating PS II or suppressing PS I via photo-oxidation of a known fraction of the P700 with steady far-red light. Together, these approaches have the potential for quantitatively probing PS II in vivo in leaf segments, with prospects for application of the latter two approaches in the field.</P>

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