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      • KCI등재

        OSI-027 alleviates rapamycin insensitivity by modulation of mTORC2/AKT/TGF-β1 and mTORC1/4E-BP1 signaling in hyperoxia-induced lung injury infant rats

        Long Li,Liang Mulin,Yanling Liu,Wang Pan,Dang Hongxing 대한독성 유전단백체 학회 2021 Molecular & cellular toxicology Vol.17 No.3

        Background The mechanism of long time and high-concentration oxygen treatment leading to acute lung injury (ALI) or developmental lung disease in infants is currently unclear. Here we found that compared with the effect of rapamycin, pan-mTOR1/2 inhibitor OSI-027, alleviates hyperoxia-induced lung injury (HILI) by modulation of mTORC2/AKT/TGF-β1 and mTORC1/4E-BP1 signaling in infant rats. Objective Infant rats were treated with continuous inhalation of 90% medical oxygen. Normal saline, rapamycin, or OSI-027 was intraperitoneally injected, and the status of lung injury was tested on days 3, 7, and 14. The activation of mTOR/AKT/TGFβ1 and mTORC1/4E-BP1 signaling was confirmed by immunohistochemistry and Western blot analysis in normal and hyperoxia-treated live precision-cut lung tissues. The inhibitory effect of OSI-027 extended to the active state of other proteins implicated in mTOR1/2 signaling was demonstrated in hyperoxia-induced injured lung tissues. Results Our data demonstrate that hyperoxia-induced serious lung inflammation and fibrosis. OSI-027 significantly attenuated the pathological process of HILI, inhibit the phosphorylation of the primary downstream targets of mTORC1/C2, and reduce the activation of TGF-β1 signaling. Conclusions The results suggest that mTORC2/AKT/TGF-β1 and the rapamycin-insensitive mTORC1/4E-BP1 (Thr37/46) signaling has an important effect during HILI with a potential meaning for the progress of novel anti-hyperoxia-injury strategies. Background The mechanism of long time and high-concentration oxygen treatment leading to acute lung injury (ALI) or developmental lung disease in infants is currently unclear. Here we found that compared with the effect of rapamycin, pan-mTOR1/2 inhibitor OSI-027, alleviates hyperoxia-induced lung injury (HILI) by modulation of mTORC2/AKT/TGF-β1 and mTORC1/4E-BP1 signaling in infant rats. Objective Infant rats were treated with continuous inhalation of 90% medical oxygen. Normal saline, rapamycin, or OSI-027 was intraperitoneally injected, and the status of lung injury was tested on days 3, 7, and 14. The activation of mTOR/AKT/TGFβ1 and mTORC1/4E-BP1 signaling was confirmed by immunohistochemistry and Western blot analysis in normal and hyperoxia-treated live precision-cut lung tissues. The inhibitory effect of OSI-027 extended to the active state of other proteins implicated in mTOR1/2 signaling was demonstrated in hyperoxia-induced injured lung tissues. Results Our data demonstrate that hyperoxia-induced serious lung inflammation and fibrosis. OSI-027 significantly attenuated the pathological process of HILI, inhibit the phosphorylation of the primary downstream targets of mTORC1/C2, and reduce the activation of TGF-β1 signaling. Conclusions The results suggest that mTORC2/AKT/TGF-β1 and the rapamycin-insensitive mTORC1/4E-BP1 (Thr37/46) signaling has an important effect during HILI with a potential meaning for the progress of novel anti-hyperoxia-injury strategies.

      • KCI등재

        Identification of QTLs associated with the anaerobic germination potential using a set of Oryza nivara introgression lines

        Licheng Liu,Xiaoxiang Li,Sanxiong Liu,Jun Min,Wenqiang Liu,Xiaowu Pan,Baohua Fang,Min Hu,Zhongqi Liu,Yongchao Li,Haiqing Zhang 한국유전학회 2021 Genes & Genomics Vol.43 No.4

        Background Rice (Oryza sativa L.) is an important crop and a staple food for half of the population around the world. The recent water and labor shortages are encouraging farmers to shift from traditional transplanting to direct-seeding. However, poor germination and slow elongation of the coleoptile constrains large-scale application of direct-seeding. Objective Thisstudy was aimed to investigate the genetic basis of the anaerobic germination(AG) potential using a set of Oryza nivara (O. nivara) introgressionlines (ILs). Methods Inthis study, a total of 131 ILs were developed by introducing O. nivara chromosomesegments into the elite indica rice variety 93-11 through advanced backcrossingand repeated selfng. A high-density genetic map has been previouslyconstructed with 1,070 bin-markers. The seeds of ILs were germinated and usedto measure coleoptile length under normal and anaerobic conditions. QTLsassociated with AG potential were determined in rice. Results Basedon the high-density genetic map of the IL population, two QTLs, qAGP1 and qAGP3 associated with AG tolerance were characterized and locatedon chromosomes 1 and 3, respectively. Each QTL explained 15% of the phenotypic variance.Specifcally, the O. nivara-derived chromosomesegments of the two QTLs were positively tolerance to anaerobic condition byincreasing coleoptile length. In a further analysis of public transcriptomedata, a total of 26 and 36 genes within qAGP1 and qAGP3 were transcriptionallyinduced by anaerobic stress, respectively. Conclusions Utilizationof O. nivara-derived alleles at qAGP1 and qAGP3 can potentially enhance tolerance to anaerobic stress at thegermination stage in rice, thereby accelerating breeding of rice varieties tobe more adaptative for direct-seeding.

      • SCIESCOPUSKCI등재
      • In-vitro elution of cisplatin and fluorouracil from bi-layered biodegradable beads

        Liu, Kuo-Sheng,Pan, Ko-Ang,Liu, Shih-Jung Techno-Press 2015 Biomaterials and Biomechanics in Bioengineering Vol.2 No.2

        This study developed biodegradable bi-layered drug-eluting beads and investigated the in-vitro release of fluorouracil and cisplatin from the beads. To manufacture the drug-eluting beads, poly[(d,l)-lactide-co-glycolide] (PLGA) with lactide:glycolide ratios of 50:50 and 75:25 were mixed with fluorouracil or cisplatin. The mixture was compressed and sintered at $55^{\circ}C$ to form bi-layered beads. An elution method was employed to characterize the release characteristic of the pharmaceuticals over a 30-day period at $37^{\circ}C$. The influence of polymer type (i.e., 50:50 or 75:25 PLGA) and layer layout on the release characteristics was investigated. The experiment suggested that biodegradable beads released high concentrations of fluorouracil and cisplatin for more than 30 days. The 75:25 PLGA released the pharmaceuticals at a slower rate than the 50:50 PLGA. In addition, the bi-layered structure reduced the release rate of drugs from the core layer of the beads. By adopting the compression sintering technique, we will be able to manufacture biodegradable beads for long-term drug delivery of various anti-cancer pharmaceuticals.

      • In-vitro elution of cisplatin and fluorouracil from bi-layered biodegradable beads

        Liu, Kuo-Sheng,Pan, Ko-Ang,Liu, Shih-Jung Techno-Press 2015 Biomaterials and biomedical engineering Vol.2 No.2

        This study developed biodegradable bi-layered drug-eluting beads and investigated the in-vitro release of fluorouracil and cisplatin from the beads. To manufacture the drug-eluting beads, poly[(d,l)-lactide-co-glycolide] (PLGA) with lactide:glycolide ratios of 50:50 and 75:25 were mixed with fluorouracil or cisplatin. The mixture was compressed and sintered at $55^{\circ}C$ to form bi-layered beads. An elution method was employed to characterize the release characteristic of the pharmaceuticals over a 30-day period at $37^{\circ}C$. The influence of polymer type (i.e., 50:50 or 75:25 PLGA) and layer layout on the release characteristics was investigated. The experiment suggested that biodegradable beads released high concentrations of fluorouracil and cisplatin for more than 30 days. The 75:25 PLGA released the pharmaceuticals at a slower rate than the 50:50 PLGA. In addition, the bi-layered structure reduced the release rate of drugs from the core layer of the beads. By adopting the compression sintering technique, we will be able to manufacture biodegradable beads for long-term drug delivery of various anti-cancer pharmaceuticals.

      • SCISCIESCOPUS

        Differently-charged graphene-based multilayer films by a layer-by-layer approach for oxygen gas barrier application

        Liu, Hongyu,Wu, Jianping,Liu, Cuiyun,Pan, Bingli,Kim, Nam Hoon,Lee, Joong Hee Elsevier 2018 Composites Part B, Engineering Vol.155 No.-

        <P><B>Abstract</B></P> <P>Polyelectrolyte-decorated graphene with positive and negative charges was prepared using graphene oxide as a precursor along with polyallylamine hydrochloride and poly (styrenesulfonate sodium) as surface modifiers, respectively. Driven by an electrostatic interaction, the as-obtained polyelectrolyte-decorated graphene sheets were self-assembled via a layer-by-layer method, producing graphene based composite multilayers. Field emission scanning electron microscopy (FE-SEM) images showed that the surface of composite film exhibited a mass of characteristic wrinkles of graphene. Interestingly, the cross-sectional FE-SEM of the film exhibited an unstratified structure, indicating a good dispersion of graphene sheets in the composite film. The results of oxygen gas permeability testing demonstrated that the resulting composite films exhibited excellent oxygen gas barrier properties. The oxygen gas transmission rate (OTR) of the composite film with 24 bilayers was as low as 1.2 cm<SUP>3</SUP> m<SUP>-2</SUP> d<SUP>-1</SUP>∙atm<SUP>−1</SUP>, exhibiting potential for use in packaging applications.</P>

      • KCI등재

        De novo transcriptome sequencing and gene expression profiling of sweetpotato leaves during low temperature stress

        Pan Jiaquan,Zhang Qian,Liu Shuai,Liu Zhiqiang,Bian Xiaofeng,Yu Tao 한국식물생명공학회 2023 Plant biotechnology reports Vol.17 No.6

        Sweetpotato [Ipomoea batatas (L.) Lam] is one of the most important crops for food, feed, industrial material, and bio-energy resource. However, since it originated in tropical regions, sweetpotato exhibits limited cold tolerance, hindering its cultivation in low-temperature areas. To comprehend the sweetpotato response to chilling stress, de novo transcriptome assembly was conducted on leaves from two sweetpotato cultivars: the cold-tolerant Liaohanshu 21 and the cold-sensitive Shenshu 28, exposed to low-temperature stress for 3 h and 24 h. 787.24 million raw reads and 763.44 million clean reads were obtained, 60.60–66.06% of clean reads successfully mapped to the reference database across all 18 libraries. 2524 unigenes were identified as transcript factors and classified into 55 families in Plant Transcription Factor Database (PlantTFDB) and 4671 unigenes were matched to 24 groups in Plant Resistance Gene Database (PRGdb). In Liaohanshu 21, 3618 genes and 8391 genes exhibited significant differential expression 3 h and 24 h of low-temperature exposure, respectively. In Shenshu 28, 13,394 genes and 11,627 genes displayed substantial differential expression after 3 h and 24 h of low-temperature exposure, respectively. The differentially expressed genes (DEGs) were further analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genome (KEGG) database. DEGs related to “active oxygen scavenging systems”, “lipid metabolism”, and “plant hormone signal transduction” were potentially associated with sweetpotato’s cold resistance. This research offers insights into the mechanisms and genes involved in cold stress in sweetpotato’s response to cold stress and will contribute valuable information for cold-tolerant breeding of sweetpotato.

      • KCI등재

        Suppression of SPARC Ameliorates Ovalbumin-induced Airway Remodeling via TGFβ1/Smad2 in Chronic Asthma

        Pan Yun,Zhang Dong,Zhang Jintao,Liu Xiaofei,Xu Jiawei,Zeng Rong,Cui Wenjing,Liu Tian,Wang Junfei,Dong Liang 대한천식알레르기학회 2024 Allergy, Asthma & Immunology Research Vol.16 No.1

        Purpose: Airway remodeling is a critical feature of asthma. Secreted protein acidic and rich in cysteine (SPARC), which plays a cardinal role in regulating cell-matrix interactions, has been implicated in various fibrotic diseases. However, the effect of SPARC in asthma remains unknown. Methods: We studied the expression of SPARC in human bronchial epithelial cells and serum of asthmatics as well as in the lung tissues of chronic asthma mice. The role of SPARC was examined by using a Lentivirus-mediated SPARC knockdown method in the ovalbumin (OVA)-induced asthma mice. The biological processes regulated by SPARC were identified using RNA sequencing. The function of SPARC in the remodeling process induced by transforming growth factor β1 (TGFβ1) was conducted by using SPARC small interfering RNA (siRNA) or recombinant human SPARC protein in 16HBE cells. Results: We observed that SPARC was up-regulated in human bronchial epithelia of asthmatics and the asthmatic mice. The levels of serum SPARC in asthmatics were also elevated and negatively correlated with the forced expiratory volume in one second (FEV1) to forced vital capacity ratio (FVC) (r = −0.485, P < 0.01) and FEV1 (%predicted) (r = −0.425, P = 0.001). In the chronic asthmatic mice, Lentivirus-mediated SPARC knockdown significantly decreased airway remodeling and airway hyper-responsiveness. According to gene set enrichment analysis, negatively enriched pathways found in the OVA + short hairpin-SPARC group included ECM organization and collagen formation. In the lung function studies, knockdown of SPARC by siRNA reduced the expression of remodeling-associated biomarkers, cell migration, and contraction by blocking the TGFβ1/Smad2 pathway. Addition of human recombinant SPARC protein promoted the TGFβ1-induced remodeling process, cell migration, and contraction in 16HBE cells via the TGFβ1/Smad2 pathway. Conclusions: Our studies provided evidence for the involvement of SPARC in the airway remodeling of asthma via the TGFβ1/Smad2 pathway.

      • KCI등재

        Shape error prediction and compensation of three-dimensional surface in flexibly-reconfigurable roll forming

        Pan Liu,구태완,강범수 대한기계학회 2015 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.29 No.10

        The Flexibly-reconfigurable roll forming (FRRF) scheme as one of the advanced continuous roll forming processes consists of upperand lower flexible rollers that can be controlled by each reconfigurable punch module. The shape error in the FRRF process often resultsin undesirable changes in the shape of the deformed surface and brings about a deviation in the precision of the deformed product. Thisstudy considers the changes in the shape error of a deformed configuration by controlling the non-uniform gap between both flexiblerollers in the transverse direction. A Non-uniform rational B-spline (NURBS) type control methodology is introduced based on the transversetarget curve and the thickness reduction ratio. The function for the transverse target curve is reconstructed by using a NURBS curve,and the function of the reduction ratios of the thickness is assumed to have linear increments. Finite element simulations are conductedfor the FRRF process with the AA5052-H32 sheet material by applying NURBS-type control methodology for both flexible rollers. Thetransverse shape error of the three-dimensional surface is predicted by using a numerical approach, and its results are experimentallyverified. A Reverse displacement compensation (RDC) method is adopted to compensate the transverse shape error of the deformedsurface. Consequently, the proposed RDC method is validated as a suitable approach to address the transverse shape error. This methodcontributes to further developing capabilities to modify the profiles of the upper and lower flexible rollers in the flexibly-reconfigurableroll forming process for various 3D surface parts.

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