Deubiquitination and Stabilization of PD-L1 by CSN5

Lim, Seung-Oe,Li, Chia-Wei,Xia, Weiya,Cha, Jong-Ho,Chan, Li-Chuan,Wu, Yun,Chang, Shih-Shin,Lin, Wan-Chi,Hsu, Jung-Mao,Hsu, Yi-Hsin,Kim, Taewan,Chang, Wei-Chao,Hsu, Jennifer L.,Yamaguchi, Hirohito,Ding Elsevier 2016 Cancer cell Vol.30 No.6

<P><B>Summary</B></P> <P>Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation </LI> <LI> Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization </LI> <LI> CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination </LI> <LI> Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing

Li Shi-Dan,Xing Wei,Wang Shao-Chuan,Li You-Bin,Jiang Hao,Zheng Han-Xuan,Li Xiao-Ming,Yang Jing,Guo De-Bin,Xie Xiao-Yu,Jiang Ren-Qing,Fan Chao,Li Lei,Xu Xiang,Fei Jun 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

Analysis of Bacterial Diversity and Communities Associated with Tricholoma matsutake Fruiting Bodies by Barcoded Pyrosequencing in Sichuan Province, Southwest China

( Qiang Li ),( Xiao Lin Li ),( Cheng Chen ),( Shu Hong Li ),( Wen Li Huang ),( Chuan Xiong ),( Xing Jin ),( Lin Yong Zheng ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.1

Endophytes play an important role in the growth and development of the host. However, the study of endophytes is mostly focused on plants, and reports on bacteria associated with fungi are relatively rare. We studied the bacteria associated with fruiting bodies of Tricholoma matsutake picked from seven main T. matsutake-producing areas in Sichuan, China, by barcoded pyrosequencing. About 8,272 reads were obtained per sample, representing 40 phyla, 103 classes, and 495 genera of bacteria and archaea, and 361.797 operational taxonomic units were observed at a 97% similarity level. The bacterial community was always both more abundant and more diverse than the archaeal community. UniFrac analysis showed there were some difference of bacterial communities among the samples sites. Three bacterial phyla, Proteobacteria, Bacteroidetes, and Firmicutes, were dominant in all samples. Correlation analysis showed there was a significant correlation between some soil properties and bacterial community associated with T. matsutake. This study demonstrated that the bacteria associated with T. matsutake fruiting bodies were diversified. Among these bacteria, we may find some strains that can promote the growth of T. matsutake.

Parental Knowledge, Concerns, and Management of Childhood Fevers in Taiwan

Li-Chuan Chang,Mei-Chih Huang 한국간호과학회 2009 한국간호과학회 학술대회 Vol.2009 No.10

Effect of Crystal Structure and Hydrogen Bond of Thermoplastic Oxidized Starch on Manufacturing of Starch-Based Biomass Composite

Chuan-Wei Zhang,Fang-Yi Li,Jianfeng Li,Qi Xie,Jie Xu,An-Fu Guo,Cheng-Zhao Wang 한국정밀공학회 2018 International Journal of Precision Engineering and Vol.5 No.3

Starch-based biomass composites were prepared with starch and plant fiber. In order to improve the properties of the compos ites, oxidized starches (OS) were prepared using hydroxyl peroxide as oxidizer, then glycerol was added into OS as plasticizer to produce thermoplastic oxidized starches (TPOS). Crystal structure, hydrogen bonds of TPOS were researched to gain comprehensive views on the mechanism of the property differences between the starch-based composites with native starch, OS and TPOS. The changes of crystal structure were analyzed by X-ray diffraction analysis. Starch intermolecular hydroxyl changes were investigated using the method of infrared spectrum analysis. It was found that the new hydrogen bonds were formed between the plasticizer, oxidizer and starch, and the starch intermolecular bonding force was weakened. The structure of starch crystallization was destructed in TPOS. Differential scanning calorimetry showed that cross reaction with oxidization and plasticization changed the crystal structure, glass transition process was not observed in TPOS. The tensile and compressive strengths of composite based on TPOS were improved greatly and mechanical properties were not weakened obviously with water content increased. All the results indicated that TPOS could improve the properties of starch-based composites.

A Novel Distributed Equivalent Circuit Model for Single-Core Cables

Li Rui-Fang,Hu Hao,Cao Xiao-Bin,Li Zhong-Mei,Li Jun-Hao,Zhu Chuan-Lin,Liu Le-Jia 대한전기학회 2024 Journal of Electrical Engineering & Technology Vol.19 No.1

The number of cables used for urban power supply increases rapidly. The sheath current in these cables, which is generated via induction, produces a current loss. When the situation is serious, the ground lead and the middle connector of the cable will be burned. In this paper, the existing single-core cable equivalent circuit model is used to calculate the sheath current of a 3-phase cable under the condition of non-transposition and cross connection. By comparing the calculated results with the simulation and the experimental results, it is found that the current distribution law for the sheath, which was obtained using the existing model, difers substantially from both the simulation and actual measurements. The error reason of the existing model is revealed, and it is found that the magnitude and phase of the current in the metal sheath of the cable varies with the position under the combined efect of distributed capacitances in the cable and the core-current fux, especially for a 3-phase cross connection, each section of the cable does not meet Kirchhof’s laws, but the sheath electric current in the existing models are considered equal everywhere. Therefore, a novel cable equivalent model is proposed in this paper, which is based on a distributed circuit, and an equation to calculate the sheath current is derived. The model presented in this paper corrects the problems of the existing model, which can be applied to power system, subway, high-speed rail, and any application of single-core cables.

Identification of six heat shock protein 70 genes in Lasioderma serricorne (Coleoptera: Anobiidae) and their responses to temperature stress

Li Mao-Ye,Huang Yan,Lei Xiao,Xu Chuan-Tao,Li Bin,Chen De-Xin,Liu Su 한국응용곤충학회 2021 Journal of Asia-Pacific Entomology Vol.24 No.3

Heat shock proteins (HSPs) play essential roles in stress tolerance in insects, such as the cigarette beetle, Lasioderma serricorne, which is an important pest of stored products. However, the function of HSPs in envi ronmental stress response in L. serricorne is poorly understood. In this study, six cDNAs encoding putative HSP70s were identified in L. serricorne (LsHSP70-1 to LsHSP70-6). The LsHSP70 proteins identified have signature motifs of insect HSP70s and exhibit high amino-acid identity with their respective orthologs from other insect species. Phylogenetic analysis showed that these LsHSP70s fall into three major clans: HSP70 in the cytosol (four genes), endoplasmic reticulum (one gene), and mitochondria (one gene). LsHSP70 genes are differentially expressed in different developmental stages. LsHSP70-4 and LsHSP70-5 are mainly expressed at the larval stage, while LsHSP70-3 shows the highest level at the pupal stage. The other genes are ubiquitously expressed. Furthermore, the expression levels of LsHSP70-1 and LsHSP70-4 are significantly upregulated upon exposure to temperatures of both 0 and 15 ◦ C, while LsHSP70-3 is inducible at 15 ◦ C and LsHSP70-6 at 0 ◦ C. In addition, treatment at 0 ◦ C causes significant downregulation of LsHSP70-2 and LsHSP70-3. Exposure to a temperature of 30 ◦ C upregulates LsHSP70-1 expression, while 35 and 40 ◦ C treatments result in significantly enhanced transcription of all the LsHSP70 genes. To the best of the authors’ knowledge, this is the first report on the sequence characteristics, phylogenetic relationships, and expression profiles of HSP70 genes in L. serricorne. The cold- and heat-inducible regulation of LsHSP70s suggests that these genes are related to tolerance of abnormal temperatures.

Roles of mTOR and p-mTOR in Gastrointestinal Stromal Tumors

Li, Jun-Chuan,Zhu, Hong-Yu,Chen, Ting-Xuan,Zou, Lan-Ying,Wang, Xiao-Yan,Zhao, Hui-Chuan,Xu, Jun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Objective: This study aimed to examine the relationship between expression of mammal target of rapamycin (mTOR) and phosphorylation of mTOR (p-mTOR) protein in the PI3K/Akt/mTOR signaling pathways in gastrointestinal stromal tumors and relatiuonships with clinical factors. Methods: Immunohistochemistry was used to detect the expression of the associated proteins mTOR, p-mTOR, and phosphorylation of the tumor suppressor genes PTEN, P27, VEGF, and EGFR in 40 cases of gastrointestinal stromal tumors, with division into a very low and low risk group as well as a moderate and high risk group. Results: The positive rate of mTOR and p-mTOR was significantly increased in the moderate and high risk group compared with the very low and low risk group. The difference was statistically significant (P<0.05). When grouped according to size, the positive mTOR expression rate exhibited a statistical difference (P<0.05), which was significantly increased in the group of tumors larger than 5 cm. The difference in the positive mTOR and p-mTOR expression rate exhibit no statistical significance among the PTEN, P27, VEGF, and EGFR expression subgroups (P>0.05). Conclusion: The different expressions of mTOR and p-mTOR in the signal transduction pathway of gastrointestinal stromal tumor in the different degree-of-risk groups suggested that the mTOR and p-mTOR of the signal transduction pathway serve an important function in the occurrence and development of gastrointestinal stromal tumors.

[ $Ce^{4+}$ ]-Stimulated Ion Fluxes Are Responsible for Apoptosis and Taxol Biosynthesis in Suspension Cultures of Taxus Cells

Li Jing-Chuan,Ge Zhi-Qiang,Yuan Ying-Jin The Korean Society for Biotechnology and Bioengine 2005 Biotechnology and Bioprocess Engineering Vol.10 No.2

Ion fluxes across the plasma membrane activated by 1 mM $Ce^{4+}$, cell apoptosis and taxol biosynthesis in suspension cultures of Taxus cusp/data were studied. The extracellular pH sharply decreased upon the addition of 1 mM $Ce^{4+}$, then increased gradually and exceeded the initial pH value over a time period of 12 h. The extracellular $Ca^{2+}$ concentration decreased within the first 3 h after the addition of $Ce^{4+}$, then gradually decreased to one third of initial value in control at about 72 h and remained unchanged afterwards. Experiments with an ion channel blocker and a $Ca^{2+}$-channel blocker indicated that the dynamic changes in extracellular pH and the $Ca^{2+}$ concentration resulted from the $Ce^{4+}$-induced activation of W uptake and $Ca^{2+}$ influx across the plasma membrane via ion channels. A pretreatment of the ion channel blocker initiated $Ce^{4+}$-treated cells to undergo necrosis, and the prior addition of the $Ca^{2+}$-channel blocker inhibited $Ce^{4+}$-induced taxol biosynthesis and apoptosis. It is thus inferred that W uptake is necessary for cells to survive a $Ce^{4+}$-caused acidic environment and is one of the mechanisms of $Ce^{4+}$-induced apoptosis. Furthermore, the $Ca^{2+}$ influx across the plasma membrane mediated both the $Ce^{4+}$-induced apoptosis and taxol biosynthesis.

Single-machine scheduling problems with an aging effect

Chuan-li Zhao,Heng-yong Tang 한국전산응용수학회 2007 Journal of applied mathematics & informatics Vol.25 No.1