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>

An Antiviral Mechanism Investigated with Ribavirin as anRNA Virus Mutagen for Foot-and-mouth Disease Virus

Li-li Shi,Cong-yi Zheng,Chao-jiang Gu,Qian Zhang,Yong Li,San-fu Qu 한국생화학분자생물학회 2006 BMB Reports Vol.39 No.1

An Antiviral Mechanism Investigated with Ribavirin as an RNA Virus Mutagen for Foot-and-mouth Disease Virus

Chao Jiang Gu,Cong Yi Zheng,Qian Zhang,Li Li Shi,Yong Li,San Fu Qu 한국생활환경학회 2006 BMB Reports Vol.39 No.1

Bearing Habits of Acer truncatum and the Relationship Between Its Branch Characteristics and Fruiting Performance

Chao Li,Xiaoling Liu,Yi Feng,Tian Bao,Changqi Ye,Dailong Li,Shuchai Su 한국원예학회 2021 원예과학기술지 Vol.39 No.2

In recent years, seeds of the Shantung maple have attracted attention for their economic and medicinal value due to the high nervonic acid content in their seed oil, which has a curative effect on some demyelinating diseases. However, few studies have investigated its fruiting habits and branch characteristics; therefore, the purpose of this research was to investigate the fruit bearing habits of A. truncatum and analyze the relationship between its branch characteristics and fruiting performance to provide a basis for management. The branch structure, flower-bearing position, and continuous fruiting ability of 200 A. truncatum individuals were recorded from 2014–2017. The results showed that parent and bearing shoots of A. truncatum were usually short (less than 10 cm) with fruit developed by terminal mixed buds of the parent shoot. A. truncatum can form a Y-shaped branch group with continuous fruiting ability for many years via a lateral shoot of the bearing shoot. The position and slenderness of the parent shoot had a significant influence on the yield of the bearing shoot and seed weight, length, and thickness. The top and basal diameters of the parent shoot had a significant influence on the yield of the bearing shoot. Group comparison results showed that the most effective and convenient method for the selection of parent shoots with high fruiting performance was based on the position and top diameter of the parent shoots, among which the parent shoots with a top diameter thicker than 3.08 mm developed by a lateral bud in a vegetative branch had greater yield, number of fruit, and seed weight.

Thermal pretreatment of poplar sawdust at 100 °C in water or with microwave heating impacts the pyrolysis behaviors

Chao Li,Baihong Li,Guoming Gao,Lijun Zhang,Shu Zhang,Lei Zhang,Jun Xiang,Song Hu,Yi Wang,Xun Hu 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.125 No.-

Drying at 100 C is a common practice for processing many biomasses for their further thermochemicalconversion via the routes such as pyrolysis. The drying temperature of 100 C is low, but might not be toolow to cause any impact on pyrolytic behaviors of a biomass feedstock. In this study, varied scenarios ofthermal pretreatment of poplar sawdust (oven-drying, boiling in water and microwave heating) at 100 Cwere screened for probing their potential influence on the pyrolytic behaviors at 500 and 750 C. Comparing with oven-drying, boiling in water (cooking) and microwave heating at 100 C could removesome oxygen-containing species, increasing carbon content of the pretreated sawdust and promotingcarbonization in pyrolysis. This enhanced formation of biochar, heavy p-conjugated organics in bio-oil,but suppressed generation of gas. The cooking or microwave heating pretreatment also promoted aromatizationto form the biochar of higher thermal stability, higher crystallinity, and higher aromatic degree,due to the enhanced deoxygenation reactions in the pyrolysis. The in-situ IR characterization suggestedthat microwave pretreatment promoted generation of unsaturated ketones and also the species with olefinicC = C, favoring their further aromatization. The cooking pretreatment impacted transformationroutes of the oxygen-containing organics, thus modifying pyrolysis behaviors of the pretreated sawdust.

An Antiviral Mechanism Investigated with Ribavirin as an RNA Virus Mutagen for Foot-and-mouth Disease Virus

Gu, Chao-Jiang,Zheng, Cong-Yi,Zhang, Qian,Shi, Li-Li,Li, Yong,Qu, San-Fu Korean Society for Biochemistry and Molecular Biol 2006 Journal of biochemistry and molecular biology Vol.39 No.1

To prove whether error catastrophe /lethal mutagenesis is the primary antiviral mechanism of action of ribavirin against foot-and-mouth disease virus (FMDV). Ribavirin passage experiments were performed and supernatants of $Rp_1$ to $Rp_5$ were harvested. Morphological alterations as well as the levels of viral RNAs, proteins, and infectious particles in the BHK-21 cells infected using the supernatants of $Rp_1$ to $Rp_5$ and control were measured by microscope, real-time RT-PCR, western-blotting and plaque assays, respectively. The mutation frequency was measured by sequencing the complete P1- and 3D-encoding region of FMDV after a single round of virus infection from ribavirin-treated or untreated FMDV-infected cells. Ribavirin treatment for FMDV caused dramatically inhibition of multiplication in cell cultures. The levels of viral RNAs, proteins, and infectious particles in the BHK-21 cells infected were more greatly reduced along with the passage from $Rp_1$ to $Rp_5$, moreover, nucleocapsid protein could not be detected and no recovery of infectious virus in the supernatant or detection of intracellular viral RNA was observed at the $Rp_5$-infected cells. A high mutation rate, giving rise to an 8-and 11-fold increase in mutagenesis and resulting in some amino acid substitutions, was found in viral RNA synthesized at a single round of virus infection in the presence of ribavirin of $1000\;{\mu}M$ and caused a 99.7% loss in viral infectivity in contrast with parallel untreated control virus. These results suggest that the antiviral molecular mechanism of ribavirin is based on the lethal mutagenesis/error catastrophe, that is, the ribavirin is not merely an antiviral reagent but also an effective mutagen.

Correlation between DNA methylation and Thymic Stromal Lymphopoietin expression in asthmatic airway epithelial cells

Yan‑Li Li,Xi‑Qian Xing,Yi Xiao,Yan‑Hong Liu,Yu‑Shan Zhou,Min Zhuang,Chao‑Qian Li 한국유전학회 2020 Genes & Genomics Vol.42 No.12

Background: The overexpression of TSLP and DNA methylation in asthma were both risk factors the relationship was not clear. Objective: This study aimed to investigate the relationship between methylation status of TSLP promoter and mRNA/protein expression in asthmatic airway epithelial cells. Methods: Human bronchial epithelial cells were cultured in vitro and divided into: Control group, treated with PBS, model group, sensitized with LPS (10 μg/mL) for 12 h (37 °C, 5% CO2). Other groups were cultured with the pCMV3 plasmid (M + NC/pCMV), pGPH1 plasmid (M + NC/pGPH), DNMT1/pCMV3 plasmid (M + DNMT1/pCMV), and DNMT1/pGPH1 plasmid (M + DNMT1/pGPH) for 48 h. The expression of DNA methyltransferase 1 and TSLP were measured using real-time PCR and western blotting. Results: Compared with the control group, TSLP mRNA (1.00 ± 0.00 vs. 2.82 ± 0.81 vs. 1, P < 0.001) and protein (1.07 ± 0.04 vs. 1.46 ± 0.11, P < 0.01) were significantly greater, and the methylation of promoter was lower (92.75 ± 1.26 vs. 58.57 ± 3.34, P < 0.05) in the model group. Compared with the model group, TSLP mRNA (2.82 ± 0.81 vs. 1.17 ± 0.10, P < 0.001) decreased, but TSLP promoter methylation increased (58.57 ± 3.34 vs. 92.58 ± 7.30, P < 0.05) in M + DNMT1/pCMV. TSLP mRNA and protein were higher (2.82 ± 0.81 vs. 5.32 ± 0.21, P < 0.001; 1.46 ± 0.11 vs. 1.94 ± 0.11, respectively, P < 0.01), TSLP promoter methylation was lower (58.57 ± 3.34 vs. 33.57 ± 4.29, P < 0.05) in M + DNMT1/pGPH. Conclusions: Overexpression of TSLP in asthmatic airway epithelial cells may be regulated by DNA demethylation.

EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-Barr Virus Associated Chronic Lymphocytic Leukemia

Dan-Min Xu,Yi-Lin Kong,Li Wang,Hua-Yuan Zhu,Jia-Zhu Wu,Yi Xia,Yue Li,Shu-Chao Qin,Lei Fan,Jian-Yong Li,Jin-Hua Liang,Wei Xu 대한암학회 2020 Cancer Research and Treatment Vol.52 No.2

Purpose The purpose of this study was to investigate the prognostic impact of Epstein-Barr virus (EBV)–microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene. Materials and Methods Quantitative reverse transcription–polymerase chain reaction and western blotting were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL. Results p53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p < 0.001) which was also an independent prognostic marker for overall survival (p=0.028; hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLL patients after adjusted with International Prognostic Index for patients with CLL. We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3- untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1- 1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines. Conclusion This study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.

Sublethal effects of beta-cypermethrin on the bird cherry-oat aphid Rhopalosiphum padi (Hemiptera: Aphididae)

Qing-Qing Zhang,Wen-Qiang Li,Zeng-Bin Lu,Li-Li Li,Yi Yu,Chao Li,Xing-Yuan Men 한국응용곤충학회 2019 Journal of Asia-Pacific Entomology Vol.22 No.3

Rhopalosiphum padi is a sap-sucking aphid and an important pest of wheat that causes considerable yield loss. Beta-cypermethrin, a synthetic pyrethroid pesticide, has a broad insecticide spectrum and is considered effective for aphid control, while its residual concentrations may have sublethal effects on R. padi. Here, the sublethal effects of beta-cypermethrin on R. padi were conducted under laboratory conditions. The acute toxicity test showed that LC 10 , LC 20 , and LC 25 of beta-cypermethrin to R. padi adults were 0.003, 0.031 and 0.079 mg L −1 , respectively. The pre-adult survival rate was significantly reduced by all three concentrations. LC 20 significantly extended the development duration of 1st instar nymphs, pre-oviposition period, and oviposition period of R. padi. The adult longevity was also reduced by LC 25 . However, the fecundity did not differ between the betacypermethrin treatment and control. For life table parameters, both the finite rate (λ) and intrinsic rate of increase (r) decreased at LC 10 and LC 20 , as well as the net reproductive rate (R 0 ) reduced at LC 10 and LC 25 , while mean generation time (T) increased at LC 20 . Thus, at the concentrations of beta-cypermethrin tested here, there were negative impacts on R. padi fitness by decreased pre-adult survival rate, λ, r, and R 0 , and delayed the development of some stages and increased T.

Anesthetic Management and Outcomes of Endovascular Treatment of Basilar Artery Occlusion: Results From the ATTENTION Registry

Tao Chunrong,Yuan Guangxiong,Xu Pengfei,Wang Hao,Zhou Peiyang,Yi Tingyu,Li Kai,Cui Tao,Gao Jun,Li Rui,Sun Jun,Zhang Chao,Wang Li,Liu Tianlong,Song Jianlong,Yin Yamei,Nguyen Thanh N.,Li Qing,Hu Wei 대한뇌졸중학회 2023 Journal of stroke Vol.25 No.3

Background and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. Methods This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. Results Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; <i>P</i>=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; <i>P</i>=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). Conclusion In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.