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>

Bioremediation of Coastal Saline-Alkali Marshy Soil by the Irrigation with Pulp & Paper Wastewater

LI Jia-liang,LU Zhao-hua,TIAN Jia-yi,WANG Lin,LI Peng-hui,XIAO Zhong-feng 대전대학교 환경문제연구소 2009 환경문제연구소 논문집 Vol.13 No.-

Based on the importance of coastal saline-alkali soil remediation in Yellow River Delta, China, the Cl-、Na+ transferring tendency in soil and the saline-alkali soil eco-remediation effects were researched by measuring soil Cl-、Na+ 、soluble salt、soil respire rate and dry biomass weight of reed, etc. periodically. The results shows: the concentration of irrigated soil Cl-、Na+ and soluble salt were decreased 57.7-70%、45.7-47.1% and 53.2-59.7%, respectively, and soil salt decreasing level were little influenced by the hydraulic load, inundation depth varies in some degree, but it was influenced by dry-wet alternative irrigating mode The concentration of soil total nitrogen、organic mass、microbial respire rate, and the reed biomass above ground were increased averagely to 2.17、1.20、1.46 and 1.34 multiple respectively afterirrigation with wastewater, which have complex remediation effects on the coastal saline-alkali wetland, but there are some differences among the different irrigating crafts.

Pre-treatment Metabolic Tumor Volume and Total Lesion Glycolysis are Useful Prognostic Factors for Esophageal Squamous Cell Cancer Patients

Li, Yi-Min,Lin, Qin,Zhao, Long,Wang, Li-Chen,Sun, Long,Dai, Ming-Ming,Luo, Zuo-Ming,Zheng, Hua,Wu, Hua Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Objectives: To study application of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) with $^{18}F$-FDG PET/CT for predicting prognosis of esophageal squamous cell cancer (ESC) patients. Methods: Eighty-six patients with ESC staged from I to IV were prospectively enrolled. Cisplatin-based chemoradiotherapy (CCRT) or palliative chemoradiotherapy were the main treatment methods and none received surgery. $^{18}F$-FDG PET/CT scans were performed before the treatment. SUVmax, MTV, and TLG were measured for the primary esophageal lesion and regional lymph nodes. Receiver operating characteristic curves (ROCs) were generated to calculate the P value of the predictive ability and the optimal threshold. Results: MTV and TLG proved to be good indexes in the prediction of outcome for the ESC patients. An MTV value of 15.6 ml and a TLG value of 183.5 were optimal threshold to predict the overall survival (OS). The areas under the curve (AUC) for MTV and TLG were 0.74 and 0.70, respectively. Kaplan-Meier analysis showed an MTV less than 15.6 ml and a TLG less than 183.5 to indicate good media survival time (p value <0.05). In the stage III-IV patient group, MTV could better predict the OS (P < 0.001), with a sensitivity and specificity of 0.80 and 0.67, respectively. Conclusions: Pre-treatment MTV and TLG are useful prognostic factors in nonsurgical ESC.

Bimodal Phenomenon of the Stress–Strain Curve During Hot Compression of LA43M Mg–Li Alloy

Yi Li,Yanjin Guan,Hu Chen,Jiqiang Zhai,Jun Lin,Liang Chen 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.10

In this study, the samples of LA43M Mg–Li alloy were compressed to the true strains of 0.12, 0.16, 0.36 and 0.60 under300 °C and the strain rate of 0.1 s−1. Under this condition, the stress–strain curves present a special bimodal phenomenon atthe early deformation stage, which is caused by twinning and dynamic recrystallization. In the process of hot compression,extension twins generated first. Twinning accommodated strain and the glide of twinning dislocations dissipated local strainenergy, resulting in the first local stress drop. Then extension twins coarsened and devoured all the matrix, leading to thechange of grain orientation. Subsequently, dislocations accumulated at the grain boundaries and resulted in the increase instress. With further strain, dynamic recrystallization occurred, discontinuous dynamic recrystallization is the main dynamicrecrystallization mechanism. The generation of dynamic recrystallization resulted in the strain softening and leaded tothe second local stress drop. Twinning retards the occurrence dynamic recrystallization and has a crucial influence on themicrostructure development during the hot compression of LA43M.

Weight Gain in Pregnancy, Maternal Age and Gestational Age in Relation to Fetal Macrosomia

( Yi Li ),( Qi-fei Liu ),( Dan Zhang ),( Ying Shen ),( Kui Ye ),( Han-lin Lai ),( Hai-qing Wang ),( Chuan-lai Hu ),( Qi-hong Zhao ),( Li Li ) 한국임상영양학회 2015 Clinical Nutrition Research Vol.4 No.2

To investigate the possible risk factors related to macrosomia. Pregnant women and their newborns (n = 1041) were recruited from a cohort study in Maternal and Child Care Center of Hefei from January 2011 to July 2012. Questionnaires were applied to collect the demographic data besides the medical records. Detailed health records of the entire pregnancy were obtained using retrospective study. Meanwhile the data of neonatal outcomes was prospectively tracked. Associations between exposure risk factors and macrosomia were analyzed using Pearson’s chi squared test. Logistic regression models were used to assess the independent association between these potential predictors and macrosomia. The incidence of macrosomia of this cohort was 11.24% of which male: female = 2.55:1. Male incidence (8.07%) of macrosomia was higher than female (3.17%), p < 0.001. Body mass index (BMI) before pregnancy (pre-BMI), maternal height, parity were not independently associated with macrosomia; multiple logistic regression analysis indicated that macrosomia was mainly independently associated with weight gain in pregnancy (OR=1.14,95% CI [1.10-1.19]), maternal age (OR = 1.09,95% CI [1.03-1.15]) and gestational age (OR = 1.62,95% CI [1.31-1.99]), respectively. Our findings indicate that weight gain in pregnancy, maternal age and gestational age should be considered as independent risk factors for macrosomia.

rs10505474 and rs7837328 at 8q24 Cumulatively Confer Risk of Prostate Cancer in Northern Han Chinese

Zhang, Lin-Lin,Sun, Liang,Zhu, Xiao-Quan,Xu, Yong,Yang, Kuo,Yang, Fan,Yang, Yi-Ge,Chen, Guo-Qiang,Fu, Ji-Cheng,Zheng, Chen-Guang,Li, Ying,Mu, Xiao-Qiu,Shi, Xiao-Hong,Zhao, Fan,Wang, Fei,Yang, Ze,Wang, Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Aims: Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer (pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previously identified variants as candidates and to define the association with PCa in Northern Han Chinese. Methods: 749 subjects from Beijing and Tianjin in Northern China were included. Six variants (rs10505474, rs7837328, rs4242384, rs7813, rs486907 and rs1058205) were genotyped by high resolution melting (HRM) assays. The individual and cumulative contribution for of the risk of PCa and clinical covariates were analyzed. Results: Among the six candidate variants, onlyrs10505474, and rs7837328, both locating at 8q24 region, were associated with PCa in our population.rs10505474 (A) was associated with PCa ($OR_{recessive}=1.56$, p=0.006); and rs7837328 (A) was associated with PCa ($OR_{dominant}=1.38$, p=0.042/$OR_{recessive}=1.99$, p=0.003). Moreover, we observed a cumulative effects between them ($p_{trend}=2.58{\times}10^{-5}$). The joint population attributable risk showed the two variants might account for 71.85% of PCa risk. In addition, we found the homozygotes of rs10505474 (A) and rs7837328 (A) were associated with PCa clinical covariants (age at onset, tumor stage, respectively) ($p_{age}=0.046$, $P_{tumorstage}=0.048$). Conclusion: rs10505474 (A) and rs7387328 (A) at 8q24 are associated with PCa and cumulatively confer risk, suggesting the two variations could determine susceptibility to PCa in the Northern Chinese Han population.

Process Design and Longitudinal Deformation Prediction in Continuous Sheet Metal Roll Forming for Three- Dimensional Surface

Zhong-Yi Cai,Lin-Lin Li,Mi Wang,Ming-Zhe Li 한국정밀공학회 2014 International Journal of Precision Engineering and Vol. No.

Continuous roll forming (CRF) is a process to form three-dimensional surface based on the rolling deformation of sheet metal. Unliketraditional rolling process where the working rolls are straight and rigid, two small-diameter bendable forming rolls are used herein,and the sheet metal is bent in longitudinal and transverse directions simultaneously after it is compressed between a pair of bendedrolls. The formed surface is controlled by the curved shapes of the forming rolls and the gap between the two rolls, and the roll gapis the crucial parameter of CRF process. In this paper, the required velocity distribution of material across the exit of roll gap forthe formation of a smooth surface is analyzed, the formulations for the CRF process design is derived and a method to predict thelongitudinal bending deformation generated by roll gap is presented. Finally, the validity of the presented methods and theoreticalmodels are demonstrated by numerical simulations and CRF tests for typical surface parts.

Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson’s Disease

Hung-Li Wang,Chin-Song Lu,Tu-Hsueh Yeh,Yu-Ming Shen,Yi-Hsin Weng,Ying-Zu Huang,Rou-Shayn Chen,Yu-Chuan Liu,Yi-Chuan Cheng,Hsiu-Chen Chang,Ying-Ling Chen,Yu-Jie Chen,Yan-Wei Lin,Chia Chen Hsu,Huang-Li 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.4

Background and Purpose It is essential to develop a reliable predictive serum biomarker for Parkinson’s disease (PD). Te accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. Te purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. Methods Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. Results The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutof age than in the group above the cutof age. Conclusions Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.

Treatment Retention Rates of 3-monthly Paliperidone Palmitate and Risk Factors Associated with Discontinuation: A Population-based Cohort Study

Chien-Heng Lin,Huang-Li Lin,Chih-Lin Chiang,Yi-Wen Chen,Yan-Fang Liu,Yen Kuang Yang,Chao-Hsiun Tang 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.3

Objective: Limited evidence exists regarding real-world 3-monthly paliperidone palmitate (PP3M) treatment retention and associated factors. Methods: We conducted a retrospective, nationwide cohort study using the Taiwan National Health Insurance Research Database between October 2017 and December 2019. Adult patients with schizophrenia initiated on PP3M were enrolled. The primary outcomes were time to PP3M discontinuation, time to psychiatric hospitalization, and the proportions of patients receiving the next PP3M dose within 120 days among first-, second-, and third-dose completers. Key covariates included prior PP1M duration and adequate PP3M initiation. Results: The PP3M treatment retention rates were 79.7%, 66.3%, and 52.5% after 6, 12, and 24 months, respectively, with 86.4%, 90.6%, and 90.0% of respective first-, second-, and third-dose completers receiving the next PP3M dose. Adequate PP3M initiation and prior PP1M treatment duration > 180 days were associated with favorable PP3M treatment retention. In multivariate analyses, PP1M durations of 180−360 days (adjusted relative risk [aRR], 1.76) or < 180 days (aRR, 2.79) were associated with PP3M discontinuation at the second dose. Inadequate PP3M initiation was associated with discontinuation at the third dose (aRR, 2.18). Patients fully adherent to PP3M treatment in the first year had a higher probability of being free from psychiatric hospitalization (86.7% at 2 years), compared with those partially adherent or non-adherent to PP3M in the first year. Conclusion: Prior PP1M duration and adequate PP3M initiation are major factors affecting PP3M treatment retention. Higher PP3M treatment retention is associated with a lower risk of psychiatric hospitalization.

A 3-Gb/s Equalizer with an Adaptive Swing Controller for TFT-LCD Interfaces

Miao-Shan Li,Yen-Chen Lin,Chai-Chi Liu,Ching-Rong Chang,Jyun-Yi Li,You-Sheng Lin,Ching-Yuan Yang 대한전자공학회 2019 Journal of semiconductor technology and science Vol.19 No.1

A 0.18-μm CMOS 3-Gb/s equalizer with an adaptive swing controller is presented for 4K2K large display panels to compensate a 24-dB channel loss. Employing the output-swing control technique, we propose the adaptive loop for the equalizer to improve adaptation accuracy without degrading the boost tuning and input swing ranges. Besides, cascading two bandpass filters (BPF) measured energy in a narrow range is much more accuracy than conventional highpass filters (HPF). The measured jitter of 3-Gb/s and 1.5-Gb/s data are 0.23-UI and 0.356-UI for 1.23-m FR4 board, respectively. The core area occupies 0.12-㎟ and the power consumption is 27-mW at 3 Gb/s from a 1.8-V supply.