Safety and Efficacy of Elbasvir/Grazoprevir in Asian Participants with Hepatitis C Virus Genotypes 1 and 4 Infection

( Wei Lai ),( Hiromitsu Kumada ),( Ponni Perumalswami ),( Tawesak Tanwandee ),( Wendy Cheng ),( Jeong Heo ),( Pin Nan Cheng ),( Peggy Hwang ),( Sheng Mei Mu ),( Xu Min Zhao ),( Michael Robertson ),( B 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is emerging in the Asia-Pacific region. We conducted an integrated analysis of the safety and efficacy of elbasvir (EBR)/grazoprevir (GZR) in self-identified Asian participants who were enrolled in 11 EBR/GZR phase 2/3 studies. Methods: All participants received EBR/GZR 50 mg/100 mg alone for 12 weeks or in combination with ribavirin (RBV) for 16 weeks. The primary endpoint of all studies was sustained virologic response (HCV RNA < 15 IU/mL) 12 weeks after end of therapy (SVR12). Results: A total of 780 Asian participants with HCV GT1 or 4 infection were included (GT1b, n=715; GT1non-b, n=63; GT4, n=2). Most participants were enrolled from Japan (n=366, 46.9%), mainland China (n=146, 18.7%), Taiwan (n=109, 14.0%) and South Korea (n=90, 11.5%). Overall, 12.4% of participants had cirrhosis, and 20.4% were treatment-experienced. SVR12 was achieved by 756/780 (96.9%, 95% CI 95.5-98.0) of all Asian participants, including 748/772 (96.9%, 95% CI 95.4- 98.0) who received EBR/GZR for 12 weeks and 8/8 (100%, 95% CI 63.1-100.0) who received EBR/GZR + RBV for 16 weeks. The frequency of safety events among Asian participants was: any adverse event (AE), 58.1% (453/780), drug-related AEs, 23.6% (184/780), serious AEs, 2.6% (20/780), and discontinuation due to an AE, 0.9% (7/780). Fifteen participants (1.9%) had elevated ALT/AST levels that met the criteria for an event of clinical interest (ALT/AST >3× baseline and >100 U/L), 3 of whom discontinued treatment. The efficacy and safety profile of EBR/GZR was comparable to that observed among non-Asians. Conclusions: The combination of EBR/GZR was safe and highly effective in this large population of Asian participants with primarily HCV GT1b infection. Late transaminase elevations were reported in approximately 2% of participants, which is consistent with the safety profile of EBR/GZR in non-Asians.

Genome-wide identification and analysis of expression pattern of REVEILLE transcription factors in castor (Ricinus communis L.)

Wei Xue,Zhang Jixing,Wang Nan,Sun Mengdi,Ding Xue,Xu Hui,Yu Xiumin,Yue Wenran,Huo Hongyan,Yu Lili,Wang Xiaoyu 한국원예학회 2024 Horticulture, Environment, and Biotechnology Vol.65 No.3

REVEILLE (RVEs) transcription factors play an important role in regulating circadian clock, plant growth and development, and stress responses. While RVEs have been identifi ed in various plant species, comprehensive genome exploration and analysis of RVEs in castor ( Ricinus communis L.) have not been previously reported. In this study, we identifi ed RcRVEs in the castor genome through sequence alignment and conducted an analysis encompassing gene structures, protein motifs, physicochemical properties, transcription patterns under cold stress, diff erent tissues, and diurnal rhythm. A total of fi ve RcRVEs were pinpointed in the castor genome. Evolutionary tree analysis categorized these RcRVEs into three distinct groups, implying that diff erent RcRVEs may fulfi ll distinct biological functions. Furthermore, several abiotic stresses and hormone-responsive cis -acting elements were found in the promoters of the RcRVEs . RNA-sequencing (RNA-seq) analysis revealed that RcRVE1 and RcRVE7 were induced by cold stress and exhibited upregulation over time, indicating their involvement in regulating cold adaptation in castor plants. Five RcRVEs have notably higher expression levels in leaves compared to other tissues. The expression of all RcRVEs displayed diurnal rhythms under light/dark cycles. This study provides valuable insights into the potential functions of RcRVEs in regulating castor’s growth and development, and responses to cold stress.

Reinforcing effect of Lewis acid–base interaction on the high-temperature colloidal stability and tribological performance of lubricating grease

Nan Xu,Wei-Min Liu,Ming Zhang,Xiaobo Wang 한국공업화학회 2017 Journal of Industrial and Engineering Chemistry Vol.46 No.-

The high-temperature tribological performance of lithium grease is enhanced by addition of Lewis acidborate ester, which could interact with Lewis base RCO2of lithium 12-hydroxystearate (LHS, constitutethe thickenerfiber network of lithium grease) to form a Lewis acid–base complex. Important detailsabout the Lewis acid–base complex and its reinforcing effect on the tribological performance areelucidated by means of SRV oscillating friction and wear tester (SRV), Fourier transformation infraredspectroscopy (FTIR), TGA–DSC, and rheological methods. The experimental results strongly suggest thatthere is a Lewis base–acid interaction between the boron atom of borate ester or boric acid and theoxygen atom of RCO2. Lewis acid centers can serve as second-level linking points to reinforce thestrength of the thickenerfiber network and further improve the colloidal stability of lubricating grease. Compared with pure LHS, the Lewis acid–base complex displays higher thermal stability, allowinglithium grease to be applied to higher temperature. Because of the enhancement of thermal stability andcolloidal stability,film-forming property under high temperature can be greatly improved, resulting in>15% friction and >95% wear reductions.

Enhanced Production of L-Tryptophan with Glucose Feeding and Surfactant Addition and Related Metabolic Flux Redistribution in the Recombinant Escherichia coli

Wei Luo,Jin Huang,Xiangcheng Zhu,Lei Huang,Jin Cai,Zhi-nan Xu 한국식품과학회 2013 Food Science and Biotechnology Vol.22 No.1

The production of L-tryptophan was investigated in a recombinant strain Escherichia coli W3110-ZDrr. It was observed that phosphate and feeding strategies are key factors to ensure the good cell growth and high production of L-tryptophan. The simple exponential feeding strategy could only produce 10.6 g/L L-tryptophan due to the improper feeding rate; while the manual glucose-feedback feeding approach could effectively control the substrate and inhibit the formation of acetate, and thus improvemed the Ltryptophan production to 25.5 g/L. The modified exponential feeding approach avoided overfeeding or underfeeding and achieved high production of L-tryptophan. Moreover, the addition of Tween 60 or PL61 could enhance the cell growth and the production of L-tryptophan in the fed-batch mode. Subsequent metabolic flux analysis showed that more carbon flux was distributed into the biosynthesis of Ltryptophan when Tween 60 or PL61 was supplied. The present work presents one base for further large-scale production of this important amino acid.

DGE analysis of changes in gene expression in response to temperature and deltamethrin stress in the silkworm (Bombyx mori)

Xu-Dong TANG,Nan LIU,Wei Wang,Jieyun Yan,Li Xu,Zhongyuan Shen 한국응용곤충학회 2016 Journal of Asia-Pacific Entomology Vol.19 No.1

The silkworm (Bombyx mori) is an important insect for various industrial applications and is also a model insect for the order Lepidoptera. The silkworm is more resistant to deltamethrin at high temperatures than at low temperatures. To elucidate the role of the negative temperature coefficient of deltamethrin in the silkworm, digital gene expression (DGE) analysis was performed for the identification of differentially expressed genes in silkworms challenged with deltamethrin at different temperatures. Compared with deltamethrin exposure at 30 °C, silkworms treated at 20 °C exhibited more severe stress responses, and gene sets associated with peptidoglycan recognition protein (PGRP),mucin, and antimicrobial peptides (AMPs)were downregulated dramatically. Similarly, a decrease in genes related to reactive oxygen species scavenging was also detected, which may have resulted in an imbalance between radical-generating and radical-scavenging systems. These results indicated that the lower mortality rate after deltamethrin treatment at high temperature was caused by a series of gene alterations (quantitative increases) rather than qualitative changes.

Extraction of microbial transglutaminase from Amycolatopsis sp. fermentation broth using aqueous two-phase system

Nan Shi,Hongwei Xu,Kaiyuan Guo,Chunyu Kang,Wei Zhang,Yingying Zhang,Liping Zhang,Jianxin Tan 한국화학공학회 2017 Korean Journal of Chemical Engineering Vol.34 No.8

Partitioning of microbial transglutaminase (MTG) from Amycolatopsis sp. in the polyethylene glycol (PEG)/salt-based ATPS was investigated for the first time. The key parameters such as the molecular weight of PEG (PEG 600-6000), the type and concentration of phase-forming salt (ammonium sulfate or phosphates), the pH of system (pH 5.0-8.5), and the concentration of neutral salt (0-6% NaCl, w/w) were determined. The partition coefficient of the enzyme was not linear with PEG molecular weight; PEG1000 gave better yield than others. The concentration of PEG1000, ammonium sulfate and NaCl, and the system pH showed effects with different extents on specific activity (SA) and yield of the enzyme. In the ATPS of 26% w/w PEG 1000 and 19% w/w ammonium sulfate in the presence of 5% w/w NaCl and at pH 6.0, MTG was partitioned into the PEG-rich phase with a maximum yield of 86.51% and SA was increased to 0.83. The results of SDS-PAGE showed the MTG produced by the test strain differed from the enzymes reported before. Thus, this study proves that ATPS can be used as a preliminary step for partial purification of MTG from Amycolatopsis sp. fermentation broth.

Clinical Implications of p57^KIP2 Expression in Breast Cancer

Xu, Xiao-Yin,Wang, Wen-Qian,Zhang, Lei,Li, Yi-Ming,Tang, Miao,Jiang, Nan,Cai, Shou-Liang,Wei, Liang,Jin, Feng,Chen, Bo Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Objective: To study the relationship between expression of $p57^{KIP2}$ and prognosis and other clinicopathological parameters in invasive breast cancers. Methods: We assessed the expression of $p57^{KIP2}$ in 89 cases of invasive breast cancer and 20 cases of normal breast tissue by immunohistochemical methods and analyzed the results with SPSS software (ver. 16.0). Result: The positive expression rates of $p57^{KIP2}$ protein in the invasive breast cancers and surrounding normal tissue were 30.3% (27/89) and 65% (13/20), respectively. Cases with no $p57^{KIP2}$ expression exhibited a significantly higher post-operative distant metastasis rate than those with $p57^{KIP2}$ expression (37.9% vs. 14.8%; P = 0.01). DFS analysis showed that $p57^{KIP2}$-/C-erbB-2+ tumors also exhibited a significantly higher post-operative distant metastasis rate than the other groups (66.7% vs. 29.2%; P = 0.007), as did $p57^{KIP2}$-/p53+ tumors (64.3% vs. 22.7%; P = 0.001). Survival analysis revealed that $p57^{KIP2}$ was associated with breast cancer-specific survival overall (P = 0.045, log-rank test). Subgroup analysis demonstrated that individuals with $p57^{KIP2}$-/C-erbB-2+tumors experienced significantly worse post-operative survival than those with $p57^{KIP2}$-/C-erbB-2- or other tumors (P = 0.006, log-rank test). $p57^{KIP2}$-/p53+ tumors were associated with significantly worse post-operative survival than $p57^{KIP2}$-/p53- or other tumors (P = 0.001, log-rank test). Cox regression analysis showed that $p57^{KIP2}$ was a non-independent prognostic factor for breast cancer (P = 0.303). Conclusions: $p57^{KIP2}$ is expressed at low levels in invasive breast cancer and is associated with better overall survival rate and disease-free survival in breast cancer patients, but it was a non-independent prognostic factor for breast cancer. Thus, the connection between $p57^{KIP2}$/p53 and $p57^{KIP2}$/C-erbB-2 may provide biomarkers for breast cancer.

CHRNA5 rs16969968 Polymorphism Association with Risk of Lung Cancer - Evidence from 17,962 Lung Cancer Cases and 77,216 Control Subjects

Xu, Zhi-Wei,Wang, Guan-Nan,Dong, Zhou-Zhou,Li, Tao-Hong,Cao, Chao,Jin, Yu-Hong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: Genetic studies have shown a possible relationship between the rs16969968 polymorphism in CHRNA5 and the risk of lung cancer. However, the results have been conflicting. Thus we rigorously conducted a meta-analysis to clarify any association. Materials and Methods: A total of 10 case-control studies involving 17,962 lung cancer cases and 77,216 control subjects were analysed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of the association. Results: We found the CHRNA5 rs16969968 polymorphism to be associated with the risk of lung cancer (AA vs GG: OR=1.60, 95%CI=1.51-1.71). On stratified analysis by smoking status, a statistically significant increased risk was observed in the smoking group (AA vs GG: OR=1.80, 95%CI=1.61-2.01). However, this polymorphism was not associated with lung cancer risk in Asians (AA vs GG: OR=0.95, 95%CI=0.35-2.59), whereas it was linked to increased risk of lung cancer among Caucasians (AA vs GG: OR=1.65, 95%CI=1.55-1.76). Conclusions: Our meta-analysis provided statistical evidence for a strong association between rs16969968 polymorphism and the risk of lung cancer, especially in smokers and Caucasians. Application of this relationship may contribute to identification of individuals at high risk of lung cancer and indicate a chemoprevention target.

Distinctions Between Clinicopathological Factors and Prognosis of Alpha-fetoprotein Negative and Positive Hepatocelluar Carcinoma Patients

Xu, Jia,Liu, Chang,Zhou, Lei,Tian, Feng,Tai, Ming-Hui,Wei, Ji-Chao,Qu, Kai,Meng, Fan-Di,Zhang, Ling-Qiang,Wang, Zhi-Xin,Zhang, Jing-Yao,Chang, Hu-Lin,Liu, Si-Nan,Xu, Xin-Shen,Song, Yan-Zhou,Liu, Jun,Z Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.2

Serum alpha-fetoprotein (AFP) is a significant marker for clinical diagnosis and prognosis evaluation in hepatocellular carcinoma (HCC) patients. However, some proportion of liver cancer patients are AFP-negative (AFP ${\leq}$20ng/ml). In order to study the differences between clinicopathological factors and prognosis of alpha-fetoprotein negative and positive patients, a total of 114 cases (41 AFP-negative and 73 AFP-positive) were selected for our research. By systematically statistical analysis, the results demonstrated that compared with AFP-negative patients, AFP-positive examples were more likely to feature cirrhosis nodules, non-complete neoplasm capsules, and a poor Edmondson-steiner grade. Furthermore, AFP-negative patients demonstrated a favorable long-term prognosis. By univariate analysis and multivariate analysis with Cox's proportional hazards model, multiple tumors were found to be independent risk factors for worse survival of AFP negative patients; however, less tumor-free margins, multiple tumors and Edmondson-steiner grades III/IV, proved to be independent risk factors leading to a poor prognosis of AFP positive cases. Finally, we can infer that high levels of AFP signify a highly malignant tumor and unfavorable prognosis.

Nonlinear Instability of Angle Section Beams under Uniformly Distributed Loads

Wei-bin Yuan,Wei Zhang,Jie Xu,Nan-ting Yu 한국강구조학회 2016 International Journal of Steel Structures Vol.16 No.2

This paper presents a study on the flattening behavior of angle-section beams of finite length subjected to uniformly distributed transverse loads. Analytical solutions for static instabilities of angle-section beams when they are bent about their weak axis are derived using energy methods. The basic assumptions used in the present study are that the total strain energy of an angle-section beam subjected to a uniformly distributed load can be simplified into a two-stage process. One is the bending response of the two legs behaving as the plate; the other is the bending response as a beam with flattened section. The nonlinear instability is derived by applying the minimum potential energy principle and the corresponding static critical moments associated with the section flattening-induced buckling are determined. To validate the analytical solution developed, nonlinear finite element analyses are also conducted. Good agreement between the present solution and the FEA results is demonstrated.