Human lactoferrin efficiently targeted into caprine beta-lactoglobulin locus with transcription activator-like effector nucleases

Yu-Guo Yuan,Shao-Zheng Song,Meng-Ming Zhu,Zheng-Yi He,Rui Lu,Ting Zhang,Fei Mi,Jin-Yu Wang,Yong Cheng 아세아·태평양축산학회 2017 Animal Bioscience Vol.30 No.8

Objective: To create genetically modified goat as a biopharming source of recombinant human lacotoferrin (hLF) with transcription activator-like effector nucleases. Methods: TALENs and targeting vector were transferred into cultured fibroblasts to insert hLF cDNA in the goat beta-lactoglobulin (BLG) locus with homology-directed repair. The gene targeted efficiency was checked using sequencing and TE7I assay. The bi-allelic gene targeted colonies were isolated and confirmed with polymerase chain reaction, and used as donor cells for somatic cell nuclear transfer (SCNT). Results: The targeted efficiency for BLG gene was approximately 10%. Among 12 Bi-allelic gene targeted colonies, five were used in first round SCNT and 4 recipients (23%) were confirmed pregnant at 30 d. In second round SCNT, 7 (53%), 4 (31%), and 3 (23%) recipients were confirmed to be pregnant by ultrasound on 30 d, 60 d, and 90 d. Conclusion: This finding signifies the combined use of TALENs and SCNT can generate bi-allelic knock-in fibroblasts that can be cloned in a fetus. Therefore, it might lay the foundation for transgenic hLF goat generation and possible use of their mammary gland as a bioreactor for large-scale production of recombinant hLF.

Modelling of the Hot Flow Behaviors for Ti-13Nb-13Zr Alloy by BP-ANN Model and Its Application

Guo-zheng Quan,Shi-ao Pu,Zong-yang Zhan,Zhen-yu Zou,Ying-ying Liu,Yu-feng Xia 한국정밀공학회 2015 International Journal of Precision Engineering and Vol. No.

The plastic deformation mechanisms and the constitutive model of flow behaviors at different deformation conditions in biomedical titanium alloy are an essential step to optimize the design of any forging process for implant productions. A series of isothermal compressions tests on Ti-13Nb-13Zr alloy in a wide range of true strain, temperature and strain rate were conducted on a thermomechanical simulator. The hot flow behaviors with different softening mechanisms, including dynamic recrystallization and dynamic recovery, were characterized based on true strain-stress curves. A back-propagational artificial neural network (BP-ANN) method was conducted to evaluate and predict this non-linear problem by self-training to be adaptable to the material characteristics. The flow stress of this material a wide deformation condition range can be predicted accurately by the BP-ANN model obtained in this study. The prediction ability of this BP-ANN Model was evaluated by three accuracy indexes, Absolute error, Relative error and Average absolute relative error. Sequently, the developed BP-ANN model was programed and implanted into the finite element (FE) analysis platform, Msc.Marc software. The results have sufficiently articulated that the well-trained ANN model has excellent capability to deal with the complex flow behaviors and has great application potentiality in hot deformation processes.

Comparison of Liver Transplantation and Liver Resection for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus Type I and Type II

Jia-Yu Lv,Ning-Ning Zhang,Ya-Wei Du,Ying Wu,Tian-Qiang Song,Ya-Min Zhang,Yan Qu,Yu-Xin Liu,Jie Gu,Ze-Yu Wang,Yi-Bo Qiu,Bing Yang,Da-Zhi Tian,Qing-Jun Guo,Li Zhang,Ji-San Sun,Yan Xie,Zheng-Lu Wang,Xin 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.1

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellularcarcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involvedand divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were comparedbefore and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR(p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longermedian RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335,respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase(AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion: LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels>200 ng/mL.

A Prediction Model Based on the Risk Factors Associated with Pathological Upgrading in Patients with Early-Stage Gastric Neoplasms Diagnosed by Endoscopic Forceps Biopsy

Zhao Yu Han,Zheng Yu,Sha Jie,Hua Hong Jin,Li Ke Dong,Lu Yu,Dang Yi Ni,Zhang Guo Xin 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.1

Background/Aims: The discrepancies between the diagnosis of preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) in patients with early gastric neoplasm (EGN) exist objectively. Among them, pathological upgrading directly influences the accuracy and appropriateness of clinical decisions. The aims of this study were to investigate the risk factors for the discrepancies, with a particular focus on pathological upgrading and to establish a prediction model for estimating the risk of pathological upgrading after EFB. Methods: We retrospectively collected the records of 978 patients who underwent ESD from December 1, 2017 to July 31, 2021 and who had a final histopathology determination of EGN. A nomogram to predict the risk of pathological upgrading was constructed after analyzing subgroup differences among the 901 lesions enrolled. Results: The ratio of pathological upgrading was 510 of 953 (53.5%). Clinical, laboratorial and endoscopic characteristics were analyzed using univariable and binary multivariable logistic regression analyses. A nomogram was constructed by including age, history of chronic atrophic gastritis, symptoms of digestive system, blood high density lipoprotein concentration, macroscopic type, pathological diagnosis of EFB, uneven surface, remarkable redness, and lesion size. The C-statistics were 0.804 (95% confidence interval, 0.774 to 0.834) and 0.748 (95% confidence interval, 0.664 to 0.832) in the training and validation set, respectively. We also built an online webserver based on the proposed nomogram for convenient clinical use. Conclusions: The clinical value of identifying the preoperative diagnosis of EGN lesions is limited when using EFB separately. We have developed a nomogram that can predict the probability of pathological upgrading with good calibration and discrimination value.

BRCA1 Gene Exon 11 Mutations in Uighur and Han Women with Early-onset Sporadic Breast Cancer in the Northwest Region of China

Cao, Yu-Wen,Fu, Xin-Ge,Wan, Guo-Xing,Yu, Shi-Ying,Cui, Xiao-Bin,Li, Li,Jiang, Jin-Fang,Zheng, Yu-Qin,Zhang, Wen-Jie,Li, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

The prevalence of BRCA1 gene mutations in breast cancer differs between diverse ethnic groups. Relatively little information is known about patterns of BRCA1 mutations in early-onset breast cancer in women of Uighur or Han descent, the major ethnic populations of the Xinjiang region in China. The aim of this study was to identify BRCA1 mutations in Uighur and Han patients with early-onset (age <35 years), and sporadic breast cancer for genetic predisposition to breast cancer. For detection of BRCA1 mutations, we used a polymerase chain reaction single-stranded conformation polymorphism approach, followed by direct DNA sequencing in 22 Uighur and 13 Han women with early-onset sporadic breast cancer, and 32 women with benign breast diseases. The prevalence of BRCA1 mutations in this population was 22.9% (8/35) among early-onset sporadic breast cancer cases. Of these, 31.8% (7/22) of Uighur patients and 7.69% (1/13) of Han patients were found to have BRCA1 mutations. In 7 Uighur patients with BRCA1 mutations, there were 11 unique sequence alterations in the BRCA1 gene, including 4 clearly disease-associated mutations on exon 11 and 3 variants of uncertain clinical significance on exon 11, meanwhile 4 neutral variants on intron 20 or 2. None of the 11 BRCA1 mutations identified have been previously reported in the Breast Cancer Information Core database. These findings reflect the prevalence of BRCA1 mutations in Uighur women with early-onset and sporadic breast cancer, which will allow for provision of appropriate genetic counseling and treatment for Uighur patients in the Xinjiang region.

Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice

Guo, Qi,Shen, Zhiyang,Yu, Hongxia,Lu, Gaofeng,Yu, Yong,Liu, Xia,Zheng, Pengyuan The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.1

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated $I{\kappa}B{\alpha}$ and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

Concomitant EGFR Inhibitors Combined with Radiation for Treatment of Non-small Cell Lung Carcinoma

Zheng, De-Jie,Yu, Guo-Hua,Gao, Jian-Feng,Gu, Jun-Dong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Epidermal growth factor receptor (EGFR) is considered to be one of the key driver genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line treatment of NSCLC. Many advances have been made in the understanding of EGFR signal transduction network and the interaction between EGFR and tumor microenvironment in mediating cancer survival and development. The concomitant targeted therapy and radiation is a new strategy in the treatment of NSCLC. A number of preclinical studies have demonstrated synergistic anti-tumor activity in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In the present review, we discuss the rationale of the combination of EGFR inhibitors and radiotherapy in the treatment of NSCLC.

Study on post-flutter state of streamlined steel box girder based on 2 DOF coupling flutter theory

Guo, Junfeng,Zheng, Shixiong,Zhu, Jinbo,Tang, Yu,Hong, Chengjing Techno-Press 2017 Wind and Structures, An International Journal (WAS Vol.25 No.4

The post-flutter state of streamlined steel box girder is studied in this paper. Firstly, the nonlinear aerodynamic self-excited forces of the bridge deck cross section were investigated by CFD dynamic mesh technique and then the nonlinear flutter derivatives were identified on this basis. Secondly, based on the 2-degree-of-freedom (DOF) coupling flutter theory, the torsional amplitude and the nonlinear flutter derivatives were introduced into the traditional direct flutter calculation method, and the original program was improved to the "post-flutter state analysis program" so that it can predict not only the critical flutter velocity but also the movement of the girder in the post-flutter state. Finally, wind tunnel tests were set to verify the method proposed in this paper. The results show that the effect of vertical amplitude on the nonlinear flutter derivatives is negligible, but the torsional amplitude is not; with the increase of wind speed, the post-flutter state of streamlined steel box girder includes four stages, namely, "little amplitude zone", "step amplitude zone", "linearly growing amplitude zone" and "divergence zone"; damping ratio has limited effect on the critical flutter velocity and the steady state response in the post-flutter state; after flutter occurs, the vibration form is a single frequency vibration coupled with torsional and vertical DOF.

Thermal Behavior Analysis and Thermal Error Compensation for Motorized Spindle of Machine Tools

Zheng-Chun Du,Si-Yu Yao,Jian-Guo Yang 한국정밀공학회 2015 International Journal of Precision Engineering and Vol. No.

The thermal error deformation of motorized spindle plays an important role in the precision machining, while error compensation has been proved to be a cost-effective way. Herein a symmetrical solution for the thermal error problem of spindle is proposed based on the thermal behavior analysis. Firstly, the heat generating and transfer mechanism are described considering the heat sources. Next, ANSYS is used to achieve the steady-state and the transient thermal field distribution as well as the related deformation with the given thermal load and boundary condition. Furthermore, the NEM is proposed to predict the thermal error under random rotating speed with no use of thermal sensors, followed by the determination of two important parameters. The verification experiment of the thermal error under random rotating speed is executed. The External Machine Zero Point Shift function of the CNC system is adopted to develop the real-time compensation system on the spindle of HDBS-63 machining center. The maximum axial thermal error is greatly reduced from 55 to 16 um, while the radial one similarly reduced from 15 to 6 um. Both are improved 73% and 63% respectively. The experiment results show that NEM method is simple but of good reliability and practicality.

Protective effect of hepatocyte-enriched lncRNA-Mir122hg by promoting hepatocyte proliferation in acute liver injury

Yu Zhenjun,Li Yuhan,Shao Shuai,Guo Beichen,Zhang Mengxia,Zheng Lina,Zhang Kun,Zhou Feng,Zhang Li,Chen Chiyi,Jiang Wentao,Hong Wei,Han Tao 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Some long noncoding RNAs (lncRNAs), which harbor microRNAs in their gene sequence and are also known as microRNA host gene derived lncRNAs (lnc-MIRHGs), play a dominant role alongside miRNAs, or both perform biological functions synergistically or independently. However, only a small number of lnc-MIRHGs have been identified. Here, multiple liver injury datasets were analyzed to screen and identify the target lncRNA Mir122hg. Mir122hg was mainly enriched in liver tissues with human-mouse homology. In both CCl4-induced acute liver injury and Dgal/LPS-induced fulminant liver failure in mice, Mir122hg was sharply downregulated at the early stage, while a subsequent significant increase was only found in the CCl4 group with liver recovery. Overexpression and silencing assays confirmed that Mir122hg played a protective role in acute injury by promoting hepatocyte proliferation in vivo and in vitro. Consistent with the results of gene enrichment analysis, Mir122hg binding to C/EBPα affected its transcriptional repression, promoted gene transcription of downstream chemokines, Cxcl2, Cxcl3, and Cxcl5, and exerted pro-proliferative effects on hepatocytes through activation of the AKT/GSK-3β/p27 signaling pathway by CXC/CXCR2 complexes. This study identifies a novel lncRNA with protective effects in acute liver injury and demonstrates that the binding of Mir122hg-C/EBPα promotes hepatocyte proliferation via upregulation of CXC chemokine and activation of AKT signaling.