In vitro evaluation of 9-(2-phosphonylmethoxyethyl)adenine ester analogues, a series of anti-HBV structures with improved plasma stability and liver release

Sha Liao,Shi-Yong Fan,Qin Liu,Chang-Kun L,Jia Chen,Jing-Lai Li,Zhi-Wei Zhang,Zhen-Qing Zhang,Bo-Hua Zhong,Jian-Wei Xie 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.11

Chronic hepatitis B virus (HBV) infection maylead to liver cirrhosis and hepatocellular carcinoma, butfew drugs are available for its treatment. Acyclic nucleosidephosphonates (ANPs) have remarkable antivirusactivities but are not easily absorbed from the gastrointestinaltract and accumulate in the kidneys, resulting innephrotoxicity. Therefore, there is a need to find effectiveliver site-specific prodrugs. The dipivaloyloxymethyl esterof 9-(2-phosphonylmethoxyethyl)adenine (PMEA)—adefovirdipivoxil (ADV)—is a first-line therapy drug forchronic hepatitis B with a low therapeutic index because ofrenal toxicity and low hepatic uptake. In this study, a seriesof PMEA derivatives were synthesized to enhance plasmastability and liver release. The metabolic stability of ADV(Chemical I) and its two analogues (Chemicals II and III)was evaluated in rat plasma and liver homogenate in vitro. An ion-pair reverse-phase HPLC–UV method and a hybridion trap and high-resolution time-of-flight mass spectrometry(LC-IT-TOF-MS) were used to evaluate the degradationrate of the analogues and to identify their intermediatemetabolites, respectively. Chemicals I and II were hydrolyzedby cleavage of the C–O bond to give monoesters. Sufficient enzymatic activation in the liver homogenatethrough a relatively simple metabolic pathway, in additionto a favorable stability profile in rat plasma, made ChemicalII an optimal candidate. Next, six analogues based onthe structure of Chemical II were synthesized and evaluatedin plasma and liver homogenate. Compared toChemical II, these compounds generated less active PMEAlevels in rat liver homogenate. Therefore, chemical modificationof Chemical II may lead to new promising PMEAderivatives with enhanced plasma stability and liveractivation.

Meta-analysis of Outcomes Compared between Robotic and Laparoscopic Gastrectomy for Gastric Cancer

Liao, Gui-Xiang,Xie, Guo-Zhu,Li, Rong,Zhao, Zhi-Hong,Sun, Quan-Quan,Du, Sha-Sha,Ren, Chen,Li, Guo-Xing,Deng, Hai-Jun,Yuan, Ya-Wei Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

This meta-analysis was performed to evaluate and compare the outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for treating gastric cancer. A systematic literature search was carried out using the PubMed database, Web of Knowledge, and the Cochrane Library database to obtain comparative studies assessing the safety and efficiency between RG and LG in May, 2013. Data of interest were analyzed by using of Review Manager version 5.2 software (Cochrane Collaboration). A fixed effects model or random effects model was applied according to heterogeneity. Seven papers reporting results that compared robotic gastrectomy with laparoscopic gastrectomy for gastric cancer were selected for this meta-analysis. Our metaanalysis included 2,235 patients with gastric cancer, of which 1,473 had undergone laparoscopic gastrectomy, and 762 had received robotic gastrectomy. Compared with laparoscopic gastrectomy, robotic gastrectomy was associated with longer operative time but less blood loss. There were no significant difference in terms of hospital stay, total postoperative complication rate, proximal margin, distal margin, numbers of harvested lymph nodes and mortality rate between robotic gastrectomy and laparoscopic gastrectomy. Our meta-analysis showed that robotic gastrectomy is a safe technique for treating gastric cancer that compares favorably with laparoscopic gastrectomy in short term outcomes. However, the long term outcomes between the two techniques need to be further examined.

Digital Control Strategy for Input-Series-Output-Parallel Modular DC/DC Converters

Sha, Deshang,Guo, Zhiqiang,Liao, Xiaozhong The Korean Institute of Power Electronics 2010 JOURNAL OF POWER ELECTRONICS Vol.10 No.3

Input-series-output-parallel (ISOP) converters consisting of multiple modular DC/DC converters can enable low voltage rating switches to be used under high voltage input applications. This paper presents a digital control strategy, which can achieve equal sharing of input voltage for a modular ISOP system consisting of two-transistor forward DC/DC converters by forcing the input voltages of neighboring modules to be equal. The proposed scheme is analyzed using small signals analysis based on the state space average method. The performance of the proposed control strategy is verified with an experimental prototype of an ISOP converter made up of three two-switch forward converters.

A Digitally Controlled Three-Phase Cycloconverter Type High Frequency AC Link Inverter Using Space Vector Modulation

Sha, Deshang,Qin, Zian,Wu, Dan,Liao, Xiaozhong The Korean Institute of Power Electronics 2011 JOURNAL OF POWER ELECTRONICS Vol.11 No.1

In this paper, a three phase cycloconverter type high frequency AC link inverter is discussed. The configuration consists of a high frequency full-bridge inverter and a high frequency transformer followed by a three phase cycloconverter whose switch is composed of anti-series connected MOSFETs with a common source. A simple digital control strategy based on space vector modulation (SVM) and repetitive control for the cycloconverter is proposed although its input voltage is a high frequency AC pulse. The operation principle of the proposed control strategy is analyzed and the equivalent working modes during one interval are also presented. The effectiveness of the proposed control strategy is verified through Matlab/Simulink simulations and experiments on a 1.45kW prototype.

Parallel Connected High Frequency AC Link Inverters Based on Full Digital Control

Sha, Deshang,Guo, Zhiqiang,Deng, Kai,Liao, Xiaozhong The Korean Institute of Power Electronics 2012 JOURNAL OF POWER ELECTRONICS Vol.12 No.4

This paper presents a full digital control strategy for parallel connected modular inverter systems. Each modular inverter is a high frequency (HF) AC link inverter which is composed of a HF inverter and a HF transformer followed by a cycloconverter. To achieve equal sharing of the load current and to suppress the circulating currents among the modules, a three-loop control strategy, consisting of a common output voltage regulation (OVR) loop, individual circulating current suppression (CCS) loops and individual inner current tracking (ICT) loops, is proposed. The ICT loops are implemented with predictive current control from which high precision current tracking can be obtained. The effectiveness of the proposed control strategy is verified by simulation and experimental results from parallel connected two full-bridge HF AC link inverter modules.

Long Noncoding RNA NEAT1 Aggravates Aβ-Induced Neuronal Damage by Targeting miR-107 in Alzheimer’s Disease

Sha Ke,Zhaohui Yang,Fei Yang,Xiaoming Wang,Juan Tan,Bo Liao 연세대학교의과대학 2019 Yonsei medical journal Vol.60 No.7

Purpose: Alzheimer’s disease (AD) is the most common neurodegenerative disease, with a rising prevalence worldwide. Longnoncoding RNAs (lncRNAs) have been found to play important roles in the development and treatment of AD. However, the exactrole of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in neuronal damage in AD is largely unknown. Materials and Methods: The AD model was established in SH-SY5Y and SK-N-SH cells via treatment with amyloid β1-42 (Aβ). Theexpression of NEAT1 and microRNA-107 (miR-107) was measured by quantitative real-time polymerase chain reaction. Cell viabilityand apoptosis were detected by MTT assay, immunocytochemistry, and flow cytometry. The expression of phosphorylated tauprotein (p-Tau) was measured by Western blot. The interaction between NEAT1 and miR-107 was explored by bioinformaticsanalysis, luciferase activity, and RNA immunoprecipitation assays. Results: NEAT1 expression was enhanced in Aβ-treated SH-SY5Y and SK-N-SH cells, and its knockdown attenuated Aβ-inducedinhibition of viability and promotion of apoptosis and p-Tau levels. NEAT1 was indicated as a decoy of miR-107. miR-107 abundancewas reduced in Aβ-treated cells, and its overexpression reversed Aβ-induced injury. Moreover, interference of miR-107 abatedsilencing of NEAT1-mediated inhibition of neuronal damage in Aβ-treated SH-SY5Y and SK-N-SH cells. Conclusion: LncRNA NEAT1 aggravated Aβ-induced neuronal damage by sponging miR-107, indicating a novel avenue for treatmentof AD.

DSP Based Series-Parallel Connected Two Full-Bridge DC-DC Converter with Interleaving Output Current Sharing

Deshang Sha,Zhiqiang Guo,Xiaozhong Liao 전력전자학회 2010 JOURNAL OF POWER ELECTRONICS Vol.10 No.6

Input-series-output-parallel (ISOP) connected DC-DC converters enable low voltage rating switches to be used in high voltage input applications. In this paper, a DSP is adopted to generate digital phase-shifted PWM signals and to fulfill the closed-loop control function for ISOP connected two full-bridge DC-DC converters. Moreover, a stable output current sharing control strategy is proposed for the system, with which equal sharing of the input voltage and the load current can be achieved without any input voltage control loops. Based on small signal analysis with the state space average method, a loop gain design with the proposed scheme is made. Compared with the conventional IVS scheme, the proposed strategy leads to simplification of the output voltage regulator design and better static and dynamic responses. The effectiveness of the proposed control strategy is verified by the simulation and experimental results of an ISOP system made up of two full-bridge DC-DC converters.

Digital Control Strategy for Input-Series-Output-Parallel Modular DC/DC Converters

Deshang Sha,Zhiqiang Guo,Xiaozhong Liao 전력전자학회 2010 JOURNAL OF POWER ELECTRONICS Vol.10 No.3

Input-series-output-parallel (ISOP) converters consisting of multiple modular DC/DC converters can enable low voltage rating switches to be used under high voltage input applications. This paper presents a digital control strategy, which can achieve equal sharing of input voltage for a modular ISOP system consisting of two-transistor forward DC/DC converters by forcing the input voltages of neighboring modules to be equal. The proposed scheme is analyzed using small signals analysis based on the state space average method. The performance of the proposed control strategy is verified with an experimental prototype of an ISOP converter made up of three two-switch forward converters.

A Digitally Controlled Three-Phase Cycloconverter Type High Frequency AC Link Inverter Using Space Vector Modulation

Deshang Sha,Zian Qin,Dan Wu,Xiaozhong Liao 전력전자학회 2011 JOURNAL OF POWER ELECTRONICS Vol.11 No.1

In this paper, a three phase cycloconverter type high frequency AC link inverter is discussed. The configuration consists of a high frequency full-bridge inverter and a high frequency transformer followed by a three phase cycloconverter whose switch is composed of anti-series connected MOSFETs with a common source. A simple digital control strategy based on space vector modulation (SVM) and repetitive control for the cycloconverter is proposed although its input voltage is a high frequency AC pulse. The operation principle of the proposed control strategy is analyzed and the equivalent working modes during one interval are also presented. The effectiveness of the proposed control strategy is verified through Matlab/Simulink simulations and experiments on a 1.45㎾ prototype.

Parallel Connected High Frequency AC Link Inverters Based on Full Digital Control

Deshang Sha,Zhiqiang Guo,Kai Deng,Xiaozhong Liao 전력전자학회 2012 JOURNAL OF POWER ELECTRONICS Vol.12 No.4

This paper presents a full digital control strategy for parallel connected modular inverter systems. Each modular inverter is a high frequency (HF) AC link inverter which is composed of a HF inverter and a HF transformer followed by a cycloconverter. To achieve equal sharing of the load current and to suppress the circulating currents among the modules, a three-loop control strategy, consisting of a common output voltage regulation (OVR) loop, individual circulating current suppression (CCS) loops and individual inner current tracking (ICT) loops, is proposed. The ICT loops are implemented with predictive current control from which high precision current tracking can be obtained. The effectiveness of the proposed control strategy is verified by simulation and experimental results from parallel connected two full-bridge HF AC link inverter modules.