• Psychiatry investigation
• /
• v.15 no.11
• /
• pp.1064-1070
• /
• 2018

Objective Several cell line studies have demonstrated thioridazine's anticancer, multidrug resistance-reversing and apoptosis-inducing properties in various tumors. We conducted this nationwide population-based study to investigate the association between thioridazine use and cancer risk among adult patients with schizophrenia. Methods Based on the Psychiatric Inpatient Medical Claim of the National Health Insurance Research Database of Taiwan, a total of 185,689 insured psychiatric patients during 2000 to 2005 were identified. After excluding patients with prior history of schizophrenia, only 42,273 newly diagnosed patients were included. Among them, 1,631 patients ever receiving thioridazine for more than 30 days within 6 months were selected and paired with 6,256 randomly selected non-thioridazine controls. These patients were traced till 2012/12/31 to see if they have any malignancy. Results The incidence rates of hypertension and cerebrovascular disease were higher among cases than among matched controls. The incidence of hyperlipidemia, coronary artery disease and chronic pulmonary disease did not differ between the two groups. By using Cox proportional hazard model for cancer incidence, the crude hazard ratio was significantly higher in age, hypertension, hyperlipidemia, cerebrovascular disease, coronary artery disease and chronic pulmornary disease. However, after adjusting for other covariates, only age and hypertension remained significant. Thioridazine use in adult patients with schizophrenia had no significant association with cancer. Conclusion Despite our finding that thioridazine use had no prevention in cancer in adult patients with schizophrenia. Based on the biological activity, thioridazine is a potential anticancer drug and further investigation in human with cancer is warranted.

• Journal of Plant Biotechnology
• /
• v.46 no.1
• /
• pp.56-60
• /
• 2019

Ginsenosides are active constituents of ginseng (Panax ginseng) that have possible anti-aging, physiological and pharmacological activities, such as anti-cancer and anti-inflammatory effects. Although the ginseng root is generally used more often than the aerial parts for medicinal purposes, the flowers also contain numerous ginsenosides, including Rb2, Rc, Rd, Re and Rg1. Therefore, an extract from the flowers of the P. ginseng could have the pharmacological efficacy of bioactive compounds including ginsenosides. The high hydrostatic pressure extraction (HHPE) is a method that is used for the efficient extraction of bioactive compounds from plant materials. In this study, we compared the yield of ginsenosides from ginseng flowers under different conditions of extraction pressure and time of HHPE. The results indicate that the total yield of the ginsenosides improved as the pressure increased from 0.1 to 80 MPa and treatment duration increased to 24 hours. In addition, the ginsenoside extracts from HHPE at 80 MPa, which possessed a higher total ginsenoside concentration, decreased the viability of the primary human epidermal keratinocytes (HEKs) significantly than the ginsenoside extracts from HHPE at 0.1 MPa. Collectively, we found that the method of HHPE that was performed for 24 hours at 80 MPa showed the highest yield of ginsenosides from the flowers of P. ginseng. In addition, our study provides a foundation for the efficient extraction of ginsenosides, which had a potent bioactivity, from flowers of P. ginseng through HHPE.

• Journal of Microbiology and Biotechnology
• /
• v.31 no.8
• /
• pp.1154-1162
• /
• 2021

The transcriptional capacities of target genes are strongly influenced by promoters, whereas few studies have focused on the development of robust, high-performance and cross-species promoters for wide application in different bacteria. In this work, four novel promoters (P_k.rtufB, P_k.r1, P_k.r2, and P_k.r3) were predicted from Ketogulonicigenium robustum and their inconsistency in the -10 and -35 region nucleotide sequences indicated they were different promoters. Their activities were evaluated by using green fluorescent protein (gfp) as a reporter in different species of bacteria, including K. vulgare SPU B805, Pseudomonas putida KT2440, Paracoccus denitrificans PD1222, Bacillus licheniformis and Raoultella ornithinolytica, due to their importance in metabolic engineering. Our results showed that the four promoters had different activities, with P_k.r1 showing the strongest activity in almost all of the experimental bacteria. By comparison with the commonly used promoters of E. coli (tufB, lac, lacUV5), K. vulgare (Psdh, Psndh) and P. putida KT2440 (JE111411), the four promoters showed significant differences due to only 12.62% nucleotide similarities, and relatively higher ability in regulating target gene expression. Further validation experiments confirmed their ability in initiating the target minCD cassette because of the shape changes under the promoter regulation. The overexpression of sorbose dehydrogenase and cytochrome c551 by P_k.r1 and P_k.r2 resulted in a 22.75% enhancement of 2-KGA yield, indicating their potential for practical application in metabolic engineering. This study demonstrates an example of applying bioinformatics to find new biological components for gene operation and provides four novel promoters with broad suitability, which enriches the usable range of promoters to realize accurate regulation in different genetic backgrounds.

• Molecules and Cells
• /
• v.45 no.4
• /
• pp.257-272
• /
• 2022

In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.

• Nutrition Research and Practice
• /
• v.16 no.4
• /
• pp.464-475
• /
• 2022

BACKGROUND/OBJECTIVES: Increased levels of uremic toxins and decreased antioxidant capacity have a significant impact on the progression of chronic kidney disease (CKD). However, it remains unclear whether they interact with each other to mediate the damage of kidney function. The purpose of this study was to investigate whether uremic toxins (i.e., homocysteine and indoxyl sulfate [IS]), as well as glutathione-dependent antioxidant enzyme activities are dependently or independently associated with kidney function during different stages of CKD patients. SUBJECTS/METHODS: One hundred thirty-two patients diagnosed with CKD at stages 1 to 5 participated in this cross-sectional study. RESULTS: Patients who had reached an advanced CKD stage experienced an increase in plasma uremic toxin levels, along with decreased glutathione peroxidase (GSH-Px) activity. Plasma homocysteine, cysteine, and IS concentrations were all positively associated with each other, but negatively correlated to GSH-Px activity levels after adjusting for potential confounders in all CKD patients. Although plasma homocysteine, cysteine, IS, and GSH-Px levels were significantly associated with kidney function, only plasma IS levels still had a significant association with kidney function after these parameters were simultaneously adjusted. In addition, plasma IS could interact with GSH-Px activity to be associated with kidney function. CONCLUSIONS: IS plays a more dominant role than homocysteine and GSH-Px activity in relation to kidney function.

• Animal Bioscience
• /
• v.35 no.4
• /
• pp.605-613
• /
• 2022

Objective: The objective was to evaluate the efficacy of increasing supplementation of Yarrowia lipolytica (YL) up to 3.0% replacing 1.6% poultry fat and 0.9% blood plasma for growth performance, intestinal health and nutrient digestibility of diets fed to nursery pigs. Methods: Twenty-four pigs weaned at 24 d of age (initial body weight at 7.2±0.6 kg) were allotted to three dietary treatments (n = 8) based on the randomized complete block. The diets with supplementation of YL (0.0%, 1.5%, and 3.0%, replacing poultry fat and blood plasma up to 1.6% and 0.9%, respectively) were fed for 21 d. Feed intake and body weight were recorded at d 0, 10, and 21. Fecal score was recorded at every odd day from d 3 to 19. Pigs were euthanized on d 21 to collect proximal and distal jejunal mucosa to measure intestinal health markers including tumor necrosis factor-alpha, interleukin-8, immunoglobulin A and immunoglobulin G. Ileal digesta was collected for apparent ileal digestibility (AID) of nutrients in diets. Data were analyzed using Proc Mixed of SAS. Results: Supplementation of YL (1.5% and 3.0%) replacing poultry fat and blood plasma did not affect growth performance, fecal score and intestinal health. Supplementation of YL at 1.5% did not affect nutrient digestibility, whereas supplementation of YL at 3.0% reduced AID of dry matter (40.2% to 55.0%), gross energy (44.0% to 57.5%), crude protein (52.1% to 66.1%), and ether extract (50.8% to 66.9%) compared to diets without supplementation. Conclusion: Yarrowia lipolytica can be supplemented at 1.5% in nursery diets, replacing 0.8% poultry fat and 0.45% blood plasma without affecting growth performance, intestinal health and nutrient digestibility. Supplementation of YL at 3.0% replacing 1.6% poultry fat and 0.9% blood plasma did not affect growth performance and intestinal health, whereas nutrient digestibility was reduced.

• Structural Engineering and Mechanics
• /
• v.86 no.4
• /
• pp.547-571
• /
• 2023

To deeply probe the actual earthquake level and fragility of typical reinforced concrete (RC) structures under multiple intensity grades, considering diachronic measurement building stock samples and actual observations of representative catastrophic earth shocks in China from 1990 to 2010, RC structures were divided into traditional RC structures (TRCs) and bottom reinforced concrete frame seismic wall masonry (BFM) structures, and the empirical damage characteristics and mechanisms were analysed. A great deal of statistics and induction were developed on the historical experience investigation data of 59 typical catastrophic earthquakes in 9 provinces of China. The database and fragility matrix prediction model were established with TRCs of 4,122.5284×104 m² and 5,844 buildings and BFMs of 5,872 buildings as empirical seismic damage samples. By employing the methods of structural damage probability and statistics, nonlinear prediction of seismic vulnerability, and numerical and applied functional analysis, the comparison matrix of actual fragility probability prediction of TRC and BFM in multiple intensity regions under the latest version of China's macrointensity standard was established. A novel nonlinear regression prediction model of seismic vulnerability was proposed, and prediction models considering the seismic damage ratio and transcendental probability parameters were constructed. The time-varying vulnerability comparative model of the sample database was developed according to the different periods of multiple earthquakes. The new calculation method of the average fragility prediction index (AFPI) matrix parameter model has been proposed to predict the seismic fragility of an areal RC structure.

• International conference on construction engineering and project management
• /
• 2017.10a
• /
• pp.32-41
• /
• 2017

Accidents on offshore oil and gas platforms (OOGPs) usually cause serious fatalities and financial losses considering demanding environment platforms locate and complex topsides structure platforms own. Evacuation planning on platforms is usually challenging. The computational tool is a good choice to plan evacuation by emergency simulation. However, the complex structure of platforms and varied evacuation behaviors usually weaken the advantages of computational simulation. Therefore, this study developed a simulation model for OOGPs to evaluate different evacuation plans to improve evacuation performance by integrating building information modeling (BIM) and agent-based model (ABM). The developed model consists of four parts: evacuation model input, simulation environment modeling, agent definition, and simulation and comparison. Necessary platform information is extracted from BIM and then used to model simulation environment by integrating matrix model and network model. During agent definition, in addition to basic characteristics, environment sensing and dynamic escape path planning functions are also developed to improve simulation performance. An example OOGP BIM topsides with different emergent scenarios is used to illustrate the developed model. The results showed that the developed model can well simulate evacuation on OOGPs and improve evacuation performance. The developed model was also suggested to be applied to other industries such as the architecture, engineering, and construction industry.

• International conference on construction engineering and project management
• /
• 2020.12a
• /
• pp.23-29
• /
• 2020

Multilayer sub-contracting is a significant practice among the world, including Hong Kong. When a principal contractor secured a project from a developer, the specific jobs will usually be breaking down and sub-contractors with the lowest bid [1]. The adoption of multilayer sub-contracting has been a controversy issue which is considered as a two-side blade. While certain studies have been carried out to examine both the contributions, damages and improvements for multi-layer subcontracting, the construction industry and researchers are still waiting for a solid measure to enhance the system. Hence, this research attempts to study the advantages, disadvantages, conducts a comparison between single and multilayer sub-contracting and measures of current Hong Kong construction industry based on literature review, questionnaire and in-depth interviews. To achieve the objectives, Analytic Hierarchy Process (AHP) and total weighted score methods are adopted to examine and rank the criterion. The findings of this study provide a good basis for understanding the major reasons and problems caused by the adoption of multilayer sub-contracting. Besides, the identified safety perspective explores a new perspective regarding to issues of multi-layer subcontracting, which will serve as a solid foundation for further research to enhance safety performance. Finally, the findings of measurements towards improvement of multilayer sub-contracting will also provide a solidsolution for construction industry.

• Nuclear Engineering and Technology
• /
• v.56 no.4
• /
• pp.1538-1543
• /
• 2024

The importance of determining the radon exhalation rate from water surface is emphasized by the increased use of radon and its daughter products as tracers in large-scale circulation studies of the atmosphere. There were many methods to measure radon exhalation from water surface. With the development of radon exhalation rate measurement methods and instruments on the surface of the soil, the rock and building materials, so the radon exhalation rate from water surface can be more accurately measured by applying these improved methods and instruments. In this paper, a cuboid accumulation chamber surrounded by foam boards and a RAD7 were used to measure the radon exhalation rate on the water surface at three different positions by Yixin lake. Each measurement was performed 2 h. The radon exhalation rate from the water surface was about 6 × 10^-3 Bq m^-2s^-1. The thoron exhalation rate from the water surface also can be estimated, it is about 0.16 Bq m^-2s^-1. These results hint that the radon transmission from the lake bottom soil to water and then into the atmosphere.