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Dae Hun Kim,1,* Jae Yeol Kim,1,* Rae Man Kim,1 Pooja Maharjan,1 Yu-Geun Ji,2 Dong-Jin Jang,3 Kyoung Ah Min,1 Tae-Sung Koo,2 Kwan Hyung Cho1 1Department of Pharmacy, Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae, Republic of Korea; 2Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Republic of Korea; 3Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of Korea *These authors contributed equally to this work Background: The present study aimed to develop orlistat-loaded solid self-nanoemulsifying drug delivery system preconcentrate (SSP) with the minimum use of lipid excipients for the enhanced solubility, in vitro dissolution, lipase inhibition, and in vivo performance. Materials and methods: In the screening of solubilizing vehicles, Solutol HS15 and Lauroglycol 90 were selected as the surfactant and oil phase, respectively. A pseudo-ternary phase diagram composed of Solutol HS15, Lauroglycol 90, and orlistat as an anti-obesity agent and lipid component was constructed, and the SSP regions were confirmed in terms of the particle size distribution in water, melting point by differential scanning calorimetry, and crystallinity by X-ray diffraction. Results: Physicochemical interaction between Solutol HS15 and orlistat resulted in SSP with various melting points in the range of 26°C~33°C. The representative maximum orlistat-loaded SSP (orlistat/Solutol HS15/Lauroglycol 90=55/40/5, weight ratio) showed the melting point of 32.23°C and constructed uniform nanoemulsion with the particle size of 141.7±1.1 nm dispersed in water. In the dissolution test at pH 1.2 without any detergent, the SSP reached 98.12%±0.83% until 45 minutes, whereas raw orlistat showed no significant dissolution rate. The dissolution samples containing SSP showed a lipase inhibition of 90.42%±1.58% within 45 minutes. In terms of the reduction level of fat absorption in rats, the intake group of SSP gave a significantly higher fat excretion into stool than the one observed in the raw orlistat group (P

Background: Tube current is an important determinant of radiation dose and image quality in X-ray-based examination. The combined automatic tube current modulation technique (ATCM) enables automatic adjustment of the tube current in various planes (x-y and z) based on the size and attenuation of the body area scanned. Purpose: To compare image quality and radiation dose of the ATCM with those of a fixed tube current technique (FTC) in CT of the abdomen and pelvis performed with a 16-slice multidetector row CT. Material and Methods: We reviewed 100 patients in whom initial and follow-up CT of the abdomen and pelvis were performed with FTC and ATCM. All acquisition parameters were identical in both techniques except for tube current. We recorded objective image noise in liver parenchyma, subjective image noise and diagnostic acceptability by using a five-point scale, radiation dose, and body mass index (BMI, kg/m(2)). Data were analyzed with parametric and non-parametric statistical tests. Results: There was no significant difference in image noise and diagnostic acceptability between two techniques. All subjects had acceptable subjective image noise in both techniques. The significant reduction in radiation dose (45.25% reduction) was noted with combined ATCM (P < 0.001). There was a significant linear statistical correlation between BMI and dose reduction (r = -0.78, P < 0.05). Conclusion: The ATCM for CT of the abdomen and pelvis substantially reduced radiation dose while maintaining diagnostic image quality. Patients with lower BMI showed more reduction in radiation dose. [ABSTRACT FROM AUTHOR]

In this paper, an intranet portal is considered as an information infrastructure (organizational memory information system, OMIS) supporting organizational learning. The properties and the hierarchical structure of information and knowledge in an intranet portal OMIS was identified as a problem for navigation tools of an intranet portal interface. The problem relates to navigation and retrieval functions of intranet portal OMIS and is expected to adversely affect user performance, satisfaction, and usefulness. To solve the problem, a conceptual model for navigation tools of an intranet portal interface was proposed and an experiment using a crossover design was conducted with 10 participants. In the experiment, a separate access method (tabbed tree tool) was compared to an unified access method (single tree tool). The results indicate that each information/knowledge repository for which a user has a different structural knowledge should be handled separately with a separate access to increase user satisfaction and the usefulness of the OMIS and to improve user performance in navigation. [ABSTRACT FROM AUTHOR]

Based on previous research and properties of organizational memory, a conceptual model for navigation and retrieval functions in an Intranet portal organizational memory information system was proposed, and two human-centred features (memory structure map and history-based tool) were developed to support user's navigation and retrieval in a well-known organizational memory. To test two hypotheses concerning the validity of the conceptual model and two human-centred features, an experiment was conducted with 30 subjects. Testing of the two hypotheses indicated the following: (1) the memory structure map's users showed 29% better performance in navigation, and (2) the history-based tool's users outperformed by 34% in identifying information. The results of the study suggest that a conceptual model and two human-centred features could be used in an user-adaptive interface design to improve user's performance in an intranet portal organizational memory information system. [ABSTRACT FROM AUTHOR]

This study sought to understand how health misperceptions develop among individuals after exposure to misinformation messages, and how eHealth literacy and situational motivation in problem solving are associated with the negative effects of misinformation exposure. We also sought to understand the differentiated effects of misinformation exposure on the four misinformation-susceptible publics. Results from two studies revealed that situational motivation was positively associated with the formation of misperceptions after misinformation exposure as well as individuals' likelihood of amplifying the misinformation message. However, eHealth literacy does not reduce misperceptions, as had been hypothesized. In fact, eHealth literacy was not significantly associated with misperceptions or with misinformation amplification likelihood. Results also provide support for the typology of misinformation-susceptible publics as misinformation-amplifying publics were the most susceptible to misinformation messages.

The visible light-induced decarboxylative cascade reaction of fluoroalkyl carboxylic acids has been achieved for the efficient synthesis of fluorinated compounds. However, most of the transformations rely on noble iridium metal complex. Herein, a visible light-induced metal-free decarboxylative cascade reaction of fluoroalkyl carboxylic acids has been realized. This protocol features simple operation, transition metal, and good functional group tolerance., (© 2024 Wiley‐VCH GmbH.)

Purpose: To construct humanistic nursing practice guidelines suitable for stroke patients., Design: This study was a development and validation study of guidelines using multiple methods, including literature review, qualitative research, questionnaire survey, thematic discussion, and Delphi expert consultation., Methods: Twenty-five experts from seven provinces and municipalities in China were interviewed over two rounds from December 2020 to February 2021. The first-level index was scored for importance and rationality, while the second-level index was scored for importance and feasibility using a five-point Likert scale. Delphi data was collected via a paper version of the questionnaire. The coefficients of variation and coordination were used to represent the degree of dispersion of expert opinions., Findings: In the two rounds of letter consultation, the questionnaire's recovery and effective rates were both 100%, while the opinion submission rates of the two rounds were 84 and 52%, respectively. Moreover, the expert authority coefficient was 0.91, and the coordination coefficients of expert opinions in the first round were as follows: importance of 0.03 and rationality of 0.07 for the first-level index; importance of 0.09 and feasibility of 0.11 for the secondary index. In round two, the coordination coefficients of expert opinions were as follows: importance of 0.04 and rationality of 0.05 for the first-level indicators; importance of 0.12 and feasibility of 0.10 for the secondary index. The results for the secondary index were P < 0.001 for the two rounds. The humanistic nursing practice guidelines for stroke patients that were ultimately formed included five first-level indicators (physiological care, safety care, emotional care, dignity care, and rehabilitation needs) and 46 s-level indicators., Conclusion: Our results show that the "Practice Guidelines for Humanistic Nursing for Stroke" established by experts adopts Maslow's hierarchy of needs as its structural framework. It meets people's basic needs and can provide a reference for the construction of a humanistic nursing specialty practice for stroke patients., Clinical Relevance: Humanistic nursing guidelines for stroke could provide a reference for the construction of humanistic nursing practice in the stroke specialty., Clinical Resources: Copeptin and long-term risk of recurrent vascular events after transient ischemic attack and ischemic stroke: population-based study https://pubmed.ncbi.nlm.nih.gov/26451023/. Effectiveness and usage of a decision support system to improve stroke prevention in general practice: a cluster randomized controlled trial https://pubmed.ncbi.nlm.nih.gov/28245247/. Guidelines for adult stroke rehabilitation and recovery: a guideline for healthcare professionals from the American Heart Association/American Stroke Association https://pubmed.ncbi.nlm.nih.gov/27145936/., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Ji, Yang and Xie.)

The nitrate electroreduction reaction (NO 3 - -ERR) is an efficient and green approach for nitrate remediation, which requires a highly active and selective electrocatalyst. In this work, porous and amorphous cobalt phosphide nanoshuttles (CoP PANSs) are successfully synthesized by using Mg 2+ ion-doped calcium carbonate nanoshuttles (Mg-CaCO 3 NSs) as the initial reaction precursor via precipitation transformation and a high-temperature phosphidation strategy. Various physical characterizations show that CoP PANSs have porous architecture, amorphous crystal structure, and big surface area. Electrochemical measurements reveal for the first time that CoP PANSs have outstanding electroactivity for NO 3 - -ERR in a neutral electrolyte. At an applied potential of -0.5 V vs reversible hydrogen electrode, CoP PANSs can achieve a high Faraday efficiency (94.24 ± 2.8%) and high yield rate (19.28 ± 0.53 mg h -1 mg cat -1 ) for ammonia production, which exceeds most reported values at various electrocatalysts for NO 3 - -ERR. Thus, the present result indicates that cobalt phosphide nanomaterials have promising application for NO 3 - -ERR.

Purpose: This study aims to design that using formative assessment as an instructional strategy in real-time online classes, and to explore the application of Bloom's taxonomy in the development of formative assessment items., Methods: We designed the instruction using formative assessment in real-time online classes, developed the items of formative assessment, analyzed the items statistically, and investigated students' perceptions of formative assessment through a survey., Results: It is designed to consist of 2-3 learning outcomes per hour of class and to conduct the formative assessment with 1-2 items after the lecture for each learning outcome. Formative assessment was 31 times in the physiology classes (total 48 hours) of three basic medicine integrated. There were nine "knowledge" items, 40 "comprehension" items, and 55 "application" items. There were 33 items (31.7%) with a correct rate of 80% or higher, which the instructor thought was appropriate. As a result of the survey on students' perceptions of formative assessment, they answered that it was able to concentrate on the class and that it was helpful in achieving learning outcomes., Conclusion: The students focused during class because they had to take formative assessment immediately after the learning outcome lecture. "Integration of lesson and assessments" was maximized by solving the assessment items as well as through the instructor's immediate explanation of answers. Through formative assessment, the students were able to utilize metacognition by learning what content they understood or did not understand. Items that consider Bloom's taxonomy allow students to remember, understand, and apply to clinical contexts.

This study aims to investigate the effects of non-driving-related tasks (NDRTs) on the transition of control in highly automated driving (HAD) by investigating the effects of NDRT physical, visual, and cognitive attributes during transition of control. A conceptual model of the takeover process is proposed by dividing this process into motor and mental reactions. A laboratory experiment was conducted to evaluate the effects of each NDRT attribute on the corresponding stage of the process of taking over control. A prediction model was developed using the results of multiple linear regression analysis. Additionally, a validation experiment with nine NDRTs and a baseline condition was conducted to determine the extent to which the developed model explains the takeover time for each NDRT condition. The results showed that the timing aspects of the transition of control in HAD largely consist of participant motor reactions that are affected by the physical attributes of NDRTs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Brain derived neurotrophic factor (BDNF) promotes maturation of dopaminergic (DAergic) neurons in the midbrain and positively regulates their maintenance and outgrowth. Therefore, understanding the mechanisms regulating the BDNF signaling pathway in DAergic neurons may help discover potential therapeutic strategies for neuropsychological disorders associated with dysregulation of DAergic neurotransmission. Because estrogen-related receptor gamma (ERRγ) is highly expressed in both the fetal nervous system and adult brains during DAergic neuronal differentiation, and it is involved in regulating the DAergic neuronal phenotype, we asked in this study whether ERRγ ligand regulates BDNF signaling and subsequent DAergic neuronal phenotype. Based on the X-ray crystal structures of the ligand binding domain of ERRγ, we designed and synthesized the ERRγ agonist, (E)-4-hydroxy-N'-(4-(phenylethynyl)benzylidene)benzohydrazide (HPB2) (K d value, 8.35 μmol/L). HPB2 increased BDNF mRNA and protein levels, and enhanced the expression of the BDNF receptor tropomyosin receptor kinase B (TrkB) in human neuroblastoma SH-SY5Y, differentiated Lund human mesencephalic (LUHMES) cells, and primary ventral mesencephalic (VM) neurons. HPB2-induced upregulation of BDNF was attenuated by GSK5182, an antagonist of ERRγ, and siRNA-mediated ERRγ silencing. HPB2-induced activation of extracellular-signal-regulated kinase (ERK) and phosphorylation of cAMP-response element binding protein (CREB) was responsible for BDNF upregulation in SH-SY5Y cells. HPB2 enhanced the DAergic neuronal phenotype, namely upregulation of tyrosine hydroxylase (TH) and DA transporter (DAT) with neurite outgrowth, both in SH-SY5Y and primary VM neurons, which was interfered by the inhibition of BDNF-TrkB signaling, ERRγ knockdown, or blockade of ERK activation. HPB2 also upregulated BDNF and TH in the striatum and induced neurite elongation in the substantia nigra of mice brain. In conclusion, ERRγ activation regulated BDNF expression and the subsequent DAergic neuronal phenotype in neuronal cells. Our results might provide new insights into the mechanism underlying the regulation of BDNF expression, leading to novel therapeutic strategies for neuropsychological disorders associated with DAergic dysregulation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lung cancer has a high mortality rate, but an early diagnosis can contribute to a favorable prognosis. A liquid biopsy that captures and detects tumor-related biomarkers in body fluids has great potential for early-stage diagnosis. Exosomes, nanosized extracellular vesicles found in blood, have been proposed as promising biomarkers for liquid biopsy. Here, we demonstrate an accurate diagnosis of early-stage lung cancer, using deep learning-based surface-enhanced Raman spectroscopy (SERS) of the exosomes. Our approach was to explore the features of cell exosomes through deep learning and figure out the similarity in human plasma exosomes, without learning insufficient human data. The deep learning model was trained with SERS signals of exosomes derived from normal and lung cancer cell lines and could classify them with an accuracy of 95%. In 43 patients, including stage I and II cancer patients, the deep learning model predicted that plasma exosomes of 90.7% patients had higher similarity to lung cancer cell exosomes than the average of the healthy controls. Such similarity was proportional to the progression of cancer. Notably, the model predicted lung cancer with an area under the curve (AUC) of 0.912 for the whole cohort and stage I patients with an AUC of 0.910. These results suggest the great potential of the combination of exosome analysis and deep learning as a method for early-stage liquid biopsy of lung cancer.

Motolimod (VTX-2337) is an agonist of toll-like receptor 8. In this study, a novel and sensitive liquid chromatography-tandem mass spectrometry method was developed for quantifying motolimod in rat plasma and subsequently used in a pharmacokinetic study. Proteins were precipitated from plasma samples using acetonitrile prior to the analysis. GS-9620 was used as an internal standard. High-performance liquid chromatography was performed using a Spursil C18-EP column (3 μm, 50 × 2.1 mm). Aqueous ammonium formate and acetonitrile were used as the mobile phase. Motolimod was detected using an electrospray ionization interface under multiple reaction monitoring conditions in the positive ion mode. The developed method produced a linear correlation over a concentration range of 1-1000 ng/mL (r = 0.9944). Intra- and inter-day precision values ranged from 4.8%-10.7% (the lower limit of quantification precision value was 16.3 %), whereas intra- and inter-day accuracy values ranged from 0.3%-9.1 %. The mean recovery of motolimod from rat plasma was 109.4 %. Additionally, motolimod was found to be stable under various conditions (three freeze-thaw cycles, 6-h storage at room temperature, short- and long-term stability tests, and processing). The developed method was successfully used in a pharmacokinetic study in rats. Motolimod showed non-linear pharmacokinetics following its intravenous administration to rats at 0.6-6 mg/kg. Additionally, very low exposure (<1 %) was obtained following oral administration of the drug to rats. The results also showed that motolimod has a low metabolic stability in the liver microsomes and exhibits extensive binding to the plasma proteins., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We aimed to investigate the effects of the visual complexity of in-vehicle information display and driver's age in a driving context. A driving simulator study was conducted where participants performed visual search tasks at different visual complexity levels while driving. Two groups were included, 20 younger drivers (mean age = 28.75 years) and 14 older drivers (mean age = 54.87 years). Older drivers were found to be more vulnerable to the effects of increased visual complexity when performing a visual search task. The task completion time of the younger group increased by about 20% (from 7.69 s to 9.30 s), while the older group increased by about 47% (from 8.92 s to 13.14 s). Further, the driving performance of the older group deteriorated, unlike the younger group. The subjective workload score supported the results of the objective performance measures. These differences can be explained by glance behavior. The total off-road glance duration of older drivers was longer than that of younger drivers, but the average off-road glance duration of younger drivers was longer. In other words, older drivers have a more conservative strategy when dealing with increased visual complexity in a driving context so as not to affect their driving. The findings of this study show that the visual complexity level has a significant effect on driving behaviors, especially in older drivers, which provides insights for designing in-vehicle information displays., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A series of gold/palladium nanoalloys stabilized by secondary phosphine oxides have been prepared for the first time. The nanocatalysts exhibit excellent regio- and chemo-selectivity in the hydrogenation of conjugated enynes, providing a mild and highly efficient way to access phosphinyl (Z) and (Z,Z)-[3]dendralenes.

A cascade alkynylation and selective hydrogenation catalyzed by covalent binaphthyl-stabilized palladium nanoparticles has been established, providing a novel and highly efficient methodology for accessing Z and Z,Z -selective phosphinyl [3]dendralenes with broad functional group tolerance and good yields. This strategy achieves the first cascade reactions of alkynylation and hydrogenation with chemoselectivity modulated by catalyst loading.

A general and efficient radical cyclization of 1H-tetrazol-5-amines and alkynes toward tetrazolo[1,5-a]quinolines is established for the first time. The annulation mediated by tert-butyl nitrite takes place expeditiously within 10 minutes under mild conditions. Without using external additives or excitation, the tetrazolo[1,5-a]quinoline derivatives are obtained in moderate to good yields, along with high regioselectivities for unsymmetrical alkynes and broad functional tolerance features. The reaction is exemplified to occur via a radical process, with aryl radicals synergistically generated from tert-butyl nitrite, water and tetrazolate-diazonium salts.

The antioxidant enzyme human extracellular superoxide dismutase (SOD3) is a promising biopharmaceutical candidate for the treatment of various diseases. To support the early development of SOD3 as a biopharmaceutical, a simple, sensitive, and rapid liquid chromatography tandem mass spectrometry procedure was developed and validated for the determination of SOD3 levels in the plasma of ICR mice. After purification with Ni-NTA magnetic beads and digestion with trypsin, SOD3 signature peptides and internal standard signature peptide (ISP) were separated via high performance liquid chromatography using a Zorbax C 18 column (2.1 × 50 mm, 3.5 μm) and a mobile phase consisting of 10 mM ammonium formate, 0.1% formic acid, and acetonitrile. The analyte and ISP were detected via a tandem mass spectrometer in electrospray ionization and multiple reaction monitoring modes to select both the signature peptide for SOD3 at m/z 669 to 969 and the ISP at m/z 655 to 941 in the positive ion mode. The calibration curves were linear (r > 0.99) between 5 and 1000 μg/mL with a lower limit of quantification of 5 μg/mL. The relative standard deviation ranged from 3.08 to 8.84% while the relative error ranged from -0.13 to -9.56%. This method was successfully applied to a preclinical pharmacokinetic study of SOD3 in male ICR mice., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study investigated the influences of takeover request (TOR) modalities on a drivers' takeover performance after they engaged in non-driving related (NDR) tasks in highly automated driving (HAD). Visual, vibrotactile, and auditory modalities were varied in the design of the experiment under four conditions: no-task, phone conversation, smartphone interaction, and video watching tasks. Driving simulator experiments were conducted to analyze the drivers' take-over performance by collecting data during the transition time of re-engaging control of the vehicle, the time taken to be on the loop, and time taken to be physically ready to drive. Data were gathered on the perceived usefulness, safety, satisfaction, and effectiveness for each TOR based on a self-reported questionnaire. Takeover and hands-on times varied considerably, as shown by high standard deviation values between modalities, especially for phone conversations and smartphone interaction tasks. Moreover, it was found that participants failed to take over control of the vehicle when they were given visual TORs for phone conversation and smartphone interaction tasks. The perceived safety and satisfaction varied for the NDR task. Results from the statistical analysis showed that the NDR task significantly influenced the takeover time, but there was no significant interaction effect between the TOR modalities and the NDR task. The results could potentially be applied to the design of safe and efficient transitions of highly controlled, automated driving, where drivers are enabled to engage in NDR tasks., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Lung cancer is the second most common cancer in the United States and the leading cause of mortality in cancer patients. Biomarkers predicting survival of patients with lung cancer have a profound effect on patient prognosis and treatment. However, predictive biomarkers for survival and their relevance for lung cancer are not been well known yet. The objective of this study was to perform machine learning with data from The Cancer Genome Atlas of patients with lung adenocarcinoma (LUAD) to find survival-specific gene mutations that could be used as survival-predicting biomarkers. To identify survival-specific mutations according to various clinical factors, four feature selection methods (information gain, chi-squared test, minimum redundancy maximum relevance, and correlation) were used. Extracted survival-specific mutations of LUAD were applied individually or as a group for Kaplan-Meier survival analysis. Mutations in MMRN2 and GMPPA were significantly associated with patient mortality while those in ZNF560 and SETX were associated with patient survival. Mutations in DNAJC2 and MMRN2 showed significant negative association with overall survival while mutations in ZNF560 showed significant positive association with overall survival. Mutations in MMRN2 showed significant negative association with disease-free survival while mutations in DRD3 and ZNF560 showed positive associated with disease-free survival. Mutations in DRD3, SETX, and ZNF560 showed significant positive association with survival in patients with LUAD while the opposite was true for mutations in DNAJC2, GMPPA, and MMRN2. These gene mutations were also found in other cohorts of LUAD, lung squamous cell carcinoma, and small cell lung cancer. In LUAD of Pan-Lung Cancer cohort, mutations in GMPPA, DNAJC2, and MMRN2 showed significant negative associations with survival of patients while mutations in DRD3 and SETX showed significant positive association with survival. In this study, machine learning was conducted to obtain information necessary to discover specific gene mutations associated with the survival of patients with LUAD. Mutations in the above six genes could predict survival rate and disease-free survival rate in patients with LUAD. Thus, they are important biomarker candidates for prognosis., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Antioxidants provide a promising therapeutic effect for the cardiovascular disease. Luteolin, a polyphenolic bioflavonoid, is known to confer cardioprotection, although the underlying mechanisms, especially the role of luteolin on the antioxidant enzymes, such as the peroxiredoxin family, remain unknown., Experimental Approach: We measured the effects of luteolin on myocardial ischaemia/reperfusion (MI/R) injury in vivo (Sprague-Dawley rats) and in vitro, together with the underlying mechanisms, with a focus on signalling by peroxiredoxins. H9c2 cells were used to assess the changes in peroxiredoxins and the other antioxidant enzymes. Oxidative stress, cardiac function, LDH release, ROS and infarct size were also assayed., Key Results: Luteolin exerted significant cardioprotective effects in vivo and in vitro via improving cardiac function, increasing the expression of anti-apoptotic protein Bcl-2 and decreasing the pro-apoptotic protein Bax and active caspases 3 and 9, associated with MI/R. Mechanistically, luteolin markedly enhanced expression of peroxiredoxin II, without significant effects on other forms of peroxiredoxin, catalase or SOD1. Molecular docking showed that luteolin could indeed bind to the enzymic active pocket of peroxiredoxin II. Furthermore, down-regulation of peroxiredoxin II by peroxiredoxin II-antisense, administered by adenovirus infection of H9c2 cardiomyocytes, and inhibition of peroxiredoxin II in vivo significantly reversed the cardioprotective effects of luteolin., Conclusions and Implications: Our findings, for the first time, demonstrate that luteolin protects against MI/R injury through promoting signalling through the endogenous antioxidant enzyme, peroxiredoxin II, indicating the important beneficial role of this antioxidant system in the heart., (© 2018 The British Pharmacological Society.)

Purpose: To investigate the effect of combined inhibition of protein kinase B (AKT) and SRC on the growth and metastatic potential of human pancreatic cancer cells., Materials and Methods: AKT and SRC were inhibited using 10-DEBC and PP2, respectively. The expression of their messenger RNAs were down-regulated by specific small interfering RNA (siRNA). Changes in pancreatic cancer cell growth and metastatic potential were determined using a cell viability assay and a xenotransplant model of pancreatic cancer, as well as cell migration and invasion assays. Signal proteins were analyzed by Western blot., Results: The inhibitors 10-DEBC and PP2 suppressed cell proliferation in a dose-dependent fashion in pancreatic cancer cell lines MIA PaCa-2 and PANC-1. The simultaneous inhibition of AKT and SRC at low concentrations resulted in a significant suppression of cell proliferation. Knockdown of AKT2 and SRC using siRNAs also significantly decreased cell proliferation. In a pancreatic cancer model, combined treatment with 10-DEBC and PP2 also significantly suppressed the growth of pancreatic cancer. Application of 10-DEBC with PP2 significantly reduced the metastatic potential of pancreatic cancer cells by inhibiting migration and invasion. The combined inhibition suppressed the phosphorylation of mTOR and ERK in pancreatic cancer cells., Conclusion: Combined targeting of AKT and SRC resulted in a synergistic efficacy against human pancreatic cancer growth and metastasis., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

Objectives: The aim of this study was to investigate the effects of the activated P2X7 receptors on the proliferation and growth of human pancreatic cancer cells., Methods: Proliferation was measured by incorporating bromodeoxyuridine into pancreatic cancer cells, MIA PaCa-2 and HPAC. Expression of P2 receptors and signal molecules was examined using quantitative reverse transcription/polymerase chain reaction and/or Western blot. Proliferative effects of the P2X7 receptors in vivo were examined using a xenotransplant model of pancreatic cancer cell lines., Results: Incubating pancreatic cancer cells with adenosine triphosphate (ATP) and 2'(3')-O-(4-Benzoylbenzoyl)ATP resulted in a dose-dependent increase of cell proliferation. The P2 receptor antagonist, KN-62, and small interfering RNA against P2X7 receptors, significantly decreased the proliferative effects of ATP. The ATP-induced proliferation was mediated by protein kinase C, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK); specifically, ATP increased the phosphorylation of ERK1/2 and JNK. The expression of inducible nitric oxide synthase was decreased by P2X7 receptor activation. In a xenotransplant model, applying ATP significantly increased the growth of induced tumors., Conclusions: The P2X7 receptor activation by extracellular nucleotides increased proliferation and growth of human pancreatic cancer cells via ERK1/2 and JNK. This supports the pathophysiological role of P2X7 receptors in pancreatic disease and recovery.

In automated driving, a driver can completely concentrate on non-driving-related tasks (NDRTs). This study investigated the flow experience of a driver who concentrated on NDRTs and tasks that induce mental workload under conditional automation. Participants performed NDRTs under different demand levels: a balanced demand-skill level (fit condition) to induce flow, low-demand level to induce boredom, and high-demand level to induce anxiety. In addition, they performed the additional N-Back task, which artificially induces mental workload. The results showed participants had the longest reaction time when they indicated the highest flow score, and had the longest gaze-on time, road-fixation time, hands-on time, and take-over time under the fit condition. Significant differences were not observed in the driver reaction times in the fit condition and the additional N-Back task, indicating that performing NDRTs that induce a high flow experience could influence driver reaction time similar to performing tasks with a high mental workload., (Copyright © 2017. Published by Elsevier Ltd.)

This study aimed at investigating the effect of two smartphone form factors (width and bottom bezel) on touch behaviors with one-handed interaction. User experiments on tapping tasks were conducted for four widths (67, 70, 72, and 74 mm) and five bottom bezel levels (2.5, 5, 7.5, 10, and 12.5 mm). Task performance, electromyography, and subjective workload data were collected to examine the touch behavior. The success rate and task completion time were collected as task performance measures. The NASA-TLX method was used to observe the subjective workload. The electromyogram signals of two thumb muscles, namely the first dorsal interosseous and abductor pollicis brevis, were observed. The task performances deteriorated with increasing width level. The subjective workload and electromyography data showed similar patterns with the task performances. The task performances of the bottom bezel devices were analyzed by using three different evaluation criteria. The results from these criteria indicated that tasks became increasingly difficult as the bottom bezel level decreased. The results of this study provide insights into the optimal range of smartphone form factors for one-handed interaction, which could contribute to the design of new smartphones., (Copyright © 2017. Published by Elsevier Ltd.)

Haptic technology is used in various fields to transmit information to the user with or without visual and auditory cues. This study aimed to provide preliminary data for use in developing a haptic interface for an antigravity (anti-G) suit. With the structural characteristics of the anti-G suit in mind, we determined five areas on the body (lower back, outer thighs, inner thighs, outer calves, and inner calves) on which to install ten bar-type eccentric rotating mass (ERM) motors as vibration actuators. To determine the design factors of the haptic anti-G suit, we conducted three experiments to find the absolute threshold, moderate intensity, and subjective assessments of vibrotactile stimuli. Twenty-six fighter pilots participated in the experiments, which were conducted in a fixed-based flight simulator. From the results of our study, we recommend 1) absolute thresholds of ∼11.98-15.84 Hz and 102.01-104.06 dB, 2) moderate intensities of 74.36 Hz and 126.98 dB for the lower back and 58.65 Hz and 122.37 dB for either side of the thighs and calves, and 3) subjective assessments of vibrotactile stimuli (displeasure, easy to perceive, and level of comfort). The results of this study will be useful for the design of a haptic anti-G suit., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

There has been great concern about mold in school environments, but few comprehensive assessments of mold have been performed in such settings. Even spore counts or microscopic enumeration only may not be sufficient for evaluating fungal exposure. We explored the levels of submicron fungal fragments with potential heath impact due to their small size in elementary schools and investigated the variation in the concentrations of such particles before and after the rainy season. The concentrations of (1,3)-β-D-glucan in submicron fungal fragments, airborne mold and bacteria, and PM10 were measured both indoors and outdoors in 70 classrooms at 8 elementary schools from May (before the rainy season) to July (after the rainy season) in 2012. Temperature and relative humidity were also monitored. We compared the levels of submicron fungal fragments among schools before and after the rainy season. The associations of the levels of submicron fungal fragments with other variables were analyzed. Overall, the concentrations of (1,3)-β-D-glucan ranged from 10 to 347 pg m(-3), and the indoor/outdoor ratios were greater than 1 in every school. After the rainy season, the (1,3)-β-D-glucan concentrations decreased by about 35%, and similar significant decreases in the concentrations of airborne mold and bacteria and PM10 were observed. This difference was prominent for PM10 (P < 0.001). Only relative humidity was negatively associated with the concentration of submicron fungal fragments (P = 0.007). Our findings confirmed the comparable amounts of submicron fungal fragments in school environments. More comprehensive exposure assessments for smaller-sized fungal particles should be performed for better understanding of their health impact, particularly with regard to seasonal changes.

This research proposes an assessment model for quantifying the perceived visual complexity (PVC) of an in-vehicle instrument cluster. An initial study was conducted to investigate the possibility of evaluating the PVC of an in-vehicle instrument cluster by estimating and analyzing the complexity of its individual components. However, this approach was only partially successful, because it did not take into account the combination of the different components with random levels of complexity to form one visual display. Therefore, a second study was conducted focusing on the effect of combining the different components. The results from the overall research enabled us to suggest a basis for quantifying the PVC of an in-vehicle instrument cluster based both on the PVCs of its components and on the integration effect., (Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

Objectives: Src is considered a rising therapeutic target for the treatment of solid tumors, and Src family kinases (SFKs) participate in cancer cell proliferation and survival. The role of SFK suppression was investigated in the proliferation, migration, and invasion of pancreatic cancer cells., Methods: Knockdown of the SFKs in pancreatic cancer cells was achieved by transfecting small interfering RNAs, and its effects were investigated using proliferation, wound, and invasion assays., Results: The SFK inhibitors suppressed proliferation and induced cell cycle arrest in pancreatic cancer cells. The SFK messenger RNA profiles showed that Yes1, Lyn, Fyn, Frk, Hck, and Src were expressed. Specific small interfering RNA transfection suppressed the messenger RNA expressions of Yes1, Lyn, Fyn, Frk, and Src, and the knockdown suppressed cell proliferation by 16.7% to 47.3% in PANC-1 cells. Knockdown of any of these 5 SFKs suppressed proliferation in other pancreatic cancer cell lines by 3.0% to 40.5%. The knockdowns significantly reduced pancreatic cancer cell migration by 24.9% to 66.7% and completely inhibited invasion., Conclusions: These results suggest that the knockdown of Yes1, Lyn, Fyn, Frk, or Src reduce human pancreatic cancer cell proliferation, migration, and invasion, and that SFKs should be viewed as critical therapeutic targets of pancreatic cancer.

Background: 5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for colorectal cancer (CRC), and the major targets of 5-FU are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1). We hypothesized that polymorphisms in the genes encoding these proteins would be associated with CRC patient survival., Patients and Methods: We genotyped the following polymorphisms in 372 CRC patients: TS enhancer region (TSER), TS 1494del6, MTHFR 677C>T and 1298A>C, and RFC1 -43T>C, 80G>A, and 696C>T. Using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between these polymorphisms and overall survival (OS)., Results: The combined TS 1494 0bp6bp+6bp6bp genotype was associated with reduced OS compared to the TS 1494 0bp0bp genotype. Among rectal cancer patients, the RFC1 -43CC and 80AA genotypes were associated with favorable OS., Conclusions: Our data suggest that TS and RFC1 polymorphisms are associated with CRC prognosis in Korean patients. Further studies are needed to verify these findings., (© 2013 Elsevier B.V. All rights reserved.)

Objective: To study the correlation between the predicted thermal dose volume (TDV) and the actual ablation volumes in MR-guided focused ultrasound surgery (MRgFUS) for symptomatic uterine fibroids, and to follow up the outcome for 12 months post-treatment., Study Design: Phase-difference fast spoiled gradient-echo MR images were used to analyze thermal change during the energy deliveries of MRgFUS in 60 consecutive patients treated for symptomatic uterine fibroids. The TDV obtained through analysis of these MR images was compared with the non-perfused volume (NPV) measured on post-treatment contrast enhanced T1-weighted images. Final values of TDV ratio and NPV ratio were obtained by dividing these values by original fibroid volume. Patients were followed for 12 months post-treatment to assess symptomatic relief using the symptom severity score (SSS)., Results: Treatments in which we managed to reach a TDV ratio larger than 27% of the treated fibroid yielded a ratio of NPV to TDV of 1.1±0.5, indicating accurate control of the non-invasive procedure. Patient symptoms, as measured by the SSS, continuously decreased from a mean baseline score of 50±22 to 19±12 (P<0.0001) 12 months post-treatment., Conclusions: At large treatment volumes (exceeding 27% TDV ratio), thermal dose estimates correspond very closely to non-perfused volumes measured immediately post treatment. These large treatment volumes result in continuous clinical improvement throughout the first 12 months after MRgFUS., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine., Methods: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247., Findings: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33)., Interpretation: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity., Funding: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to investigate the effect of uridine triphosphate (UTP) on the proliferation of human cancerous pancreatic duct epithelial cells., Methods: Proliferation was measured by immunoassay for bromodeoxyuridine incorporation into the pancreatic cell line PANC-1. Effect of UTP was assayed using selective P2 agonist and antagonist, small interfering RNA, intracellular signal inhibitors, and Western blot., Results: Incubation of PANC-1 cells with UTP or MRS2768, a selective P2Y2 receptor agonist, resulted in a dose- and time-dependent increase of proliferation. The messenger RNA transcript and protein of P2Y2 receptor were expressed in PANC-1 cells. P2 receptor antagonist suramin and small interfering RNA against P2Y2 receptor significantly decreased the proliferative effect of UTP and MRS2768. Activation of P2Y2 receptor by UTP transduced to phospholipase C, inositol 1,4,5-triphosphate (IP3), and protein kinase C. Uridine triphosphate-induced proliferation was mediated by protein kinase D, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, phosphatidylinositol 3-kinase (PI3K), Akt, and phospholipase D. Uridine triphosphate increased phosphorylation of Akt through protein kinase C, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, and PI3K., Conclusions: Uridine triphosphate increases proliferation of human pancreatic duct epithelial cells by activation of P2Y2 receptor and PI3K/Akt pathway. This could be helpful for discovering the long-term roles of P2Y2 receptor in pancreatic cells.

Objectives: The aim of this study was to investigate the effect of P2Y receptor activation on proliferation of human pancreatic duct epithelial cells., Methods: Proliferation was measured by immunoassay for bromodeoxyuridine incorporation into a pancreatic duct epithelial cell line, PANC-1. Expression of P2Y receptors was examined using quantitative reverse transcription-polymerase chain reaction and Western blot., Results: Extracellular nucleotides, adenosine diphosphate (ADP) and uridine diphosphate (UDP), stimulated proliferation of pancreatic duct cells in a concentration-dependent manner. The nucleotide efficacy order was ADP > UDP > uridine triphosphate (UTP) > adenosine triphosphate. P2Y(1) and P2Y(6) receptor blockers, MRS2500 and MRS2578, blocked the effect of ADP and UDP. The signal that transmitted the proliferative activity of ADP and UDP was transducted to phospholipase C, inositol 1,4,5-triphosphate receptor, and protein kinase C. These results indicate involvement of P2Y(1) and P2Y(6) receptors in ADP- and UDP-stimulated proliferation. Pancreatic duct cells expressed the messenger RNA transcripts of P2Y receptors, P2Y(1) , P2Y(2), and P2Y(6), and P2Y(1) and P2Y(6) receptor protein., Conclusions: Extracellular nucleotides increase proliferation of human pancreatic duct epithelial cells by activation of P2Y(1) and P2Y(6) receptors. This provides the basic model for the effect of P2Y receptors on the proliferation of pancreatic duct epithelial cells.

Background: The purpose of this study was to evaluate whether measuring the ratio of descending aortic enhancement (DAE) to main pulmonary artery enhancement (MPAE) on pulmonary computed tomography angiography (PCTA) can predict poor outcome in patients with acute massive or submassive pulmonary embolism (PE)., Methods: We retrospectively, reviewed computed tomgraphy findings and charts of 37 patients with acute PE and right ventricular dysfunction. We divided the enrolled patients into 3 groups; group Ia (n=8), comprised of patients with major adverse event (MAE); group Ib (n=5), consisted of those with PE-related MAE; and group II (n=29), those without MAE. We analyzed the right ventricular diameter (RVD)/left ventricular diameter (LVD) and DAE/MPAE on PCTA., Results: For observer 1, RVD/LVD in group Ia (1.9±0.36 vs. 1.44±0.38, p=0.009) and group Ib (1.87±0.37 vs. 1.44±0.38, p=0.044) were significantly higher than that of group II. For observer 2, RVD/LVD in group Ia (1.71±0.18 vs. 1.41±0.47, p=0.027) was significantly greater than that of group II, but RVD/LVD of group Ib was not (1.68±0.2 vs. 1.41±0.47, p=0.093). For both observers, there was a significant difference of DAE/MPAE between group Ib and group II (0.32±0.15 vs. 0.64±0.24, p=0.005; 0.34±0.16 vs. 0.64±0.22, p=0.004), but no significant difference of DAE/MPAE between group Ia and group II (0.51±0.3 vs. 0.64±0.24, p=0.268; 0.53±0.29 vs. 0.64±0.22, p=0.302). Intra-class correlation coefficient (ICC) for the measurement of DAE/MPAE (ICC=0.97) was higher than that of RVD/LVD (ICC=0.74)., Conclusion: DAE/MPAE measured on PCTA may predict PE-related poor outcomes in patients with massive or submassive PE with an excellent inter-observer agreement.

Objectives: This study aimed to identify proteins important for the primitive gut tube differentiation from human embryonic stem cells (hESCs) by derivation method for pancreatic cells., Methods: Proteins with altered expression levels in the process of differentiating to primitive gut tube from definitive endoderm of hESCs were investigated by comparative proteomic analysis using 2-dimensional gel electrophoresis and mass spectrometric analyses., Results: Differentiation to primitive gut tube from hESCs was analyzed using differentiation marker genes and proteins. Twenty-seven protein spots with significant changes in intensity were found by 2-dimensional gel electrophoresis, and 24 proteins were further identified. These proteins were functionally annotated based on gene ontology. The expression levels of 3 proteins, RREB1, PDE6B, and CD209, involved in signal transduction, were validated using quantitative reverse transcription-polymerase chain reaction and Western blot. Their mRNA and protein expression levels increased in primitive gut tube but not in definitive endoderm or embryonic body., Conclusions: The increase in expression of RREB1, PDE6B, and CD209 suggests that these proteins might play important roles in the differentiation of primitive gut tube cells from hESCs and in human primitive gut tube development into pancreas. Therefore, they could be developed as differentiation markers for identifying primitive gut tube cells.

Objectives: This study was aimed to investigate important proteins associated with endoderm differentiation by pancreatic derivation protocol from human embryonic stem cells (hESCs)., Methods: Comparative proteomic analysis of endoderm cells differentiated from hESCs by activin A and low serum was performed. Proteins with altered expression levels during endoderm differentiation were investigated by 2-dimensional gel electrophoresis (2-DE) with mass spectrometric analysis., Results: Thirty-four protein spots with significantly changed intensities were identified. These were functionally annotated based on gene ontology. The messenger RNA expression levels of 5 genes, APC, CCNB3, HSPA9, CCT2, and YWHAE, were correlated with 2-DE analysis. We further validated the protein expression levels of adenomatous polyposis coli (APC) and cyclin B3 (CCNB3) by using Western blot analysis and immunocytochemistry. They are involved in the regulation of cell cycle, thus, cyclins and cyclin-dependent kinases, which regulate the cell cycle, were examined. Cyclin A1, cyclin D2, and cyclin E2 were upregulated, and other cyclins and cyclin-dependent kinases were downregulated in endoderm cells., Conclusions: The increase in expression of APC and CCNB3 suggests that these proteins will be important markers for identifying endoderm cells differentiated from hESCs, and they can play important roles in the differentiation of endoderm cells from hESCs or in human endoderm development for pancreas.

Taking BF gene as one of the candidate genes influencing on reproductive traits in present study, this study used PCR-RFLP analyzised the polymorphism of intron 1 of BF gene in Large White sows. A single nucleotide polymorphism (SNP) named as BF-intron 1-C79T was detected. And the three genotypes of CC, CT, TT got fitted Hardy-Weinberg equilibrium with chi2-fitness test. An association analysis was tested between the genetic polymorphism at intron 1 and total number born (TNB), number born alive (NBA), born weight (BW) and placental efficiency (PE) respectively. It showed that, at first parity, the TNB, NBA, BW and PE with CC genotype were higher than those with CT genotype but not significant (P>0.05). Meanwhile, in multiparous sow population, the TNB, NBA and PE with CC genotype were significantly more than those with TT genotype (P<0.05), with increase of 3.45, 3.92, and 23.80%, respectively. Thus BF-intron 1-C79T is suggested to be a potential genetic marker for the breeding on the reproductive traits and placental efficiency.

Objective: To evaluate the effect of silicon and latex urinary catheters on urinary mucosa., Methods: A randomized, controlled prospective clinical trial was carried out in 60 patients admitted in the Department of Neurosurgery, who required long-term use of an indwelling urinary catheter. The patients were divided into 2 equal groups with placement of silicon or latex urinary catheter, and routine laboratory urine test was performed on a regular basis and the patients feelings during catheter retention were recorded., Results: Patients with placement of indwelling silicone catheters reported no obvious discomfort in relation to the catheter placement and had significantly lower incidence of hematuria identified microscopically than those with common latex catheters., Conclusion: Compared with latex catheters, silicone catheters cause less injuries and reduce substantially irritation of the urinary mucosa, and we suggest the use of silicone catheter in patients requiring long-term indwelling urinary catheters.

The mutant plasmid pAmy413C, in which G takes the place of A at the 271 position of alpha-amylase gene on the pAmy413 from B. licheniformis, was constructed by site-direct mutagenesis. At the N-terminus of the mature alpha-amylase, amino acid +2Asn was substituted by +3Asp in the wild type protein. Then, the alpha-amylase output of the mutant plasmid pAmy413C in B. subtilis was 2.02-2.57 times higher than that of the wild type pAmy413C in the same strain. The amino acid sequencing at the N-terminus of the matural alpha-amylase revealsed that the recognition site of signal peptidase I moved one amino acid upstream, from Ala-(+2)Asn to AlaAla-(+3) Asp. That is, the +2Asn of the wild type was changed to the +3Asp of the mutant. The secondary structural analysis showed that a 14-cycle structure formed in the alpha-amylase mRNA when the free energy was -51.7 kcal. In this case, the mutant is identical with the wild type. The difference between them is that G at 271 position is no longer paired with U at 211 position, hence, a G-overhang is formed. The secondary structural analysis of protein showed that one amino acid diminished in the turn structure of amino acid at 33-37 position, and this very amino acid is involed in an alpha-helix structure. In short, all the changes mentioned above in conformation and charged amino acids contribute to the increase in the protein secretion in B. subtilis.