Comparing the efficacy of combined versus single immune cell adaptive therapy targeting colorectal cancer.

PURPOSE: Colorectal cancer (CRC) is the most frequent cancer with limited therapeutic achievements. Recently, adoptive cellular immunotherapy has been developed as an antitumor therapy. However, its efficacy has not been tested in CRC. This study investigated the ability of an immune cell cocktail of dendritic cells (DCs), T cells, and natural killer (NK) cells to overcome immunological hurdles and improve the therapeutic efficacy of cell therapy for CRC. METHODS: CRC lysate-pulsed monocyte-derived DCs (Mo-DCs), CRC antigen-specifically expanded T cells (CTL), and in vitro-expanded NK cells were cultured from patient peripheral blood mononuclear cells (PBMC). The ability of the combined immune cells to kill autologous tumor cells was investigated by co-culturing the combined immune cells with patient-derived tumor cells. RESULTS: The Mo-DCs produced expressed T cell co-stimulating molecules like CD80, CD86, human leukocyte antigen (HLA)-DR and HLA-ABC, at high levels and were capable of activating naive T cells. The expanded T cells were predominantly CD8 T cells with high levels of CD8 effector memory cells and low levels of regulatory T cells. The NK cells expressed high levels of activating receptors and were capable of killing other cancer cell lines (K562 and HT29). The immune cell cocktail demonstrated a higher ability to kill autologous tumor cells than single types. An in vivo preclinical study confirmed the safety of the combined immune cell adaptive therapy showing no therapy-related death or general toxicity symptoms. CONCLUSION: The results suggested that combined immune cell adaptive therapy could overcome the limited efficacy of cell immunotherapy.

Developing a national surveillance system for stroke and acute myocardial infarction using claims data in the Republic of Korea: a retrospective study.

BACKGROUND: Limited information is available concerning the epidemiology of stroke and acute myocardial infarction (AMI) in the Republic of Korea. This study aimed to develop a national surveillance system to monitor the incidence of stroke and AMI using national claims data. METHODS: We developed and validated identification algorithms for stroke and AMI using claims data. This validation involved a 2-stage stratified sampling method with a review of medical records for sampled cases. The weighted positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the sampling structure and the corresponding sampling rates. Incident cases and the incidence rates of stroke and AMI in the Republic of Korea were estimated by applying the algorithms and weighted PPV and NPV to the 2018 National Health Insurance Service claims data. RESULTS: In total, 2,200 cases (1,086 stroke cases and 1,114 AMI cases) were sampled from the 2018 claims database. The sensitivity and specificity of the algorithms were 94.3% and 88.6% for stroke and 97.9% and 90.1% for AMI, respectively. The estimated number of cases, including recurrent events, was 150,837 for stroke and 40,529 for AMI in 2018. The age- and sex-standardized incidence rate for stroke and AMI was 180.2 and 46.1 cases per 100,000 person-years, respectively, in 2018. CONCLUSION: This study demonstrates the feasibility of developing a national surveillance system based on claims data and identification algorithms for stroke and AMI to monitor their incidence rates.

National Smoking Cessation Services (NSCS) enrollment and their effect on long-term tobacco cessation in Korea: Results from a 1-year prospective follow-up of NSCS participants.

INTRODUCTION: The study aimed to identify predictors associated with long-term tobacco cessation at 12-month follow-up among users of the National Smoking Cessation Services (NSCS) in Korea. METHODS: To measure the long-term effect of NSCS delivery, the target sample size of 5167 adult smokers registered in the NSCS in 2018 was enrolled with proportional random sampling. A multiple logistic regression analysis (crude, adjusted) was performed to identify the changes in smoking status at the 12-month follow-up after the last NSCS enrollment and the potential factors associated with changes in smoking status. RESULTS: The response rate to reach the number of subjects targeted was 22.4%. A total of 41.2% of the tobacco users enrolled had successfully quit at baseline, and the 7-day point prevalence of tobacco cessation at the follow-up at 12 months, via a telephone survey, was 34.4%. Factors positively associated with cessation at the 12-month follow-up were longer experience with tobacco abstinence and additional quitting attempts with or without NSCS enrollment, although every additional quit attempt with NSCS use had a better outcome. In addition, having a successful quit outcome with NSCS use at the baseline and having more satisfaction with the service of professional counseling or incentives than others provided by NSCS, increased cessation at follow-up after adjustment of other factors considered. CONCLUSIONS: In addition to multiple quitting attempts, longer experience with tobacco abstinence, and additional enrollment in NSCS, the service experience, and satisfaction with the content that NSCS offered, might improve the lasting success of abstinence. These results might be considered to improve the contents and protocols of the NSCS for better outcomes.

Design of a Bioinspired Robust Three-Dimensional Cross-Linked Polymer Binder for High-Performance Li-Ion Battery Applications.

Si has the highest theoretical capacity (4200 mA h g-1) among conventional anode materials, such as graphite (372 mA h g-1), but its large volume expansion leads to deterioration of the battery performance. To overcome this problem (issue), we investigated the use of polysaccharide-based 3D cross-linked network binders for Si anodes, in which the polysaccharide formed an effective 3D cross-linked network around Si particles via cross-linking of polysaccharide with citric acid (CA). Sodium alginate (SA), a natural polysaccharide extracted from brown algae, is a suitable binder material for Si anodes because its abundant hydroxyl (-OH) and carboxyl (-COOH) groups form hydrogen and covalent bonds with the -OH groups present on the Si surface. We found that CA-cross-linked (CA-SA) could effectively prevent the volume expansion of Si anodes through the formation of 3D cross-linked network structures. In addition, the CA-SA binders provide enhanced adhesion strength, enabling the fabrication of more robust electrodes than those prepared using binders with linear structures ("linear binders"). In particular, the fabricated Si-based electrode (high mass loading of 1.5 mg cm-2) with CA-SA binder exhibited outstanding areal capacity (∼2.7 mA h cm-2) and excellent cycle retention (∼100% after 100 cycles).

Estrogen Regulates the Expression and Localization of YAP in the Uterus of Mice.

The dynamics of uterine endometrium is important for successful establishment and maintenance of embryonic implantation and development, along with extensive cell differentiation and proliferation. The tissue event is precisely and complicatedly regulated as several signaling pathways are involved including two main hormones, estrogen and progesterone signaling. We previously showed a novel signaling molecule, Serine/threonine protein kinase 3/4 (STK3/4), which is responded to hormone in the mouse uterine epithelium. However, the role and regulation of its target, YES-associated protein (YAP) remains unknown. In this study, we investigated the expression and regulation of YAP in mouse endometrium. We found that YAP was periodically expressed in the endometrium during the estrous cycle. Furthermore, periodic expression of YAP was shown to be related to the pathway under hormone treatment. Interestingly, estrogen was shown to positively modulate YAP via endometrial epithelial receptors. In addition, the knockdown of YAP showed that YAP regulated various target genes in endometrial cells. The knockdown of YAP down-regulated numerous targets including ADAMTS1, AMOT, AMOTL1, ANKRD1, CTNNA1, MCL1. On the other hand, the expressions of AREG and AXL were increased by its knockdown. These findings imply that YAP responds via Hippo signaling under various intrauterine signals and is considered to play a role in the expression of factors important for uterine endometrium dynamic regulation.

Preparation and Electrochemical Characterization of Si@C Nanoparticles as an Anode Material for Lithium-Ion Batteries via Solvent-Assisted Wet Coating Process.

Silicon-based electrodes are widely recognized as promising anodes for high-energy-density lithium-ion batteries (LIBs). Silicon is a representative anode material for next-generation LIBs due to its advantages of being an abundant resource and having a high theoretical capacity and a low electrochemical reduction potential. However, its huge volume change during the charge-discharge process and low electrical conductivity can be critical problems in its utilization as a practical anode material. In this study, we solved the problem of the large volume expansion of silicon anodes by using the carbon coating method with a low-cost phenolic resin that can be used to obtain high-performance LIBs. The surrounding carbon layers on the silicon surface were well made from a phenolic resin via a solvent-assisted wet coating process followed by carbonization. Consequently, the electrochemical performance of the carbon-coated silicon anode achieved a high specific capacity (3092 mA h g-1) and excellent capacity retention (~100% capacity retention after 50 cycles and even 64% capacity retention after 100 cycles at 0.05 C). This work provides a simple but effective strategy for the improvement of silicon-based anodes for high-performance LIBs.

Association between perceived harm of tobacco and intention to quit: a cross-sectional analysis of the Vietnam Global Adult Tobacco Survey.

BACKGROUND: Perception of harm plays an important role in predicting intention to quit-an integral part of the cessation process. Perception on harm from bamboo waterpipe tobacco was unknown, even the predominant of this type of tobacco use. This study investigated the effects of perceived harm from cigarette and bamboo waterpipe tobacco on intention to quit among adult male Vietnamese tobacco users. METHODS: From the nationally-representative 2015 Global Adult Tobacco Survey, we included 1,351 adult males (≥ 18 years old) who used cigarettes, bamboo waterpipes, or both. Demographic characteristics, tobacco use behaviors, perceived harm from tobacco use, and regulation/policy exposure were measured. Effects of perceived harm from cigarette and bamboo waterpipe tobacco on intention to quit were assessed by logistic regression. RESULTS: Intention to quit prevalence was 59.0%, 55.0%, and 58.4% for cigarette, waterpipe, and dual users, respectively. Tobacco users who perceived that "using cigarettes and/or waterpipe could cause severe illness" and "waterpipe use is less harmful than cigarette smoking", had tobacco use bans at home, or were exposed to anti-smoking campaigns or encouragement to quit information were more likely to intend to quit. When analyzed by tobacco users, intention to quit was more likely for those users who perceived their tobacco product as more harmful than the other product type, although statistical significance was only observed for cigarette users. CONCLUSIONS: Misperceptions regarding harm from tobacco use could negatively affect intention to quit. Dissemination of accurate information on the risks from all forms of tobacco use and enforcement of tobacco control policies are important for encouraging intention to quit.

A Deep Dive: SIWV Tetra-Peptide Enhancing the Penetration of Nanotherapeutics into the Glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor. It is difficult to regulate GBM using conventional chemotherapy-based methods due to its anatomical structure specificity, low drug targeting ability, and limited penetration depth capability to reach the tumor interior. Numerous approaches have been proposed to overcome such issues, including nanoparticle-based drug delivery system (DDS) with the development of GBM site targeting and penetration depth enhancing moieties (e.g., peptides, sugars, proteins, etc.). In this study, we prepared four different types of nanoparticles, which are based on porous silicon nanoparticles (pSiNPs) incorporating polyethylene glycol (PEG), iRGD peptide (well-known cancer targeting peptide), and SIWV tetra-peptide (a recently disclosed GBM-targeting peptide), and analyzed their deep-tumor penetration abilities in cell spheroids, in GBM patient-derived tumoroids, and in GBM xenograft mice. We found that SIWV tetra-peptide significantly enhanced the penetration depth of pSiNPs, and its therapeutic formulation (temozolomide-loaded/SIWV-functionalized pSiNPs) showed a higher anticancer efficacy compared with other formulations. These findings hold great promise for the development of nanotherapeutics and peptide-conjugated drugs for GBM.

Perceptions of Heated Tobacco Products (HTPs) and Intention to Quit Among Adult Tobacco Users in Korea.

BACKGROUND: The popularity of heated tobacco products (HTPs) has been growing globally but, limited information exists on tobacco use behaviors and its impact on tobacco control. This study investigates awareness and perception of HTPs among tobacco users and whether perceptions of HTPs are associated with HTP use and intention to quit. METHODS: We invited 2,000 tobacco users aged 19-65 years with countrywide representation to an online survey in November 2018. Information on general characteristics, tobacco use behaviors, awareness and perception of HTPs, and intention to quit were gathered. Multinomial logistic regression analysis and ANCOVA were used for estimation of association and comparison. RESULTS: Among all tobacco users, 36.8% were classified as ever users, whereas 28.3% had used HTPs in the past 30 days, which was higher than expected. Users of liquid-based e-cigarettes (odds ratio [OR] 1.578; 95% confidence interval [CI], 1.210-2.056) and poly-product users (OR 2.029; 95% CI, 1.121-3.671) showed higher intention to quit within 1 month when compared to users of conventional cigarettes (CCs), whereas HTP users and dual product users did not. HTP users rated HTPs more favorably than CCs in terms of smoke, smell, harm, aid in quitting, design, and price than users of other products did (P-value < 0.001). CONCLUSION: We find that positive perception of HTPs following strategic marketing from tobacco companies could have contributed to a greater increase in HTP use than expected in Korea. However, HTPs might not be considered substitutes for CCs for quitting tobacco use because a significant proportion of dual product users reported a lower intention to quit.

Analysis of electric cigarette liquid effect on mouse brain tumor growth through EGFR and ERK activation.

INTRODUCTION: Recently, electric cigarettes with liquid (e-liquid) were introduced as an alternative to tobacco smoking. They were promoted as possible cessation aids and were considered to be potentially less harmful than traditional tobacco-based cigarettes. However, there is little information on the toxicants present in e-liquids and their possible carcinogenic effects. METHODS: Western blot analysis was performed to identify the protein levels of cancer progression related signal transducers. Patient-derived brain tumor cells (CSC2) were injected into mouse brains and tumor growth was then observed by performing magnetic resonance imaging (MRI) and hematoxylin and eosin (H&E) staining of the whole brain. Immunohistochemistry (IHC) staining and Immunofluorescence staining were performed to study the expression of pEGFR and pERK. RESULTS: Western blotting revealed that e-liquids increased pEGFR and pERK expression in a dose dependent manner. Animal experiments revealed that the e-liquid treated group had accelerated tumor growth and poor prognosis compared to the vehicle group. Histological staining showed activation of pEGFR and pERK in the e-liquid treated group. CONCLUSION: Our study revealed that e-liquid activates pEGFR and pERK, leading to accelerated brain tumor growth and poor prognosis.

Social competence, leisure time activities, and smoking trajectories among adolescent boys: data from the Korean Children & Youth Panel Survey.

OBJECTIVES: The purpose of this study was to identify the trajectories and potential predictors of tobacco use during adolescence in Korea and to develop appropriate strategies for the implementation of tobacco use prevention programs. METHODS: The trajectory of tobacco use and associated predictors were analyzed for 1,169 male students from grade 6 (age 11-12) to grade 10 (age 15-16) in the Korean Children & Youth Panel Survey from 2012 to 2016. RESULTS: Three trajectories of smoking experience were identified: non-smokers (class 1: n=775, 82.3%), temporary users (class 2: n=32, 3.4%), and regular users (class 3: n=135, 14.3%). When compared to non-smokers, temporary users had a higher likelihood of living with a single parent, dissatisfaction with grades, having a girlfriend, having been victimized at least once, and having at least 1 delinquent friend in grade 7 (when smoking experimentation was at its peak). Significant factors associated with regular use included having a girlfriend, committing at least 1 type of delinquent behavior, and being a non-reader. Committing at least 1 type of delinquent behavior and having at least 1 delinquent friend were associated with regular users, distinguishing them from temporary users. CONCLUSIONS: Understanding why adolescents exhibit different trajectories of tobacco use by identifying the factors associated with each trajectory can contribute to the development of tailored prevention strategies and early cessation programs for adolescents.

Potential of Bioactive Food Components against Gastric Cancer: Insights into Molecular Mechanism and Therapeutic Targets.

Gastric cancer, also known as stomach cancer, is a cancer that develops from the lining of the stomach. Accumulated evidence and epidemiological studies have indicated that bioactive food components from natural products play an important role in gastric cancer prevention and treatment, although its mechanism of action has not yet been elucidated. Particularly, experimental studies have shown that natural bioactive food products display a protective effect against gastric cancer via numerous molecular mechanisms, such as suppression of cell metastasis, anti-angiogenesis, inhibition of cell proliferation, induction of apoptosis, and modulation of autophagy. Chemotherapy remains the standard treatment for advanced gastric cancer along with surgery, radiation therapy, hormone therapy, as well as immunotherapy, and its adverse side effects including neutropenia, stomatitis, mucositis, diarrhea, nausea, and emesis are well documented. However, administration of naturally occurring bioactive phytochemical food components could increase the efficacy of gastric chemotherapy and other chemotherapeutic resistance. Additionally, several studies have suggested that bioactive food components with structural stability, potential bioavailability, and powerful bioactivity are important to develop novel treatment strategies for gastric cancer management, which may minimize the adverse effects. Therefore, the purpose of this review is to summarize the potential therapeutic effects of natural bioactive food products on the prevention and treatment of gastric cancer with intensive molecular mechanisms of action, bioavailability, and safety efficacy.

Factors to improve distress and fatigue in Cancer survivorship; further understanding through text analysis of interviews by machine learning.

BACKGROUND: From patient-reported surveys and individual interviews by health care providers, we attempted to identify the significant factors related to the improvement of distress and fatigue for cancer survivors by text analysis with machine learning techniques, as the secondary analysis using the single institute data from the Korean Cancer Survivorship Center Pilot Project. METHODS: Surveys and in-depth interviews from 322 cancer survivors were analyzed to identify their needs and concerns. Among the keywords in the surveys, including EQ-VAS, distress, fatigue, pain, insomnia, anxiety, and depression, distress and fatigue were focused. The interview transcripts were analyzed via Korean-based text analysis with machine learning techniques, based on the keywords used in the survey. Words were generated as vectors and similarity scores were calculated by the distance related to the text's keywords and frequency. The keywords and selected high-ranked ten words for each keyword based on the similarity were then taken to draw a network map. RESULTS: Most participants were otherwise healthy females younger than 50 years suffering breast cancer who completed treatment less than 6 months ago. As the 1-month follow-up survey's results, the improved patients were 56.5 and 58.4% in distress and fatigue scores, respectively. For the improvement of distress, dyspepsia (p = 0.006) and initial scores of distress, fatigue, anxiety, and depression (p < 0.001, < 0.001, 0.043, and 0.013, respectively) were significantly related. For the improvement of fatigue, economic state (p = 0.021), needs for rehabilitation (p = 0.035), initial score of fatigue (p < 0.001), any intervention (p = 0.017), and participation in family care program (p = 0.022) were significant. For the text analysis, Stress and Fatigue were placed at the center of the keyword network map, and words were intricately connected. From the regression anlysis combined survey scores and the quantitative variables from the text analysis, participation in family care programs and mention of family-related words were associated with the fatigue improvement (p = 0.033). CONCLUSION: Common symptoms and practical issues were related to distress and fatigue in the survey. Through text analysis, however, we realized that the specific issues and their relationship such as family problem were more complicated. Although further research needs to explore the hidden problem in cancer patients, this study was meaningful to use personalized approach such as interviews.

Effect of Application Amounts on In Vitro Dermal Absorption Test Using Caffeine and Testosterone.

Dermal absorption of chemicals is a key factor in risk assessment. This study investigated the effects of different amounts of application on dermal absorption and suggested an appropriate application dose for proper dermal absorption. Caffeine and testosterone were chosen as test compounds. An in vitro dermal absorption test was performed using a Franz diffusion cell. Different amounts (5, 10, 25, and 50 mg (or µL)/cm2) of semisolid (cream) and liquid (solution) formulations containing 1% caffeine and 0.1% testosterone were applied to rat and minipig (Micropig®) skins. After 24 h, the concentrations of both compounds remaining on the skin surface and in the stratum corneum, dermis and epidermis, and receptor fluid were determined using LC-MS / MS or HPLC. Dermal absorption of both compounds decreased with increasing amounts of application in both skin types (rat and minipig) and formulations (cream and solution). Especially, dermal absorptions (%) of both compounds at 50 mg (or µL)/cm2 was significantly lower compared to 5 or 10 mg (or µL)/cm2 in both rat and minipig skins. Therefore, a low dose (5 or 10 mg (or µL)/cm2) of the formulation should be applied to obtain conservative dermal absorption.

Seven-Month Analysis of Five SARS-CoV-2 Antibody Assay Results after ChAdOx1 nCoV-19 Vaccination: Significant Decrease in SARS-CoV-2 Antibody Titer.

We investigated the longevity rates of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after a complete ChAdOx1 nCoV-19 vaccination, which are rare and important to estimate their efficacy and establish a vaccination strategy. We assessed the positivity rates and changes of titers before (T0) and at one month (T1), four months (T2), and seven months (T3) after a ChAdOx1 nCoV-19 vaccination using five SARS-CoV-2 antibody assays. A total of 874 serum samples were obtained from 228 (T0 and T1), 218 (T2), and 200 (T3) healthcare workers. The positive rates for all five assays were 0.0-0.9% at T0, 66.2-92.5% at T1, 98.2-100.0% at T2, and 66.0-100.0% at T3. The positive rates at T3 were decreased compared to those at T2. The median antibody titers of all the assays at T3 were significantly decreased compared to those at T2 (860.5 to 232.0 U/mL for Roche total, 1041.5 to 325.5 AU/mL for Abbott IgG, 10.9 to 2.3 index for Siemens IgG, 99.5% to 94.7% for SD Biosensor V1, and 88.5% to 38.2% for GenScript). A third-dose scheme can be considered based on our data generated from five representative assays. Our findings contribute insights into SARS-CoV-2 antibody assays and appropriate vaccination strategies.

Effect of Additional Motivational Interviewing on Smoking Abstinence for 1-Year among Korean Adolescents: Results from A Comparative Retrospective Study in Quitline.

The aim of this study was to evaluate the effect of additional motivational enhancement through telephone-based counseling on short- and long-term smoking abstinence among Korean adolescents. METHODS: A comparative retrospective study was conducted based on the longitudinal follow up in Quitline from 2010 to 2017. A total of 533 and 178 adolescent smokers voluntarily participated in the 1-year quitting counseling only (group A, who were ready to quit) and the additional 4-week motivational interviewing before 1-year quitting counseling (group B, who were ambivalent about quitting), respectively. The outcomes were self-reported continuous abstinence at 30-day, 6-month, and 1-year follow up. Logistic regression was applied to estimate the effect of potential factors, including motivational enhancement, on cessation outcome. RESULTS: At baseline, adolescents in group B had a lower motivation to quit than those in group A (p < 0.001). The successful quit rates at 30-day, 6-month, and 1-year follow up were 37.2%, 12.8%, and 11.4% in group A and 33.7%, 15.2%, and 11.2% in group B, respectively. After adjusting factors as appropriate, successful quit rates in group B were not significantly different from the rates in group A. Higher self-efficacy increased the successful quit rate at 30-day, 6-month, and 1-year follow up, similar in subgroup analysis by gender. Never-drinking showed significant association with 30-day successful quit in the whole population and among boys. The lower number of smoking triggers was associated with an increased 30-day successful quit rate among boys only. CONCLUSIONS: Counseling for motivational enhancement could be a promising approach for better quitting outcomes. Improving self-efficacy and eliminating smoking triggers should be continuously strengthened during the quitting process.

Factors associated with psychological stress and distress among Korean adults: the results from Korea National Health and Nutrition Examination Survey.

The prevalence of stress and distress has been increasing and being important public health issues; nevertheless, few studies have assessed the factors associated at the population level. This study identified factors associated and how they differentially influence stress and distress. A total of 35,105 individuals aged 19 years and older using nationally representative data from the Korea National Health and Nutrition Examination Survey (2007-2012) were included in the study. Subjects were differentiated by gender and psychological state (no symptoms, stress, distress). The associations of socio-demographics, psychosocial factors, health behaviours, and chronic illness with psychological states were analysed by gender. Socio-demographics and psychosocial factors such as lower household income, lower education level, living alone or negative outcome of marriage, and unemployment were associated with distress in both genders. Male and female educated higher and with short sleep duration, male living alone and with higher household income, and female married and with a lower household income was associated with stress. A perceived body image of slim or fat was associated with distress and stress in both genders. Behavioural factors, such as smoking, higher alcohol consumption, and abnormal calorie intake, were associated with stress and distress in both genders, with the exception of alcohol consumption in distress and abnormal calorie intake in stress of male. Socio-economic deprivation and negative psychosocial and behavioural factors were differently associated with psychological distress or stress by gender. Intervention strategies for distress and stress should be specifically tailored regarding these differences.

Erratum: Tong, T., et al. α-Ionone Protects Against UVB-Induced Photoaging in Human Dermal Fibroblasts. Molecules 2019, 24, 1804.

The authors wish to make the following change to their paper [...].

STAT3 is a key molecule in the oncogenic behavior of diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) is one of the most lethal childhood brain tumors. This tumor is unique because it is detected exclusively in the ventral pons of patients aged between 6 and 7 years, which suggests a developmental nature of its formation. Signal transducer and activator of transcription 3 (STAT3) is a critical molecule for the differentiation of neural stem cells into astrocytes during neurodevelopment. Additionally, STAT3 is associated with oncogenesis and the epithelial-mesenchymal transition (EMT) in various types of tumor. In recent years, several studies have demonstrated the oncogenic role of STAT3 in high-grade gliomas. However, the role of STAT3 in DIPG at the cellular level remains unknown. To assess the possible association between gliogenesis and DIPG, the expression levels of various molecules participating in the differentiation of neural stem cells were compared between normal brain control tissues and DIPG tissues using open public data. All of the screened genes exhibited significantly increased expression in DIPG tissues compared with normal tissues. As STAT3 expression was the most increased, the effect of STAT3 inhibition in a DIPG cell line was assessed via STAT3 short hairpin (sh)RNA transfection and treatment with AG490, a STAT3 inhibitor. Changes in viability, apoptosis, EMT and radiation therapy efficiency were also evaluated. Downregulation of STAT3 resulted in decreased cyclin D1 expression and cell viability, migration and invasion. Additionally, treatment with STAT3 shRNA or AG490 suppressed the EMT phenotype. Finally, when radiation was administered in combination with STAT3 inhibition, the therapeutic efficiency, assessed by cell viability and DNA damage repair, was increased. The present results suggest that STAT3 is a potential therapeutic target in DIPG, especially when combined with radiation therapy.

A Theoretical and Empirical Investigation of Design Characteristics in a Pb(Zr,Ti)O3-Based Piezoelectric Accelerometer.

A theoretical and experimental study on the design-to-performance characteristics of a compression-mode Pb(Zr,Ti)O3-based piezoelectric accelerometer is presented. Using the metamodeling to approximate the relationship between the design variables and the performances, the constituent components were optimized so that the generated electric voltage, representing sensitivity, could be maximized at different set values of the resonant frequency (25-40 kHz). Four kinds of optimized designs were created and fabricated into the accelerometer modules for empirical validation. The accelerometer modules fabricated according to the optimized designs were highly reliable with a broad range of resonant frequency as well as sufficiently high values of charge sensitivity. The fixed (or mounted) resonant frequency was between 16.1-30.1 kHz based on the impedance measurement. The charge sensitivity decreased from 296.8 to 79.4 pC/g with an increase of the resonant frequency, showing an inverse relation with respect to the resonant frequency. The design-dependent behaviors of the sensitivity and resonant frequency were almost identical in both numerical analysis and experimental investigation. This work shows that the piezoelectric accelerometer can be selectively prepared with best outcomes according to the requirements for the sensitivity and resonant frequency, fundamentally associated with trade-off relation.