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Functional somatic syndromes (such as chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome) are often comorbid. Whether these syndromes are distinct constructs and whether they have different psychological features are interesting questions. We perform a cluster analysis based on a nationwide survey in Taiwan to answer these questions.A score of at least 5 on the Patient Health Questionnaire-15 (PHQ-15, measuring somatic symptoms) indicated somatic syndromes and the data of 550 subjects were included. According to the gastrointestinal, pain-fatigue and cardiovascular subdimension scores of the PHQ-15, we performed a two-step cluster analysis. The demographic data and the cluster scores of the Health Anxiety Questionnaire and the Patient Health Questionnaire-4 (measuring depression and anxiety) were compared. Multinomial logistic and multiple linear regression analyses were used to clarify the associations between clusters/somatic symptoms and demographics/psychological features.Four clusters were generated and named according to their somatic features: "high gastrointestinal symptoms", "high pain-fatigue and comorbid somatic symptoms", "middle to high pain-fatigue symptoms" and "high cardiovascular symptoms". The high pain-fatigue and comorbid somatic symptom cluster had the highest levels of extent to which symptoms interfere with a person's life, depression and anxiety. The high cardiovascular symptom cluster was featured by high excessive worry over health and illness and low educational level. The high gastrointestinal symptom cluster had relatively low psychopathologies.The results of this population-based analysis supported the existence of distinct somatic syndromes that are not parts of a single whole somatic syndrome and have different psychological features.

INTRODUCTION Routine HIV testing is expected to facilitate early diagnosis and treatment. Nevertheless, to date, limited data are available on the presumed benefit of early detection with improved outcomes through routine HIV testing. METHODS This study was based on the Taiwan national HIV/AIDS registry, with follow-up data validated through December 31, 2014. Outcomes of people diagnosed with HIV infection through the routine (routinely offered in specific settings, opt-out) versus through nonroutine (individual risk-based) testing were compared. The main outcomes of the study were late diagnosis, HIV-related mortality, and all-cause mortality. Individuals were matched by year of HIV diagnosis and adjusted for age, sex, transmission routes, and SES. Analyses were conducted in 2019-2020. RESULTS This study included all 28,674 people diagnosed with HIV infection during 1986-2014 (8,431 [29%] by routine testing, 18,305 [64%] by individual risk-based testing) with a mean follow-up time of 6.2 years. Routine testing was associated with an 80% lower likelihood of late HIV diagnosis (AOR=0.20, 95% CI=0.18, 0.23, p

Backgrounds Socioeconomic factors influence suicide risk but a systematic understanding of the role of financial hardship is unclear. We examined whether financial hardship had cumulative or contemporaneous impacts on suicide ideation and any gender and age differences in a large Korean sample. Methods Data of 67,728 observations from 14,321 individuals were extracted from seven waves of Korean Welfare Panel Study. The association of financial hardship at baseline and its change over two years with suicide ideation was investigated using generalized estimation equation to account for repeated measurements within an individual, adjusting for other socioeconomic factors. Results Financial hardship was associated with suicide ideation but the magnitude of association varied across age and gender groups. Specifically, the impact of financial hardship was persistent over two years presenting a cumulative effect among men aged 50-64 years and ≥65 years; e.g., adjusted OR (adjusted odds ratio) = 3.87, 95 % CI = 2.71–5.54 for emergent hardship group vs adjusted OR = 4.22, 95 %CI = 3.00–5.93 for persistent group in those aged ≥65 years. Financial hardship increased the risk of suicide ideation incrementally with age, although the pattern was less clear among women. Limitations Financial hardship was identified as having changing nature, though it was assumed to occur over two years. Conclusion In general, financial hardship plays a role in amplifying suicide ideation in a contemporaneous way but also in a cumulative way, predominantly among late-middle-aged and elderly men. Monitoring and intervention for financial hardship would be a promising strategy for suicide prevention.

To clarify the mechanism of semicarbazide-modified α-lactalbumin (SEM-LA)-mediated cytotoxicity, we investigated its effect on human U937 leukemia cells and MCF-7 breast cancer cells in the current study. SEM-LA induced apoptosis in U937 cells, which showed increased NOX4 expression, procaspase-8 degradation, and t-Bid production. FADD depletion inhibited SEM-LA-elicited caspase-8 activation, t-Bid production, and cell death, indicating that SEM-LA activated death receptor-mediated apoptosis in U937 cells. SEM-LA stimulated Ca2+-mediated Akt activation, which in turn increased Sp1- and p300-mediated NOX4 transcription. The upregulation of NOX4 expression promoted ROS-mediated p38 MAPK phosphorylation, leading to protein phosphatase 2A (PP2A)-regulated tristetraprolin (TTP) degradation. Remarkably, TTP downregulation increased the stability of TNF-α mRNA, resulting in the upregulation of TNF-α protein expression. Abolishment of Ca2+-NOX4-ROS axis-mediated p38 MAPK activation attenuated SEM-LA-induced TNF-α upregulation and protected U937 cells from SEM-LA-mediated cytotoxicity. The restoration of TTP expression alleviated the effect of TNF-α upregulation and cell death induced by SEM-LA. Altogether, the data in this study demonstrate that SEM-LA activates TNF-α-mediated apoptosis in U937 cells through the NOX4/p38 MAPK/PP2A axis. We think that a similar pathway can also explain the death of MCF-7 human breast cancer cells after SEM-LA treatment.

Made available in DSpace on 2022-04-28T19:40:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-07-01 Background: The COVID-19 pandemic is having profound mental health consequences for many people. Concerns have been expressed that, at their most extreme, these consequences could manifest as increased suicide rates. We aimed to assess the early effect of the COVID-19 pandemic on suicide rates around the world. Methods: We sourced real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature. Between Sept 1 and Nov 1, 2020, we searched the official websites of these countries’ ministries of health, police agencies, and government-run statistics agencies or equivalents, using the translated search terms “suicide” and “cause of death”, before broadening the search in an attempt to identify data through other public sources. Data were included from a given country or area if they came from an official government source and were available at a monthly level from at least Jan 1, 2019, to July 31, 2020. Our internet searches were restricted to countries with more than 3 million residents for pragmatic reasons, but we relaxed this rule for countries identified through the literature and our networks. Areas within countries could also be included with populations of less than 3 million. We used an interrupted time-series analysis to model the trend in monthly suicides before COVID-19 (from at least Jan 1, 2019, to March 31, 2020) in each country or area within a country, comparing the expected number of suicides derived from the model with the observed number of suicides in the early months of the pandemic (from April 1 to July 31, 2020, in the primary analysis). Findings: We sourced data from 21 countries (16 high-income and five upper-middle-income countries), including whole-country data in ten countries and data for various areas in 11 countries). Rate ratios (RRs) and 95% CIs based on the observed versus expected numbers of suicides showed no evidence of a significant increase in risk of suicide since the pandemic began in any country or area. There was statistical evidence of a decrease in suicide compared with the expected number in 12 countries or areas: New South Wales, Australia (RR 0·81 [95% CI 0·72–0·91]); Alberta, Canada (0·80 [0·68–0·93]); British Columbia, Canada (0·76 [0·66–0·87]); Chile (0·85 [0·78–0·94]); Leipzig, Germany (0·49 [0·32–0·74]); Japan (0·94 [0·91–0·96]); New Zealand (0·79 [0·68–0·91]); South Korea (0·94 [0·92–0·97]); California, USA (0·90 [0·85–0·95]); Illinois (Cook County), USA (0·79 [0·67–0·93]); Texas (four counties), USA (0·82 [0·68–0·98]); and Ecuador (0·74 [0·67–0·82]). Interpretation: This is the first study to examine suicides occurring in the context of the COVID-19 pandemic in multiple countries. In high-income and upper-middle-income countries, suicide numbers have remained largely unchanged or declined in the early months of the pandemic compared with the expected levels based on the pre-pandemic period. We need to remain vigilant and be poised to respond if the situation changes as the longer-term mental health and economic effects of the pandemic unfold. Funding: None. Centre for Mental Health Melbourne School of Population and Global Health University of Melbourne Swansea University Medical School Translational Health Research Institute Western Sydney University Ministry of Public Health Department of Health Promotion National Confidential Inquiry into Suicide and Safety in Mental Health University of Manchester Centre for Mental Health and Safety and National Institute for Health Research Patient Safety Translational Research Centre University of Manchester School of Public Health National Suicide Research Foundation University College Cork Australian Institute for Suicide Research and Prevention School of Applied Psychology Griffith University Institute for Life Course Health Research Department of Global Health Stellenbosch University Working Group on Prevention of Suicide and Depression at Public Health Council Department of Psychiatry Blekinge Hospital Botucatu Medical School Universidade Estadual Paulista Instituto Nacional de Psiquiatría Ramon de la Fuente Muñiz University of Rochester Medical Center Region Friuli Venezia Giulia Central Health Directorate Outpatient and Inpatient Care Service Department of Medicine University of Udine Institute of Health Behaviors and Community Sciences College of Public Health National Taiwan University Thames Valley Local Criminal Justice Board Department of Psychiatry Psychotherapy and Psychosomatics Medical University of Innsbruck Center for Outcomes Research and Evaluation Yale School of Medicine Coroners Court of Victoria Danish Research Institute for Suicide Prevention Department of Mental Health Johns Hopkins School of Public Health Centre for Mental Health Research Australian National University Brigham and Women's Hospital Department of Emergency Medicine School of Population Health University of Auckland Magistrates Court of Tasmania (Coronial Division) Bureau of Vital Records and Statistics Louisiana Office of Public Health Ministry of Public Health Undersecretary of Health Services Research Department, 113 Suicide Prevention Departments of Psychiatry and Epidemiology Columbia University Medical Center/New York State Psychiatric Institute Centre for Suicide Research University of Oxford Louisiana Department of Health Greater Manchester Mental Health NHS Foundation Trust Department of Psychiatry Aga Khan University KU Leuven Center for Contextual Psychiatry Population Health Sciences Bristol Medical School University of Bristol South Asian Clinical Toxicology Research Collaboration Faculty of Medicine University of Peradeniya World Health Organization Country Office for Nepal Karolinska Institutet Bekhterev National Medical Research Center of Psychiatry and Neurology Pavlov First Saint Petersburg State Medical University Unit Suicide Research and Mental Health Promotion Department of Social and Preventive Medicine Center for Public Health Medical University of Vienna Department of Child and Adolescent Psychiatry Medical University of Vienna School of Psychology University of Nottingham Self-Harm Research Group School of Psychology University of Nottingham Mental Health Centre Copenhagen Department of Psychiatry and Psychotherapy Klinikum Klagenfurt am Wörthersee Suicidal Behaviour Research Lab University of Glasgow Preventing Deaths from Poisoning Research Group University of Edinburgh Usher Institute University of Edinburgh Suicide Research and Prevention Center Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Departments of Psychiatry and Epidemiology Columbia University Department of Child and Adolescent Psychiatry and Psychotherapy University of Ulm Psychosocial Services in Vienna National Centre for Suicide Research and Prevention Institute of Clinical Medicine University of Oslo Department of Child and Adolescent Psychiatry Psychotherapy and Psychosomatics University Hospital Leipzig Department of Psychiatry and Psychotherapeutic Medicine Landeskrankenhaus Villach Department of Psychiatry Psychosomatic Medicine and Psychotherapy University Hospital Frankfurt Department of Borderline Disorders and Psychotherapy Bekhterev National Medical Research Center of Psychiatry and Neurology Saint Petersburg State University Department of Psychiatry Health Authority Frankfurt am Main Department of Addictive Disorders Psychiatry and Psychotherapy LVR-Klinik Köln Department of Psychiatry Psychosomatic Medicine and Psychotherapy Goethe-University Organizational-Scientific Department Bekhterev National Medical Research Center of Psychiatry and Neurology Department of Psychiatry University of Toronto Department of Psychiatry Sunnybrook Health Sciences Centre Waseda University Faculty of Political Science and Economics Sneha—Suicide Prevention Centre Voluntary Health Services Department of Community Medicine Faculty of Medicine and Allied Sciences Rajarata University of Sri Lanka Department of Psychiatry Sackler School of Medicine Tel Aviv University and Geha Mental Health Center Division of Molecular Imaging and Neuropathology New York State Psychiatric Institute and Department of Psychiatry Columbia University National Institute of Health Research Biomedical Research Centre University Hospitals Bristol and Weston NHS Foundation Trust University of Bristol Department for Psychiatry University Psychiatric Hospital Vrapče School of Medicine University of Zagreb Botucatu Medical School Universidade Estadual Paulista

Background Suicides by carbon monoxide poisoning from burning charcoal increased markedly and contributed to a rise in overall suicides in Taiwan in the early 2000s. A previous study indicated short-term effectiveness on reducing suicides of a charcoal restriction programme, which involved voluntary actions from large chain retail stores to move charcoal bags from open shelves to locked cabinets starting from 1st May 2012, in New Taipei City, Taiwan. We investigated the longer-term effect of this programme. Methods We calculated quarterly age-standardised charcoal-burning and overall suicide rates in New Taipei City and two comparison cities in 2007-2017. Controlled interrupted time-series analysis was used to examine the effect of the charcoal restriction programme. Results There was no difference between the intervention and comparison cities in step changes in the rates (per 100,000) of charcoal-burning suicide (intervention minus comparison = -0.336, 95% confidence interval -1.173 to 0.502) and overall suicide (-0.270, -1.844 to 1.303) after the intervention, or changes in trends (slopes) in charcoal-burning suicide rates (0.007, -0.055 to 0.069) and overall suicide rates (0.049, -0.138 to 0.236) before and after the intervention. Limitations There was no legislative requirement to enforce the charcoal restriction. The programme was also restricted to a subset of retail stores. Conclusion The charcoal restriction programme in New Taipei City showed no effect on reducing charcoal-burning or overall suicides in the five years after its implementation. Future means restriction strategies for suicide prevention should optimise the programme sustainability, ensure the comprehensive means restriction, and monitor the long-term intervention effectiveness.

Background/Purpose We examined the prevalence of probable common mental disorders (CMDs) in commercial low-dose computed tomography (LDCT) lung cancer screening consumers relative to the general population and to determine the correlates of probable CMDs among screening participants. Methods Commercial LDCT lung cancer screening consumers (N = 1323) were compared with a nationally representative sample from the Taiwan Social Change Survey (TSCS) (N = 2034). Respondents scoring ≥3 on the Chinese Health Questionnaire were classified as having a probable CMD. Logistic regression was used to investigate differences between the two groups and correlates of probable CMDs among LDCT lung cancer screening participants. Results The prevalence of probable CMDs was higher among LDCT lung cancer screening participants (25.47%) than among TSCS adults (21.56%). Compared with the TSCS sample, the screening participants had a higher probability of CMDs (OR = 1.40, 95% CI = 1.13–1.73), higher education levels (OR = 7.95, 95% CI = 6.00–10.53), and a history of drinking (OR = 11.85, 95% CI = 9.45–14.85) or betel-quid use (OR = 5.43, 95% CI = 3.98–7.42) but were less likely to smoke (OR = 0.52, 95% CI = 0.40–0.68). Among the screening participants, being female (OR = 1.37, 95% CI = 1.02–1.84) and a current smoker (OR = 1.74, 1.19–2.54) and living near ≥2 smoking family members (OR = 2.30, 95% CI 1.57–3.38) were associated with an increased likelihood of having CMDs. Conclusion Commercial LDCT lung cancer screening users may have a positive association with probable CMDs compared to the general population. Screening programs should consider including criteria and providing psychoeducation to improve the physical and mental outcomes of participants. Clinical trial registration Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) do not require registration.

To further investigate the reinforcing factors on the adhesion strength of SiO2 and TiB2 modified SiBCN-based adhesives, the thermal stability analysis, microstructure observations and phase composition analysis were performed on four kinds of modified PSNB (Polyborosilazane) adhesives. With the different Si/B ratio and SiO2 content, the room temperature adhesion strength reach up to 18.95, 12.04, 32.44 and 13.69 MPa for PPT-1, PPT-2, PPTS and PST respectively, after synthesized at 1000 degrees C in air. And then, the high temperature adhesion strength reach up to 12.3 and 16.4 MPa for PPT-1 and PPTS at 1000 degrees C in vacuum, respectively. Interestingly, it has been found that temperature, PSO, solid content and SiO2 content all have a great influence on the adhesion performance of SiO2 and TiB2 modified SiBCN-based adhesives.

In this study, we reported on the successful fabrication of a novel heterojunction photocatalyst (in particulate system) with a Type II band alignment between 1D-ZnO nanorods and BiVO4 nanocrystals. Pristine 1D-ZnO nanorods and BiVO4 nanocrystals were first fabricated through hydrothermal reaction followed by heterojunction formation via the wet chemical reaction. The 1D-ZnO/xBiVO4 heterojunction photocatalyst (x = weight ratio of BiVO4 in g) that found optimum when x = 0.08 g was used for the degradation of salicylic acid (SA) and Reactive Black 5 (RB5) resulting in high pseudo-first-order reaction rate constants of 0.0049 min−1 and 0.0132 min−1, respectively. Electrochemical studies proved that the 1D-ZnO/0.08BiVO4 heterojunction photocatalyst demonstrated a fast charge mobility and the most efficient photogenerated charge carriers separation among other heterojunction samples as analysed from PL spectra. Besides, UV–vis spectroscopic measurement and optical characterisation showed that the improved photoactivity in 1D-ZnO/BiVO4 is attributed to the formation of a Type II heterojunction staggered arrangement that enables a broader visible-light harvesting ability. Finally, a postulation photocatalytic mechanism was proposed based on the theoretical band alignment diagram between the 1D-ZnO nanorods and BiVO4 nanocrystals as well as portraying the fundamental charge carriers transfer within the 1D-ZnO/BiVO4 heterojunction photocatalyst.

The nationwide prevalence of somatic symptom disorder (SSD) has not yet been investigated in Asia. SSD is often comorbid with depression and anxiety, and the effects of these conditions on medical utilization await clarification. We hence performed a study in Taiwan to explore these issues.Using telephone-based sampling and interview, we obtained data for 3161 participants whose age, gender and living area were compatible with the Taiwan population. We gathered scores of the Patient Health Questionnaire-15 (PHQ-15), Health Anxiety Questionnaire (HAQ) and Patient Health Questionnaire-4 (PHQ-4). Individuals with a PHQ-15 score of at least 4 and a HAQ score of at least 17 were considered to have SSD. Descriptive statistics were used to clarify the prevalence and normative data of the questionnaires. We used multiple logistic regression analyses to investigate the relation between diagnoses and medical utilization.The prevalence of SSD was 5.00% and women had a higher SSD prevalence than men; participants aged 40-49 years had the highest SSD prevalence. In SSD patients, 33.58% had depression or anxiety. After correcting for demographics, SSD and anxiety (but not depression) were associated with a significantly high level of outpatient/emergency department attendance. Comorbid depression or anxiety did not significantly increase the medical utilization of SSD patients.The nationwide SSD prevalence in Taiwan is compatible with the description in the DSM-5. The comorbidity of SSD and depression/anxiety is common, but depression or anxiety does not significantly increase the SSD patients' medical utilization.

In this study, we investigated whether modification of the carboxyl group with semicarbazide-enabled myoglobin (Mb) exhibits membrane-perturbing activity in physiological solutions. Mass spectrometry analysis showed that semicarbazide molecules were coupled to 19 of the 22 carboxyl groups in semicarbazide-modified Mb (SEM-Mb). Measurements of the absorption and circular dichroism spectra indicated that SEM-Mb lost its heme group and reduced the content of the α-helix structure in Mb. The microenvironment surrounding Trp residues in Mb changes after blocking negatively charged residues, as shown by fluorescence quenching studies. The results of the trifluoroethanol-induced structural transition indicated that SEM-Mb had higher structural flexibility than that of Mb. SEM-Mb, but not Mb, induced the permeability of bilayer membranes. Both proteins showed similar lipid-binding affinities. The conformation of SEM-Mb and Mb changed upon binding to lipid vesicles or a membrane-mimicking environment composed of SDS micelles, suggesting that membrane interaction modes differ. Unlike lipid-bound Mb, Trp residues in lipid-bound SEM-Mb are located at the protein-lipid interface. Altogether, our data indicate that modifying negatively charged groups relieves the structural constraints in Mb, consequently switching Mb structure to an active conformation that exhibits membrane-permeabilizing activity.

Suicide in the working-age population is an important public health issue. This group is heterogeneous regarding marital status, education level, and employment status, which are generally important socioeconomic factors for suicide, and has a wide age range. This study aims to explore the individual and combined effect of these socioeconomic factors on suicide in different age groups among the working-age population.This study utilized a population-based case-control design for the working-age population in South Korea. Suicide cases were identified in Korean Governmental Death Registry from 2008 to 2017, and eight controls from Korea Community Health Survey were matched to each case by gender, age group, and year of suicide. Conditional logistic regression models estimated the relationship between marital status and socioeconomic status (SES) including educational attainment and employment status and suicide and examined the combined effect of the SES indicators and marital status on suicide.Low education, single status, and unemployment or economically inactive status were associated with suicide, but their magnitude varied across SES indicators. The association between SES and suicide was more pronounced in younger adults. The suicide risk was highest among divorced women aged 25-34 years (OR = 7.93; 95% CI: 7.21-8.72). Individuals experiencing two social adversities among SES or marital status had a significantly increased suicide risk. Those who are divorced and unemployed or economically inactive have the highest suicide risk, specifically among men aged 24-35 years (OR = 17.53; 95% CI: 14.96-20.55).Marital status, education attainment, and employment status have a separate and combined impact on suicide among the working-age population. Specifically, the divorced and unemployed or economically inactive status amplified suicide risk, predominantly among young adults. Monitoring and intervention for those young adults should be considered for suicide prevention.

In the present work, SiBCNO-based ceramic as high temperature adhesives are fabricated by polymer derived ceramic route. The effect of polysiloxane (PSO) and TiB 2 on the microstructure and high temperature strength is studied, and the toughing effect of TiB 2 is discussed. The highest adhesion strength of the joint (S12) reached up to 18.95 MPa at room temperature and 12.3 MPa at 1000 °C in vacuum after pyrolysis at 1000 °C in air for 2 h. It is interesting to find that the crystallization of nano-SiO 2 reinforces the strength and thermal stability of glass phase with the addition of PSO, besides, the TiB 2 plays the important role in improving adhesion strength by bearing load and facilitating the formation of stable SiO 2 -B 2 O 3 -TiO 2 glass.

Albendazole (ABZ) is a microtubule-targeting anthelmintic that acts against a variety of human cancer cells, but the dependence of its cytotoxicity on non-mitotic effect remains elusive. Thus, we aimed to explore the mechanistic pathway underlying the cytotoxicity of ABZ in human leukemia U937 cells. ABZ-induced apoptosis of U937 cells was characterized by mitochondrial ROS generation, p38 MAPK activation, TNF-α upregulation and activation of the death receptor-mediated pathway. Meanwhile, ABZ induced tubulin depolymerization and G2/M cell cycle arrest. ABZ-induced SIRT3 degradation elicited ROS-mediated p38 MAPK activation, leading to pyruvate kinase M2-mediated tristetraprolin (TTP) degradation. Inhibition of TTP-mediated TNF-α mRNA decay elicited TNF-α upregulation in ABZ-treated cells. Either the overexpression of SIRT3 or abolishment of ROS/p38 MAPK activation suppressed TNF-α upregulation and rescued the viability of ABZ-treated cells. In contrast to the inhibition of ROS/p38 MAPK pathway, SIRT3 overexpression attenuated tubulin depolymerization and G2/M arrest in ABZ-treated cells. Treatment with a SIRT3 inhibitor induced TNF-α upregulation and cell death without the induction of G2/M arrest in U937 cells. Taken together, our data indicate that ABZ-induced SIRT3 downregulation promotes its microtubule-destabilizing effect, and that the non-mitotic effect of ABZ largely triggers apoptosis of U937 cells via SIRT3/ROS/p38 MAPK/TTP axis-mediated TNF-α upregulation. Notably, the same pathway is involved in the ABZ-induced death of HL-60 cells.

Human leukemia U937 cells that were continuously treated with hydroquinone (HQ) were transformed into U937/HQ cells with increased MCL1 and BCL2L1 expression. Compared with their parental cells, U937/HQ cells were less sensitive to ABT-263 (BCL2/BCL2L1 inhibitor)/ABT-199 (BCL2 inhibitor) cytotoxicity. The combination of WEHI-539 (BCL2L1 inhibitor) with either ABT-199 or ABT-263 showed synergistic cytotoxicity to U937 and U937/HQ cells. Therefore, we further investigated the cytotoxic mechanism induced by the combination of WEHI-539 and ABT-199. The combined treatment of WEHI-539 and ABT-199 induced NOX4/ROS/p38 MAPK axis-mediated autophagy, which in turn accelerated β-TrCP mRNA turnover. Downregulation of β-TrCP increased Sp1 expression, thereby promoting Sp1-mediated NOXA transcription, which in turn induced NOXA-dependent MCL1 degradation. Enforced expression of MCL1 alleviated the cytotoxicity of WEHI-539 plus ABT-199 to induce the loss of mitochondrial membrane potential and cell viability. WEHI-539 alone induced Sp1/NOXA axis-mediated MCL1 downregulation, while ABT-199 significantly decreased the dose of WEHI-539 by approximately 350- and 50-fold to induce MCL1 suppression in parental and HQ-selected cells, respectively. Furthermore, WEHI-539 sensitized ABT-199-resistant U937 cells to ABT-199 cytotoxicity by inducing NOXA-mediated degradation of MCL1. Collectively, the data in this study indicate that ABT-199 and WEHI-539 cooperatively induce NOXA-dependent MCL1 degradation, and the inhibition of MCL1 mainly explains their combined cytotoxicity in parental, HQ-selected, and ABT-199-resistant U937 cells.

Studies have shown that hydroquinone (HQ), a benzene metabolite, induces autophagy and apoptosis in leukemia cells. We found that HQ-induced autophagy was cytotoxic to acute myeloid leukemia U937 cells but had a protective effect against apoptosis in chronic myeloid leukemia (CML) K562 cells. HQ-induced autophagy downregulated p62 expression in U937 cells, whereas it upregulated p62 expression in K562 cells regardless of autophagic flux. We also investigated the mechanism of p62 expression induction by HQ in K562 cells. Increased p62 expression in K562 cells reduced BIM mRNA stability and protein expression, which conferred resistance against the BH3 mimetics ABT-199 (BCL2 inhibitor) and A-1210477 (MCL1 inhibitor). K562/HQ cells, selected by the continuous exposure of K562 cells to HQ, also showed increased p62 expression and decreased BIM expression. HQ-induced SIRT3 expression promoted the upregulation of TET3 expression and JNK-mediated Sp1 phosphorylation, thereby increasing p62 expression in K562 and K562/HQ cells. Chromatin immunoprecipitation assay revealed that TET3-mediated DNA demethylation and JNK-mediated Sp1 phosphorylation promoted Sp1 recruitment to the p62 promoter. In CML KU812 cells, HQ induced p62 expression and downregulated BIM expression via a similar pathway. Collectively, our data indicate that HQ induces the upregulation of p62 expression in K562, KU812, and K562/HQ cells, increasing their resistance to BCL2 and MCL1 inhibition by reducing BIM expression. Thus, our findings propose a mechanism by which HQ induces the malignant progression of CML cells.

Background: In the last half of the 20th century, many countries have already abolished anti-suicide laws; however, more than 20 countries still adopt them. This paper is the first to systematically explore the association between criminalization of suicide and national suicide rates in 174 countries/regions to examine the deterring effects of the anti-suicide laws. Methods: In 2012, 23 countries were identified to carry anti-suicide laws. A Negative Binominal Model was adopted to explore the association between national suicide rates and criminalization of suicide in the world in 2012, having controlled for the Human Development Index (“HDI”), size of Muslim population, and the national unemployment rate. Stratified analyses based on sex, size of the Muslim population and the HDI were performed to explore whether the anti-suicide laws had differential impact on different subgroups. Findings: Strong association was found in females (β estimate=0.51, P

An air stable high temperature adhesive synthesized via the polymer-derived-ceramic route had received increased attention in the last two decades. To improve the thermal stability and adhesion strength of a polysilazane (PSNB) adhesive, TiB2 was added as active filler to join SiC ceramic discs. The thermal stability, phase composition and microstructure were investigated by using TGA, XRD, FT-IR, BSE and SEM measurements. Effects of the pyrolysis temperature and active filler TiB2 on the microstructure and adhesion strength have been investigated. After curing and heat-treating at 120 degrees C and 1000 degrees C in air for 2 h, respectively, the adhesion strength of the modified adhesive reached up to 10.07 MPa (3 times higher than that of pure PSNB) at room temperature, and, more importantly, retained a strength of 8.0 MPa at 800 degrees C in air. It should be noted that the formation of a glass comprised of SiO2-B2O3-TiO2 and the emergence of the hexagonal and granular TiB2 in the adhesive layer are mainly responsible for the enhanced high temperature strength.

The high temperature adhesives are required in most critical applications such as nuclear and aerospace technology. To obtain an adhesive with high temperature bond strength and low synthesis temperature, polysilazane (PSNB) was modified by PBSZ, PSO, nano-Al 2 O 3 additives. Effect of the SiO 2 to B 2 O 3 ratio and curing pressure on microstructure and high temperature bond strength has been investigated. After curing and heat-treating at comparatively lower temperatures, the bond strength of the modified adhesive reached up to 12.08 MPa, at room temperature, and, more significantly, retained the strength of 6.65 MPa at 1000 °C. The bond strength of modified adhesive is two-times higher than pure PSNB adhesive at elevated temperature. We demonstrate that optimum level of fluidity and applied pressure should be established in order to attain maximum bond strength. This paper open up avenues for further research in modifying existing adhesives for high temperature applications.

Mannosylated ovalbumin (Man-OVA) prepared by modification of carboxyl groups with p-aminophenyl α-d-mannopyranoside shows an increase of net positive charge, which may enhance its binding to bacterial membrane. Thus, we aimed to investigate whether Man-OVA exerts antibacterial activity on Escherichia coli and Staphylococcus aureus via membrane-perturbing effect. Man-OVA inhibited the growth of E. coli and S. aureus, whereas ovalbumin (OVA) did not show any antibacterial activity. Moreover, Man-OVA induced an increase in the membrane permeability of E. coli and S. aureus, which was positively correlated to its bactericidal action. Morphological examination using scanning electron microscopy revealed that Man-OVA disrupted the bacterial membrane integrity. Destabilization of the lipopolysaccharide (LPS) layer and inhibition of lipoteichoic acid (LTA) biosynthesis in the cell wall increased the bactericidal effect of Man-OVA. In contrast to OVA, Man-OVA also induced leakage of bacterial membrane-mimicking liposomes. Color transformation of phospholipid/polydiacetylene membrane assay revealed that the membrane-interaction mode of Man-OVA was distinct from that of OVA. LPS and LTA suppressed the membrane-damaging activity of Man-OVA, whereas an increase in the Man-OVA concentration attenuated the inhibitory action of LPS and LTA. Taken together, our data indicate that the bactericidal activity of Man-OVA depends strongly on its ability to induce membrane permeability.

This study aimed to systematically evaluate and determine the specific roles of reactive oxygen species (ROS) and Zn2+ ions in governing the antibacterial properties of different ZnO nanoarchitectures. This could differ greatly on model bacteria under different irradiation conditions and affects on the design and scale-up of ZnO-based photocatalytic system for wastewater applications. Various ZnO nanostructures were synthesized, characterised and systematically evaluated for their antibacterial properties on both Gram-positive and Gram-negative bacteria under dark, UV-light, and simulated solar irradiation conditions. Results showed that the 1D-ZnO nanorods possessed the highest photo-deactivation ability with a 3.5-log reduction for B. subtilis and a 4.2-log reduction for E. coli under UV light conditions. This is precisely linked to the 1D rod-like ZnO nanostructures with a higher exposed polar surface that favours the dissolution kinetics of Zn2+ ions. Besides, the surface oxygen vacancies were found to be strongly correlated to the intracellular ROS concentration that imparts bactericidal effect at different extents depending on the ZnO nanostructures used. The photo-deactivation kinetics were found to be best-fitted using the empirical Hom model, as it could represent the non-linear bacterial inactivation kinetics profile with a prolonged tailing characteristic. Finally, the Friedman non-parametric test showed that all experimental datasets for B. subtilis and E. coli surviving cases were significantly different (p-value

This work investigates the hot carrier effect in via-contact type amorphous indium gallium zinc oxide thin film transistors with various source/drain materials and structures. According to previous research, the redundant drain electrode plays an important role in hot carrier stress-induced degradation, which leads to carrier-trapping in the etch stop layer between the active layer and the redundant drain electrode. Hot carrier stress has different influences on device characteristics, depending on materials and structure. Hot carrier stress causes more electron trapping in the etch stop layer below the redundant drain electrode in the presence of smaller source/drain metal work function or a longer redundant drain electrode. To further verify the mechanisms of the degradation behavior, the barrier height for Fowler-Nordheim-tunneling is extracted by a fitting charge trapping model. It is found that the barrier height for Fowler-Nordheim-tunneling is different for different source/drain materials.

Zinc oxide (ZnO) with a high potentiality for tunable morphology is gaining immense research interests for targeted environmental remediation of emerging micropollutants in source waters. Various three-dimensional (3D) flower-like nanostructures of ZnO were synthesized by following a facile and low-temperature hydrothermal synthesis approach, using Zn(CH3COO)2∙2H2O as the starting precursor reagent, in the presence of different bases at varying concentrations as the structure-directing reagents. BET studies indicated that the ZnO-flowers 1 were more superior than ZnO-flowers 2 and 3, as it possessed the highest specific surface area (10.83 m2/g), pore volume (0.054 cm3/g) and pore size (23.52 nm). Subsequently, the photoactivities of ZnO-flowers on the degradation of emerging salicylic acid micropollutant under UV-A illumination were examined. Batch studies suggested that the ZnO-flowers were photoactive and photocatalysed optimally under neutral pH condition that are aligned with the cost-effective and practical implementation for water/wastewater treatment. ZnO-flowers 1 demonstrated the highest photoactivity according to its reaction rate constant, where the kinetics data was well-fitted using the pseudo-first order Langmuir-Hinshelwood rate equation. This finding was well correlated to the BET studies, where the high photoactivity in ZnO-flowers 1 could be ascribed to its exceptional surface morphology that maximises the surface contact area with salicylic acid during photodegradation. Finally, the radicals trapping experiments were carried out in order to validate the role of primary photogenerated holes (h+) and various secondary reactive oxygen species (ROS) in the photodegradation of salicylic acid using ZnO-flowers photocatalysts. It was confirmed that the active species of photogenerated h+, •OH, and •O2− were responsible for the photodegradation process. The plausible mechanistic pathways for the reaction between scavenging reagents and the reactive transitory species to form by-products and intermediates were also proposed.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Background Non-alcoholic fatty liver disease (NAFLD) is associated with features of metabolic syndrome. The aim of this study was to investigate the association between NAFLD and metabolic syndrome in a Chinese population. Methods Data from subjects were retrospectively collected from 2006 to 2009. The exclusion criteria included significant consumption of alcohol and chronic hepatitis B and C. The patients were assigned to two groups according to ultrasound findings: normal group and fatty liver group. The liver function of patients was determined by assessing serum alanine aminotransferase (ALT). Metabolic syndrome was diagnosed based on the 2005 International Diabetes Federation criteria. Results A total of 7568 subjects were enrolled and 5736 (75.8%) and 1832 (24.2%) patients were assigned to the normal and fatty liver groups, respectively. The fatty liver group had significant male predominance (69.7% vs 56.0%), higher body mass index (mean, 26.67 vs 23.55 kg/m2) compared with the normal group. There were 441 (7.7%) and 377 (20.6%) cases with metabolic syndrome in the normal and fatty liver groups, respectively, with significant difference (P=0.001), and the subgroup of 385 cases with fatty liver and elevated ALT had higher prevalence (28.8%) of metabolic syndrome. The strongest association of an individual component of metabolic syndrome with NAFLD was hyperlipidemia (adjusted OR=2.55, 95% CI: 2.22-2.94). Conclusion The individuals with NAFLD had a higher ratio of metabolic syndrome. Hyperlipidemia had the strongest positive association with NAFLD.

The objective of this study was to investigate the growth, photochemical reflectance, and antioxidant properties of P. frutescens species in response to temperature- and water-stress conditions. Two independent experiments were carried out in growth chambers and an environmentally controlled greenhouse for periods of five weeks in each experiment. Pots of red and green Perilla cultivars were planted under day/night temperatures of 15/10 °C, 20/15 °C, 25/20 °C (control), 30/25 °C, and 35/30 °C. Moreover, plants were subjected to four irrigation levels as measured by volumetric water content (VWC): 65 % (control), 40 %, 30 %, and 15 %. Changes in plant height and fresh and dry weights of shoots and leaves indicated that those at 10 °C suffered more severely than at 35 °C. When plants were treated with 15 °C and 15 % VWC stressing for five weeks, all plants exhibited harmful effects to their leaves compared to 25 °C and 65 % VWC treatments (control). The maximal quantum yield of PSII photochemistry values of all plants displayed significant decreases in severe-stress treatments (35 °C, 15 °C, and 15 % VWC) compared to controls, indicating that this parameter is suitable for evaluating the growth of these plants under temperature and water stressing sufficient to result in photoinhibitory effects. The normalized difference vegetation index values of all plants in 35 °C and 15 % VWC treatments were significantly lower than controls. In addition, red Perilla plants exhibited better temperature and drought tolerance than green plants due to their higher soil-plant analysis development values under the same temperature and VWC treatments. Therefore, these indices can be used as indicators to characterize the physiology of these plants. The increases in 2,2-diphenyl-1- picrylhydrazyl radical scavenging activity and total phenolics (TP) content of green Perilla leaf extract (PLE) were clearly manifested with 35 °C treatment compared to controls. However, there were clear increases in the TP content of all PLE with 15 % VWC treatment compared to controls. Thus, Perilla plants subjected to heat and water stresses can be used as a health food and for medicinal purposes due to high TP content, but the use of stressed plants for food purposes would be limited due to low marketability. Green- and red-leaf Perilla contained higher rosmarinic acid (RA) and caffeic acid (CA) content, respectively, in each VWC treatment, implying that their genotypes exhibited different abilities and specificities of photosynthetic metabolites.

Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pH 10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50 nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid.

The purpose of this paper is to introduce and study the split equality variational inclusion problems in the setting of Banach spaces. For solving this kind of problems, some new iterative algorithms are proposed. Under suitable conditions, some strong convergence theorems for the sequences generated by the proposed algorithm are proved. As applications, we shall utilize the results presented in the paper to study the split equality feasibility problems in Banach spaces and the split equality equilibrium problem in Banach spaces. The results presented in the paper are new.

Background Most previous studies on sleep duration and coronary heart disease (CHD) have been small and have inadequately controlled for cardiovascular risk factors and chronic diseases. Therefore, our aim was to prospectively examine the associations of sleep duration with CHD while accounting for these factors. Methods Prospective cohort study of 392 164 adults at age 20years or older who attended a health check-up program from 1994 to 2011 in Taiwan and who have information on sleep duration, sleep medications and potential confounders. Participants answered the question: "How long do you sleep for?"—there were four response categories: (a) 0–4h; (b) 4–6h; (c) 6–8h and (d) >8h. The participants were then followed for CHD mortality from the Taiwanese cause-of-death register. Results When compared to those who slept 6–8h per night, the risk of dying from CHD was increased by 34% (HR 1.34, 95% Confidence Interval [CI] 0.87–2.07) and 35% (HR 1.35, 95% CI 1.11–1.65) in those who slept less than 4h per night and more than 8h per night, respectively. When stratifying by sex and age, we found some evidence for a stronger U-shaped association in females than in males and in older adults than in younger adults (p for interaction=0.01 and 0.13, respectively). Conclusions Adequate sleep duration should be considered an important component of a healthy lifestyle. Further studies are needed to better elucidate the underlying mechanisms.

ABT-263 induces MCL1 upregulation in cancer cells, which confers resistance to the drug. An increased understanding of the mechanism underlying ABT-263-induced MCL1 expression may provide a strategy to improve its tumor-suppression activity. The present study revealed that ABT-263 reduced the turnover of MCL1 mRNA, thereby upregulating MCL1 expression in human K562 leukemia cells. Furthermore, ABT-263-induced EGFR activation promoted AGO2 phosphorylation at Y393 and reduced miR-125b maturation. Treatment with EGFR inhibitors mitigated MCL1 upregulation induced by ABT-263. Additionally, lithium chloride (LiCl) alleviated ABT-263-induced MCL1 upregulation through EGFR-AGO2 axis-modulated miR-125b suppression. Ectopic expression of dominant negative AGO2(Y393F) or transfection with miR-125b abolished ABT-263-induced upregulation of MCL1 mRNA and protein levels. Co-treatment with either EGFR inhibitors or LiCl collaboratively enhanced ABT-263 cytotoxicity, while MCL1 overexpression eliminated this synergistic effect. Collectively, our data reveal that ABT-263 increases EGFR-mediated AGO2 phosphorylation, which in turn suppresses miR-125b-mediated MCL1 mRNA degradation in K562 cells. The suppression of this signaling pathway results in the synergistic cytotoxic effect of EGFR inhibitors or LiCl and ABT-263.

In this study, we investigated the mechanisms underlying arsenic trioxide (ATO)-induced death of human BCR-ABL1-positive K562 and MEG-01 cells. ATO-induced apoptotic death in K562 cells was characterized by ROS-mediated mitochondrial depolarization, MCL1 downregulation, p38 MAPK activation, and Akt inactivation. ATO-induced BCR-ABL1 downregulation caused Akt inactivation but not p38 MAPK activation. Akt inactivation increased GSK3β-mediated MCL1 degradation, while p38 MAPK-mediated NFκB activation coordinated with HDAC1 suppressed MCL1 transcription. Inhibition of p38 MAPK activation or overexpression of constitutively active Akt increased MCL1 expression and promoted the survival of ATO-treated cells. Overexpression of MCL1 alleviated mitochondrial depolarization and cell death induced by ATO. The same pathway was found to be involved in ATO-induced death in MEG-01 cells. Remarkably, YM155 synergistically enhanced the cytotoxicity of ATO on K562 and MEG-01 cells through suppression of MCL1 and survivin. Collectively, our data indicate that ATO-induced p38 MAPK- and Akt-mediated MCL1 downregulation triggers apoptosis in K562 and MEG-01 cells, and that p38 MAPK activation is independent of ATO-induced BCR-ABL1 suppression.

While bulk zinc oxide (ZnO) is of non-toxic in nature, ZnO nanoarchitectures could potentially induce the macroscopic characteristics of oxidative, lethality and toxicity in the water environment. Here we report a systematic study through state-of-the-art controllable synthesis of multi-dimensional ZnO nanoarchitectures (i.e. 0D-nanoparticle, 1D-nanorod, 2D-nanosheet, and 3D-nanoflowers), and subsequent in-depth understanding on the fundamental factor that determines their photoactivities. The photoactivities of resultant ZnO nanoarchitectures were interpreted in terms of the photodegradation of salicylic acid as well as inactivation of Bacillus subtilis and Escherichia coli under UV-A irradiation. Photodegradation results showed that 1D-ZnO nanorods demonstrated the highest salicylic acid photodegradation efficiency (99.4%) with a rate constant of 0.0364 min−1. 1D-ZnO nanorods also exhibited the highest log reductions of B. subtilis and E. coli of 3.5 and 4.2, respectively. Through physicochemical properties standardisation, an intermittent higher k value for pore diameter (0.00097 min−1 per mm), the highest k values for crystallite size (0.00171 min−1 per nm) and specific surface area (0.00339 min−1 per m2/g) contributed to the exceptional photodegradation performance of nanorods. Whereas, the average normalised log reduction against the physicochemical properties of nanorods (i.e. low crystallite size, high specific surface area and pore diameter) caused the strongest bactericidal effect.

Patient Initials or Identifier Number SHC00015211 ### Relevant Clinical History and Physical Exam This 38-year-old gentleman presented with reduced effort tolerance for one year associated with intermittent angina. He had shortness of breath on walking for 300 meters however no previous

The aim of this study is to explore the spatial association of critical genomic elements in the effect of TNF-α on matrix metalloproteinase-9 (MMP-9) expression in human leukemia U937 cells. TNF-α up-regulated MMP-9 protein expression and mRNA level in U937 cells, and Akt-mediated-NFκB/p65 activation and JNK-mediated c-Jun activation were proven to be involved in TNF-α-induced MMP-9 up-regulation. Promoter luciferase activity assay revealed that NFκB (nt-600) and AP-1 (nt-79) binding sites were crucial for TNF-α-induced transcription of MMP-9 gene. The results of a chromatin immunoprecipitation assay indicated that TNF-α reduced histone deacetylase-1 (HDAC-1) recruitment but increased p300 (a histone acetyltransferase) recruitment to MMP-9 promoter regions surrounding NFκB and AP-1 binding sites. Consistently, TNF-α increased enrichment of the acetylated histone H3 mark on MMP-9 promoter regions. DNA affinity purification assay revealed that p300 and HDAC1 could bind oligonucleotides containing AP-1/c-Jun and NFκB/p65 binding sites. Chromosome conformation capture assay showed that TNF-α stimulated chromosomal loops in the MMP-9 promoter via NFκB/p65 and AP-1/c-Jun. The p300-associated acetyltransferase activity was crucial for p65/c-Jun-mediated DNA looping, and inhibition of HDAC activity increased the level of DNA looping. Reduction in the level of DNA looping eliminated all TNF-α-stimulated MMP-9 up-regulation. Taken together, our data suggest that p65/c-Jun-mediated DNA looping is involved in TNF-α-induced MMP-9 up-regulation and that the recruitment of p300 or HDAC1 to NFκB and AP-1 binding sites modifies the level of DNA looping.

Although previous studies have revealed the anti-cancer activity of quinacrine, its effect on leukemia is not clearly resolved. We sought to explore the cytotoxic effect and mechanism of quinacrine action in human leukemia K562 cells. Quinacrine induced K562 cell apoptosis accompanied with ROS generation, mitochondrial depolarization, and down-regulation of BCL2L1 and BCL2. Upon exposure to quinacrine, ROS-mediated p38 MAPK activation and ERK inactivation were observed in K562 cells. Quinacrine-induced cell death and mitochondrial depolarization were suppressed by the p38MAPK inhibitor SB202190 and constitutively active MEK1 over-expression. Activation of p38 MAPK was shown to promote BCL2 degradation. Further, ERK inactivation suppressed c-Jun-mediated transcriptional expression of BCL2L1. Over-expression of BCL2L1 and BCL2 attenuated quinacrine-evoked mitochondrial depolarization and rescued the viability of quinacrine-treated cells. Taken together, our data indicate that quinacrine-induced K562 cell apoptosis is mediated through mitochondrial alterations triggered by p38 MAPK-mediated BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression.

Alicyclobacillus spp. is of significance to the fruit juice industry due to the production of guaiacol. Studies on Alicyclobacillus regarding guaiacol focus mainly on novel ways to detect guaiacol or evaluate guaiacol-producing potential of isolated Alicyclobacillus. Basic studies on factors that induce or affect the production of guaiacol and the conversion pathway of vanillic acid to guaiacol are not available. The goal of this study was to evaluate how extrinsic factors can affect the production of guaiacol by Alicyclobacillu s isolates. Guaiacol-producing Alicyclobacillus isolates 1016 and 1101 were used in this study and the effects of temperature (25 to 55 °C), pH (3.0 to 5.5), and oxygen concentration on guaiacol production in laboratory media was investigated. Maximum production of guaiacol by isolate 1016 was detected within 9 h when incubated at 43 °C, pH 4.0, under microaerophilic conditions. Isolate 1101 produced detectable amounts of guaiacol within 8 h at pH 5.0. However, maximum guaiacol production was achieved within 14 h by isolate 1101 when incubated at 50 °C. Our results indicate that the production of guaiacol, contrary to common belief, is a rapid reaction under desirable conditions specific to each isolate. The results of this study can be useful for developing rapid guaiacol monitoring methods for Alicyclobacillus-related spoilage or be applied to more detailed enzyme-related studies.

The purpose of this paper is to introduce and study a new class of generalized vector variational-like inequalities and generalized vector variational inequalities in fuzzy environment. By using the KKM-technique, Maximal Element Lemma and under suitable conditions, some existence theorems of solutions for these two kinds of vector variational inequalities in fuzzy environment are proved. The results presented in the paper extend and improve some recent results announced by some authors.

The purpose of this paper is to introduce the mixed Agarwal-O'Regan-Sahu type iterative scheme (Agarwal et al., 2007) for finding a common fixed point of the multi-valued nonexpansive mappings in the setting of hyperbolic spaces. Under suitable conditions, some Δ -convergence theorems of the iterative sequence generated by the proposed scheme to approximate a common fixed point of multi-valued nonexpansive mappings are proved. The results presented in the paper extend and improve some recent results announced in the current literature.

Radiotherapy (RT) plays a much more important role in the treatment of colorectal cancer when it can be used to reduce the size of a tumor prior to the local excision of the cancer. In order to find other factors possibly related to radiosensitivity, we evaluated the relationships between circulating blood cell counts and RT effects. In 81 cases of rectal cancer, we examined white blood cell and platelet counts, as well as hemoglobin (Hb) levels, prior to RT, and also investigated their associations with the treatment response rate and with other clinicopathological factors. The patients with anemia had significantly worse RT responses, whereas patients with high white blood cell counts (≥7400/μL) showed better responses (p