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BTEX exposure and metabolite levels in Taiwan schoolchildren near petrochemical areas
No full text[[abstract]]Introduction: Benzene, toluene, ethylbenzene, and xylenes (BTEX) in ambient air pose significant health risks for residents near petrochemical facilities. However, limited research has investigated the correlation between BTEX exposure and urinary metabolites in children. This is the first study to determine this association among primary school children near petrochemical industrial parks (PIPs) in Taiwan. Methods: Between October 2019 and December 2020, 1295 children from 20 primary schools near PIPs were recruited. Morning midstream urine samples were collected, and urinary BTEX metabolites concentrations were analyzed using isotope dilution and modified liquid chromatography-tandem mass spectrometry (LC-MS/MS). Ambient BTEX at the schools was measured using 6-L stainless-steel canisters over three consecutive days before urine collection, following US EPA Method TO-15. Multivariate linear regression was employed to assess the relationship between ambient BTEX and urinary metabolites. Results: The mean ambient BTEX concentrations were 0.44, 5.17, 0.21, and 0.75 ppb, respectively. Geometric mean urinary concentrations of S-phenyl mercapturic acid (SPMA), benzyl mercapturic acid (BMA), phenyl glyoxylic acid (PGA), and methyl hippuric acids (MHAs) were 0.18, 6.63, 214.01, and 178.33 μg/g creatinine, respectively. Children within 1 km of PIPs exhibited significantly higher SPMA (0.21 μg/g creatinine) and BMA (6.67 μg/g creatinine) levels. A positive correlation was observed between ambient benzene levels and urinary SPMA (beta = 0.19, p = 0.017). Conclusions: The study reveals that children attending schools within 1 km of PIPs face higher benzene exposure. This comprehensive research highlights elevated BTEX levels and urinary metabolites, emphasizing the need for monitoring and safeguarding vulnerable children
PRTN3 promotes IL33/Treg-mediated tumor immunosuppression by enhancing the M2 polarization of tumor-associated macrophages in lung adenocarcinoma
No full text[[abstract]]The immunosuppressive tumor microenvironment (TME) shaped by tumor-associated macrophages (TAMs) is essential for lung adenocarcinoma (LUAD) immune tolerance and tumor progression. Here, we first reported that proteinase 3 (PRTN3) promoted the alternative activation (M2) of TAMs and enhanced IL33/regulatory T cells (Tregs)-mediated tumor immunosuppression in LUAD. Firstly, clinical analysis revealed PRTN3 was highly expressed in TAMs and correlated with the tumor progression and poor prognosis in LUAD patients. Meanwhile, by using the myeloid cells-specific Prtn3-knockout mouse model, we demonstrated Prtn3 deficiency in macrophages remolded the immunosuppressive TME and suppressed tumor growth. The mechanism studies uncovered a novel signaling pathway that PRTN3 up-regulated IL33 expression in TAMs by suppressing AKT-mediated ubiquitinated degradation of FOXO1, which subsequently activated Il33 transcription. Furthermore, lack of PRTN3 or FOXO1 in macrophages greatly restrained IL33-induced Treg differentiation. Importantly, selective knockout of Prtn3 in macrophages significantly enhanced the antitumor effect of anti-PD1 therapy in the mouse model of LUAD. Thus, our work demonstrated that PRTN3 in macrophages, served as a key immunoregulator, contributed to impede the antitumor immune response through reinforcing the TAMs/Tregs crosstalk, which provided valuable insights to improve the immunotherapeutic effect by functional remodeling of TAMs to alleviate immunosuppression in LUAD
Influence of pension availability on the association between work conditions and labor market exit for health reasons: evidence from a Taiwanese older adults cohort
No full text[[abstract]]BackgroundWhile the impact of poor working conditions on workers' intention to leave the job is well-established, limited research has examined how the availability of pension benefits influences the association between adverse psychosocial work conditions and labor market exit for health reasons among middle-aged and older workers. This study explored the association of psychosocial and physical work conditions with labor market exit for health reasons among individuals with varying pension statuses.MethodsThis study utilized data from the Healthy Aging Longitudinal Study in Taiwan (HALST), which investigated reasons for labor market exit among 2,143 adults aged 55 and older. Work conditions were aggregated by occupation based on data from the Occupational Safety and Health Surveys, which included nationally representative employees, and subsequently linked to HALST data. We examined the differential impact of psychosocial and physical work conditions on health-related labor market exit, compared to old age retirement, among individuals with and without pension coverage.ResultsAmong 2,143 study participants, 7.3% left the labor market due to health reasons, and 39.9% reported not having a pension. Individuals with low job control (adjusted odds ratio [aOR] = 2.23, 95% confidence interval [CI] = 1.05 to 4.73) and high physical demands (aOR = 2.72, 95% CI = 1.26 to 5.85) were more likely to exit the labor market for health reasons compared to old age retirement. Among participants without a pension, adverse work conditions were significantly associated with labor market exit for health reasons.ConclusionsAdverse work conditions were associated with labor market exit for health reasons particularly among older adults without pension coverage. Implementing policies to improve psychosocial work conditions and enhance the pension system is warranted
Infection of neuronal cells by severe case enterovirus A71 enhances NF-κB activity and increases NF-κB related pro-inflammatory cytokines
No full text[[abstract]]Enterovirus A71 (EV-A71) is the main pathogen of hand-foot-and-mouth disease and sometimes causes neurological disease complications in severe cases. The most recent large EV-A71 outbreak in Taiwan occurred in 2012. We aimed to investigate the gene expression profile of human neuroblastoma cells infected with mild and severe case EV-A71 isolates. EV-A71-infected SK-N-SH cells were sent for RNA sequencing using Illumina Hiseq. Functional gene analysis, qRT-PCR, and luciferase reporter assay were used to investigate the findings obtained from RNA-seq analysis. Expression profile analysis identified 59 significant differentially expressed genes (DEGs) between mild and severe case EV-A71 infection. Gene ontology analysis showed that most of the genes were involved in the regulation of transcription. KEGG pathway enrichment analysis also showed that the DEGs were mainly enriched in the tumor necrosis factor and nuclear factor kappa B (NF-kappa B) signaling. We found that EV-A71 may affect neurons to enhance the disease severity by mediating pro-inflammatory cytokines through NF-kappa B signaling. Additionally, infection with severe case EV-A71 enhances NF-kappa B activity, increases pro-inflammatory cytokines, and reduces cell survival. These results indicate that possible pathogenic mechanisms that were linked to the neuropathogenesis of EV-A71 infection and the above genes might be potential biomarkers or antiviral targets for the prevention of neuronal complications in severe EV-A71 infections in the future
Automatic movement recognition for evaluating the gross motor development of infants
No full text[[abstract]]Objective: The objective of this study was to early-detect gross motor abnormalities through video detection in Taiwanese infants aged 2-6 months. Background: The current diagnosis of infant developmental delays primarily relies on clinical examinations. However, during clinical visits, infants may show atypical behaviors due to unfamiliar environments, which might not truly reflect their true developmental status. Methods: This study utilized videos of infants recorded in their home environments. Two pediatric neurologists manually annotated these clips to identify whether an infant possessed the characteristics of gross motor delays through an assessment of his/her gross motor movements. Using transfer learning techniques, four pose recognition models, including ViTPose, HRNet, DARK, and UDP, were applied to the infant gross motor dataset. Four machine learning classification models, including random forest, support vector machine, logistic regression, and XGBoost, were used to predict the developmental status of infants. Results: The experimental results of pose estimation and tracking indicate that the ViTPose model provided the best performance for pose recognition. A total of 227 features related to kinematics, motions, and postures were extracted and calculated. A one-way ANOVA analysis revealed 106 significant features that were retained for constructing prediction models. The results show that a random forest model achieved the best performance with an average F1-score of 0.94, a weighted average AUC of 0.98, and an average accuracy of 94%
5-Methoxytryptophan attenuates oxidative stress-induced downregulation of PINK1 and mitigates mitochondrial damage and apoptosis in cardiac myocytes
No full text[[abstract]]Mitochondrial dysfunction is a hallmark of the pathogenesis of various cardiovascular diseases. 5-Methoxytryptophan (5-MTP), an intrinsic amino acid metabolite, exerts cardioprotective effects potentially through the preservation of mitochondrial integrity. This study investigates the mechanisms and contexts in which 5-MTP positively impacts mitochondrial function using cultured human cardiac myocyte cells and HL-1 cardiac cells subjected to oxidative stress (OS). We first demonstrated that 5-MTP up-regulates the expression of PINK1, a key regulator of mitochondrial homeostasis. PINK1 knockdown attenuated the beneficial effects of 5-MTP on cardiomyocyte apoptosis. Furthermore, in cells exposed to OS, 5-MTP pretreatment led to a notable decrease in mitochondrial superoxide generation. Fluorescence imaging and network analysis showed that 5-MTP preserved mitochondrial membrane potential and enhanced mitochondrial network integrity. Reduced phosphorylation of dynamin-related protein 1, which is involved in mitochondrial fission, uncovered the role of 5-MTP in maintaining mitochondrial dynamics. Notably, 5-MTP attenuated OS-induced mitophagy, as evidenced by reduced mitophagy detection dye fluorescence and lower mitochondrial Parkin levels, suggesting that mechanisms beyond the PINK1/Parkin pathway are involved. Restoration of AKT phosphorylation and reduced mitochondrial Bax localization further revealed an additional pathway contributing to mitochondrial protection. Moreover, 5-MTP attenuated pro-apoptotic Bax levels and enhanced PINK1 expression in a rat model of ischemic cardiomyopathy, corroborating its cardioprotective role. Collectively, these findings demonstrate that 5-MTP mitigates mitochondrial dysfunction through coordinated regulation of PINK1, AKT, and Bax, offering potential as a therapeutic agent to enhance cellular resilience in OS-driven mitochondrial damage
Prognostic role of claudin-18.2 in intrahepatic cholangiocarcinoma
No full text[[abstract]]Claudins are key components of tight junctions, essential for maintaining cellular adhesion, regulating intercellular molecule transport, and preserving cell polarity. Altered claudin expression can lead to tight junction dysfunction, potentially disrupting signaling pathways and contributing to the development of epithelial cancers. This study aims to explore the understudied role of CLDN18.2 in intrahepatic cholangiocarcinoma and its relationship with clinical outcomes. We analyzed tissue samples from 182 patients who underwent curative surgery for intrahepatic cholangiocarcinoma. Our research examined the relationship between CLDN18.2 expression and various clinical factors, including patient characteristics, pathological findings, and survival metrics such as overall survival (OS), disease-free survival (DFS), metastasis-free survival (MeFS), and local recurrence-free survival (LRFS). Overexpression of CLDN18.2 showed significant associations with R1 resection (p = 0.032) and advanced T stage (p = 0.043). Univariate analysis revealed that high CLDN18.2 expression was correlated with poorer OS (p = 0.0002), DFS (p < 0.0001), LRFS (p < 0.0001), and MeFS (p < 0.0001). Multivariate analysis further confirmed that high CLDN18.2 expression was independently associated with worse OS (p = 0.015), DFS (p < 0.001), LRFS (p < 0.001), and MeFS (p < 0.001). Overexpression of CLDN18.2 was associated with unfavorable clinical prognosis and adverse pathological features in intrahepatic cholangiocarcinoma. These findings suggest that CLDN18.2 could serve as a potential prognostic biomarker for intrahepatic cholangiocarcinoma
The lunar new year holiday is associated with differential suicide risks by gender and marital status in Taiwan
No full text[[abstract]]BACKGROUND: Suicide risk fluctuates during the Christmas holidays, suggesting a role for social integration in suicide prevention. In Taiwan, the Lunar New Year is the longest and most culturally significant family holiday. This study examines gender-specific suicide risks during the Lunar New Year and Western New Year holidays. METHODS: Daily suicide data between 2012 and 2022 were obtained from national cause-of-death data. A Poisson regression model compared the suicide risk seven days before and after the Lunar and Western New Year's Day with that of the remainder of the year, stratified by gender and marital status. A moderation analysis by gender was conducted. RESULTS: Suicide risks in married and divorced men decreased before Lunar New Year's Day, but the risk was elevated in divorced men a few days after both the Lunar and Western New Year's Days. Compared to men, divorced women had a higher suicide risk on Lunar New Year's Day. Divorced women had a lower suicide risk after the Lunar New Year holiday, whereas married women had a higher suicide risk. CONCLUSION: The differential suicide risk by marital status and gender offers important implications for suicide prevention, particularly concerning temporal landmarks, social integration, and caregiving burdens during holidays
Cebadores, marcadores snp y método para genotipar mycobacterium tuberculosis
No full text[[abstract]]La presente invención se refiere a una serie de cebadores para genotipar M. tuberculosis seleccionada a partir del grupo que consiste de series de cebadores 1-25 (SEC ID Nos. 1-50), y también provee un cebador de extensión para genotipar M. tuberculosis seleccionado a partir del grupo que consiste de SEC ID Nos. 51-75. La presente solicitud provee una combinación de marcadores de polimorfismo de un nucleótido de M. tuberculosis. Además, la presente solicitud provee un método y un paquete para genotipar M. tuberculosis
The contribution of copy number variants to schizophrenia: From a genome-wide study in east asian populations
No full text[[abstract]]Individual Abstract: Here, we present a study on rare copy number variants (rCNVs) in schizophrenia, emphasizing the shift from traditional European (EUR) populations to a large East Asian (EAS) cohort, the largest to date, with 20,903 cases and 23,258 controls. The study confirms previous findings about the heightened genome-wide rCNV burden in schizophrenia patients within this EAS cohort. A combined meta-analysis of EAS and EUR cohorts, totaling 38,409 cases and 40,009 controls, identified 15 significant rCNV loci. Of these, five were novel, found at locations 1q21.2, 8p21.3, 11q13.1, 19p13.3, and 19q13.42. The comparison between EAS and EUR data suggested that differences in rCNV frequencies contribute to variability in discovery power across these populations rather than differences in genetic effect sizes. Among the eight rCNV loci implicated in the PGC EUR study with genome-wide significance, seven had rCNVs captured in the EAS dataset, among which three achieved genome-wide significance (P<6.88e-5, 22q11.21 deletion, 3q29 deletion, and 16p11.2 duplication) and an additional three reached nominal significance (P < 0.05, 1q21.1 deletion, 16p11.2 deletion, and 7q11.23 duplication). None of these loci showed a significant difference in effect size between the two populations. rCNVs, particularly, are significant as they have a pronounced potential to disrupt neuronal development and synaptic connectivity. The discovery of novel rCNV loci in the EAS population enriches our understanding of the genetic architecture of schizophrenia and underscores the potential influence of rCNVs on neurodevelopmental processes. Comparing rCNV profiles between EAS and EUR cohorts illuminates how population-specific genomic structures can influence the prevalence and impact of these genetic variations. The current findings underscore the variability in genetic factors influencing schizophrenia across different populations and highlight the necessity of expanding genetic studies to include diverse populations beyond those of European descent. Identifying novel loci in the EAS population not only enriches our understanding of the genetic architecture of schizophrenia but also suggests that population-specific genetic variations could be crucial for tailoring more effective diagnostics and treatments. Furthermore, this study enhances our understanding of the genetic diversity and complexity of schizophrenia, contributing valuable insights into how different populations may exhibit unique genetic profiles that influence the disease. By exploring these distinctions, the research advocates for a more inclusive approach to genetic research, which is essential for developing global health strategies and interventions sensitive to genetic diversity. This aligns with the conference theme by emphasizing the importance of including diverse genetic backgrounds to achieve a more comprehensive understanding of psychiatric disorders