Size distributions of atmospheric particulate matter and associated trace metals in the multi-industrial city of Ulsan, Korea

Particulate matter (PM) was collected using micro-orifice uniform deposit impactors from a residential (RES) site and an industrial (IND) site in Ulsan, South Korea, in September-October 2014. The PM samples were measured based on their size distributions (11 stages), ranging from 0.06 ??m to over 18.0 ??m. Nine trace metals (As, Se, Cr, V, Cd, Pb, Ba, Sb, and Zn) associated with PM were analyzed. The PM samples exhibited weak bimodal distributions irrespective of sampling sites and events, and the mean concentrations of total PM (TPM) measured at the IND site (56.7 ??g/m3) was higher than that measured at the RES site (38.2 ??g/m3). The IND site also showed higher levels of nine trace metals, reflecting the influence of industrial activities and traffic emissions. At both sites, four trace metals (Ba, Zn, V, and Cr) contributed to over 80% of the total concentrations in TPM. The modality of individual trace metals was not strong except for Zn; however, the nine trace metals in PM2.5 and PM10 accounted for approximately 50% and 90% of the total concentrations in TPM, respectively. This result indicates that the size distributions of PM and trace metals are important to understand how respirable PM affects public health

Titanium dioxide nanoparticles oral exposure to pregnant rats and its distribution

Background: Titanium dioxide (TiO2) nanoparticles are among the most manufactured nanomaterials in the industry, and are used in food products, toothpastes, cosmetics and paints. Pregnant women as well as their conceptuses may be exposed to TiO2 nanoparticles; however, the potential effects of these nanoparticles during pregnancy are controversial, and their internal distribution has not been investigated. Therefore, in this study, we investigated the potential effects of oral exposure to TiO2 nanoparticles and their distribution during pregnancy. TiO2 nanoparticles were orally administered to pregnant Sprague-Dawley rats (12 females per group) from gestation days (GDs) 6 to 19 at dosage levels of 0, 100, 300 and 1000 mg/kg/day, and then cesarean sections were conducted on GD 20. Results: In the maternal and embryo-fetal examinations, there were no marked toxicities in terms of general clinical signs, body weight, food consumption, organ weights, macroscopic findings, cesarean section parameters and fetal morphological examinations. In the distribution analysis, titanium contents were increased in the maternal liver, maternal brain and placenta after exposure to high doses of TiO2 nanoparticles. Conclusion: Oral exposure to TiO2 during pregnancy increased the titanium concentrations in the maternal liver, maternal brain and placenta, but these levels did not induce marked toxicities in maternal animals or affect embryo-fetal development. These results could be used to evaluate the human risk assessment of TiO2 nanoparticle oral exposure during pregnancy, and additional comprehensive toxicity studies are deemed necessary considering the possibility of complex exposure scenarios and the various sizes of TiO2 nanoparticles

Photoemission and x-ray absorption study of MgC_(1-x)Ni_3

We investigated electronic structure of MgC_(1-x)Ni_3 with photoemission and x-ray absorption spectroscopy. Both results show that overall band structure is in reasonable agreement with band structure calculations including the existence of von Hove singularity (vHs)near E_F. However, we find that the sharp vHs peak theoretically predicted near the E_F is substantially suppressed. As for the Ni core level and absorption spectrum, there exist the satellites of Ni 2p which have a little larger energy separation and reduced intensity compared to the case of Ni-metal. These facts indicate that correlation effects among Ni 3d electrons may be important to understand various physical properties.Comment: 12 pages, 4 figure

The cascade of care for latent tuberculosis infection in congregate settings:a national cohort 1 analysis, Korea, 2017-18

BACKGROUND: In 2017, Korea implemented a nationwide project to screen and treat latent tuberculosis infection (LTBI) in high-risk for transmission public congregate settings. We aimed to assess programme success using a cascade of care framework. MATERIALS AND METHODS: We undertook a cohort study of people from three congregate settings screened between March 2017 and December 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities. We report percentages of participants with LTBI completing each step in the cascade of care model. Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment. RESULTS: Among the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively. Compared to those aged 20-34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated. Using public health centres rather than private hospitals was associated with people "not initiating treatment" (adjusted risk ratio [aRR], 3.72; 95% confidence interval [CI], 3.95-3.86). Nine-month isoniazid monotherapy therapy was associated with "not completing treatment," compared to 3-month isoniazid and rifampin therapy (aRR, 1.28; 95% CI, 1.16-1.41). CONCLUSION: Among participants with LTBI from three congregate settings, less than one third completed treatment. Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade

Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD

The oral multi-target kinase inhibitor regorafenib, which targets the oncogenic receptor tyrosine kinase (RTK), is an effective therapeutic for patients with advanced gastrointestinal stromal tumors or metastatic colorectal cancer. However, whether regorafenib treatment has beneficial effects on neuroinflammation and Alzheimer&apos;s disease (AD) pathology has not been carefully addressed. Here, we report the regulatory function of regorafenib in neuroinflammatory responses and AD-related pathology in vitro and in vivo. Regorafenib affected AKT signaling to attenuate lipopolysaccharide (LPS)-mediated expression of proinflammatory cytokines in BV2 microglial cells and primary cultured microglia and astrocytes. In addition, regorafenib suppressed LPS-induced neuroinflammatory responses in LPS-injected wild-type mice. In 5x FAD mice (a mouse model of AD), regorafenib ameliorated AD pathology, as evidenced by increased dendritic spine density and decreased Aβ plaque levels, by modulating APP processing and APP processing-associated proteins. Furthermore, regorafenib-injected 5x FAD mice displayed significantly reduced tau phosphorylation at T212 and S214 (AT100) due to the downregulation of glycogen synthase kinase-3 beta (GSK3β) activity. Taken together, our results indicate that regorafenib has beneficial effects on neuroinflammation, AD pathology, and dendritic spine formation in vitro and in vivo.1

Analysis of spike protein variants evolved in a novel in vivo long-term replication model for SARS-CoV-2

IntroductionThe spectrum of SARS-CoV-2 mutations have increased over time, resulting in the emergence of several variants of concern. Persistent infection is assumed to be involved in the evolution of the variants. Calu-3 human lung cancer cells persistently grow without apoptosis and release low virus titers after infection.MethodsWe established a novel in vivo long-term replication model using xenografts of Calu-3 human lung cancer cells in immunodeficient mice. Virus replication in the tumor was monitored for 30 days and occurrence of mutations in the viral genome was determined by whole-genome deep sequencing. Viral isolates with mutations were selected after plaque forming assays and their properties were determined in cells and in K18-hACE2 mice.ResultsAfter infection with parental SARS-CoV-2, viruses were found in the tumor tissues for up to 30 days and acquired various mutations, predominantly in the spike (S) protein, some of which increased while others fluctuated for 30 days. Three viral isolates with different combination of mutations produced higher virus titers than the parental virus in Calu-3 cells without cytopathic effects. In K18-hACE2 mice, the variants were less lethal than the parental virus. Infection with each variant induced production of cross-reactive antibodies to the receptor binding domain of parental SARS-CoV-2 S protein and provided protective immunity against subsequent challenge with parental virus.DiscussionThese results suggest that most of the SARS-CoV-2 variants acquired mutations promoting host adaptation in the Calu-3 xenograft mice. This model can be used in the future to further study SARS-CoV-2 variants upon long-term replication in vivo

A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids

Developing effective drugs for Alzheimer’s disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, we report an efficient, network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of AD with human iPSC-derived cerebral organoids (iCOs), including CRISPR-Cas9-edited isogenic lines. We use 1300 organoids from 11 participants to build a high-content screening (HCS) system and test blood–brain barrier-permeable FDA-approved drugs. Our study provides a strategy for precision medicine through the convergence of mathematical modeling and a miniature pathological brain model using iCOs. © 2021, The Author(s).1