Prevalence of Neutralizing Antibodies to Japanese Encephalitis Virus among High-Risk Age Groups in South Korea, 2010

After an extensive vaccination policy, Japanese encephalitis (JE) was nearly eliminated since the mid-1980s in South Korea. Vaccination in children shifted the affected age of JE patients from children to adults. However, an abrupt increase in JE cases occurred in 2010, and this trend has continued. The present study aimed to investigate the prevalence of neutralizing antibodies to the JE virus (JEV) among high-risk age groups (≥40 years) in South Korea. A plaque reduction neutralization test was conducted to evaluate the prevalence of neutralizing antibodies to JEV in 945 subjects within four age groups (30–39, 40–49, 50–59, and 60–69 years) in 10 provinces. Of the 945 enrolled subjects, 927 (98.1%) exhibited antibodies against JEV. No significant differences were found in the prevalence of neutralizing antibodies according to sex, age, or occupation. However, there were significant differences in the plaque reduction rate according to age and occupation; oldest age group had a higher reduction rate, and subjects who were employed in agriculture or forestry also had a higher value than the other occupations. We also found that three provinces (Gangwon, Jeonnam, and Gyeongnam) had a relatively lower plaque reduction rate than the other locations. In addition, enzyme-linked immunosorbent assays were conducted to determine recent viral infections and 12 (2.2%) subjects were found to have been recently infected by the virus. In conclusion, the present study clearly indicated that the prevalence of neutralizing antibodies has been maintained at very high levels among adult age groups owing to vaccination or natural infections, or both. In the future, serosurveillance should be conducted periodically using more representative samples to better understand the population-level immunity to JE in South Korea.     

Induction of MiR-21 by Stereotactic Body Radiotherapy Contributes to the Pulmonary Fibrotic Response

Radiation-induced lung fibrosis, the most serious effect of lung cancer radiotherapy on normal tissue, remains a major technical obstacle to the broader application of radiotherapy to patients with lung cancer. This study describes the use of an image-guided irradiation system in mice mimicking stereotactic body radiotherapy (SBRT) to examine the molecular features of chronic fibrotic response after radiation injury. MicroRNA (miR) array analysis of injured pulmonary tissue identified a set of miRs whose expression was significantly increased in damaged lung tissue. In particular, miR-21 expression was increased at the radiation injury site, concurrent with collagen deposition. Although the inhibition of miR-21 by its specific inhibitor anti-miR-21 only marginally affected endothelial-mesenchymal transition (EndMT) in lung endothelial cells, this inhibition significantly reduced collagen synthesis in lung fibroblasts. Furthermore, ectopic expression of miR-21 was sufficient to promote a fibrotic response in lung fibroblasts, enhancing Smad2 phosphorylation concurrent with Smad7 downregulation. These findings indicate that the induction of miR-21 expression is responsible for fibrotic responses observed in mesenchymal cells at the injury site through the potentiation of TGF-β signaling. Local targeting of miR-21 at the injured area could have potential therapeutic utility in mitigating radiation-induced lung fibrosis.     

Time-Staged Gamma Knife Stereotactic Radiosurgery for Large Cerebral Arteriovenous Malformations: A Preliminary Report

ObjectiveWe retrospectively analyzed our experience with time-staged gamma knife stereotactic radiosurgery (GKS) in treating large arteriovenous malformation(AVM)s;≥ 10 cm³).MethodsForty-five patients who underwent time-staged GKS (2-stage, n = 37;3-stage,n = 8) between March 1998 and December 2011 were included. The mean volume treated was 20.42±6.29 cm³ (range, 10.20–38.50 cm³). Obliteration rates of AVMs and the associated complications after GKS were evaluated.ResultsMean AVM volume (and median marginal dose) at each GKS session in the 37 patients who underwent 2-stage GKS was 19.67±6.08 cm³ (13 Gy) at session 1 and 6.97±6.92 cm³ (17 Gy) at session 2. The median interval period was 39 months. After follow-up period of 37 months, the complete obliteration rate was 64.9%. The mean AVM volume (and median marginal dose) at each GKS session in the 8 patients who underwent 3-stage GKS was 23.90±6.50 cm³ (12.25 Gy), 19.43±7.46 cm³ (13.5 Gy), 7.48±6.86 cm³ (15.5 Gy) at session 1, 2, and 3, respectively. The median interval duration between each GKS session was 37.5 and 38 months, respectively. After a median follow-up period of 47.5 months, 5 patients (62.5%) achieved complete obliteration. Postradiosurgical hemorrhage developed in 5 patients (11.1%) including one case of major bleeding and 4 cases of minor bleeding. No patient suffered from clinically symptomatic radiation necrosis following radiation.ConclusionTime-staged GKS could be an effective and safe treatment option in the management of large AVMs.     

Suppression of Recombination Losses in Polymer:Nonfullerene Acceptor Organic Solar Cells due to Aggregation Dependence of Acceptor Electron Affinity

Here, it is investigated whether an energetic cascade between mixed and pure regions assists in suppressing recombination losses in non‐fullerene acceptor (NFA)‐based organic solar cells. The impact of polymer‐NFA blend composition upon morphology, energetics, charge carrier recombination kinetics, and photocurrent properties are studied. By changing film composition, morphological structures are varied from consisting of highly intermixed polymer‐NFA phases to consisting of both intermixed and pure phase. Cyclic voltammetry is employed to investigate the impact of blend morphology upon NFA lowest unoccupied molecular orbital (LUMO) level energetics. Transient absorption spectroscopy reveals the importance of an energetic cascade between mixed and pure phases in the electron–hole dynamics in order to well separate spatially localized electron–hole pairs. Raman spectroscopy is used to investigate the origin of energetic shift of NFA LUMO levels. It appears that the increase in NFA electron affinity in pure phases relative to mixed phases is correlated with a transition from a relatively planar backbone structure of NFA in pure, aggregated phases, to a more twisted structure in molecularly mixed phases. The studies focus on addressing whether aggregation‐dependent acceptor LUMO level energetics are a general design requirement for both fullerene and NFAs, and quantifying the magnitude, origin, and impact of such energetic shifts upon device performance.     

Gene‐Centric Metagenome Analysis Reveals Gene Clusters for Carbon Monoxide Conversion and Validates Isolation of a Clostridial Acetogen for C2 Chemical Production

Syngas fermentation is largely dependent on acetogens that occur in various anaerobic environmental samples including soil, sediment, and feces. Here the authors report the metagenomic isolation of acetogens for C2 chemical production from syngas. Screening acetogens for C2 chemical production typically involves detecting the presence of the Wood‐Ljungdahl Pathway for carbon monoxide conversion. The authors collect samples from river‐bed sediments potentially having conditions suitable for carbon monoxide‐converting anaerobes, and enrich the samples under carbon monoxide selection pressure. Changes in the microbial community during the experimental procedure are investigated using both amplicon and shotgun metagenome sequencing. Combined next‐generation sequencing techniques enabl in situ tracking of the major acetogenic bacterial group and lead to the discovery of a 16 kb of gene cluster for WLP. The authors isolat an acetogenic clostridial strain from the enrichment culture (strain H21‐9). The functional activity of H21‐9 is confirmed by its high level of production of C2 chemicals from carbon monoxide (77.4 mM acetate and 2.5 mM of ethanol). This approach of incorporating experimental enrichment with metagenomic analysis can facilitate the discovery of novel strains from environmental habitats by tracking target strains during the screening process, combined with validation of their functional activity.     

Newly Identified HNP‐F from Human Neutrophil Peptide‐1 Promotes Hemostasis

Active hemostatic agents can play a crucial role in saving patients’ lives during surgery. Active hemostats have several advantages including utilization of natural blood coagulation and biocompatibility. Among them, although human neutrophil peptide‐1 (HNP‐1) has been previously reported with the hemostatic mechanism, which part of HNP‐1 facilitates the hemostatic activity is not known. Here, a partial peptide (HNP‐F) promoting hemostasis, originating from HNP‐1, has been newly identified by the blood coagulation ability test. HNP‐F shows the best hemostatic effect between the anterior half and posterior half of peptides. Moreover, microscopic images show platelet aggregation and an increase in the concentration of platelet factor 4, and the scanning electron microscope image of platelets support platelet activation by HNP‐F. Thromboelastography indicates decreased clotting time and increased physical properties of blood clotting. Mouse liver experiments demonstrate improved hemostatic effect by treatment of peptide solution. Cell viability and hemolysis assays confirm the HNP‐F's biosafety. It is hypothesized that the surface charge and structure of HNP‐F could be favorable to interact with fibrinogen or thrombospondin‐1. Collectively, because HNP‐F as an active peptide hemostat has many advantages, it could be expected to become a potent hemostatic biomaterial, additive or pharmaceutical candidate for various hemostatic applications.     

Proteomic identification of macrophage migration-inhibitory factor upon exposure to TiO2 particles

Inhalation of particulate matter aggravates respiratory symptoms in patients with chronic airway diseases, but the mechanisms underlying this response remain poorly understood. We used a proteomics approach to examine this phenomenon. Treatment of epithelial cells with BSA-coated titanium dioxide (TiO(2)) particles altered 20 protein spots on the two-dimensional gel, and these were then analyzed by nano-LC-MS/MS. These proteins included defense-related, cell-activating, and cytoskeletal proteins implicated in the response to oxidative stress. The proteins were classified into four groups according to the time course of their expression patterns. For validation, RT-PCR was performed on extracts of in vitro TiO(2)-treated cells, and lung issues from TiO(2)-treated rats were analyzed by immunohistochemical staining and enzyme immunoassay. TiO(2) treatment was found to increase the amount of mRNA for macrophage migration-inhibitory factor (MIF). MIF was expressed primarily in epithelium and was elevated in lung tissues and bronchoalveolar lavage fluids of TiO(2)-treated rats as compared with sham-treated rats. Carbon black and diesel exhaust particles also induced expression of MIF protein in the epithelial cells.