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Interferon regulatory factor (IRF) 3 and IRF7 are important innate immune-related genes that induce type I interferon (IFN). In this study, PmIRF3 and PmIRF7 were identified from red sea bream (Pagrus major) infected by red sea bream iridovirus (RSIV), and expression and functional analyses were performed. PmIRF3 and PmIRF7 consisted of 465 and 436 amino acids, respectively, and contained a well-conserved IRF domain, IRF3 domain, and serine-rich domain (SRD). PmIRF3 and PmIRF7 are ubiquitously expressed in the liver and gills in normal fish, and with a high expression being recorded in kidney and spleen during RSIV infection. In P. major fin cells (PMF cells), pAcGFP-PmIRF3 and pAcGFP-PmIRF7 were localized to the cytoplasm, and overexpression of PmIRF3 and PmIRF7 using the pcDNA3.1 vector induced type I IFN. In addition, in the experiment in vitro, PMF cells overexpressed with PmIRF3 or PmIRF7 exhibited antiviral activity against RSIV and significantly reduced viral genome copies and virus titer. Therefore, PmIRF3 and PmIRF7 may have antiviral activity through the induction of type I IFN against RSIV infection of red sea bream.

Lipid is one of the most important nutritional factors affecting growth and survival of larval fish. This study aims to determine optimum level of lipid in formulated microdiets for the 10-day old rockfish (Sebastes schlegeli) larvae. Five granulated microdiets (CL11, CL14, CL17, CL20, and CL23) containing various (11%, 14%, 17%, 20%, and 23%, respectively) levels of lipid were prepared, and their lipid levels were controlled by adding fish oil at the expense of dextrin. The effects of feeding rockfish larvae with these formulated microdiets were compared with two commercial microdiets (Belgium and Japan), and local crumble diet. At the end of the 29-day feeding trial, weight gain (%) and total length (mm) of larval fish fed the CL20 diet were significantly (P 0.05) affected by the experimental diets. Crude lipid content of the whole-body fish was relatively well reflected from lipid levels of the experimental diets. In conclusion, the greatest weight gain and longest total length were obtained in larval fish fed the CL20 diet among the experimentally formulated microdiets. The optimum lipid level in the experimentally formulated microdiet was estimated to be 17.3% for rockfish larvae based on the broken-line analysis.

To delineate a livestock manure-derived groundwater plume (LDGP) in agro-livestock farming areas with the extensive use of chemical fertilizers, multilevel monitoring wells (MLWs) were installed for depth-specific sampling of groundwater, and then hydrochemical, nitrate N-O isotopic and microbiological data of shallow groundwater collected from the MLWs were evaluated with the help of multivariate statistical tools. The LDGP was distinguished from the pervasive agricultural contamination based on δ15Nnitrate (10‰). Fecal coliforms and Escherichia coli were not observed in the LDGP, whereas bovine enterovirus type 2 was detected at a sample collected at a depth of 18 m below ground level (bgl) downgradient manure piles, indicating a potential virus risk. Among hydrochemical parameters, Ca2+, Mg2+, Na+, Cl- and SiO2(aq) were shown to be effective indicators to trace the LDGP. On the other hand, nitrate was not effective to discriminate the LDGP because of denitrification in deep parts (>6 m bgl) within the LDGP, although nitrate contamination was serious at shallow parts (≤6 m bgl; 62.4 to 119.1 mg/L, median 97.9 mg/L). Thus, an integrated hydrochemical index consisting of Ca2+, Mg2+, Na+, Cl- and SiO2(aq) was suggested based on the result of principal component analysis with isometric log-ratio transformed data to delineate the LDGP in shallow unconsolidated aquifers overlying silicate bedrocks, and a threshold of the index was determined to be 1.17. The application of the index to three other agro-livestock farming areas with prevalent agricultural contamination successfully distinguished the groundwater samples within the LDGP (11 of 40 samples) that showed the index values exceeding the threshold and a median δ15Nnitrate of 12.5 ‰. The study results show that the hydrochemical index can be used for the quick evaluation of a LDGP in agro-livestock farming areas given its cost efficiency and easily accessible analysis devices for water chemistry compared to isotopes, although the broad use of the index to determine LDGPs needs to be further verified by application to various geology and land uses. Livestock manures should be carefully managed to protect groundwater resources, including impermeable covers above or beneath the manure piles, given the potential risk of virus at deep parts and nitrate at shallow parts within the LDGP. The methodology to select hydrochemical indicators for distinguishing a LDGP and the combination of the indicators to develop an index suggested in this study will be useful to build new indices adapted to local conditions.

Olive flounder (Paralichthys olivaceus) is a vital aquaculture species in East Asia. However, few studies that estimate the genetic parameters of this species have been conducted. We estimated the genetic parameters of growth traits and designed an optimum breeding programme for this species. Heritability, genetic and phenotypic correlations, and breeding values were estimated for growth traits: body weight (BW), total length (TL), and condition factor (CF). A linear mixed animal model using the restricted maximum likelihood (REML) algorithm was applied to the statistical analysis of 9 traits (BW, TL, and CF at 11, 18, and 22 months of age) for a total of 54,159 animals from 7 generations. Increases of 13%, 8%, and 6.5% in BW, TL, and CF at the harvest stage were observed, respectively, after 7 generations of selection. The heritabilities of all growth traits were moderate, ranging from 0.35 to 0.46. The phenotypic and genetic correlations between BW and TL were high and positive in all three stages (0.91 and 0.92, 0.91 and 0.93, and 0.88 and 0.91). The estimated breeding values of BW and TL increased over the generations; however, the estimated breeding value of CF fluctuated. The optimum progeny number within full-sib families for an accuracy of 0.632 is suggested to be between 10 and 25. Findings indicated that a considerable response to selection and single-trait selection based on BW would be effective in olive flounder.

In this review, we describe the application of thermosensitive hydrogels composed of poloxamer in medicine, especially for oral cavities. Thermosensitive hydrogels remain fluid at room temperature; at body temperature, they become more viscous gels. In this manner, the gelling system can remain localized for considerable durations and control and prolong drug release. The chemical structure of the poloxamer triblock copolymer leads to an amphiphilic aqueous solution and an active surface. Moreover, the poloxamer can gel by forming micelles in an aqueous solution, depending on its critical micelle concentration and critical micelle temperature. Owing to its controlled-release effect, a thermosensitive gel based on poloxamer 407 (P407) is used to deliver drugs with different characteristics. As demonstrated in studies on poloxamer formulations, an increase in gelling viscosity decreases the drug release rate and gel dissolution time to the extent that it prolongs the drug’s duration of action in disease treatment. This property is used for drug delivery and different therapeutic applications. Its unique route of administration, for many oral diseases, is advantageous over traditional routes of administration, such as direct application and systemic treatment. In conclusion, thermosensitive gels based on poloxamers are suitable and have great potential for oral disease treatment.

Abstract Background Whole-genome sequencing (WGS) analyses have found higher genetic burden in autistic females compared to males, supporting higher liability threshold in females. However, genomic evidence of sex differences has been limited to European ancestry to date and little is known about how genetic variation leads to autism-related traits within families across sex. Methods To address this gap, we present WGS data of Korean autism families (n = 2255) and a Korean general population sample (n = 2500), the largest WGS data of East Asian ancestry. We analyzed sex differences in genetic burden and compared with cohorts of European ancestry (n = 15,839). Further, with extensively collected family-wise Korean autism phenotype data (n = 3730), we investigated sex differences in phenotypic scores and gene-phenotype associations within family. Results We observed robust female enrichment of de novo protein-truncating variants in autistic individuals across cohorts. However, sex differences in polygenic burden varied across cohorts and we found that the differential proportion of comorbid intellectual disability and severe autism symptoms mainly drove these variations. In siblings, males of autistic females exhibited the most severe social communication deficits. Female siblings exhibited lower phenotypic severity despite the higher polygenic burden than male siblings. Mothers also showed higher tolerance for polygenic burden than fathers, supporting higher liability threshold in females. Conclusions Our findings indicate that genetic liability in autism is both sex- and phenotype-dependent, expanding the current understanding of autism’s genetic complexity. Our work further suggests that family-based assessments of sex differences can help unravel underlying sex-differential liability in autism.

Abstract Low-level somatic mutations in the human brain are implicated in various neurological disorders. The contribution of low-level brain somatic mutations to autism spectrum disorder (ASD), however, remains poorly understood. Here, we performed high-depth exome sequencing with an average read depth of 559.3x in 181 cortical, cerebellar, and peripheral tissue samples to identify brain somatic single nucleotide variants (SNVs) in 24 ASD subjects and 31 controls. We detected ~2.4 brain somatic SNVs per exome per single brain region, with a variant allele frequency (VAF) as low as 0.3%. The mutational profiles, including the number, signature, and type, were not significantly different between the ASD patients and controls. Intriguingly, when considering genes with low-level brain somatic SNVs and ASD risk genes with damaging germline SNVs together, the merged set of genes carrying either somatic or germline SNVs in ASD patients was significantly involved in ASD-associated pathophysiology, including dendrite spine morphogenesis (p = 0.025), mental retardation (p = 0.012), and intrauterine growth retardation (p = 0.012). Additionally, the merged gene set showed ASD-associated spatiotemporal expression in the early and mid-fetal cortex, striatum, and thalamus (all p

Oxidative stress plays a vital role in neurodegenerative diseases. Cornus officinalis (CC) has a wide range of pharmacological activities (e.g., antioxidant, neuroprotective, and anti-inflammatory). The present study was undertaken to elucidate the neuroprotective mechanism of CC and fermented CC (FCC) on stress and H2O2-induced oxidative stress damage in rats and SH-SY5Y cells. A dose of 100 mg/kg CC or FCC was orally administered to rats 1 h prior to immobilization 2 h per day for 14 days. CC, especially FCC administration decreased immobility time in forced swim test (FST), effectively alleviated the oxidative stress, and remarkably decreased corticosterone, β-endorphin and increased serotonin levels, respectively. In cells, CC and FCC significantly inhibited reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release and significantly increased the genes expression of antioxidant and neuronal markers, such as superoxide dismutase (SOD), catalase (CAT), and brain-derived neurotrophic factor (BDNF). Moreover, the pro-apoptotic factor Bax and anti-apoptotic factor Bcl-2 (Bax/Bcl-2) ratio was regulated by CC and FCC pretreatment. Both in rats and cells, CC and FCC downregulated mitogen-activated protein kinase (MAPK) phosphorylation. Taken together, these results demonstrated that CC and particularly FCC ameliorated oxidative stress and may be used on the neuroprotection.

Study DesignA prospective sonographic study.PurposeTo verify the effectiveness of simultaneous application of two landmarks, Doppler image of the vertebral artery and shape of the transverse tubercle of the seventh cervical (C7) vertebra.Overview of LiteratureCounting upwards from the C7 vertebra which only has a posterior tubercle of the transverse process is a commonly used method for ultrasound-guided cervical nerve root block. However, each transverse process has a different shape.MethodsSonograms of 20 volunteers were examined. At first, we identified the C7 transverse process based on the presence of the vertebral artery without the anterior tubercle. The C5 and C6 transverse processes were identified based on the presence of anterior tubercle without the vertebral artery. Subsequently, we placed needles on the C5, C6, and C7 transverse processes and the location and direction of needles were confirmed by fluoroscopy.ResultsIn the 120 segments, 93.3% of needles were placed correctly as desired; 97.5% of needles were placed on the 5C transverse process; 97.5% of needles were placed on the C6 transverse process; and 85.0% of needles were placed on the C7 transverse process, respectively. Both sides showed the same accuracy of 93.3%.ConclusionsSimultaneous application of Doppler image of the vertebral artery and shape of the C7 transverse tubercle showed 93.3% accuracy in identifying the target cervical level. Therefore, Doppler image of the vertebral artery can be considered to be a useful landmark for ultrasound-guided cervical nerve root block.

We investigated the impacts of leachates from a swine carcass burial site and a cow manure heap on the geochemical and microbiological properties of agricultural water samples, including leachate, groundwater from monitoring wells and background wells, and stream water. The leachate from the livestock burial site showed extremely high electrical conductivity, turbidity, and major ion concentrations, but low redox potential and dissolved oxygen levels. The groundwater in the monitoring wells adjacent to both sites showed severe contamination from the leachate, as indicated by the increases in EC, turbidity, Cl-, and SO42-. Bacteria from the phylum Firmicutes and Bacteriodetes and Archaea from the phylum Euryarchaeota were the major phyla in both the leachates and manure heap. However, the class- or genus-level components of these phyla differed markedly between the leachate and manure heap samples. The relative abundance of Firmicutes decreased from 35% to 0.3~13.9% in the monitoring wells and background wells at both sites. The Firmicutes in these wells was unlikely to have originated from the transportation of leachate to the surrounding environment because Firmicutes genera differed drastically between the leachate and monitoring wells. Meanwhile, sulfate-reducing bacteria (SRB) from the livestock carcass burial site were detected in the monitoring wells close to the leachate. This was likely because the release of carcass decomposition products, such as organic acids, to adjacent areas improved the suitability of the local environments for SRB, which were not abundant in the leachate. This study highlights the need to better understand microbial community dynamics along groundwater flow paths to evaluate bacterial transport in subsurface environments and provides new insights into the effective management of groundwater quality at both farm and regional scales.

To assess the groundwater−river water interaction in a point-bar alluvial aquifer as a crucial step in site assessment for riverbank filtration, hydrochemical and hydrogeologic investigations were performed on a riverine island at the low reach of the Nakdong River, South Korea. The site was evaluated for the application of large-scale bank filtration. Unconsolidated sediments (~40 m thick) of the island comprise fine- to medium-grained sand (upper aquifer), silty sand with clay intercalations, and sandy gravel (lower aquifer) in descending order. The intermediate layer represents an impermeable aquitard and extends below the river bottom. A total of 66 water samples were collected for this study; groundwater (n = 57) was sampled from both preexisting irrigation wells, and three multi-level monitoring wells (each 35 m deep). Groundwater chemistry is highly variable, but it shows a distinct hydrochemical change with depth: shallow groundwater (3− and SO42−, due to agricultural contamination from the land surface, while deeper groundwater (>25 m deep) from the lower aquifer is generally free of NO3− and relatively rich in F. The lower aquifer groundwater is also higher in pH, and concentrations of K+, Mg2+, and HCO3−, indicating that the aquifer is likely fed by regional groundwater flow. Such separation of groundwater into two water bodies is the result of the existence of an impermeable layer at intermediate depth. In addition, the hyporheic flow of river water is locally recognized at the upstream part of the upper aquifer as the zone of low TDS (Total Dissolved Solids) values (

Objectives The purpose of this study was to determine the optimal master apical file size with minimal transportation and optimal efficiency in removing infected dentin. We evaluated the transportation of the canal center and the change in untouched areas after sequential preparation with a #25 to #40 file using 3 different instruments: stainless steel K-type (SS K-file) hand file, ProFile and LightSpeed using microcomputed tomography (MCT). Materials and Methods Thirty extracted human mandibular molars with separated orifices and apical foramens on mesial canals were used. Teeth were randomly divided into three groups: SS K-file, Profile, LightSpeed and the root canals were instrumented using corresponding instruments from #20 to #40. All teeth were scanned with MCT before and after instrumentation. Cross section images were used to evaluate canal transportation and untouched area at 1- , 2- , 3- , and 5- mm level from the apex. Data were statistically analyzed according to' repeated nested design'and Mann-Whitney test (p = 0.05). Results In SS K-file group, canal transportation was significantly increased over #30 instrument. In the ProFile group, canal transportation was significantly increased after preparation with the #40 instrument at the 1- and 2- mm levels. LightSpeed group showed better centering ability than ProFile group after preparation with the #40 instrument at the 1 and 2 mm levels. Conclusions SS K-file, Profile, and LightSpeed showed differences in the degree of apical transportation depending on the size of the master apical file.

Stress can lead to inflammation, accelerated aging, and some chronic diseases condition. Mentha arvensis (MA) is a traditional medicine having antioxidant and anti-inflammatory activities. The present study investigated the anti-stress role of MA and fermented MA (FMA) extract in immobilized rats. We studied the lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells and rats were immobilized for 2 h per day for 14 days using a restraining cage. MA (100 mg/kg) and FMA (100 mg/kg) were orally administered to rats 1 h prior to immobilization. Using high-performance liquid chromatography (HPLC) analysis, we determined the rosmarinic acid content of MA and FMA. The generation of malondialdehyde (MDA) and nitric oxide (NO) in RAW 246.7 cells were suppressed by both MA and FMA. In rats, MA and FMA notably improved the body weight, daily food intake, and duodenum histology. MDA and NO level were gradually decreased by MA and FMA treatment. MA and FMA significantly controlled the stress-related hormones by decreasing corticosterone and β-endorphin and increasing serotonin level. Moreover, protein expression levels of mitogen activated protein kinases (MAPK) and cyclooxygenase-2 (COX-2) were markedly downregulated by MA and FMA. Taken together, MA and FMA could ameliorate immobilized-stress by reducing oxidative stress, regulating stress-related hormones, and MAPK/COX-2 signaling pathways in rats. Particularly, FMA has shown greater anti-stress activities than MA.

North Korea has shown more aggressive nuclear behavior during the Kim Jong Un era as has been evident in the rapid acceleration of its nuclear weapons development and its delivery system diversification, especially in 2016. This study seeks to determine why was there such an urgency in progressing its nuclear capability in the first few years following Kim Jong Un's ascent to power after the death of his father in 2011. It confines its research scope to Pyongyang's external motivations - its political and economic relations with the biggest regime backer, China - to conduct an academic investigation on whether Kim Jong Un's North Korea could still perceive China as a reliable patron. It concludes that the bilateral political and economic relations took a notable and simultaneous downturn, prompting it to focus on internal balancing, exemplifying the core principles of the IR theory of defensive realism. [ABSTRACT FROM AUTHOR]