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Salterns are hypersaline environments that are inhabited by diverse halophilic microorganisms, including fungi. In this study, we isolated a fungal strain SK1-1 from a saltern in the Republic of Korea, which was identified as Asperillus reticulatus. This is the first reported saline-environment-derived A. reticulatus that belongs to the Aspergillus penicillioides clade and encompasses xerophilic fungi. SK1-1 was halophilic, obligately requiring NaCl for growth, with a maximum radial growth of 6%–9% (w/v) NaCl. To facilitate the biotechnological application of halophilic fungi, we screened the SK1-1 strain for proteolytic activity. Proteases have widespread applications in food processing, detergents, textiles, and waste treatment, and halophilic proteases can enable protein degradation in high salt environments. We assessed the proteolytic activity of the extracellular crude enzyme of SK1-1 using azocasein as a substrate. The crude protease exhibited maximum activity at 40–50 °C, pH 9.5–10.5, and in the absence of NaCl. It was also able to retain up to 69% of its maximum activity until 7% NaCl. Protease inhibitor assays showed complete inhibition of the proteolytic activity of crude enzymes by Pefabloc® SC. Our data suggest that the halophilic A. reticulatus strain SK1-1 produces an extracellular alkaline serine protease.

The function of peripheral nociceptors is frequently tuned by the action of G protein-coupled receptors (GPRs) that are expressed in them, which contribute to pain alteration. Expanding new information on such GPRs and predicting their potential outcomes can help to construct new analgesic strategies based on their modulations. In this context, we attempted to present a new GPR not yet acknowledged for its pain association. Gpr83 exhibits relatively high expressions in the peripheral nervous system compared to other tissues when we mined and reconstructed Gene Expression Omnibus (GEO) metadata, which we confirmed using immunohistochemistry on murine dorsal root ganglia (DRG). When Gpr83 expression was silenced in DRG, neuronal and behavioral nociception were all downregulated. Pathologic pain in hind paw inflammation and chemotherapy-induced peripheral neuropathy were also alleviated by this Gpr83 knockdown. Dependent on exposure time, the application of a known endogenous Gpr83 ligand PEN showed differential effects on nociceptor responses in vitro. Localized PEN administration mitigated pain in vivo, probably following Gq/11-involved GPR downregulation caused by the relatively constant exposure. Collectively, this study suggests that Gpr83 action contributes to the tuning of peripheral pain sensitivity and thus indicates that Gpr83 can be among the potential GPR targets for pain modulation.

Genotyping of

Human CtIP maintains genomic integrity primarily by promoting 5′ DNA end resection, an initial step of the homologous recombination (HR). A few mechanisms have been suggested as to how CtIP recruitment to damage sites is controlled, but it is likely that we do not yet have full understanding of the process. Here, we provide evidence that CtIP recruitment and functioning are controlled by the SIAH2 E3 ubiquitin ligase. We found that SIAH2 interacts and ubiquitinates CtIP at its N-terminal lysine residues. Mutating the key CtIP lysine residues impaired CtIP recruitment to DSBs and stalled replication forks, DSB end resection, overall HR repair capacity of cells, and recovery of stalled replication forks, suggesting that the SIAH2-induced ubiquitination is important for relocating CtIP to sites of damage. Depleting SIAH2 consistently phenocopied these results. Overall, our work suggests that SIAH2 is a new regulator of CtIP and HR repair, and emphasizes that SIAH2-mediated recruitment of the CtIP is an important step for CtIP’s function during HR repair.

Migratory birds disperse ticks and associated tick-borne pathogens along their migratory routes. Four selected pathogens of medical importance (Coxiella burnetii, Rickettsia spp., Francisella tularensis, and Toxoplasma gondii) were targeted for detection in 804 ticks (365 pools) collected from migratory birds at Hong and Heuksan Islands in the Republic of Korea (ROK) from 2010 to 2011 and 2016. Toxoplasma gondii and Rickettsia spp., were detected in 1/365 (0.27%) and 34/365 (9.32%) pools of ticks, respectively. T. gondii and five rickettsial species were recorded in ticks collected from migratory birds for the first time in ROK. The five rickettsial species (R. monacensis, Candidatus Rickettsia longicornii, R. japonica, R. raoultii, and R. tamurae) were identified using sequence and phylogenetic analysis using ompA and gltA gene fragments. Rickettsia spp. are important pathogens that cause rickettsiosis in humans, with cases recorded in the ROK. These results provide important evidence for the potential role of migratory birds in the introduction and dispersal of T. gondii and Rickettsia spp. along their migratory routes and raise awareness of potential transmission of zoonotic tick-borne pathogens associated with migratory birds in the ROK.

Studies on marine fungi (termed as ‘marine-derived fungi’ in this paper) have been significantly increasing worldwide because of the critical role displayed by marine fungi in the marine ecosystem and their potential as sources of bioactive compounds. Korea is surrounded by three seas containing abundant marine resources. In this review, to facilitate research and applications of marine fungi, we summarized previously studied marine fungi in Korea focusing on published research articles in peer-reviewed journals over the last two decades. Approximately 79% of the studies (66 articles) were published in the 2010s and described a total of 818 strains (isolates) of 266 species belonging to 3 phyla, 8 classes, 21 orders, 43 families, and 76 genera. The most prevalent fungi belong to the genera Penicillium/Eupenicillium/Talaromyces, accounting for 40.2% of all species (107 species), followed by Aspergillus/Eurotium/Neosartorya (13.9%, 37 strains). Approximately 67% of fungal strains were originated from the eastern (44.6%, 365 strains) and western coasts (22.1%, 181 strains), and their main isolation sources were coastal plants/halophytes, marine animals, sediment, and marine algae. More than 35% of the strains (292 strains) produced novel and/or bioactive compounds with enzymatic, antimicrobial, antioxidant, anti-cancer, anti-inflammatory, anti-diabetic, or multi-functional activities. This review provides insights into current knowledge and future perspectives regarding marine-derived fungi in Korea.

The South Korean population is rapidly aging, and the number of older patients in long-term-care hospitals (LTCHs) continues to increase. This study aims to investigate the epidemiologic data, characteristics, and clinical outcomes of patients aged 65 years and older transferred from LTCHs to emergency departments (EDs). This is a retrospective study based on National Emergency Department Information System data from 2014 to 2019. Of the 6,209,695 older patients visiting EDs for disease treatment, 211,141 (3.4%) were transferred from LTCHs. Among patients from LTCHs (211,141), 24.2% were discharged from EDs, 43.0% were admitted to general wards, 20.7% were hospitalized in intensive care units, 3.1% were transferred to another hospital, 6.1% returned to LTCHs, and 2.1% died in EDs. ED stays were the longest for those returning to LTCHs (710.49 ± 1127.43 min). Foley catheterization (40.3%) was most frequently performed in preventable ED visits. In South Korea, older patients being discharged from the ED or returning to LTCHs, after being transferred from LTCHs to EDs, increased. ED stays among older LTCH patients were longer than among non-LTCH older patients, contributing to congestion. To reduce avoidable transfer to EDs from LTCHs, it is necessary to discuss policies, such as expanding appropriate medical personnel and transitional treatment.

Purpose: To assess the expression levels of YAP and TAZ in patient-derived HCC tissue and identify the effects of YAP/TAZ inhibition depending on the baseline YAP/TAZ expression when combined with sorafenib using a patient-derived multicellular tumor spheroid (MCTS) model. Methods: Primary HCC cell lines were established from patient-derived tissue. Six patient-derived HCC cell lines were selected according to YAP/TAZ expression on Western blot: high, medium, low. Then, MCTS was generated by mixing patient-derived HCC cells and stroma cells (LX2, WI38, and HUVECs) and YAP/TAZ expression was assessed using Western blot. Cell viability of MCTS upon 48 h of drug treatment (sorafenib, sorafenib with CA3 0.1 µM, and CA3 (novel YAP1 inhibitor)) was analyzed. Results: Out of six patient-derived HCC cell lines, cell lines with high YAP/TAZ expression at the MCTS level responded more sensitively to the combination therapy (Sorafenib + CA3 0.1 μM) despite the potent cytotoxic effect of CA3 exhibited in all of the patient-derived HCCs. Conclusion: Targeting YAP/TAZ inhibition using the novel YAP1 inhibitor CA3 could be a promising therapeutic strategy to enhance sensitivity to sorafenib especially in HCCs with high YAP/TAZ expression in MCTS.

Objective To evaluate the impact of surgical simulation training using a three-dimensional (3D)-printed model of tetralogy of Fallot (TOF) on surgical skill development. Materials and methods A life-size congenital heart disease model was printed using a Stratasys Object500 Connex2 printer from preoperative electrocardiography-gated CT scans of a 6-month-old patient with TOF with complex pulmonary stenosis. Eleven cardiothoracic surgeons independently evaluated the suitability of four 3D-printed models using composite Tango 27, 40, 50, and 60 in terms of palpation, resistance, extensibility, gap, cut-through ability, and reusability of. Among these, Tango 27 was selected as the final model. Six attendees (two junior cardiothoracic surgery residents, two senior residents, and two clinical fellows) independently performed simulation surgeries three times each. Surgical proficiency was evaluated by an experienced cardiothoracic surgeon on a 1-10 scale for each of the 10 surgical procedures. The times required for each surgical procedure were also measured. Results In the simulation surgeries, six surgeons required a median of 34.4 (range 32.5-43.5) and 21.4 (17.9-192.7) minutes to apply the ventricular septal defect (VSD) and right ventricular outflow tract (RVOT) patches, respectively, on their first simulation surgery. These times had significantly reduced to 17.3 (16.2-29.5) and 13.6 (10.3-30.0) minutes, respectively, in the third simulation surgery (p = 0.03 and p = 0.01, respectively). The decreases in the median patch appliance time among the six surgeons were 16.2 (range 13.6-17.7) and 8.0 (1.8-170.3) minutes for the VSD and RVOT patches, respectively. Summing the scores for the 10 procedures showed that the attendees scored an average of 28.58 ± 7.89 points on the first simulation surgery and improved their average score to 67.33 ± 15.10 on the third simulation surgery (p = 0.008). Conclusion Inexperienced cardiothoracic surgeons improved their performance in terms of surgical proficiency and operation time during the experience of three simulation surgeries using a 3D-printed TOF model using Tango 27 composite.

Background/aim Non-structural maintenance of chromosomes condensin I complex subunit H (NCAPH) is implicated in correct chromosome condensation and segregation during mitosis. However, the functional role of NCAPH in the pathogenesis of non-small-cell lung cancer (NSCLC) remains unclear. The aim of this study was to elucidate the role of NCAPH in NSCLC cells. Materials and methods A549 and H1299 NSCLC cells were transfected with small-interfering RNA (siRNA) against NCAPH. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony-formation assay and flow cytometry analysis were performed to reveal the role of NCAPH in NSCLC cells. In addition, migration and invasion assay were also performed. Results NCAPH knockdown inhibited cell proliferation, induced cell-cycle arrest at G2/M phase, and prevented colony formation, migration and invasion by NSCLC cells. Conclusion NCAPH is involved in NSCLC progression and development, and may be a potential therapeutic target for NSCLC treatment.

Marine yeasts have tremendous potential in industrial applications but have received less attention than terrestrial yeasts and marine filamentous fungi. In this study, we have screened marine yeasts for amylolytic activity and identified an amylase-producing strain PH-Gra1 isolated from sea algae. PH-Gra1 formed as a coral-red colony on yeast–peptone–dextrose (YPD) agar; the maximum radial growth was observed at 22 °C, pH 6.5 without addition of NaCl to the media. Based on the morphology and phylogenetic analyses derived from sequences of internal transcribed spacer (ITS) and a D1/D2 domain of large subunit of ribosomal DNA, PH-Gra1 was designated Sporidiobolus pararoseus. S. pararoseus is frequently isolated from marine environments and known to produce lipids, carotenoids, and several enzymes. However, its amylolytic activity, particularly the optimum conditions for enzyme activity and stability, has not been previously characterized in detail. The extracellular crude enzyme of PH-Gra1 displayed its maximum amylolytic activity at 55 °C, pH 6.5, and 0%–3.0% (w/v) NaCl under the tested conditions, and the activity increased with time over the 180-min incubation period. In addition, the crude enzyme hydrolyzed potato starch more actively than corn and wheat starch, and was stable at temperatures ranging from 15 °C to 45 °C for 2 h. This report provides a basis for additional studies of marine yeasts that will facilitate industrial applications.

Background/aim Alpha/beta-hydrolase domain containing 12 (ABHD12) is a serine hydrolase that regulates immunological and neurological mechanisms. This study aimed to elucidate the oncogenic effect of ABHD12 on human breast cancer. Materials and methods ABHD12 expression was confirmed in breast cancer tissues and breast cancer cell lines by immunohistochemistry and quantitative RT-PCR. To determine the role of ABHD12, ABHD12 siRNA-suppressed breast cancer cells (MCF7 and MDA-MB-231 cells) were investigated for cell proliferation, migration, and invasion capabilities using MTT assays, EdU assays, colony formation assays, and Boyden chamber assays. Results Immunohistochemical staining showed a higher ABHD12 expression in breast cancer tissues than in normal tissues. Additionally, ABHD12 knockdown was found to inhibit cell growth, proliferation, migration, and invasion in breast cancer cells. Conclusion ABHD12 plays a crucial role in cell proliferation, migration, and invasion of breast cancer cells.

Blast furnace slag (BFS), a byproduct of iron-producing process, has been applied as silicate fertilizer in rice paddy. Silicate fertilizer contains lime and silicate as main components and iron and manganese as electron acceptors. This amendment improves soil productivity and mitigates methane (CH

Salterns are hypersaline environments that are inhabited by diverse halophilic microorganisms, including fungi. In this study, we isolated a fungal strain SK1-1 from a saltern in the Republic of Korea, which was identified as Asperillus reticulatus. This is the first reported saline-environment-derived A. reticulatus that belongs to the Aspergillus penicillioides clade and encompasses xerophilic fungi. SK1-1 was halophilic, obligately requiring NaCl for growth, with a maximum radial growth of 6%–9% (w/v) NaCl. To facilitate the biotechnological application of halophilic fungi, we screened the SK1-1 strain for proteolytic activity. Proteases have widespread applications in food processing, detergents, textiles, and waste treatment, and halophilic proteases can enable protein degradation in high salt environments. We assessed the proteolytic activity of the extracellular crude enzyme of SK1-1 using azocasein as a substrate. The crude protease exhibited maximum activity at 40–50 °C, pH 9.5–10.5, and in the absence of NaCl. It was also able to retain up to 69% of its maximum activity until 7% NaCl. Protease inhibitor assays showed complete inhibition of the proteolytic activity of crude enzymes by Pefabloc® SC. Our data suggest that the halophilic A. reticulatus strain SK1-1 produces an extracellular alkaline serine protease.

Genotyping of Coxiella burnetii using multispacer sequence typing (MST) and multiple locus variable number tandem repeat analysis (MLVA) was conducted from infected animals for the first time in the Republic of Korea. C. burnetii was detected by real-time PCR, and followed by MST and MLVA genotyping. The result showed that detected C. burnetii all had the same MLVA genotype, 6-13-2-7-9-10 for markers MS23-MS24-MS27-MS28-MS33-MS34, respectively, and genotype group 61 for MST. The same genotypes were previously identified in Poland. Importantly, this MLVA type was detected in humans in France, suggesting that the Korean strain can also potentially cause Q fever in humans. MST and MLVA were very useful tools for analyzing the molecular epidemiology of C. burnetii and helpful for interpreting the epidemiological relationship between isolates from domestic and international resources.

The horse industry has grown rapidly as a leisure industry in the Republic of Korea (ROK) in parallel with an increased demand for equestrian activities. As a result, there has been an increase in horse breeding and equestrian population and potential exposure to ticks and their associated pathogens. To provide a better understanding of the potential disease risks of veterinary and medical importance, a study was conducted to determine the geographical distribution and diversity of ticks collected from horses and vegetation associated with horse racetracks/ranches throughout the ROK. This included a survey of five associated common pathogens, Anaplasma phagocytophilum, Ehrlichia chaffeensis, Borrelia spp., Babesia caballi, and Theileria equi. A total 9220 ticks were collected from horses and associated pastures. Ticks were identified to species, stage of development, and sex. Two species of ticks, Haemaphysalis longicornis (99.9%) and Ixodes nipponensis (0.1%) were identified. Two of the target pathogens, A. phagocytophilum and Borrelia spp., were detected in 5/1409 tick pools (0.35%) and 4/1409 pools (0.28%) of H. longicornis, respectively, both of which are zoonotic pathogens of medical importance. The results of 16S rRNA phylogenetic analysis of A. phagocytophilum showed a close relationship to strains distributed in China, USA, Germany, Italy, Turkey, and Poland. Borrelia spp. showed a close relationship, based on 16S rRNA gene, to the strains reported from the USA (B. burgdorferi and B. americana) and Japan (B. tanukii and B. garinii). These results provide information about the potential risks of veterinary and medical importance and the development of mitigation strategies for disease prevention.

Rice is the main staple food for more than half of the world's population. Yet, rice cultivation is subjected to criticism because of its important role in methane (CH4) emissions. Although several agronomic practices such as controlled irrigation and conservation tillage have been widely adopted to mitigate CH4 emissions from rice cultivation, the benefits gained by these practices are highly dependent on site-specific soil and climate conditions, and often offset by yield reduction. The use of plant growth regulating compounds having the potential to increase the crop yield and mitigate CH4 emissions may be an innovative approach to sustainable agriculture. Ethylene (C2H4), a plant growth regulator is known to have a strong inhibitory effect on methanogenesis. However, due to gaseous form and low water solubility, C2H4 has not been used to suppress methanogenesis in paddy fields. To develop C2H4 as a prospective soil amendment for reducing methane (CH4) emissions, ethephon (2-Chloroethylphosphonic acid), a precursor of C2H4 was tested. We found that ethephon reduced CH4 formation by 43%, similar to other well known methanogenic inhibitors (2-Bromoethanesulfonate, 2-Chlomoethanesulfonate, 2-Mercaptoethanesulfonate). However, ethephon rapidly hydrolyzed to C2H4 and methanogenic activity recuperated completely after C2H4 removal. To slow down the release of C2H4, ethephon was mixed with bio-degradable polymers such as cellulose acetate and applied to paddy soils. We found that compared with the control, the C2H4 release of ethephon slowed down to 90 days, and the CH4 emissions were reduced by 90%. The application of ethephon at lower concentrations did not significantly alter bacterial communities, their relative abundance, and the abundance of methanotrophs, but it significantly reduced archaeal communities and the relative abundance and expression level of methanogens in paddy soils. Results suggest that cellulose acetate-mixed ethephon has great promise to suppress CH4 emissions in rice paddies while ensuring sustainable yields.

Nitrous oxide (N2O) is a major greenhouse gas (GHG) with high global warming potential. A majority of the N2O flux comes from agricultural sources, mainly due to nitrogen (N) fertilization. The soil N2O flux, induced by N fertilization, mainly originated from two different sources, i.e., fertilizer and soil organic nitrogen (SON). It is essential to know the individual contribution of these two different sources in total N2O flux for planning necessary mitigation strategies. It is also indispensable to know the seasonal difference of emission factors (EF) for having more accurate N2O inventory. Therefore, an experiment was conducted in a South Korean upland soil during summer and winter seasons using 15N labeled urea as an artificial N source and source specific N2O emissions were distinguished under different environmental conditions. To characterize the N2O emissions from urea, 0, 50, 100 and 200% of the Korean N recommendation rate was selected for specified crops. The Korean N recommendation rate for red pepper (Capsicum annuum) and garlic (Allium sativum) was 190 and 250 kg N ha−1, respectively. Direct emissions from urea were estimated from the difference of 15N2O flux emitted from 15N-urea treated soil and the natural abundance of 15N2O. From total N2O fluxes, urea originated N2O flux was 0.87% and 0.13% of the applied N in warm and cold seasons, respectively and the rest comes from SON. Nitrous oxide EF in the warm season was 2.69% of applied N and in the cold season that was 0.25%. Nitrous oxide fluxes showed a significant exponential relationship with soil temperature. The results show the necessity of considering the different N2O EF for warm and cold cropping seasons to reduce uncertainty in N2O inventory. The findings of this research may help better understand N2O source partitioning and the emission budget from warm and cold cropping seasons.

Ticks are important vectors of various pathogens that result in clinical illnesses in humans and domestic and wild animals. Information regarding tick infestations and pathogens transmitted by ticks is important for the identification and prevention of disease. This study was a large-scale investigation of ticks collected from dogs and their associated environments in the Republic of Korea (ROK). It included detecting six prevalent tick-borne pathogens (Anaplasma spp., A. platys, Borrelia spp., Babesia gibsoni, Ehrlichia canis, and E. chaffeensis). A total of 2293 ticks (1110 pools) were collected. Haemaphysalis longicornis (98.60%) was the most frequently collected tick species, followed by Ixodes nipponensis (0.96%) and H. flava (0.44%). Anaplasma spp. (24/1110 tick pools, 2.16%) and Borrelia spp. (4/1110 tick pools, 0.36%) were detected. The phylogenetic analyses using 16S rRNA genes revealed that the Anaplasma spp. detected in this study were closely associated with A. phagocytophilum reported in humans and rodents in the ROK. Borrelia spp. showed phylogenetic relationships with B. theileri and B. miyamotoi in ticks and humans in Mali and Russia. These results demonstrate the importance of tick-borne disease surveillance and control in dogs in the ROK.

Modulation of the function of somatosensory neurons is an important analgesic strategy, requiring the proposal of novel molecular targets. Many G-protein-coupled receptors (GPRs) have been deorphanized, but the receptor locations, outcomes due to their activations, and their signal transductions remain to be elucidated, regarding the somatosensory nociceptor function. Here we report that GPR171, expressed in a nociceptor subpopulation, attenuated pain signals via Gi/o-coupled modulation of the activities of nociceptive ion channels when activated by its newly found ligands. Administration of its natural peptide ligand and a synthetic chemical ligand alleviated nociceptor-mediated acute pain aggravations and also relieved pathologic pain at nanomolar and micromolar ranges. This study suggests that functional alteration of the nociceptor neurons by GPR171 signaling results in pain alleviation and indicates that GPR171 is a promising molecular target for peripheral pain modulation.

Excessive nutrient balance is a very crucial issue for environmental hazards. The constant addition of high-amounts of nutrient sources in agricultural production generates negative environmental conditions in Korea and Japan yet to be resolved. Therefore, it is obligatory to comprehend the nutrient (nitrogen (N) and phosphorus (P)) balance that is assessed by the difference between nutrient input and output in the soil surface in Korea and Japan. Among 34 Economic Co-operation and Development (OECD) countries, Korea and Japan had the highest N and P balances and thus both countries are primarily responsible for severe environmental pollution via nutrient release. The cultivable land area in both countries has constantly decreased during 1990–2017 at approximately 20 and 15% in Korea and Japan, respectively. Even N and P use efficiency sharply decreased with increasing N and P balance in both targeted countries. Japanese P balance, Korean N and P balances were decreased after the mid-1990s whereas, Japanese N balance almost unchanged for the last 28 years. Unlike chemical fertilizer input, Korean manure input level significantly increased from 78 kg N ha−1 in 1990 to 157 kg N ha−1 in 2017. Japanese manure input level was higher than that of chemical fertilizer without any big change for the last 28 years. The lion share of high N and P balance in both countries could generate from manure inputs, therefore, the number of livestock and their produced debris need to be used with more cautious for the reduction of national N and P surpluses at a benchmark level. These findings ensure to make a more environment friendly policy that can further reduce nutrient balance as well as improve soil health.