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Melanomas reprogram their metabolism to rapidly adapt to therapy-induced stress conditions, allowing them to persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKi) through a concerted metabolic reprogramming mediated by peroxisomes and UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, by repressing PEX3 expression, potentiates the pro-apoptotic effects of MAPKi via an induction of ceramides, an effect limited by UGCG-mediated ceramide metabolism. Co-targeting PEX3 and UGCG selectively eliminates a subset of metabolically active, drug-tolerant CD36+melanoma persister cells, thereby sensitizing melanoma to MAPKi and delaying resistance. Increased levels of peroxisomal genes andUGCGare found in patient-derived MAPKi-relapsed melanomas, and simultaneously inhibiting PEX3 and UGCG restores MAPKi sensitivity in multiple models of therapy resistance. Finally, triple therapy comprised of a newly identified inhibitor of the PEX3-PEX19 interaction, a UGCG inhibitor and a MAPKi demonstrates potent anti-tumor activity in pre-clinical melanoma models, thus representing a promising approach for melanoma treatment.HighlightsInhibiting peroxisome biogenesis uncovers a metabolic vulnerability in melanomaCD36+persister melanoma cells tolerate MAPK-targeted therapy through peroxisome/UGCG mediated metabolic rewiringDual blockade of PEX3 and UGCG potentiates melanoma response to MAPK-targeted therapies and restores therapeutic sensitivity in MAPKi-resistant tumorsNNC 55-0396 is a PEX3-PEX19 binding inhibitor with potent anti-tumor activity in melanoma

Background Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans, with a case fatality rate of approximately 35%, thus posing a considerable threat to public health. The lack of approved vaccines or antivirals currently constitutes a barrier in controlling disease outbreaks and spread. Methods In this study, using a mammalian expression system, which is advantageous for maintaining correct protein glycosylation patterns, we constructed chimeric MERS-CoV virus-like particles (VLPs) and determined their immunogenicity and protective efficacy in mice. Results Western blot and cryo-electron microscopy analyses demonstrated that MERS-CoV VLPs were efficiently produced in cells co-transfected with MERS-CoV spike (S), envelope, membrane and murine hepatitis virus nucleocapsid genes. We examined their ability as a vaccine in a human dipeptidyl peptidase 4 knock-in C57BL/6 congenic mouse model. Mice immunized with MERS VLPs produced S-specific antibodies with virus neutralization activity. Furthermore, MERS-CoV VLP immunization provided complete protection against a lethal challenge with mouse-adapted MERS-CoV and improved virus clearance in the lung. Conclusions Overall, these data demonstrate that MERS-CoV VLPs have excellent immunogenicity and represent a promising vaccine candidate.

This study examined the quarantine experiences of workers at the senior care institutions that excersized cohort quarantine due to Corona 19 thoroughly, and analyzed those experiences with a consensual qualitative research method. The study derived total 9 categories with 23 subcategories from 5 domains. The results are as follows. The degrees of understanding and acceptance of cohort quarantine were different with respect to the individual’s environment and personality characteristics. Even though they experienced psychological conflict and stress before the cohort quarantine was decided, they gave up and accepted, thinking that it could secure the safety of themselves and society. In addition, the receptive attitude of co-workers, active support and consensus of the people around them made them survive through the isolation period. The isolation experience awakedned the importance of family and home and increase the satisfaction about their job. What is necessary for the isolated life is a high demand for a loyal and active attitude to the life of family members, positive and supportive feedback from neighbors, and for sleep and privacy of a quality.

Idiopathic hypertrophic spinal pachymeningitis (IHSP) is a rare, diffuse inflammatory fibrosis of the dura mater that can lead to spinal cord compression. Though the optimal treatment is controversial, some reports recommend decompressive surgery and postoperative steroid therapy. However, we encountered a case of pachymeningitis that worsened after decompressive surgery. A 79-year-old woman presented with gait disturbance and bilateral lower extremity weakness that began 6 months prior. She had radiating pain on the C5 and T1 dermatomes and clumsiness in both hands. Magnetic resonance imaging (MRI) revealed diffuse thickening of the posterior longitudinal ligament of C6 to T4/5 and ligamentum flavum of C3/4 to T4/5, causing central canal stenosis and compressive myelopathy. She underwent posterior decompressive laminectomy from C4 to T1 total (T2 subtotal) and cervicothoracic screw fixation. During surgery, we found severe adhesion of the posterior longitudinal ligament and ligamentum flavum to the dura mater. Chronic inflammation with fibrosis and lymphoplasmacytic infiltration were present. After surgery, the patient's motor weakness worsened. Despite steroid treatment, her symptom severity fluctuated. Follow-up MRI obtained 3 months postoperation revealed high signal intensity from C5 to T2, possibly indicating aggravated compressive myelopathy. Thus, in this case, decompressive surgery and steroid therapy were detrimental.

Objective To analyze motor vehicle accidents in two different traffic environments and compare differences in severity between both regions. Methods Injury data were collected by the Emergency Medicine and Traffic Accident Research Team as part of the Korean In-Depth Accident Study. Patients admitted to emergency medical centers located in Wonju, Gangwon province (population 345,143, rural, group A) and Bucheon, Gyeonggi province (population 870,735, urban, group B) between January 2011 and December 2017 were included for analysis. Injury severity was classified into four categories based on Injury Severity Score (ISS): minor (1≤ Results Overall, 1,807 patients were included (group A, 1,484; group B, 323). There was a higher proportion of daytime accidents, accidents involving larger cars, passenger injuries, and accidents involving lack of seat belt use in group A than in group B. The mean ISS value was 8.98 in group A and 4.62 in group B (P Conclusion Patients in a rural city who visited the emergency room owing to motor vehicle accidents had more severe injuries than those in an urban city.

X-ray absorption near-edge structure (XANES) imaging is a powerful tool to visualize the chemical state distribution of transition-metal-based materials at synchrotron radiation facilities. In recent years, the electrochemical working rechargeable battery has been the most studied material in XANES imaging owing to the large increase of portable electronics and electric vehicles. This work acknowledges the importance of battery analysis and has developed the XANES imaging system on BL7C at Pohang Light Source-II (PLS-II). BL7C employs an undulator taper configuration to obtain an energy band >130 eV near the K-absorption edge of the target element with a minimum energy interval >0.2 eV. While measuring energy-dependent images, the zone plate translation maintains the best focus, and then various data processes such as background correction, image registration and clustering allow single XANES spectrum extraction and chemical distribution mapping. Here, the XANES imaging process is described, the XANES spectrum quality is identified and the chemical states of the partially charged cathode material used in lithium-ion batteries as an application example are examined.

본 연구는 청소년의 삶의 목표에 영향을 미치는 요인으로 학업성취만족도, 또래관계, 부모양육방식, 자아정체감과의 관계를 구조적으로 분석하였다. 이를 위하여 한국아동 · 청소년패널조사(KCYPS) 제7차년도 자료 중 총 3,981명의 중, 고등학생 데이터를 활용하여 분석하였다. 주요 분석 결과는 다음과 같다. 첫째, 청소년의 삶의 목표에 직접적인 영향을 주는 요인은 또래관계와 부모양육방식, 자아정체감이었다. 둘째, 학업성취만족도와 또래관계, 부모양육방식은 자아정체감에 직접적인 영향을 미치는 것으로 나타났다. 셋째, 학업성취만족도, 또래관계, 부모양육방식이 청소년의 삶의 목표에 미치는 영향에서 자아정체감의 매개효과를 확인하였다. 이 연구는 청소년 삶의 목표에 영향을 미치는 관련 요인을 규명하고 영향관계를 분석한 결과를 제시하였으며, 청소년기 삶의 목표의 설정과 안정적 추구를 위한 다양한 측면에서의 정책적 · 실천적 방안을 제시하였다.

Herein, the size dependent behavior of cobalt ferrite nanoparticles was investigated using synchrotron radiation based techniques. Scanning electron micrographs revealed the enhancement of particle/crystallite size with increase of annealing temperature. Moreover, the shape of these particles also changed with increase of crystallite size. Saturation magnetization increased with increase of crystallite size. The higher saturation magnetization for larger crystallite size nanoparticles was attributed to a cation distribution similar to that of bulk CoFe2O4. The optical band-gap of these nanoparticles decreased from 1.9 eV to 1.7 eV with increase of crystallite size. The enhancement of the optical band-gap for smaller crystallites was due to phenomena of optical confinement occurring in the nanoparticles. Fe L Co L-edge near edge extended X-ray absorption fine structure (NEXAFS) measurements showed that Fe and Co ions remain in the 3+ and 2+ state in these nanoparticles. The results obtained from Fe & Co K-edge X-ray absorption near edge structure (XANES)-imaging experiments further revealed that this oxidation state was possessed by even the crystallites. Extended X-ray absorption fine structure (EXAFS) measurements revealed distribution of Fe and Co ions among tetrahedral (A) and octahedral (B) sites of the spinel structure which corroborates the results obtained from Rietveld refinement of X-ray diffraction patterns (XRD). X-ray magnetic circular di-chroism (XMCD) measurements revealed negative exchange interaction among the ions situated in tetrahedral (A) and octahedral (B) sites. Theoretical and experimental calculated magnetic moments revealed the dominancy of size effects rather than the cation redistribution in the spinel lattice of CoFe2O4 nanoparticles.

Metavalent bonding is crucial for the determination of phase transition and improvement of device performance in phase-change materials, which are attracting interest for use in memory devices. Although monitoring dielectric and phononic parameters provides a direct measure of the metavalent bonding, the control of phase-change phenomena and metavalent bonding in the dynamical regime has yet to be demonstrated. This study reports the photoenhanced metavalent bonding and resulting hidden metallic crystalline state of Ti-doped Sb

The scission rates of polystyrene and fluorinated polystyrene irradiated in an irradiation facility with Co-60 γ-rays were determined using molecular dynamics simulation and gel permeation chromatography (GPC) molecular weight distributions. The prediction was based on the assumption that γ-ray energy is transferred to the initial velocity of the primary knock-on atom. We employed a molecular dynamics simulation procedure to compute the changes in bond length between the connections for selected values of the absorbed dose and compared the calculated values with measurements made on the irradiated samples. The samples were exposed to four different absorbed doses of 25, 50, 75, and 100 kGy. The scission process and scission ratio were simulated with LAMMPS with ReaxFF potential for each bond, and we compared the simulation results with the experimental data especially measuring average molecular weight to evaluate the effect of fluorination on radiation enhancement.

Because the porcine epidemic diarrhea virus (PEDV) is a critical pathogen resulting in rapid spreading and high mortality rates in piglets, understanding of the transmission route of PEDV is required for its controlling. Until now, it is well known that PEDV transmission routes are various, such as fecal–oral route, contaminated feed, farmworkers, and transport vehicles. However, unlike several swine-infected viruses, there were no reports of vertical transmission with PEDV. In our study, we confirmed possible vertical transmission of PEDV. We confirmed PEDV in piglet testicles and umbilical cords from PEDV-positive sow. These findings are direct evidence that PEDV is transmitted vertically through placenta. This is the first report on transplacental transmission of PEDV and will be very important information for controlling PED.

For the in situ and sensitive detection of benthic dinoflagellates, we have established an integrated loop-mediated isothermal amplification (LAMP) assay based on Ostreopsis cf. ovata and Amphidinium massartii. To detect the two species, a set of species-specific primers was constructed between the ITS gene and D1–D6 LSU gene, and the reaction temperature, time, and buffer composition were optimized to establish this method. In addition, the specificity of the LAMP primers was verified both in strains established in the laboratory and in field samples collected from the Jeju coastal waters, Korea. With the LAMP assay, the analysing time was within 45 to 60 min, which may be shorter than that with the conventional PCR. The detection sensitivity of the LAMP assay for O. cf. ovata or A. massartii was comparable to other molecular assays (PCR and quantitative PCR (qPCR)) and microscopy examination. The detection limit of LAMP was 0.1 cell of O. cf. ovata and 1 cell of A. massartii. The optimized LAMP assay was successfully applied to detect O. cf. ovata and A. massartii in field samples. Thus, this study provides an effective method for detecting target benthic dinoflagellate species, and could be further implemented to monitor phytoplankton in field surveys as an altenative.

The genus Oxyrrhis is a heterotrophic dinoflagellate found in diverse marine environments. Oxyrrhis spp. have received attention owing to their ecological and industrial importance, high lipid contents, and docosahexaenoic acid formation. To the best of our knowledge, contrary to O. marina, ecophysiological characterization studies on O. maritima have not yet been reported. Therefore, we investigated the taxonomy and ecophysiology of four strains of O. marina from coastal waters and two strains of O. maritima from the littoral tidepool waters of Korea. Based on phylogenetic trees constructed using internal transcribed spacer ribosomal DNA (ITS rDNA) and SSU rDNA of dinoflagellates, the clade of all four O. marina strains was divergent from that of the two O. maritima strains. We measured the growth rates of both species at various water temperatures (10–36 °C), salinities (5–90), and light intensities (0–100 µE·m−2·s−1). The lowest (O. marina and O. maritima: 10 °C) and highest temperatures (O. marina: &lt, 35 °C, O. maritima: &gt, 35 °C) revealed that O. maritima has more tolerance to high salinity. This study provides a basis for understanding the ecophysiology of O. marina and O. maritima and their population dynamics in marine ecosystems.

We found the euryhaline microalga, Tetraselmis jejuensis sp. nov., which was adapted to supralittoral tide pools with salinities varying from 0.3–3.1%. Fifteen strains of T. jejuensis were isolated from Daejeong (DJ) and Yongduam (YO), and clonal cultures were established in the laboratory. Morphological characterization revealed that the cells have a compressed shape, four flagella emerging from a depression near the apex in two opposite pairs, a cup-shaped chloroplast containing one pyrenoid surrounded by starch, and eyespot regions not located near the flagellar base. T. jejuensis cells showed distinct characteristics compared to other Tetraselmis species. First, a regular subunit pattern with honeycomb-like structures was predominantly displayed on the surface in the middle of the cell body. Second, the pyrenoid was invaded by both cytoplasmic channels comprising electron-dense material separated from the cytoplasm, and two branches of small cytoplasmic channels (canaliculi) in various directions, which characterize the subgenus Tetrathele. Eyespot regions containing a large number of osmiophilic globules, packed closely together and arranged in subcircular close packing of diverse sizes, were dispersed throughout the chloroplast. In the phylogenetic analysis of small subunit (SSU) rDNA sequences, the 15 strains isolated from DJ and YO separated a newly branched clade in the Chlorodendrophyceae at the base of a clade comprising the T. carteriiformi/subcordiformis clade, T. chuii/suecica clade, and T. striata/convolutae clade. The strains in the diverging clade were considered to belong to the same species. The SSU rDNA sequences of the DJ and YO strains showed a maximum difference of 1.53% and 1.19% compared to Tetraselmis suecica (MK541745), the closest species of the family based on the phylogenetic analysis, respectively. Based on morphological, molecular, and physiological features, we suggest a new species in the genus Tetraselmis named Tetraselmis jejuensis, with the species name “jejuensis” referring to the collection site, Jeju Island, Korea.