Alpha-tocopherol exerts protective function against the mucotoxicity of particulate matter in amphibian and human goblet cells

Exposure to particulate matter (PM) in ambient air is known to increase the risk of cardiovascular disorders and mortality. The cytotoxicity of PM is mainly due to the abnormal increase of reactive oxygen species (ROS), which damage cellular components such as DNA, RNA, and proteins. The correlation between PM exposure and human disorders, including mortality, is based on long-term exposure. In this study we have investigated acute responses of mucus-secreting goblet cells upon exposure to PM derived from a heavy diesel engine. To this end, we employed the mucociliary epithelium of amphibian embryos and human Calu-3 cells to examine PM mucotoxicity. Our data suggest that acute exposure to PM significantly impairs mucus secretion and results in the accumulation of mucus vesicles in the cytoplasm of goblet cells. RNA-seq analysis revealed that acute responses to PM exposure significantly altered gene expression patterns; however, known regulators of mucus production and the secretory pathway were not significantly altered. Interestingly, pretreatment with alpha-tocopherol nearly recovered the hyposecretion of mucus from both amphibian and human goblet cells. We believe this study demonstrates the mucotoxicity of PM and the protective function of alpha-tocopherol on mucotoxicity caused by acute PM exposure from heavy diesel engines

Hybrid star HD 81817 accompanied by brown dwarf or substellar companion

HD 81817 is known as a hybrid star. Hybrid stars have both cool stellar wind properties and Ultraviolet (UV) or even X-ray emission features of highly ionized atoms in their spectra. A white dwarf companion has been suggested as the source of UV or X-ray features. HD 81817 has been observed since 2004 as a part of a radial velocity (RV) survey program to search for exoplanets around K giant stars using the Bohyunsan Observatory Echelle Spectrograph at the 1.8 m telescope of Bohyunsan Optical Astronomy Observatory in Korea. We obtained 85 RV measurements between 2004 and 2019 for HD 81817 and found two periodic RV variations. The amplitudes of RV variations are around 200 m s^-1, which are significantly lower than that expected from a closely orbiting white dwarf companion. Photometric data and relevant spectral lines were also analyzed to help determine the origin of the periodic RV variations. We conclude that 627.4-day RV variations are caused by intrinsic stellar activities such as long-term pulsations or rotational modulations of surface activities based on H{\alpha} equivalent width (EW) variations of a similar period. On the other hand, 1047.1-day periodic RV variations are likely to be caused by a brown dwarf or substellar companion, which is corroborated by a recent GAIA proper motion anomaly for HD 81817. The Keplerian fit yields a minimum mass of 27.1 M_Jup, a semimajor axis of 3.3 AU, and an eccentricity of 0.17 for the stellar mass of 4.3 M_sun for HD 81817. The inferred mass puts HD 81817 b in the brown dwarf desert

Active contour configuration model for estimating the posterior ablative margin in image fusion of real-time ultrasound and 3D ultrasound or magnetic resonance images for radiofrequency ablation: an experimental study

Purpose The purpose of this study was to evaluate the accuracy of an active contour model for estimating the posterior ablative margin in images obtained by the fusion of real-time ultrasonography (US) and 3-dimensional (3D) US or magnetic resonance (MR) images of an experimental tumor model for radiofrequency ablation. Methods Chickpeas (n=12) and bovine rump meat (n=12) were used as an experimental tumor model. Grayscale 3D US and T1-weighted MR images were pre-acquired for use as reference datasets. US and MR/3D US fusion was performed for one group (n=4), and US and 3D US fusion only (n=8) was performed for the other group. Half of the models in each group were completely ablated, while the other half were incompletely ablated. Hyperechoic ablation areas were extracted using an active contour model from real-time US images, and the posterior margin of the ablation zone was estimated from the anterior margin. After the experiments, the ablated pieces of bovine rump meat were cut along the electrode path and the cut planes were photographed. The US images with the estimated posterior margin were compared with the photographs and post-ablation MR images. The extracted contours of the ablation zones from 12 US fusion videos and post-ablation MR images were also matched. Results In the four models fused under real-time US with MR/3D US, compression from the transducer and the insertion of an electrode resulted in misregistration between the real-time US and MR images, making the estimation of the ablation zones less accurate than was achieved through fusion between real-time US and 3D US. Eight of the 12 post-ablation 3D US images were graded as good when compared with the sectioned specimens, and 10 of the 12 were graded as good in a comparison with nicotinamide adenine dinucleotide staining and histopathologic results. Conclusion Estimating the posterior ablative margin using an active contour model is a feasible way of predicting the ablation area, and US/3D US fusion was more accurate than US/MR fusion

gene amplification in patients with metastatic cancer

Purpose Neurotropic tropomyosin receptor kinase (NTRK) fusions have been identified in a variety of cancers, and tyrosine kinase inhibitors targeting the tropomyosin receptor kinase (TRK) receptor are currently in clinical trials. However, no reports are available on the effects of NTRK gene amplification. Methods Samples from patients enrolled in the sequencing program were analyzed using a next-generation sequencing (NGS) cancer panel. For cases in which NTRK amplification (defined as ≥ 4.0 copies) was identified, panTRK immunohistochemical (IHC) staining of tissue microarrays was performed. Results A total of 1,250 tumor specimens collected between February 2014 and January 2016 were analyzed using the NGS cancer panel. NTRK amplification was detected in 28 cases of various types of cancer. Among 27 cases, only four were positive for pan-TRK IHC. These four cases were melanoma, sarcoma, lung cancer, and gastric cancer. We found that 2.2% of cancer patients showed NTRK amplification using NGS cancer panel and NTRK amplification resulted in protein overexpression in 14.8% of these patients. Conclusion Patients with NTRK amplification and increased TRK protein expression may be considered for inclusion in clinical trials for NTRK inhibitors

Modelling charge transport and electro-optical characteristics of quantum dot light-emitting diodes

Abstracts: Quantum dot light-emitting diodes (QD-LEDs) are considered as competitive candidate for next-generation displays or lightings. Recent advances in the synthesis of core/shell quantum dots (QDs) and tailoring procedures for achieving their high quantum yield have facilitated the emergence of high-performance QD-LEDs. Meanwhile, the charge-carrier dynamics in QD-LED devices, which constitutes the remaining core research area for further improvement of QD-LEDs, is, however, poorly understood yet. Here, we propose a charge transport model in which the charge-carrier dynamics in QD-LEDs are comprehensively described by computer simulations. The charge-carrier injection is modelled by the carrier-capturing process, while the effect of electric fields at their interfaces is considered. The simulated electro-optical characteristics of QD-LEDs, such as the luminance, current density and external quantum efficiency (EQE) curves with varying voltages, show excellent agreement with experiments. Therefore, our computational method proposed here provides a useful means for designing and optimising high-performance QD-LED devices

Truly form-factor–free industrially scalable system integration for electronic textile architectures with multifunctional fiber devices

Funding Information: This work was supported by the European Commission (H2020, 1D-NEON, grant agreement ID: 685758). J.M.K. and L.G.O. acknowledge the support from the U.K. Research and Innovation (EPSRC, EP/P027628/1). We thank Y. Bernstein and J. Faulkner for helping with grammar check. Funding Information: Acknowledgments Funding:ThisworkwassupportedbytheEuropeanCommission(H2020,1D-NEON,grant agreementID:685758).J.M.K.andL.G.O.acknowledgethesupportfromtheU.K.Researchand Innovation(EPSRC,EP/P027628/1).W ethankY .BernsteinandJ.Faulknerforhelpingwith grammarcheck.Authorcontributions:S.L.andJ.M.K.conceivedtheproject.S.L.,L.G.O.,P .B., R.Martins,andJ.M.K.supervisedtheproject.S.L.andH.L.developedF-PD.S.L.,Y .-W .L., G.-H.A., D.-W .S., J.I.S.,andS.C.developedF-SC.C.L.F ., A.S.,R.I.,P .B., andR.Martinsdevelopedfiber transistor.S.L.,H.L.,andS.C.developedF-LED.ThefiberdeviceswereevaluatedbyS.L.,H.W .C., D.-W .S., H.L.,S.J.,S.D.H.,S.Y .B., S.Z.,W .H.-C., Y .-H.S., X.-B.F ., T .H.L., J.-W .J., andY .K. The developmentofweavingprocesswasconductedbyS.L.,H.W .C., F .M.M., P .J., andV .G.C. Thelaser interconnectionwasdevelopedbyS.L.,H.W .C., K.U.,M.E.,andM.S.Thetextiledemonstrations werecharacterizedbyS.L.,H.W .C., D.-W .S., J.Y ., S.S.,U.E.,S.N.,A.C.,A.M.,R.Momentè,J.G.,N.D., S.M.,C.-H.K.,M.L.,A.N.,D.J.,M.C.,andY .C. ThismanuscriptwaswrittenbyS.L.andJ.M.K.and reviewed by H.W .C., D.-W .S., M.C.,L.G.O., P .B., E.F ., and G.A.J.A. All authors discussed the results andcommentedonthemanuscript.Competinginterests:Theauthorsdeclarethattheyhave nocompetinginterests.Dataandmaterialsavailability:Alldataneededtoevaluatethe conclusionsinthepaperarepresentinthepaperand/ortheSupplementaryMaterials. Publisher Copyright: Copyright © 2023 The Authors, some rights reserved.An integrated textile electronic system is reported here, enabling a truly free form factor system via textile manufacturing integration of fiber-based electronic components. Intelligent and smart systems require freedom of form factor, unrestricted design, and unlimited scale. Initial attempts to develop conductive fibers and textile electronics failed to achieve reliable integration and performance required for industrial-scale manufacturing of technical textiles by standard weaving technologies. Here, we present a textile electronic system with functional one-dimensional devices, including fiber photodetectors (as an input device), fiber supercapacitors (as an energy storage device), fiber field-effect transistors (as an electronic driving device), and fiber quantum dot light-emitting diodes (as an output device). As a proof of concept applicable to smart homes, a textile electronic system composed of multiple functional fiber components is demonstrated, enabling luminance modulation and letter indication depending on sunlight intensity.publishersversionpublishe

Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans

Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets.OAIID:RECH_ACHV_DSTSH_NO:T201615370RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A003535CITE_RATE:11.329FILENAME:4. ncomms12766.pdfDEPT_NM:농생명공학부EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/fce63c4a-7de7-4741-996f-d8d24af38905/linkCONFIRM:

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Practical application of DNA markers for high-throughput authentication of Panax ginseng and Panax quinquefolius from commercial ginseng products

Korean ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) are widely used medicinal plants with similar morphology but different medicinal efficacy. Roots, flowers, and processed products of Korean and American ginseng can be difficult to differentiate from each other, leading to illegal trade in which one species is sold as the other. This study was carried out to develop convenient and reliable chloroplast genome-derived DNA markers for authentication of Korean and American ginseng in commercial processed products. One codominant marker could reproducibly identify both species and intentional mixtures of the two species. We further developed a set of species-unique dominant DNA markers. Each species-specific dominant marker could detect 1% cross contamination with other species by low resolution agarose gel electrophoresis or quantitative polymerase chain reaction. Both markers were successfully applied to evaluate the original species from various processed ginseng products purchased from markets in Korea and China. We believe that high-throughput application of this marker system will eradicate illegal trade and promote confident marketing for both species to increase the value of Korean as well as American ginseng in Korea and worldwide