Severe fever with thrombocytopenia syndrome (SFTS) is caused by infection with Dabie bandavirus formerly SFTS virus (SFTSV) and is an emerging zoonotic disease. Dogs can be infected with SFTSV, but ...its pathogenicity and transmissibility have not been fully elucidated. In experiment 1, immunocompetent dogs were intramuscularly inoculated with SFTSV. In experiment 2, immunosuppressed dogs (immunosuppressed group; oral azathioprine 5 mg/kg/day for 30 days) were intramuscularly inoculated with SFTSV. Both immunosuppressed and immunocompetent contact dogs were co‐housed with the SFTSV‐inoculated dogs that had been immunosuppressed. Immunocompetent SFTSV‐infected dogs did not show any clinical symptom. However, immunosuppressed SFTSV‐infected dogs showed high fever and weight loss without lethality. In all SFTSV‐infected dogs, viral RNA could be measured in the serum only after 3 days post infection (DPI) and neutralizing antibodies were detected in the serum beginning 9 DPI. SFTSV shedding in the urine and faeces of some infected dogs occurred between 4 and 6 DPI. The immunocompromised SFTSV‐infected dogs showed thrombocytopenia beginning 3 DPI to the end of the experiment (24 DPI). We confirmed SFTSV transmission to one of three immunocompetent co‐housed dogs. This dog showed a high fever, weight loss, and shed viral RNA by urine. Viral RNA and neutralizing antibodies were also detected in the serum. These results demonstrated that intramuscular inoculation with SFTSV induced minor clinical symptoms in dogs, and intraspecies SFTSV transmission in dogs can occur by contact.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Esophageal cancer (EC) is one of the leading causes to cancer death in the worldwide and major population of EC is esophageal squamous cell carcinoma (ESCC). Still, ESCC‐targeted therapy has not been ...covered yet. In the present study we have identified that Licochalcone B (Lico B) inhibited the ESCC growth by directly blocking the Janus kinase (JAK) 2 activity and its downstream signaling pathway. Lico B suppressed KYSE450 and KYSE510 ESCC cell growth, arrested cell cycle at G2/M phase and induced apoptosis. Direct target of Lico B was identified by kinase assay and verified with in vitro and ex vivo binding. Computational docking model predicted for Lico B interaction to ATP‐binding pocket of JAK2. Furthermore, treatment of JAK2 clinical medicine AZD1480 to ESCC cells showed similar tendency with Lico B. Thus, JAK2 downstream signaling proteins phosphorylation of STAT3 at Y705 and S727 as well as STAT3 target protein Mcl‐1 expression was decreased with treatment of Lico B. Our results suggest that Lico B inhibits ESCC cell growth, arrests cell cycle and induces apoptosis, revealing the underlying mechanism involved in JAK2/STAT3 signaling pathways after Lico B treatment. It might provide potential role of Lico B in the treatment of ESCC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Patients with non‐small‐cell lung cancer (NSCLC) containing epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to tyrosine kinase inhibitor gefitinib; ...however, the treatment is less effective over time. Gefitinib resistance mechanisms include MET gene amplification. A therapeutic strategy targeting MET as well as EGFR can overcome resistance to gefitinib. In the present study we identified Echinatin (Ecn), a characteristic chalcone in licorice, which inhibited both EGFR and MET and strongly altered NSCLC cell growth. The antitumor efficacy of Ecn against gefitinib‐sensitive or –resistant NSCLC cells with EGFR mutations and MET amplification was confirmed by suppressing cell proliferation and anchorage‐independent colony growth. During the targeting of EGFR and MET, Ecn significantly blocked the kinase activity, which was validated with competitive ATP binding. Inhibition of EGFR and MET by Ecn decreases the phosphorylation of downstream target proteins ERBB3, AKT and ERK compared with total protein expression or control. Ecn induced the G2/M cell cycle arrest, and apoptosis via the intrinsic pathway of caspase‐dependent activation. Ecn induced ROS production and GRP78, CHOP, DR5 and DR4 expression as well as depolarized the mitochondria membrane potential. Therefore, our results suggest that Ecn is a promising therapeutic agent in NSCLC therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although hexagonal boron nitride (h-BN) is a good candidate for gate-insulating materials by minimizing interaction from substrate, further applications to electronic devices with available ...two-dimensional semiconductors continue to be limited by flake size. While monolayer h-BN has been synthesized on Pt and Cu foil using chemical vapour deposition (CVD), multilayer h-BN is still absent. Here we use Fe foil and synthesize large-area multilayer h-BN film by CVD with a borazine precursor. These films reveal strong cathodoluminescence and high mechanical strength (Young's modulus: 1.16 ± 0.1 TPa), reminiscent of formation of high-quality h-BN. The CVD-grown graphene on multilayer h-BN film yields a high carrier mobility of ∼ 24,000 cm(2) V(-1) s(-1) at room temperature, higher than that (∼ 13,000 (2) V(-1) s(-1)) with exfoliated h-BN. By placing additional h-BN on a SiO2/Si substrate for a MoS2 (WSe2) field-effect transistor, the doping effect from gate oxide is minimized and furthermore the mobility is improved by four (150) times.
Of 103 serum samples collected from dogs in South Korea, 3 (2.9%) were positive for severe fever with thrombocytopenia syndrome virus (SFTSV) and 22 (21.4%) were positive for antibodies against ...SFTSV. A dog-derived isolate of SFTSV clustered with many South Korea SFTSV strains in the Japanese clade.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report the synthesis of centimeter-scale, uniform 1T′- and 2H-MoTe2 thin films via the tellurization of Mo thin films. 1T′-MoTe2 was initially grown and converted gradually to 2H-MoTe2 over a ...prolonged growth time under a Te atmosphere. Maintaining excessive Te was essential for obtaining the stable stoichiometric 2H-MoTe2 phase. Further annealing under a lower partial pressure of Te at the same temperature, followed by a rapid quenching, led to the reverse phase transition from 2H-MoTe2 to 1T′-MoTe2. The orientation of the 2H-MoTe2 film was determined by the tellurization rate. Slow tellurization was the key for obtaining a highly oriented 2H-MoTe2 film over the entire area, while fast tellurization led to a 2H-MoTe2 film with a randomly oriented c-axis.
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IJS, KILJ, NUK, PNG, UL, UM
Although functional association between Wnt signaling and bone homeostasis has been well described through genetic ablation of Wntless (Wls), the mechanisms of how osteoblastic Wls regulates the fate ...of bone marrow stromal cells (BMSCs) and hematopoietic stem cells (HSCs) in relation to age are not yet understood. Here, we generated Col2.3‐Cre;Wlsfl/fl mice that were free from premature lethality and investigated age‐related impacts of osteoblastic Wls deficiency on hematopoiesis, BM microenvironment, and maintenance of BMSCs (also known as BM‐derived mesenchymal stem/stromal cells) and HSCs. Ablation of osteoblastic Wls deteriorated BM microenvironment and bone mass accrual along with age‐independent effects on functions of BMSCs. Osteoblastic Wls deletion impaired HSC repopulation and progeny with skewing toward myeloid lineage cells only at old stage. As proven by hallmarks of stem cell senescence, osteoblastic Wls ablation differentially induced senescence of BMSCs and HSCs in relation to age without alteration in their BM frequency. Our findings support that deletion of Wls in Col2.3‐expressing cells induces senescence of BMSCs and impairs BM microenvironment in age‐independent manner. Overall, long‐term deterioration in BM microenvironment contributes to age‐related HSC senescence with impaired progeny and hematopoiesis, which also suggests possible roles of osteoblastic Wls on the maintenance of BM HSCs.
We investigated age‐related impacts of osteoblastic Wls deficiency on bone marrow (BM) and on the functions of BM‐conserved stem cells. Wls deletion in Col2.3‐expressing cells induces oxidative stress and senescence of bone marrow stromal cells (BMSCs) and impairs BM microenvironment and bone mass accrual in age‐independent manner. However, this ablation causes senescence of hematopoietic stem cells (HSCs) and deteriorates hematopoietic progenitor cell progeny and hematopoietic development only at old age.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Anaplasmosis, cat-scratch disease, and Lyme disease are emerging vector-borne infectious diseases in Korea. Although the prevalence of vector-borne pathogens (VBPs) in domestic animals and vector ...arthropods has been documented, there is limited information on the presence of VBPs in wild animals. The raccoon dog (
), a wild canid found in East Asia and Europe, represents a potential wildlife reservoir for zoonotic diseases. To investigate the prevalence of VBPs in raccoon dogs, 142 carcasses and 51 blood samples from captured raccoon dogs were collected from 2003 to 2010 and from 2008 to 2009, respectively, in Korea. In addition, 105
(14 larvae, 43 nymphs, 32 males, and 16 females) and nine
(all female) were collected from three raccoon dogs. Samples of the spleen and blood were tested for the presence of VBPs by using nested polymerase chain reaction. Among the samples collected from 193 raccoon dogs and 114 ticks, two samples were positive for
, four for
, two for
, and two for
. To the best of our knowledge, this study is the largest survey of raccoon dogs aimed at the analysis of VBPs in this species. Moreover, the present study represents the first identification of
,
, and
in raccoon dogs in their native habitat (East Asia).
Deoxypodophyllotoxin (DPT) derived from
(L.) Hoffm has attracted considerable interest in recent years because of its anti-inflammatory, antitumor, and antiviral activity. However, the mechanisms ...underlying DPT mediated antitumor activity have yet to be fully elucidated in esophageal squamous cell carcinoma (ESCC). We show here that DPT inhibited the kinase activity of epidermal growth factor receptor (EGFR) directly, as well as phosphorylation of its downstream signaling kinases, AKT, GSK-3β, and ERK. We confirmed a direct interaction between DPT and EGFR by pull-down assay using DPT-beads. DPT treatment suppressed ESCC cell viability and colony formation in a time- and dose-dependent manner, as shown by MTT analysis and soft agar assay. DPT also down-regulated cyclin B1 and cdc2 expression to induce G2/M phase arrest of the cell cycle and upregulated p21 and p27 expression. DPT treatment of ESCC cells triggered the release of cytochrome c via loss of mitochondrial membrane potential, thereby inducing apoptosis by upregulation of related proteins. In addition, treatment of KYSE 30 and KYSE 450 cells with DPT increased endoplasmic reticulum stress, reactive oxygen species generation, and multi-caspase activation. Consequently, our results suggest that DPT has the potential to become a new anticancer therapeutic by inhibiting EGFR mediated AKT/ERK signaling pathway in ESCC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The field distribution of the oral rabies vaccine is effective in controlling the spread of rabies. The present study aimed to investigate efficient distribution locations based on the environment, ...contact rate, and consumption by target wildlife species in South Korea. The target species (Korean raccoon dogs, domestic dogs, and feral cats) accounted for 945 contacts (52.2%), in total 1,808 contacts. There were 863 (47.8%) contacts by non-target species. Raccoon dogs, a main reservoir of rabies in South Korea, had the highest contact rate (34.1%) among all species. The contact rate by target species was highest at riparian sites and bushy mountainous vegetation, where raccoon dogs are abundant. There was remarkable contact by raccoon dogs in mountainous areas below 150 m with bushy vegetation. Our results indicate that these locations are efficient areas for vaccine distribution, especially targeting the raccoon dog. Vaccines were continuously contacted with intervals ranging from one hour to one day. Vaccines at 94.4% of the distribution points were completely consumed within two weeks. The mean consumption rate was 95.2 ± 1.93% during the overall study period. These findings suggest that the oral rabies vaccine attracts wildlife including domestic dogs and feral cats. Our results suggest that low sections of mountainous areas with bushy vegetation and/or neighboring riparian areas are rich in target wildlife species (especially raccoon dogs) and are efficient locations for vaccine distribution to control rabies in South Korea.
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