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Aluminium–copper composite materials were successfully fabricated using spark plasma sintering with Al and Cu powders as the raw materials. Al–Cu composite powders were fabricated through a ball milling process, and the effect of the Cu content was investigated. Composite materials composed of Al–20Cu, Al–50Cu, and Al–80Cu (vol.%) were sintered by a spark plasma sintering process, which was carried out at 520 °C and 50 MPa for 5 min. The phase analysis of the composite materials by X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS) indicated that intermetallic compounds (IC) such as CuAl2 and Cu9Al4 were formed through reactions between Cu and Al during the spark plasma sintering process. The mechanical properties of the composites were analysed using a Vickers hardness tester. The Al–50Cu composite had a hardness of approximately 151 HV, which is higher than that of the other composites. The thermal conductivity of the composite materials was measured by laser flash analysis, and the highest value was obtained for the Al–80Cu composite material. This suggests that the Cu content affects physical properties of the Al–Cu composite material as well as the amount of intermetallic compounds formed in the composite material.

L -Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of L -ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of L -ascorbic acid. In this study, we demonstrate that L -ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of L -ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose L -ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose L -ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of L -ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that L -ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.

Paramyxoviruses, negative-sense single-stranded RNA viruses, pose a critical threat to human public health. Currently, 78 species, 17 genera, and 4 subfamilies of paramyxoviruses are harbored by multiple natural reservoirs, including rodents, bats, birds, reptiles, and fish. Henipaviruses are critical zoonotic pathogens that cause severe acute respiratory distress and neurological diseases in humans. Using reverse transcription-polymerase chain reaction, 115 Crocidura species individuals were examined for the prevalence of paramyxovirus infections. Paramyxovirus RNA was observed in 26 (22.6%) shrews collected at five trapping sites, Republic of Korea. Herein, we report two genetically distinct novel paramyxoviruses (genus: Henipavirus): Gamak virus (GAKV) and Daeryong virus (DARV) isolated from C. lasiura and C. shantungensis, respectively. Two GAKVs and one DARV were nearly completely sequenced using next-generation sequencing. GAKV and DARV contain six genes (3′-N-P-M-F-G-L-5′) with genome sizes of 18,460 nucleotides and 19,471 nucleotides, respectively. The phylogenetic inference demonstrated that GAKV and DARV form independent genetic lineages of Henipavirus in Crocidura species. GAKV-infected human lung epithelial cells elicited the induction of type I/III interferons, interferon-stimulated genes, and proinflammatory cytokines. In conclusion, this study contributes further understandings of the molecular prevalence, genetic characteristics and diversity, and zoonotic potential of novel paramyxoviruses in shrews.

Flu disease, with high mortality and morbidity, is caused by the influenza virus. Influenza infections are most effectively prevented through vaccination, but it requires annual reformulation due to the antigenic shift or drift of hemagglutinin and neuraminidase proteins. Increasing resistance to available anti-influenza drugs was also recently reported. The M2 surface protein of the influenza virus is an attractive target for universal vaccine development as it is highly conserved and multifunctional throughout the viral life cycle. This study aimed to discover a single-chain variable fragment (scFv) targeting the M2 protein of influenza A H1N1/PR8, showing neutralizing activity through plaque inhibition in virus replication. Several candidates were isolated using bio-panning, including scFv and single-domain V L target M2 protein, which was displayed on the yeast surface. The scFv/V L proteins were obtained with high yield and high purity through soluble expression in E . coli BL21 (DE3) pLysE strains. A single-domain V L -M2-specific antibody, NVLM10, exhibited the highest binding affinity to influenza virions and was engineered into a bivalent format (NVL2M10) to improve antigen binding. Both antibodies inhibited virus replication in a dose-dependent manner, determined using plaque reduction- and immunocytochemistry assays. Furthermore, bivalent anti-M2 single-domain V L antibodies significantly reduced the plaque number and viral HA protein intensity as well as viral genome ( HA and NP ) compared to the monovalent single-domain V L antibodies. This suggests that mono- or bivalent single-domain V L antibodies can exhibit neutralizing activity against influenza virus A, as determined through binding to virus particle activity.

Emerging and re-emerging RNA viruses pose significant public health, economic, and societal burdens. Hantaviruses (genus Orthohantavirus , family Hantaviridae , order Bunyavirales ) are enveloped, negative-sense, single-stranded, tripartite RNA viruses that are emerging zoonotic pathogens harbored by small mammals such as rodents, bats, moles, and shrews. Orthohantavirus infections cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome in humans (HCPS). Active targeted surveillance has elucidated high-resolution phylogeographic relationships between patient- and rodent-derived orthohantavirus genome sequences and identified the infection source by temporally and spatially tracking viral genomes. Active surveillance of patients with HFRS entails 1) recovering whole-genome sequences of Hantaan virus (HTNV) using amplicon (multiplex PCR-based) next-generation sequencing, 2) tracing the putative infection site of a patient by administering an epidemiological questionnaire, and 3) collecting HTNV-positive rodents using targeted rodent trapping. Moreover, viral genome tracking has been recently performed to rapidly and precisely characterize an outbreak from the emerging virus. Here, we reviewed genomic epidemiological and active surveillance data for determining the emergence of zoonotic RNA viruses based on viral genomic sequences obtained from patients and natural reservoirs. This review highlights the recent studies on tracking viral genomes for identifying and characterizing emerging viral outbreaks worldwide. We believe that active surveillance is an effective method for identifying rodent-borne orthohantavirus infection sites, and this report provides insights into disease mitigation and preparedness for managing emerging viral outbreaks.

Orthohantaviruses, negative-sense single-strand tripartite RNA viruses, are a global public health threat. In humans, orthohantavirus infection causes hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Whole-genome sequencing of the virus helps in identification and characterization of emerging or re-emerging viruses. Next-generation sequencing (NGS) is a potent method to sequence the viral genome, using molecular enrichment methods, from clinical specimens containing low virus titers. Hence, a comparative study on the target enrichment NGS methods is required for whole-genome sequencing of orthohantavirus in clinical samples. In this study, we used the sequence-independent, single-primer amplification, target capture, and amplicon NGS for whole-genome sequencing of Hantaan orthohantavirus (HTNV) from rodent specimens. We analyzed the coverage of the HTNV genome based on the viral RNA copy number, which is quantified by real-time quantitative PCR. Target capture and amplicon NGS demonstrated a high coverage rate of HTNV in Apodemus agrarius lung tissues containing up to 10 3 –10 4 copies/μL of HTNV RNA. Furthermore, the amplicon NGS showed a 10-fold (10 2 copies/μL) higher sensitivity than the target capture NGS. This report provides useful insights into target enrichment NGS for whole-genome sequencing of orthohantaviruses without cultivating the viruses.

Orthohantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. Despite the significant mortality and morbidity, effective antiviral therapeutics or vaccines for orthohantavirus infections are currently unavailable. This study aimed to investigate the prevalence of HFRS-associated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern Republic of Korea (ROK). We collected small mammals on Jeju Island during 2018-2020. We detected the Hantaan virus (HTNV)-specific antibodies and RNA using an indirect immunofluorescence assay test and reverse transcription-polymerase chain reaction on Apodemus agrarius chejuensis (A. chejuensis). The prevalence of anti-HTNV antibodies among rodents was 14.1%. A total of six seropositive mice harbored HTNV RNA. The amplicon-based next-generation sequencing provided nearly full-length tripartite genomic sequences of six HTNV harbored by A. chejuensis. Phylogenetic and tanglegram analyses were conducted for inferring evolutionary relationships between orthohantaviruses with their reservoir hosts. Phylogenetic analyses identified a novel distinct HTNV genotype. The detected HTNV genomic sequences were phylogenetically related to a viral sequence derived from HFRS patient in southern ROK. Tanglegram analysis demonstrated the segregation of HTNV genotypes corresponding to Apodemus spp. divergence. Our results suggest that A. chejuensis-borne HTNV may be a potential etiological agent of HFRS in southern ROK. Ancestral HTNV may infect A. chejuensis prior to geological isolation between the Korean peninsula and Jeju Island, supporting the co-evolution of orthohantaviruses and rodents. This study arises awareness among physicians for HFRS outbreaks in southern ROK.

Developing thin-film sheets made of oxide-based solid electrolytes is essential for fabricating surface-mounted ultracompact multilayer oxide solid-state batteries. To this end, solid-electrolyte slurry must be optimized for excellent dispersibility. Although oxide-based solid electrolytes for multilayer structures require sintering, high processing temperatures cause problems such as Li-ion volatilization and reactions with graphite anodes. Thus, low-temperature sinterable oxide-based solid-electrolyte materials should be devised. We successfully developed the conditions for producing thin films from 21 μm thick solid-electrolyte sheets of Li2O-B2O3-Al2O3, one of the most promising candidates for multilayer solid-state batteries. A comprehensive analysis of the fabricated thin films included X-ray diffraction (XRD) to confirm their amorphous structure, scanning electron microscopy (SEM) for particle morphology, and contact angle measurements to verify surface hydrophilicity. Evaluation of a 32-layer bulk sample of solid-electrolyte sheets revealed an ionic conductivity of 2.33 × 10−7 S/cm and charge transfer resistance of 100.1 kΩ at a sintering temperature of 430 °C. Based on these results, cathode and anode active materials will be applied to develop high-energy-density multilayer ceramic batteries with hundreds of layers in future work.

In this study, to fabricate neutron shielding material, boron carbide (B4C)-reinforced aluminum (Al) alloy composites were successfully fabricated by stir casting followed by a hot rolling process. Microstructural analysis of B4C/Al6061 composites with different volume fractions (5, 10, 20, 25, and 30%) revealed that the composites had volume ratios similar to the target volume ratios of B4C. Furthermore, B4C reinforcements were uniformly dispersed in the Al matrix, forming multi-interfacial layers of Al4C3/(Ti,Cr)B2. The interfacial layer generated during stir casting maintained its own structure after the hot rolling process, indicating strong interfacial bonding strength. The tensile strengths of the B4C/Al6061 composites increased to 20 vol.% and stayed above the value for Al6061, even reaching 30 vol.%. The measured thermal neutron shielding rate increased with increasing B4C content, and the highest thermal neutron shielding rate was observed at 30 vol.% composite, which corresponds to 95.6% neutron shielding at 0.158-cm thickness.

Background Whole-genome sequencing plays a critical role in the genomic epidemiology intended to improve understanding the spread of emerging viruses. Dabie bandavirus, causing severe fever with thrombocytopenia syndrome (SFTS), is a zoonotic tick-borne virus that poses a significant public health threat. We aimed to evaluate a novel amplicon-based nanopore sequencing tool to obtain whole-genome sequences of Dabie bandavirus, also known as SFTS virus (SFTSV), and investigate the molecular prevalence in wild ticks, Republic of Korea (ROK). Principal findings A total of 6,593 ticks were collected from Gyeonggi and Gangwon Provinces, ROK in 2019 and 2020. Quantitative polymerase chain reaction revealed the presence of SFSTV RNA in three Haemaphysalis longicornis ticks. Two SFTSV strains were isolated from H. longicornis captured from Pocheon and Cheorwon. Multiplex polymerase chain reaction-based nanopore sequencing provided nearly full-length tripartite genome sequences of SFTSV within one hour running. Phylogenetic and reassortment analyses were performed to infer evolutionary relationships among SFTSVs. Phylogenetic analysis grouped SFTSV Hl19-31-4 and Hl19-31-13 from Pocheon with sub-genotype B-1 in all segments. SFTSV Hl20-8 was found to be a genomic organization compatible with B-1 (for L segment) and B-2 (for M and S segments) sub-genotypes, indicating a natural reassortment between sub-genotypes. Conclusion/Significance Amplicon-based next-generation sequencing is a robust tool for whole-genome sequencing of SFTSV using the nanopore platform. The molecular prevalence and geographical distribution of SFTSV enhanced the phylogeographic map at high resolution for sophisticated prevention of emerging SFTS in endemic areas. Our findings provide important insights into the rapid whole-genome sequencing and genetic diversity for the genome-based diagnosis of SFTSV in the endemic outbreak.