Ganglioside GD3 Regulates Inflammation and Epithelial-to-Mesenchymal Transition in Human Nasal Epithelial Cells.

Chronic sinusitis with nasal polyps (CRSwNP) is one of the most common chronic inflammatory diseases, and involves tissue remodeling. One of the key mechanisms of tissue remodeling is the epithelial-mesenchymal transition (EMT), which also represents one of the pathophysiological processes of CRS observed in CRSwNP tissues. To date, many transcription factors and forms of extracellular stimulation have been found to regulate the EMT process. However, it is not known whether gangliosides, which are the central molecules of plasma membranes, involved in regulating signal transmission pathways, are involved in the EMT process. Therefore, we aimed to determine the role of gangliosides in the EMT process. First, we confirmed that N-cadherin, which is a known mesenchymal marker, and ganglioside GD3 were specifically expressed in CRSwNP_NP tissues. Subsequently, we investigated whether the administration of TNF-α to human nasal epithelial cells (hNECs) resulted in the upregulation of ganglioside GD3 and its synthesizing enzyme, ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialytransferase 1 (ST8Sia1), and the consequently promoted inflammatory processes. Additionally, the expression of N-cadherin, Zinc finger protein SNAI2 (SLUG), and matrix metallopeptidase 9 (MMP-9) were elevated, but that of E-cadherin, which is known to be epithelial, was reduced. Moreover, the inhibition of ganglioside GD3 expression by the siRNA or exogenous treatment of neuraminidase 3 (NEU 3) led to the suppression of inflammation and EMT. These results suggest that gangliosides may play an important role in prevention and therapy for inflammation and EMT.

Porcine interferon-α linked to the porcine IgG-Fc induces prolonged and broad-spectrum antiviral effects against foot-and-mouth disease virus.

Foot-and-mouth disease (FMD) is an economically important disease, and the FMD virus (FMDV) can spread rapidly in susceptible animals. FMD is usually controlled through vaccination. However, commercial FMD vaccines are only effective 4-7 days after vaccination. Furthermore, FMDV comprises seven serotypes and various topotypes, and these aspects should be considered when selecting a vaccine. Antiviral agents could provide rapid and broad protection against FMDV. Therefore, this study aimed to develop a fusion protein of consensus porcine interferon-α and Fc portion of porcine antibody IgG (poIFN-α-Fc) using a baculovirus expression system to develop a novel antiviral agent against FMDV. We measured the antiviral effects of the poIFN-α-Fc protein against FMDV and the enhanced duration in vitro and in vivo. The broad-spectrum antiviral effects were tested against seven FMDV serotypes, porcine reproductive and respiratory syndrome virus (PRRSV), and bovine enterovirus (BEV). Furthermore, the early protective effects and neutralizing antibody levels were tested by co-injecting poIFN-α-Fc and an FMD-inactivated vaccine into mice or pigs. Sustained antiviral effects in pig sera and mice were observed, and pigs injected with a combination of the poIFN-α-Fc and an inactivated FMD vaccine were protected against FMDV in a dose-dependent manner at 2- and 4-days post-vaccination. In addition, combined with the inactivated FMD vaccine, poIFN-α-Fc increased the neutralizing antibody levels in mice. Therefore, poIFN-α-Fc is a potential broad-spectrum antiviral and adjuvant candidate that can be used with inactivated FMD vaccines to protect pigs against FMDV.

BacMam Expressing Highly Glycosylated Porcine Interferon Alpha Induces Robust Antiviral and Adjuvant Effects against Foot-and-Mouth Disease Virus in Pigs.

Foot-and-mouth disease (FMD) is an acute contagious disease that affects cloven-hoofed animals and has severe global economic consequences. FMD is most commonly controlled by vaccination. Currently available commercial FMD vaccines contain chemically inactivated whole viruses, which are thought to be slow acting as they are effective only 4 to 7 days following vaccination. Hence, the development of a novel rapid vaccine or alternative measures, such as antiviral agents or the combination of vaccines and antiviral agents for prompt FMD virus (FMDV) outbreak containment, is desirable. Here, we constructed a recombinant baculovirus (BacMam) expressing consensus porcine interferon alpha (IFN-α) that has three additional N-glycosylation sites driven by a cytomegalovirus immediate early (CMV-IE) promoter (Bac-Con3N IFN-α) for protein expression in mammalian cells. Bac-Con3N IFN-α expressing highly glycosylated porcine IFN-α protein increased the duration of antiviral effects. We evaluated the antiviral effects of Bac-Con3N IFN-α in swine cells and mice and observed sustained antiviral effects in pig serum; additionally, Bac-Con3N IFN-α exhibited sustained antiviral effects in vivo as well as adjuvant effects in combination with an inactivated FMD vaccine. Pigs injected with a combination of Bac-Con3N IFN-α and the inactivated FMD vaccine were protected against FMDV at 1, 3, and 7 days postvaccination. Furthermore, we observed that in combination with the inactivated FMD vaccine, Bac-Con3N IFN-α increased neutralizing antibody levels in mice and pigs. Therefore, we suggest that Bac-Con3N IFN-α is a strong potential antiviral and adjuvant candidate for use in combination with inactivated FMD vaccines to protect pigs against FMDV. IMPORTANCE Early inhibition of foot-and-mouth disease (FMD) virus (FMDV) replication in pigs is highly desirable as FMDV transmission and shedding rates are higher in pigs than in cattle. However, commercial FMD vaccines require at least 4 to 7 days postvaccination (dpv) for protection, and animals are vulnerable to heterologous viruses before acquiring high antibody levels after the second vaccination. Therefore, the development of antiviral agents for use in combination with FMD vaccines is essential. We developed a novel antiviral and immunostimulant, Bac-Con3N IFN-α, which is a modified porcine IFN-α-expressing recombinant baculovirus, to improve IFN stability and allow its direct delivery to animals. We present a promising candidate for use in combination with inactivated FMD vaccines as pigs applied to the strategy had early protection against FMDV at 1 to 7 dpv, and their neutralizing antibody levels were higher than those in pigs administered the vaccine only.

A Vaccine Strain of the A/ASIA/Sea-97 Lineage of Foot-and-Mouth Disease Virus with a Single Amino Acid Substitution in the P1 Region That Is Adapted to Suspension Culture Provides High Immunogenicity.

There are seven viral serotypes of foot-and-mouth disease virus (FMDV): A, O, C, Asia 1, and Southern African Territories 1, 2, and 3 (SAT 1-3). Unlike serotype O FMDV vaccine strains, vaccine strains of serotype A FMDV do not provide broad-range cross-reactivity in serological matching tests with field isolates. Therefore, the topotype/lineage vaccine strain circulating in many countries and a highly immunogenic strain might be advantageous to control serotype A FMDV. We developed a new vaccine strain, A/SKR/Yeoncheon/2017 (A-1), which belongs to the A/ASIA/Sea-97 lineage that frequently occurs in Asian countries. Using virus plaque purification, we selected a vaccine virus with high antigen productivity and the lowest numbers of P1 mutations among cell-adapted virus populations. The A/SKR/Yeoncheon/2017 (A-1) vaccine strain has a single amino acid mutation, VP2 E82K, in the P1 region, and it is perfectly adapted to suspension culture. The A/SKR/Yeoncheon/2017 (A-1) experimental vaccine conferred high immunogenicity in pigs. The vaccine strain was serologically matched with various field isolates in two-dimensional virus neutralization tests using bovine serum. Vaccinated mice were protected against an A/MAY/97 virus that was serologically mismatched with the vaccine strain. Thus, A/SKR/Yeoncheon/2017 (A-1) might be a promising vaccine candidate for protection against the emerging FMDV serotype A in Asia.

Chemistry of ruthenium as an electrode for metal-insulator-metal capacitor application.

Notwithstanding its excellent properties such as high work function and low resistance, Ru has not been widely applied in the preparation of electrodes for various electronic devices. This is because of the occurrence of severe morphological degradation in the actual devices employing Ru. Herein, we investigated Ru chemistry for electrode application and the degradation mechanism of Ru during subsequent processes such as thin film deposition or thermal annealing. We revealed that subsurface oxygen induces Ru degradation owing to the alteration of Ru chemistry by the pretreatment under various gas ambient conditions and due to the growth behavior of TiO2 deposited via atomic layer deposition (ALD). The degradation of Ru is successfully ameliorated by conducting an appropriate pretreatment prior to ALD. The TiO2 thin film deposited on the pretreated Ru electrode exhibited a rutile-phased crystal structure and smooth surface morphology, thereby resulting in excellent electrical properties. This paper presents an important development in the application of Ru as the electrode that can facilitate the development of various next-generation electronic devices.

Sustainable resistance switching performance from composite-type ReRAM device based on carbon Nanotube@Titania core-shell wires.

A novel nanocomposite-based non-volatile resistance switching random access memory device introducing single-walled carbon nanotube (SWCNT)@TiO2 core-shell wires was proposed for flexible electronics. The SWCNT was de-bundled by ultrasonication with sodium dodecylbenzene sulfonate (SDBS), and then the TiO2 skin layer on the SWCNT surface was successfully introduced by adding benzyl alcohol as a weak surfactant. The nanocomposite resistance switching layer was composed of the SWCNT@TiO2 core-shell wires and poly(vinyl alcohol) (PVA) matrix by a simple spin-coating method. The device exhibited reproducible resistance switching performance with a remarkably narrow distribution of operating parameters (VSET and VRESET were 2.63 ± 0.16 and 0.95 ± 0.11 V, respectively) with a large RON/ROFF ratio of 105 for 200 consecutive switching cycles. Furthermore, the excellent resistance switching behavior in our device was maintained against mechanical stress up to 105 bending test. We believe that the nanocomposite memory device with SWCNT@TiO2 core-shell wires would be a critical asset to realize practical application for a flexible non-volatile memory field.

Analysis of Amino Acid Mutations of the Foot-and-Mouth Disease Virus Serotype O Using both Heparan Sulfate and JMJD6 Receptors.

Foot-and-mouth disease (FMD) is an economically devastating animal disease. Adapting the field virus to cells is critical to the vaccine production of FMD viruses (FMDV), and heparan sulfate (HS) and Jumonji C-domain-containing protein 6 (JMJD6) are alternative receptors of cell-adapted FMDV. We performed serial passages of FMDV O/SKR/Andong/2010, classified as the O/Mya-98 topotype/lineage and known as a highly virulent strain, to develop a vaccine seed virus. We traced changes in the amino acid sequences of the P1 region, plaque phenotypes, and the receptor usage of the viruses, and then structurally analyzed the mutations. VP3 H56R and D60G mutations were observed in viruses using the HS receptor and led to changes in the hydrogen bonding between VP3 56 and 60. A VP1 P208L mutation was observed in the virus using the JMJD6 receptor during cell adaptation, enabling the interaction with JMJD6 through the formation of a new hydrogen bond with JMJD6 residue 300. Furthermore, VP1 208 was near the VP1 95/96 amino acids, previously reported as critical mutations for JMJD6 receptor interactions. Thus, the mutation at VP1 208 could be critical for cell adaptation related to the JMJD6 receptor and may serve as a basis for mechanism studies on FMDV cell adaptation.

Vaccine strain of O/ME-SA/Ind-2001e of foot-and-mouth disease virus provides high immunogenicity and broad antigenic coverage.

Foot-and-mouth disease (FMD) is an economically devastating animal disease. There are seven serotypes, A, O, C, Asia 1, Southern African Territories 1, 2, and 3 (SAT1, SAT2, and SAT3), among which serotype O shows the greatest distribution worldwide. Specifically, the O/ME-SA/Ind-2001 lineage, which was reported in India in 2001, has since emerged worldwide, with the O/ME-SA/Ind-2001d and O/ME-SA/Ind-2001e sublineages recently emerging in North Africa, Middle East Asia, Southeast Asia, and East Asia. The antigenic relationship (r1) value for the O1 Manisa and O/Mya-98 lineage inactivated vaccine against various O/ME-SA/Ind-2001 lineages of FMDV isolates, were matching (r1 > 0.3) or non-matching (r1 < 0.3), indicating that the vaccine based on the O/ME-SA/Ind-2001 lineage FMDV, is valuable. In this study, we developed a new vaccine strain, O/SKR/Boeun/2017 isolate, belonging to the O/ME-SA/Ind-2001e sublineage as an outbreak of this sublineage occurred in 2017 in the Boeun county of the Republic of Korea (O/SKR/Boeun/2017). This experimental vaccine exhibited high immunogenicity in pigs and cattle and was antigenically matched with representative FMDV lineages (ME-SA, O/ME-SA/PanAsia, O/SEA/Mya-98, and O/Cathay) in Asia, as demonstrated by two-dimensional virus neutralization tests (2D-VNT). In addition, a 100% survival rate in C56BL/6 mice vaccinated with 1/15 of a pig dose was observed following challenge with FMDV O/VIT/2013 (O/ME-SA/PanAsia) at 10 days post-vaccination. Further, we analyzed the major antigenic sites of the O/SKR/Boeun/2017 vaccine strain as well as other viruses, by 2D-VNT. These results suggest that the O/ME-SA/Ind-2001e sublineage is a promising vaccine strain candidate in Asia, and other countries, for protection against the emerging FMDV.

Needleless intradermal vaccination for foot-and-mouth disease induced granuloma-free effective protection in pigs.

Vaccination is one of the most effective ways of controlling and preventing foot-and-mouth disease (FMD) outbreaks. The effective prevention of this disease requires the use of high-quality vaccines to meet the criteria that enable customers to use them simply. The administration of FMD vaccines containing oil-based adjuvants in pigs can induce the formation of granuloma in the muscle of the vaccinated, which makes these vaccines a less preferable option. Therefore, it is important to establish an FMD vaccine and vaccine delivery tool that offers better immunity and safer application. This study compared the immune responses of intramuscular and needleless intradermal vaccination in pigs. When the same amount of an FMD virus (FMDV) antigen was administered to pigs, both the intradermally and intramuscularly vaccinated groups were protected completely against a challenge of the homologous FMDV, but the intramuscularly vaccinated group showed an overall higher level of neutralizing antibodies. Importantly, the formation of granuloma in muscle could be excluded in the intradermally vaccinated group. Of the oil-based adjuvants selected in this study, ISA 207 was effective in eliciting immunogenicity in intradermal vaccination. In conclusion, a new vaccine formula can be chosen for the delivery of intradermal route to exclude the possibility of local reactions in the muscle and generate protective immunity against an FMDV challenge.

One-half of Korean adults studied had marginal vitamin B12 status assessed by plasma vitamin B12.

Information is limited on the current vitamin B12 status of South Koreans, including the results of biochemical indices. The objective of this study was to assess vitamin B12 status with vitamin B12 intake, major food sources, and plasma vitamin B12 concentration in Korean adults. We hypothesized that vitamin B12 intake and status would be different between sex and age groups. Three consecutive 24-hour recalls and fasting blood samples were obtained from healthy 20- to 64-year-old adults (N=141). The dietary vitamin B12 intake of the men (10.77±6.11 µg/d) was significantly higher than that of the women (7.93±5.01 µg/d). The mean dietary vitamin B12 intake was significantly lower in the subjects aged 20-29 years than in the subjects aged 50-64 years. Only 2.1% of the subjects consumed less vitamin B12 than the estimated average requirement for Koreans. The top 4 major food sources of vitamin B12 were seafood, which provided 35.36% of the dietary vitamin B12 intake. There was no significant difference in plasma vitamin B12 concentration between sex and among age groups. Approximately 17% of total subjects had a plasma vitamin B12 concentration <125 pmol/L, indicating vitamin B12 deficiency, and 36.2% had marginal vitamin B12 status (125 to <250 pmol/L). The reported vitamin B12 intake was affected by both sex and age. However, plasma vitamin B12 concentration did not differ between sex and among age groups. One-half of the subjects had marginal vitamin B12 status using plasma vitamin B12.

Recent Trends in Nanomaterials-Based Colorimetric Detection of Pathogenic Bacteria and Viruses.

Rapid, sensitive, selective, convenient, and cost-effective pathogen diagnosis is important to prevent further spread of pandemic diseases, minimize social and economic losses, and to facilitate right clinical therapy. Over the past few years, various sensor-based diagnostic systems outperforming conventional pathogenic diagnostic assays have been developed. Among them, colorimetric biosensors detecting target molecules by the naked eye have attracted much attention due to their simplicity, practicality, and cost-effectiveness. Recently, nanomaterials have been adopted as a versatile signal transduction and amplification tool for rapid and sensitive detection of pathogenic bacteria and viruses. Here, recent trends and advances are reviewed in detecting and diagnosing pathogenic bacteria and viruses using colorimetric biosensors employing various nanomaterials. In addition, it is discussed how nanomaterials and bioreceptors can be better integrated together to develop rapid and sensitive colorimetric detection system in the future.

Bacterial cellulose as an example product for sustainable production and consumption.

Life cycle of bacterial cellulose. Sustainable production and consumption of bio-based products are showcased using bacterial cellulose as an example.

A Mobile Application for Wound Assessment and Treatment: Findings of a User Trial.

The D+Wound Solution is a mobile phone application (app) that assists users in the assessment and treatment of the wound. The app has 6 components for assessment: need for debridement, infection control, revascularization, and exudate control; whether it is chronic; and finally, the top surface of the skin. These components are named D.I.R.E.C.T. The app makes you review these components as an algorithm to provide a reasonable solution for dressing. It is designed to understand the status of the wound and provide a practical treatment idea for wound care providers. A total of 118 nurses were divided into 2 groups, designated as experienced and less-experienced groups, and surveyed. Both groups found the app to be helpful in making a treatment plan. However, the less-experienced group found it to be significantly more useful in assessing the wound ( P = .026) but difficult to understand the logic. The experienced group found the logic to be significantly easier to understand ( P = .018) and had significantly higher similarities ( P = .015) in treatment protocols compared with the less-experienced group. We may conclude that this app has a logical algorithm resembling experienced wound caregivers and is more useful in the less-experienced group.

The effects of exercise training and acute exercise duration on plasma folate and vitamin B12.

BACKGROUND/OBJECTIVES: Energy production and the rebuilding and repair of muscle tissue by physical activity require folate and vitamin B12 as a cofactor. Thus, this study investigated the effects of regular moderate exercise training and durations of acute aerobic exercise on plasma folate and vitamin B12 concentrations in moderate exercise trained rats. MATERIALS/METHODS: Fifty rats underwent non-exercise training (NT, n = 25) and regular exercise training (ET, n = 25) for 5 weeks. The ET group performed moderate exercise on a treadmill for 30 min/day, 5 days/week. At the end of week 5, each group was subdivided into 4 groups: non-exercise and 3 exercise groups. The non-exercise group (E0) was sacrificed without exercising and the 3 exercise groups were sacrificed immediately after exercising on a treadmill for 0.5 h (E0.5), 1 h (E1), and 2 h (E2). Blood samples were collected and plasma folate and vitamin B12 were analyzed. RESULTS: After exercise training, plasma folate level was significantly lower and vitamin B12 concentration was significantly higher in the ET group compared with the NT group (P < 0.05). No significant associations were observed between plasma folate and vitamin B12 concentrations. In both the NT and ET groups, plasma folate and vitamin B12 were not significantly changed by increasing duration of aerobic exercise. Plasma folate concentration of E0.5 was significantly lower in the ET group compared with that in the NT group. Significantly higher vitamin B12 concentrations were observed in the E0 and E0.5 groups of the ET group compared to those of the NT group. CONCLUSION: Regular moderate exercise training decreased plasma folate and increased plasma vitamin B12 levels. However, no significant changes in plasma folate and vitamin B12 concentrations were observed by increasing duration of acute aerobic exercise.

Robust Real-Time Reverse Transcription-PCR for Detection of Foot-and-Mouth Disease Virus Neutralizing Carryover Contamination.

During an outbreak of foot-and-mouth disease (FMD), real-time reverse transcription-PCR (rRT-PCR) is the most commonly used diagnostic method to detect viral RNA. However, while this assay is often conducted during the outbreak period, there is an inevitable risk of carryover contamination. This study shows that the carryover contamination can be prevented by the use of target-specific restriction endonuclease in that assay.

Complete Genome Sequence of a Foot-and-Mouth Disease Virus of Serotype A Isolated from Vietnam in 2013.

The complete genome sequence of a foot-and-mouth disease virus (FMDV) found in an isolate collected in northern Vietnam in 2013 appears to be closely related to a genetic cluster formed with isolates from China, Mongolia, and Russia in 2013. All of these are classified to fall within the Sea-97 lineage, for which little complete genome data are available.

Antigenic properties and virulence of foot-and-mouth disease virus rescued from full-length cDNA clone of serotype O, typical vaccine strain.

We cloned the full-length cDNA of O Manisa, the virus for vaccinating against foot-and-mouth disease. The antigenic properties of the virus recovered from the cDNA were similar to those of the parental virus. Pathogenesis did not appear in the pigs, dairy goats or suckling mice, but neutralizing antibodies were raised 5-6 days after the virus challenge. The utilization of O Manisa as a safe vaccine strain will increase if recombinant viruses can be manipulated by inserting or removing a marker gene for differential serology or replacing the protective gene from another serotype.

Monoclonal and polyclonal antibodies specific for foot and mouth disease virus type A and type O VP1.

The foot and mouth disease virus (FMDV) is an RNA virus composed of single stranded positive sense RNA. FMDV has been known to infect cloven-hoofed animals, including pigs, cattle, and sheep. FMDV is rapidly spreading outward to neighboring regions, often leading to a high mortality rate. Thus, early diagnosis of FMDV is critical to suppress propagation of FMDV and minimize economic losses. In this study, we report the generation and characterization of polyclonal and six monoclonal antibodies against VP1 through immunoblotting and immunofluorescence microscopy analyses. These VP1 antibodies will be useful as tools to detect serotypes A and O of FMDVs for diagnostic usage.