Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS; OMIM #260400) is caused by variants in SBDS (Shwachman-Bodian-Diamond syndrome gene), which encodes a protein that plays an important role in ribosome assembly. Recent reports suggest that recessive variants in EFL1 are also responsible for SDS. However, the precise genetic mechanism that leads to EFL1-induced SDS remains incompletely understood. Here we present 3 unrelated Korean SDS patients who carry biallelic pathogenic variants in EFL1 with biased allele frequencies, resulting from a bone marrow-specific somatic uniparental disomy in chromosome 15. The recombination events generated cells that were homozygous for the relatively milder variant, allowing for the evasion of catastrophic physiologic consequences. However, the milder EFL1 variant was still solely able to impair 80S ribosome assembly and induce SDS features in cell line and animal models. The loss of EFL1 resulted in a pronounced inhibition of terminal oligopyrimidine element-containing ribosomal protein transcript 80S assembly. Therefore, we propose a more accurate pathogenesis mechanism of EFL1 dysfunction that eventually leads to aberrant translational control and ribosomopathy.

Comparison of the Prevalence of Antibodies to SARS-CoV-2 in 9954 Recruits in the Korean Army Training Center with the General Korean Population of Equivalent Age Between September and November, 2020.

BACKGROUND Understanding the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be a useful tool when studying spread of the disease. This study aimed to compare the prevalence of antibodies to SARS-CoV-2 in 9954 recruits in the Korean Army Training Center with the general Korean population age <30 years between September and November, 2020. MATERIAL AND METHODS At the Korean Army Training Center, samples were taken from 9954 men from September to November, 2020. Participants were randomly enlisted healthy adult men. The data were compared with 4,205,265 samples from the Korean general population. Men age <30 years were used, as this is similar to the age range of the military recruits. RESULTS Among military recruits, 31 subjects (0.31%) were positive for the antibody, while the Korean male population had 3757 (0.09%) positive individuals. Among these 31 men, 13 were previously diagnosed by PCR, while 18 (58.06%) had no history related to the disease. Positive military recruits were mostly from 2 regional clusters. The first cluster was Daegu and Gyeongbuk areas (1.97% and 0.80%, respectively), which had an outbreak in March, 2020. The second cluster was Gyeonggi and Seoul, or capital areas (0.23% and 0.20%, respectively), which currently has high PCR positivity. Overall, seroprevalence was 3.49 times higher in study subjects. CONCLUSIONS The high seroprevalence of antibodies to SARS-CoV-2 between September and November 2020 in a densely populated military academy in Korea may have been an indicator for the resulting outbreak of COVID-19 in winter 2020-21, which highlights the importance of asymptomatic spread from the young and healthy to the general population.

Atorvastatin Inhibits Endothelial PAI-1-Mediated Monocyte Migration and Alleviates Radiation-Induced Enteropathy.

Intestinal injury is observed in cancer patients after radiotherapy and in individuals exposed to radiation after a nuclear accident. Radiation disrupts normal vascular homeostasis in the gastrointestinal system by inducing endothelial damage and senescence. Despite advances in medical technology, the toxicity of radiation to healthy tissue remains an issue. To address this issue, we investigated the effect of atorvastatin, a commonly prescribed hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor of cholesterol synthesis, on radiation-induced enteropathy and inflammatory responses. We selected atorvastatin based on its pleiotropic anti-fibrotic and anti-inflammatory effects. We found that atorvastatin mitigated radiation-induced endothelial damage by regulating plasminogen activator inhibitor-1 (PAI-1) using human umbilical vein endothelial cells (HUVECs) and mouse model. PAI-1 secreted by HUVECs contributed to endothelial dysfunction and trans-endothelial monocyte migration after radiation exposure. We observed that PAI-1 production and secretion was inhibited by atorvastatin in irradiated HUVECs and radiation-induced enteropathy mouse model. More specifically, atorvastatin inhibited PAI-1 production following radiation through the JNK/c-Jun signaling pathway. Together, our findings suggest that atorvastatin alleviates radiation-induced enteropathy and supports the investigation of atorvastatin as a radio-mitigator in patients receiving radiotherapy.

Alloyed 2D Metal-Semiconductor Heterojunctions: Origin of Interface States Reduction and Schottky Barrier Lowering.

The long-term stability and superior device reliability through the use of delicately designed metal contacts with two-dimensional (2D) atomic-scale semiconductors are considered one of the critical issues related to practical 2D-based electronic components. Here, we investigate the origin of the improved contact properties of alloyed 2D metal-semiconductor heterojunctions. 2D WSe2-based transistors with mixed transition layers containing van der Waals (M-vdW, NbSe2/WxNb1-xSe2/WSe2) junctions realize atomically sharp interfaces, exhibiting long hot-carrier lifetimes of approximately 75,296 s (78 times longer than that of metal-semiconductor, Pd/WSe2 junctions). Such dramatic lifetime enhancement in M-vdW-junctioned devices is attributed to the synergistic effects arising from the significant reduction in the number of defects and the Schottky barrier lowering at the interface. Formation of a controllable mixed-composition alloyed layer on the 2D active channel would be a breakthrough approach to maximize the electrical reliability of 2D nanomaterial-based electronic applications.

Alloyed 2D Metal-Semiconductor Atomic Layer Junctions.

Heterostructures of compositionally and electronically variant two-dimensional (2D) atomic layers are viable building blocks for ultrathin optoelectronic devices. We show that the composition of interfacial transition region between semiconducting WSe2 atomic layer channels and metallic NbSe2 contact layers can be engineered through interfacial doping with Nb atoms. WxNb1-xSe2 interfacial regions considerably lower the potential barrier height of the junction, significantly improving the performance of the corresponding WSe2-based field-effect transistor devices. The creation of such alloyed 2D junctions between dissimilar atomic layer domains could be the most important factor in controlling the electronic properties of 2D junctions and the design and fabrication of 2D atomic layer devices.

Electrohydrodynamic printing for scalable MoS2 flake coating: application to gas sensing device.

Scalable sub-micrometer molybdenum disulfide ([Formula: see text]) flake films with highly uniform coverage were created using a systematic approach. An electrohydrodynamic (EHD) printing process realized a remarkably uniform distribution of exfoliated [Formula: see text] flakes on desired substrates. In combination with a fast evaporating dispersion medium and an optimal choice of operating parameters, the EHD printing can produce a film rapidly on a substrate without excessive agglomeration or cluster formation, which can be problems in previously reported liquid-based continuous film methods. The printing of exfoliated [Formula: see text] flakes enabled the fabrication of a gas sensor with high performance and reproducibility for [Formula: see text] and [Formula: see text].

Immune Correlates of Resistance to Trichinella spiralis Reinfection in Mice.

The immune correlate of host resistance induced by reinfection of Trichinella spiralis remains unclear. In this study, we investigated immune correlates between the resistance and serum IgG antibody level, CD23+ IgM+ B cells, and eosinophil responses induced by T. spiralis reinfection. Mice were primarily infected with 10 or 100 T. spiralis larvae (10 TS, 100 TS), respectively, and after 4 weeks, they were challenge infected with 100 T. spiralis larvae (10-100 TS, 100-100 TS). Upon challenge infections, 10-100 TS mice induced significantly higher levels of T. spiralis-specific total IgG antibody responses in sera and antibody secreting cell responses in spleens compared to 100-100 TS mice, resulting in significantly reduced worm burdens in 10-100 TS mice (60% and 70% reductions for adult and larvae, respectively). Higher levels of eosinophils were found in mice primarily infected with 10 TS compared to those of 100 TS at week 8 upon challenge. CD23+ IgM+ B cells were found to be increased significantly in mice primarily infected with 10 TS. These results indicate that primary infection of 10 larvae of T. spiralis, rather than 100 larvae, induces significant resistance against reinfection which closely correlated with T. spiralis-specific IgG, eosinophil, and CD23+ IgM+ B cell responses.

Ramie Leaf Extracts Suppresses Adipogenic Differentiation in 3T3-L1 Cells and Pig Preadipocytes.

The present study was carried out to evaluate the anti-obesity effect of different concentrations of extracts of hot air-dried ramie leaf (HR) and freeze-dried ramie leaf (FR) in 3T3-L1 cells and pig preadipocytes. To analyze the effect on cell proliferation, cells were treated with 25 µg/mL or 100 µg/mL HR or FR extract for 2 days. Cell differentiation was evaluated by measuring glycerol-3-phosphate dehydrogenase and lipoprotein lipase (LPL) activities and intracellular triglyceride content. Treatment with either HR or FR extracts inhibited the proliferation of 3T3-L1 cells and pig preadipocytes in a dose-dependent manner. HR extract treatment inhibited the differentiation of both cell types more effectively than FR treatment. The extent of triglyceride accumulation decreased significantly in both cells following either HR or FR treatment. Furthermore, LPL activity significantly decreased after treatment with HR or FR extract. These results indicated that HR and FR extracts may inhibit proliferation and differentiation of 3T3-L1 cells and pig preadipocytes. Further studies are needed to explore the anti-obesity effect of HR and FR extracts.

Metal Decoration Effects on the Gas-Sensing Properties of 2D Hybrid-Structures on Flexible Substrates.

We have investigated the effects of metal decoration on the gas-sensing properties of a device with two-dimensional (2D) molybdenum disulfide (MoS2) flake channels and graphene electrodes. The 2D hybrid-structure device sensitively detected NO2 gas molecules (>1.2 ppm) as well as NH3 (>10 ppm). Metal nanoparticles (NPs) could tune the electronic properties of the 2D graphene/MoS2 device, increasing sensitivity to a specific gas molecule. For instance, palladium NPs accumulate hole carriers of graphene/MoS2, electronically sensitizing NH3 gas molecules. Contrarily, aluminum NPs deplete hole carriers, enhancing NO2 sensitivity. The synergistic combination of metal NPs and 2D hybrid layers could be also applied to a flexible gas sensor. There was no serious degradation in the sensing performance of metal-decorated MoS2 flexible devices before/after 5000 bending cycles. Thus, highly sensitive and endurable gas sensor could be achieved through the metal-decorated 2D hybrid-structure, offering a useful route to wearable electronic sensing platforms.

Delineation of the role of glycosylation in the cytotoxic properties of quercetin using novel assays in living vertebrates.

Quercetin is a plant-derived flavonoid and its cytotoxic properties have been widely reported. However, in nature, quercetin predominantly occurs as various glycosides. Thus far the cytotoxic activity of these glycosides has not been investigated to the same extent as quercetin, especially in animal models. In this study, the cytotoxic properties of quercetin (1), hyperoside (quercetin 3-O-galactoside, 2), isoquercitrin (quercetin 3-O-glucoside, 3), quercitrin (quercetin 3-O-rhamnoside, 4), and spiraeoside (quercetin 4'-O-glucoside, 5) were directly compared in vitro using assays of cancer cell viability. To further characterize the influence of glycosylation in vivo, a novel zebrafish-based assay was developed that allows the rapid and experimentally convenient visualization of glycoside cleavage in the digestive tract. This assay was correlated with a novel human tumor xenograft assay in the same animal model. The results showed that 3 is as effective as 1 at inhibiting cancer cell proliferation in vivo. Moreover, it was observed that 3 can be effectively deglycosylated in the digestive tract. Collectively, these results indicate that 3 is a very promising drug candidate for cancer therapy, because glycosylation confers advantageous pharmacological changes compared with the aglycone, 1. Importantly, the development of a novel and convenient fluorescence-based assay for monitoring deglycosylation in living vertebrates provides a valuable platform for determining the metabolic fate of naturally occurring glycosides.

Correction: Virus-Like Nanoparticle Vaccine Confers Protection against Toxoplasma gondii.

[This corrects the article DOI: 10.1371/journal.pone.0161231.].

Factors Influencing Compliance With Social Distancing as a Nonpharmaceutical Intervention Before Vaccine Availability During the COVID-19 Pandemic: A Cross-Sectional Study in South Korea.

This study aimed to identify factors influencing compliance with social distancing, a key nonpharmaceutical intervention during the early stages of the coronavirus disease (COVID-19) pandemic. The study population comprised 182 758 Koreans who participated in the 2020 Community Health Survey. Personal characteristics were classified into sociodemographic, health behavioral, and psychosocial factors, and factors associated with social distancing compliance were identified. Health behaviors and psychosocial factors were highly related to compliance with social distancing. Approximately 13% of smokers were less likely to practice physical distancing and 50% of high-risk drinkers were less likely to limit going out or attending gatherings and events. Higher concern about COVID-19 and a more positive perception of the government's response policy were associated with a higher compliance with social distancing. Strategic public health policies considering the characteristics of the public are needed to enhance compliance with nonpharmaceutical interventions during disease outbreaks lacking effective treatments and vaccines.

Improved Immunogenicity of the Inactivated F Genotype Mumps Vaccine against Diverse Circulating Mumps Viruses in Mice.

Mumps is an acute infectious disease caused by the mumps virus (MuV). Despite high global vaccination coverage, mumps outbreaks continue to occur, even in vaccinated populations. Therefore, we aimed to identify candidate vaccines that can induce an immunogenic response against diverse MuV genotypes with greater efficacy than the currently available options. Vaccine candidates were sourced using formalin-inactivated viral strains. The inactivated vaccines were administered to BALB/c mice (through a primer and booster dose administered after a three-week interval). We tested the neutralizing antibodies of the candidate vaccines against various MuV genotypes to determine their overall efficacy. The formalin-inactivated F genotype vaccine was found to have higher cross-neutralizing titers against genotypes F, H, and G as well as significant Th1 cytokines responses, IFN-γ, TNF-α, and IL-2 than the Jeryl Lynn (JL) vaccine. Our findings suggest that the inactivated F genotype mumps vaccine has higher immunogenicity than the JL vaccine against diverse circulating MuVs.

A Bioinspired Ultra Flexible Artificial van der Waals 2D-MoS2 Channel/LiSiOx Solid Electrolyte Synapse Arrays via Laser-Lift Off Process for Wearable Adaptive Neuromorphic Computing.

Wearable electronic devices with next-generation biocompatible, mechanical, ultraflexible, and portable sensors are a fast-growing technology. Hardware systems enabling artificial neural networks while consuming low power and processing massive in situ personal data are essential for adaptive wearable neuromorphic edging computing. Herein, the development of an ultraflexible artificial-synaptic array device with concrete-mechanical cyclic endurance consisting of a novel heterostructure with an all-solid-state 2D MoS2 channel and LiSiOx (lithium silicate) is demonstrated. Enabled by the sequential fabrication process of all layers, by excluding the transfer process, artificial van der Waals devices combined with the 2D-MoS2 channel and LiSiOx solid electrolyte exhibit excellent neuromorphic synaptic characteristics with a nonlinearity of 0.55 and asymmetry ratio of 0.22. Based on the excellent flexibility of colorless polyimide substrates and thin-layered structures, the fabricated flexible neuromorphic synaptic devices exhibit superior long-term potentiation and long-term depression cyclic endurance performance, even when bent over 700 times or on curved surfaces with a diameter of 10 mm. Thus, a high classification accuracy of 95% is achieved without any noticeable performance degradation in the Modified National Institute of Standards and Technology. These results are promising for the development of personalized wearable artificial neural systems in the future.

Comparison of Humoral Response between Third and Fourth Doses of COVID-19 Vaccine in Hemodialysis Patients.

Dialysis patients are more likely to die or become hospitalized from coronavirus disease 2019 (COVID-19). Currently, only a few studies have evaluated the efficacy of a fourth booster vaccination in hemodialysis (HD) patients and there is not enough evidence to recommend for or against a fourth booster vaccination. This study compared the humoral response and disease severity of patients on HD who received either three or four doses of COVID-19 vaccine. A total of 88 patients were enrolled. Humoral response to vaccination was measured by quantifying immunoglobulin G levels against the receptor binding domain of SARS-CoV-2 (anti-RBD IgG) at five different times and plaque reduction neutralization tests (PRNT) at two different times after vaccination over a period of 18 months. Antibody levels were measured at approximately two-month intervals after the first and second dose, then four months after the third dose, and then one to six months after the fourth dose of vaccine. PRNT was performed two months after the second and four months after the third dose of vaccine. We classified patients into four groups according to the number of vaccine doses and presence of COVID-19 infection. Severe infection was defined as hospital admission for greater than or equal to two weeks or death. There was no difference in antibody levels between naïve and infected patients except after a fourth vaccination, which was effective for increasing antibodies in infection-naïve patients. Age, sex, body mass index (BMI), dialysis vintage, and presence of diabetes mellitus (DM) did not show a significant correlation with antibody levels. Four patients who experienced severe COVID-19 disease tended to have lower antibody levels prior to infection. A fourth dose of SARS-CoV-2 vaccine significantly elevated antibodies in infection-naïve HD patients and may be beneficial for HD patients who have not been previously infected with SARS-CoV-2 for protection against severe infection.

Virus-like particles coexpressing the PreF and Gt antigens of respiratory syncytial virus confer protection in mice.

Aims: The purpose of this study was to assess the protective efficacy of virus-like particles (VLPs) co-expressing the pre-fusogenic (PreF) and G protein with tandem repeats (Gt) antigens of respiratory syncytial virus (RSV) in mice. Materials & methods: VLP constructs expressing PreF, Gt or both were used to immunize mice, and the protective efficacies were evaluated using antibody responses, neutralizing antibody titers, T-cell responses, histopathological assessment and plaque assay. Results: PreF+Gt VLP immunization elicited strong RSV-specific antibody responses and pulmonary T-cell responses that contributed to lessening virus titer and inflammation. Conclusion: Our findings suggest that coexpressing PreF and Gt antigens elicits better protection than either one alone. This combinatorial approach could assist in future RSV vaccine development.

Comparison of plaque reduction and focus reduction neutralization tests for the measurement of neutralizing antibody titers against japanese encephalitis virus.

Japanese encephalitis is prevalent throughout the temperate and tropical regions of Asia and is caused by the Japanese encephalitis virus (JEV), a mosquito-borne viral pathogen. The plaque reduction neutralization test (PRNT) is currently recommended as the gold standard test for detecting human antibodies against JEV. The plaque assay is the most widely used method for detecting infectious virions and involves counting discrete plaques in cells. However, it is time-consuming, and results can be subjective (owing to analyst variability during manual plaque counting). The focus reduction neutralization test (FRNT), which is based on an immuno-colorimetric assay, can be used to automatically count foci formed by the JEV. Here, we compared the efficacy of PRNT and FRNT in measuring the neutralizing antibody titers using 102 serum samples from vaccinated and unvaccinated individuals. We observed positive correlations between these neutralization assays against the Nakayama and Beijing strains (R2 = 0.98 and 0.77, respectively). Thus, FRNT may be preferable to PRNT for evaluating the efficacy of JEV vaccines in large-scale serological studies.

Seroprevalence of SARS-CoV-2 antibodies in the community based on participants in the 2020 Korea National Health and Nutrition Examination Survey.

OBJECTIVES: The Korea National Health and Nutrition Examination Survey (KNHANES) is a nationwide cross-sectional surveillance system that assesses the health and nutritional status of the Korean population. To evaluate the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the community, we investigated the prevalence of anti-SARS-CoV-2 antibodies in the sera of KNHANES participants. METHODS: Subjects were recruited between April 24 and December 12, 2020. In total, 5,284 subjects aged 10-90 years from 17 regions participated. SARS-CoV-2 antibodies were screened using the Elecsys Anti-SARS-CoV-2 assay. Positive samples were verified using 4 different SARS-CoV-2 antibody assays and the plaque reduction neutralizing test. The final seropositivity criteria were a positive screening test and at least 1 positive result from the 5 additional tests. RESULTS: Almost half (49.2%; 2,600/5,284) of participants were from metropolitan areas, 48.9% were middle-aged (40-69 years), and 20.5% were in their 20s or younger. The seropositivity rate was 0.09% (5/5,284). Three of the 5 antibody-positive subjects had a history of infection, of whom 2 were infected abroad and 1 was infected in a local cluster outbreak. CONCLUSIONS: The low SARS-CoV-2 antibody seroprevalence in Korea indicates that there have been few coronavirus disease 2019 (COVID-19) cases due to successful COVID-19 management measures (e.g., diagnostic tests for overseas arrivals, national social distancing, and strict quarantine measures). Moreover, asymptomatic infections were uncommon due to active polymerase chain reaction testing. However, hidden infections may exist in the community, requiring the continuation of quarantine and vaccination measures.

Robust 2D MoS2 Artificial Synapse Device Based on a Lithium Silicate Solid Electrolyte for High-Precision Analogue Neuromorphic Computing.

High-precision artificial synaptic devices compatible with existing CMOS technology are essential for realizing robust neuromorphic hardware systems with reliable parallel analogue computation beyond the von Neumann serial digital computing architecture. However, critical issues related to reliability and variability, such as nonlinearity and asymmetric weight updates, have been great challenges in the implementation of artificial synaptic devices in practical neuromorphic hardware systems. Herein, a robust three-terminal two-dimensional (2D) MoS2 artificial synaptic device combined with a lithium silicate (LSO) solid-state electrolyte thin film is proposed. The rationally designed synaptic device exhibits excellent linearity and symmetry upon electrical potentiation and depression, benefiting from the reversible intercalation of Li ions into the MoS2 channel. In particular, extremely low cycle-to-cycle variations (3.01%) during long-term potentiation and depression processes over 500 pulses are achieved, causing statistical analogue discrete states. Thus, a high classification accuracy of 96.77% (close to the software baseline of 98%) is demonstrated in the Modified National Institute of Standards and Technology (MNIST) simulations. These results provide a future perspective for robust synaptic device architecture of lithium solid-state electrolytes stacked with 2D van der Waals layered channels for high-precision analogue neuromorphic computing systems.

Seroprevalence of SARS-CoV-2 antibodies during the third wave of COVID-19 in the Seoul metropolitan area of Korea.

OBJECTIVES: After the third wave of coronavirus disease 2019 (COVID-19), by mid-February 2021, approximately 0.16% of the Korean population was confirmed positive, which appeared to be among the lowest rates worldwide at that time. However, asymptomatic transmission is challenging for COVID-19 surveillance. Therefore, a community-based serosurvey of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted to understand the effectiveness of Korea's strong containment strategy. METHODS: We collected 5,002 residual sera samples from January 30 to March 3, 2021, from 265 medical facilities in Seoul, 346 in Gyeonggi Province, and 57 in Incheon. Sixty samples from tertiary institutions were excluded. We defined the sub-regions according to the addresses of the medical facilities where the specimens were collected. Elecsys Anti-SARS-CoV-2 was used for screening, and positivity was confirmed using the SARS-CoV-2 sVNT Kit. Prevalence was estimated using sampling weights and the Wilson score interval for a binomial proportion with a 95% confidence interval. RESULTS: Among the 4,942 specimens, 32 and 25 tested positive for COVID-19 in the screening and confirmatory tests, respectively. The overall crude prevalence of SARS-CoV-2 antibodies was 0.51%. The population-adjusted overall prevalence was 0.55% in women and 0.38% in men. The region-specific estimation was 0.67% and 0.30% in Gyeonggi Province and Seoul, respectively. No positive cases were detected in Incheon. CONCLUSIONS: The proportion of undetected cases in Korea remained low as of early 2021. Therefore, an infection control strategy with exhaustive tracing and widespread pre-emptive testing appears to be effective in containing community spread of COVID-19.