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Influenza B virus (IBV) is one of the human respiratory viruses and one of the targets of seasonal vaccination. However, the bifurcation of two antigenically distinct lineages of IBVs makes it difficult to arrange proper medical countermeasures. Moreover, compared with pathogenicity-related molecular markers known for influenza A virus, little has been known for IBVs. To understand pathogenicity caused by IBVs, we investigated the molecular determinants of IBV pathogenicity in animal models. After serial lung-to-lung passages of Victoria lineage B/Brisbane/60/ 2008 (Vc_BR60) and Yamagata lineage B/Wisconsin/01/2010 (Ym_WI01) viruses in BALB/c mice, we identified the mouse-adapted Vc_BR60 (maVc_BR60) and Ym_WI01 (maYm_WI01) viruses, respectively. To find a molecular clue(s) to the increased pathogenicity of maVc_BR60 and maYm_WI01, we determined their genetic sequences. Several amino acid mutations were identified in the PB2, PB1, PA, BM2, and/or NS1 protein-coding regions, and one concurrent lysine (K)-to-arginine (R) mutation in PA residue 338 (PA K338R) was found in both maVc_BR60 and maYm_WI01 viruses. When analyzed using viruses rescued through reverse genetics, it was shown that PA K338R alone could increase the pathogenicity of both IBVs in mice and viral replication in the respiratory tracts of ferrets. In a subsequent minireplicon assay, the effect of PA K338R was highlighted by the enhancement of viral polymerase complex activity of both Vc_BR60 and Ym_WI01 viruses. These results suggest that the PA K338R mutation may be a molecular determinant of IBV pathogenicity via modulating the viral polymerase function of IBVs. IMPORTANCE To investigate molecular pathogenic determinants of IBVs, which are one of the targets of seasonal influenza vaccines, we adapted both Victoria and Yamagata lineage IBVs independently in mice. The recovered mouse-adapted viruses exhibited increased virulence, and of the various mutations identified from both mouse-adapted viruses, a concurrent amino acid mutation was found in the PA protein-coding region. When analyzed using viruses rescued through reverse genetics, the PA mutation alone appeared to contribute to viral pathogenicity in mice within the compatible genetic constellation between the IBV lineages and to the replication of IBVs in ferrets. Regarding the potential mechanism of increased viral pathogenicity, it was shown that the PA mutation could upregulate the viral polymerase complex activity of both IBV lineages. These results indicate that the PA mutation could be a newly defined molecular pathogenic determinant of IBVs that substantiates our understanding of the viral pathogenicity and public health risks of IBVs. [ABSTRACT FROM AUTHOR]

The article focuses on microporous polymers with cascaded cavities for controlled transport of small gas molecules. Topics icnlude the membrane-based separation, molecular size differences relative to membrane pore sizes govern mass flux and separation efficiency, and the applications requiring complex molecular differentiation, such as in natural gas processing, cascaded pore size distributions in membranes allow different permeate molecules to be separated without a reduction in throughput.

Background: Coronavirus disease 2019 (COVID-19) outbreaks occur in hospitals in many parts of the world. In hospital settings, the possibility of airborne transmission needs to be investigated thoroughly. Materials and Methods: There was a nosocomial outbreak of COVID-19 in a hematologic ward in a tertiary hospital, Seoul, Korea. We found 11 patients and guardians with COVID-19 through vigorous contact tracing and closed-circuit television monitoring. We found one patient who probably had acquired COVID-19 through airborne-transmission. We performed airflow investigation with simulation software, whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Of the nine individuals with COVID-19 who had been in the hematologic ward, six stayed in one multi-patient room (Room 36), and other three stayed in different rooms (Room 1, 34, 35). Guardian in room 35 was close contact to cases in room 36, and patient in room 34 used the shared bathroom for teeth brushing 40 minutes after index used. Airflow simulation revealed that air was spread from the bathroom to the adjacent room 1 while patient in room 1 did not used the shared bathroom. Airflow was associated with poor ventilation in shared bathroom due to dysfunctioning air-exhaust, grill on the door of shared bathroom and the unintended negative pressure of adjacent room. Conclusion: Transmission of SARS-CoV-2 in the hematologic ward occurred rapidly in the multi-patient room and shared bathroom settings. In addition, there was a case of possible airborne transmission due to unexpected airflow. [ABSTRACT FROM AUTHOR]

Combating influenza is one of the perennial global public health issues to be managed. Antiviral drugs are useful for the treatment of influenza in the absence of an appropriate vaccine. However, the appearance of resistant strains necessitates a constant search for new drugs. In this study, we investigated novel anti-influenza drug candidates using in vitro and in vivo assays. We identified anti-influenza hit compounds using a high throughput screening method with a green fluorescent protein-tagged recombinant influenza virus. Through subsequent analyses of their cytotoxicity and pharmacokinetic properties, one candidate (IY7640) was selected for further evaluation. In a replication kinetics analysis, IY7640 showed greater inhibitory effects during the early phase of viral infection than the viral neuraminidase-inhibitor oseltamivir. In addition, we observed that hemagglutinin (HA)-mediated membrane fusion was inhibited by the IY7640 treatment, indicating that the HA stalk region, which is highly conserved across various (sub)types of influenza viruses, may be the molecular target of IY7640. In an escape mutant analysis in cells, amino acid mutations were identified at the HA stalk region of the 2009 pandemic H1N1 (pH1N1) virus. Even though the in vivo efficacy of IY7640 did not reach to complete protection in a lethal challenge study in mice, these results suggest that IY7640 has potential to be developed as a new type of anti-influenza drug. [ABSTRACT FROM AUTHOR]

Background Harassed with extensive epithelial burn wounds, patients can be affected by complications, such as infection, hypovolemic shock, hypothermia, and respiratory failure. Immediate first aid and followed supportive cares are critical for the prevention of severe complications. However, secondary bacterial infection is hard to be controlled in burn patients, and Pseudomonas aeruginosa (P. aeruginosa) is one of the top listed pathogens perturbing burn wounds beyond the antibiotics spectrum. Results To find the way for efficacious protection from the pseudomonas-mediated complications in burn patients, we assessed the in vitro and in vivo inhibitory values of human β-defensin 4 (hBD4), which is known as a member of the cationic, antimicrobial peptides found in human cells of many kinds. The Newcastle disease virus (NDV) was used as a viral vector for the expression of hBD4 in burn wounds. Expressed from the recombinant NDV (rNDV-hBD4), hBD4 effectively inhibited the pseudomonal growths in cell culture media. In a mouse model, severely burn-injured skin was recovered by the direct installation of the rNDV-hBD4 infected cells in the burn wounds whereas that of control mice remained severely damaged. Conclusions We suggest that the application of hBD4 may protect burn patients from secondary pseudomonal infection and provide a therapeutic potential for burn wound treatment. [ABSTRACT FROM AUTHOR]

배경 The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. However, until now, no specific treatment or vaccine has been identified for COVID-19 infections, and it is not yet known how long the antibodies, including defensive neutralizing antibody (Nab), will last in patients with COVID-19. In order to treat for the COVID-19 infection and to have data for the development of SARS-CoV-2 vaccines, research of antibody characteristics according to clinical manifestation is urgently needed. 방법 From Jun 3rd to Jun 23th, blood samples were collected from 143 PCR-confirmed COVID-19 recovered patients who agreed to participate in the antibody tracking study at the Kyungpook National University Hospital. Patients under 18 years or with mental illness were excluded. Nab analysis (plaque reduction neutralization test; PRNT) was conducted by Korea University. A survey of clinical features was conducted through an individualized questionnaire, and an epidemiological and clinical data from Daegu City. We evaluated the relations of the clinical characteristics and Nab titer (≥1:40 or <1:40). 결과 Of the total 143 patients, 68 (47.6 %) were male and 75 (52.4 %) were female. Age distribution was as follows: 34 (23.8%) patients age range 20-29; 24 (16.8%) patients age range 30-39; 25 (17.5%) patients age range 40-49; 27 (18.9%) patients age range 50-59; and 33 (23.1%) patients age range 60-69. The average days taken from the symptom onset to the blood collection date was 109.0 [104.0; 115.0]. 32 patients (22.4%) showed < 1:40 Nab titer and 111 patients (77.6%) showed ≥1:40. As time went by, the rate of Nab titer ≥1:40 showed a tendency to slow decrease (figure 1). As the age was older, the rate of Nab titer ≥1:40 showed a statistically significance increasing tendency (p<0.001)(figure 2). The symptoms of dyspnea and presence of pneumonia were statistically significantly higher in groups of ≥1:40, but there were no other symptoms differences, including fever, sore throat, ageusia, anosmia and upper respiratory symptoms. No statistical differences were identified in gender, underlying diseases and ICU admission history between the two groups. 결론 After 3 months of COVID-19 infection, all recovered patients were found to have Nab, and 77.6% showed Nab levels ≥1:40. In order to prepare the convalescent serum antibody treatment and to establish vaccine policies in the near future, continuous tracking of changes in Nab is needed. [ABSTRACT FROM AUTHOR]