Avian influenza virus remains a threat for humans, and vaccines preventing both avian and human influenza virus infections are needed. Since virus-like particles (VLPs) expressing single ...neuraminidase (NA) subtype elicited limited heterosubtypic protection, VLPs expressing multiple NA subtypes would enhance the extent of heterosubtypic immunity. Here, we generated avian influenza VLP vaccines displaying H5 hemagglutinin (HA) antigen with or without avian NA subtypes (N1, N6, N8) in different combinations. BALB/c mice were intramuscularly immunized with the VLPs to evaluate the resulting homologous and heterosubtypic immunity upon challenge infections with the avian and human influenza viruses (A/H5N1, A/H3N2, A/H1N1). VLPs expressing H5 alone conferred homologous protection but not heterosubtypic protection, whereas VLPs co-expressing H5 and NA subtypes elicited both homologous and heterosubtypic protection against human influenza viruses in mice. We observed that VLP induced neuraminidase inhibitory activities (NAI), virus-neutralizing activity, and virus-specific antibody (IgG, IgA) responses were strongly correlated with the number of different NA subtype expressions on the VLPs. VLPs expressing all 3 NA subtypes resulted in the highest protection, indicated by the lowest lung titer, negligible body weight changes, and survival in immunized mice. These results suggest that expressing multiple neuraminidases in avian HA VLPs is a promising approach for developing a universal influenza A vaccine against avian and human influenza virus infections.
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•A highly effective strategy to expose numerous edge sites of WS2 for chemoresistive gas sensor applications.•Extremely high gas response and excellent recovery characteristics ...achieved by WS2-based gas sensors at room temperature.•Interpretation of extremely high NO2 selectivity achieved by edge-exposed WS2 through DFT calculation.
One of the well-known pathways toward low power consuming chemoresistive gas sensors is the utilization of 2-dimensional materials. Especially, transition metal dichalcogenides (TMDs), which are usually atomically thin semiconductors, have a notable characteristic of their highly reactive edge sites. The edge sites of TMDs having high d-orbital electron density can serve as highly favorable chemically active sites for direct interaction with target gas molecules. In this study, WS2 was synthesized on highly porous SiO2 nanorods template to have numerous edge-exposed WS2 flakes in a limited active area taking advantage of 1-dimensional nanostructures with extremely high surface-to-volume ratio. The fabricated WS2 on 1D nanostructures exhibited a gas response of 151.2 % toward 5 ppm NO2, which has not been reported in performance-wise at room temperature to the best of the author’s knowledge. Density functional theory calculations theoretically supported the highly sensitive and selective NO2 detection with a theoretical detection limit of 13.726 ppb.
Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of ...aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases.
The sera of patients with MOGAD (from during an attack and remission;
=19 and
=9, respectively) and AQP4-NMOSD (
=35 and
=17), and healthy controls (
=38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9).
In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all,
<0.001), while the level of sC5b-9 was increased only in the NMOSD group. In MOGAD, there were no differences in the concentrations of complement analytes based on disease status. However, within AQP4-NMOSD, remission samples indicated a higher C1-INH level than attack samples (p=0.003). Notably, AQP4-NMOSD patients on medications during attack showed lower levels of iC3b (
<0.001) and higher levels of C3 (
=0.008), C1-INH (
=0.004), and sC5b-9 (
<0.001) compared to those not on medication. Among patients not on medication at the time of attack sampling, serum MOG-IgG cell-based assay (CBA) score had a positive correlation with iC3b and C1-INH levels (rho=0.764 and
=0.010, and rho=0.629 and
=0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836,
=0.003).
This study indicates a higher prominence of complement pathway activation and subsequent C3 degradation in MOGAD compared to AQP4-NMOSD. On the other hand, the production of terminal complement complexes (TCC) was found to be more substantial in AQP4-NMOSD than in MOGAD. These findings suggest a strong regulation of the complement system, implying its potential involvement in the pathogenesis of MOGAD through mechanisms that extend beyond TCC formation.
As most of patients with Myasthenia Gravis have limitations in their physical functioning, many experience changes in psychological states and often have depression. The objective of the current ...study was to examine the roles of communication with medical professionals, patients' loneliness, and patients' depression, in relation to their effects on the patients' quality of life.
For 120 patients with MG of 18 years and older, demographic variables, along with communication with medical professionals, loneliness, depression, and quality of life were measured.
As a result, people suffering from MG experienced lower quality of life when their career has changed due to the illness. At the same time, depression was a significant predictor of their quality of life, both in physical and mental domains.
The implications for clinical settings and the suggestions for future research are discussed.
We describe a 40-year-old female patient who presented with sleep disturbance, intermittent headache, and gradual subjective cognitive decline. sup.18F-fluorodeoxyglucose (FDG) positron emission ...tomography (PET) showed mild FDG hypometabolism in bilateral parietal and temporal lobes. However, sup.18F-florbetaben (FBB) amyloid PET revealed diffuse amyloid retention in the lateral temporal cortex, frontal cortex, posterior cingulate cortex/precuneus, parietal cortex, and cerebellum. This finding supports the clinical significance of amyloid imaging in diagnostic work-up of early-onset Alzheimer's disease (EOAD).
We describe a 40-year-old female patient who presented with sleep disturbance, intermittent headache, and gradual subjective cognitive decline. 18F-fluorodeoxyglucose (FDG) positron emission ...tomography (PET) showed mild FDG hypometabolism in bilateral parietal and temporal lobes. However, 18F-florbetaben (FBB) amyloid PET revealed diffuse amyloid retention in the lateral temporal cortex, frontal cortex, posterior cingulate cortex/precuneus, parietal cortex, and cerebellum. This finding supports the clinical significance of amyloid imaging in diagnostic work-up of early-onset Alzheimer’s disease (EOAD).
Background and Purpose- Blood pressure dynamics in patients with acute ischemic stroke may serve as an important modifiable and prognostic factor. Methods- A total of 8376 patients with acute ...ischemic stroke were studied from a prospective multicenter registry. Patients were eligible if they had been admitted within 24 hours of symptom onset and had ≥5 systolic blood pressure (SBP) measurements during the first 24 hours of hospitalization. SBP trajectory groups in the first 24 hours were identified using the TRAJ procedure in SAS software with delta-Bayesian Information Criterion and prespecified modeling parameters. Vascular events, including recurrent stroke, myocardial infarction, and death, were prospectively collected. The risk of having vascular events was calculated using the frailty model to adjust for clustering by hospital. Results- The group-based trajectory model classified patients with acute ischemic stroke into 5 SBP trajectory groups: low (22.3%), moderate (40.8%), rapidly stabilized (11.9%), acutely elevated (18.5%), and persistently high (6.4%) SBP. The risk of having vascular events was increased in the acutely elevated (hazard ratio, 1.28 95% confidence interval, 1.12-1.47) and the persistently high SBP groups (hazard ratio, 1.67 95% confidence interval, 1.37-2.04) but not in the rapidly stabilized group (hazard ratio, 1.13 95% confidence interval, 0.95-1.34), when compared with the moderate SBP group. Conclusions- SBP during the first 24 hours after acute ischemic stroke may be categorized into distinct trajectory groups, which differ in relation to stroke characteristics and frequency of subsequent recurrent vascular event risks. The findings may help to recognize potential candidates for future blood pressure control trials.
Existing data for the association between late-life body mass index (BMI) and the risk of Alzheimer's disease (AD) in the underweight population are limited with conflicting results. A large ...population-based cohort study of 148,534 individuals aged ≥ 65 years who participated in the national health screening program from 2002 to 2005 was performed using the Korean National Health Insurance Service-Senior cohort database 2006-2015. The risk of AD according to BMI category (kg/m
) in Asians was evaluated using a multivariable Cox regression model, after adjustments for age, sex, lifestyle, low-income status, and comorbidities. To evaluate the association between BMI and AD risk, the underweight population was further subdivided according to the degree of thinness. During the 10-year follow-up period, 22,279 individuals developed AD. Relative to the normal-weight population, the estimated adjusted hazard ratio (HR) for incident AD in the underweight, overweight, and obese populations was 1.17 (95% confidence interval CI, 1.09-1.24), 0.90 (0.87-0.93), and 0.83 (0.80-0.85), respectively. In the underweight population, AD risk increased as the degree of thinness increased (p for the trend, < .001). Late-life BMI showed a significant inverse relationship with AD risk, especially in the underweight population. Public health strategies to screen for AD more actively in the underweight population and improve their weight status may help reduce the burden of AD.
Prion diseases are incurable neurodegenerative disorders caused by proteinase K‐resistant prion protein (PrPSc) derived from normal prion protein (PrPC) encoded by the prion protein gene (PRNP). ...Although the cervid PRNP gene plays a pivotal role in the pathological mechanism of chronic wasting disease (CWD), there is no existing association analysis between susceptibility to CWD and genetic polymorphisms of the PRNP gene in sika deer. We investigated genetic polymorphisms of the PRNP gene using amplicon sequencing in sika deer. In addition, to identify a genetic susceptibility factor, we compared the genotype, allele and haplotype frequencies of the PRNP gene between CWD‐positive and CWD‐negative sika deer. Furthermore, to assess the effect of the genetic polymorphisms on sika deer prion protein (PrP), we performed in silico analysis using PolyPhen‐2, PROVEAN and AMYCO. Finally, we analysed the tertiary structure and electrostatic potential of sika deer PrP based on single nucleotide polymorphisms (SNPs) using the SWISS‐MODEL and Swiss‐PdbViewer programs. We found a total of 24 SNPs of the PRNP gene, including 22 novel SNPs (10 synonymous SNPs and 12 nonsynonymous SNPs), in sika deer. Among the nonsynonymous SNPs, we found a strong association of susceptibility to CWD with c.56G > A (Ser19Asn). In addition, we found that c.56G > A (Ser19Asn), c.296A > T (His99Leu) and c.560T > A (Val187Asp) were predicted to have damaging effects on sika deer PrP. Furthermore, we observed significant alterations in the electrostatic potential of sika deer PrP by genetic polymorphisms of the 187Asp allele. To the best of our knowledge, this was the first association study between genetic polymorphisms of the PRNP gene and susceptibility to CWD in sika deer.
RNA-binding proteins (RBPs) regulate gene expression at many post-transcriptional levels, including mRNA stability and translation. The RBP nucleolin, with four RNA-recognition motifs, has been ...implicated in cell proliferation, carcinogenesis and viral infection. However, the subset of nucleolin target mRNAs and the influence of nucleolin on their expression had not been studied at a transcriptome-wide level. Here, we globally identified nucleolin target transcripts, many of which encoded cell growth- and cancer-related proteins, and used them to find a signature motif on nucleolin target mRNAs. Surprisingly, this motif was very rich in G residues and was not only found in the 3′-untranslated region (UTR), but also in the coding region (CR) and 5′-UTR. Nucleolin enhanced the translation of mRNAs bearing the G-rich motif, since silencing nucleolin did not change target mRNA stability, but decreased the size of polysomes forming on target transcripts and lowered the abundance of the encoded proteins. In summary, nucleolin binds G-rich sequences in the CR and UTRs of target mRNAs, many of which encode cancer proteins, and enhances their translation.
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