Small and Medium Amplitude Oscillatory Shear Rheology of Model Branched Polystyrene (PS) Melts

Linear and nonlinear rheological properties of model comb polystyrenes (PS) with loosely to densely grafted architectures were measured under small and medium amplitude oscillatory shear (SAOS and MAOS) flow. This comb PS set had the same length of backbone and branches but varied in the number of branches from 3 to 120 branches. Linear viscoelastic properties of the comb PS were compared with the hierarchical model predictions. The model underpredicted zero-shear viscosity and backbone plateau modulus of densely branched comb with 60 or 120 branches because the model does not include the effect of side chain crowding. First- and third-harmonic nonlinearities reflected the hierarchy in the relaxation motion of comb structures. Notably, the low-frequency plateau values of first-harmonic MAOS moduli scaled with M$^{-2}$$_{w}$ (total molecular weight), reflecting dynamic tube dilution (DTD) by relaxed branches. Relative intrinsic nonlinearity Q$_{0}$ exhibited the difference between comb and bottlebrush via no low-frequency Q$_{0}$ peak of bottlebrush corresponding to backbone relaxation, which is probably related to the stretched backbone conformation in bottlebrush

Development and characterization of stable cell lines constitutively expressing the porcine reproductive and respiratory syndrome virus nucleocapsid protein

Despite global efforts to control porcine reproductive and respiratory syndrome virus (PRRSV) infection, the virus continues to cause economic problems in the swine industry worldwide. In this study, we attempted to generate and characterize a panel of stable BHK cell lines that constitutively express the nucleocapsid (N) protein of type 1 or type 2 PRRSV. The established BHK cell lines were found to react well with N-specific antibodies as well as the hyperimmune serum of pigs raised against each genotype of PRRSV. Taken together, the data implicate a potential usefulness for the newly generated stable cell lines as a diagnostic reagent for PRRSV serology

Immediate Effects of Mental Singing While Walking on Gait Disturbance in Hemiplegic Stroke Patients: A Feasibility Study

ObjectiveTo investigate the immediate therapeutic effects of mental singing while walking intervention on gait disturbances in hemiplegic stroke patients.MethodsEligible, post-stroke, hemiplegic patients were prospectively enrolled in this study. The inclusion criteria were a diagnosis of hemiplegia due to stroke, and ability to walk more than 10 m with or without gait aids. Each patient underwent structured music therapy sessions comprising 7 consecutive tasks, and were trained to sing in their mind (mental singing) while walking. Before, and after training sessions, gait ability was assessed using the 10-Meter Walk Test (10MWT), the Timed Up and Go test (TUG), gait velocity, cadence and stride length.ResultsTwenty patients were enrolled in the interventions. Following the mental singing while walking intervention, significant improvement was observed in the 10MWT (13.16±7.61 to 12.27±7.58; p=0.002) and the TUG test (19.36±15.37 to 18.42±16.43; p=0.006). Significant improvement was also seen in gait cadence (90.36±29.11 to 95.36±30.2; p<0.001), stride length (90.99±33.4 to 98.17±35.33; p<0.001) and velocity (0.66±0.45 to 0.71±0.47; p<0.002).ConclusionThese results indicate the possible effects of mental singing while walking on gait in patients diagnosed with hemiplegic stroke

Strategies for developing flavonoids with multiple reactivities against pathological features in Alzheimer’s disease

The etiology of Alzheimer’s disease (AD) is still unknown because of its complicated nature associated with various pathological components, including free radicals, acetylcholinesterase, and metal-free and metal-bound amyloid-beta. Thus, chemical reagents with modulating reactivities against multiple pathogenic factors are necessary for advancing our understanding of the complex pathogenesis. Here we report rational strategies for developing flavonoids that can control multiple pathological elements found in the brains of AD patients. Our investigations employing a series of flavonoids illuminated structural features critical for regulatory reactivities against desired targets. Moreover, the most promising flavonoid with multiple functions was developed based on our complete structure–activity relationship. Mechanistic studies confirmed that such versatile reactivities of the flavonoid are achieved by its redox potential and direct interactions with pathogenic factors. Overall, our studies demonstrate the feasibility of devising small molecules as multifunctional chemical reagents against pathological features found in AD

Designing multi-target-directed flavonoids: a strategic approach to Alzheimer's disease

The underlying causes of Alzheimer's disease (AD) remain a mystery, with multiple pathological components, including oxidative stress, acetylcholinesterase, amyloid-b, and metal ions, all playing a role. Here we report a strategic approach to designing flavonoids that can effectively tackle multiple pathological elements involved in AD. Our systematic investigations revealed key structural features for flavonoids to simultaneously target and regulate pathogenic targets. Our findings led to the development of a highly promising flavonoid that exhibits a range of functions, based on a complete structure–activity relationship analysis. Furthermore, our mechanistic studies confirmed that this flavonoid's versatile reactivities are driven by its redox potential and direct interactions with pathogenic factors. This work highlights the potential of multi-target-directed flavonoids as a novel solution in the fight against AD

APP‐C31: An Intracellular Promoter of Both Metal‐Free and Metal‐Bound Amyloid‐β40 Aggregation and Toxicity in Alzheimer's Disease

Abstract Intracellular C‐terminal cleavage of the amyloid precursor protein (APP) is elevated in the brains of Alzheimer's disease (AD) patients and produces a peptide labeled APP‐C31 that is suspected to be involved in the pathology of AD. But details about the role of APP‐C31 in the development of the disease are not known. Here, this work reports that APP‐C31 directly interacts with the N‐terminal and self‐recognition regions of amyloid‐β40 (Aβ40) to form transient adducts, which facilitates the aggregation of both metal‐free and metal‐bound Aβ40 peptides and aggravates their toxicity. Specifically, APP‐C31 increases the perinuclear and intranuclear generation of large Aβ40 deposits and, consequently, damages the nucleus leading to apoptosis. The Aβ40‐induced degeneration of neurites and inflammation are also intensified by APP‐C31 in human neurons and murine brains. This study demonstrates a new function of APP‐C31 as an intracellular promoter of Aβ40 amyloidogenesis in both metal‐free and metal‐present environments, and may offer an interesting alternative target for developing treatments for AD that have not been considered thus far

A Glycosylated Prodrug to Attenuate Neuroinflammation and Improve Cognitive Deficits in Alzheimer&apos;s Disease Transgenic Mice

We report a prodrug, Glu-DAPPD, to overcome the shortcomings of an anti-neuroinflammatory molecule, N,N&apos;-diacetyl-p-phenylenediamine (DAPPD), in biological applicability for potential therapeutic applications. We suspect that Glu-DAPPD can release DAPPD through endogenous enzymatic bioconversion. Consequently, Glu-DAPPD exhibits in vivo efficacies in alleviating neuroinflammation, reducing amyloid-beta aggregate accumulation, and improving cognitive function in Alzheimer&apos;s disease transgenic mice. Our studies demonstrate that the prodrug approach is suitable and effective toward developing drug candidates against neurodegeneration

Genetic Characterization and Pathogenesis of H5N1 High Pathogenicity Avian Influenza Virus Isolated in South Korea during 2021–2022

High pathogenicity avian influenza (HPAI) viruses of clade 2.3.4.4 H5Nx have been circulating in poultry and wild birds worldwide since 2014. In South Korea, after the first clade 2.3.4.4b H5N1 HPAI viruses were isolated from wild birds in October 2021, additional HPAIV outbreaks occurred in poultry farms until April 2022. In this study, we genetically characterized clade 2.3.4.4b H5N1 HPAIV isolates in 2021–2022 and examined the pathogenicity and transmissibility of A/mandarin duck/Korea/WA585/2021 (H5N1) (WA585/21) in chickens and ducks. Clade 2.3.4.4b H5N1 HPAI viruses caused 47 outbreaks in poultry farms and were also detected in multiple wild birds. Phylogenetic analysis of HA and NA genes indicated that Korean H5N1 HPAI isolates were closely related to Eurasian viruses isolated in 2021–2022. Four distinct genotypes of H5N1 HPAI viruses were identified in poultry, and the majority were also found in wild birds. WA585/21 inoculated chickens showed virulent pathogenicity with high mortality and transmission. Meanwhile, ducks infected with the virus showed no mortality but exhibited high rates of transmission and longer viral shedding than chickens, suggesting that they may play an important role as silent carriers. In conclusion, consideration of both genetic and pathogenic traits of H5N1 HPAI viruses is required for effective viral control