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Abstract Passive antibody therapies, typically administered via parenteral routes, have played a crucial role in the initial response to the COVID-19 pandemic. However, the ongoing evolution of SARS-CoV-2 has revealed significant limitations of this approach, primarily due to mutational escape and the inadequate delivery of antibodies to the upper respiratory tract. To overcome these challenges, we propose a novel prophylactic strategy involving the intranasal delivery of an antibody in combination with an Fc-binding nanodisc. This nanodisc, engineered to specifically bind to the Fc regions of IgG antibodies, served two key functions: extending the antibody's half-life in the larynx and trachea, and enhancing its neutralization efficacy. Notably, Sotrovimab, an FDA-approved monoclonal antibody that has experienced a significant decline in neutralizing potency due to viral evolution, exhibited robust antiviral activity when complexed with the nanodisc against all tested Omicron variants. Furthermore, the Fc-binding nanodisc significantly boosted the antiviral efficacy of the soluble angiotensin-converting enzyme 2 (sACE2) Fc fusion protein, which possesses broad but modest antiviral activity. In ACE2 transgenic mice, the Fc-binding nanodisc protected better than sACE2-Fc alone with two more log reduction in lung viral titer. Therefore, the intranasal Fc-binding nanodisc offers a promising and powerful approach to counteract the diminished antiviral activity of neutralizing antibodies caused by mutational escape, effectively restoring antiviral efficacy against various evolving SARS-CoV-2 variants.

This study developed a defect-monitoring system with an artificial intelligence model, YOLOv7, which is tailored for processing image data from an ultrasonic visualization system within sodium fast reactor (SFR) internal structures. For the safety of SFR internal structures, although it is a crucial inspection for defect monitoring, it is difficult to identify structural defects because of the invisible environment. Therefore, we applied the YOLOv7 model in this study; however, we encountered challenges including decreased accuracy with complex defect shapes and complications from data augmentation during pre-training. To solve these problems, we additionally applied the enhanced super-resolution generative adversarial network for higher resolution and a Sobel noise-filtering algorithm to enhance the defect detection accuracy. And we evaluated our system by comparing it with a confidence score. This underscores the effectiveness of the approach in enhancing the defect detection capabilities. Therefore, this defect-monitoring system should be designed to preemptively identify internal structure deformations and enhance SFR safety and maintenance practices.

Understanding the mammalian pathogenesis and interspecies transmission of HPAI H5N8 virus hinges on mapping its adaptive markers. We used deep sequencing to track these markers over five passages in murine lung tissue. Subsequently, we evaluated the growth, selection, and RNA load of eight recombinant viruses with mammalian adaptive markers. By leveraging an integrated non-linear regression model, we quantitatively determined the influence of these markers on growth, adaptation, and RNA expression in mammalian hosts. Furthermore, our findings revealed that the interplay of these markers can lead to synergistic, additive, or antagonistic effects when combined. The elucidation distance method then transformed these results into distinct values, facilitating the derivation of a risk score for each marker. In vivo tests affirmed the accuracy of scores. As more mutations were incorporated, the overall risk score of virus heightened, and the optimal interplay between markers became essential for risk augmentation. Our study provides a robust model to assess risk from adaptive markers of HPAI H5N8, guiding strategies against future influenza threats.

This paper provides a comparative evaluation of the mechanical properties, corrosion resistance, and gamma-ray shielding performance of four different types of tungsten carbide (WC)-NiCr coatings deposited on cold-rolled steel surfaces, which are used as materials for low- and intermediate-level radioactive waste (LILW) storage containers. The four types of coatings were classified as WC-85, WC-73, WC-66, and WC-39 according to their WC content and were applied to the cold-rolled steel surfaces using the High-Velocity Oxygen Fuel (HVOF) spraying process. The performance of the layered coatings was analyzed in terms of their microstructure, hardness, wear resistance, adhesion strength, corrosion properties, and gamma-ray shielding characteristics. Coatings with elevated WC contents showed enhanced mechanical properties and gamma-ray shielding effectiveness, whereas coatings with relatively lower WC contents and higher NiCr contents exhibited greater corrosion resistance. This paper discusses the performance of WC-NiCr coatings from the viewpoint of enhancing the durability and safety of commercial LILW storage containers.

The water radiolysis in-core at light water reactors (LWRs) produces various radicals with other ionic species/molecules and radioactive nitrogen species in the reactor coolant. Nitrogen species can exist in many different chemical forms and recirculate in water and steam, and consequently contribute to what extent the environmental safety at nuclear power plants. Therefore, a clear understanding of formation kinetics and chemical behaviors of nitrogen species under irradiation is crucial for better insight into the characteristics of major radioactive species released to the main steam or relevant coolant systems and eventually development of advanced processes/methodologies to enhance the environmental safety at nuclear power plants. This paper thus focuses on basic principles on electrochemical interaction kinetics of radiolytic molecules and various nitrogen species in high temperature water, fundamental approaches for calculating thermodynamic values to predict their stability and domain in LWRs, and the effect of nitrogen species on crevice chemistry/corrosion and intergranular stress corrosion cracking (IGSCC) susceptibility of structure materials in high temperature water.

Abstract Sarcopenia, characterized by reduced muscle mass and fiber number leading to muscular atrophy, has been associated with serious socioeconomic challenges among the elderly in developed countries. Therefore, preventing sarcopenia could be a promising strategy for achieving a healthy aging society. Nutmeg (Myristica fragrans) has been used as a spice to increase flavor and prevent putrefaction of food. Nutmeg contains various bioactive components that improve muscle activity. To determine the potential effect of lignan-enriched nutmeg extract (LNX) on sarcopenia, LNX (100 mg/kg body weight)-fed aged mice were subjected to forced exercise. Herein, aged (22-month-old) mice fed LNX for three weeks exhibited a shortened and thickened soleus muscle. The ratio of the soleus muscle mass (%) to body weight was significantly increased in LNX-fed aged mice. The relative increase in muscle mass in LNX-fed aged mice improved exercise activities, including rotarod, swimming, and grip strength test results. Proteome profiles of the soleus muscle of LNX-fed mice were used to analyze protein–protein interaction network. Several myosin heavy chain isoforms were found to interact with actin, ACTA1, which functions as a hub protein. Furthermore, the expression of myogenic proteins, such as MYH1, MYH4, and ACTA1, was dose-dependently increased in vivo. In result, our functional proteomic analysis revealed that feeding LNX restored muscle proteins in aged mice.

ABSTRACT Enteroviruses (EVs) have been associated with several human diseases. Due to their continuous emergence and divergence, EV species have generated more than 100 types and recombinant strains, increasing the public health threat caused by them. Hence, an efficient and universal cloning system for reverse genetics (RG) of highly divergent viruses is needed to understand the molecular mechanisms of viral pathology and evolution. In this study, we generated a versatile human EV whole-genome cDNA template by enhancing the template-switching method and designing universal primers capable of simultaneous cloning and rapid amplification of cDNA ends (RACE)-PCR of EVs. Moreover, by devising strategies to overcome limitations of previous cloning methods, we simplified significant cloning steps to be completed within a day. Of note, we successfully verified our efficient universal cloning system enabling RG of a broad range of human EVs, including EV-A (EV-A71), EV-B (CV-B5, ECHO6, and ECHO30), EV-C (CV-A24), and EV-D (EV-D68), with viral titers and phenotypes comparable to those of their wild types. This rapid and straightforward universal EV cloning strategy will help us elucidate molecular characteristics, pathogenesis, and applications of a broad range of EV serotypes for further development of genetic vaccines and delivery tools using various replication systems. IMPORTANCE Due to the broad spread, incidence, and genetic divergence of enteroviruses (EVs), it has been challenging to deal with this virus that causes severe human diseases, including aseptic meningitis, myocarditis, encephalitis, and poliomyelitis. Therefore, an efficient and universal cloning system for the reverse genetics of highly divergent EVs contributes to an understanding of the viral pathology and molecular mechanisms of evolution. We have simplified the important cloning steps, hereby enhancing the template-switching method and designing universal primers, which enable the important cloning steps to be completed in a day. We have also successfully demonstrated recovery of a broad range of human EVs, including EV-A to -D types, using this advanced universal cloning system. This rapid and robust universal EV cloning strategy will aid in elucidating the molecular characteristics, pathogenesis, and applications of a wide range of EVs for further development of genetic vaccines and antiviral screening using various replication systems.

During the long-term cooling (LTC) phase of a loss-of-coolant accident (LOCA) in a pressurized water reactor (PWR), water is supplied from the containment sump to the reactor coolant system (RCS) by the flooded sump water to the Reactor Vessel (RV) through the broken pipes. As part of the technical efforts for resolving GSI-191 [( Reid and Crytzer, May. 2007) 1, consideration is needed for the consequences of debris penetrating the sump screen and propagating downstream into the RV. Injection of debris (fiberglass) into the RV during the LTC recirculation phase needs special attention to assure that reactor core cooling is maintained. The point of concern is the potential for debris to adversely affect the reactor core flow paths or heat transfer [2]. However, all the experiments for proving the coolability of RV have been done with the assumption of the most of debris would be transferred to the RV and the bottom nozzle of the FAs.The purpose of the tests is to quantify the amount of the debris that would be accumulated at the lower plenum and the debris that passes through the FAs since non-conservatism of other researches assumptions that have been used in the past experimental or analytical programs.