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The article discusses the development of a trivalent SARS-CoV-2 virus-like particle vaccine, RBDV14 M, targeting newly emerged variants such as XBB.1, BQ.1.1, EG.5, and BA.2.86. The vaccine induced superior antibody responses and provided protection against these variants in preclinical studies. The study highlights the potential of RBDV14 M as a next-generation SARS-CoV-2 vaccine candidate, demonstrating broad-spectrum neutralization and protection against specific variants. [Extracted from the article]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune response. However, their expressions in infected cells and immunogenicity in infected humans and mice are still not fully understood. This study utilized various techniques such as luciferase immunoprecipitation system (LIPS), immunofluorescence assay (IFA), and western blot (WB) to detect accessory protein-specific antibodies in sera of COVID-19 patients. Specific antibodies to proteins 3a, 3b, 7b, 8 and 9c can be detected by LIPS, but only protein 3a antibody was detected by IFA or WB. Antibodies against proteins 3a and 7b were only detected in ICU patients, which may serve as a marker for predicting disease progression. Further, we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a, 6, 7a, 8, and 9b. We also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a, 6, 7a, 8, 9b and 9c were able to induce measurable antibody productions, but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 infection. Our findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response, providing a basis for protein detection assays and their role in pathogenesis. [ABSTRACT FROM AUTHOR]

Although the SARS-CoV-2 vaccine has been widely used worldwide, not all individuals can produce neutralization antibodies, so it is still urgent to find and prepare neutralization antibodies for COVID-19 prevention or treatment. In this study, we created a new strategy to effectively obtain neutralizing antibodies or complementary determining region 3 (CDR3) of neutralizing antibodies against SARS-CoV-2. We first predicted and synthesized several B cell epitopes on RBD and adjacent RBD of S protein, then the B cell epitopes were used to prepare affinity chromatography columns respectively and purify the binding IgG from serum samples of convalescent COVID-19 patients. After these IgGs were identified to have neutralizing activity, the peptide sequences of the antigen-binding regions (variable region) of neutralizing antibodies were analyzed by protein mass spectrometry. Subsequently, the B cells from the same individual were sorted and used to obtain their full BCR repertoire by 5' RACE combined with highthroughput of PacBio sequencing method. Then, the peptide sequence of neutralizing antibody variable region by protein mass spectrometry was mapped to the full BCR repertoire and found the full variable region sequence of neutralizing antibodies. Finally, we obtained and synthesized numerous CDR3 peptides of neutralizing antibodies to confirm the neutralizing activity for SARS-CoV-2 infection. Our results indicate that the novel scheme will be suitable for rapid screening of neutralizing antibodies, including screening neutralizing antibodies against SARS-CoV-2 and other pathogenic microorganisms. [ABSTRACT FROM AUTHOR]

Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV-specific neutralizing antibodies were detected for 6 years postinfection. [ABSTRACT FROM AUTHOR]

Rapalogs, inhibitors of mTORC1 (mammalian target of rapamycin complex 1), increase life span and delay age-related phenotypes in many species. However, the molecular mechanisms have not been fully elucidated. We determined gene expression changes comparing 6- and 24-month-old rats in the kidney, liver, and skeletal muscle, and asked which of these changes were counter-regulated by a clinically-translatable (short-term and low-concentration) treatment, with a rapalog (RAD001). Surprisingly, RAD001 had a more pronounced effect on the kidney under this regimen in comparison to the liver or skeletal muscle. Histologic evaluation of kidneys revealed that the severity of chronic progressive nephropathy lesions was lower in kidneys from 24-month-old rats treated with RAD001 compared with vehicle. In addition to other gene expression changes, c-Myc, which has been shown to regulate aging, was induced by aging in the kidney and counter-regulated by RAD001. RAD001 caused a decrease in c-Myc protein, which could be rescued by a proteasome inhibitor. These findings point to settings for use of mTORC1 inhibitors to treat age-related disorders, and highlight c-Myc regulation as one of the potential mechanisms by which mTORC1 inhibition is perturbing age-related phenotypes. [ABSTRACT FROM AUTHOR]

Nitrogen (N) is an essential macronutrient for plant growth and excessive application rates can decrease crop yield and increase N loss into the environment. Field experiments were carried out to understand the effects of N fertilizers on N utilization, crop yield and net income in wheat and maize rotation system of the North China Plain (NCP). Compared to farmers' N rate (FN), the yield of wheat and maize in reduction N rate by 21-24% based on FN (RN) was improved by 451 kg ha-1, N uptakes improved by 17 kg ha-1 and net income increased by 1671 CNY ha-1, while apparent N loss was reduced by 156 kg ha-1. The controlled-release fertilizer with a 20% reduction of RN (CRF80%), a 20% reduction of RN together with dicyandiamide (RN80%CDCD) and a 20% reduction of RN added with nano-carbon (RN80%CNC) all resulted in an improvement in crop yield and decreased the apparent N losses compared to RN. Contrasted with RN80%CNC, the total crop yield in RN80%CDCD improved by 1185 kg ha-1, N uptake enhanced by 9 kg ha-1 and net income increased by 3929 CNY ha-1, while apparent N loss was similar. Therefore, a 37-39% overall decrease in N rate compared to farmers plus the nitrification inhibitor, DCD, was effective N control measure that increased crop yields, enhanced N efficiencies, and improved economic benefits, while mitigating apparent N loss. There is considerable scope for improved N use effieincy in the intensive wheat-maize rotation of the NCP. [ABSTRACT FROM AUTHOR]

West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab')2 fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab')2 fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab')2 passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV. [ABSTRACT FROM AUTHOR]

Bone morphogenetic protein 9 (BMP9), also known as growth differentiation factor 2, plays a key role in promoting osteosarcoma growth. However, the underlying mechanism remains to be determined. The aim of the present study was to determine the mechanism of BMP9 promoting the growth of osteosarcoma mediated by the Notch signaling pathway. Osteosarcoma cell lines, 143B and MG63, were used for the in vitro experiments. Cell proliferation, cell migration and cell cycle transformation were monitored under various settings. The control and experimental groups used in the present study were BMP9 adenovirus (AdBMP9), a recombinant adenovirus expressing the dominant-negative mutant of Notch1 (AdR-dnNotch1), AdBMP9+AdR-dnNotch1 and AdBMP9+compound E (blocker of the Notch signaling pathway). The results showed that Notch ligands DLL1, JAG1 and JAG2, as well as Notch receptors Notch1, Notch2 and Notch3 were markedly expressed in the two cell lines. Cell proliferation and migration ability increased in the AdBMP9 group and were higher than that in the AdBMP9+AdR-dn Notch1 and AdBMP9+compound E group. Cell proliferation and migration in the AdR-dnNothc1 group was lower than that in the AdBMP9 group, although the differences were not statistically significant (P>0.05). The cell cycle ratio in the S/G2 phase increased significantly in the AdBMP9 group and was higher than that in the AdBMP9+AdR-dnNotch1 and AdBMP9+compound E groups. By contrast, the ratio of the cell cycle in S/G2 phase in the AdR-dnNotch1 group was lower than that in the AdBMP9 group. The differences were not statistically significant (P>0.05). In conclusion, the results showed that the Notch signaling pathway plays an important role in mediating the growth of osteosarcoma promoted by BMP9. [ABSTRACT FROM AUTHOR]

Generation of complex libraries of defined nucleic acid sequences can greatly aid the functional analysis of protein and gene function. Previously, such studies relied either on individually synthesized oligonucleotides or on cellular nucleic acids as the starting material. As each method has disadvantages, we have developed a rapid and cost-effective alternative for construction of small-fragment DNA libraries of defined sequences. This approach uses in situ microarray DNA synthesis for generation of complex oligonucleotide populations. These populations can be recovered and either used directly or immortalized by cloning. From a single microarray, a library containing thousands of unique sequences can be generated. As an example of the potential applications of this technology, we have tested the approach for the production of plasmids encoding short hairpin RNAs (shRNAs) targeting numerous human and mouse genes. We achieved high-fidelity clone retrieval with a uniform representation of intended library sequences. [ABSTRACT FROM AUTHOR]

Presents a study which examined the sources of impedance change for both band-electrode and spot-electrode impedance cardiography (ICG) using the finite-element method. Background on ICG; Computational approach used; Findings and discussion.

Deals with a study which examined the application to the estimation of defibrillation efficacy of a finite-element model that incorporates myocardial anisotropy. Principle behind a finite-element model; Data and methods used; Findings and discussion.

Presents a globally adaptive pixel-decimation algorithm for block-motion estimation. Techniques used for the estimation of bock-motion vectors; Hilbert-scan-based globally adaptive pixel decimation; Principles in the selection of pixel-decimation algorithm; Use of mean absolute difference for the evaluation of block matching in view of its low computation cost.

A conference paper about the identification and functional validation of non-coding RNAs (ncRNAs) that causes changes in the structure of chromatin is presented. It states that Bmi1 which is a component of Polycomb group (PcG) and a stable FLAG-Bmi1 were immunoprecipitated from the chromatin extract and then Bmi1-associated ncRNAs were biochemically isolated. It further states that messenger-RNA exons enriched in RNA immunoprecipitations eliminates other false isolated products.