It is widely known that the degeneration of neural circuits is prominent in the brains of Alzheimer’s disease (AD) patients. The reciprocal connectivity of the medial septum (MS) and hippocampus, which constitutes the septo-hippocampo-septal (SHS) loop, is known to be associated with learning and memory. Despite the importance of the reciprocal projections between the MS and hippocampus in AD, the alteration of bidirectional connectivity between two structures has not yet been investigated at the mesoscale level. In this study, we adopted AD animal model, five familial AD mutations (5XFAD) mice, and anterograde and retrograde tracers, BDA and DiI, respectively, to visualize the pathology-related changes in topographical connectivity of the SHS loop in the 5XFAD brain. By comparing 4.5-month-old and 14-month-old 5XFAD mice, we successfully identified key circuit components of the SHS loop altered in 5XFAD brains. Remarkably, the SHS loop began to degenerate in 4.5-month-old 5XFAD mice before the onset of neuronal loss. The impairment of connectivity between the MS and hippocampus was accelerated in 14-month-old 5XFAD mice. These results demonstrate, for the first time, topographical evidence for the degradation of the interconnection between the MS and hippocampus at the mesoscale level in a mouse model of AD. Our results provide structural and functional insights into the interconnectivity of the MS and hippocampus, which will inform the use and development of various therapeutic approaches that target neural circuits for the treatment of AD.

Porcine epidemic diarrhea (PED), a highly contagious and lethal enteric disease in piglets, is characterized by diarrhea, vomiting, and dehydration, with high mortality in neonatal piglets. Despite the nationwide use of attenuated and inactivated vaccines, the outbreak of PED is still a major problem in the swine industry. Virus-like particles (VLPs) are artificial nanoparticles similar to viruses that are devoid of genetic material and are unable to replicate. VLPs have good safety profiles and elicit robust cellular and humoral immune responses. Here, we generated PED VLPs in eukaryotic cells and examined their immune responses in mice. We found that the M protein is essential for the formation of PED VLPs. Interestingly, PED VLP formation was decreased in the presence of E proteins and increased in the presence of N proteins. Both IgG and IgA antibodies were induced in mice immunized with PED VLPs. Moreover, these antibodies protected against PED virus infection in Vero cells. PED VLPs immunization induced Th2-dominant immune responses in mice. Our results indicate that PED VLPs induce strong immune responses in mice, suggesting that the VLP-based vaccine is a promising vaccine candidate.

Highly pathogenic avian influenza (HPAI) virus is a causative agent of systemic disease in poultry, characterized by high mortality. Rapid diagnosis is crucial for the control of HPAI. In this study, we aimed to develop a differential diagnostic method that can distinguish HPAI from low pathogenic avian influenza (LPAI) viruses using dual split proteins (DSPs). DSPs are chimeras of an enzymatic split, Renilla luciferase (RL), and a non-enzymatic split green fluorescent protein (GFP). Nanoparticles expressing DSPs, sialic acid, and/or transmembrane serine protease 2 (TMPRSS2) were generated, and RL activity was determined in the presence of HPAI or LPAI pseudotyped viruses. The RL activity of nanoparticles containing both DSPs was approximately 2 × 10⁶ RLU, indicating that DSPs can be successfully incorporated into nanoparticles. The RL activity of nanoparticles containing half of the DSPs was around 5 × 10¹ RLU. When nanoparticles containing half of the DSPs were incubated with HPAI pseudotyped viruses at low pH, RL activity was increased up to 1 × 10³ RLU. However, LPAI pseudotyped viruses produced RL activity only in the presence of proteases (trypsin or TMPRSS2), and the average RL activity was around 7 × 10² RLU. We confirmed that nanoparticle fusion assay also diagnoses authentic viruses with specificity of 100% and sensitivity of 91.67%. The data indicated that the developed method distinguished HPAI and LPAI, and suggested that the diagnosis using DSPs could be used for the development of differential diagnostic kits for HPAI after further optimization.