A multi-cohort study of the hippocampal radiomics model and its associated biological changes in Alzheimer’s Disease

Abstract There have been no previous reports of hippocampal radiomics features associated with biological functions in Alzheimer’s Disease (AD). This study aims to develop and validate a hippocampal radiomics model from structural magnetic resonance imaging (MRI) data for identifying patients with AD, and to explore the mechanism underlying the developed radiomics model using peripheral blood gene expression. In this retrospective multi-study, a radiomics model was developed based on the radiomics discovery group (n = 420) and validated in other cohorts. The biological functions underlying the model were identified in the radiogenomic analysis group using paired MRI and peripheral blood transcriptome analyses (n = 266). Mediation analysis and external validation were applied to further validate the key module and hub genes. A 12 radiomics features-based prediction model was constructed and this model showed highly robust predictive power for identifying AD patients in the validation and other three cohorts. Using radiogenomics mapping, myeloid leukocyte and neutrophil activation were enriched, and six hub genes were identified from the key module, which showed the highest correlation with the radiomics model. The correlation between hub genes and cognitive ability was confirmed using the external validation set of the AddneuroMed dataset. Mediation analysis revealed that the hippocampal radiomics model mediated the association between blood gene expression and cognitive ability. The hippocampal radiomics model can accurately identify patients with AD, while the predictive radiomics model may be driven by neutrophil-related biological pathways

Epstein-Barr Virus Promotes Inflammatory Cytokine Production in Human Gingival Fibroblasts

Background: Periodontitis is one of the most common chronic oral inflammatory diseases. Over the past decade, herpes viruses, particularly Epstein-Barr virus (EBV), have been considered promising pathogenic candidates for periodontitis. However, the specific mechanism by which EBV contributes to the development of periodontitis is still unknown. This study aimed to explore the mechanism of EBV underlying the inflammatory response in human gingival fibroblasts (HGFs). Materials and methods: HGFs were stimulated with different concentrations of EBV (104, 105, 106, 107, and 108 DNA copies/mL) for 0, 8, 24, or 48 hours. The mRNA levels of interleukin (IL)-1β, tumour necrosis factor-α (TNF-α), IL-8, monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor 9 (TLR9) were measured using quantitative real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assays (ELISAs) were performed for determining the mRNA and protein levels of IL-1β, TNF-α, IL-8, and MCP-1. Real-time PCR and ELISA were performed to determine the protein levels of IL-1β, TNF-α, IL-8, and MCP-1. Activation of the TLR9/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) pathway was evaluated using western blotting. Results: The expressions of IL-1β, TNF-α, IL-8, and MCP-1 were significantly upregulated in HGFs under EBV stimulation in a concentration- and time-dependent manner. EBV promoted TLR9 and MyD88 expression and induced NF-κB transcription. On the contrary, the upregulation of these factors and the activation of NF-κB pathway were drastically inhibited by TLR9 antagonists. Conclusions: Our findings demonstrate that EBV promotes the production of inflammatory cytokines IL-1β and TNF-α and chemokines IL-8 and MCP-1 in HGFs through the TLR9/MyD88/NF-κB pathway

Orthohantaviruses infections in humans and rodents in Baoji, China.

In recent years, hemorrhagic fever with renal syndrome (HFRS) incidence has been becoming a severe public health problem again due to its significant increase in Shaanxi Province, China. Baoji, located in the Guanzhong Plain in the central part of Shaanxi Province, has been severely affected by HFRS since its first emergence in 1955. To better understand the epidemiology of orthohantaviruses infection in humans and the causative agents carried by the rodents, the long-term incidence patterns were analyzed and a molecular epidemiological investigation of orthohantaviruses infection in humans and rodents was performed. During 1984-2019, 13,042 HFRS cases were registered in Baoji, including 275 death cases. Except the first high prevalence of HFRS in 1988-1993, another two epidemic peaks were observed in 1998-2003 and 2012, respectively, although vaccination project was started since 1996. During the same period, HFRS cases in Baoji mainly were recorded in winter suggesting they may be caused by Hantaan orthohantavirus (HTNV), while a small peak of HFRS was also found in summer with unknown reason. Nucleotide identity and phylogenetic analyses demonstrated that a novel clade of HTNV sequences recovered from HFRS cases were closely related to those from rodents, including species close contact with humans, suggesting a direct viral transmission from rodents to humans and the important role in the HTNV transmission the nontraditional rodent hosts may play. Moreover, two distant related Dabieshan orthohantavirus (DBSV) lineages were also identified in Niviventer niviventer in this area demonstrating its considerable genetic diversity. Our data indicated that continual spillover of HTNV from rodents to humans, contributing to the high prevalence of HFRS in humans in Baoji

An Aptamer Affinity Column for Extraction of Four Aminoglycoside Antibiotics from Milk

This article introduces the aptamer affinity column (AAC) with nucleic acid aptamer as an affinity ligand for the extraction of four aminoglycoside antibiotics (AGs). The AAC was prepared by loading the aptamer functionalized Sepharose into an extraction column, which was conjugated by covalent binding between NHS-activated Sepharose and amino-modified aptamers with a coupling time of 2 h. After the sample solution flowed through the AAC, the AGs were retained because of the affinity between the AGs and aptamer, then AGs were eluted and analyzed by UPLC-MS/MS. Under the optimized conditions, the maximum adsorption of AGs on the AAC could reach 8.0 μg. Moreover, the proposed AAC could be reused more than 20 times. The resultant AAC that conjugated with the aptamer was successfully applied in the enrichment and purification of four AGs in a milk sample and good recovery results in the range of 83.3–98.8% were obtained (with RSD in the range of 0.6–5.8%). The proposed AAC for recognition of multi-target AGs exhibited good enrichment and purification effects, showing great application potential for targets with their related aptamers

An Aptamer Affinity Column for Extraction of Four Aminoglycoside Antibiotics from Milk

This article introduces the aptamer affinity column (AAC) with nucleic acid aptamer as an affinity ligand for the extraction of four aminoglycoside antibiotics (AGs). The AAC was prepared by loading the aptamer functionalized Sepharose into an extraction column, which was conjugated by covalent binding between NHS-activated Sepharose and amino-modified aptamers with a coupling time of 2 h. After the sample solution flowed through the AAC, the AGs were retained because of the affinity between the AGs and aptamer, then AGs were eluted and analyzed by UPLC-MS/MS. Under the optimized conditions, the maximum adsorption of AGs on the AAC could reach 8.0 μg. Moreover, the proposed AAC could be reused more than 20 times. The resultant AAC that conjugated with the aptamer was successfully applied in the enrichment and purification of four AGs in a milk sample and good recovery results in the range of 83.3–98.8% were obtained (with RSD in the range of 0.6–5.8%). The proposed AAC for recognition of multi-target AGs exhibited good enrichment and purification effects, showing great application potential for targets with their related aptamers

FERONIA receptor kinase pathway suppresses abscisic acid signaling in Arabidopsis by activating ABI2 phosphatase

Plant growth and development are controlled by a delicate balance of hormonal cues. Growth-promoting hormones and growth-inhibiting counterparts often antagonize each other in their action, but the molecular mechanisms underlying these events remain largely unknown. Here, we report a cross-talk mechanism that enables a receptor-like kinase, FERONIA (FER), a positive regulator of auxin-promoted growth, to suppress the abscisic acid (ABA) response through activation of ABI2, a negative regulator of ABA signaling. The FER pathway consists of a FER kinase interacting with guanine exchange factors GEF1, GEF4, and GEF10 that, in turn, activate GTPase ROP11/ARAC10. Arabidopsis mutants disrupted in any step of the FER pathway, including fer, gef1gef4gef10, or rop11/arac10, all displayed an ABA-hypersensitive response, implicating the FER pathway in the suppression mechanism. In search of the target for the FER pathway, we found that the ROP11/ARAC10 protein physically interacted with the ABI2 phosphatase and enhanced its activity, thereby linking the FER pathway with the inhibition of ABA signaling