Potential effects of specific gut microbiota on periodontal disease: a two-sample bidirectional Mendelian randomization study

IntroductionPeriodontal disease (PD) presents a substantial global health challenge, encompassing conditions from reversible gingivitis to irreversible periodontitis, often culminating in tooth loss. The gut-oral axis has recently emerged as a focal point, with potential gut microbiota dysbiosis exacerbating PD.MethodsIn this study, we employed a double-sample bidirectional Mendelian randomized (MR) approach to investigate the causal relationship between specific gut microbiota and periodontal disease (PD) and bleeding gum (BG) development, while exploring the interplay between periodontal health and the gut microenvironment. We performed genome-wide association studies (GWAS) with two cohorts, totalling 346,731 (PD and control) and 461,113 (BG and control) participants, along with data from 14,306 participants’ intestinal flora GWAS, encompassing 148 traits (31 families and 117 genera). Three MR methods were used to assess causality, with the in-verse-variance-weighted (IVW) measure as the primary outcome. Cochrane’s Q test, MR-Egger, and MR-PRESSO global tests were used to detect heterogeneity and pleiotropy. The leave-one-out method was used to test the stability of the MR results. An F-statistic greater than 10 was accepted for instrument exposure association.Results and conclusionSpecifically, Eubacterium xylanophilum and Lachnoclostridium were associated with reduced gum bleeding risk, whereas Anaerotruncus, Eisenbergiella, and Phascolarctobacterium were linked to reduced PD risk. Conversely, Fusicatenibacter was associated with an elevated risk of PD. No significant heterogeneity or pleiotropy was detected. In conclusion, our MR analysis pinpointed specific gut flora with causal connections to PD, offering potential avenues for oral health interventions

Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation

IntroductionHypoxia is an environmental risk factor for many disorders throughout life. Perinatal hypoxia contributes to autism spectrum disorder (ASD), while hypoxic conditions in the elderly facilitate memory deficits. However, the effects of hypoxia on adolescence remains elusive. CNTNAP2 is a critical molecule in ASD pathogenesis with undefined mechanisms. We investigate hypoxia’s impact on adolescence and the underlying mechanism related to CNTNAP2.MethodsThree-chamber social approach test, Y maze, Morris Water Maze and Open Field Test were applied to evaluate behavioral alterations. Immunoblotting, 5′- RACE and dual-luciferase reporter assay were performed to examine CNTNAP2 protein expression, transcription start site (TSS) of human CNTNAP2 gene and CNTNAP2 promoter activity, respectively.ResultsIntermittent hypoxia treatment improved social behaviors and working memory in adolescent mice. CNTNAP2 was increased in the brains of hypoxia-treated mice. The sequencing results identified the TSS at 518 bp upstream of the translation start site ATG. Hypoxia upregulated CNTNAP2 by interacting with functional hypoxia response elements in CNTNAP2 promoter.ConclusionIntermittent hypoxia enhanced sociability and working memory associated with CNTNAP2 upregulation. Our study provides novel insights into intermittent hypoxia’s impact on development and the interaction between genetic and environmental risk factors in ASD pathogenesis

A FRACTAL APPROACH TO SPONTANEOUS IMBIBITION HEIGHT IN NATURAL POROUS MEDIA

Spontaneous imbibition of wetting liquids in porous media is of great importance in many fields. In this paper, an analytical model for characterizing spontaneous imbibition height versus time in natural porous media was derived using fractal approach. The average imbibition height in porous media is in terms of porosity, fractal dimensions, maximum pore size and viscosity, surface tension and liquid-solid interactions. The developed model is consistent with previous results and is tested against available experimental data showing fair agreements

Regulation of global gene expression in brain by TMP21

TMP21, a type I transmembrane protein of thep24 protein family, mediates protein trafficking and maturation. Dysregulation of TMP21 is implicated in the pathogenesis of Alzheimer’s disease (AD). However, underlying mechanisms remain elusive. To reveal the function of TMP21 in the brain and the pathogenic role of TMP21 in the brain of AD, the global gene expression was profiled in the brain of TMP21 knockdown mice. We found that 8196 and 8195 genes are significantly altered in the hippocampus and cortex, respectively. The genes are involved in a number of brain function-related pathways, including glutamatergic synapse pathway, serotonergic synapse pathway, synaptic vesicle pathway, and long-term depression pathway. Moreover, the network analysis suggests that the TMP21 may contribute to the pathogenesis of AD by regulatingPI3K/Akt/GSK3β signalling pathway. Our study provides an insight into the physiological function of TMP21 in the brain and pathological role of TMP21 in AD.Medicine, Faculty ofNon UBCPsychiatry, Department ofReviewedFacult

Enniatin B1 induces damage to Leydig cells via inhibition of the Nrf2/HO-1 and JAK/STAT3 signaling pathways

Enniatin B1 (ENN B1) is a mycotoxin that can be found in various foods. However, whether ENN B1 is hazardous to the reproductive system is still elusive. Leydig cells are testosterone-generating cells that reside in the interstitial compartment between seminiferous tubules. Dysfunction of Leydig cells could result in male infertility. This study aimed to examine the toxicological effects of ENN B1 against TM3 Leydig cells. ENN B1 significantly inhibited cell viability in a dose-dependent manner. ENN B1 treatment also decreased the expression of functional genes in Leydig cells. Moreover, ENN B1 induced Leydig cells apoptosis and oxidative stress. Mechanistically, ENN B1 leads to the upregulation of Bax and downregulation of Bcl-2 in Leydig cells. In addition, ENN B1 inhibited the Nrf2/HO-1 pathway, which is critical for the induction of oxidative stress. Additionally, ENN B1 treatment repressed the JAK/STAT3 signaling pathway in Leydig cells. Rescue experiments showed that activation of STAT3 resulted in alleviation of ENN B1-induced damage in Leydig cells. Collectively, our study demonstrated that ENN B1 induced Leydig cell dysfunction via multiple mechanisms

A viscous continuum traffic flow model based on the cooperative car‐following behaviour of connected and autonomous vehicles

Abstract Connected and Autonomous Vehicles (CAVs) can receive various information from surrounding vehicles through Vehicle‐to‐Everything (V2X) communication technologies and adjust their car‐following behaviour accordingly. Although several studies have evaluated the impact of CAVs on traffic flow stability in a small segment of networks, most approaches are focused on their specific applications considering the trajectory information, and there is a lack of studies analyzing the impact of CAVs on a large‐scale network. This paper proposes a novel viscous continuum traffic model considering the anticipation of space headway, the throttle angle, and brake torque information during cooperative car‐following. The methods employed to develop the new car‐following model and its counterpart continuum traffic model have been described. The linear and non‐linear stability analyses of the newly developed model have been conducted to obtain the critical stability factors in small perturbations. Numerical simulations have been carried out to investigate the effect of the anticipation, the throttle angle, and brake torque information on traffic stability, fuel consumption, and exhaust emissions. The numerical results reveal that the anticipation of space headway and the transmission of the throttle angle and brake torque information during cooperative car‐following manoeuvres can improve the traffic flow stability and reduce fuel consumption and emissions