Causal relationship between the immune cells and ankylosing spondylitis: univariable, bidirectional, and multivariable Mendelian randomization

BackgroundAnkylosing spondylitis (AS) is an autoimmune disease that affects millions of individuals. Immune cells have been recognized as having a crucial role in the pathogenesis of AS. However, their relationship has not been fully explored.MethodsWe chose to employ Mendelian randomization (MR) to investigate the potential correlation between immune cells and AS. We sourced the data on immune cells from the latest genome-wide association studies (GWASs). We obtained data on AS from the FinnGen consortium. Our comprehensive univariable MR analysis covered 731 immune cells to explore its potential causal relationship with AS. The primary analysis method was inverse-variance weighted (IVW). Additionally, we used Cochran’s Q test and the MR-Egger intercept test to assess the presence of pleiotropy and heterogeneity. We examined whether our results could be influenced by individual single-nucleotide polymorphisms (SNPs) using the leave-one-out test. We conducted a bidirectional MR to investigate the reverse relationship. We also applied multivariable MR to decrease the potential influence between the immune cells.ResultsOverall, our univariable MR analysis revealed eight immune cells associated with AS. Among these, four immune cells contributed to an increased risk of AS, while four immune cells were identified as protective factors for AS. However, the Bonferroni test confirmed only one risk factor and one protective factor with a significance level of p < 6.84E−05. CD8 on effector memory CD8+ T cell could increase the risk of AS (p: 1.2302E−05, OR: 2.9871, 95%CI: 1.8289–4.8786). HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 1.2301E−06, OR: 0.5446, 95%CI: 0.4260–0.6962). We also identified a bidirectional relationship between CD4 on CD39+ activated CD4 regulatory T cells and AS utilizing the bidirectional MR. To address potential confounding among immune cells, we employed multivariable MR analysis, which revealed that only one immune cell had an independent effect on AS. HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 2.113E−06, OR: 0.0.5423, 95%CI: 0.4210–0.6983). Our findings were consistently stable and reliable.ConclusionsOur findings indicated a potential link between immune cells and AS, which could provide a new idea for future research. Nevertheless, the specific underlying mechanisms require further exploration

A Mobile Localization Method in Smart Indoor Environment Using Polynomial Fitting for Wireless Sensor Network

The main factor affecting the localization accuracy is nonline of sight (NLOS) error which is caused by the complicated indoor environment such as obstacles and walls. To obviously alleviate NLOS effects, a polynomial fitting-based adjusted Kalman filter (PF-AKF) method in a wireless sensor network (WSN) framework is proposed in this paper. The method employs polynomial fitting to accomplish both NLOS identification and distance prediction. Rather than employing standard deviation of all historical data as NLOS detection threshold, the proposed method identifies NLOS via deviation between fitted curve and measurements. Then, it processes the measurements with adjusted Kalman filter (AKF), conducting weighting filter in the case of NLOS condition. Simulations compare the proposed method with Kalman filter (KF), adjusted Kalman filter (AKF), and Kalman-based interacting multiple model (K-IMM) algorithms, and the results demonstrate the superior performance of the proposed method. Moreover, experimental results obtained from a real indoor environment validate the simulation results

Insight into atomic-scale adhesion at the C/Cu interface during the initial stage of nanoindentation

Adhesion is a common phenomenon in nanomachining which affects processing accuracy and repeatability. As material removal approaches the atomic or close-to-atomic scale, quantum mechanics becomes the dominant principle behind the atomic-level interaction. However, atomic-scale effects cannot be properly described by empirical potential function-based molecular dynamics simulations. This study uses a first-principles method to reveal the atomic-scale adhesion between a diamond tip and a copper slab during initial-stage nanoindentation. Using a simplified tip and slab model, adhesion energy, electronic distribution and density of states are analysed based on quantum chemistry calculation. Results show that atomic adhesion is primarily due to the covalent bonding interaction between C and Cu atoms, which can induce structural changes to the diamond tip and copper slab. The effects of tip position and angles on adhesion are further studied through a series of simulation. The results show that adhesion between the tip and slab is sensitive to the lattice structure and a variant in angstroms is enough to cause different adhesion and structural changes. The actual determinants of adhesion can only be the atomic and electronic structures at the tip-slab interface. Bond rotation and breakage are observed during simulation and their effects on adhesion are further discussed. To conclude, the first-principles method is important for the analysis of an atomic-scale interaction system, even if only as an aid to describing adhesion at atomic and electronic scales

Resistance mechanisms and remediation potential of hexavalent chromium in Pseudomonas sp. strain AN-B15

The understanding of bacterial resistance to hexavalent chromium [Cr(VI)] are crucial for the enhancement of Cr(VI)-polluted soil bioremediation. However, the mechanisms related to plant-associated bacteria remain largely unclear. In this study, we investigate the resistance mechanisms and remediation potential of Cr(VI) in a plant-associated strain, AN-B15. The results manifested that AN-B15 efficiently reduced Cr(VI) to soluble organo-Cr(III). Specifically, 84.3 % and 56.5 % of Cr(VI) was removed after 48 h in strain-inoculated solutions supplemented with 10 and 20 mg/L Cr(VI) concentrations, respectively. Transcriptome analyses revealed that multiple metabolic systems are responsible for Cr(VI) resistance at the transcriptional level. In response to Cr(VI) exposure, strain AN-B15 up-regulated the genes involved in central metabolism, providing the reducing power by which enzymes (ChrR and azoR) transformed Cr(VI) to Cr(III) in the cytoplasm. Genes involved in the alleviation of oxidative stress and DNA repair were significantly up-regulated to neutralize Cr(VI)-induced toxicity. Additionally, genes involved in organosulfur metabolism and certain ion transporters were up-regulated to counteract the starvation of sulfur, molybdate, iron, and manganese induced by Cr(VI) stress. Furthermore, a hydroponic culture experiment showed that toxicity and uptake of Cr(VI) by plants under Cr(VI) stress were reduced by strain AN-B15. Specifically, strain AN-B15 inoculation increased the fresh weights of the wheat root and shoot by 55.5 % and 18.8 %, respectively, under Cr(VI) stress (5 mg/L). The elucidation of bacterial resistance to Cr(VI) has an important implication for exploiting microorganism for the effective remediation of Cr(VI)-polluted soils

DataSheet_1_Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization.zip

BackgroundIntervertebral disc degeneration (IVDD) is a prominent contributor to chronic low back pain, impacting millions of individuals annually. Current research on disc degeneration is placing a growing emphasis on the role of the immune system in this process. Nevertheless, the precise relationship between immunity and disc degeneration remains to be fully elucidated.MethodWe obtained GWAS data for immune cells from the latest summary-level GWAS, including 6,620 individuals from Sardinian and 746,667 individuals from five global populations. Summary results for IVDD were sourced from the FinnGen consortium, comprising 20,001 cases and 164,682 controls. We conducted a comprehensive univariable Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and IVDD. Primary estimation was carried out using Inverse-Variance Weighting (IVW). To ensure robustness, we employed additional MR methods such as MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. Various tests were employed to assess pleiotropy and heterogeneity, including the Cochran Q test, leave-one-out test, MR-Egger intercept analysis and MR-PRESSO test. To account for potential confounding factors among the immune cells, we conducted a multivariable MR analysis. Finally, we investigated the possibility of a reverse association between immune cells and IVDD through bidirectional MR.ResultIn total, our study identified 15 immune cells significantly associated with IVDD through univariable MR. Among these, 9 immune cell types were indicated as potential contributors to IVDD, while 6 were found to have protective effects. Importantly, we observed no evidence of heterogeneity or pleiotropy, signifying the robustness of our results. To mitigate confounding among immune cells, we utilized multivariable MR, leading to the discovery that only 9 immune cell types exerted independent effects on IVDD. These encompassed 7 as risk factors and 2 as protective factors. Additionally, our analysis revealed a bidirectional causal relationship between CD39+ CD4+ T cell �4+ T cell and IVDD.ConclusionOur findings suggest a connection between immune cells and the risk of IVDD, shedding light on potential therapeutic avenues for modulating immune cell function in individuals with IVDD. However, the specific underlying mechanisms warrant further investigation in future experiments.</p

The versatile functions of Sox9 in development, stem cells, and human diseases

AbstractThe transcription factor Sox9 was first discovered in patients with campomelic dysplasia, a haploinsufficiency disorder with skeletal deformities caused by dysregulation of Sox9 expression during chondrogenesis. Since then, its role as a cell fate determiner during embryonic development has been well characterized; Sox9 expression differentiates cells derived from all three germ layers into a large variety of specialized tissues and organs. However, recent data has shown that ectoderm- and endoderm-derived tissues continue to express Sox9 in mature organs and stem cell pools, suggesting its role in cell maintenance and specification during adult life. The versatility of Sox9 may be explained by a combination of post-transcriptional modifications, binding partners, and the tissue type in which it is expressed. Considering its importance during both development and adult life, it follows that dysregulation of Sox9 has been implicated in various congenital and acquired diseases, including fibrosis and cancer. This review provides a summary of the various roles of Sox9 in cell fate specification, stem cell biology, and related human diseases. Ultimately, understanding the mechanisms that regulate Sox9 will be crucial for developing effective therapies to treat disease caused by stem cell dysregulation or even reverse organ damage

DataSheet_1_Causal relationship between the immune cells and ankylosing spondylitis: univariable, bidirectional, and multivariable Mendelian randomization.zip

BackgroundAnkylosing spondylitis (AS) is an autoimmune disease that affects millions of individuals. Immune cells have been recognized as having a crucial role in the pathogenesis of AS. However, their relationship has not been fully explored.MethodsWe chose to employ Mendelian randomization (MR) to investigate the potential correlation between immune cells and AS. We sourced the data on immune cells from the latest genome-wide association studies (GWASs). We obtained data on AS from the FinnGen consortium. Our comprehensive univariable MR analysis covered 731 immune cells to explore its potential causal relationship with AS. The primary analysis method was inverse-variance weighted (IVW). Additionally, we used Cochran’s Q test and the MR-Egger intercept test to assess the presence of pleiotropy and heterogeneity. We examined whether our results could be influenced by individual single-nucleotide polymorphisms (SNPs) using the leave-one-out test. We conducted a bidirectional MR to investigate the reverse relationship. We also applied multivariable MR to decrease the potential influence between the immune cells.ResultsOverall, our univariable MR analysis revealed eight immune cells associated with AS. Among these, four immune cells contributed to an increased risk of AS, while four immune cells were identified as protective factors for AS. However, the Bonferroni test confirmed only one risk factor and one protective factor with a significance level of p + T cell could increase the risk of AS (p: 1.2302E−05, OR: 2.9871, 95%CI: 1.8289–4.8786). HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 1.2301E−06, OR: 0.5446, 95%CI: 0.4260–0.6962). We also identified a bidirectional relationship between CD4 on CD39+ activated CD4 regulatory T cells and AS utilizing the bidirectional MR. To address potential confounding among immune cells, we employed multivariable MR analysis, which revealed that only one immune cell had an independent effect on AS. HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 2.113E−06, OR: 0.0.5423, 95%CI: 0.4210–0.6983). Our findings were consistently stable and reliable.ConclusionsOur findings indicated a potential link between immune cells and AS, which could provide a new idea for future research. Nevertheless, the specific underlying mechanisms require further exploration.</p