Pain, obesity, adenosine salvage disruption, and smoking behavior mediate the effect of gut microbiota on sleep disorders: results from network Mendelian randomization and 16S rDNA sequencing.

Objectives: The objective of this study is to investigate the indirect causalities between gut microbiota and sleep disorders. Methods: In stage 1, we utilized 196 gut microbiota as the exposure factor and conducted a two-sample univariable Mendelian randomization (MR) analysis on five sleep disorders: insomnia, excessive daytime sleepiness (EDS), sleep-wake rhythm disorders (SWRD), obstructive sleep apnea (OSA), and isolated REM sleep behavior disorder (iRBD). In stage 2, we validated the MR findings by comparing fecal microbiota abundance between patients and healthy controls through 16S rDNA sequencing. In stage 3, we explored the indirect pathways by which the microbiota affects sleep, using 205 gut microbiota metabolic pathways and 9 common risk factors for sleep disorders as candidate mediators in a network MR analysis. Results: In stage 1, the univariable MR analysis identified 14 microbiota potentially influencing five different sleep disorders. In stage 2, the results from our observational study validated four of these associations. In stage 3, the network MR analysis revealed that the Negativicutes class and Selenomonadales order might worsen insomnia by increasing pain [mediation: 12.43% (95% CI: 0.47, 24.39%)]. Oxalobacter could raise EDS by disrupting adenosine reuptake [25.39% (1.84, 48.95%)]. Allisonella may elevate OSA risk via obesity promotion [36.88% (17.23, 56.54%)], while the Eubacterium xylanophilum group may lower OSA risk by decreasing smoking behavior [7.70% (0.66, 14.74%)]. Conclusion: Triangulation of evidence from the MR and observational study revealed indirect causal relationships between the microbiota and sleep disorders, offering fresh perspectives on how gut microbiota modulate sleep.

Causal associations between modifiable risk factors and isolated REM sleep behavior disorder: a mendelian randomization study.

Objectives: This Mendelian randomization (MR) study identified modifiable risk factors for isolated rapid eye movement sleep behavior disorder (iRBD). Methods: Genome-wide association study (GWAS) datasets for 29 modifiable risk factors for iRBD in discovery and replication stages were used. GWAS data for iRBD cases were obtained from the International RBD Study Group. The inverse variance weighted (IVW) method was primarily employed to explore causality, with supplementary analyses used to verify the robustness of IVW findings. Co-localization analysis further substantiated causal associations identified via MR. Genetic correlations between mental illness and iRBD were identified using trait covariance, linkage disequilibrium score regression, and co-localization analyses. Results: Our study revealed causal associations between sun exposure-related factors and iRBD. Utilizing sun protection (odds ratio [OR] = 0.31 [0.14, 0.69], p = 0.004), ease of sunburn (OR = 0.70 [0.57, 0.87], p = 0.001), childhood sunburn occasions (OR = 0.58 [0.39, 0.87], p = 0.008), and phototoxic dermatitis (OR = 0.78 [0.66, 0.92], p = 0.003) decreased iRBD risk. Conversely, a deep skin color increased risk (OR = 1.42 [1.04, 1.93], p = 0.026). Smoking, alcohol consumption, low education levels, and mental illness were not risk factors for iRBD. Anxiety disorders and iRBD were genetically correlated. Conclusion: Our study does not corroborate previous findings that identified smoking, alcohol use, low education, and mental illness as risk factors for iRBD. Moreover, we found that excessive sun exposure elevates iRBD risk. These findings offer new insights for screening high-risk populations and devising preventive measures.

Plasma Soluble Podoplanin as a Biomarker of Hypercoagulability and Cellular Immunity Status in Patients With Non-small Cell Lung Cancer.

Podoplanin (PDPN) is known to play a role in thrombosis, metastasis of tumor cells, the epithelial-mesenchymal transition (EMT), and immune response. The present study aim to evaluate the clinical significance of soluble PDPN (sPDPN) in hypercoagulability and cellular immune status in patients with non-small cell lung cancer (NSCLC). Enzyme-linked immunosorbent assay (ELISA) was used to determine plasma sPDPN levels, and T-lymphocyte distribution was determined using flow cytometry. The levels of sPDPN were markedly higher in the NSCLC group than control group, and sPDPN was higher in patients with advanced-stage and with distant metastases. The high-sPDPN group had lower absolute numbers of CD3+, CD4+, and CD4+/CD8+ ratio than low-sPDPN group. Correlation analysis indicated that sPDPN was positively linked to platelet (r = 0.50, P < .001), D-dimer (r = 0.52, P < .001), and fibrinogen (r = 0.37, P < .001); and inversely correlated with CD3+ (r = -0.37, P < .001), CD4+ (r = -0.44, P < .001), and CD4+/CD8+ (r = -0.37, P < .001). Multivariate logistic regression analysis indicated that sPDPN (odds ratio [OR] = 2.293; 95% CI, 1.559-3.373) and tumor stage (OR = 15.857; 95% CI, 1.484-169.401) were separate risk indicators for hypercoagulability. The receiver operating characteristic curves (ROC) indicated that sPDPN had high diagnostic values for hypercoagulability in NSCLC patients. In conclusion, plasma sPDPN was not only linked to hypercoagulability, but it may also be an indicator of the body's cellular immune status in NSCLC patients.

[Preparation of Magnetic Biomass Carbon by Thermal Decomposition of Siderite Driven by Wheat Straw and Its Adsorption on Cadmium].

C-Fe3O4 composite material [magnetic biomass char (MBC)] was prepared by pyrolysis of a mixture of wheat straw and siderite at 500℃. The MBC was characterized by XRF, FTIR, XRD, SEM, XPS, and a magnetic susceptibility device. The effect of contact time, pH value, initial Cd2+ concentration, and ionic strength on the adsorption capacity of the MBC to Cd2+ was investigated. The results showed that the BET surface areas of the MBC and biomass char (BC) were 23.38 m2·g-1 and 7.20 m2·g-1, respectively, total pore volumes were 1.04×10-1 cm3·g-1 and 2.23×10-2 cm3·g-1, and average pore diameters were 17.74 nm and 12.38 nm. The magnetic susceptibility of the MBC was 42900×10-8 m3·kg-1. FTIR showed that phenolic hydroxyl and carboxyl functional groups bound metal ions on the surface of the MBC and BC. The kinetic data of the MBC were described well by the pseudo-second-order model. Isothermal adsorption of Cd2+ by MBC and BC was fitted well by the Freundlich equation. The adsorption velocity increased with an increase of pH in the region 3-6 and then stabilized in the region 6-9. The adsorption capacity of Cd2+ decreased slightly when ionic strength increased from 1 mmol·L-1 to 100 mmol·L-1, whereas the desorption rate increased from 0.51% to 8.5%. The adsorption properties and characterization results illustrated that the removal mechanism of Cd2+ likely was through adsorption and ion exchange on the surface of the MBC with a high amount of functional groups. In addition, magnetic adsorbents offered a significant advantage compared to other adsorbents in the aspect of separation from aqueous solution.