Relationships between apolipoprotein E and insulin resistance in patients with obstructive sleep apnoea: a large-scale cross-sectional study.

BACKGROUND: Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA. METHODS: A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA. RESULTS: Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (ß = 0.107, ß = 0.102, ß = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425-2.017; OR = 2.371, 95% confidence interval (CI): 2.009-2.816; OR = 3.392, 95% CI: 2.853-4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women. CONCLUSIONS: This study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.

Melatonin mediates intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients.

BACKGROUND: Intestinal barrier dysfunction and systemic inflammation are common in obstructive sleep apnoea (OSA). We aimed to investigate the role of melatonin, an anti-inflammatory mediator, in mediating the relationships between OSA, intestinal barrier dysfunction and systemic inflammation. METHODS: Two hundred and thirty-five male participants who complained with sleep problems and underwent whole night polysomnography at our sleep centre between 2017 and 2018 were enrolled. Polysomnographic data, anthropometric measurements and biochemical indicators were collected. Serum melatonin, intestinal barrier function biomarker zonula occludens-1 (ZO-1) and inflammatory biomarkers C-reactive protein (CRP) with lipopolysaccharide (LPS) were detected. Spearman's correlation analysis assessed the correlations between sleep parameters, melatonin and biomarkers (ZO-1, LPS and CRP). Mediation analysis explored the effect of OSA on intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients. RESULTS: As OSA severity increased, serum melatonin decreased, whereas ZO-1, LPS and CRP increased. Spearman's correlation analysis showed that serum melatonin was significantly negatively correlated with ZO-1 (r = -0.19, p < .05) and LPS (r = -0.20, p < .05) in the moderate-OSA group; serum melatonin was significantly negatively correlated with ZO-1 (r = -0.46, p < .01), LPS (r = -0.35, p < .01) and CPR (r = -0.30, p < .05) in the severe-OSA group. Mediation analyses showed melatonin explain 36.12% and 35.38% of the effect of apnoea-hypopnea index (AHI) on ZO-1 and LPS in moderate to severe OSA patients. CONCLUSIONS: Our study revealed that melatonin may be involved in mediating intestinal barrier dysfunction and systemic inflammation in moderate-to-severe OSA patients.

Degradation of Sodium Acetate by Catalytic Ozonation Coupled with MnOx/NiOOH-Modified Fly Ash.

Fly ash, a type of solid waste generated in power plants, can be utilized as a catalyst carrier to enhance its value-added potential. Common methods often involve using a large amount of alkali for preprocessing, resulting in stable quartz and mullite forming silicate dissolution. This leads to an increased specific surface area and pore structure. In this study, we produced a catalyst composed of MnOx/NiOOH supported on fly ash by directly employing nickel hydroxide and potassium permanganate to generate metal active sites over the fly ash surface while simultaneously creating a larger specific surface area and pore structure. The ozone catalytic oxidation performance of this catalyst was evaluated using sodium acetate as the target organic matter. The experimental results demonstrated that an optimal removal efficiency of 57.5% for sodium acetate was achieved, surpassing even that of MnOx/NiOOH supported catalyst by using γ-Al2O3. After loading of MnOx/NiOOH, an oxygen vacancy is formed on the surface of fly ash, which plays an indirect oxidation effect on sodium acetate due to the transformation of ozone to •O2- and •OH over this oxygen vacancy. The reaction process parameters, including varying concentrations of ozone, sodium acetate, and catalyst dosage, as well as pH value and the quantitative analysis of formed free radicals, were examined in detail. This work demonstrated that fly ash could be used as a viable catalytic material for wastewater treatment and provided a new solution to the added value of fly ash.

Isomerization Engineering of Solid Additives Enables Highly Efficient Organic Solar Cells via Manipulating Molecular Stacking and Aggregation of Active Layer.

Morphology control is crucial in achieving high-performance organic solar cells (OSCs) and remains a major challenge in the field of OSC. Solid additive is an effective strategy to fine-tune morphology, however, the mechanism underlying isomeric solid additives on blend morphology and OSC performance is still vague and urgently requires further investigation. Herein, two solid additives based on pyridazine or pyrimidine as core units, M1 and M2, are designed and synthesized to explore working mechanism of the isomeric solid additives in OSCs. The smaller steric hindrance and larger dipole moment facilitate better π-π stacking and aggregation in M1-based active layer. The M1-treated all-small-molecule OSCs (ASM OSCs) obtain an impressive efficiency of 17.57%, ranking among the highest values for binary ASM OSCs, with 16.70% for M2-treated counterparts. Moreover, it is imperative to investigate whether the isomerization engineering of solid additives works in state-of-the-art polymer OSCs. M1-treated D18-Cl:PM6:L8-BO-based devices achieve an exceptional efficiency of 19.70% (certified as 19.34%), among the highest values for OSCs. The work provides deep insights into the design of solid additives and clarifies the potential working mechanism for optimizing the morphology and device performance through isomerization engineering of solid additives.

Genetic variations of low-density lipoprotein cholesterol on metabolic disorders in obstructive sleep apnea.

BACKGROUND: The study aimed to explore the relationship between low-density lipoprotein cholesterol (LDL-C) genetic variants and obstructive sleep apnea (OSA) and its complications, including cardiovascular diseases (CVD), insulin resistance (IR), and metabolic syndrome (MS). METHOD: 4329 individuals with suspected OSA who underwent a comprehensive assessment of anthropometric, biochemical, and polysomnography (PSG) data, along with 30 LDL-C single nucleotide polymorphisms (SNPs) were enrolled. The 10-year Framingham CVD risk score (FRS), IR and MS were evaluated for each subject. Linear regression and logistic regression were utilized to examine the correlations among these variables. RESULTS: After the Benjamini-Hochberg correction, linear regression results indicated positive correlations between variants rs3741297 and rs629301 with FRS (ß = 0.031, PBH=0.002; ß = 0.026, PBH=0.015). Logistic regression revealed that rs3741297 increased MS risk among total subjects [OR = 1.67 (95% CI:1.369-2.038), PBH=1.32 × 10- 5] and increased IR risk in females [OR = 3.475 (95% CI:1.653-7.307), PBH=0.03]. In males, rs2642438 decreased MS risk [OR = 0.81 (95% CI:0.703-0.933), PBH=0.045]. CONCLUSIONS: The rs3741297 variant correlated with susceptibility to CVD, IR, and MS in the OSA population. OSA, CVD, IR and MS share a potentially common genetic background, which may promote precision medicine. CINICAL TRIAL REGISTRATION: The study protocol was registered with the Chinese Clinical Trial Registry (ChiCTR1900025714).

Independent relationship between sleep apnea-specific hypoxic burden and glucolipid metabolism disorder: a cross-sectional study.

OBJECTIVES: Obstructive sleep apnea (OSA) is associated with abnormal glucose and lipid metabolism. However, whether there is an independent association between Sleep Apnea-Specific Hypoxic Burden (SASHB) and glycolipid metabolism disorders in patients with OSA is unknown. METHODS: We enrolled 2,173 participants with suspected OSA from January 2019 to July 2023 in this study. Polysomnographic variables, biochemical indicators, and physical measurements were collected from each participant. Multiple linear regression analyses were used to evaluate independent associations between SASHB, AHI, CT90 and glucose as well as lipid profile. Furthermore, logistic regressions were used to determine the odds ratios (ORs) for abnormal glucose and lipid metabolism across various SASHB, AHI, CT90 quartiles. RESULTS: The SASHB was independently associated with fasting blood glucose (FBG) (ß = 0.058, P = 0.016), fasting insulin (FIN) (ß = 0.073, P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (ß = 0.058, P = 0.011), total cholesterol (TC) (ß = 0.100, P < 0.001), total triglycerides (TG) (ß = 0.063, P = 0.011), low-density lipoprotein cholesterol (LDL-C) (ß = 0.075, P = 0.003), apolipoprotein A-I (apoA-I) (ß = 0.051, P = 0.049), apolipoprotein B (apoB) (ß = 0.136, P < 0.001), apolipoprotein E (apoE) (ß = 0.088, P < 0.001) after adjustments for confounding factors. Furthermore, the ORs for hyperinsulinemia across the higher SASHB quartiles were 1.527, 1.545, and 2.024 respectively, compared with the lowest quartile (P < 0.001 for a linear trend); the ORs for hyper-total cholesterolemia across the higher SASHB quartiles were 1.762, 1.998, and 2.708, compared with the lowest quartile (P < 0.001 for a linear trend) and the ORs for hyper-LDL cholesterolemia across the higher SASHB quartiles were 1.663, 1.695, and 2.316, compared with the lowest quartile (P < 0.001 for a linear trend). Notably, the ORs for hyper-triglyceridemia{1.471, 1.773, 2.099} and abnormal HOMA-IR{1.510, 1.492, 1.937} maintained a consistent trend across the SASHB quartiles. CONCLUSIONS: We found SASHB was independently associated with hyperinsulinemia, abnormal HOMA-IR, hyper-total cholesterolemia, hyper-triglyceridemia and hyper-LDL cholesterolemia in Chinese Han population. Further prospective studies are needed to confirm that SASHB can be used as a predictor of abnormal glycolipid metabolism disorders in patients with OSA. TRIAL REGISTRATION: ChiCTR1900025714 { http://www.chictr.org.cn/ }; Prospectively registered on 6 September 2019; China.

T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea.

BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) is recognized as a crucial regulator in lipid metabolism. Acetyl-CoA carboxylases (ACACAs) play a role in the ß-oxidation of fatty acids. Yet, the functions of ANGPTL4 and ACACA in dyslipidemia of obstructive sleep apnea (OSA) remain unclear. METHODS: This study included 125 male OSA subjects from the Shanghai Sleep Health Study (SSHS) who were matched for age, body mass index (BMI), and lipid profile. Serum ANGPTL4 levels were measured via ELISA. The ANGPTL4 T266M variants of 4455 subjects along with their anthropometric, fasting biochemical, and standard polysomnographic parameters were collected. Linear regression was used to analyze the associations between quantitative traits and ANGPTL4 T266M. Molecular docking and molecular dynamic simulation were employed to compare the effects of the wild-type ANGPTL4 and its T266M mutation on ACACA. RESULTS: Serum ANGPTL4 levels significantly decreased with increasing OSA severity (non-OSA: 59.6 ± 17.4 ng/mL, mild OSA: 50.0 ± 17.5 ng/mL, moderate OSA: 46.3 ± 15.5 ng/mL, severe OSA: 19.9 ± 14.3 ng/mL, respectively, p = 6.02 × 10-16). No associations were found between T266M and clinical characteristics. Molecular docking indicated that mutant ANGTPL4 T266M had stronger binding affinity for the ACACA protein, compared with wild-type ANGPTL4. In terms of protein secondary structure, mutant ANGTPL4 T266M demonstrated greater stability than wild-type ANGPTL4. CONCLUSIONS: Serum ANGTPL4 levels were significantly decreased in OSA patients, particularly among individuals with severe OSA. Although functional ANGTPL4 T266M variants were not associated with lipid levels in OSA, ANGTPL4 T266M could enhance binding affinity for the ACACA protein, potentially regulating lipid metabolism.

Amino-Functionalized Graphdiyne Derivative as a Cathode Interface Layer with High Thickness Tolerance for Highly Efficient Organic Solar Cells.

Efficient cathode interfacial materials (CIMs) are essential components for effectively enhancing the performance of organic solar cells (OSCs). Although high-performance CIMs are desired to meet the requirements of various OSCs, potential candidates for CIMs are scarce. Herein, an amino-functionalized graphdiyne derivative (GDY-N) is developed, which represents the first example of GDY that exhibits favorable solubility in alcohol. Utilizing GDY-N as the CIM, an outstanding champion PCE of 19.30% for devices based on the D18-Cl:L8-BO (certified result: 19.05%) is achieved, which is among the highest efficiencies reported to date in OSCs. Remarkably, the devices based on GDY-N exhibit a thickness-insensitive characteristic, maintaining 95% of their initial efficiency even with a film thickness of 25 nm. Moreover, the GDY-N displays wide universality and facilitates exceptional stability in OSCs. This work not only enriches the diversity of GDY derivatives, but also demonstrates the feasibility of GDY derivatives as CIMs with high thickness tolerance in OSCs.

High-Temperature Oxidized Mo2CTx MXene for a High-Performance Supercapacitor.

Molybdenum carbide (Mo2CTx MXene) did not possess suitable properties for supercapacitors. Herein, a short oxidation method of Mo2CTx in air at moderately high temperatures is proposed for fabricating a Mo2C/MoO3 heterostructure. The stability of Mo2CTx in air up to 700 °C and the phase transition at higher temperatures are confirmed. Such a heterostructure is beneficial in reducing the diffusion energy barrier of H+. In the aqueous system, the Mo2C/MoO3 electrode delivers a capacitance of up to 811 F g-1. A fully assembled symmetric solid-state supercapacitor delivers 224 F g-1 with an excellent retention rate of 91.05% after 7500 cycles. Besides, the supercapacitor can work at the low temperature of -60°, showing good low-temperature properties. The approach presented in this work opens a promising way to turn a neglected MXene, assumed to be unsuitable for supercapacitors, into one of the top-performing supercapacitor electrodes.

Photochemical synthesis of group 10 metal nanoclusters for electrocatalysis.

Four group 10 metal nanoclusters, Ni10(4-MePhS)20, Ni11(PhS)22, Pd9(PhS)18 and Pd10(PhS)20 were synthesized from disulfides based on a photochemical reduction-oxidation cascade process, which proceeds via a different mechanism to that of the conventional two-step reduction process. The as-obtained nanoclusters possess oxidative resistance and structural robustness under different conditions. Their atomically precise structures are determined to be nickel or palladium rings in which the metal atoms are bridged by Ar-S groups. Their catalytic performance in oxygen reduction reaction was compared, and the ring size-dependent catalytic activity of the group 10 metal nanoclusters was revealed. This work provides an efficient route to atomically precise and structurally stable group 10 metal nanoclusters, and sheds light on their further applications in electrocatalysis.

Overall Obesity Not Abdominal Obesity Has a Causal Relationship with Obstructive Sleep Apnea in Individual Level Data.

Objective: Both obstructive sleep apnea (OSA) and obesity are highly prevalent worldwide, and are intrinsically linked. Previous studies showed that obesity is one of the major risk factors for OSA, but the causality of the relationship is still unclear. The study was to investigate the causal relationships of overall obesity and abdominal obesity with OSA and its quantitative traits. Methods: In this case-control study, a total of 7134 participants, including 4335 moderate-to-severe OSA diagnosed by standard polysomnography and 2799 community-based controls were enrolled. Anthropometric and biochemical data were collected. Mendelian randomization (MR) analyses were performed using the genetic risk score, based on 29 body mass index (BMI)- and 11 waist-hip-ratio (WHR)-associated single nucleotide polymorphisms as instrumental variables. The causal associations of these genetic scores with OSA and its quantitative phenotypes were analyzed. Results: Obesity was strongly correlated with OSA in observational analysis (ß= 0.055, P = 3.7 × 10-5). In MR analysis, each increase by one standard deviation in BMI was associated with increased OSA risk [odds ratio (OR): 2.21, 95% confidence interval (CI): 1.62-3.02, P = 5.57 × 10-7] and with 2.72-, 4.68-, and 3.25-fold increases in AHI, ODI, and MAI, respectively (all P < 0.05) in men. However, no causal associations were found between WHR and OSA risk or OSA quantitative traits in men and women. Conclusion: Compared to abdominal obesity, overall obesity showed a causal relationship with OSA and its quantitative traits, especially in men.

Melatonin attenuates chronic intermittent hypoxia-induced intestinal barrier dysfunction in mice.

BACKGROUND AND PURPOSE: Chronic intermittent hypoxia (CIH) triggers subclinical intestinal barrier disruption prior to systemic low-grade inflammation. Increasing evidence suggests therapeutic effects of melatonin on systemic inflammation and gut microbiota remodelling. However, whether and how melatonin alleviates CIH-induced intestinal barrier dysfunction remains unclear. EXPERIMENTAL APPROACH: C57BL/6 J mice and Caco-2 cell line were treated. We evaluated gut barrier function spectrophotometrically using fluorescein isothiocyanate (FITC)-labelled dextran. Immunohistochemical and immunofluorescent staining were used to detect morphological changes in the mechanical barrier. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) revealed the expression of tight junctions, signal transducer and activator of transcription 3 (STAT3) levels. 16 S rRNA analysis of the colonic contents microflora. Flow cytometry was used to detect cytokines and Th17 cells with and without melatonin supplementation. KEY RESULTS: We found that CIH could induce colonic mucosal injury, including reduction in the number of goblet cells and decrease the expression of intestinal tight junction proteins. CIH could decrease the abundance of the beneficial genera Clostridium, Akkermansia, and Bacteroides, while increasing the abundance of the pathogenic genera Desulfovibrio and Bifidobacterium. Finally, CIH facilitated Th17 differentiation via the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in vitro and elevated the circulating pro-inflammatory cytokine in vivo. Melatonin supplementation ameliorated CIH-induced intestinal mucosal injury, gut microbiota dysbiosis, enteric Th17 polarization, and systemic low-grade inflammation reactions mentioned-above. CONCLUSION AND IMPLICATIONS: Melatonin attenuated CIH-induced intestinal barrier dysfunction by regulating gut flora dysbiosis, mucosal epithelium integrity, and Th17 polarization via STAT3 signalling.

The use of the sleep apnea-specific hypoxic burden to predict obstructive sleep apnea hypopnea syndrome: Evidence from a large cross-sectional study.

OBJECTIVES: Obstructive sleep apnea hypopnea syndrome (OSA) is an independent risk factor for neurocognitive and behavioral problems and cardiovascular and metabolic morbidities, ultimately increasing mortality. However, OSA diagnosis is time-consuming, labor-intensive, and expensive. We evaluated the predictive utility of the sleep apnea-specific hypoxic burden (SASHB) in terms of OSA and the severity thereof in Han Chinese individuals. METHODS: From January 2019 to July 2022, subjects with suspected OSA were recruited in the sleep center of the Shanghai Sixth People's Hospital during sleep evaluation via standard polysomnography. Basic anthropometric measurements and polysomnographic indicators were collected; SASHB was calculated based on the SpO2 trends of apnea or hypopnea events. Models predictive of OSA were established via logistic regression in the experimental group and verified in an independent group by drawing receiver operating characteristic (ROC) curves. RESULTS: A total of 2303 subjects with suspected OSA (1200 in the experimental group and 1103 in the validation group) were included. SASHB was positively correlated with the apnea-hyponea index (AHI) in all subjects (r = 0.823, P < 0.001). SASHB distinguished OSA from non-OSA subjects in both the experimental group {area under the curve (AUC) 0.948 [0.934∼0.962]} and the validation group (AUC 0.931 [0.913∼0.949]). SASHB predicted OSA severity well, better than did the neck, waist, or hip circumference; the lowest or mean oxygen saturation; and the Epworth sleepiness scale score. CONCLUSION: SASHB predicted OSA both accurately and efficiently in a Chinese Han population. Further studies are warranted to verify our findings in community samples.

FKBP5 genetic variants are associated with respiratory- and sleep-related parameters in Chinese patients with obstructive sleep apnea.

Introduction: Obstructive sleep apnea (OSA) has been associated with psychiatric disorders, especially depression and posttraumatic stress disorder (PTSD). FKBP5 genetic variants have been previously reported to confer the risk of depression and PTSD. This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the FKBP5 gene with OSA and OSA-related quantitative traits. Methods: Four SNPs within the FKBP5 gene (rs1360780, rs3800373, rs9296158, rs9470080) were genotyped in 5773 participants with anthropometric and polysomnography data. Linear regression and logistic regression analyses were performed to evaluate the relationship between FKBP5 SNPs and OSA-related traits. Binary logistic regression was used to assess the effect of SNPs on OSA susceptibility. Interacting genes of SNPs were assessed based on the 3DSNP database, and expression quantitative trait loci (eQTL) analysis for SNPs was adopted to examine the correlation of SNPs with gene expression. Gene expression analyses in human brains were performed with the aid of Brain Atlas. Results: In moderate-to-severe OSA patients, all four SNPs were positively associated with AHIREM, and rs9296158 showed the strongest association (ß = 1.724, p = 0.001). Further stratified analyses showed that in men with moderate OSA, rs1360780, rs3800373 and rs9470080 were positively associated with wake time (p = 0.0267, p = 0.0254 and p = 0.0043, respectively). Rs1360780 and rs3800373 were 28 and 29.4%more likely to rate a higher ordered MAI category (OR (95% CI) = 1.280 (1.042 - 1.575), p = 0.019; OR (95% CI) = 1.294 (1.052 - 1.592), p = 0.015, respectively). Rs9296158 and rs9470080 increased the risk of low sleep efficiency by 25.7 and 28.1% (OR (95% CI) = 1.257 (1.003 - 1.575), p = 0.047; OR (95% CI) = 1.281 (1.026-1.6), p = 0.029, respectively). Integrated analysis of eQTL and gene expression patterns revealed that four SNPs may exert their effects by regulating FKBP5, TULP1, and ARMC12. Conclusion: Single nucleotide polymorphisms in the FKBP5 gene were associated with sleep respiratory events in moderate-to-severe OSA patients during REM sleep and associated with sleep architecture variables in men with moderate OSA. FKBP5 variants may be a potential predisposing factor for sleep disorders, especially in REM sleep.

Anthropometric Determinants of Autonomic Control in Obstructive Sleep Apnea: A Large-Scale Study.

OBJECTIVE: Autonomic dysfunction is an independent risk factor for cardiovascular disease (CVD). Both obesity and obstructive sleep apnea (OSA) are associated with heart rate variability (HRV) (a hall marker of sympathetic arousal) and increased risk of CVD. This study aims to investigate whether anthropometric parameters could predict reduced HRV in adult OSA during wakefulness. STUDY DESIGN: Cross-sectional study. SETTING: Sleep center of Shanghai Jiao Tong University Affiliated Sixth Hospital from 2012 to 2017. METHODS: Total of 2134 subjects (503 non-OSA and 1631 OSA) were included. Anthropometric parameters were recorded. HRV was recorded during a 5-minute wakefulness period and analyzed by using time-domain method and frequency-domain method. Multiple step-wise linear regressions were performed to determine significant predictors of HRV with and without adjustments. Multiplicative interactions between gender, OSA, and obesity on HRV were also determined and evaluated. RESULTS: Waist circumference (WC) was significant negative determinant of root mean square of successive NN intervals (ß = -.116, p < .001) and high-frequency power (ß = -.155, p < .001). Age was the strongest determining factor of HRV. Significant multiplicative interactions between obesity and OSA on HRV, gender, and obesity on cardiovascular parameters were observed. CONCLUSION: Anthropometric parameters could predict reduced HRV during wakefulness in patients with OSA, especially WC was the strongest influenceable factor. Obesity and OSA had significant multiplicative interaction on HRV. Gender and obesity had significant multiplicative interaction on cardiovascular parameters. Early intervention for obesity, especially centripetal obesity, may improve reduction of autonomic function and risk of CVD.

Effects of obstructive sleep apnea during rapid eye movement sleep on cardiac autonomic dysfunction: Results from the Shanghai sleep health study cohort.

In our large-scale study, the correlation between obstructive sleep apnea (OSA) related to rapid eye movement (REM) sleep and cardiac autonomic dysfunction was assessed by standard polysomnography (PSG). Cardiac autonomic dysfunction was evaluated by the measurement of heart rate variability (HRV). The cardiovascular disease (CVD) risk was determined using the cross-sectional prevalence of CVD and its overall 10 year risk according to the Framingham risk score (FRS). 4152 individuals were included in the study. A higher apnea-hypopnea index during REM sleep (AHIREM ) was correlated with increased CVD risk. The adjusted odds ratios (95% CIs) for CVD prevalence and its high 10 year risk in participants having severe OSA during REM sleep (AHIREM ≥30 events/h) were 1.452 (1.012-2.084) and 1.904 (1.470-2.466) in the demographic adjusted model and 1.175 (0.810-1.704) and 1.716 (1.213-2.427) in the multivariate adjusted model, respectively, compared with the group with a AHIREM of <5 events/h. Fully adjusted multivariate linear regression models showed the independent association between AHIREM and a more elevated ratio of low-frequency and high-frequency (LF/HF) and LF in normalised units [LF (n.u.)] (P = 0.042, P = 0.027 in all participants and P = 0.033, P = 0.029 in participants with AHI during non-REM sleep <5 events/h, respectively). Mediation analysis demonstrated that OSA during REM sleep and CVD risk was significantly mediated by LF/HF and LF (n.u.). OSA during REM sleep may be a marker behind CVD risk because it promotes cardiac autonomic dysfunction.

The Associations of Platelet Activation and Coagulation Parameters with Obstructive Sleep Apnoea: A Large-Scale Observational Study.

Objectives: Obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease, with alterations in coagulability suspected as the mediating factor. This study explored blood coagulability and breathing-related parameters during sleep in patients with OSA. Design: Cross-sectional observational study. Setting. Shanghai Sixth People's Hospital. Participants. 903 patients diagnosed by standard polysomnography. Main Outcome and Measures. The relationships between coagulation markers and OSA were evaluated using Pearson's correlation, binary logistic regression, and restricted cubic spline (RCS) analyses. Results: The platelet distribution width (PDW) and activated partial thromboplastin time (APTT) decreased significantly with increasing OSA severity (both p < 0.001). PDW was positively associated with the apnoea-hypopnea index (AHI), oxygen desaturation index (ODI), and microarousal index (MAI) (ß = 0.136, p < 0.001; ß = 0.155, p < 0.001; and ß = 0.091, p = 0.008, respectively). APTT was negatively correlated with AHI (ß = -0.128, p < 0.001) and ODI (ß = -0.123, p = 0.001). PDW was negatively correlated with percentage of sleep time with oxygen saturation below 90%(CT90) (ß = -0.092, p = 0.009). The minimum arterial oxygen saturation (SaO2) correlated with PDW (ß = -0.098, p = 0.004), APTT (ß = 0.088, p = 0.013), and prothrombin time (PT) (ß = 0.106, p = 0.0003). ODI was risk factors for PDW abnormalities (odds ratio (OR) = 1.009, p = 0.009) after model adjustment. In the RCS, a nonlinear dose-effect relationship was demonstrated between OSA and the risk of PDW and APTT abnormalities. Conclusion: Our study revealed nonlinear relationships between PDW and APTT, and AHI and ODI, in OSA, with AHI and ODI increasing the risk of an abnormal PDW and thus also the cardiovascular risk. This trial is registered with ChiCTR1900025714.

Changes in the oral and nasal microbiota in pediatric obstructive sleep apnea.

Background: Several clinical studies have demonstrated that pediatric obstructive sleep apnea (OSA) is associated with dysbiosis of airway mucosal microbiota. However, how oral and nasal microbial diversity, composition, and structure are altered in pediatric OSA has not been systemically explored. Methods: 30 polysomnography-confirmed OSA patients with adenoid hypertrophy, and 30 controls who did not have adenoid hypertrophy, were enrolled. Swabs from four surface oral tissue sites (tongue base, soft palate, both palatine tonsils, and adenoid) and one nasal swab from both anterior nares were collected. The 16S ribosomal RNA (rRNA) V3-V4 region was sequenced to identify the microbial communities. Results: The beta diversity and microbial profiles were significantly different between pediatric OSA patients and controls at the five upper airway sites. The abundances of Haemophilus, Fusobacterium, and Porphyromonas were higher at adenoid and tonsils sites of pediatric patients with OSA. Functional analysis revealed that the differential pathway between the pediatric OSA patients and controls involved glycerophospholipids and amino acid metabolism. Conclusions: In this study, the oral and nasal microbiome of pediatric OSA patients exhibited certain differences in composition compared with the controls. However, the microbiota data could be useful as a reference for studies on the upper airway microbiome.

Fibroblast growth factor 21 is an independent predictor of prevalent and incident obstructive sleep apnea.

Fibroblast growth factor 21 (FGF21) is a metabolic regulator and a potential biomarker of metabolic diseases. Limited data are available on the association between FGF21 and obstructive sleep apnea (OSA), which is considered as a manifestation of metabolic syndrome. In the present cross-sectional and longitudinal analyses, the FGF21 level was associated with OSA. This analysis of two clinical cohorts is the first to show that the FGF21 level increased significantly with OSA severity and was an independent predictor of incident OSA in Chinese adults. The circulating FGF21 level could serve as a potential serum biomarker of OSA and its comorbidities and thus aid risk evaluation and early intervention.

Heparan sulfate regulates IL-21 bioavailability and signal strength that control germinal center B cell selection and differentiation.

In antibody responses, mutated germinal center B (BGC) cells are positively selected for reentry or differentiation. As the products from GCs, memory B cells and antibody-secreting cells (ASCs) support high-affinity and long-lasting immunity. Positive selection of BGC cells is controlled by signals received through the B cell receptor (BCR) and follicular helper T (TFH) cell-derived signals, in particular costimulation through CD40. Here, we demonstrate that the TFH cell effector cytokine interleukin-21 (IL-21) joins BCR and CD40 in supporting BGC selection and reveal that strong IL-21 signaling prioritizes ASC differentiation in vivo. BGC cells, compared with non-BGC cells, show significantly reduced IL-21 binding and attenuated signaling, which is mediated by low cellular heparan sulfate (HS) sulfation. Mechanistically, N-deacetylase and N-sulfotransferase 1 (Ndst1)-mediated N-sulfation of HS in B cells promotes IL-21 binding and signal strength. Ndst1 is down-regulated in BGC cells and up-regulated in ASC precursors, suggesting selective desensitization to IL-21 in BGC cells. Thus, specialized biochemical regulation of IL-21 bioavailability and signal strength sets a balance between the stringency and efficiency of GC selection.