Expression alteration of serum exosomal circular RNAs in obstructive sleep apnea patients with acute myocardial infarction.

PURPOSE: Circular RNAs (circRNAs) are recently identified as a class of non-coding RNAs that participate in the incidence of acute myocardial infarction (AMI). However, circRNAs expression pattern in obstructive sleep apnea (OSA) with AMI remains unknown. The aim was to investigate circRNAs expression alteration in serum exosomes derived from OSA patients with AMI. METHODS: The serum exosomal circRNAs profile of three healthy subjects, three OSA without AMI and three OSA with AMI were analyzed using high-throughput sequencing. Bioinformatic analyses were carried out to assess potential core circRNAs and functional analyses were conducted to study biological functions. RESULTS: Compared to healthy subjects, there were 5225 upregulated and 5798 downregulated circRNAs in exosomes from OSA with AMI patients. And our study also identified 5210 upregulated and 5813 downregulated circRNAs in OSA with AMI patients compared to OSA without AMI. The differential expression of 2 circRNAs (hsa_circRNA_101147, hsa_circRNA_101561) between healthy subjects and OSA without AMI, and 4 circRNAs (hsa_circRNA_101328, hsa_circRNA_104172, hsa_circRNA_104640, hsa_circRNA_104642) between healthy subjects and OSA with AMI were confirmed by qRT-PCR. In addition, we demonstrated that miR-29a-3p targeted hsa_circRNA_104642 directly. CONCLUSIONS: This study demonstrated that there were a number of dysregulated circRNAs in exosomes from OSA with AMI patients, which might be effectively served as a promising diagnostic biomarker and therapeutic targets.

Relationship between Obstructive Sleep Apnea and Liver Abnormalities in Older Patients: A Cross-Sectional Study.

Background: Older age is a risk factor for obstructive sleep apnea (OSA), which is associated with the development of nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the correlation between OSA and liver injury among older patients. Study Design. This is a cross-sectional study. Methods: Consecutive older (≥60 years) snoring patients were included. Subjects were divided into no OSA, mild OSA, moderate OSA, and severe OSA groups according to the apnea-hypopnea index (AHI) and were also separated into liver injury and nonliver injury groups based on liver function. Logistic regression analysis was applied to analyze the independent risk factors for liver injury. Results: We studied 227 patients (155 male, 72 female). The prevalence of liver injury exhibited an increasing trend among groups with mild-to-severe OSA. In addition, body mass index, AHI, and TG showed significant differences between the liver injury and nonliver injury groups. Logistic regression analysis revealed that AHI and TG were the major contributing factors for liver injury in older patients (adjusted odds ratio [OR] = 1.055, p=0.013, and OR = 1.485, p=0.039, respectively). Conclusions: Older patients with OSA have an increased risk of liver injury and NAFLD, and sleep apnea and high TG are important factors in contributing to the development of liver injury.

Self-reported sleep quality and oligo/astheno/teratozoospermia among men attending an infertility clinic: a longitudinal study.

OBJECTIVE: We aimed to examine the influence of sleep disturbances on the risk of oligo/astheno/teratozoospermia (OAT) in men attending an infertility clinic. METHODS: We consecutively enrolled men attending an infertility clinic from July 2020 to June 2021. Semen parameters were obtained at initial presentation, and the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale score, and the STOP-BANG Questionnair were completed to assess sleep quality. Embryo outcomes were evaluated after infertility treatment. RESULTS: Of 466 men enrolled, 119 had OAT (OAT group) and 347 had normozoospermia (NS group). There were no differences between the two groups regarding Epworth Sleepiness Scale and STOP-BANG Questionnaire scores. The prevalence of poor sleep quality (Pittsburgh Sleep Quality Index score ≥ 5) in the OAT group was significantly higher than that in the NS group (42% vs. 29%, p = 0.009). A higher rate of poor subjective sleep quality was observed in the OAT group compared with the NS group (p = 0.005) and Pearson's correlations revealed a negative relationship between subjective sleep quality and semen quality. Logistic regression found that subjective sleep quality was independently associated with an increased risk of OAT (adjusted odds ratio = 0.610, p = 0.007). CONCLUSIONS: Men with OAT attending an infertility clinic exhibited poor subjective sleep quality. Improving sleep disturbances may be a target intervention to reduce the risk of OAT. This possibility warrants further investigation.

Relationship between severity of obstructive sleep apnea and benign prostatic hyperplasia.

PURPOSE: The cause of benign prostatic hyperplasia (BPH) is controversial, local hypoxia and inflammation being the main two possibilities proposed. The aim of this study was to evaluate the relationship between obstructive sleep apnea (OSA) and BPH. METHODS: The study cohort comprised men from January 2016 to December 2020 in our Sleep Center. These patients were classified into four groups (no, mild, moderate, severe OSA) by apnea-hypopnea indexes (AHI). Logistic regression was used to identify independent risk factors for BPH, after which participants were stratified into younger (age ≤ 40 years) and older groups (age > 40 years) for further analysis. RESULTS: The study cohort comprised 467 patients including 135 younger subjects and 332 older subjects. The prevalence of BPH in the above listed AHI categories was 37.5%, 55.0%, 62.9%, and 52.3%, respectively (p = 0.075). Logistic regression analysis of all patients identified age as a risk factor for BPH (p < 0.001). Stratified analysis according to AHI category found a prevalence of BPH of 0.0%, 13.0%, 33.3%, and 43.9%, respectively, in younger group (p = 0.006), and 52.2%, 71.9%, 71.1%, and 56.3%, respectively, in older group (p = 0.038). Logistic regression analysis found age and AHI were independent risk factors for BPH in younger group (both p < 0.05), whereas only age was identified as a risk factor for BPH in older group (p < 0.001). CONCLUSIONS: Age is an independent risk factor for BPH in men with OSA. AHI is also an independent risk factor for BPH in younger men, suggesting that OSA may affect development of BPH in younger men.

Dexmedetomidine Attenuates Ferroptosis-Mediated Renal Ischemia/Reperfusion Injury and Inflammation by Inhibiting ACSL4 via α2-AR.

Ischemia-reperfusion (I/R) injury is a serious clinical pathology associated with acute kidney injury (AKI). Ferroptosis is non-apoptotic cell death that is known to contribute to renal I/R injury. Dexmedetomidine (Dex) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate the detailed molecular mechanism of Dex protects kidneys against I/R injury through inhibiting ferroptosis. We established the I/R-induced renal injury model in mice, and OGD/R induced HEK293T cells damage in vitro. RNA-seq analysis was performed for identifying the potential therapeutic targets. RNA-seq analysis for differentially expressed genes (DEGs) reported Acyl-CoA synthetase long-chain family member 4 (ACSL4) related to ferroptosis and inflammation in I/R mice renal, which was validated in rodent renal. Liproxstatin-1, the specific small-molecule inhibitor of ferroptosis, significantly attenuated ferroptosis-mediated renal I/R injury with decreased LPO, MDA, and LDH levels, and increased GSH level. Inhibiting the activity of ACSL4 by the Rosiglitazone (ROSI) resulted in the decreased ferroptosis and inflammation, as well as reduced renal tissue damage, with decreasing LPO, MDA and LDH level, increasing GSH level, reducing COX2 and increasing GPx4 protein expression, and suppressing the TNF-α mRNA and IL-6 mRNA levels. Dex as a α2-adrenergic receptor (α2-AR) agonist performed renal protective effects against I/R-induced injury. Our results also revealed that Dex administration mitigated tissue damage, inhibited ferroptosis, and downregulated inflammation response following renal I/R injury, which were associated with the suppression of ACSL4. In addition, ACSL4 overexpression abolishes Dex-mediated protective effects on OGD/R induced ferroptosis and inflammation in HEK293T cells, and promotion of ACSL4 expression by α2-AR inhibitor significantly reversed the effects on the protective role of Dex. This present study indicated that the Dex attenuates ferroptosis-mediated renal I/R injury and inflammation by inhibiting ACSL4 via α2-AR.

Bright Quantum Dot Single-Photon Emitters at Telecom Bands Heterogeneously Integrated on Si.

Whereas the Si photonic platform is highly attractive for scalable optical quantum information processing, it lacks practical solutions for efficient photon generation. Self-assembled semiconductor quantum dots (QDs) efficiently emit photons in the telecom bands (1460-1625 nm) and allow for heterogeneous integration with Si. In this work, we report on a novel, robust, and industry-compatible approach for achieving single-photon emission from InAs/InP QDs heterogeneously integrated with a Si substrate. As a proof of concept, we demonstrate a simple vertical emitting device, employing a metallic mirror beneath the QD emitter, and experimentally obtained photon extraction efficiencies of ∼10%. Nevertheless, the figures of merit of our structures are comparable with values previously only achieved for QDs emitting at shorter wavelength or by applying technically demanding fabrication processes. Our architecture and the simple fabrication procedure allows for the demonstration of high-purity single-photon generation with a second-order correlation function at zero time delay, g (2)(τ = 0) < 0.02, without any corrections at continuous wave excitation at the liquid helium temperature and preserved up to 50 K. For pulsed excitation, we achieve the as-measured g (2)(0) down to 0.205 ± 0.020 (0.114 ± 0.020 with background coincidences subtracted).

Assessment of bone mineral density and bone metabolism in young men with obstructive sleep apnea: a cross-sectional study.

BACKGROUND: Hypoxia in obstructive sleep apnea (OSA) patients during sleep may have an effect on bone metabolism. Few data regarding evaluation of bone metabolism in young individuals diagnosed with OSA. In this study, we aim to identify the association between bone mineral density and OSA in young men (≤ 40 years old of age). METHODS: Consecutive male subjects who underwent polysomnography were enrolled. Serum calcium, 25-hydroxyvitamin-D3, ß-isomerized form C-terminal telopeptide of type I collagen, osteocalcin and procollagen type 1 N-propeptide were measured in all participants, and bone mineral density (BMD) at lumbar spine (L1-L4), femoral neck and hip total were determined by dual energy X-ray absorption (DXA). RESULTS: The population consisted of 85 subjects (mean age 35.53 years). The BMD at lumbar spine (L1-L4) in moderate OSA patients was higher than control and severe OSA group significantly (p = 0.036). After adjustment for confounding factors, stepwise multiple linear regression analyses showed LaSO2 (ß = 0.340, p = 0.008) as an independent explanatory variable for Lumbar L1-L4 BMD, LaSO2 (ß = 0.304, p = 0.037), BMI (ß = 0.393, p = 0.008) for femur neck BMD and BMI (ß = 0.720, p = 0.002) for hip total BMD. CONCLUSIONS: Our finding indicated that there was a relationship between OSA and bone metabolism in younger men, and moderate OSA-related hypoxia positively related with BMD. This study also showed that different degrees of recurrent hypoxia had different effects on bone metabolism, a finding that required further investigation.

Impact of upper airway configuration on CPAP titration assessed by CT during Müller's maneuver in OSA patients.

PURPOSE: Continuous positive airway pressure (CPAP) is the current gold-standard treatment for moderate to severe obstructive sleep apnea (OSA), and upper airway anatomy plays an increasingly important role in evaluating the efficacy of CPAP therapy. The aim of this observational study was to investigate the influence of upper airway anatomy on CPAP titration in OSA patients assessed by computed tomography (CT) during Müller's maneuver. METHODS: Consecutive patients under investigation for OSA by undergoing polysomnography and CT scan of the upper airway while awake were enrolled. Successful full-night manual titration was performed to determine the optimal CPAP pressure level for OSA patients in supine position using a nasal mask. RESULTS: A total of 157 subjects (134 males and 23 females) were included. Both apnea-hypopnea index (AHI) and LaSO2 significantly correlated with CPAP titration level, upper airway length (UAL), distance from mandibular plane to hyoid bone (MPH), and neck circumference (all p < 0.05). There were significant positive correlations between CPAP titration level and UAL (r = 0.348, p = 0.000) and MPH (r = 0.313, p = 0.002). Stepwise multiple linear regression analyses were performed to evaluate the independent predictors of AHI, LaSO2, and CPAP titration level. CPAP titration level was identified as an independent explanatory variable for AHI and LaSO2 after adjustment for confounders. Multiple linear regression analyses also indicated that body mass index (BMI) and UAL were independently associated with CPAP titration level (all p < 0.05). CONCLUSIONS: Upper airway abnormalities combined with anthropometric parameters play important roles in CPAP titration for OSA patients, providing additional insight into the factors influencing OSA treatment strategies. UAL and BMI should be taken into consideration when choosing CPAP titration level to improve CPAP compliance.

Thioredoxin H (TrxH) contributes to adversity adaptation and pathogenicity of Edwardsiella piscicida.

Thioredoxins (Trxs) play an important role in defending against oxidative stress and keeping disulfide bonding correct to maintain protein function. Edwardsiella piscicida, a severe fish pathogen, has been shown to encode several thioredoxins including TrxA, TrxC, and TrxH, but their biological roles remain unknown. In this study, we characterized TrxH of E. piscicida (named TrxHEp) and examined its expression and function. TrxHEp is composed of 125 residues and possesses typical thioredoxin H motifs. Expression of trxHEp was upregulated under conditions of oxidative stress, iron starvation, low pH, and during infection of host cells. trxHEp expression was also regulated by ferric uptake regulator (Fur), an important global regulatory of E. piscicida. Compared to the wild type TX01, a markerless trxHEp in-frame mutant strain TX01∆trxH exhibited markedly compromised tolerance of the pathogen to hydrogen peroxide, acid stress, and iron deficiency. Deletion of trxHEp significantly retarded bacterial biofilm growth and decreased resistance against serum killing. Pathogenicity analysis shows that the inactivation of trxHEp significantly impaired the ability of E. piscicida to invade host cells, reproduce in macrophages, and infect host tissues. Introduction of a trans-expressed trxH gene restored the lost virulence of TX01∆trxH. There is likely to be a complex relationship of functional complementation or expression regulation between TrxH and another two thioredoxins, TrxA and TrxC, of E. piscicida. This is the first functional report of TrxH in fish pathogens, and the findings suggest that TrxHEp is essential for coping with adverse circumstances and contributes to host infection of E. piscicida.

Experimental demonstration of quantum pigeonhole paradox.

We experimentally demonstrate that when three single photons transmit through two polarization channels, in a well-defined pre- and postselected ensemble, there are no two photons in the same polarization channel by weak-strength measurement, a counterintuitive quantum counting effect called the quantum pigeonhole paradox. We further show that this effect breaks down in second-order measurement. These results indicate the existence of the quantum pigeonhole paradox and its operating regime.

The association between glycometabolism and nonalcoholic fatty liver disease in patients with obstructive sleep apnea.

PURPOSE: Growing evidence has revealed that nonalcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes. This study aimed to assess the association between glycometabolism and NAFLD in patients with obstructive sleep apnea (OSA). METHODS: Patients with suspected OSA were enrolled consecutively and then underwent polysomnography, liver ultrasound, and biochemical measurements. Logistic regressions were used to identify factors associated with NAFLD. RESULTS: In total, 415 patients were included. The prevalence of NAFLD in the non-OSA, mild OSA, moderate OSA, and severe OSA groups was 37.21%, 69.09%, 68.34%, and 78.08%, respectively. Stepwise logistic regression suggested that percentage of total sleep time spent with oxygen saturation of < 90% (TS90), lowest oxygen saturation (LaSO2), and homeostatic model assessment of insulin resistance (HOMA-IR) were independently associated with NAFLD in all subjects, after adjusting for confounders (odds ratio [OR] = 1.037, p = 0.014; OR = 1.056, p = 0.004; OR = 0.732, p = 0.009; respectively). TS90, LaSO2, and HOMA-IR were also independent predictors for NAFLD in patients with mild and moderate OSA, whereas TS90, LaSO2, and ODI were independent predictors for NAFLD in patients with severe OSA. CONCLUSIONS: There is a relationship between OSA and NAFLD, and the combination of disordered glycometabolism and intermittent hypoxia may act as a "two hit" mechanism to promote the development of NAFLD. Furthermore, intermittent hypoxia alone was an independent predictor for NAFLD in severe OSA patients.

Association Between ADRB2 Genetic Polymorphisms and the Risk of Chronic Obstructive Pulmonary Disease: A Case-Control Study in a Chinese Population.

OBJECTIVE: This study was designed to investigate the association between single nucleotide polymorphisms (SNPs) of the ß2-adrenergic receptor (ADRB2) gene and the risk of chronic obstructive pulmonary disease (COPD) in a Chinese population. METHODS: From January 2010 to October 2014, 261 COPD patients were selected as the case group and 239 healthy subjects were selected as the control group. Pulmonary function tests were performed to detect forced vital capacity (FVC), 1-s forced expiratory volume (FEV1), and FEV1/FVC (%). rs1042711, rs1042714, and rs1042718 were selected as tagSNPs of the ADRB2 gene from the HapMap database in accordance with previous studies. The ADRB2 genotypes were established by real-time polymerase chain reaction assays using TaqMan-labeled probes. The relationships between the ADRB2 polymorphisms and COPD risk were estimated using logistic regression analyses. RESULTS: The frequency of the genotypes and alleles of rs1042711 in ADRB2 showed a significant difference between the COPD and control groups (p < 0.05); compared with the CC genotype, the non-CC genotypes showed an increased COPD risk (p = 0.002). Compared with the CC haplotype, the TG haplotype increased COPD risk, while the CG haplotype reduced COPD risk for normal individuals. Compared with the CC genotype, the TT genotype showed significantly lower FEV1 and FEV1/FVC (p = 0.022, p = 0.0191, respectively). Both the TC and TG haplotypes showed lower FEV1 and FEV1/FVC in comparison with the CC haplotype (both p < 0.05). The results of logistic regression analysis showed that rs1042711 of ADRB2 and smoking history were associated with COPD risk (both p < 0.05). CONCLUSION: It is indicated that the TT genotype of rs1042711 and smoking pack years are both risk factors for COPD.

The effect of CPAP treatment on venous lactate and arterial blood gas among obstructive sleep apnea syndrome patients.

PURPOSE: The aim of this observational study was to investigate the influence of continuous positive airway pressure (CPAP) on arterial blood gas and venous lactate, markers of tissue hypoxia, among obstructive sleep apnea syndrome (OSAS) patients, and determine the risk factor of serum lactate and hydrogen ion concentration (PH) in OSAS patients. MATERIALS AND METHODS: One-hundred and nine patients with newly diagnosed OSAS were enrolled in the study. All individuals were treated with CPAP for one night. Venous lactate and arterial blood gas were gathered from all subjects in the morning at the end of polysomnography and the next morning after CPAP treatment. RESULTS: Of the 109 selected subjects, the average lactate level was 2.23 ± 0.59 mmol/L, and the mean PH, PaO2, and PaCO2 were 7.380 ± 0.23, 88.14 ± 17.83 mmHg, and 38.70 ± 4.28 mmHg, respectively. Compared to baseline, lactic acid significantly decreased (2.10 ± 0.50 mmol/L, p = 0.03), while PH increased (7.388 ± 0.27, p < 0.05) after CPAP treatment. In addition, neck circumference and the polysomnographic parameters, including apnea-hypopnea index, oxygen desaturation index (ODI), mean oxygen saturation (SpO2), and the percentage of sleep time with SpO2 <90 % (TS90 %), positively correlated with lactate, while age correlated negatively with lactate (all p < 0.05). Significantly positive associations were found between age, neck circumference, and PH; furthermore, a negative correlation was found between ODI and PH. Finally, after adjusting for confounding factors, TS90 % was the major contributing predictor for elevated lactate (p < 0.05), and age was a predictor for an increase in PH (p < 0.05). CONCLUSIONS: The results indicated that CPAP treatment could reduce serum lactate and increase PH in OSAS patients and might alleviate acid-base balance disorders in OSAS. Furthermore, TS90 % was a risk factor for elevated lactate, and age was independently associated with PH.

Assessment of Upper-Airway Configuration in Obstructive Sleep Apnea Syndrome With Computed Tomography Imaging During Müller Maneuver.

BACKGROUND: The purpose of this observational study was to investigate the relationship between upper-airway configuration assessed by CT imaging during the Müller maneuver state and the severity of obstructive sleep apnea syndrome (OSAS). METHODS: A total of 358 snoring subjects who underwent standard polysomnography and upper-airway configuration by using CT imaging were enrolled. According to the apnea-hypopnea index (AHI), subjects were classified into 4 groups: snoring group (simple snoring), AHI < 5; mild OSAS, 5 ≤ AHI < 15; moderate OSAS, 15 ≤ AHI < 30; and severe OSAS, AHI ≥ 30. We also divided the upper airway into 3 parts, named the nasopharynx, oropharynx, and hypopharynx, from the CT scan and evaluated the minimal cross-sectional area (mCSA) and the shape of each airway level and calculated upper-airway length and distance from mandibular plane to hyoid bone (MPH). RESULTS: Multivariate logistic stepwise regression analysis identified body mass index (BMI), mCSA of nasopharynx, upper-airway length, and MPH as risk factors for the severity of OSAS. When subdivided for BMI and sex, upper-airway length was a risk factor for OSAS in non-obese (BMI < 27 kg/m2) and male subjects, and MPH was a risk factor only in obese (BMI ≥ 27 kg/m2) subjects. Meanwhile, mCSA of nasopharynx was significantly associated with the severity of OSAS independent of BMI. CONCLUSIONS: Subjects with severe OSAS have more significant abnormalities of the upper airway. Obesity, mCSA of nasopharynx, upper-airway length, and MPH may contribute to the severity of OSAS. Obesity and sex should be taken into account when evaluating the abnormalities of upper-airway anatomy in snorers and patients with OSAS.

Applicability of visceral adiposity index in predicting metabolic syndrome in adults with obstructive sleep apnea: a cross-sectional study.

BACKGROUND: Obstructive sleep apnea (OSA) is severely affected by visceral adiposity (VA) that correlates to another disorder-metabolic syndrome (MetS). However, little is known concerning the relation of visceral adiposity index (VAI)-a novel and simple indicator of VA, with OSA and MetS. The objective of the study was to analyze the association of VAI with both disorders and applicability to identify OSA patients at risk of MetS. METHODS: Consecutive individuals undergoing polysomnography and biochemical tests were enrolled, and differences in all subjects grouped by apnea-hypopnea index (AHI) were analyzed. Spearman correlation was performed for assessing the relationship between VAI, OSA-related indices and metabolic score-total number of the positive diagnostic criteria of MetS. Receiver operating characteristic (ROC) curve was conducted to obtain a cut-off value of VAI for predicting incident MetS by sex. Then, the risk of MetS in OSA patients according to the cut-offs was attained by logistic regression. RESULTS: A total of 411 individuals were enrolled. Of whom, 361 subjects were diagnosed OSA (mild in 67 patients, moderate in 89 and severe in 205, respectively). A significant increasing trend based on AHI was observed in the variables of blood pressure, triglycerides, fasting glucose, incident MetS, metabolic score and VAI (all p < 0.05). Irrespective of gender, VAI was all significantly correlated with PSG characteristics as AHI, mean nocturnal oxygen saturation, the lowest oxygen saturation, metabolic score(all p < 0.05). A VAI of 2.282, 2.105, 2.511 (for all subjects, males and females, separately) were calculated to determine the occurrence of MetS. According to the cut-offs, OSA patients tended to suffer from greater risk in MetS (odds ratio [OR] = 10.237, p = 0.000; OR = 13.556, p = 0.000; OR = 21.458, p = 0.000). CONCLUSIONS: The present study suggested that VAI was significantly associated with MetS and OSA. As a simple and alternative approach obtained in everyday practice, it may offer a powerful tool to identify patients with OSA at risk of MetS.