The characteristics of microbiome in the upper respiratory tract of COVID-19 patients.

BACKGROUND: Co-infection with other pathogens in coronavirus disease 2019 (COVID-19) patients exacerbates disease severity and impacts patient prognosis. Clarifying the exact pathogens co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is premise of the precise treatment for COVID-19 patients. METHODS: Sputum samples were collected from 17 patients in the COVID-19 positive group and 18 patients in the COVID-19 negative group. DNA extraction was performed to obtain the total DNA. Sequencing analysis using 16S and ITS rRNA gene was carried out to analyze the composition of bacterial and fungal communities. Meanwhile, all the samples were inoculated for culture. RESULTS: We did not observe significant differences in bacterial composition between the COVID-19 positive and negative groups. However, a significantly higher abundance of Candida albicans was observed in the upper respiratory tract samples from the COVID-19 positive group compared to the COVID-19 negative group. Moreover, the Candida albicans strains isolated from COVID-19 positive group exhibited impaired secretion of aspartyl proteinases. CONCLUSION: COVID-19 positive patients demonstrate a notable increase in the abundance of Candida albicans, along with a decrease in the levels of aspartyl proteinases, indicating the alteration of microbiota composition of upper respiratory tract.

Study on flame retardancy of EPDM reinforced by ammonium polyphosphate.

Currently, the most widely used material for solid rocket motor (SRM) insulation is ethylene propylene diene monomer (EPDM) filled with flame-retardant and ablation-resistant fillers. Researchers have been working hard to find a flame-retardant filler that can simultaneously meet the complex requirements of mechanical strength, density, flame retardancy and ablative performance of the insulation layer. This requires research on the flame retardant properties of flame retardants in oxygen-poor environments. In this paper, ammonium polyphosphate (APP) is used as a flame retardant filler, which is filled into an EPDM premix (p-EPDM) containing fumed silica and aluminum hydroxide to prepare composite materials. By creating an anoxic environment, the flame retardant behavior of APP under anoxic conditions on EPDM was studied. The results show that composites prepared with APP show better flame retardant properties in tests such as limiting oxygen index and UL-94, with less impact on mechanical strength and density. The surface morphology and elemental composition of the composite combustion residues were studied using Raman spectroscopy, scanning electron microscopy (SEM) and energy dispersion spectroscopy (EDS). In an oxygen-depleted environment, APP will thermally decompose to form ammonia, water vapor and phosphorus-containing acidic substances. These gases dilute the flammable gas and reduce the thermal conductivity. The acidic substances containing phosphorus are concentrated on the surface of the pyrolysis layer to promote the formation of the carbon layer. This provides guidance for us to design insulation layer materials with properties that are more in line with actual use requirements.

Facile synthesis of NiCoSe2@carbon anode for high-performance sodium-ion batteries.

Sodium-ion batteries offer significant advantages in terms of low-temperature performance and safety. In this study, we present a straightforward synthetic approach to produce bimetallic selenide NiCoSe2 nanoparticles grown on a three-dimensional porous carbon framework for application as anode materials in sodium-ion batteries. This unique architecture enhances reaction kinetics and structural stability. The three-dimensional interconnected porous carbon network establishes a continuous pathway of electronic conductive, while increasing specific surface area and mitigating volume expansion. Consequently, these features expedite ion transfer and enhance electrolyte interaction. Notably, compared to CoSe, NiCoSe2 exhibits reduced ion transport distances and lower sodium diffusion barriers. Leveraging these attributes, NiCoSe2/N, Se co-doped carbon composite materials (NiCoSe2/NSC) demonstrate a high specific capacity of 320.8 mAh/g, even after 1000 cycles at 5.0 A/g, with a capacity retention rate of 85.1%. The study further delves into the revelation of the reaction mechanism and ion transport pathway through in-situ X-ray diffraction (XRD) analysis and theoretical calculations. The development of these anode materials is poised to pave the way for advancements in sodium-ion battery technology.

Bismuth-based liquid metals: advances, applications, and prospects.

Bismuth-based liquid metals (LMs) are a large group of alloys with melting points slightly above room temperature. They are associated with fewer encapsulation constraints than room temperature LMs such as mercury, sodium-potassium alloys, and gallium-based alloys and are more likely to remain stable in the natural environment. In addition, their low melting point properties enable them to soften and melt via easy control. Bismuth-based alloys can also be modified with metal-based, carbon-based, and ceramic-based micro/nano particles as well as polymeric materials to create a series of novel composites owing to their outstanding functions. Based on these considerations, this review provides a comprehensive overview of bismuth-based LMs. The categories of bismuth and bismuth-based LMs are first briefly introduced to better systematize the physical and chemical properties of bismuth-based LMs. Based on these properties, bismuth-based LMs have been prepared using various methods, and this review briefly categorizes these preparation methods based on their finished forms (lumps, powders, and films). In addition, this review details the research progress of bismuth-based LMs in the fields of printed electronics, 3D printing, thermal management, biomedicine, chemical engineering, and deformable robotics. Finally, the challenges and future opportunities of bismuth-based LMs in the development process are discussed and visualized from different perspectives.

Peroxymonosulfate Activation by Cu-OMS-2 Nanofibers for Efficient Degradation of N-Containing Heterocycles in Aquatic Solution.

In this research, the degradation of different types of N-containing heterocycle (NHC) contaminants by Cu-OMS-2 via peroxymonosulfate (PMS) activation in an aqueous environment was investigated. First, the effects of different reaction parameters were optimized using benzotriazole (BTR) as the model contaminant, and the optimal reaction conditions were 8 mM PMS, 0.35 g/L Cu-OMS-2, and 30 °C. Nine different types of NHC contaminants were effectively degraded under these reaction conditions, and the degradation efficiencies and the mineralization rates of those NHCs were more than 68 and 46%, respectively. Moreover, the Cu-OMS-2/PMS process presented excellent performance at a wide pH ranging from 3.0 to 11.0 and in the presence of some representative anions (NO3- and SO42-) and dissolved organic matter (fumaric acid). The inhibition sequence of anions on BTR removal during the Cu-OMS-2/PMS process was H2PO4- > HCO3- > Cl- > CO32- > NO3- > SO42-. It was also found that 74.5 and 71.3% BTR degradation rates were achieved in actual water bodies, such as tap water and Yellow River water, respectively. Besides, the Cu-OMS-2 heterogeneous catalyst had excellent stability and reusability, and the degradation rate of BTR was still at 77.0% after 5 cycles. Finally, electron paramagnetic resonance analysis and scavenging tests showed that 1O2 and SO4- • were the primary reactive oxygen species. Accordingly, Cu-OMS-2 nanomaterial was an efficient and sustainable heterogeneous catalyst to activate PMS for the decontamination of BTR in water remediation.

Liquid Metal-Based Flexible Bioelectrodes for Management of In-Stent-Restenosis: Potential Application.

Although vascular stents have been widely used in clinical practice, there is still a risk of in-stent restenosis after their implantation. Combining conventional vascular stents with liquid metal-based electrodes with impedance detection, irreversible electroporation, and blood pressure detection provides a new direction to completely solve the restenosis problem. Compared with conventional rigid electrodes, liquid metal-based electrodes combine high conductivity and stretchability, and are more compliant with the implantation process of vascular stents and remain in the vasculature for a long period of time. This perspective reviews the types and development of conventional vascular stents and proposes a novel stent that integrates liquid metal-based electrodes on conventional vascular stents. This vascular stent has three major functions of prediction, detection and treatment, and is expected to be a new generation of cardiovascular implant with intelligent sensing and real-time monitoring.

Impact of 1-week preoperative auto-CPAP treatment on postoperative outcomes in patients undergoing heart valve replacement surgery: a prospective randomized controlled trial.

Background: Whether preoperative continuous positive airway pressure (CPAP) treatment improves postoperative outcomes in patients undergoing cardiac valve replacement (CVR) remains unknown. Hypothesis: This study was to evaluate the effects of 1-week perioperative auto-continuous positive airway pressure (CPAP) treatment on postoperative heart and pulmonary outcomes in patients with obstructive sleep apnea (OSA) and valvular heart disease. Methods: Thirty-two patients with OSA and valvular heart disease were randomly assigned to 1-week CPAP (n = 15) group and non-CPAP treatments (n = 17) group. After the treatment, all patients underwent CVR surgery. The length of ICU and hospital stays, postoperative cardiac and respiratory complications were assessed and compared between the 2 groups. Results: The results showed there was no significant difference in the baseline characteristics between the CPAP and non-CPAP treatment groups. The length of postoperative ICU and hospital stays, as well as the duration of mechanical ventilation were significantly reduced in the CPAP treatment group compared to the non-CPAP treatment group; however, there were no significant differences in cardiac complications (postoperative arrhythmias, pacemaker use, first dose of dopamine in the ICU, and first dose of dobutamine in the ICU), and respiratory complications (reintubation and pneumonia). Conclusion: We concluded that in patients underwent CVR, preoperative use of auto-CPAP for OSA significantly decreased the duration of mechanical ventilation, and postoperative stays in the ICU and hospital.Clinical Trial Registration: https://ClinicalTrials.gov, identifier NCT03398733.

New perspective on exploring the predictive factors of blood pressure reduction during CPAP treatment in people with severe OSA and hypertension: a prospective observational study.

BACKGROUND: The predictive factors of blood pressure (BP) response to continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) are still being explored. We aimed to assess the antihypertensive effect of CPAP considering the obstructive respiratory event-triggered BP surge profiles in 130 subjects with severe OSA and untreated hypertension. METHODS: Nocturnal BP was monitored continuously and synchronised with polysomnography. Event-triggered BP surge profiles were studied: BP surge as the value of event-related systolic BP (SBP) elevation; BP index as the number of BP surge events of ≥10 mm Hg per hour. Patients were then divided into two groups according to the median BP index (high and low BP surge groups) and assigned to 4 weeks of CPAP. Changes in BPs and plasma biomarkers were compared. After the initial evaluation, patients with a better BP response in the high BP surge group were then followed up for the second evaluation at 24 months. RESULTS: Overall, a modest decrease was observed in both office and asleep BPs at the 4-week follow-up; however, BPs dropped more markedly in patients in the high BP surge group than those in the low BP surge group, in both office SBP (5.3 mm Hg vs 2.2 mm Hg, p=0.003) and diastolic BP (4.0 mm Hg vs 1.2 mm Hg, p<0.001), especially the asleep SBP (9.0 mm Hg vs 2.1 mm Hg, p<0.001). For 30 cases in the high BP surge group, optimal BP control was achieved in 60.0% of patients and BP<140/90 mm Hg reached up to 83.3% after 24 months of CPAP. Linear regression revealed that BP index was significantly associated with BP decrease during CPAP treatment. CONCLUSIONS: Our results suggested that high event-triggered BP surge was a sensitive predictor of BP response to CPAP in patients with severe OSA and untreated hypertension. TRIAL REGISTRATION NUMBER: Clinical Trials.gov Identifier: NCT03246022; https://clinicaltrials.gov/ct2/show/NCT03246022?term=NCT+03246022&draw=2&rank=1.

Liquid Metal-Based Electrode Array for Neural Signal Recording.

Neural electrodes are core devices for research in neuroscience, neurological diseases, and neural-machine interfacing. They build a bridge between the cerebral nervous system and electronic devices. Most of the neural electrodes in use are based on rigid materials that differ significantly from biological neural tissue in flexibility and tensile properties. In this study, a liquid-metal (LM) -based 20-channel neural electrode array with a platinum metal (Pt) encapsulation material was developed by microfabrication technology. The in vitro experiments demonstrated that the electrode has stable electrical properties and excellent mechanical properties such as flexibility and bending, which allows the electrode to form conformal contact with the skull. The in vivo experiments also recorded electroencephalographic signals using the LM-based electrode from a rat under low-flow or deep anesthesia, including the auditory-evoked potentials triggered by sound stimulation. The auditory-activated cortical area was analyzed using source localization technique. These results indicate that this 20-channel LM-based neural electrode array satisfies the demands of brain signal acquisition and provides high-quality-electroencephalogram (EEG) signals that support source localization analysis.

Characteristics of phenotypic antibiotic resistance of Helicobacter pylori and its correlation with genotypic antibiotic resistance: A retrospective study in Ningxia.

BACKGROUND: Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data are essential. We evaluated the current status of H. pylori resistance in Ningxia, analyzed resistance-related factors, and assessed the concordance of phenotypic and genotypic resistance. METHODS: Strains were isolated from the gastric mucosa of patients infected with H. pylori in Ningxia and relevant clinical information was collected. Phenotypic antibiotic susceptibility assays (Kirby-Bauer disk diffusion) and antibiotic resistance gene detection (Sanger sequencing) were performed. RESULTS: We isolated 1955 H. pylori strains. The resistance rates of H. pylori to amoxicillin, levofloxacin, clarithromycin, and metronidazole were 0.9%, 42.4%, 40.4%, and 94.2%, respectively. Only five tetracycline-resistant and one furazolidone-resistant strain were identified. Overall, 3.3% of the strains were sensitive to all six antibiotics. Multidrug-resistant strains accounted for 22.9%, of which less than 20% were from Wuzhong. Strains isolated from women and patients with nonulcerative disease had higher rates of resistance to levofloxacin and clarithromycin. Higher rates of resistance to metronidazole, levofloxacin, and clarithromycin were observed in the older age group than in the younger age group. The kappa coefficients of phenotypic resistance and genotypic resistance for levofloxacin and clarithromycin were 0.830 and 0.809, respectively, whereas the remaining antibiotics showed poor agreement. CONCLUSION: H. pylori antibiotic resistance is severe in Ningxia. Therefore, furazolidone, amoxicillin, and tetracycline are better choices for the empirical therapy of H. pylori infection in this region. Host sex, age, and the presence of ulcerative diseases may affect antibiotic resistance of the bacteria. Personalized therapy based on genetic testing for levofloxacin and clarithromycin resistance may be a future direction for the eradication therapy of H. pylori infection in Ningxia.

First Report of Valsa nivea (Hoffm.) Fr. Causing Valsa Canker on Korla Pear (Pyrus sinkiangensis Yü) in the World.

Korla pear (Pyrus sinkiangensis Yü) is an important commercial fruit tree that originated in China (Zhou et al. 2020). In April 2020, a survey was conducted in Aksu region, Xinjiang (40°55'37"N, 80°28'42"E), China. Some Korla pear trees (>15 years old) exhibited symptoms of branch dieback and branch cankers. Cankers observed on the trunk and branches of the tree were sunken, dark ulcerative lesions sometimes exhibiting signs of stromata erumpent through the bark and exuding yellow to reddish-orange spore tendrils. Of the 180 plants surveyed, 80% were symptomatic. Thirty samples of symptomatic tissues of infected branches were taken to the laboratory. Bark and cortical wood samples containing necrotic and healthy tissue were excised with flame-sterilized scalpels, surface disinfected with 75% ethanol and 1% NaClO, placed on PDA plates, and incubated at 25°C. A total of 30 fungal isolates were obtained. Among them, 28 isolates were identified as Valsa mali var. pyri (Lu. 1992) based on morphological and molecular identification, and two isolates (ALE6T-GP21 and ALE7T-GP23) were identified as Valsa nivea (Hoffm.) Fr. Valsa nivea isolates had a fine villi form mycelium that was initially white, turned grayish-green over time and grew close to the medium surface. Cultures also contained black ostiolate pycnidia in a stroma that consisted of multiple irregular locules. Conidiophores were hyaline, occasionally branched at the bases and (15.50-)16.48-17.94(-18.50)×(1.00-)1.13-1.37(-1.50) µm (n=20). Conidiogenous cells were phialidic and subcylindrical that taper towards the apex. Conidia were hyaline, banana-like and (5.47-)6.13-6.97(-7.64)×(1.02-)1.06-1.20(-1.23) µm (n=10). The molecular characteristics are consistent with the previous description of V. nivea (Adams et al. 2006). The internal transcribed spacer (ITS), transcription elongation factor (tef-1α) and ß-tubulin (Tub2) gene were sequenced using ITS1/ITS4, EF1-728F/EF1-986R and Bt2a/Bt2b primers, respectively (Zhang et al. 2014). BLAST (Basic Local Alignment Search Tool) searches against the NCBI database revealed that the ITS sequence had 99.83% homology (ON843984.1 and ON843987.1), tef-1α gene had 99.22% homology (MH015266.1 and MH015267.1), and the Tub2 sequence had 99.57% and 100% homologies (KT934364.1 and KT934364.1) with V. nivea sequences. The amplified sequences of ITS region (OK442665 and OK442666), tef-1α (OK510871 and OK510872) and Tub2 (OK510869 and OK510870) were deposited in the GenBank. A phylogenetic analysis was performed using MEGA7 that shows 100% bootstrap support that ALE6T-GP21 and ALE7T-GP23 were V. nivea. A pathogenicity trial was conducted with isolate ALE6T-GP21 inoculated onto 1-year-old shoots of 15-year-old Korla pear trees in Alar city, Xinjiang, China. Five shoots were inoculated by making 5-mm deep wounds using a sterile scalpel then inoculating with a 50 µL conidia suspension (1×106 mL-1). Additionally, five shoots served as the negative control and were inoculated in the same way using 50 µL ddH2O. The trees were kept under ambient conditions. Inoculated branches developed symptoms 18 days post inoculation, whereas the control branches showed no symptoms. V. nivea was re-isolated from the symptomatic areas and the isolate confirmed as ALE6T-GP21 by sequence analysis. Currently, the proven hosts of V. nivea are Populus, Elaeagnus, Juglans, Malus and Salix (Adams et al. 2006; Wang et al. 2020). To our knowledge, this is the first report of pathogenic V. nivea occurring on P. sinkiangensis in the world. It will provide a basis for research into the occurrence, distribution of V. nivea on Korla Pear.

Pyrolytic Evidence for Unsubstituted Aromatics as Potential Oil-Oil/Source Correlation Indicators.

Most oil source correlation indicators are invalid because of the high maturity of the deep marine strata. Thus, a suitable indicator with high thermal stability requires to be established. In this study, to understand the effect of thermal maturation on the carbon isotopic composition of unsubstituted aromatics, we performed a number of anhydrous thermal simulation experiments involving two typical Chinese shales (lacustrine and marine shales), their corresponding expelled oils, three crude oils, and their associated oil fractions, that is, saturates, aromatics, resins, and asphaltenes (SARA). The generated unsubstituted aromatics were examined in terms of molecular distributions and carbon isotopic composition. The results show that unsubstituted aromatics in different types of samples demonstrated similar variation characteristics. Phenanthrene can be formed continuously in 0.45%/0.55-2.30% R o (equivalent vitrinite reflectance), especially in the high-over maturity stage. However, their carbon isotope composition shows minor variations. The unsubstituted aromatic carbon isotopic information in source rocks can be preserved during the whole pyrolysis process. Their carbon isotopic values in source rocks and their corresponding expelled oils are extremely similar. Furthermore, no evident difference exists in the carbon isotopes of unsubstituted aromatics formed by crude oil and associated oil fractions. These results indicate that these types of parameters are suitable for oil-oil/source correlation in deep marine strata with high-over maturity.

Globular adiponectin protects hepatocytes against intermittent hypoxia-induced injury via Pink1/Parkin-mediated mitophagy induction.

PURPOSE: This study sought to determine the effect of Pink1/Parkin-mediated mitophagy on liver cells exposed to intermittent hypoxia (IH) and the roles of globular adiponectin (gAPN). METHODS: The hepatocyte model of IH was established. Cell apoptosis was assessed using flow cytometry. Mitochondrial membrane potential (MMP) level was determined using JC-1, and mitophagy was assessed using a confocal laser. Mitochondrial injury associated protein levels of bax and bcl-2, and protein levels of Pink1 and Parkin were evaluated via western blotting. We downregulated Parkin expression by transfecting the cells with Parkin siRNA. RESULTS: Pink1 and Parkin protein levels, mitophagy, and cell apoptosis rate were high, while the MMP level and protein level ratio of bcl-2/bax were low in IH-treated hepatocyte. gAPN upregulated Pink1 and Parkin protein levels, MMP level, protein level ratio of bcl-2/bax, and mitophagy while it reduced the rate of cell apoptosis in IH-treated hepatocytes. Inhibiting Parkin expression significantly reduced mitophagy and increased mitochondrial injury and the rate of hepatocyte apoptosis under IH or IH with gAPN. CONCLUSION: gAPN alleviated IH-induced mitochondrial injury and hepatocyte apoptosis by upregulating Pink1/Parkin-mediated mitophagy.

Depression of Non-Neuronal Cholinergic System May Play a Role in Co-Occurrence of Subjective Daytime Sleepiness and Hypertension in Patients with Obstructive Sleep Apnea Syndrome.

PURPOSE: Simultaneous occurrence of hypertension and excessive daytime sleepiness (EDS) is very common in obstructive sleep apnea syndrome (OSAS), although no study has specifically addressed this issue. The present study explored the risk factors for co-occurrence of OSAS-related EDS and hypertension. PATIENTS AND METHODS: A total of 161 OSAS patients were studied after undergoing an eight-hour in-laboratory polysomnography for one night. The OSAS severity assessment depends on the number of breathing disturbances per hour of sleep. EDS was defined using the Epworth Sleepiness Scale (ESS) scores of ≥13. Hypertension was defined according to direct cuff blood pressure (BP) measurements. Beat-to-beat R-R interval data were incorporated in polysomnography for heart rate variability analysis. The low-frequency/high-frequency band ratio was used to reflect sympathovagal balance. The study participants were divided into four groups based on the presence of EDS and/or hypertension: EDS with hypertension (n = 53), EDS without hypertension (n = 27), no EDS with hypertension (n = 38), and no EDS or hypertension (n = 43). Clinical, polysomnographic and heart rate data were compared and studied among the four groups. Plasma acetylcholine (ACh) levels were assessed to explore the effects of the non-neuronal cholinergic system and the co-occurrence of EDS and hypertension. RESULTS: Patients with EDS and hypertension had more severe OSAS severity indices compared to control patients. Increased cardiac sympathovagal imbalance and nocturnal hypoxemia regulated the presence of EDS and hypertension. Further plasma biomarker analysis revealed that both ESS scores and BP levels were associated with significantly elevated plasma norepinephrine, interleukin-6 and superoxide dismutase levels and significantly decreased ACh levels. Logistic regression analyses showed that ACh was the only factor significantly associated with co-occurrence of EDS and hypertension after controlling for confounders using odds ratio of 0.932, with a 95% confidence interval of 0.868 to 1.000 (P = 0.049). CONCLUSION: The results suggested that OSAS coupled with both EDS and hypertension is a more severe phenotype of the respiratory disorder. The presence of EDS and hypertension was accompanied by sympathovagal imbalance, and co-occurrence of these two conditions may be related to decreased plasma ACh levels.

Adiponectin Ameliorated Pancreatic Islet Injury Induced by Chronic Intermittent Hypoxia through Inhibiting the Imbalance in Mitochondrial Fusion and Division.

Objective This study aimed to assess the protective value of adiponectin (APN) in pancreatic islet injury induced by chronic intermittent hypoxia (CIH). Methods Sixty rats were randomly divided into three groups: normal control (NC) group, CIH group, and CIH with APN supplement (CIH+APN) group. After 5 weeks of CIH exposure, we conducted oral glucose tolerance tests (OGTT) and insulin released test (IRT), examined and compared the adenosine triphosphate (ATP) levels, mitochondrial membrane potential (MMP) levels, reactive oxygen species (ROS) levels, enzymes gene expression levels of Ant1, Cs, Hmox1, and Cox4i1 which represented mitochondrial tricarboxylic acid cycle function, the protein and gene expression levels of DRP1, FIS1, MFN1, and OPA1 which represented mitochondrial fusion and division, and the protein expression levels of BAX, BCL-2, cleaved Caspase-3, and cleaved PARP which represented mitochondrial associated apoptosis pathway of pancreatic islet. Results OGTT and IRT showed blood glucose and insulin levels had no differences among the NC, CIH and CIH+APN groups (both P>0.05) at 0 min, 20 min, 30 min, 60 min, 120 min. However, we found that compared to NC group, CIH increased the ROS level, reduced ATP level and MMP level. The islets of CIH exposed rats showed reduced gene expression levels of Ant1, Cs, Hmox1, and Cox4i1, decreased protein and gene expression levels of MFN1 and OPA1, increased protein and gene expression levels of DRP1 and FIS1, increased protein expression levels of cleaved Caspase-3 and cleaved PARP, with lower ratio of BCL-2/BAX at protein expression level. All the differences among three groups were statistically significant. APN treated CIH rats showed mitigated changes in the above measurements associated with islet injuries. Conclusion APN may ameliorate the pancreatic islet injury induced by CIH via inhibiting the imbalance in mitochondrial fusion and division.

The rate of decrease in oxygen desaturation during severe obstructive sleep apnea syndrome is correlated with subjective excessive daytime sleepiness.

PURPOSE: To explore factors that influence subjective excessive daytime sleepiness (EDS) in patients with severe obstructive sleep apnea syndrome (OSAS). METHODS: Patients with snoring seen at the Sleep Medicine Center of The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University between October 2018 and November 2019 were included in this study. All patients underwent polysomnography (PSG). Noninvasive frequency-domain analysis was used to assess the autonomic nervous system regulation of the heart, with the low frequency (LF)/high frequency (HF) power ratio used to represent the sympathetic-parasympathetic balance. Daytime sleepiness was evaluated by the Epworth sleepiness scale (ESS). Overnight apnea episodes were included for analyses. The rate of pulse oxyhemoglobin saturation (SpO2) decrease was measured as the change in the percentage of SpO2 per second after obstructive apnea and was expressed as the oxygen desaturation rate (ODR). RESULTS: A total of 101 patients with severe OSAS were enrolled in this study and were further divided into two groups: the EDS group (ESS > 10, n = 52) and the non-EDS group (ESS ≤ 10, n = 49). The apnea-hypopnea index (AHI), respiratory effort-related arousals (RERAs), and LF/HF power ratio were significantly higher in the EDS group than in the non-EDS group (AHI: 69.9 ± 14.5 vs. 57.9 ± 16.1 events/h; RERAs: 42.2 ± 16.7 vs. 30.4 ± 13.7 events/h; LF/HF power ratio: 2.9 ± 0.8% vs. 2.4 ± 0.9%, all p < 0.001). Multiple linear regression analyses revealed that after adjusting for covariates expected to affect this relationship, ESS scores were correlated with ODR (ß = 0.520, p < 0.001) and LF/HF power ratio (ß = 0.155, p = 0.028), rather than with the traditional sleep-disordered breathing parameters. CONCLUSIONS: Compared with the traditional PSG parameters, both ODR and an increased LF/HF power ratio were more closely related to daytime sleepiness, especially ODR.

The role of mitophagy in the mechanism of genioglossal dysfunction caused by chronic intermittent hypoxia and the protective effect of adiponectin.

PURPOSE: Dysfunction of the genioglossus muscle is important in the pathogenesis of obstructive sleep apnea due to chronic intermittent hypoxia (CIH). Mitochondrial impairment resulting from hypoxia is mitigated by mitophagy to avoid cell apoptosis in cardiomyocytes. This project was designed to explore the effects of CIH on mitophagy in the genioglossus muscle and the impact of adiponectin (Ad). METHODS: One hundred eighty male SD rats were randomly divided into 3 groups (normal control [NC], CIH, and CIH + Ad groups), with 60 rats in each group observed for 5 weeks. Comparisons of serum Ad levels, mitochondrial structure and function, mitophagy, and cell apoptosis in the genioglossus were made at different time points. RESULTS: (1) The CIH group was significantly different from the NC group as follows: During the first 3 weeks, serum Ad levels, the reactive oxygen species (ROS), relative proteins and mRNA of mitophagy, autophagy biomarker LC3-II, and autophagosomes increased, while during the last 2 weeks, most parameters decreased. (2) There was no difference among the 3 groups in mitochondrial structure and function-associated mRNA during the first 3 weeks, while damaged mitochondrial structures were growing during the last 2 weeks. Exacerbation of apoptosis was also detected in the last 2 weeks. (3) All of the damage was partially alleviated in the CIH + Ad group in contrast to CIH group at the end of this study. CONCLUSION: Disturbances of genioglossal mitophagy could be related to damaged mitochondrial structure and function induced by CIH, which could be alleviated by supplementation of exogenous Ad via increasing mitophagy.

Adiponectin ameliorates lung injury induced by intermittent hypoxia through inhibition of ROS-associated pulmonary cell apoptosis.

PURPOSE: Obstructive sleep apnea hypopnea syndrome has been reported to be associated with pulmonary hypertension (PH). Adiponectin (Ad) has many protective roles in the human body, including its function as an anti-inflammatory and an anti-oxidant, as well as its role in preventing insulin resistance and atherosclerosis. This study aimed to investigate the molecular mechanism of chronic intermittent hypoxia (CIH)-induced pulmonary injury and the protective role of Ad in experimental rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into three groups with 10 rats in each group: normal control (NC) group, CIH group, and CIH + Ad group. Rats in the NC group were kept breathing room air for 12 weeks. Rats in the CIH group were intermittently exposed to a hypoxic environment for 8 h/day for 12 weeks. Rats in the CIH + Ad group received 10 µg Ad twice weekly via intravenous injection. After 12 weeks of CIH exposure, we detected the pulmonary function, pulmonary artery pressure, lung histology, pulmonary cell apoptosis, pulmonary artery endothelial cell apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) level. We also analyzed expression proteins involved in the mitochondria-, endoplasmic reticulum (ER) stress-, and Fas receptor-associated pulmonary apoptosis pathways, as well as the SIRT3/SOD2 pathway. RESULTS: CIH exposure for 12 weeks did not lead to abnormal pulmonary function, PH, or pulmonary artery endothelial cell apoptosis. However, we observed a significant increase in the rate of pulmonary cell apoptosis, the expression of proteins involved in mitochondria-, ER stress-, and Fas receptor-associated pulmonary apoptosis pathways, and the generation of ROS in the CIH group compared with the NC group. In contrast, the MMP and protein expressions of SIRT3/SOD2 pathway were significantly decreased in the CIH group compared with the NC group. Ad supplementation in the CIH + Ad group partially improved these changes induced by CIH. CONCLUSION: Even though CIH did not cause abnormal pulmonary function or PH, early lung injury was detected at the molecular level in rats exposed to CIH. Treatment with Ad ameliorated the pulmonary injury by activating the SIRT3/SOD2 pathway, reducing ROS generation, and inhibiting ROS-associated lung cell apoptosis.

Globular adiponectin alleviates chronic intermittent hypoxia-induced H9C2 cardiomyocytes apoptosis via ER-phagy induction.

This study evaluated the effects of endoplasmic reticulum autophagy (ER-phagy) and globular adiponectin (gAPN) on chronic intermittent hypoxia (CIH)-induced H9C2 cardiomyocytes injury while investigating potential mechanisms of action. The CIH model of H9C2 cardiomyocytes was established in this study. CCK-8 assay was used to determine cell viability post-exposure to various CIH times and gAPN concentrations. Flow cytometry was used to observe H9C2 cardiomyocytes apoptosis and immunofluorescence was used to measure ER-phagy and SEC62 activation. Western blot was used to observe ER stress and AMPK pathway. Results indicated that ER stress was activated in H9C2 cardiomyocytes exposed to CIH. Inhibition of ER stress reduced CIH-induced cell apoptosis. gAPN attenuated CIH-induced ER stress and H9C2 cardiomyocytes apoptosis. ER-phagy and SEC62 protein level were induced by CIH, while gAPN highly enhanced these changes. Inhibition of SEC62 expression reduced ER-phagy and increased ER stress and H9C2 cardiomyocytes apoptosis. Moreover, gAPN induced AMPK expression. Inhibition of AMPK expression reduced SEC62-mediated ER-phagy and increased the H9C2 cardiomyocytes apoptosis. Altogether, our study suggested that gAPN upregulated SEC62-mediated ER-phagy to extenuate ER stress, and mitigated H9C2 cardiomyocytes apoptosis induced by CIH through AMPK activation.

How Does Chronic Intermittent Hypoxia Influence Upper Airway Stability in Rats?

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway collapse during sleep. The contraction of upper airway dilator muscles plays a crucial role in maintaining UA patency. Chronic intermittent hypoxia (CIH) is the most important pathophysiological process of OSA. Exposure to CIH induced not only the damage of dilator muscles but also the plasticity of the muscles. This study aimed to dynamically assess the influence of CIH on the upper airway. METHODS: The experiments were performed on 44 rats. They were randomly divided into a normoxia (NO) group (n=22) and CIH group (n=22). In each group (n=6, respectively), EMG, transcranial magnetic stimulation (TMS) response, and critical pressure (Pcrit) value were recorded on day 0 (the day before exposure), and the 7th, 14th, 21st, and 28th day of air/CIH exposure. For each group, 16 rats were used for transmission electron microscopy observations on day 0, and the 7th, 14th and 28th day of air/CIH exposure (n=4 for every time point). RESULTS: Compared to the NO group at the same point, the CIH group showed a damaged ultrastructure of genioglossus, increased activity of genioglossus corticomotor area, and increased Pcrit of the upper airway from the 7th to the 28th day of CIH. Increased EMG activity occurred at the 14th day of CIH and lasted for 2 weeks. CONCLUSION: The elevated genioglossus corticomotor excitability in response to the CIH could not counterbalance the damage effect of CIH on upper airway dilator muscles, which ultimately increased the collapsibility of the upper airway.