Cyanidin-3-O-glucoside alleviates ethanol-induced liver injury by promoting mitophagy in a Gao-binge mouse model of alcohol-associated liver disease.

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading cause of liver disease-related deaths worldwide. Unfortunately, approved medications for the treatment of this condition are quite limited. One promising candidate is the anthocyanin, Cyanidin-3-O-glucoside (C3G), which has been reported to protect mice against hepatic lipid accumulation, as well as fibrosis in different animal models. However, the specific effects and mechanisms of C3G on ALD remain to be investigated. EXPERIMENTAL APPROACH: In this report, a Gao-binge mouse model of ALD was used to investigate the effects of C3G on ethanol-induced liver injury. The mechanisms of these C3G effects were assessed using AML12 hepatocytes. RESULTS: C3G administration ameliorated ethanol-induced liver injury by suppressing hepatic oxidative stress, as well as through reducing hepatic lipid accumulation and inflammation. Mechanistically, C3G activated the AMPK pathway and enhanced mitophagy to eliminate damaged mitochondria, thus reducing mitochondria-derived reactive oxidative species in ethanol-challenged hepatocytes. CONCLUSIONS: The results of this study indicate that mitophagy plays a potentially important role underlying the hepatoprotective action of C3G, as demonstrated in a Gao-binge mouse model of ALD. Accordingly, C3G may serve as a promising, new therapeutic drug candidate for use in ALD.

Passive Self-Sustained Thermoelectric Devices Powering the 24 h Wireless Transmission via Radiation-Cooling and Selective Photothermal Conversion.

The rapid development of the Internet of Things has triggered a huge demand for self-sustained technology that can provide a continuous electricity supply for low-power electronics. Here, a self-sustained power supply solution is demonstrated that can produce a 24 h continuous and unipolar electricity output based on thermoelectric devices by harvesting the environmental temperature difference, which is ingeniously established utilizing radiation cooling and selective photothermal conversion. The developed prototype system can stably maintain a large temperature difference of about 1.8 K for a full day despite the real-time changes in environmental temperature and solar radiation, thereby driving continuous electricity output using the built-in thermoelectric device. Specifically, the large output voltage of >102 mV and the power density of >4.4 mW m-2 could be achieved for a full day, which are outstanding among the 24 h self-sustained thermoelectric devices and far higher than the start-up values of the wireless temperature sensor and also the light-emitting diode, enabling the 24 h remote data transmission and lighting, respectively. This work highlights the application prospects of self-sustained thermoelectric devices for low-power electronics.

Hypoxia Induces Tumor-Derived Exosome SNHG16 to Mediate Nasopharyngeal Carcinoma Progression through the miR-23b-5p/MCM6 Pathway.

This study aims to investigate the mechanism of tumor-derived exosomal (EVs) SNHG16 in promoting the progression of nasopharyngeal carcinoma (NPC). QRT-PCR was used to detect the expression of SNHG16, miR-23b-5p and MCM6 in NPC. MTT, flow cytometry and transwell were used to detect the effects of them on the proliferation, cycle, apoptosis and invasion ability of NPC. Transmission electron microscopy, Western blotting and BCA were used to verify the regulation of exosome secretion under different oxygen environments. Our results showed that hypoxia induces tumor-derived exosome SNHG16 to mediate NPC progression through the miR-23b-5p/MCM6 pathway.

The hepatic GABAergic system promotes liver macrophage M2 polarization and mediates HBV replication in mice.

Macrophages display functional phenotypic plasticity. Hepatitis B virus (HBV) infection induces polarizations of liver macrophages either to M1-like pro-inflammatory phenotype or to M2-like anti-inflammatory phenotype. Gamma-aminobutyric acid (GABA) signaling exists in various non-neuronal cells including hepatocytes and some immune cells. Here we report that macrophages express functional GABAergic signaling components and activation of type A GABA receptors (GABAARs) promotes M2-polarization thus advancing HBV replication. Notably, intraperitoneal injection of GABA or the GABAAR agonist muscimol increased HBV replication in HBV-carrier mice that were generated by hydrodynamical injection of adeno-associated virus/HBV1.2 plasmids (pAAV/HBV1.2). The GABA-augmented HBV replication in HBV-carrier mice was significantly reduced by the GABAAR inhibitor picrotoxin although picrotoxin had no significant effect on serum HBsAg levels in control HBV-carrier mice. Depletion of liver macrophages by liposomal clodronate treatment also significantly reduced the GABA-augmented HBV replication. Yet adoptive transfer of liver macrophages isolated from GABA-treated donor HBV-carrier mice into the liposomal clodronate-pretreated recipient HBV-carrier mice restored HBV replication. Moreover, GABA or muscimol treatment increased the expression of "M2" cytokines in macrophages, but had no direct effect on HBV replication in the HepG2.2.15 cells, HBV1.3-transfected Huh7, HepG2, or HepaRG cells, or HBV-infected Huh7-NTCP cells. Taken together, these results suggest that increasing GABA signaling in the liver promotes HBV replication in HBV-carrier mice by suppressing the immunity of liver macrophages, but not by increasing the susceptibility of hepatocytes to HBV infection. Our study shows that a previously unknown GABAergic system in liver macrophage has an essential role in HBV replication.

Subtypes of obstructive sleep apnea in children and related factors.

STUDY OBJECTIVES: To investigate the prevalence of positional obstructive sleep apnea (P-OSA) and rapid eye movement-related OSA (REM-OSA) in children with OSA and identify related factors. METHODS: This was a cross-sectional study among children aged 2-12 years diagnosed with OSA using overnight polysomnography (PSG) between August 1, 2020, and July 31, 2021. Demographics, anthropometrics, PSG, and OSA-18 questionnaire data were recorded. RESULTS: Data from a total of 474 children were available for analysis. Children had a median age of 4.8 (4.1, 6.4) years, 66.7% were male, and 23.2% were obese. The prevalence of P-OSA was 38.2% and that of REM-OSA was 43.0%. P-OSA was correlated with age and obstructive apnea-hypopnea index (OAHI; odds ratio [OR] = 1.172, 0.947; P = .005, < 0.001, respectively), but not sex, obesity, and adenoid and tonsil size (OR = 1.265, 0.785, 0.826, 0.989; P = .258, 0.327, 0.153, 0.905, respectively). REM-OSA was correlated with age, adenoid size, tonsil size, and OAHI (OR = 0.876, 1.320, 1.387, 1.021; P = .024, 0.040, 0.001, 0.042) but not with sex and obesity (OR = 0.910, 1.281; P = .643, 0.315). CONCLUSIONS: The prevalence of P-OSA was 38.2% and that of REM-OSA was 43.0% in children with OSA. Age was correlated with both the prevalence of P-OSA and REM-OSA, with an increasing and decreasing prevalence as children grew older, respectively. The severity of OSA was significantly associated with the prevalence of both P-OSA and REM-OSA. Adenoid and tonsil size were correlated with the prevalence of REM-OSA but not P-OSA. Obesity and sex were not associated with the prevalence of P-OSA or REM-OSA. CITATION: Wu Y, Zheng L, Cui G, Xu Z, Ni X. Subtypes of obstructive sleep apnea in children and related factors. J Clin Sleep Med. 2022;18(10):2397-2404.

The effect of different intervention on disease outcomes and urinary leukotriene levels in pediatric sleep-disordered breathing.

BACKGROUND: The prognosis in children with sleep-disordered breathing (SDB) undergoing adenotonsillectomy (T&A), medication, and watchful waiting with supportive care, and the changes of urine cysteinyl leukotriene E4 (uLTE4) at pretreatment and post-treatment are not well studied. METHODS: Children aged 3-14 yrs suffering from SDB were enrolled. All children underwent polysomnography (PSG), completed OSA-18 Quality of Life questionnaire and uLTE4 levels were measured pre- and post-T&A, medication and watchful waiting with supportive care about six months later. Children with obstructive sleep apnea who demonstrated a resolution of disease (OAHI<1) were defined as remission. The remission in children with primary snoring (PS) was defined as the absence of snoring at the follow-up. Deterioration was defined as a progression of disease severity, such as PS progressing to OSA, mild OSA progressing to moderate-to-severe OSA, and moderate OSA progressing to severe OSA. All the others were defined as unchanged. RESULTS: A total of 78 children were enrolled. After treatment, 10 (50.0%), 6 (18.2%), and 7 (28.0%) children in T&A, medication, and watchful waiting were in remission respectively. PSG variables and OSA-18 Quality of Life scores were significantly improved in the T&A group and remission population. The levels of uLTE4 were not significantly different pre- and post-treatment in T&A group nor in the remission population. CONCLUSIONS: T&A can significantly reduce PSG variables and improve the Quality of Life in children with moderate to severe OSA. The levels of uLTE4 did not change after T&A nor in the remission population after six-month follow-up.

Detection of pediatric obstructive sleep apnea using a multilayer perceptron model based on single-channel oxygen saturation or clinical features.

PURPOSE: This study was performed to develop and evaluate a method of detecting pediatric obstructive sleep apnea (OSA) using a multilayer perceptron (MLP) model based on single-channel nocturnal oxygen saturation (SpO2) with or without clinical data. METHODS: Polysomnography data for 888 children with OSA and 417 unaffected children were included. An MLP model was proposed based on the features obtained from SpO2 and combined features of SpO2 and clinical data to screen symptomatic children for OSA. The performance of the overall classification was evaluated with the receiver operating characteristics curve and the metrics of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and accuracy. RESULTS: The sensitivity, specificity, PPV, NPV, LR+, LR-, and accuracy of the MLP model for SpO2 of an obstructive apnea-hypopnea index (OAHI) cutoff value of 1, 5, and 10 were 0.62-0.96, 0.11-0.97, 0.70-0.81, 0.55-0.93, 1.08-21.0, 0.39-0.39, and 0.69-0.91, respectively. The area under the receiver operating characteristics curve of an OAHI cutoff value of 1, 5, and 10 was 0.720, 0.842, and 0.922, respectively. After adding the clinical data of age, sex, body mass index, weight category, adenoid grade, or tonsil scale, the performance of the MLP model was basically at the same level as only single-channel SpO2. CONCLUSIONS: Application of this MLP model using single-channel SpO2 in children with snoring has high accuracy in the diagnosis of moderate to severe OSA but a poor effect in the diagnosis of mild OSA. The combination of clinical data did not significantly improve the diagnostic performance of the MLP model.

Generation and characterization of iPSC lines (BCH001) from a boy with intron 14 mutation in the ret proto-oncogene (RET) gene.

Congenital central hypoventilation syndrome (CCHS) is characterized by an alteration of the ventilatory response to hypercapnia and hypoxia, and is classically presented in neonates with abnormalities of the autonomic nervous system. Here, we generated human induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) isolated from a male patient clinically diagnosed with CCHS. These iPSC lines carry a heterozygous RET mutation (c.2608-125C > T), express pluripotency markers, have the capacity to differentiate into the normal teratoma tissue, retain the RET mutation and display the normal karyotype, which will also provide a useful resource to study the pathogenesis of CCHS.

Analysis of genomics and immune infiltration patterns of epithelial-mesenchymal transition related to metastatic breast cancer to bone.

OBJECTIVE: This study aimed to design a weighted co-expression network and a breast cancer (BC) prognosis evaluation system using a specific whole-genome expression profile combined with epithelial-mesenchymal transition (EMT)-related genes; thus, providing the basis and reference for assessing the prognosis risk of spreading of metastatic breast cancer (MBC) to the bone. METHODS: Four gene expression datasets of a large number of samples from GEO were downloaded and combined with the dbEMT database to screen out EMT differentially expressed genes (DEGs). Using the GSE20685 dataset as a training set, we designed a weighted co-expression network for EMT DEGs, and the hub genes most relevant to metastasis were selected. We chose eight hub genes to build prognostic assessment models to estimate the 3-, 5-, and 10-year survival rates. We evaluated the models' independent predictive abilities using univariable and multivariable Cox regression analyses. Two GEO datasets related to bone metastases from BC were downloaded and used to perform differential genetic analysis. We used CIBERSORT to distinguish 22 immune cell types based on tumor transcripts. RESULTS: Differential expression analysis showed a total of 304 DEGs, which were mainly related to proteoglycans in cancer, and the PI3K/Akt and the TGF-ß signaling pathways, as well as mesenchyme development, focal adhesion, and cytokine binding functionally. The 50 hub genes were selected, and a survival-related linear risk assessment model consisting of eight genes (FERMT2, ITGA5, ITGB1, MCAM, CEMIP, HGF, TGFBR1, F2RL2) was constructed. The survival rate of patients in the high-risk group (HRG) was substantially lower than that of the low-risk group (LRG), and the 3-, 5-, and 10-year AUCs were 0.68, 0.687, and 0.672, respectively. In addition, we explored the DEGs of BC bone metastasis, and BMP2, BMPR2, and GREM1 were differentially expressed in both data sets. In GSE20685, memory B cells, resting memory T cell CD4 cells, T regulatory cells (Tregs), γδ T cells, monocytes, M0 macrophages, M2 macrophages, resting dendritic cells (DCs), resting mast cells, and neutrophils exhibited substantially different distribution between HRG and LRG. In GSE45255, there was a considerable difference in abundance of activated NK cells, monocytes, M0 macrophages, M2 macrophages, resting DCs, and neutrophils in HRG and LRG. CONCLUSIONS: Based on the weighted co-expression network for breast-cancer-metastasis-related DEGs, we screened hub genes to explore a prognostic model and the immune infiltration patterns of MBC. The results of this study provided a factual basis to bioinformatically explore the molecular mechanisms of the spread of MBC to the bone and the possibility of predicting the survival of patients.

Analysis of the impact of allergic rhinitis on the children with sleep disordered breathing.

OBJECTIVES: We assessed the influence of allergic rhinitis (AR) on sleep disordered breathing (SDB) in children with adenotonsillar hypertrophy (ATH), and compared sleep quality and polysomnographic data in habitually snoring children with or without AR. METHODS: Children with snoring resulting from adenoid/tonsils hypertrophy were recruited between Jan 1st, 2018 and Jun 30th, 2018. The exclusion criteria were congenital disorders, metabolic disorders, neurological disorders and pulmonary diseases, such as, asthma etc. Overnight polysomnography (PSG) and Sleep Questionnaire (SQ) were assessed on each participant to identify children with obstructive sleep apnea (OSA). Cross-sectional study design was used to examine PSG and SQ data. The diagnosis of AR was based upon history of allergies and positive clinical examinations, then confirmed by allergen test. Participants were categorized into four groups (AR and Non-OSA group; AR and OSA group; Non-AR and Non-OSA group; Non-AR and OSA group). Non-parametric rank sum test was used for statistical analysis. RESULTS: Six hundred and sixty children (age between 3yrs and 14yrs) with SDB were enrolled in the study (mean age 6.7 ± 2.1yrs, 67.4% male). The number of children diagnosed with OSA was 495 (74.3%). The prevalence of AR among all participating SDB children was 25.8%, and AR with OSA was19.4%. The behavioral problems scores in SQ showed significant difference among SDB children with AR (P<.0001). No difference was observed in the OAHI (obstructive apnea-hypopnea index) and AHI (apnea-hypopnea index) between the groups of children with and without AR regardless whether OSA was coexisting. The percentage of time spent in the rapid eye movement (REM) sleep stage was shortened among children with AR without OSA (P = 0.031), however, the percentage of time spent in the REM sleep stage was not different among children with OSA (P = 0.98). The total sleep time was shorter among children with AR (OSA P = 0.02; without OSA P = 0.03). CONCLUSIONS: Despite the high prevalence of AR in patients with SDB, AR is not an aggravating factor for the severity of AHI. High risk behavioral problems link to SDB with AR. AR is associated with shortened REM sleep stage in children with SDB without sleep apnea, and shortened total sleep time in children with SDB.

Risk factors of obstructive sleep apnea syndrome in children.

BACKGROUND: The known risk factors of childhood OSAS include tonsillar and adenoidhypertrophy, obesity, craniofacial anomalies, neuromuscular disorders and African-American (AA) ancestry. Whether other factors such as allergic rhinitis (AR), premature, environmental tobacco smoking (ETS) are associated with OSAS are inconsistent in different studies. Our study enrolled children of a broad age range and included potential risk factors of OSAS derived from previous studies and our own experience. Our objective is to identify risk factors of OSAS in children in a clinical setting. METHODS: Children between 2 and 15 years of age exhibiting snoring symptoms who visited the sleep center for polysomnography (PSG) were enrolled. All children completed a questionnaire, physical examination and PSG. The questionnaire included demographic data and information related to potential risk factors for sleep disorders. A physical examination included measurements of height, weight, neck circumference, waist and hip ratio, visual evaluation of the tonsils and the degree of adenoid obstruction. Children with obstructive apnea-hypopnea index (OAHI) ≥ 1 were defined as OSAS. RESULTS: A total of 1578 children were enrolled and1009 children exhibited OSAS. Univariate analyses showed that snoring occurring for ≥ 3 months, male gender, preterm birth, breastfeeding, obesity, neck circumference ≥ 30 cm, waist/hip ratio ≥ 0.95, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. The proportion of low educational level was higher in parents who breastfed their babies than those who didn't. Multivariate analysis showed that snoring for ≥ 3 months, male gender, obesity, breastfeeding, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. Confounders such as socioeconomic status, parental occupation, and health-related behaviors should be explored further to investigate the relationship between breastfeeding and OSAS. CONCLUSION: The independent risk factors for OSAS in children included snoring ≥ 3 months, male gender, obesity, breastfeeding, tonsillar and adenoid hypertrophy. The study was registered on Clinical Trials government (NCT02447614). The name of the trial is "Follow-up Studies of Primary Snoring (PS) and Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in Chinese Children" and the URL is https://clinicaltrials.gov/.