SENP1 regulates intermittent hypoxia-induced microglia mediated inflammation and cognitive dysfunction via wnt/ß-catenin pathway.

Obstructive sleep apnea syndrome (OSAS), characterized by repeated narrow or collapse of the upper airway during sleep, resulting in periodic reductions or cessations in ventilation, consequent hypoxia, hypercapnia, increased sympathetic activity and sleep fragmentation, places a serious burden on society and health care. Intermittent hypoxia (IH), which cause central nervous system (CNS) inflammation, and ultimately lead to neuropathy, is thought to be a crucial contributor to cognitive impairment in OSAS. Wnt signaling pathway exerts an important role in the regulation of CNS disorders. Particularly, it may be involved in the regulation of neuroinflammation and cognitive dysfunction. However, its underlying mechanism remains poorly understood. Accumulating evidence demonstrated that Wnt signaling pathway may inhibited in a variety of neurological disorders. Recently studies revealed that SUMOylation was participated in the regulation of neuroinflammation. Members of Wnt/ß-catenin pathway may be targets of SUMOylation. In vitro and in vivo molecular biology experiments explored the regulatory mechanism of SUMOylation on Wnt/ß-catenin in IH-induced neuroinflammation and neuronal injury, which demonstrated that IH induced the SUMOylation of ß-catenin, microglia mediated inflammation and neuronal damage. Moreover, SENP1 regulated the de-SUMOylation of ß-catenin, triggered Wnt/ß-catenin pathway, and alleviated neuroinflammation and neuronal injury, thus improving IH-related mice cognitive dysfunction.

Sleep disordered breathing and neurobehavioral deficits in children and adolescents: a systematic review and meta-analysis.

BACKGROUND: Sleep disordered breathing (SDB) is broadly recognized to be associated with neurobehavioral deficits, which have significant impacts on developing-aged children and adolescents. Therefore, our study aimed to quantify the proportion of neurobehavioral impairments attributed to SDB in general children and adolescents by population attributable fraction (PAF). METHODS: The study was registered at PROSPERO (ID: CRD42023388143). We collected two types of literature on the prevalence of SDB and the risk of SDB-related neurobehavioral deficits from ten electronic databases and registers, respectively. The pooled effect sizes (Pe, Pc, RR) by random-effects meta-analysis were separately substituted into Levin's formula and Miettinen's formula to calculate PAFs. RESULTS: Three prevalence literature and 2 risk literature, all with moderate/high quality, were included in the quantitative analysis individually. The prevalence of SDB was 11% (95%CI 2%-20%) in children and adolescents (Pe), while the SDB prevalence was 25% (95%CI 7%-42%) in neurobehavioral patients (Pc). SDB diagnosis at baseline was probably associated with about threefold subsequent incidence of neurobehavioral deficits (pooled RR 3.24, 95%CI 1.25-8.41), after multi-adjustment for key confounders. Up to 19.8% or 17.3% of neurobehavioral consequences may be attributed to SDB from Levin's formula and Miettinen's formula, respectively. CONCLUSIONS: A certain number of neurobehavioral consequences may be attributable to SDB. It is essential for clinicians to identify and treat SDB timely, as well as screen for SDB in patients with neurobehavioral impairments. More longitudinal studies of SDB and neurobehavioral deficits are needed in the future to further certify the association between them.

How is Obstructive Sleep Apnea Associated with High Blood Pressure and Diabetes Mellitus Type 2? Clues from a Two-Step Mendelian Randomized Study.

Background: Obstructive sleep apnea (OSA), high blood pressure (HBP), and type 2 diabetes mellitus (T2DM) have a close clinical relationship, but whether and how OSA affects HBP and T2DM is unclear. Study Design and Methods: Two-step, two-sample Mendelian randomization techniques were applied using single-nucleotide polymorphisms as genetic instruments for exposure and mediators, thus minimizing bias due to confounding factors and reverse causality. The total effect of OSA on HBP and T2DM was categorized into direct and mediating effects based on the mediating factors. Results: Two-sample MR analysis showed that OSA increased the risk of HBP (odds ratio [OR] = 1.010, 95% confidence interval [CI], 1.002-1.018; P = 0.0121) and T2DM (OR = 1.140, 95% CI, 1.059-1.228; P = 0.0005). In the process of OSA caused by HBP, sex hormone-binding globulin (SHBG) (female, 4.47% mediation; male, 2.76% mediation), total testosterone (TT) (male, 3.72% mediation), bioavailable testosterone (BioT) (female, 7.74% mediation), high-density lipoprotein cholesterol (HDL-C) (3.25% mediation), and apolipoprotein A1 (ApoA1) (1.31% mediation) were individual contributors. SHBG (female, 4.10% mediation; male, 1.58% mediation), TT (male, 3.69% mediation), BioT (female, 2.58% mediation), HDL-C (3.32% mediation), ApoA1 (2.14% mediation), and omega-6 fatty acids (2.33% mediation) may have mediating roles to varying degrees in the process of OSA caused by T2DM. Interpretation: This MR study showed that OSA is a risk factor for HBP and T2DM, and the evaluation of mediators may help further reveal the specific mechanism by which OSA causes HBP and T2DM.

Commemoration and Emotional Sustenance: A Text Analysis of Students' Motivations Behind Online Mourning of Dr Li Wenliang.

As one of the first doctors issued a protective warning to the public, Dr. Li Wenliang was known as "whistleblower" of COVID-19 pandemic. After his death of COVID-19, students entered to his Sina Weibo to display their condolences and sorrow. We conduct text analysis and sentiment classification to investigate the motivation behind online mourning for Dr. Li among students on Sina Weibo. Our results indicate that, a) there always more than one motivation behind online mourning exists in each time period. b) continuing connection and semi-interaction with the deceased is the main motivation when students mourn online. c) there exists positive correlation between the influence of the deceased and the motivation--sharing information with the community of fans and creating social support in a time of loss and social support. d) the motivation--honoring the dead and expressing sadness and resentment can gradually lose over time.