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Abstract Background Obstructive sleep apnoea (OSA) is a sleep-disordered breathing characterized by intermittent hypoxia (IH) that may cause cognitive dysfunction. However, the impact of IH on molecular processes involved in cognitive function remains unclear. Methods C57BL / 6 J mice were exposed to either normoxia (control) or IH for 6 weeks. DNA hydroxymethylation was quantified by hydroxymethylated DNA immunoprecipitation (hMeDIP) sequencing. ten-eleven translocation 1 (Tet1) was knocked down by lentivirus. Specifically, cognitive function was assessed by behavioral experiments, pathological features were assessed by HE staining, the hippocampal DNA hydroxymethylation was examined by DNA dot blot and immunohistochemical staining, while the Wnt signaling pathway and its downstream effects were studied using qRT-PCR, immunofluorescence staining, and Luminex liquid suspension chip analysis. Results IH mice showed pathological changes and cognitive dysfunction in the hippocampus. Compared with the control group, IH mice exhibited global DNA hydroxylmethylation in the hippocampus, and the expression of three hydroxylmethylases increased significantly. The Wnt signaling pathway was activated, and the mRNA and 5hmC levels of Wnt3a, Ccnd2, and Prickle2 were significantly up-regulated. Further caused downstream neurogenesis abnormalities and neuroinflammatory activation, manifested as increased expression of IBA1 (a marker of microglia), GFAP (a marker of astrocytes), and DCX (a marker of immature neurons), as well as a range of inflammatory cytokines (e.g. TNFa, IL3, IL9, and IL17A). After Tet1 knocked down, the above indicators return to normal. Conclusion Activation of Wnt signaling pathway by hippocampal Tet1 is associated with cognitive dysfunction induced by IH. Graphical Abstract

BackgroundAlterations gastrointestinal diseases (GDs) were reported in individuals with obstructive sleep apnea (OSA), however, the genetic background between OSA and GDs is still unclear.MethodsThis investigation employed Mendelian randomization (MR) analyses to evaluate the causal effect between OSA and 19 types of GDs (gastroesophageal reflux disease (GERD), ulcerative colitis, celiac disease, Crohn’s disease, chronic gastritis, irritable bowel syndrome, primary biliary cholangitis, diverticular disease, gastroduodenal ulcer, acute pancreatitis, non-alcoholic fatty liver disease, primary sclerosing cholangitis, cirrhosis, calculus of bile duct, calculus of gallbladder, pancreatic cancer, gastric cancer, colorectal cancer, and esophageal cancer). The inverse-variance weighted (IVW) method was used to evaluate the main effects model of causality.ResultsThis MR study suggests that OSA may play a causal role inflammation-related GDs (GERD, PIVW=5.94×10-9; gastroduodenal ulcer, PIVW=1×10-4; chronic gastritis, PIVW=0.0214; ulcerative colitis, PIVW=0.0296), and gallstones (calculi of the gallbladder, PIVW=0.0429; calculi of the bile duct, PIVW=0.0068). After accounting for obesity, type 2 diabetes, smoking, and alcohol consumption, the multivariate MR (MVMR) analysis identified that OSA is an independent risk factor for GERD, gastroduodenal ulcer, and calculus of the bile duct. The reverse MVMR analysis showed a causal effect of GERD on OSA. Besides, we did not find that the predisposition to OSA was associated with 4 cancers.ConclusionThis MR analysis provides compelling evidence of an independent causal relationship between genetically predicted OSA and an elevated risk of inflammation-related GDs. Besides, no causal association was observed between OSA and cancers. Further studies should be carried out to verify our findings.

Paediatric obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder resulting in chronic intermittent hypoxia (CIH) that has been linked to metabolism and endocrine impairment. Protein acetylation, which is a frequently occurring posttranslational modification, plays pivotal roles in the regulation of hypothalamic processes. However, the effects of CIH-induced global protein acetylation on hypothalamic function and endocrine metabolism remain poorly understood. To bridge this knowledge gap, we conducted a study utilizing liquid chromatography–mass spectrometry to analyse the lysine acetylome and proteome of the hypothalamus in healthy infantile mice exposed to 3 weeks of intermittent hypoxia (as a CIH model) compared to normoxic mice (as controls). Our analysis identified and quantified 2699 Kac sites in 2453 proteins. These acetylated proteins exhibited disruptions primarily in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Additionally, we observed significant down-regulation of proteins that are known to be involved in endocrine hormone secretion. This study aimed to elucidate the molecular mechanisms underlying CIH-induced alterations in protein acetylation within the hypothalamus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hypothalamic function, our findings contribute to a deeper understanding of the consequences stemming from CIH-induced changes in protein acetylation within the hypothalamus as well as its potential role in endocrine impairment.

Abstract Background Phosphodiesterases (PDEs) have been associated with psychiatric disorders in observational studies; however, the causality of associations remains unestablished. Methods Specifically, cyclic nucleotide PDEs were collected from genome-wide association studies (GWASs), including PDEs obtained by hydrolyzing both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (PDE1A, PDE2A, and PDE3A), specific to cGMP (PDE5A, PDE6D, and PDE9A) and cAMP (PDE4D and PDE7A). We performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the relationship between PDEs and nine psychiatric disorders. The inverse-variance-weighted (IVW) method, MR-Egger, and weighted median were used to estimate causal effects. The Cochran’s Q test, MR-Egger intercept test, MR Steiger test, leave-one-out analyses, funnel plot, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for sensitivity analyses. Results The PDEs specific to cAMP were associated with higher-odds psychiatric disorders. For example, PDE4D and schizophrenia (SCZ) (odds ratios (OR) = 1.0531, P IVW = 0.0414), as well as major depressive disorder (MDD) (OR = 1.0329, P IVW = 0.0011). Similarly, PDE7A was associated with higher odds of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.0861, P IVW = 0.0038). Exploring specific PDE subtypes and increase intracellular cAMP levels can inform the development of targeted interventions. We also observed PDEs (which hydrolyzes both cAMP and cGMP) was associated with psychiatric disorders [OR of PDE1A was 1.0836 for autism spectrum disorder; OR of PDE2A was 0.8968 for Tourette syndrome (TS) and 0.9449 for SCZ; and OR of PDE3A was 0.9796 for MDD; P

IntroductionChronic intermittent hypoxia (CIH) can negatively affect hippocampal function through various molecular mechanisms. Protein acetylation, a frequently occurring modification, plays crucial roles in synaptic plasticity and cognitive processes. However, the global protein acetylation induced by CIH in the hippocampus and its specific effects on hippocampal function and behavior remain poorly understood.MethodsTo address this gap, we conducted a study using liquid chromatography-tandem mass spectrometry to analyze the lysine acetylome and proteome of the hippocampus in healthy adult mice exposed to intermittent hypoxia for 4 weeks (as a CIH model) compared to normoxic mice (as a control).ResultsWe identified and quantified a total of 2,184 lysine acetylation sites in 1,007 proteins. Analysis of these acetylated proteins revealed disturbances primarily in oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and glycolysis, all of which are localized exclusively to mitochondria. Additionally, we observed significant changes in the abundance of 21 proteins, some of which are known to be associated with cognitive impairments.DiscussionThis study helps to elucidate the molecular mechanisms underlying CIH-induced changes in protein acetylation in the hippocampus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hippocampal function, our findings contribute to a better understanding of the consequences of CIH-induced changes in protein acetylation in the hippocampus and the potential role of CIH in cognitive impairment.

IntroductionEpstein-Barr virus (EBV) is a highly dangerous virus that is globally prevalent and closely linked to the development of nasopharyngeal cancer (NPC). Plasma EBV DNA analysis is an effective strategy for early detection, prognostication and monitoring of treatment response of NPC.MethodsHere, we present a novel molecular diagnostic technique termed EBV-MCDA-LFB, which integrates multiple cross displacement amplification (MCDA) with nanoparticle-based lateral flow (LFB) to enable simple, rapid and specific detection of EBV. In the EBV-MCDA-LFB system, a set of 10 primers was designed for rapidly amplifying the highly conserved tandem repeat BamHI-W region of the EBV genome. Subsequently, the LFB facilitate direct assay reading, eliminating the use of extra instruments and reagents.ResultsThe outcomes showed that the 65°C within 40 minutes was the optimal reaction setting for the EBV-MCDA system. The sensitivity of EBV-MCDA-LFB assay reached 7 copies per reaction when using EBV recombinant plasmid, and it showed 100% specificity without any cross-reactivity with other pathogens. The feasibility of the EBV-MCDA-LFB method for EBV detection was successfully validated by 49 clinical plasma samples. The complete detection process, consisting of rapid template extraction (15 minutes), MCDA reaction (65°C for 40 minutes), and LFB result reading (2 minutes), can be finalized within a 60-minutes duration.DiscussionEBV-MCDA-LFB assay designed here is a fast, extremely sensitive and specific technique for detecting EBV in field and at the point-of-care (PoC), which is especially beneficial for countries and regions with a high prevalence of the disease and limited economic resources.

BackgroundOlfaction is one of the five basic senses of human beings. As such, olfactory dysfunction seriously affects patients' quality of life and can even endanger them. In recent years, olfactory dysfunction has attracted greater research interest, and numerous studies have been published on olfactory dysfunction. However, there are few studies on olfactory dysfunction through bibliometric analysis. This study aims to describe the current situation and identify the foci and potential new research directions of olfactory dysfunction using a bibliometric approach.MethodsArticles related to olfactory dysfunction published from 2002 to 2021 were located in the Web of Science Core Collection of Clarivate Analytics (London, UK). Bibliometric analyses were conducted with the CiteSpace (Chaomei Chen, Drexel University, Philadelphia, PA, USA) and VOSviewer (Center for Science and Technology Studies, Leiden University, Leiden, Netherlands) software programs.ResultsThe number of articles published each year showed an upward trend, especially in 2020, where a sharp increase had occurred due to the coronavirus disease 2019 (COVID-19) pandemic. The United States was the country with the most publications and the strongest international cooperation. In terms of institutions, the greatest number of publications from a single institution came from Dresden University of Technology. Thomas Hummel was the author who had contributed the most articles. An analysis of co-citation networks and burst keywords in the field revealed a shift from “gonadotropin-releasing hormone” and “apoptosis” earlier on to “olfactory training,” “COVID-19,” and “Parkinson's disease” more recently. “Outcome,” “COVID-19,” “infection,” and “pathogenesis” are topics of the research frontier and hotspots.ConclusionMore attention has been paid to olfactory dysfunction as the understanding of it has improved in the past 20 years. This study provides researchers with an objective, systematic, and comprehensive analysis of the literature on olfactory dysfunction. The current frontier areas and hotspots in the field focus on the pathological mechanisms of olfactory dysfunction after infection with COVID-19 and its different prognoses. The pathophysiological mechanism of olfactory dysfunction in neurodegenerative diseases and COVID-19 will be a primary future research direction.

From a theoretical viewpoint, dark matter is a prerequisite entity in the formation processes of large-scale structures on the cosmological (galactic) scales of space and time. The behaviours of Jeans modes for gravitational systems composed of dark and baryonic matters are restudied in the framework of Kaniadakis' statistics and kinetic theory. The results show that the [Formula: see text] parameter and density ratio of dark to baryonic matter [Formula: see text] have significant effects on the gravitational instabilities of such systems. As a test of the viability of this generalized context, we also prove that the dispersion relations for the Maxwellian case is recovered in the limitation of [Formula: see text]. Related results in the present work can provide scientific reference for structure formation on the cosmic Jeans scale.

Based on the framework of nonextensive statistics and its related kinetic theory, the Jeans instability in a self-gravitational system composed of dark and bright matters is restudied. The results show that the nonextensivity, the presence of dark matter, has significant effects on the dynamics of Jeans modes. With the increase in the q parameter and the ratio of dispersion velocities, as well as the decreased ratio of densities of dark to bright matters, both critical wave-numbers and growth rates of the instabilities are increased. In addition, as expected, when q → 1, the corresponding results for Maxwellian velocity distribution are recovered. The present results may shed new light on the comprehension of the intrinsic physical mechanism responsible for the collapse of interstellar gas clouds.