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Migraine ranks among the most prevalent disorders worldwide, leading to disability and decreased quality of life in patients. Recently, neurogenic inflammation has been recognized as a potential underlying pathology contributing to the migraine pain pathway. Mast cells reside in the meninges and have been implicated in contributing to the pathophysiology of migraine. Here we report for the first time that the mouse Mas-Related G-protein-coupled Receptor B2 (MrgprB2), is expressed on meningeal connective tissue mast cells and contributes to Pituitary Adenylate Cyclase Activating Peptide (PACAP)-induced migraine-like pain behavior. We also found that PACAP was able to dose-dependently lead to enzyme release from human mast cells via activation of MRGPRX2; the human homolog of MrgprB2. Using a transgenic MRGPRX2 mouse, we observed significant increases in PACAP-induced migraine-like pain behavior in MRGPRX2 + mice vs mice lacking the receptor. These results reveal both MrgprB2 and MRGPRX2 as important contributors to neuropeptide-induced migraine pain.

Polymer solid electrolytes (SEs) with high safety and flexibility are ideal for advanced lithium‐metal solid‐state batteries (SSBs). Among various polymer SEs, polyvinylidene fluoride‐co‐hexafluoropropylene (PVDF‐HFP) polymer SEs have gained increased attention for their high dielectric constants, high ionic conductivity, and excellent flexibility. However, severe side reactions at the interface caused by the decomposition of residual DMF solvent significantly reduce the cycle life of PVDF‐HFP‐based SSBs. Herein, La2O3 nanoparticles are used as new inorganic fillers to form a PVDF‐HFP/LiFSI/La2O3‐40% composite polymer electrolyte (PVDF‐HFP/La2O3 CPE). Benefiting from the interaction between La2O3 and N,N‐dimethylformamide (DMF) solvent molecules, the cell cycling stability is greatly improved. In addition, the PVDF‐HFP/LiFSI solid electrolyte (PVDF‐HFP SE) containing 40 wt% La2O3 has the highest ionic conductivity of 1.33 × 10−3 S cm−1 at 25 °C. It also exhibits a higher lithium‐ion transference number of 0.52 and lower polarization. The PVDF‐HFP/La2O3 CPE here ensures high ionic conductivity and stable interface chemistry in SSB, demonstrating a promising application potential. A novel La2O3 filler introduced into a polymer electrolyte to stabilize residual solvent ensures advanced solid‐state lithium‐metal batteries. The PVDF‐HFP/LiFSI solid electrolyte containing 40 wt% La2O3 has the highest ionic conductivity of 1.33 × 10−3 S cm−1 at 25 °C. Moreover, the full cell assembled with PVDF‐HFP/LiFSI/La2O3 presents greatly improved cycling stability, demonstrating a promising application potential.

To determine the effects of mild blast-induced traumatic brain injury (bTBI), several groups of rats were subjected to blast injury or sham injury in a compressed air-driven shock tube. The effects of bTBI on relative cerebral perfusion (laser Doppler flowmetry [LDF]), and mean arterial blood pressure (MAP) cerebral vascular resistance were measured for 2 h post-bTBI. Dilator responses to reduced intravascular pressure were measured in isolated middle cerebral arterial (MCA) segments, ex vivo, 30 and 60 min post-bTBI. Neuronal injury was assessed (Fluoro-Jade C [FJC]) 24 and 48 h post-bTBI. Neurological outcomes (beam balance and walking tests) and working memory (Morris water maze [MWM]) were assessed 2 weeks post-bTBI. Because impact TBI (i.e., non-blast TBI) is often associated with reduced cerebral perfusion and impaired cerebrovascular function in part because of the generation of reactive oxygen and nitrogen species such as peroxynitrite (ONOO−), the effects of the administration of the ONOO− scavenger, penicillamine methyl ester (PenME), on cerebral perfusion and cerebral vascular resistance were measured for 2 h post-bTBI. Mild bTBI resulted in reduced relative cerebral perfusion and MCA dilator responses to reduced intravascular pressure, increases in cerebral vascular resistance and in the numbers of FJC-positive cells in the brain, and significantly impaired working memory. PenME administration resulted in significant reductions in cerebral vascular resistance and a trend toward increased cerebral perfusion, suggesting that ONOO− may contribute to blast-induced cerebral vascular dysfunction.

This study was aimed at investigating the functional connectivity (FC) changes between the insular subregions and whole brain in patients with obstructive sleep apnea (OSA) after 6 months of continuous positive airway pressure (CPAP) treatment and at exploring the relationship between resting-state FC changes and cognitive impairment in OSA patients. Data from 15 patients with OSA before and after 6 months of CPAP treatment were included in this study. The FC between the insular subregions and whole brain was compared between baseline and after 6 months of CPAP treatment in OSA. After 6 months of treatment, OSA patients had increased FC from the right ventral anterior insula to the bilateral superior frontal gyrus and bilateral middle frontal gyrus and increased FC from the left posterior insula to the left middle temporal gyrus and left inferior temporal gyrus. Hyperconnectivity was found from the right posterior insula to the right middle temporal gyrus, bilateral precuneus, and bilateral posterior cingulate cortex, which mainly involved the default mode network. There are changes in functional connectivity patterns between the insular subregions and whole brain in OSA patients after 6 months of CPAP treatment. These changes provide a better understanding of the neuroimaging mechanisms underlying the improvement in cognitive function and emotional impairment in OSA patients and can be used as potential biomarkers for clinical CPAP treatment.

Background and Purpose: Previous studies have found that abnormal local spontaneous brain activity in patients with obstructive sleep apnea (OSA) was associated with cognitive impairment, and dynamic functional connections can capture the time changes of functional connections during magnetic resonance imaging acquisition. The purpose of this study was to investigate the dynamic characteristics of regional brain connectivity and its relationship with cognitive function in patients with OSA and to explore whether the dynamic changes can be used to distinguish them from healthy controls (HCs). Methods: Seventy-nine moderate and severe male OSA patients without any treatment and eighty-four HCs with similar age and education were recruited, and clinical data and resting functional magnetic resonance imaging data were collected. The dynamic regional homogeneity (dReHo) was calculated using a sliding window technique, and a double-sample t test was used to test the difference in the dReHo map between OSA patients and HCs. We explored the relationship between dReHo and clinical and cognitive function in OSA patients using Pearson correlation analysis. A support vector machine was used to classify the OSA patients and HCs based on abnormal dReHo. Result: Compared with HCs, OSA patients exhibited higher dReHo values in the right medial frontal gyrus and significantly lower dReHo values in the right putamen, right superior temporal gyrus, right cingulate gyrus, left insula and left precuneus. The correlation analysis showed that the abnormal dReHo values in multiple brain regions in patients with OSA were significantly correlated with nadir oxygen saturation, the oxygen depletion index, sleep period time, and Montreal cognitive assessment score. The support vector machine classification accuracy based on the dReHo difference in brain regions was 81.60%, precision was 81.01%, sensitivity was 81.01%, specificity was 82.14%, and area under the curve was 0.89. Conclusion: The results of this study suggested that there was abnormal dynamic regional spontaneous brain activity in OSA patients, which was related to clinical and cognitive evaluation and can be used to distinguish OSA patients from HCs. The dReHo is a potential objective neuroimaging marker for patients with OSA that can further the understanding of the neuropathological mechanism of OSA patients.

Background There is a paucity of data from large prospective study evaluating the prognostic significance of the residual Synergy between percutaneous intervention with Taxus drug-eluting stents and cardiac surgery (SYNTAX) Score (rSS) in patients with obstructive sleep apnea (OSA) and Acute Coronary Syndrome (ACS). Methods ACS patients who undergoing percutaneous coronary angiography and completing a sleep study during hospitalization were prospectively enrolled. The baseline SYNTAX Score (bSS) and the rSS after revascularization were assessed. Complete revascularization (CR, rSS = 0) and incomplete revascularization (ICR, rSS > 0) were categorized. OSA (apnea hypopnea index, AHI ≥ 15) and non-OSA (AHI < 15) were grouped according to AHI. The primary endpoint of the study was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for UAP or heart failure. Results Overall, 752 patients were prospectively enrolled. At a median follow-up of 1 year, the incidence of MACCEs was significantly higher in the OSA than in the non-OSA group (hazard ratio [HR]:1.68; 95% confidence interval [CI]:1.04–2.72; P  = .034). ICR was associated with a higher risk of MACCEs in the non-OSA group (HR:3.34;95% CI:1.0–11.12; P  = .05). The OSA patients with ICR had a 5.1 higher risk of MACCEs compared with the non-OSA with CR group, P  = .007. The OSA patients with CR had a similar 1-year MACCEs as all the non-OSA patients (HR:1.10; 95% CI:0.515–2.349; P  = 0.806). Conclusions ACS patients with OSA and ICR have a high rate of MACCEs at 1 year. In contrast, the prognosis of ACS patients with OSA but CR is favorable and similar to patients without OSA. Adequate level of revascularization is recommended to optimize clinical outcomes in ACS patients with OSA. Trial registration Clinicaltrials.gov identifier NCT03362385.

Objective: Many studies have explored the neural mechanisms of cognitive impairment in chronic obstructive pulmonary disease (COPD) patients using the functional MRI. However, the dynamic properties of brain functional networks are still unclear. The purpose of this study was to explore the changes in dynamic functional network attributes and their relationship with cognitive impairment in stable COPD patients. Materials and Methods: The resting-state functional MRI and cognitive assessments were performed on 19 stable COPD patients and 19 age-, sex-, and education-matched healthy controls (HCs). We conducted the independent component analysis (ICA) method on the resting-state fMRI data, and obtained seven resting-state networks (RSNs). After that, the static and dynamic functional network connectivity (sFNC and dFNC) were respectively constructed, and the differences of functional connectivity were compared between COPD patients and the HC groups. In addition, the correlation between dynamic functional network attributes and cognitive assessments was analyzed in COPD patients. Results: Compared to HCs, there were significant differences in sFNC among COPD patients between and within networks. COPD patients showed significantly longer mean dwell time and higher fractional windows in weaker connectivity State I than HCs. Besides, in comparison to HCs, COPD patients had more extensive functional connectivity abnormalities in weaker connectivity state I and state IV, and less abnormal functional connectivity in relatively stronger connectivity state II and state III, which were mainly located in the default mode network, executive control network, and visual network. In addition, the dFNC properties including mean dwell time and fractional windows are significantly correlated with some essential clinical indicators such as FEV1, FEV1/FVC and c-reactive protein in COPD patients. Conclusion: These findings highlight the differences in static and dynamic functional connectivity in patients with COPD, which may serve as an important biomarker of cognitive performance. And this also provides a new perspective for understanding the cognitive neural mechanisms of COPD.

Purpose: Previous studies found abnormal low-frequency spontaneous brain activity related to cognitive impairment in patients with obstructive sleep apnea (OSA). However, it is unclear if low-frequency spontaneous brain activity is related to specific frequency bands in OSA patients. In this study, we used the amplitude of low-frequency fluctuation (ALFF) method in patients with OSA to explore characteristics of spontaneous brain activity in the classical (0.01–0.1 Hz) and five sub-frequency bands (slow-2 to slow-6) and analyzed the relationship between spontaneous brain activity and clinical evaluation was analyzed. Patients and Methods: Resting-state magnetic resonance imaging data and clinical assessments were collected from 52 newly-diagnosed OSA patients and 62 healthy controls (HCs). We calculated the individual group ALFF values in the classical and five different sub-frequency bands. A two-sample t-test compared ALFF differences, and one-way analysis of variance explored interactions in frequency bands between the two groups. Results: ALFF values in the OSA group were lower than those in the HC group in the bilateral precuneus/posterior cingulate cortex, bilateral angular gyrus, left inferior parietal lobule, brainstem, and right fusiform gyrus. In contrast, ALFF values in the OSA group were higher than those in the HC group in the bilateral cerebellum posterior lobe, bilateral superior frontal gyrus, bilateral middle frontal gyrus, left inferior frontal gyrus, left inferior temporal gyrus, and left fusiform gyrus. Some ALFF values in altered brain regions were associated with body mass index, apnea-hypopnea index, neck circumference, minimum SaO2, average SaO2, arousal index, oxygen reduction index, deep sleep period naming, abstraction, and delayed recall in specific frequency bands. Conclusion: Our results indicated the existence of frequency-specific differences in spontaneous brain activity in OSA patients, which were related to cognitive and other clinical symptoms. This study identified frequency-band characteristics related to brain damage, expanded the cognitive neuroimaging mechanism, and provided additional OSA neuroimaging markers.

Objective: Many neuroimaging studies have used static functional connectivity of magnetic resonance imaging methods to explore the neural mechanisms of obstructive sleep apnea (OSA) patients. Dynamic functional connectivity captures the temporal changes in functional connectivity during MRI acquisition and is used to understand the neural mechanisms in patients with OSA. The purpose of this study was to investigate the dynamic functional network connectivity (dFNC) and its relationship with cognitive function in OSA patients. Material and Methods: 82 OSA patients and 48 healthy controls (HCs) were included in this study. Clinical and resting-state fMRI data were collected, and 8 resting-state networks were determined by independent component analysis. Then, a sliding-window approach was used to construct the dFNC, and differences of temporal properties and functional connectivity strength were compared between OSA patients and the HC groups. Furthermore, the relationship between temporal properties and clinical assessments such as cognition were analysed in OSA patients. Results: Two different connection states were identified, namely, state I with stronger connection and lower frequency, and state II with lower connection and relatively high frequency. Compared to HCs, OSA patients had a longer mean dwell time and higher fractional window in stronger connectivity states I, and showed shorter mean dwell time and lower fractional window in state II, which was mainly reflected in OSA-MCI patients, but was not significantly different in OSA-NC. Although the number of transitions was no different between OSA patients and HCs, there was an increasing trend in OSA-MCI patients, and the number of transitions was positively correlated with cognitive assessment. Compared with HCs, OSA patients had extensive functional connectivity abnormalities in stronger connectivity state I and less reduced functional connectivity in lower connectivity state II, which were mainly located in the salience network, default mode network and executive control network. Conclusions: Our study found that OSA patients showed abnormal dFNC properties, which was a continuous trend from HC, and OSA-NC to OSA-MCI, and OSA patients showed abnormal dynamic functional connection strength. These changes were associated with cognitive impairment, which may provide new insights into the neural mechanisms in OSA patients.