Detection of apoptotic cells based on in situ hybridization chain reaction using specific hairpins.

There are an increasing number of experiments to study programmed cell death/apoptosis, one of the characteristics of which is DNA fragmentation. The only current method for in situ detection of DNA fragmentation is Terminal deoxynucleotidyl transferase mediated-dUTP Nick End Labeling, TUNEL. In this study, a new method for in situ detection of apoptotic DNA fragments, namely In Situ Hybridization Chain Reaction, isHCR, was established. The principle of the assay is that the sticky end sequence of the apoptotic cell DNA fragment non-specifically initiates a hybridization chain reaction that specifically detects the apoptotic cell. The results of the combined TUNEL and isHCR method demonstrated that the majority of isHCR-positive cells were also labeled by TUNEL. In situ HCR often detect DNA fragments in the cytoplasm that the classical TUNEL method couldnot, and these cells may be in the early stages of apoptosis. It also indicates that DNA fragments are transferred to the cytoplasm during apoptosis. Because the staining process does not require terminal deoxynucleotidyl transferase as TUNEL staining does, isHCR staining cost low and can be performed on a large number of tissue specimens. It is believed that isHCR has the potential to detect DNA fragmentation of apoptotic cells in situ.

Emissive Platinum(II) Cages with Reverse Fluorescence Resonance Energy Transfer for Multiple Sensing.

It is quite challenging to realize fluorescence resonance energy transfer (FRET) between two chromophores with specific positions and directions. Herein, through the self-assembly of two carefully selected fluorescent ligands via metal-coordination interactions, we prepared two tetragonal prismatic platinum(II) cages with a reverse FRET process between their faces and pillars. Bearing different responses to external stimuli, these two emissive ligands are able to tune the FRET process, thus making the cages sensitive to solvents, pressure, and temperature. First, these cages could distinguish structurally similar alcohols such as n-butanol, t-butanol, and i-butanol. Furthermore, they showed decreased emission with bathochromic shifts under high pressure. Finally, they exhibited a remarkable ratiometric response to temperature over a wide range (223-353 K) with high sensitivity. For example, by plotting the ratio of the maximum emission (I600/I480) of metallacage 4b against the temperature, the slope reaches 0.072, which is among the highest values for ratiometric fluorescent thermometers reported so far. This work not only offers a strategy to manipulate the FRET efficiency in emissive supramolecular coordination complexes but also paves the way for the future design and preparation of smart emissive materials with external stimuli responsiveness.

Multicomponent Porphyrin-Based Tetragonal Prismatic Metallacages and their Photophysical Properties.

Multicomponent coordination-driven self-assembly has proved to be a convenient approach to prepare advanced supramolecular coordination complexes (SCCs), especially for those with three-dimensional structures. Herein, we report the preparation of three tetragonal prismatic cages via the self-assembly of Pt(PEt3)2(OTf)2, three different linear dipyridyl ligands and porphyrin-based sodium benzoate ligands. Due to the efficient charge separation in the coordination process of Pt(PEt3)2(OTf)2 with pyridine and carboxylic acid and the directionality of metal-coordination bonds, these cages were prepared in high isolated yields (more than 90%). The absorption and emission properties as well as the singlet oxygen quantum yields of these cages were also studied, showing their potential applications as contrast agents for bio-imaging and photosensitizers for photodynamic therapy.

Improved Pedestrian Dead Reckoning Based on a Robust Adaptive Kalman Filter for Indoor Inertial Location System.

Pedestrian dead reckoning (PDR) systems based on a microelectromechanical-inertial measurement unit (MEMS-IMU) providing advantages of full autonomy and strong anti-jamming performance are becoming a feasible choice for pedestrian indoor positioning. In order to realize the accurate positioning of pedestrians in a closed environment, an improved pedestrian dead reckoning algorithm, mainly including improved step estimation and heading estimation, is proposed in this paper. Firstly, the original signal is preprocessed using the wavelet denoising algorithm. Then, the multi-threshold method is proposed to ameliorate the step estimation algorithm. For heading estimation suffering from accumulated error and outliers, robust adaptive Kalman filter (RAKF) algorithm is proposed in this paper, and combined with complementary filter to improve positioning accuracy. Finally, an experimental platform with inertial sensors as the core is constructed. Experimental results show that positioning error is less than 2.5% of the total distance, which is ideal for accurate positioning of pedestrians in enclosed environment.

Aqueous Platinum(II)-Cage-Based Light-Harvesting System for Photocatalytic Cross-Coupling Hydrogen Evolution Reaction.

Photosynthesis is a process wherein the chromophores in plants and bacteria absorb light and convert it into chemical energy. To mimic this process, an emissive poly(ethylene glycol)-decorated tetragonal prismatic platinum(II) cage was prepared and used as the donor molecule to construct a light-harvesting system in water. Eosin Y was chosen as the acceptor because of its good spectral overlap with that of the metallacage, which is essential for the preparation of light-harvesting systems. Such a combination showed enhanced catalytic activity in catalyzing the cross-coupling hydrogen evolution reaction, as compared with eosin Y alone. This study offers a pathway for using the output energy from the light-harvesting system to mimic the whole photosynthetic process.

Inhibition of P2X7 receptors improves outcomes after traumatic brain injury in rats.

Traumatic brain injury (TBI) is the leading cause of death and disability for people under the age of 45 years worldwide. Neuropathology after TBI is the result of both the immediate impact injury and secondary injury mechanisms. Secondary injury is the result of cascade events, including glutamate excitotoxicity, calcium overloading, free radical generation, and neuroinflammation, ultimately leading to brain cell death. In this study, the P2X7 receptor (P2X7R) was detected predominately in microglia of the cerebral cortex and was up-regulated on microglial cells after TBI. The microglia transformed into amoeba-like and discharged many microvesicle (MV)-like particles in the injured and adjacent regions. A P2X7R antagonist (A804598) and an immune inhibitor (FTY720) reduced significantly the number of MV-like particles in the injured/adjacent regions and in cerebrospinal fluid, reduced the number of neurons undergoing apoptotic cell death, and increased the survival of neurons in the cerebral cortex injured and adjacent regions. Blockade of the P2X7R and FTY720 reduced interleukin-1ßexpression, P38 phosphorylation, and glial activation in the cerebral cortex and improved neurobehavioral outcomes after TBI. These data indicate that MV-like particles discharged by microglia after TBI may be involved in the development of local inflammation and secondary nerve cell injury.

Low-Dose Atypical Antipsychotic Risperidone Improves the 5-Year Outcome in Alzheimer's Disease Patients with Sleep Disturbances.

Sleep disturbances (SD) accelerate the progression of Alzheimer's disease (AD) and increase the stress of caregivers. However, the long-term outcome of disturbed nocturnal sleep/wake patterns in AD and on increased stress of spousal caregivers is unclear. This study assessed the 5-year effect of nocturnal SD on the long-term outcome in AD patients. A total of 156 donepezil-treated mild-moderate AD patients (93 AD + SD and 63 AD - SD as a control group) were recruited. The AD + SD patients were formed into 4 subgroups according to the preferences of spousal caregivers for treatment with atypical antipsychotics (0.5-1 mg risperidone, n = 22), non-benzodiazepine hypnotic (5-10 mg zolpidem tartrate, n = 33), melatonin (2.55 mg, n = 9), or no-drug treatment (n = 29). SD were evaluated by polysomnography, sleep scale, and cognitive scale examinations. Moreover, all spousal caregivers of AD patients were assessed using a series of scales, including sleep, anxiety, mood, and treatment attitude scales. Our data showed that nocturnal sleep/wake disturbances were significantly associated with lower 5-year outcomes for AD patients, earlier nursing home placement, and more negative emotions of spousal caregivers. Treatment with low-dose atypical antipsychotic risperidone improved the 5-year outcome in AD + SD patients. In conclusion, low-dose atypical antipsychotic risperidone improves the 5-year outcome in AD patients with SD. Moreover, improvement of nocturnal sleep problems in AD patients will also bring better emotional stability for AD caregivers.

The effect of IGF-1 on symptoms of sleep deprivation in a rat model of inflammatory heart disease and metabolic syndrome.

Sleep deprivation (SD) has become a worldwide public health concern due to the many negative health consequences associated with suboptimal sleep. SD has been linked to a catabolic hormone signature, heart disease, hypertension, diabetes, and an increase in morbidity and mortality. Herein, we investigated the effects and mechanism of SD on cardiac and metabolic health and evaluated the impact of exogenously supplied IGF-1 on these symptoms. In the present study, we show that 5 days of acute SD negatively impacted all of the various indicators of cardiac and metabolic health. All symptoms of SD were ameliorated by daily administration of IGF-1, however. IGF-1 administration also reduced the phosphorylation of Akt and expression of Bax, a promoter of apoptosis. Conversely, the expression of Bcl-2, an inhibitor of apoptosis, was elevated by IGF-1, and all IGF-1 effects were suppressed by the PI3K/Akt inhibitor LY294002, reaffirming the importance of the PI3K/Akt pathway in the maintenance of cardiac and metabolic health.

ChartKG: A Knowledge-Graph-Based Representation for Chart Images.

Chart images, such as bar charts, pie charts, and line charts, are explosively produced due to the wide usage of data visualizations. Accordingly, knowledge mining from chart images is becoming increasingly important, which can benefit downstream tasks like chart retrieval and knowledge graph completion. However, existing methods for chart knowledge mining mainly focus on converting chart images into raw data and often ignore their visual encodings and semantic meanings, which can result in information loss for many downstream tasks. In this paper, we propose ChartKG, a novel knowledge graph (KG) based representation for chart images, which can model the visual elements in a chart image and semantic relations among them including visual encodings and visual insights in a unified manner.Further, we develop a general framework to convert chart images to the proposed KG-based representation. It integrates a series of image processing techniques to identify visual elements and relations, e.g., CNNs to classify charts, yolov5 and optical character recognition to parse charts, and rule-based methods to construct graphs. We present four cases to illustrate how our knowledge-graph-based representation can model the detailed visual elements and semantic relations in charts, and further demonstrate how our approach can benefit downstream applications such as semantic-aware chart retrieval and chart question answering. We also conduct quantitative evaluations to assess the two fundamental building blocks of our chart-to-KG framework, i.e., object recognition and optical character recognition. The results provide support for the usefulness and effectiveness of ChartKG.

Associations between sleep disorders and anxiety in patients with tinnitus: A cross-sectional study.

Objective: To investigate the characteristics of sleep disorders and anxiety in patients with tinnitus, their influencing factors, and the role of sleep disorders as mediators. Methods: The general conditions and disease characteristics of 393 patients with tinnitus presented to the Changzheng Hospital of the Naval Medical University from 2018 to 2021 were collected. All patients accepted questionnaires such as Tinnitus Handicap Inventory (THI), Pittsburgh Sleep Quality Index (PSQI) and Self-rating Anxiety Scale (SAS), and then the characteristics and the influencing factors of sleep disorders and anxiety were analyzed. Results: Among the 393 tinnitus patients, 213 cases (54.19%) were diagnosed with sleep disorders, and 78 cases (19.85%) were diagnosed with anxiety, including 25 men (32.1%) and 53 women (67.9%). Binary regression showed that gender, hearing loss, tinnitus severity, and sleep disorders severity were positively associated with anxiety. Multiple logistic regression analysis showed that female gender (OR = 2.526, P = 0.008), hearing loss (OR = 2.901, P = 0.003, tinnitus severity (OR = 1.863, P = 0.003) and sleep disorders (OR = 2.510, P = 0.001) were the independent risk factors of anxiety. The mediating effect of sleep disorders between tinnitus severity and anxiety accounted for 27.88% of the total effect size. Conclusion: Females patients with hearing loss, moderate to severe tinnitus, and sleep disorders were at greater risk for anxiety, with sleep disorders partially mediating the anxiety associated with tinnitus.

Combining a CDK4/6 Inhibitor With Pemetrexed Inhibits Cell Proliferation and Metastasis in Human Lung Adenocarcinoma.

Background: Recent clinical trials of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in human lung adenocarcinoma (LUAD) have not achieved satisfactory results. The disappointing results of single-drug treatments have prompted studies about synergistic therapies of CDK4/6i with other drugs. We aimed to test the anti-tumor effect of ribociclib (a CDK4/6i) combined with pemetrexed on LUAD and the potential mechanisms. Methods: Cell lines were exposed to ribociclib and pemetrexed at different doses. Antitumor effects were measured using growth inhibition. Cell cycle distribution and apoptosis were evaluated using flow cytometry. Cell migration and invasion were measured using wound healing and transwell invasion assays, respectively. The expression levels of proteins were analyzed using western blotting. Mice xenograft models were used for validation in vivo. Results: Synergism was associated with a combination of cell cycle effects from both agents. Cell cycle analysis revealed that pemetrexed blocked cells in the S phase, whereas ribociclib arrested cells in the G1 phase. Concomitant treatment with pemetrexed and ribociclib resulted in a significantly stronger antitumor ability than treatment alone. We also found that ribociclib strongly enhanced the pro-apoptotic activity of pemetrexed via the caspase/bcl-2 signaling pathway. In addition, we report for the first time that combination treatment with ribociclib and pemetrexed significantly inhibits the migration and invasion of LUAD cells. Conclusions: Combining ribociclib and pemetrexed showed a powerful ability to inhibit cancer proliferation, invasion, and metastasis, and it holds potential as a novel effective combinative therapy for patients with LUAD.

Expression of P2X6 receptors in the enteric nervous system of the rat gastrointestinal tract.

Expression of P2X(4) and P2X(6) receptor subunits in the gastrointestinal tract of the rat was studied with double-labeling fluorescence immunohistochemistry. The results showed that P2X(6) receptors were expressed widely in the submucosal and myenteric plexuses. In the myenteric plexus, P2X(6) receptors were expressed mainly in large size neurons which resembled Dogiel type II neurons. These P2X(6) receptor-immunoreactive (ir) neurons also expressed calbindin 28K, calretinin and neuronal nuclei (NeuN), proteins that are markers of intrinsic sensory neurons. In the submucosal plexus, all the calbindin 28K, calretinin and NeuN-ir cells were immunoreactive for P2X(6) receptors. P2X(6) receptors do not form homomultimers, but rather heteromultimers with either P2X(2) or P2X(4) receptors. P2X(4) receptors were not expressed in neurons, but were expressed in macrophages of the rat gastrointestinal tract. These data indicate that P2X(6) receptors are mainly expressed on intrinsic sensory neurons and that ATP, via P2X(6) receptors probably in heteromeric combination with P2X(2) receptors, may be involved in regulating the physiological functions of these neurons.

Mst1 knockdown alleviates cardiac lipotoxicity and inhibits the development of diabetic cardiomyopathy in db/db mice.

Diabetic cardiomyopathy (DCM) accounts for increasing deaths of diabetic patients, and effective therapeutic targets are urgently needed. Myocardial lipotoxicity, which is caused by cardiac non-oxidative metabolic fatty acids and cardiotoxic fatty acid metabolites accumulation, has gained more attention to explain the increasing prevalence of DCM. However, whether mammalian Ste20-like kinase 1 (Mst1) plays a role in lipotoxicity in type 2 diabetes-induced cardiomyopathy has not yet been illustrated. Here, we found that Mst1 expression was elevated transcriptionally in the hearts of type 2 diabetes mellitus mice and palmitic acid-treated neonatal rat ventricular myocytes. Adeno-associated virus 9 (AAV9)-mediated Mst1 silencing in db/db mouse hearts significantly alleviated cardiac dysfunction and fibrosis. Notably, Mst1 knockdown in db/db mouse hearts decreased lipotoxic apoptosis and inflammatory response. Mst1 knockdown exerted protective effects through inactivation of MAPK/ERK kinase kinase 1 (MEKK1)/c-Jun N-terminal kinase (JNK) signaling pathway. Moreover, lipotoxicity induced Mst1 expression through promoting the binding of forkhead box O3 (FoxO3) and Mst1 promoter. Conclusively, we elucidated for the first time that Mst1 expression is regulated by FOXO3 under lipotoxicity stimulation and downregulation of Mst1 protects db/db mice from lipotoxic cardiac injury through MEKK1/JNK signaling inhibition, indicating that Mst1 abrogation may be a potential treatment strategy for DCM in type 2 diabetic patients.

Neural Consequences of Chronic Short Sleep: Reversible or Lasting?

Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep. This common practice of weekend recovery sleep reduces subjective sleepiness, yet recent studies demonstrate that one weekend of recovery sleep may not be sufficient in all persons to fully reverse all neurobehavioral impairments observed with chronic sleep loss, particularly vigilance. Moreover, recent studies in animal models demonstrate persistent injury to and loss of specific neuron types in response to chronic short sleep (CSS) with lasting effects on sleep/wake patterns. Here, we provide a comprehensive review of the effects of chronic sleep disruption on neurobehavioral performance and injury to neurons, astrocytes, microglia, and oligodendrocytes and discuss what is known and what is not yet established for reversibility of neural injury. Recent neurobehavioral findings in humans are integrated with animal model research examining long-term consequences of sleep loss on neurobehavioral performance, brain development, neurogenesis, neurodegeneration, and connectivity. While it is now clear that recovery of vigilance following short sleep requires longer than one weekend, less is known of the impact of CSS on cognitive function, mood, and brain health long term. From work performed in animal models, CSS in the young adult and short-term sleep loss in critical developmental windows can have lasting detrimental effects on neurobehavioral performance.

Sleep-wake patterns, non-rapid eye movement, and rapid eye movement sleep cycles in teenage narcolepsy.

BACKGROUND: To further characterize sleep disorders associated with narcolepsy, we assessed the sleep-wake patterns, rapid eye movement (REM), and non-REM (NREM) sleep cycles in Chinese teenagers with narcolepsy. METHODS: A total of 14 Chinese type 1 narcoleptic patients (13.4 ± 2.6 years of age) and 14 healthy age- and sex-matched control subjects (13.6 ± 1.8 years of age) were recruited. Ambulatory 24-h polysomnography was recorded for two days, with test subjects adapting to the instruments on day one and the study data collection performed on day two. RESULTS: Compared with the controls, the narcoleptic patients showed a 1.5-fold increase in total sleep time over 24 h, characterized by enhanced slow-wave sleep and REM sleep. Frequent sleep-wake transitions were identified in nocturnal sleep with all sleep stages switching to wakefulness, with more awakenings and time spent in wakefulness after sleep onset. Despite eight cases of narcolepsy with sleep onset REM periods at night, the mean duration of NREM-REM sleep cycle episode and the ratio of REM/NREM sleep between patients and controls were not significantly different. CONCLUSION: Our study identified hypersomnia in teenage narcolepsy despite excessive daytime sleepiness. Sleep fragmentation extended to all sleep stages, indicating impaired sleep-wake cycles and instability of sleep stages. The limited effects on NREM-REM sleep cycles suggest the relative conservation of ultradian regulation of sleep.

Effect of low-intensity pure tone auditory stimulation on patients with rapid eye movement sleep behavior disorder.

OBJECTIVE: This study aimed to investigate the influence of low-intensity pure tone auditory stimulation on patients with rapid eye movement (REM), sleep behavior disorder (RBD), and attempt to identify a new method of RBD intervention. METHODS: Patients diagnosed with idiopathic RBD (iRBD) or symptomatic RBD (sRBD) were given auditory stimulation of low-intensity pure tones during their REM sleep. Sleep parameters including sleep process, sleep architecture as well as eye movements (EMs) frequency, and amplitude were recorded by polysomnography monitoring at pre-, intra-, and post-stimulation. RESULTS: Thirteen iRBD and 18 sRBD patients completed this study. Auditory stimulation significantly reduced the EMs frequency and amplitude in iRBD and sRBD patients (p < 0.05). In the iRBD group, the intra-stimulated FSL increased significantly than the pre-stimulated FSL (p < 0.05). After stimulation, patients had similar sleep latency (FSL), rapid eye movement sleep latency (RSL) and periodic limb movements in sleep (PLMS) compared with control. In the sRBD group, the intra-stimulated total sleep time, sleep efficiency was significantly increased, whereas the RSL and PLMS were significantly reduced compared with the pre-stimulated ones (all p < 0.05). The sRBD patients had similar time in bed, FSL and RBD episodes compared with control (all p < 0.05) in spite of significant difference before stimulation (all p < 0.05). However, the sleep architecture was not influenced by the stimulation despite the decrease in N3% in iRBD group (p < 0.05). CONCLUSION: Low-intensity pure tone auditory stimulation may be a potentially effective intervention for RBD, especially for sRBD.

Metabolic abnormality of pontine tegmentum in patients with REM sleep behavior disorder analyzed using magnetic resonance spectroscopy.

OBJECTIVES: We aimed to evaluate the metabolism differences in pontine tegmentum among patients with idiopathic RBD (iRBD), secondary RBD (sRBD) and healthy control groups using magnetic resonance spectroscopy ((1)H-MRS) and whether metabolic changes are correlated with age in patients with RBD. PATIENTS AND METHODS: The iRBD, sRBD, and control groups were composed of 18, 26, and 29 patients, respectively. All participants underwent magnetic resonance imaging (MRI) and (1)H-MRS detection at 17:00 for approximately 15min. All NAA/Cr, Cho/Cr and NAA/Cho ratios were automatically generated using FuncTool and the correlation between metabolism and age was analyzed by Pearson's correlation analysis. RESULTS: Significant difference in NAA/Cr ratio was found between the sRBD group and the other groups (p<0.05). Significant difference in NAA/Cho ratio was found among all groups (p<0.05). Cho/Cr ratio remarkably increased in the control group (p<0.05) compared with the other groups. NAA/Cr ratio had an adverse correlation with age in the control, iRBD, and sRBD groups (r=-0.822, p=0.000 vs r=-0.663, p=0.003 vs r=-0.583, p=0.002). However, there was no correlation between participants age and Cho/Cr (r=-0.054, p=0.651) or NAA/Cho (r=0.029, p=0.805). CONCLUSION: Neurons in the sRBD group were lost or damaged; however, this damage was not obvious in the iRBD group. Nevertheless, NAA and Cho levels were reduced in the local nerve cells of both RBD groups; these changes might indicate the sensitive pathogenic areas among patients with RBD.

Body weight and basal metabolic rate in childhood narcolepsy: a longitudinal study.

OBJECTIVES: The aims of this study were to document the trajectory of weight gain and body mass index (BMI) in children with type 1 narcolepsy, and to analyze basal metabolic rate (BMR). METHODS: A total of 65 Chinese children with type 1 narcolepsy with a disease duration ≤12 months were included. In addition, 79 healthy age-matched students were enrolled as controls. Height and body weight were measured every six months for up to 36 months to calculate BMI growth. BMR was measured using COSMED K4b2 indirect calorimetry in 34 patients and 30 healthy controls at six months. At the end of 36 months, the BMR was compared among 18 patients and 16 healthy controls. RESULTS: The children with type 1 narcolepsy showed higher BMIs at follow-up assessments. At the end of the study, 38.46% of the patients were obese and an additional 26.15% were overweight. The patients' BMI growth at six, 12, 18, 24 and 30 months of follow-up was significantly higher, but not at month 36. The patients' basal energy expenditure was significantly lower than that of the controls at six months but not at 36 months. CONCLUSION: BMI increased rapidly in children with type 1 narcolepsy after disease onset, but BMI growth decreased gradually with prolonged disease. Decreased BMR is an important cause underlying rapid weight gain. The gradual restoration of BMI growth and BMR in narcolepsy emphasizes the importance of compensatory metabolic mechanisms in this disease.

Interleukin-1ß Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.

Sleep alleviates Alzheimer's disease (AD)-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL)-1ß and APOEε4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysomnography and measurement of Epworth Sleepiness Scale (ESS) scores for sleep-wake disturbance. Their genomic DNA was analyzed for IL-1ß and APOEε4 SNPs using ligase detection reaction (LDR) technology. Blood levels of IL-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) were measured using ELISA after lipopolysaccharide (LPS) stimulation. The odds ratio and 95% confidence interval for genotype-specific risk were calculated using an unconditional logistic regression model and adjusted by age, gender, educational levels, body mass index (BMI), and activities of daily living (ADL). Compared to the non-APOEε4/ε4 genotype, APOEε4/ε4 significantly increased the risk of AD (APOEε4/ε4 vs. non-APOEε4/ε4, adjusted OR = 4.33, 95% CI = 1.33-14.10, p = 0.015). Compared to the IL-1ß CC genotype (-31), the TT genotype significantly increased the risk of AD (TT vs. CC, adjusted OR = 1.72, 95% CI = 1.13-2.61, p = 0.010). AD patients carrying the APOEε4 allele and the IL-1ß TT genotype showed less time in bed, longer sleep latency and REM latency, more awakenings, and a lower SWS percentage than those carrying CC/CT combined genotypes. In addition, blood IL-1ß levels were significantly greater in AD patients carrying both the APOEε4 allele and the IL-1ß-31TT genotype than in those carrying the APOEε4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1ß-31TT genotype and homozygous APOEε4 combined are associated with increased risk of developing AD with sleep disturbance.

Xylaria nigripes mitigates spatial memory impairment induced by rapid eye movement sleep deprivation.

We aimed to investigate the effects of Xylaria nigripes (XN) extracts on the rapid eye movement sleep deprivation (REMSD)-induced memory impairment, and explore related mechanism. Male Sprague Dawley rats were randomly divided into 6 groups: cage control (CC)-NaCl group; tank control (TC)-NaCl group; sleep deprivation (SD)-NaCl group; CC-XN group; TC-XN group and SD-XN group. The rats were administered with intragastric XN and 0.9% of sodium chloride. SD group rats were deprived of REM sleep for 72 h. Morris water maze (MWM) was used to assess the effects of XN on spatial learning and memory. The expression of cAMP-response element binding protein (CREB) and p-CREB were also investigated in all groups. Result showed rats in SD-NaCl group had significantly longer mean escape latencies in finding the platform as compared to the control rats (p<0.05) in MWM test. The SD-NaCl group spent significantly less time in goal quadrant compared with the SD-XN group. REMSD and XN did not alter CREB expression in the hippocampus, while sleep deprivation resulted in reduced phosphorylation of CREB in the hippocampus, which was reversed by XN. XN mitigates spatial memory impairment induced by REMSD in rat. Phosphorylation of CREB in hippocampus might be one of the mechanisms.