The association between sleep duration, bedtime, and cognitive ability in Chinese adults: Evidence from the China family panel studies.

Introduction: Dementia is marked by a steady decline or worsening in cognitive abilities, affecting memory, logic, and social competencies. While many studies suggest a potential link between the amount of sleep and dementia risk, the outcomes are not yet consistent. This research delved into the relationship between sleep length and bedtime on cognitive abilities using an extensive dataset from the China Family Panel Studies (CFPS) from 2014 to 2020. Methods: Data from 175,702 observations were collected, including cognitive function test data from 22,848 participants. Various cognitive tests were used to assess cognitive function. Restricted cubic spline (RCS) models were used for data analysis. Results: The optimal sleep duration for cognitive function was found to be 6-7 h, and the optimal bedtime was generally between 22:00-23:00. Longitudinal analysis revealed that sleep duration four years prior had a significant impact on current cognitive function. After accounting for various factors, those who slept for 7-8 h and over 8 h displayed lower cognitive function scores. Conversely, individuals sleeping less than 6 h had higher scores on the Vocabulary Test. Bedtime before 22:00 was associated with lower scores on the Vocabulary Test and Mathematical Test. Subgroup analyses based on age, gender, and urban residence showed variations in optimal sleep duration for different populations. Propensity Score Matching (PSM) analysis supported the findings. Conclusions: Maintaining a sleep duration of 6-7 h and a regular bedtime between 22:00-23:00 is important for optimizing cognitive performance.

Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis.

JOURNAL/nrgr/04.03/01300535-202410000-00029/figure1/v/2024-02-06T055622Z/r/image-tiff Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-ß precursor protein and mutant human presenilin 1 (APP/PS1). Here, we performed 16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-L-threonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesium-L-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins (zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

Structural Insights Uncover the Specific Phosphoinositide Recognition by the PH1 Domain of Arap3.

Arap3, a dual GTPase-activating protein (GAP) for the small GTPases Arf6 and RhoA, plays key roles in regulating a wide range of biological processes, including cancer cell invasion and metastasis. It is known that Arap3 is a PI3K effector that can bind directly to PI(3,4,5)P3, and the PI(3,4,5)P3-mediated plasma membrane recruitment is crucial for its function. However, the molecular mechanism of how the protein recognizes PI(3,4,5)P3 remains unclear. Here, using liposome pull-down and surface plasmon resonance (SPR) analysis, we found that the N-terminal first pleckstrin homology (PH) domain (Arap3-PH1) can interact with PI(3,4,5)P3 and, with lower affinity, with PI(4,5)P2. To understand how Arap3-PH1 and phosphoinositide (PIP) lipids interact, we solved the crystal structure of the Arap3-PH1 in the apo form and complex with diC4-PI(3,4,5)P3. We also characterized the interactions of Arap3-PH1 with diC4-PI(3,4,5)P3 and diC4-PI(4,5)P2 in solution by nuclear magnetic resonance (NMR) spectroscopy. Furthermore, we found overexpression of Arap3 could inhibit breast cancer cell invasion in vitro, and the PIPs-binding ability of the PH1 domain is essential for this function.

Biochemical and NMR studies reveal specific interaction between STIMATE C-tail and PI(4,5)P2 or PI(3,4,5)P3-containing membrane.

STIMATE is an endoplasmic reticulum (ER) resident membrane protein that plays key roles in regulating calcium signaling occurring at ER-plasma membrane (PM) junctions. It is also involved in the regulation of ER-PM junction maintenance. STIMATE contains multiple putative transmembrane domains with a polybasic C tail (STIMATE-CT) that directly interacts with stromal interaction molecule 1 (STIM1) to promote STIM1 conformational switch. Here using liposome pulldown assay, we show that STIMATE-CT can specifically interact with PI(4,5)P2 or PI(3,4,5)P3-containing membrane. NMR analysis indicates that STIMATE-CT is intrinsically disordered. Furthermore, NMR titration with bicelles and mutation analysis reveal that the regions of 242VRYR245 and 284KKKK287 in STIMATE-CT are both essential for its membrane binding.

Identification of candidate genes associated with clinical onset of Alzheimer's disease.

Background and objective: Alzheimer's disease (AD) is the most common type of dementia, with its pathology like beta-amyloid and phosphorylated tau beginning several years before the clinical onset. The aim is to identify genetic risk factors associated with the onset of AD. Methods: We collected three microarray data of post-mortem brains of AD patients and the healthy from the GEO database and screened differentially expressed genes between AD and healthy control. GO/KEGG analysis was applied to identify AD-related pathways. Then we distinguished differential expressed genes between symptomatic and asymptomatic AD. Feature importance with logistic regression analysis is adopted to identify the most critical genes with symptomatic AD. Results: Data was collected from three datasets, including 184 AD patients and 132 healthy controls. We found 66 genes to be differently expressed between AD and the control. The pathway enriched in the process of exocytosis, synapse, and metabolism and identified 19 candidate genes, four of which (VSNL1, RTN1, FGF12, and ENC1) are vital. Conclusion: VSNL1, RTN1, FGF12, and ENC1 may be the essential genes that progress asymptomatic AD to symptomatic AD. Moreover, they may serve as genetic risk factors to identify high-risk individuals showing an earlier onset of AD.

Radius and Orientation Measurement for Cylindrical Objects by a Light Section Sensor.

In this paper, an efficient method based on a light section sensor is presented for measuring cylindrical objects' radii and orientations in a robotic application. By this method, the cylindrical objects can be measured under some special conditions, such as when the cylindrical objects are welded with others, or in the presence of interferences. Firstly, the measurement data are roughly identified and accurately screened to effectively recognize ellipses. Secondly, the data are smoothed and homogenized to eliminate the effect of laser line loss or jump and reduce the influence of the inhomogeneity of measurement data on the ellipse fitting to a minimum. Finally, the ellipse fitting is carried out to obtain the radii and orientations of the cylindrical objects. Measuring experiments and results demonstrate the effective of the proposed radius and orientation measurement method for cylindrical object.

Inside-out Ca(2+) signalling prompted by STIM1 conformational switch.

Store-operated Ca(2+) entry mediated by STIM1 and ORAI1 constitutes one of the major Ca(2+) entry routes in mammalian cells. The molecular choreography of STIM1-ORAI1 coupling is initiated by endoplasmic reticulum (ER) Ca(2+) store depletion with subsequent oligomerization of the STIM1 ER-luminal domain, followed by its redistribution towards the plasma membrane to gate ORAI1 channels. The mechanistic underpinnings of this inside-out Ca(2+) signalling were largely undefined. By taking advantage of a unique gain-of-function mutation within the STIM1 transmembrane domain (STIM1-TM), here we show that local rearrangement, rather than alteration in the oligomeric state of STIM1-TM, prompts conformational changes in the cytosolic juxtamembrane coiled-coil region. Importantly, we further identify critical residues within the cytoplasmic domain of STIM1 (STIM1-CT) that entail autoinhibition. On the basis of these findings, we propose a model in which STIM1-TM reorganization switches STIM1-CT into an extended conformation, thereby projecting the ORAI-activating domain to gate ORAI1 channels.

[Effects of RFRP-3 on reproductive function and energy balance in mammals].

The hypothalamo-pituitary-gonadal (HPG) axis integrates internal and external cues via a balance of stimulatory and inhibitory neurochemical systems to regulate reproductive function in mammals. However, RFRP-3 is a unique inhibitor of HPG axis at the hypothalamuic level in mammals to date. A large number of previous studies have confirmed that RFamide-related peptide (RFRP-3) suppresses gonadotropin-releasing hormone (GnRH) system and luteinizing hormone (LH) secretion, thereby affecting the reproduction. However, whether the inhibition of LH secretion by RFRP-3 occurs at the pituitary level or the hypothalamus level is not clear. It is interesting that RFRP-3 is also related to signal pathway of melatonin modulating mammal seasonal reproduction, but little is known about the effects of melatonin on the RFRP-3 neuron up to now. In addition, RFRP-3 also plays an important role in the regulation of energy balance and behavior. The regulatory mechanism of RFRP-3 in HPG axis and role of RFRP-3 in modulating mammalian energy balance, as well as behavior, are systematically elaborated and the remaining unsolved problems are also discussed in this paper.

[The neuroendocrine regulatory mechanisms of mammalian seasonal reproduction].

The seasonal reproduction of mammal means the reproduction experiences an annual period from quiescence to renaissance. Studies have shown that kisspeptin and RFRP play an important role in the reproductive seasonality. The non-breeding season is characterized by an increase in the negative feedback effect of estrogen on GnRH, and this effect is transmitted by kisspeptin neurons, which may be an important factor affecting the reproduction activities. The expression of RFRP depends on melatonin secretion, and shows an apparent inhibition on reproduction in non-breeding season. In addition, thyroid hormones influence termination of the breeding season. Dopaminergic neuron A14/A15 also contributes to the seasonal changes in estrogen negative feedback. These neural systems may synergistically modulate the seasonal changes of reproductive function with the photoperiod. This review makes a systematic expatiation on the relationship between seasonal reproduction and these neural systems.