Compact speckle spectrometer using femtosecond laser-induced double-sided surface nanostructures.

The utilization of light scattering in disordered media has shown promise in the design of highly sensitive speckle spectrometers. Significant advances have been made in the research of all-fiber speckle spectrometers, and various planar scattering media have also garnered the attention of many researchers. In this study, we designed a compact speckle spectrometer employing a femtosecond laser to induce double-sided nanostructures on a quartz glass as a scattering medium. Once the transmission matrix is calibrated, the spectrum can be reconstructed over a bandwidth of 100 nm, achieving a spectral resolution of 0.1 nm. A 5 pm spectral resolution has been demonstrated by integrating a neural network to recognize speckle patterns in 100 pm bandwidths at 1500, 1550, and 1600 nm. By combining ResNet-50 and GRU, a simulated continuous spectrum spinning a bandwidth of 2 nm can be accurately reconstructed. This innovative, compact spectrometer features low cost, small size, simple preparation, and repeatability.

Circ-ZNF236 mediates stem cells from apical papilla differentiation by regulating LGR4-induced autophagy.

AIM: Human stem cells from the apical papilla (SCAPs) are an appealing stem cell source for tissue regeneration engineering. Circular RNAs (circRNAs) are known to exert pivotal regulatory functions in various cell differentiation processes, including osteogenesis of mesenchymal stem cells. However, few studies have shown the potential mechanism of circRNAs in the odonto/osteogenic differentiation of SCAPs. Herein, we identified a novel circRNA, circ-ZNF236 (hsa_circ_0000857) and found that it was remarkably upregulated during the SCAPs committed differentiation. Thus, in this study, we showed the significance of circ-ZNF236 in the odonto/osteogenic differentiation of SCAPs and its underlying regulatory mechanisms. METHODOLOGY: The circular structure of circ-ZNF236 was identified via Sanger sequencing, amplification of convergent and divergent primers. The proliferation of SCAPs was detected by CCK-8, flow cytometry analysis and EdU incorporation assay. Western blotting, qRT-PCR, Alkaline phosphatase (ALP) and Alizarin red staining (ARS) were performed to explore the regulatory effect of circ-ZNF236/miR-218-5p/LGR4 axis in the odonto/osteogenic differentiation of SCAPs in vitro. Fluorescence in situ hybridization, as well as dual-luciferase reporting assays, revealed that circ-ZNF236 binds to miR-218-5p. Transmission electron microscopy (TEM) and mRFP-GFP-LC3 lentivirus were performed to detect the activation of autophagy. RESULTS: Circ-ZNF236 was identified as a highly stable circRNA with a covalent closed loop structure. Circ-ZNF236 had no detectable influence on cell proliferation but positively regulated SCAPs odonto/osteogenic differentiation. Furthermore, circ-ZNF236 was confirmed as a sponge of miR-218-5p in SCAPs, while miR-218-5p targets LGR4 mRNA at its 3'-UTR. Subsequent rescue experiments revealed that circ-ZNF236 regulates odonto/osteogenic differentiation by miR-218-5p/LGR4 in SCAPs. Importantly, circ-ZNF236 activated autophagy, and the activation of autophagy strengthened the committed differentiation capability of SCAPs. Subsequently, in vivo experiments showed that SCAPs overexpressing circ-ZNF236 promoted bone formation in a rat skull defect model. CONCLUSIONS: Circ-ZNF236 could activate autophagy through increasing LGR4 expression, thus positively regulating SCAPs odonto/osteogenic differentiation. Our findings suggested that circ-ZNF236 might represent a novel therapeutic target to prompt the odonto/osteogenic differentiation of SCAPs.

The Role of Microglia with Mitochondrial Dysfunction and Its Therapeutic Prospects in Alzheimer's Disease.

Alzheimer's disease (AD), a primary cause of dementia, is rapidly emerging as one of the most financially taxing, lethal, and burdensome diseases of the 21st century. Increasing evidence suggests that microglia-mediated neuroinflammation plays a key role in both the initiation and progression of AD. Recently, emerging evidence has demonstrated mitochondrial dysfunction, particular in microglia where precedes neuroinflammation in AD. Multiple signaling pathways are implicated in this process and pharmaceutical interventions are potentially involved in AD treatment. In this review, advance over the last five years in the signaling pathways and pharmaceutical interventions are summarized and it is proposed that targeting the signaling pathways in microglia with mitochondrial dysfunction could represent a novel direction for AD treatment.

Poster Session: Investigating temporal evolutions of perceptual choice within biological and artificial neural networks.

Perceptual decisions involve a process that evolves over time until it reaches a decision boundary. It's important to understand how this process unfolds. Recent psychophysical data indicates that the visual system extracts motion axis information faster than motion direction information (Kwon et al., 2015, J Vision). To understand the underlying mechanisms, we developed a biophysically realistic cortical network model of decision making. We generalized the two-variable reduced spiking neural network (Wong et al., 2006, J Neuroscience) to four-variable. The network input is based on motion energy (Adelson et al., 1985, Josa a) and the temporal profile of surround influence (Tadin et al., 2006, J Neuroscience). The model reproduces the prior experimental findings, showing the motion axis extraction before direction extraction. It reveals a stronger axis-wise inhibitory connection between the selective neural populations than the direction-wise inhibitory connection. We further designed a recurrent deep neural network to validate the neural population connectivity pattern. Our model provides a quantitative explanation for the temporal evolution of motion direction judgments. The results show that the spatiotemporal filtering for visual motion integration, the center-surround antagonism, and stronger axis-wise inhibitory connection between the selective neural populations can explain how the visual system can extract motion axis orientation before detecting motion direction.

Aggregation-induced chemiluminescence system for sensitive detection of mercury ions.

As mercury ions (Hg2+) are emanated to surroundings in the course of various natural events and human activities, an accurate sensing of Hg2+ is essential for human health and environmental protection. Herein, a new aggregation-induced chemiluminescence (CL) sensor for fast, sensitive, and selective detection of Hg2+ is developed, based on the CL enhancement of bis(2,4,6-trichlorophenyl)oxalate (TCPO)-H2O2 system by thiolate-protected gold complexes (Au(I)-thiolate complexes) in the aggregated state. Because Hg2+ has a strong interaction with hydrosulfuryl (-SH) groups in Au(I)-thiolate complexes, the aggregation is disrupted and the CL is quenched. The decrease of CL intensity is proportional to Hg2+ contents with a linear range of 0.005-10 µg mL-1 and the limit of detection (LOD) is 3 ng mL-1. To the best of our knowledge, this is the first AIE CL sensor for Hg2+ detection. The study opens up attractive perspectives for developing simple and rapid aggregation-induced CL methods in monitoring heavy metals.

Potassium dihydrogen phosphate promotes the proliferation and differentiation of human periodontal ligament stem cells via nuclear factor kappa B pathway.

INTRODUCTION: Periodontal ligament stem cells (PDLSCs) are vital for the regeneration of periodontal tissues. Potassium dihydrogen phosphate (KH2PO4) has recently been applied as a component of the mineralization inducing medium (MM), which can be used to induce osteogenic differentiation of dental stem cells. However, whether KH2PO4 has effects on PDLSCs has not been studied. MATERIALS AND METHODS: PDLSCs were isolated by magnetic activated cell sorting and cultured. Alkaline phosphatase (ALP) activity and ALP protein expression of PDLSCs treated with different concentrations of KH2PO4 were examined to make sure the optimal concentration of KH2PO4 for the following experiments. The effects of KH2PO4 on the proliferation and differentiation of PDLSCs were investigated by flow cytometry, cell counting kit-8 assay, alizarin red staining, real-time RT-PCR, and Western blot. The involvement of nuclear factor kappa B (NF-κB) pathway in KH2PO4-treated PDLSCs was analyzed by Western blot and alizarin red staining. RESULTS: ALP activity assay and ALP protein expression examination revealed that 1.8 mmol/L KH2PO4 was the optimal concentration for the induction of hPDLSCs by KH2PO4. The proliferation and mineralization capacity of PDLSCs treated with KH2PO4 were enhanced as compared with the control group. PDLSCs treated with KH2PO4 showed an improved proliferation capacity in logarithmic growth phase at day 7. As PDLSCs were treated with KH2PO4, the expression of odonto/osteogenic markers (OCN/OCN, DSP/DSPP, OSX/OSX, RUNX2/RUNX2, and ALP/ALP) in cells were up-regulated at day 3 or 7. Moreover, the expression of IκBα in cytoplasm was down-regulated, along with an increased expression of p-P65 in cytoplasm and an up-regulated expression of P65 in nucleus. When treated with BMS345541 (the specific NF-κB inhibitor), the odonto/osteogenic differentiation of KH2PO4-treated PDLSCs was significantly attenuated. CONCLUSION: KH2PO4 can improve the proliferation and odonto/osteogenic differentiation capacity of PDLSCs via NF-κB pathway, and thus represents a potential target involved in the regeneration of periodontium for clinical treatments.

Remodeling the Th1 polarized systemic environment contributes to neurogenesis and cognitive function via the Wnt7a pathway in neonatal mice.

Neonatal Bacillus Calmette-Guérin (BCG) vaccination results in a positive effect on hippocampal neurogenesis and cognition. Serum cytokines are considered to be the chief culprit. In this study, serum from BCG-treated mice was identified as Th1 polarized serum. The serum showed an increased ratio of IFN-γ to IL-4 and decreased levels of TNF-α and IL-6. After Th1 polarized serum was injected intraperitoneally into postnatal mice, the levels of cytokines and ratio of IFN-γ to IL-4 in the serum and hippocampus of postnatal mice showed a similar alteration as those in Th1 polarized serum. This result indicated that the immune homeostatic milieu in postnatal mice was broken and the Th1 polarized systemic environment in the BCG-serum group was remodeled. The BCG-serum group displayed more BrdU+/DCX+ cells, BrdU+/NeuN+ cells, Nestin+ cells and better cognitive abilities. In neural stem cells, the Wnt7a/ß-catenin signaling pathway was activated and exposure to the Wnt7a antagonist Dickkopf-1 inhibited BCG-serum-induced Wnt7a/ß-catenin signaling, neurogenesis and cognitive function. Additionally, BCG-serum was associated with elevations in hippocampal brain-derived neurotrophic factor (BDNF) levels, and BDNF expression in the BCG-serum group was offset by Dickkopf-1 treatment. By rebalancing the Th1 polarized systemic environment in neonatal mice, it is possible that treatment with BCG-serum promotes hippocampal neurogenesis and improves cognitive functions, which are associated with Wnt7a/ß-catenin-BDNF signaling.

Vision-based estimation of fatigue and engagement in cognitive training sessions.

Computerized cognitive training (CCT) is a scalable, well-tolerated intervention that has promise for slowing cognitive decline. The effectiveness of CCT is often affected by a lack of effective engagement. Mental fatigue is a the primary factor for compromising effective engagement in CCT, particularly in older adults at risk for dementia. There is a need for scalable, automated measures that can constantly monitor and reliably detect mental fatigue during CCT. Here, we develop and validate a novel Recurrent Video Transformer (RVT) method for monitoring real-time mental fatigue in older adults with mild cognitive impairment using their video-recorded facial gestures during CCT. The RVT model achieved the highest balanced accuracy (79.58%) and precision (0.82) compared to the prior models for binary and multi-class classification of mental fatigue. We also validated our model by significantly relating to reaction time across CCT tasks (Waldχ2=5.16,p=0.023). By leveraging dynamic temporal information, the RVT model demonstrates the potential to accurately measure real-time mental fatigue, laying the foundation for future CCT research aiming to enhance effective engagement by timely prevention of mental fatigue.

Bionic e-skin with precise multi-directional droplet sliding sensing for enhanced robotic perception.

Electronic skins with deep and comprehensive liquid information detection are desired to endow intelligent robotic devices with augmented perception and autonomous regulation in common droplet environments. At present, one technical limitation of electronic skins is the inability to perceive the liquid sliding information as realistically as humans and give feedback in time. To this critical challenge, in this work, a self-powered bionic droplet electronic skin is proposed by constructing an ingenious co-layer interlaced electrode network and using an overpass connection method. The bionic skin is used for droplet environment reconnaissance and converts various dynamic droplet sliding behaviors into electrical signals based on triboelectricity. More importantly, the two-dimensional sliding behavior of liquid droplets is comprehensively perceived by the e-skin and visually fed back in real-time on an indicator. Furthermore, the flow direction warning and intelligent closed-loop control of water leakage are also achieved by this e-skin, achieving the effect of human neuromodulation. This strategy compensates for the limitations of e-skin sensing droplets and greatly narrows the gap between artificial e-skins and human skins in perceiving functions.

GLP-1R-positive neurons in the lateral septum mediate the anorectic and weight-lowering effects of liraglutide in mice.

Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, is approved for obesity treatment, but the specific neuronal sites that contribute to its therapeutic effects remain elusive. Here, we show that GLP-1 receptor-positive (GLP-1R-positive) neurons in the lateral septum (LSGLP-1R) play a critical role in mediating the anorectic and weight-loss effects of liraglutide. LSGLP-1R neurons were robustly activated by liraglutide, and chemogenetic activation of these neurons dramatically suppressed feeding. Targeted knockdown of GLP-1 receptors within the LS, but not in the hypothalamus, substantially attenuated liraglutide's ability to inhibit feeding and lower body weight. The activity of LSGLP-1R neurons rapidly decreased during naturalistic feeding episodes, while synaptic inactivation of LSGLP-1R neurons diminished the anorexic effects triggered by liraglutide. Together, these findings offer critical insights into the functional role of LSGLP-1R neurons in the physiological regulation of energy homeostasis and delineate their instrumental role in mediating the pharmacological efficacy of liraglutide.

Mechanism of action of Panax ginseng alcohol extract based on orexin-mediated autophagy in the treatment of sleep and cognition in aged sleep-deprived rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng (P. ginseng) C. A. Meyer. has been used extensively globally as a medicine. It has a therapeutic effect on sleep and is an attractive alternative for patients with insomnia. The United States Patent of Invention has approved the use of P. ginseng alcohol extract (GAE) in nutraceuticals or food to improve sleep. It has shown promise as an effective therapeutic agent for improving sleep and cognition. However, its mechanism of action is not yet fully understood. AIM OF THE STUDY: To investigate the therapeutic benefits of GAE on sleep and cognition and its underlying mechanism in aged sleep-deprived rats, with a focus on orexin-mediated autophagy function. MATERIALS AND METHODS: We conducted in vivo tests in an aged sleep-deprivation rat model produced using p-chlorophenylalanine (PCPA) coupled with modified multi-platform method to examine the therapeutic effects and mechanisms of GAE. A pentobarbital sodium-induced sleep test and water maze were used to assess sleep and cognitive performance, respectively. An enzyme-linked immunosorbent assay was used to determine orexin levels and aging and sleep markers in serum and hypothalamic tissues. Hematoxylin-eosin staining and Nissl staining were used to assess histopathological changes, and autophagy levels were assessed using transmission electron microscopy, immunofluorescence. Western blot and immunohistochemical staining were performed to detect the levels of orexin, orexin-receptor proteins, and autophagy-associated proteins to study the effects of GAE on hippocampal neurons, and the underlying mechanisms. RESULTS: In aged sleep-deprived rats, GAE treatment prolonged sleep duration, improved cognitive function, prevented hippocampal neuronal damage, increased the number of Nissl bodies, improved aging and sleep markers, and enhanced the LC3A/B expression in autophagosomes and neurons. The amount of orexin in serum and hypothalamic tissue and OX1R, OX2R, and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) proteins also reduced, which resulted in the inhibition of the PI3K/Akt/mTOR pathway and activation of the autophagy process. CONCLUSIONS: GAE may reduce hypothalamic orexin secretion and interact with orexin receptors to inhibit the PI3K/Akt/mTOR signalling network and activate autophagy. This may be a potential mechanism of action of GAE in regulating sleep-related cognitive function.

Fatigue assessment of sedentary office workers using smartphones: a preliminary study.

Objectives. Smartphone-based gait assessment provides a novel method to evaluate fatigue. This study aimed to examine self-reported fatigue and gait parameters recorded using a smartphone before and after an 8-h work day in bank workers, and identify the relationship between self-reported fatigue and gait parameters. Methods. One hundred bank workers (aged 20-45 years) were tested before and after an 8-h work day using a reaction time test, self-reported fatigue scale and gait test. Spearman correlation coefficient analysis and partial least squares regression were used to identify the relationship between self-reported fatigue and gait parameters. Results. Reaction time and self-reported fatigue increased significantly after work. Gait parameters (step frequency, minimum acceleration, acceleration root mean square, step regularity and step counts) decreased; step time and step time variability increased significantly (p < 0.05). We found a significant correlation between changes (Δ) for Δwork engagement and Δstep frequency (r = -0.20, p < 0.05), Δwork engagement and Δstep time (r = 0.21, p < 0.05), and Δwork tasks and Δstep symmetry (r = -0.20, p < 0.05). Conclusion. This study suggests that step frequency, step time and step symmetry measured using a smartphone have the potential to be used as predictors of work fatigue.

Ketogenic Diet as a Promising Non-Drug Intervention for Alzheimer's Disease: Mechanisms and Clinical Implications.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is mainly characterized by cognitive deficits. Although many studies have been devoted to developing disease-modifying therapies, there has been no effective therapy until now. However, dietary interventions may be a potential strategy to treat AD. The ketogenic diet (KD) is a high-fat and low-carbohydrate diet with adequate protein. KD increases the levels of ketone bodies, providing an alternative energy source when there is not sufficient energy supply because of impaired glucose metabolism. Accumulating preclinical and clinical studies have shown that a KD is beneficial to AD. The potential underlying mechanisms include improved mitochondrial function, optimization of gut microbiota composition, and reduced neuroinflammation and oxidative stress. The review provides an update on clinical and preclinical research on the effects of KD or medium-chain triglyceride supplementation on symptoms and pathophysiology in AD. We also detail the potential mechanisms of KD, involving amyloid and tau proteins, neuroinflammation, gut microbiota, oxidative stress, and brain metabolism. We aimed to determine the function of the KD in AD and outline important aspects of the mechanism, providing a reference for the implementation of the KD as a potential therapeutic strategy for AD.

Competitor-Weighted Centrality and Small-World Clusters in Competition Networks on Firms' Innovation Ambidexterity: Evidence from the Wind Energy Industry.

A firm's embedding structures in a technology competition network can influence its propensity for innovation ambidexterity. Using PCT (patent cooperation treaty) patent data of wind energy companies between 2010 and 2019, we adopted social network analysis and fixed-effects panel negative binomial regression to examine the impacts of network structural features on firm innovation ambidexterity. The results show that competitor-weighted centrality contributes to a firm's propensities for both incremental and radical green innovation. In contrast, a firm's embeddedness in small-world clusters can moderate the effect of the firm's competitor-weighted centrality positively on its incremental innovation but negatively on its radical innovation. The study makes three theoretical contributions. First, it enriches the understanding of how the competition network affects innovation ambidexterity. Second, it provides new insights into the relationship between competition network structures and technology innovation strategy. Finally, it contributes to bridging the research on the social embeddedness perspective and green innovation literature. The findings of this study have important implications for enterprises in the wind energy sector regarding how competitive relationships affect green technology innovation. The study underscores the importance of considering the competitiveness of a firm's rivals and the embedded structural features when devising green innovation strategies.

Dynamic Surface Reconstruction of Amphoteric Metal (Zn, Al) Doped Cu2 O for Efficient Electrochemical CO2 Reduction to C2+ Products.

The recognition of the surface reconstruction of the catalysts during electrochemical CO2 reduction (CO2RR) is essential for exploring and comprehending active sites. Although the superior performance of Cu-Zn bimetallic sites toward multicarbon C2+ products has been established, the dynamic surface reconstruction has not been fully understood. Herein, Zn-doped Cu2 O nano-octahedrons are used to investigate the effect of the dynamic stability by the leaching and redeposition on CO2RR. Correlative characterizations confirm the Zn leaching from Zn-doped Cu2 O, which is redeposited at the surface of the catalysts, leading to dynamic stability and abundant Cu-Zn bimetallic sites at the surface. The reconstructed Zn-doped Cu2 O catalysts achieve a high Faradaic efficiency (FE) of C2+ products (77% at -1.1 V versus reversible hydrogen electrode (RHE)). Additionally, similar dynamic stability is also discovered in Al-doped Cu2 O for CO2RR, proving its universality in amphoteric metal-doped catalysts. Mechanism analyses reveal that the OHC-CHO pathway can be the C-C coupling processes on bare Cu2 O and Zn-doped Cu2 O, and the introduction of Zn to Cu can efficiently lower the energy barrier for CO2RR to C2 H4 . This research provides profound insight into unraveling surface dynamic reconstruction of amphoteric metal-containing electrocatalysts and can guide rational design of the high-performance electrocatalysts for CO2RR.

Electric-Eel-Type Bi-Ionic Gradient Battery.

Electric eels generate electricity with a discharge voltage of up to 860 V under ionic gradients, providing a fascinating example to inspire viable and flexible power sources. However, hitherto reported eel-related devices are strictly restricted by complicated fabrication and environmental energy input. Herein, an electric-eel-type bi-ionic gradient battery (BGB) is performed by cationic and anionic polyelectrolyte hydrogels featuring simplified units and self-energy supply. Benefiting from ionic bonds with opposite charges in the polymer chain, bianion gradients as well as ion selective migration pathways are synchronously constructed and integrated units are enabled. As a result, an open-circuit voltage of 0.54 V and a short-circuit current density of 13 µA cm-2 are generated by a BGB unit. Moreover, a voltage output up to 60 V is derived from integrated BGB devices, demonstrating the potential to drive wearable and implantable electronics. In this case, these artificial electric systems could overcome the great challenges of environmentally friendly, biocompatible, low-cost, and soft power sources, providing in-depth insights into the development of clean and sustainable power generation technologies.

Novel quadruple fluorescence properties of two benzoylthiourea isomers.

Two benzoylthiourea isomers, N-2-flurobenzoy-N'-4- (N,N-dimethyl)amidophenylthiourea (2FBDAPT) and N-4-fluro-benzoy-N'-4- (N,N-dimethyl)amidophenylthiourea (4FBDAPT) were determined by fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and X-ray diffraction. It was found that intra- and intermolecular hydrogen bonds played an important role in determining their conformations. Electronic spectra of the two compounds were investigated by UV absorption and steady-state fluorescence methods. The intermolecular hydrogen bond between the title compounds and methanol molecules caused the long wavelength absorption bands in methanol to weaken and vanish indeed. Quadruple fluorescence bands in ultraviolet and visible region were observed in the studied solvents upon the variable excitation wavelength. As same as Azumaya's suggestions for benzanilide (BA), F4 fluorescence bands with the maximum wavelength (λ(max)) between 546 nm and 622 nm were characteristic of TICT fluorescence. F3 bands of λ(max) from 434 nm to 483 nm were explained by the ESIPT model of the S1 state of the thiol tautomer to the S1 state of the keto tautomer. The new proposition was that F2 bands with λ(max) at about 365 nm were attributed to ESIPT from the S1 state of the thiol tautomer to the S0 state of the enol tautomer. And F1 fluorescence emissions with λ(max) at about 310 nm originated from the local S1 transitions of the enol tautomer. All experimental results were supported by MP2, CASSCF and CASPT2 quantum chemical calculations.

Ketogenic diet ameliorates cognitive impairment and neuroinflammation in a mouse model of Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is the most common neurodegenerative disorder that causes dementia and affects millions of people worldwide. Although it has devastating outcomes for patients and tremendous economic costs to society, there is currently no effective treatment available. AIMS: The high-fat, low-carbohydrate ketogenic diet (KD) is an established treatment for refractory epilepsy with a proven efficacy. Although the considerable interest has emerged in recent years for applying KD in AD patients, only few interventional studies in animals and humans have addressed the effects of KD on cognitive impairments, and the results were inconclusive. The aim of this study was to explore the impact of KD on cognitive functions and AD pathology in 5XFAD mice-a validated animal model of AD. RESULTS: Four months of a ketogenic diet improved spatial learning, spatial memory and working memory in 5XFAD mice. The improvement in cognitive functions was associated with a restored number of neurons and synapses in both the hippocampus and the cortex. Ketogenic diet treatment also reduced amyloid plaque deposition and microglial activation, resulting in reduced neuroinflammation. The positive effect of ketogenic diet on cognitive functions depended on the starting time and the duration of the diet. A shorter period (2 months) of ketogenic diet treatment had a weaker effect. Ketogenic diet initiated at late stage of AD (9 months of age) displayed no effect on cognitive improvement. CONCLUSIONS: These findings indicate positive effects of ketogenic diet on both cognitive function and histopathology in Alzheimer's disease, which could be due to reduced microglial activation and neuroinflammation. Our findings provide new insights and therapeutic interventions for the treatment of Alzheimer's disease.

Chloral Hydrate Alters Brain Activation Induced by Methamphetamine-Associated Cue and Prevents Relapse.

Methamphetamine is a highly addictive drug and its abuse leads to serious health and social problems. Until now, no effective medications are yet available for the treatment of methamphetamine addiction. Our study reveals that chloral hydrate, a clinical sedative drug, suppresses the seeking desire for methamphetamine. After 5 days of continuous administration (subanesthetic dose 50 mg/kg and 100 mg/kg), methamphetamine-seeking behavior of rats was inhibited in the condition place preference and intravenous self-administration tests. Furthermore, chloral hydrate treatment robustly suppressed cue-induced methamphetamine relapse. The whole brain c-fos immunostaining revealed that chloral hydrate treatment suppressed neuronal activity in the rhomboid thalamic nucleus (Rh), dorsal endopiriform nucleus (dEn), and claustrum (Cl) while enhanced zona incerta (ZI) activity during cue-induced methamphetamine relapse. Therefore, chloral hydrate could remodel neural network activity and serve as a potential medicine to treat methamphetamine addiction.