Prediction of survival of persons with advanced dementia using the advanced dementia prognostic tool: A 2-year prospective study.

BACKGROUND: In this prospective study, we evaluated the usefulness of the advanced dementia prognostic tool (ADEPT) for estimating the 2-year survival of persons with advanced dementia (AD) in China. METHODS: The study predicted the 2-year mortality of 115 persons with AD using the ADEPT score. RESULTS: In total, 115 persons with AD were included in the study. Of these persons, 48 died. The mean ADEPT score was 13.0. The AUROC for the prediction of the 2-year mortality rate using the ADEPT score was 0.62. The optimal threshold of the ADEPT score was 11.2, which had an AUROC of 0.63, specificity of 41.8, and sensitivity of 83.3. CONCLUSIONS: The ADEPT score based on a threshold of 11.2 may serve as a prognostic tool to determine the 2-year survival rate of persons with AD in Chongqing, China. However, further studies are needed to explore the nature of this relationship.

Natural Fracture Development Characteristics and Their Relationship with Gas Contents-A Case Study of Wufeng-Longmaxi Formation in Luzhou Area, Southern Sichuan Basin, China.

Natural fractures are critical factors that should be considered in shale reservoir evaluation, storage condition analysis, horizontal well design, and fracturing stimulation, which also play a non-negligible role in the occurrence state of shale gas in the reservoir. This paper discussed the influence of fracture development on gas-bearing properties based on the analysis results of core observation, scanning electron microscopy, mineral composition, and gas-bearing properties after the development characteristics of fractures and their longitudinal variation law were clarified. In this way, the development characteristics of organic-rich marine shale fractures in the Longmaxi Formation in the 203 well area of the Luzhou member of the Sichuan Basin and their effects on the gas-bearing properties can be analyzed. The results show that the Longmaxi Formation shale develops shear fractures, extensional fractures of tectonic origin, bedding fractures, dissolution fractures, and abnormally high-pressure fractures of nonstructural origin. Specifically, interlayer fractures, intercrystalline fractures, organic matter contraction fractures, and fractures between clay layers are microfractures. Fracture development is characterized by short longitudinal extension, small opening, high degrees of composite filling, and large density changes, with calcite and pyrite as the filling materials. The fracture density has a "three-stage" variation pattern longitudinally, and the bottom is dominated by thin siliceous shale development, together with a small amount of shale mixed with calcareous and calcareous materials. Moreover, the fracture is dominated by "splitting" and "shearing" failure, crossing stratification with the fracture density. The highest fracture density was found in the 2 sub-layer, featuring the joint development of horizontal and vertical fractures, which form the mesh fracture system through mutual cutting and restriction. The lithofacies in the 4 sub-layer are dominated by clay siliceous shale with a small amount of mixed shale of calcareous and siliceous materials. The formation of fractures always expands along the lamellation direction, which has concentrated development members of top and bottom fractures, with the development of horizontal fractures dominated and vertical fractures less developed. Furthermore, a synergistic effect can be found among the total organic carbon (TOC) content, fracture density, and gas-bearing property of the shale in Longmaxi Formation. It is worth noting that a high TOC content and siliceous content are conducive to the formation of microfractures, while the development of fracture contributes to the total gas-bearing property, especially to the increase in free gas content. To be concrete, the free gas content in the fracture development member accounts for more than 55% of the total gas content, thanks to a channel provided by fractures for the desorption of shale gas.

GPR120 modulates epileptic seizure and neuroinflammation mediated by NLRP3 inflammasome.

BACKGROUND: The complex pathophysiology of epilepsy hampers the development of effective treatments. Although more than ten kinds of anti-seizures drugs (ASDs) have good effects on seizure control worldwide, about 30% of patients still display pharmacoresistance against ASDs. Neuroinflammation seems to play a crucial role in disease progression. G protein-coupled receptor 120 (GPR120) has been shown to negatively regulate inflammation and apoptosis. However, the role of GPR120 in epilepsy remains unclear. In this study, we aimed to explore the mechanism of GPR120 in epilepsy. METHODS: Male adult C57BL/6 mice were intracranially injected with kainic acid (KA) to establish epilepsy model, and the adeno associated virus (AAV) was administered intracranially at 3 weeks before KA injection. VX765 was administered by intragastric administration at 30 min before KA induced and an equal dose administrated twice a day (10 a.m. and 4 p.m.) lasting 7 days until the mice were killed. Western blot analysis, immunofluorescence staining, video monitoring of seizure, LFP recording, Nissl staining were performed. RESULTS: GPR120 was increased in both the hippocampus and cortex in the KA-induced model with temporal lobe epilepsy (TLE), and both were most highly expressed at 7 days after KA injection. Overexpression of GPR120 significantly alleviated epileptic activity, reduced neuronal death after status epilepticus (SE), downregulated the expression of IL-1ß, IL-6, IL-18, and pyrin domain-containing protein 3 (NLRP3) inflammasome, whereas knockdown GPR120 showed the opposite effect. The effects of GPR120 knockdown were reversed by VX765 inhibition cysteinyl aspartate specific proteinase-1 (Caspase-1). CONCLUSION: GPR120 modulates epileptic seizure activity and affects neuronal survival in KA-induced mouse model of temporal lobe epilepsy. Furthermore, GPR120 regulated neuroinflammation in epileptic animals through NLRP3/Caspase-1/IL-1ß signaling pathway.

The inhibition of PGAM5 suppresses seizures in a kainate-induced epilepsy model via mitophagy reduction.

Background: Epilepsy is a common neurological disease, and excessive mitophagy is considered as one of the major triggers of epilepsy. Mitophagy is a crucial pathway affecting reactive oxygen species. Phosphoglycerate mutase 5 (PGAM5) is a protein phosphatase present in mitochondria that regulates many biological processes including mitophagy and cell death. However, the mechanism of PGAM5 in epilepsy remains unclear. The purpose of the present study was to examine whether PGAM5 affects epilepsy through PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy. Methods: After the knockdown of PGAM5 expression by the adeno-associated virus, an epilepsy model was created by kainic acid. Next, the seizure activity was recorded by local field potentials before evaluating the level of mitochondrial autophagy marker proteins. Lastly, the ultrastructure of mitochondria, neuronal damage and oxidative stress levels were further observed. Results: A higher PGAM5 level was found in epilepsy, and its cellular localization was in neurons. The interactions between PGAM5 and PINK1 in epilepsy were further found. After the knockdown of PGAM5, the level of PINK1 and light chain 3B was decreased and the expression of the translocase of the inner mitochondrial membrane 23 and translocase of the outer mitochondrial membrane 20 were both increased. Knockdown of PGAM5 also resulted in reduced neuronal damage, decreased malondialdehyde levels, decreased reactive oxygen species production and increased superoxide dismutase activity. In addition, the duration of spontaneous seizure-like events (SLEs), the number of SLEs and the time spent in SLEs were all reduced in the epilepsy model after inhibition of PGAM5 expression. Conclusion: Inhibition of PGAM5 expression reduces seizures via inhibiting PINK1-mediated mitophagy.

Triggering receptor expressed on myeloid cells 2 activation downregulates toll-like receptor 4 expression and ameliorates cognitive impairment in the Aß1-42 -induced Alzheimer's disease mouse model.

Increasing evidence suggests that changes in the triggering receptor expressed on myeloid cells 2 (TREM2) is closely correlated with the pathological development of Alzheimer's disease (AD). However, the biological function and related role of this change remain poorly understood. Higher TREM2 expression has been reported in the brain of AD patients than in normal controls. Here, levels of TREM2 gene and protein levels were observed to be higher in both cortex and hippocampus of the Aß1-42 -induced AD mice than in those of the wild type mice. Together with in vitro experimental data, we found that the anti-inflammatory role of TREM2 was, to some extent, limited and potentially counteracted by the hyperactive toll-like receptor 4 (TLR4) in the AD mice. In this context, Interleukin 4 (IL-4), as an agonist of TREM2, was administered to the AD mice to persistently activate TREM2. Interestingly, TREM2 activation in IL-4-treated AD mice led to an elevation in lysosomes and microtubule-associated protein 1 light chain 3 (LC3) II/I expression, demonstrating that the level of microglia autophagy was increased. Increased autophagy significantly downregulated the expression levels of caspase recruitment domain-containing protein 9 (CARD9) and TLR4, potentially weakening the CARD9-TLR4 pathway and suppressing the TLR4-mediated pro-inflammatory effect in IL-4-treated AD mice. Furthermore, data acquired from Morris water maze testing indicated that IL-4 administration could ameliorate cognitive impairment in the AD mice. In conclusion, the findings from in vitro and in vivo experiments suggest that TREM2 might represent a potential drug target to treat neuroinflammation in AD.