Search

Aims: Islet cell autoantigen 1 (ICA1) is involved in autoimmune diseases and may affect synaptic plasticity as a neurotransmitter. Databases related to Alzheimer's disease (AD) have shown decreased ICA1 expression in patients with AD. However, the role of ICA1 in AD remains unclear. Here, we report that ICA1 expression is decreased in the brains of patients with AD and an AD mouse model. Results: The ICA1 increased the expression of amyloid precursor protein (APP), disintegrin and metalloprotease 10 (ADAM10), and disintegrin and metalloprotease 17 (ADAM17), but did not affect protein half‐life or mRNA levels. Transcriptome sequencing analysis showed that ICA1 regulates the G protein‐coupled receptor signaling pathway. The overexpression of ICA1 increased PKCα protein levels and phosphorylation. Conclusion: Our results demonstrated that ICA1 shifts APP processing to non‐amyloid pathways by regulating the PICK1‐PKCα signaling pathway. Thus, this study suggests that ICA1 is a novel target for the treatment of AD. [ABSTRACT FROM AUTHOR]

To investigate the distribution characteristics of spontaneous combustion disaster (SCD) zones in the goaf of "110" mining method with U + L ventilation system and formulate corresponding fire prevention measures, enclosed coal oxidation experiments were carried out to measure the oxidation characteristics of Dongrong Coal Mine bituminous coal sample. A coupled 3DEC-CFD (3 dimensional Distinct Element Code) model was established. The 3D transient distribution characteristics of SCD zones in the "110" mining goaf under U+L ventilation condition were analyzed. Nitrogen injection in the tailgate was proposed for coal spontaneous combustion prevention. The results show that air leakage changed the distribution of oxygen and temperature fields in the "110" goaf, causing the region 20~60 m parallel to the retained roadway to remain in the oxidation zone for spontaneous combustion. As the working face advanced, the area change curve of SCD zones in the "110" goaf exhibited a "double inflection point" pattern. Eliminating the "retained roadway oxidation zone" can effectively reduce the spontaneous combustion risks in the "110" goaf and ensure mining safety. This study enriches the mechanisms of coal spontaneous combustion. [ABSTRACT FROM AUTHOR]

Background: Down syndrome (DS) is caused by an extra copy of all or part of chromosome 21. The patients with DS develop typical Alzheimer's disease (AD) neuropathology, indicating the role of genes on human chromosome 21 (HSA21) in the pathogenesis of AD. Purkinje cell protein 4 (PCP4), also known as brain-specific protein 19, is a critical gene located on HSA21. However, the role of PCP4 in DS and AD pathogenesis is not clear. Objective: To explore the role of PCP4 in amyloid-β protein precursor (AβPP) processing in AD. Methods: In this study, we investigated the role of PCP4 in AD progression in vitro and in vivo. In vitro experiments, we overexpressed PCP4 in human Swedish mutant AβPP stable expression or neural cell lines. In vitro experiments, APP23/PS45 double transgenic mice were selected and treated with AAV-PCP4. Multiple topics were detected by western blot, RT-PCR, immunohistochemical and behavioral test. Results: We found that PCP4 expression was altered in AD. PCP4 was overexpressed in APP23/PS45 transgenic mice and PCP4 affected the processing of AβPP. The production of amyloid-β protein (Aβ) was also promoted by PCP4. The upregulation of endogenous AβPP expression and the downregulation of ADAM10 were due to the transcriptional regulation of PCP4. In addition, PCP4 increased Aβ deposition and neural plaque formation in the brain, and exuberated learning and memory impairment in transgenic AD model mice. Conclusion: Our finding reveals that PCP4 contributes to the pathogenesis of AD by affecting AβPP processing and suggests PCP4 as a novel therapeutic target for AD by targeting Aβ pathology. [ABSTRACT FROM AUTHOR]

It is difficult to accurately determine the risk of spontaneous combustion in the U + L ventilation goaf of the first mining face when using the method of roof cutting gob-side entry retaining (RCGSER). To address this problem, the I2101 working face of Qipanjing Mine was considered as the research object in this study. Laboratory experiments, field measurements, and CFD numerical simulation were used to study the continuous oxygen consumption characteristics of coal samples and the distribution of spontaneous combustion danger areas in U + L goaf. The results showed that the oxygen consumption capacity of the coal samples was weak. The continuous oxygen consumption rate of the coal samples had a negative exponential distribution, and the oxygen volume fraction in the smothering zone (critical) was 15%. Furthermore, the three likely areas for spontaneous combustion in the RCGSER goaf were near the open-off cut, within 5–10 m near the RCGSER roadway, and behind the working face. Additionally, the relationship between the dangerous area ( S f ) and the different positions (x) of the working face was expressed as S f = a + b ⋅ exp c ⋅ x b < 0 , c < 0 . On this basis, the fire prevention and extinguishing measures of nitrogen injection was recommended near the open-off cut as well as inhibitor injection at the RCGSER roadway. Because the maximum width of the spontaneous combustion oxidation zone in Qipanjing Mine is 80 m and the minimum daily advancing speed is 1.2 m, spontaneous combustion risk did not exist. This research slightly fills the theoretical gap in the relatively new field of fire prevention in RCGSER goaf. [ABSTRACT FROM AUTHOR]

The 11101 working face of Qipanjing Mine was taken as the research object to explore the dynamic change law of the spontaneous combustion of the remaining coal in the gob-side entry retaining goaf area. A sealed oxygen consumption experiment was conducted to determine the (critical) oxygen volume fraction in the suffocation zone and continuous oxygen consumption rate of coal samples. The parameters of the working face were measured on site, and the air volume fraction in the goaf was monitored using a beam tube. Considering upward ventilation and the effect of gravity, a UDF control program for the falling medium in the gob-side entry retaining goaf was written. Based on the experimental results, a control program for the continuous oxygen consumption rate of the remnant coal was compiled, the dynamic distribution of the flow field in the gob-side entry retaining goaf was simulated with different advancing positions and air leakage at the working face, and a prediction model for the spontaneous combustion danger area was established. Finally, fire prevention measures via grouting in the return air lane side and nitrogen injection in the retaining lane side were put forward. The results showed that with the variation in the advancing position of the working face or in the air leakage of the air intake lane, the range of the natural hazardous area of the gob-side entry retaining goaf presents a distribution with a power function SF = xn+b (0 < n < 1). The theoretically proposed fire-fighting measures can effectively reduce the risk of spontaneous combustion of coal. [ABSTRACT FROM AUTHOR]

Background: Chronic alcohol consumption can alter the structure of the central nervous system and disrupt cognitive function. Alcoholics are more likely to develop neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, the role of alcohol in promoting neurotoxicity and neurodegeneration remains unclear.Objective: In this study, we aimed at estimating the effects of chronic binge alcohol exposure on brain transcriptome and behavior changes in a chronic "Drinking in the Dark" (DID) mouse model.Methods: The adult C57BL/6J male mice were exposed to alcohol for 4 weeks. RNA-seq was applied to assess the effects of chronic alcohol exposure on transcriptome in brain. The open field test and novel object recognition test were used to assess the changes of anxiety level, locomotive function, and short-term memory induced by alcohol. RNA-seq analysis revealed that chronic alcohol exposure caused significant change in the brain transcriptome, especially in prefrontal cortex.Results: The gene dysregulation caused by chronic alcohol exposure includes pathways related to mitochondrial energy metabolism (such as oxidative phosphorylation) and multiple neurodegenerative diseases (such as AD and PD). Furthermore, the pathway and network analyses suggest that the genes involved in mitochondrial energy metabolism, ubiquitin-proteasome system, Wnt signaling pathway, and microtubules may attribute to the neurotoxicity and neurodegeneration caused by chronic alcohol consumption. Additionally, locomotive function was also significantly impaired.Conclusion: This work provides gene transcriptional profile data for future research on alcohol-induced neurodegenerative diseases, especially AD and PD. [ABSTRACT FROM AUTHOR]

To investigate the impact of stratified mining on the spontaneous combustion characteristics of lower coal in thick coal seams, an analysis was conducted on the macro pore structure, temperature rise, oxygen consumption characteristics, chemical structure, surface chemical properties, and functional group distribution of the upper and lower stratified coal samples (LSC, LSR) from the LinSheng Mine 1202 re-mining face. Post re-mining, the specific surface area, average pore diameter for adsorption, micropore volume, and mesopore volume of LSR showed a significant increase compared to LSC. The maximum mass loss rate for LSR was approximately three times that of LSC, and the characteristic temperature of LSR was lower. When the volumetric fraction of oxygen exceeded 12%, the oxygen consumption rate and CO generation rate of LSR surpassed those of LSC. The alkyl carbon content in LSR was 2% lower compared to LSC, while the oxygenated carbon content was higher by 4.37%. The oxygen content in LSR and the O/C ratio were higher than those in LSC. The structural order of LSR was lower by 11.3%, and the oxygen-containing functional groups were higher by 1.15%. These findings suggest that stratified mining increases the spontaneous combustion risk of lower coal layers. This study underscores the need for careful consideration of mining strategies to mitigate potential risks. [ABSTRACT FROM AUTHOR]

To explore the macro–micro coal oxidation characteristics for the purpose of preventing coal spontaneous combustion and achieving efficient coal conversion and utilization, the enclosed coal oxidation characteristics of KunNing coal sample (KN) under 25–70 °C were investigated. KN coal molecular models were constructed based on analysis and testing results of X-ray Photoelectron Spectroscopy (XPS), Carbon-13 Nuclear Magnetic Resonance Spectroscopy (13C NMR), Fourier Transform Infrared Spectroscopy (FTIR) and other techniques. The pyrolysis processes of coal-oxygen reaction systems with different oxygen contents were simulated using ReaxFF force field. The results show that the oxygen consumption rate, CO release rate, CO 2 release rate and oxidation heat release intensity of coal increase exponentially with rising temperature. The ratio of aromatic bridge carbon to peripheral carbon in KN coal molecular structure is 0.08, and the molecular formula is C 149 H 76 O 15 N 2 S 2. In the later stage of the experimental and molecular dynamics simulation processes, the CO content decreased while the growth rate of CO 2 increased. Different indicator gases exhibit varied responses to oxygen content. The C-atom labeling and traceback results for the four indicator gas molecules demonstrate that CO 2 mainly comes from aldehyde, hydroxyl, carboxyl and methoxy groups in coal molecules, CO is primarily generated from esters, phenols, carbonyls, C 2 H 2 is predominantly derived from ring-opening and cracking of cycloalkanes, and the source of C 2 H 4 is related to cycloalkanes and alcohols. [ABSTRACT FROM AUTHOR]

Background: Wieacker‐Wolff syndrome (WWS) is a congenital X‐linked neuromuscular disorder, which was firstly reported in 1985. Zinc finger C4H2‐type containing (ZC4H2) gene has been found to be associated with the disease pathogenesis. However, the underlying mechanism remains elusive. Methods: Whole‐exome sequencing was performed to identify the mutations. Expression plasmids were constructed and cell culture and immune‐biochemical assays were used to examine the effects of the mutation. Results: We reported a female patient with classical symptoms of WWS and discovered a novel nonsense heterozygous mutation (p.R67X; c.199C>T) in ZC4H2 gene in the patient but not in her parents. The mutation resulted in a 66 amino‐acid truncated ZC4H2 protein. The mutation is located in the key helix domain and it altered the subcellular locations of the mutant ZC4H2 protein. X‐chromosome inactivation (XCI) pattern analysis revealed that the XCI ratio of the proband was 22:78. Conclusion: Female heterozygous carriers with nonsense mutation with a truncated ZC4H2 protein could lead to the pathogenesis of Wieacker‐Wolff syndrome and our study provides a potential new target for the disease treatment. [ABSTRACT FROM AUTHOR]

SIL1, an endoplasmic reticulum (ER)-resident protein, is reported to play a protective role in Alzheimer's disease (AD). However, the effect of SIL1 on amyloid precursor protein (APP) processing remains unclear. In this study, the role of SIL1 in APP processing was explored both in vitro and in vivo . In the in vitro experiment, SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695. In the in vivo experiment, AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates. Western blotting (WB), immunohistochemistry, RNA sequencing (RNA-seq), and behavioral experiments were performed to evaluate the relevant parameters. Results indicated that SIL1 expression decreased in APP23/PS45 mice. Overexpression of SIL1 significantly decreased the protein levels of APP, presenilin-1 (PS1), and C-terminal fragments (CTFs) of APP in vivo and in vitro . Conversely, knockdown of SIL1 increased the protein levels of APP, β-site APP cleavage enzyme 1 (BACE1), PS1, and CTFs, as well as APP mRNA expression in 2EB2 cells. Furthermore, SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice. Importantly, Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice. These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

Background: Astrocytes are essential for synaptic transmission, and their dysfunction can result in neuropsychiatric disorders such as anxiety and depression. Many studies have shown that global knockout of Melatonin receptor 2 ( Mtnr1b ) is associated with the development of various mental disorders., Aim: This study aimed to investigate the effects of astrocyte ablation of Mtnr1b on cognitive function and anxiety-like behavior in mice, as well as the potential biological mechanisms., Methods: A conditional Cre-loxP system allowing deletion of Mtnr1b from astrocytes was developed to investigate the specific role Mtnr1b . Control and Mtnr1b cKO𝐺𝑓𝑎𝑝 mice were selected for cognitive function behavioral testing (Morris water maze test, novel object recognition test) and emotion-related behavioral testing (open field, elevated plus maze). After testing, brain tissue was collected and examined by immunofluorescence for the expression of neuronal nuclei (NeuN), glutamate decarboxylase 67 (GAD67), and vesicular glutamate transporter 1 (vGluT1). RNA-seq was performed on hippocampal tissue from control and Mtnr1b cKO𝐺𝑓𝑎𝑝 mice to identify differentially expressed genes. Additional confirmation of differential gene expression was performed using real-time quantitative polymerase chain reaction (qRT-PCR)., Results: Mtnr1b cKO𝐺𝑓𝑎𝑝 mice were not significantly different from control mice in the Morris water maze and novel object recognition tests. Results from the open field and elevated plus maze tests showed that Mtnr1b cKO𝐺𝑓𝑎𝑝 mice exhibited significantly more anxiety-like behavior than did controls. Immunofluorescence revealed that the number of mature neurons did not differ significantly between Mtnr1b cKO𝐺𝑓𝑎𝑝 mice and controls. The expression of GAD67 in the hippocampal CA1 and CA3 areas of Mtnr1b cKO𝐺𝑓𝑎𝑝 mice was significantly lower than in the control group, but no significant difference was detected for vGluT1 expression. RNA-seq and qRT-PCR results showed that Mtnr1b knockout in astrocytes led to a decrease in the levels of gamma-aminobutyric acid sub-type A (GABAA) receptors and Kir2.2., Conclusions: The astrocyte-specific knockout in Mtnr1b cKO𝐺𝑓𝑎𝑝 mice results in anxiety-like behavior, which is caused by down-regulation of gamma-aminobutyric acid-ergic (GABAergic) synaptic function., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Neuroinflammation is a leading cause of secondary neuronal injury in neonatal hypoxic-ischemic encephalopathy (HIE). Regulation of neuroinflammation may be beneficial for treatment of HIE and its secondary complications. Gallic acid (GA) has been shown to have anti-inflammatory and antioxidant effects. In this report we found that oxygen-glucose deprivation and/reoxygenation (OGD/R)-induced cell death, and the generation of excessive reactive oxygen species (ROS) and inflammatory cytokines by microglia were inhibited by GA treatment. Furthermore, GA treatment reduced neuroinflammation and neuronal loss, and alleviated motor and cognitive impairments in rats with hypoxic-ischemic brain damage (HIBD). Together, our results reveal that GA is an effective regulator of neuroinflammation and has potential as a pharmaceutical intervention for HIE therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Dong, Luo, Hu, Cao, Wang, Meng, Feng, Zhou and Song.)