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 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.)