Disease-Associated Neurotoxic Astrocyte Markers in Alzheimer Disease Based on Integrative Single-Nucleus RNA Sequencing.

Alzheimer disease (AD) is an irreversible neurodegenerative disease, and astrocytes play a key role in its onset and progression. The aim of this study is to analyze the characteristics of neurotoxic astrocytes and identify novel molecular targets for slowing down the progression of AD. Single-nucleus RNA sequencing (snRNA-seq) data were analyzed from various AD cohorts comprising about 210,654 cells from 53 brain tissue. By integrating snRNA-seq data with bulk RNA-seq data, crucial astrocyte types and genes associated with the prognosis of patients with AD were identified. The expression of neurotoxic astrocyte markers was validated using 5 × FAD and wild-type (WT) mouse models, combined with experiments such as western blot, quantitative real-time PCR (qRT-PCR), and immunofluorescence. A group of neurotoxic astrocytes closely related to AD pathology was identified, which were involved in inflammatory responses and pathways related to neuron survival. Combining snRNA and bulk tissue data, ZEP36L, AEBP1, WWTR1, PHYHD1, DST and RASL12 were identified as toxic astrocyte markers closely related to disease severity, significantly elevated in brain tissues of 5 × FAD mice and primary astrocytes treated with Aß. Among them, WWTR1 was significantly increased in astrocytes of 5 × FAD mice, driving astrocyte inflammatory responses, and has been identified as an important marker of neurotoxic astrocytes. snRNA-seq analysis reveals the biological functions of neurotoxic astrocytes. Six genes related to AD pathology were identified and validated, among which WWTR1 may be a novel marker of neurotoxic astrocytes.

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 psychological impact on patients with memory disorders and their caregivers during COVID-19.

BACKGROUND: COVID-19 is erupting globally. Mass quarantine had been implemented all around China which could influence the psychological status of patients with memory disorders and their caregivers. AIM: To investigate the psychological impact of mass quarantine on patients with memory disorders and their caregivers in China. METHODS: We completed a cross-sectional study in 787 patients and their caregivers registered from 2010 to 2019 in Memory Clinic, The First Affiliated Hospital of Chongqing Medical University, by telephone interviews. The performance in neuropsychiatric symptoms (NPSs), sleep, nutrition, chronic diseases of patients, and the burden of care, anxiety and depression of caregivers was assessed by six assessment scales (MNA-SF, PSQI, NPI, RSS, PHQ-9 and GAD-7). RESULTS: Only 68 (8.6%) patients worried about the outbreak of COVID-19. The prevalence of NPSs among all subjects was nearly 60.0%. Approximately 50.0% of the caregivers reported distress. More than 70.0% of patients remained stable in NPSs. However, anxiety, depression, aberrant motor disorder and delusion were exacerbated (22.9%, 18.6%, 17.1% and 16.8%, respectively). Appetite and eating disorder led alleviation rate by 25.8% while disappearing rate of agitation led by 5.8%. 7.5% of caregivers manifested depressive symptoms while 4.9% expressed anxiety symptoms, and 40.8% showed care burden. The coefficients of RSS and PHQ-9, RSS and GAD-7, RSS and NPI-D, PHQ-9 and GAD-7 were 0.7, 0.5, 0.5 and 0.6, respectively (p < 0.01). CONCLUSION: Changes in NPSs during COVID-19 were observed in some patients with memory disorders and their caregivers, and adherence to medication contributed to the stabilization of NPSs.

[Study of the Detection of Histidine Based on "On-Off" Fluorescence Probe of Carbon Dots].

An new type of switch "On-Off" fluorescence probe was constructed based on fluorescence carbon dots as a novel strategy to analyze trace histidine(His) which was proposed for the first time. In water solution with pH 7.6, the fluorescence of CDs was quenched with Ru3+ due to the formation of ground state compound through electrostatic attraction, and the system was thus "turned-off". The fluorescence intensity of CDs was "turned-on" due to the competition between His and Ru towards the surface of CDs. The effect of critical parameters including pH, buffer solutions, reaction temperature and time needed to grow the fluorescence intensity of CDs was studied. Results show thatin water solution with pH 7.6, and when the temperature was between 20~25 ℃, the fluorescence intensity of the released CDs displayed a linear relationship in the range of (6.5~219.3)×10-6 mol·L-1 of captopril. Lower limit of detection for His, at the signal-to-noise ratio of 3/(3δ), was 2.15×10-6 mol·L-1. The methodology was successfully applied for the determination of His in Compound Amino Acid Injections, with the RSD≤2.07%, and the recovery rate was between 95.7%～102.4%. The result of the experiment was satisfactory. On the one hand, the excellent optical character CDs was acted as "On-Off" fluorescence probe, which could be extent the application of CDs, on the other hand, the excellent performance of the proposed fluorescence probe shows that this method possesses the potential for practical application.

Novel Carbazole-Based Porous Organic Polymer for Efficient Iodine Capture and Rhodamine B Adsorption.

A new porous organic polymer (CTF-CAR), which takes carbazole as the electron-rich center unit and thiophenes as the auxiliary group, has been synthesized through catalyst-free Schiff-base polymerization. At the same time, the structure, thermal stability, morphology, and other basic properties of the polymer were analyzed by IR, NMR, TGA, and SEM. Then, CTF-CAR was applied to iodine capture and rhodamine B adsorption. Due to its strong electron donor ability and abundant heteroatom binding sites, which have a positive effect on the interaction between the polymer network and adsorbates, CTF-CAR exhibits high uptake capacities for iodine vapor and rhodamine B as 2.86 g g-1 and 199.7 mg g-1, respectively. The recyclability test also confirmed that it has good reusability. We found that this low-cost and catalyst-free synthetic porous organic polymer has great potential for the treatment of polluted water and iodine capture.

The Valuable Role of ARMC1 in Invasive Breast Cancer as a Novel Biomarker.

Background: Invasive breast carcinoma (BRCA) is a common type of breast cancer with a high clinical incidence. Thus, it is significant to find effective biomarkers for BRCA diagnosis and treatment. Although some members of armadillo (ARM) repeat family of proteins are confirmed to be biomarkers in cancers, the role of armadillo repeat-containing 1 (ARMC1) in BRCA remains unknown. Methods: We firstly analyzed the ARMC1 expression in normal breast tissues and BRCA samples and its association with overall survival by the public database. Next, the χ 2 test was used to evaluate the prognostic significance of ARMC1 expression in TCGA-BRCA patient samples. The ARMC1 mutations in BRCA were explored in the cBioportal database. Besides, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore the biological functions of ARMC1 in BRCA. Finally, immunohistochemistry and immunofluorescence staining were performed to validate the ARMC1 expression in BRCA. Results: ARMC1 expression in tumor samples was significantly higher than that in normal tissues, and higher expression of ARMC1 was related to lower survival. Moreover, the tumor stage and histology of BRCA patients were associated with ARMC1 expression. ARMC1 genetic mutations occurred in 32% of BRCA patients, and the amplification and high expression of ARMC1 accounted for most of them. Furthermore, functional enrichment analysis suggested that ARMC1 might be involved in the cell cycle in BRCA. Ultimately, increased ARMC1 expression was found in clinical breast carcinoma tissues by our confirmatory experiments. Conclusions: ARMC1 may play a significant role in BRCA and act as a biomarker, which provides valuable clues for the treatment and diagnosis of BRCA.

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.

The Neuropsychiatric Changes After COVID-19 Quarantine in Patients With Cognitive Impairment and Their Caregivers in Chongqing, China: A Cohort Study.

BACKGROUND: The follow-up study on neuropsychiatric changes after the lifting of coronavirus disease 2019 (COVID-19) quarantine in patients with cognitive impairment and their caregivers is still lacking, and relative information is needed to formulate more comprehensive healthcare prevention measures worldwide. AIMS: To provide data on the changes in neuropsychiatric performance after the lifting of COVID-19 quarantine in patients with cognitive disorders and their caregivers. METHODS: Two surveys in Chongqing, China were conducted via telephonic interview with 531 patients and their caregivers. The baseline survey was performed from February 11 to 23, 2020, and the follow-up was from October 24 to November 9, 2020. The data of neuropsychiatric symptoms (NPSs), sleep, nutrition, and chronic diseases of patients, as well as the burden of care, anxiety, and depression of caregivers were evaluated. RESULTS: Significant alleviation of NPSs after the lifting of COVID-19 quarantine was observed in patients with mild cognitive impairment (MCI) and dementia (both P < 0.05). Compared with baseline, the prevalence for NPSs of all participants dropped from 57.94 to 38.82%. Among NPS subdomains, apathy displayed the biggest decline at follow-up by 10.72%, followed by nighttime behavior by 8.65%. Mixed effect generalized estimation equation analysis showed significant amelioration in hallucination, depression, apathy, irritability, aberrant motor behavior, and nighttime behavior (all P < 0.05), with the most prominent changes in nighttime behavior and apathy. Among the patients with unsatisfactory control of chronic disease, the medication adherence rate dropped by approximately 30% after the lifting of quarantine. More importantly, around 13% increase of care burden was observed among the caregivers at follow-up, with both depression and anxiety rising by nearly 4%. CONCLUSION: The prolonged quarantine may exacerbate NPS in patients with memory disorders, while the care burden and mental stability of the caregivers after the pandemic should also be concerned.

Platinum nanowire array electrochemical sensor: fabrication and characterization.

Platinum nanowire array sensors were prepared by alternating current electrochemical deposition of platinum into the pores of anodic aluminum oxide template. The nanostructure displayed perfect electrochemical stability with 10 segments of the cyclic voltammetry curves coincided completely, and the oxide-current peak of H2O2 was in the range of 0.3-0.6 V. Moreover, the response current has an excellent linear relationship with the H2O2 concentration at the range from 4.5 x 10(-3) mM to 2.3 x 10(-1) mM, and the detection limit was about 0.56 microM. After dissolving AAO template in 0.3 M KOH for 20 min, the sensitivity of the sensor was increased from 34.76 microA mM(-1) mm(-2) to 62.35 microA mM(-1) mm(-2), and the detection limit was lowered from 0.56 microM to 0.28 microM. Furthermore, the platinum nanowire array sensors presented good stability and repeatability.

Catalytic resonance scattering spectral determination of ultratrace horseradish peroxidase using rhodamine S.

A highly sensitive and selective resonance scattering spectral assay was proposed for the determination of horseradish peroxidase (HRP), based on its catalytic effect on the H2O2 oxidation of KI to form I3(-). The I3(-) combined respectively with rhodamine (Rh) dye such as rhodamine S (RhS), rhodamine 6G (Rh6G), rhodamine B (RhB) and butyl-rhodamine B (b-RhB), to form association particles (Rh-I3(n). The four Rh systems all exhibit a stronger resonance scattering (RS) peak at 424 nm. For the RhS, Rh6G, RhB and b-RhB systems, HRP concentration in the range of 3.2 x 10(-12) to 4.8 x 10(-9), 2 x 10(-11) to 3.2 x 10(-9), 1.6 x 10(-11) to 3.2 x 10(-9) and 1.6 x 10(-11) to 4 x 10(-9) g/mL was linear to its RS intensity at 424 nm, with a detection limit of 2.2 x 10(-12), 2.5 x 10(-12), 4.4 x 10(-12) and 2.6 x 10(-12 )g/mL, respectively. This RhS system was most sensitive and stable, and was applied for the determination of HRP in the hepatitis B surface antibody labeling HRP and water samples, with satisfactory results.

Carbon dots as fluorescent probe for "off-on" Detecting sodium dodecyl-benzenesulfonate in aqueous solution.

In this paper, we propose an "off-on" approach for the detection of sodium dodecyl-benzenesulfonate (SDBS) using carbon dots (CDs) as fluorescent probe. We firstly demonstrated that the fluorescence of CDs decreased apparently in the presence of ruthenium (Ru), and the system was thus "turn-off". The resulting CDs-Ru system was found to be sensitive to SDBS, SDBS not only serves to shelter the CDs effectively from being quenched, but also to reverse the quenching and restore the fluorescence due to its ability to remove Ru from the surface of CDs (turn-on). An eco-friendly, simple and sensitive platform for the detection of SDBS based on the CDs-Ru probes has been proposed. After the experimental conditions were optimized, the linear range for detection SDBS was 0.10-7.50 µg/mL, with correlation coefficient (r) 0.9988, detection limit was 0.033 µg/mL (3σ). This method is facile, rapid, low cost, environment-friendly, and possesses the potential for practical application.

A carbon dots-CdTe quantum dots fluorescence resonance energy transfer system for the analysis of ultra-trace chlortoluron in water.

In this paper, a fluorescence resonance energy transfer (FRET) system between fluorescence carbon dots (CDs, donor) and CdTe quantum dots (CdTe, acceptor) was constructed, and a novel platform for sensitive and selective determination of chlortoluron was accordingly proposed. It was found that in Tris-HCl buffer solution at pH=8.7, energy transfer from CDs to CdTe occurred, which resulted in a great enhancement of the fluorescence intensity of CdTe. Upon the addition of chlortoluron, in terms of strong interaction between chlortoluron and CdTe QDs through the formation of chlortoluron-CdTe ground state complex, resulted in CdTe fluorescence quenching. Under optimal conditions, in range of 2.4×10(-10)molL(-1)-8.5×10(-8)molL(-1), the change of CdTe fluorescence intensity was in good linear relationship with the chlortoluron concentration, and the detection limit was 7.8×10(-11)molL(-1) (S/N=3). Most of common relevant substance, cations and anions did not interfere with the detection of chlortoluron. The proposed method was applied to determine chlortoluron in water samples with satisfactory results.

A highly sensitive resonance scattering spectral assay for IgG using Fehling reagent-glucose-immunonanogold reaction.

Nanogold exhibits strong catalytic effect on the slow reaction between glucose and Fehling reagent at 70 degrees C. The production of Cu(2)O particles have two stronger resonance scattering (RS) peaks at 390 nm and 505 nm. The catalytic effect of nanogold-labeled goat anti-human IgG (AuIgG) on the reaction was investigated with the RS technique. Coupled the immunoreaction and the immunonanogold catalytic reaction and centrifugal technique, a highly sensitive and selective RS method was developed for the detection of immunoglobulin G (IgG) as a model. With the concentration of IgG increased, the RS intensity at 505 nm decreased. The decreased intensity at 505 nm DeltaI(505)(nm) was proportional to IgG concentration in the range of 0.13-53.3 ng mL(-1), with a detection limit of 0.04 ng mL(-1) IgG. This new immunonanogold-catalytic Cu(2)O-particle RS bioassay was applied to the determination of IgG in serum sample, with high sensitivity, good selectivity, and low cost.