As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between ...exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina.
We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study.
We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk.
Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants.
Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.
The PI3K/Akt signalling pathway is associated with the occurrence and development of tumours and significantly affects the prognosis of patients. We established a predictive signature based on the ...PI3K/Akt pathway to predict the prognosis of patients. The RNA-seq and clinical data of laryngeal cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. Three lncRNAs (MNX1-AS1, LINC00330, LSAMP-AS1) were selected through univariate, multivariate Cox and log-rank test analysis to establish a prognostic signature. The patients were then divided into high-risk and low-risk groups based on their risk score. In the TCGA training set, the survival time of the high-risk group was shorter than that of the low-risk group (P < 0.01). Follicular helper T cells were lower in the high-risk group (P = 0.022), and CCR, inflammation promotion, parainflammation, and type I IFN immune function were suppressed. The results of the drug sensitivity analysis suggest that the high-risk group is sensitive to AKT inhibitors. The establishment of the signature was also verified based on the clinical data. Three lncRNAs can facilitate the migration, invasion, and vitality of cancer cells in vitro, and vice versa. Moreover, p-AKT (Ser473) and p-PI3K were highly activated in the cells overexpressing the abovementioned three lncRNAs. The PI3K/Akt signalling pathway-associated prognosis signature has a good predictive effect.
Background
Uric acid (UA) transporters mediate the uptake and outflow of UA, and are greatly involved in the control of UA concentrations. Glucose transporter 9 (GLUT9), one of the UA transporters, ...has been confirmed to be expressed in human umbilical vein endothelial cells (HUVECs). This study aimed to characterize GLUT9’s effect on intracellular UA accumulation in HUVECs in a high-UA environment and to explore the mechanism of cellular dysfunction.
Methods and results
HUVECs were treated with UA to establish a model of cellular dysfunction. Then, UA uptake, GLUT9 expression and endothelial nitric oxide synthase (eNOS) and reactive oxygen species (ROS) amounts were measured. UA uptake was concentration- and time-dependent, and UA treatment significantly reduced nitric oxide (NO) levels and eNOS activity. UA also upregulated pro-inflammatory molecules and GLUT9, and increased intracellular ROS amounts in HUVECs. GLUT9 knockdown reduced UA uptake and ROS content, but antioxidant treatment did not reduce GLUT9 expression. To assess the function of JAK2/STAT3 signaling, HUVECs were treated with UA, and the phosphorylation levels of JAK2, STAT3, IL-6 and SOCS3 were increased by a high concentration of UA. In addition, GLUT9 knockdown reduced the phosphorylation of JAK2/STAT3 intermediates and increased p-eNOS amounts.
Conclusions
GLUT9 mediated the effects of high UA levels on HUVECs by increasing the cellular uptake of UA, activating JAK2/STAT3 signaling, and reduced the production of active eNOS and NO in HUVECs.
•High glycolysis level indicates poor prognosis of patients with head and neck squamous cell carcinoma.•RNA bulk and single cell RNA sequencing database of head and neck squamous cell carcinoma ...analysis showed that patients with high glycolysis levels had less infiltration of macrophages, T cells and monocytes.•The risk signature was verified by the external verification dataset, and the results show that the prediction effect is good.•In vitro functional and Western blot assays confirmed that the above five risk genes(MUCL1,TRIML2,RAB3B,SPINK6,IGSF11) affect tumor function and related to the process of glycolysis.
Glycolysis is an indispensable process for tumor cell,but the effect of glycolysis on the prognosis and immune cell infiltration of head and neck squamous cell carcinoma is not clear.
Based on RNA bulk and single cell RNA sequencing data of head and neck squamous cell carcinoma from The Cancer Genome Atlas(TCGA) and GSE195832, the effect of glycolysis level on immune cell infiltration was analyzed. Then, we obtained the prognostic genes related to glycolysis through survival analysis to construct prognostic risk signature. Our sample and GSE65858 datasets are used as external verification datasets to verify the validity of the signature. Finally, we used Western blot and cell function assays to determine the relationship between risk genes and glycolysis and the function of prognostic genes.
The level of glycolysis was related to the prognosis of head and neck tumors (P = 0.0044). The results of immune infiltration analysis of TCGA database showed that high level glycolysis subgroup had less infiltration of macrophages, T cells and monocytes. Results of single cell sequencing analysis validates the above results. Additionally, Five risk genes(MUCL1,TRIML2,RAB3B,SPINK6,IGSF11) were selected to construct signature.Risk score was an independent prognostic factor(P < 0.01). The external validation set also shows the same result. In vitro functional and Western blot assays confirmed that the above five genes affect tumor function and related to the process of glycolysis.
Glycolysis-related risk signatures can be used to predict the prognosis and immune infiltration of head and neck squamous cell carcinoma.
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•MA exposure leads to lower Nrf2 expression and higher Drp1, Cyt-c, and Caspase 3 expression in the MA abusers and rats.•Oxidative stress and mitochondrial fission contribute to ...neuronal apoptosis.•These identified markers hold the potential for assessing brain damage in forensic cases associated with MA abuse.•Nrf2 may play a key role in MA-induced neurotoxicity, underscoring the need for further investigation.
Methamphetamine (MA), a representative amphetamine-type stimulant, is one of the most abused drugs worldwide. Studies have shown that MA-induced neurotoxicity is strongly associated with oxidative stress and apoptosis. While nuclear factor E2-related factor 2 (Nrf2), an antioxidant transcription factor, is known to exert neuroprotective effects, its role in MA-induced dopaminergic neuronal apoptosis remains incompletely understood. In the present study, we explored the effects of MA on the expression levels of Nrf2, dynamin-related protein 1 (Drp1), mitofusin 1 (Mfn1), cytochrome c oxidase (Cyt-c), and cysteine aspartate-specific protease 3 (Caspase 3), as well as the correlations between Nrf2 and mitochondrial dynamics and apoptosis. Brain tissue from MA abusers was collected during autopsy procedures. An MA-dependent rat model was also established by intraperitoneal administration of MA (10 mg/kg daily) for 28 consecutive days, followed by conditioned place preference (CPP) testing. Based on immunohistochemical staining and western blot analysis, the protein expression levels of Nrf2 and Mfn1 showed a decreasing trend, while levels of Drp1, Cyt-c, and Caspase 3 showed an increasing trend in the cerebral prefrontal cortex of both MA abusers and MA-dependent rats. Notably, the expression of Nrf2 was positively associated with the expression of Mfn1, but negatively associated with the expression levels of Drp1, Cyt-c, and Caspase 3. These findings suggest that oxidative stress and mitochondrial fission contribute to neuronal apoptosis, with Nrf2 potentially playing a critical role in MA-induced neurotoxicity.
Inflammatory responses after intracerebral hemorrhage (ICH) contribute to severe secondary brain injury, leading to poor clinical outcomes. However, the responsible genes for effective ...anti-inflammation treatment in ICH remain poorly elucidated. The differentially expressed genes (DEGs) of human ICH were explored by online GEO2R. Go and KEGG were used to explore the biological function of DEGs. Protein–protein interactions (PPI) were built in the String database. Critical modules of PPI were identified by a molecular complex detection algorithm (MCODE). Cytohubba was used to determine the hub genes. The mRNA-miRNA interaction network was built in the miRWalk database. The rat ICH model was applied to validate the key genes. A total of 776 DEGs were identified in ICH. Go and KEGG analyses indicated that DEGs were mainly involved in neutrophil activation and the TNF signaling pathway. GSEA analysis presented that DEGs were significantly enriched in TNF signaling and inflammatory response. PPI network was constructed in the 48 differentially expressed inflammatory response-related genes. The critical module of the PPI network was constructed by 7 MCODE genes and functioned as the inflammatory response. The top 10 hub genes with the highest degrees were identified in the inflammatory response after ICH. CCL20 was confirmed as a key gene and mainly expressed in neurons in the rat ICH model. The regulatory network between CCL20 and miR-766 was built, and the miR-766 decrease was confirmed in a human ICH dataset. CCL20 is a key biomarker of inflammatory response after intracerebral hemorrhage, providing a potential target for inflammatory intervention in ICH.
Pathogenic fungi cause severe postharvest diseases on tomato, which has led to tremendous economic losses. In this study, we isolate 125 antagonistic bacteria from the roots of Fraxinus hupehensis, ...and screened them for antagonistic activity against Botrytis cinerea, Phytophthora infestans and Alternaria solani. Finally, the strain B17-12 was selected for further experiments. Based on sequence analyses of the 16S rDNA and rpoB genes, strain B17-12 was identified as Pseudomonas koreensis. The strain can produce volatile organic compounds (VOCs) that efficiently inhibit B. cinerea, P. infestans and A. solani, 25 VOCs were identified with solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS), and 7 VOCs had been reported to exhibit antimicrobial activity. P. koreensis B17-12 rapidly colonized on the root of tomato. The genome of B17-12 reveals numerous membrane-related genes and 7 secondary metabolite synthesis gene clusters that are crucial for its biological control properties. The study highlights that B17–12 may be an excellent candidate for biological control of postharvest diseases of tomato blight and gray mold.
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•Isolate B17-12 from Fraxinus hupehensis was identified as Pseudomonas koreensis.•The fermentation broth and VOCs of B17-12 showed highest antagonistic activity.•The B17-12 exhibited stable colonization in tomato plants, persisting for at least 29 days.
Psychological
suzhi
, as a set of comprehensive, integrated, and positive psychological qualities in Chinese culture, is a concept that has emerged in the field of Chinese quality-oriented education ...and that attempts to serve as a comprehensive overview of a given individual’s mental health. More recently, however, researchers have determined that while psychological
suzhi
is a significant predictor of psychological outcomes, its individual components (cognitive, individuality, and adaptability qualities) all have a distinct impact on these outcomes. The present study was therefore designed to assess whether psychological
suzhi
and/or components thereof play a mediating role in the relationship between perceived social support (PSS) and life satisfaction among adolescents. In total, 2227 participants (
M
age
= 15.71 ± 0.82 years, 67.49% male) from western China were recruited for this study, and were assessed using adapted versions of the Multidimensional Scale of Perceived Social Support, the Satisfaction with Life Scale, and the Brief Psychological
Suzhi
Questionnaire for Middle School Students. Our analyses ultimately revealed that there were significant positive correlations between PSS, psychological
suzhi
and components thereof, and life satisfaction. We additionally employed a structural equation modeling approach which indicated that overall psychological
suzhi
partially mediated the relationship between PSS and life satisfaction, whereas the cognitive, individuality, and adaptability components of
suzhi
did not mediate this same relationship. This suggests that psychological
suzhi
may be an important regulator of the relationship between PSS and life satisfaction such that educators and legal guardians may be able to improve the life satisfaction of adolescents either via offering social support or via bolstering their psychological
suzhi
.
Whole transcriptome sequencing (RNA-Seq) has gained prominence for the detection of fusions in solid tumors. Here, we describe the development and validation of an in-house RNA-Seq-based test system ...(FusionSeq™ 2.0) for the detection of clinically actionable gene fusions, in formalin-fixed paraffin-embedded (FFPE) specimens, using seventy tumor samples with varying fusion status. Conditions were optimized for RNA input of 50 ng, shown to be adequate to call known fusions at as low as 20% neoplastic content. Evaluation of assay performance between FFPE and fresh-frozen (FF) tissues exhibited little to no difference in fusion calling capability. Performance analysis of the assay validation data determined 100% accuracy, sensitivity, specificity, and reproducibility. This clinically developed and validated RNA-Seq-based approach for fusion detection in FPPE samples was shown to be on par if not superior to off-the-shelf commercially offered assays. With gene fusions implicated in a variety of cancer types, offering high-quality, low-cost molecular testing services for FFPE specimens will serve to best benefit the patient and the advancement of precision medicine in molecular oncology.
Key messages
A custom RNA-Seq-based test system (FusionSeq™ 2.0) for the detection of clinically actionable gene fusions,
Evaluation of assay performance between FFPE and fresh-frozen (FF) tissues exhibited little to no difference in fusion calling capability.
The assay can be performed with low RNA input and neoplastic content.
Performance characteristics of the assay validation data determined 100% accuracy, sensitivity, specificity, and reproducibility.
In order to realize the multifunctional purpose, the rear column of the car transporter is replaced by a lifting mechanism which can be regarded as a four-bar mechanism. However, for the ...multifunctional car transporter, lifting difficulty and lifting lock occur shortly after the beginning of lifting. Dynamic analysis of the lifting mechanism is carried out, and the computational results reveal that the unreasonable structure of the lifting mechanism is the main reason for the above problems. In order to overcome lifting difficulty and lifting lock, and to improve lifting performance, a back push bar combined lifting mechanism is proposed to replace the original lifting mechanism, and dynamic analysis and finite element analysis (FEA) are carried out in both lifting mechanisms. After using the back push bar combined lifting mechanism, the numerical results show that the required hydraulic cylinder thrust is reduced to a certain degree, and the horizontal pulling force imposed on the front column by the upper platform is declined sharply; the lifting test shows that the lifting process becomes fluent and labor-saving.
Multifunctional car transporter; Lifting mechanism; Dynamic analysis; FEA
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