Exposure of endocrine disrupting chemicals (EDCs) is closely related to induction of obesity, nonalcoholic fatty liver disease (NAFLD) and other lipid-metabolism diseases. Herein, we compared the ...effects of three EDCs exposure (triclosan, bisphenol A and fluorene-9-bisphenol) on lipid metabolism in zebrfish (Danio rerio). The differential lipid-metabolism disorders were analyzed in depth through RNA-Seq and qRT-PCR, as well as assessment of the relationship between lipid disorder and RNA methylation. Histopathological observation along with varying physiological and biochemical indexes all identified that triclosan and bisphenol A induced liver fat accumulation in acute and chronic exposure. RNA-Seq analysis showed that triclosan exposure disrupted multiple physiological processes including drug metabolism, sucrose metabolism, fat metabolism and bile secretion. The dysregulation of lipid-metabolism related genes indicated that liver steatosis in triclosan and BPA-exposed zebrafish resulted from increased fatty acid synthetase, and uptake and suppression of β-oxidation. Besides, the dysregulation of pro-inflammatory genes and endoplasmic reticulum stress showed that triclosan and bisphenol A exposure not only induced occurrence of NAFLD, but also promoted progression of hepatic inflammation. However, no significant effect on lipid metabolism was observed in fluorene-9-bisphenol-exposed treatment although the larval phenotypic malformation was found compared to the control group. Moreover, EDCs exposure led to decreased global m6A level and abnormal expression of m6A modulators in larvae. Especially, the expression of demethylase FTO (fat mass and obesity-associated protein) was significantly increased in triclosan-exposure treatment. These findings are conductive for us to deeply understand the underlying molecular mechanisms regarding the obesity and NAFLD from EDCs exposure.
•Triclosan and bisphenol A exposure results in lipid metabolism disorder in zebrafish.•TCS exposure increases lipogenesis and lipid transport, and inhibits lipid oxidation.•TCS exposure affect drug, fatty acid and sucrose metabolism pathways in zebrafish.•TCS and BPA induce the abnormal expression of ER and inflammation related genes.•Reduced global RNA m6A methylation upon exposure to three endocrine disruptors.
Given both the popularity of street vendors and the government resistance to them in tourism governance, we interview vendors between September 2014 and May 2021 to gain insights into the ...interactions and conflicts between vendors, local enterprises and government departments in Canton, China. We derive a theory of ‘He Wei Gui’ from Chinese Confucian culture and adopt discourse analysis to investigate how informal tourism photography vendors in the Canton Tower Scenic Area resolve their conflicts. We argue that photography vendors have developed a harmonious but fragile coexistence through the use of measures such as fuzzification of public space, flexible industry regulations, output of emotional capital and normalised ways, thereby demonstrating the business acumen of little people. In contrast to the existing trend of ‘rigid governance’, the authors suggest applying ‘flexible management’ in the informal economy and tourism governance, and giving prominence to the principal role of informal operators or little people. In addition, this flexible management reflects the tacit consent from all the stakeholders, the active suing for nonviolent solution from the vulnerable and the willingness of modifying or even creating rules for balancing the distribution of the interests from the dominant stakeholder. The key to this flexible management is that authorities take the investment of emotional capital of the vulnerable groups into consideration. This leads to fuzzy governance which blurs and integrates emotions into the rules, making it possible to solve the conflicts in a more flexible way.
The adoption of high-performance computing (HPC) in healthcare has gained significant attention in recent years, driving advancements in medical research and clinical practice. Exploring the ...literature on HPC implementation in healthcare is valuable for decision-makers as it provides insights into potential areas for further investigation and investment. However, manually analyzing the vast number of scholarly articles is a challenging and time-consuming task. Fortunately, topic modeling techniques offer the capacity to process extensive volumes of scientific literature, identifying key trends within the field. This paper presents an automatic literature analysis framework based on a state-of-art vector-based topic modeling algorithm with multiple embedding techniques, unveiling the research trends surrounding HPC utilization in healthcare. The proposed pipeline consists of four phases: paper extraction, data preprocessing, topic modeling and outlier detection, followed by visualization. It enables the automatic extraction of meaningful topics, exploration of their interrelationships, and identification of emerging research directions in an intuitive manner. The findings highlight the transition of HPC adoption in healthcare from traditional numerical simulation and surgical visualization to emerging topics such as drug discovery, AI-driven medical image analysis, and genomic analysis, as well as correlations and interdisciplinary connections among application domains.
In the age of big data, the Internet big data can finely reflect public attention to air pollution, which greatly impact ambient PM
2.5
concentrations; however, it has not been applied to PM
2.5
...prediction yet. Therefore, this study introduces such informative Internet big data as an effective predictor for PM
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, in addition to other big data. To capture the multi-scale relationship between PM
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concentrations and multi-source big data, a novel multi-source big data and multi-scale forecasting methodology is proposed for PM
2.5
. Three major steps are taken: 1) Multi-source big data process, to collect big data from different sources (e.g., devices and Internet) and extract the hidden predictive features; 2) Multi-scale analysis, to address the non-uniformity and nonalignment of timescales by withdrawing the scale-aligned modes hidden in multi-source data; 3) PM
2.5
prediction, entailing individual prediction at each timescale and ensemble prediction for the final results. The empirical study focuses on the top highly-polluted cities and shows that the proposed multi-source big data and multi-scale forecasting method outperforms its original forms (with neither big data nor multi-scale analysis), semi-extended variants (with big data and without multi-scale analysis) and similar counterparts (with big data but from a single source and multi-scale analysis) in accuracy.
It is widely accepted that eutrophication has played an important role in the formation of harmful cyanobacterial blooms in recent decades, which impacts water quality and ecological environment and ...causes huge economic losses. Algicidal bacteria have a promising application prospect in controlling cyanobacterial blooms in aquaculture water. Here, the process of the algicidal bacterium Brevibacillus laterosporus strain Bl-zj acting on Microcystis aeruginosa was explored using transcriptome analysis to elucidate the algicidal mechanism. The results of the co-culture of bacterium and alga showed a strong alga-lysing effect of B. laterosporus against M. aeruginosa with an extreme morphology deformation of the algal cells. A total of 2744 differentially expressed genes of B. laterosporus were identified, which were mainly involved in the metabolism of amino acid, carbohydrate, and lipid. In the co-cultured group, the expression of genes mainly enriched in valine, leucine and isoleucine degradation, and fatty acid degradation were significantly increased. However, the expression of the genes related to ribosome were mainly inhibited. Transcriptome analysis showed that B. laterosporus obtained ATP and energy by the degradation of valine, leucine, isoleucine, and fatty acids, and destroyed algal cells by efflux pump transporters, secretion of hydrolytic enzymes, antibiotics, proteases, and other secondary metabolites, resulting in algal death and achieving the algicidal effect.
Phosphorylation is a widespread posttranslational modification that regulates numerous biological processes. Viruses can alter the physiological activities of host cells to promote virus particle ...replication, and manipulating phosphorylation is one of the mechanisms. Senecavirus A (SVA) is the causative agent of porcine idiopathic vesicular disease. Although numerous studies on SVA have been performed, comprehensive phosphoproteomics analysis of SVA infection is lacking. The present study performed a quantitative mass spectrometry-based phosphoproteomics survey of SVA infection in Instituto Biologico-Rim Suino-2 (IBRS-2) cells. Three parallel experiments were performed, and 4,520 phosphosites were quantified on 2,084 proteins. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that many phosphorylated proteins were involved in apoptosis and spliceosome pathways, and subcellular structure localization analysis revealed that more than half were located in the nucleus. Motif analysis of proteins with differentially regulated phosphosites showed that proline, aspartic acid, and glutamic acid were the most abundant residues in the serine motif, while proline and arginine were the most abundant in the threonine motif. Forty phosphosites on 27 proteins were validated by parallel reaction monitoring (PRM) phosphoproteomics, and 30 phosphosites in 21 proteins were verified. Nine proteins with significantly altered phosphosites were further discussed, and eight SRRM2, CDK13, DDX20, DDX21, BAD, ELAVL1, PDZ-binding kinase (PBK), and STAT3 may play a role in SVA infection. Finally, kinase activity prediction showed 10 kinases' activity was reversed following SVA infection. It is the first phosphoproteomics analysis of SVA infection of IBRS-2 cells, and the results greatly expand our knowledge of SVA infection. The findings provide a basis for studying the interactions of other picornaviruses and their mammalian host cells.
Bronchopulmonary Dysplasia (BPD) has a high incidence and affects the health of preterm infants. Cuproptosis is a novel form of cell death, but its mechanism of action in the disease is not yet ...clear. Machine learning, the latest tool for the analysis of biological samples, is still relatively rarely used for in-depth analysis and prediction of diseases.
First, the differential expression of cuproptosis-related genes (CRGs) in the GSE108754 dataset was extracted and the heat map showed that the expression of NFE2L2 gene was significantly higher in the control group whereas the expression of GLS gene was significantly higher in the treatment group. Chromosome location analysis showed that both the genes were positively correlated and associated with chromosome 2. The results of immune infiltration and immune cell differential analysis showed differences in the four immune cells, significantly in Monocytes cells. Five new pathways were analyzed through two subgroups based on consistent clustering of CRG expression. Weighted correlation network analysis (WGCNA) set the screening condition to the top 25% to obtain the disease signature genes. Four machine learning algorithms: Generalized Linear Models (GLM), Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGB) were used to screen the disease signature genes, and the final five marker genes for disease prediction. The models constructed by GLM method were proved to be more accurate in the validation of two datasets, GSE190215 and GSE188944.
We eventually identified two copper death-associated genes, NFE2L2 and GLS. A machine learning model-GLM was constructed to predict the prevalence of BPD disease, and five disease signature genes NFATC3, ERMN, PLA2G4A, MTMR9LP and LOC440700 were identified. These genes that were bioinformatics analyzed could be potential targets for identifying BPD disease and treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metastasis, a major challenge during the treatment of lung cancer, causes deterioration in patient health outcomes. Thus, to address this problem, this study aimed to explore the role and ...contribution of Cholesterol 25-Hydroxylase (CH25H) as a potential diagnostic and prognostic marker in lung cancer. Online public databases were used to analyze the expression level, prognostic value, gene-pathway enrichment, and immune infiltration of CH25H in lung cancer patients. The Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to analyze and detect the CH25H expression levels in leukocytes from lung cancer patients. The expression level of CH25H was significantly reduced in lung adenocarcinoma (LUAD), which is associated with a higher disease stage, but not in lung squamous cell carcinoma (LUSC). Kaplan-Meier survival analysis indicated that LUAD patients with low CH25H expression had a worse prognosis. Mechanistically, our results showed that in LUAD, CH25H may be a regulatory factor affecting the immune cell infiltration level, and the resultant tumor development. Experimental data showed that low expression of CH25H in leukocytes was significantly associated with LUAD metastasis (P < 0.01). Our study suggests that CH25H may function as a prognostic and risk stratification biomarker for LUAD.
Although EGFR-TKI resistance mechanisms in non-small cell lung cancer (NSCLC) have been extensively studied, certain patient subgroups remain with unclear mechanisms. This retrospective study ...analysed mutation data of NSCLC patients with EGFR-sensitive mutations and high programmed death-ligand 1 (PD-L1) expression or high TMB to identify primary resistance mechanisms.
Hybrid capture-based next-generation sequencing (NGS) was used to analyse mutations in 639 genes in tumor tissues and blood samples from 339 NSCLC patients. PD-L1 immunohistochemical staining was also performed on the same cell blocks. Molecular and pathway profiles were compared among patient subgroups.
TMB was significantly higher in lung cancer patients with EGFR-sensitive mutations and high PD-L1 expression. Compared with the high-expression PD-L1 or high TMB and low-expression or TMB groups, the top 10 genes exhibited differences in both gene types and mutation rates. Pathway analysis revealed a significant mutations of the PI3K signaling pathway in the EGFR-sensitive mutation group with high PD-L1 expression (38% versus 12%, p < 0.001) and high TMB group (31% versus 13%, p < 0.05). Notably, PIK3CA and PTEN mutations emerged as the most important differentially mutated genes within the PI3K signaling pathway.
Our findings reveal that the presence of PI3K signaling pathway mutations may be responsible for inducing primary resistance to EGFR-TKIs in NSCLC patients with EGFR-sensitive mutations along with high PD-L1 expression or high TMB. This finding is of great significance in guiding subsequent precision treatments in NSCLC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This present study examined the effect of Tamibarotene (AM80) in APP/PS1 mice, a well-established AD mouse model. AM80 was intraperitoneal administered to 3-month-old APP/PS1 mice at a dose of ...5 mg/kg/day for 16 weeks. The results clearly showed that AM80 could reduce amyloid-β peptides through impact on APP processing and reduce microglia and astrocyte activation in APP/PS1 mice. The most notable finding in the present study was that inhibitory effect on BACE1 mediated by NF-κB pathway underlies the anti-inflammatory action of AM80. Moreover, AM80 could significantly decrease synaptic loss and enhance the expressions of Synapsin and Drebrin. Therefore, AM80 treatment may have the preclinical prevention of AD with new therapeutic strategies.
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