Ferroptosis is a novel process of programmed cell death driven by excessive lipid peroxidation that is associated with the development of lung adenocarcinoma. N6-methyladenosine (m6a) modification of ...multiple genes is involved in regulating the ferroptosis process, while the predictive value of N6-methyladenosine- and ferroptosis-associated lncRNA (FMRlncRNA) in the prognosis of patients remains with LUAD remains unknown.
Unsupervised cluster algorithm was applied to generate subcluster in LUAD according to ferroptosis-associated lncRNA. Stepwise Cox analysis and LASSO algorithm were applied to develop a prognostic model. Cellular location was detected by single-cell analysis. Also, we conducted Gene set enrichment analysis (GSEA) enrichment, immune microenvironment and drug sensitivity analysis. In addition, the expression and function of the LINC01572 were investigated by several
experiments including qRT-PCR, cell viability assays and ferroptosis assays.
A novel ferroptosis-associated lncRNAs-based molecular subtype containing two subclusters were determined in LUAD. Then, we successfully created a risk model according to five ferroptosis-associated lncRNAs (LINC00472, MBNL1-AS1, LINC01572, ZFPM2-AS1, and TMPO-AS1). Our nominated model had good stability and predictive function. The expression patterns of five ferroptosis-associated lncRNAs were confirmed by polymerase chain reaction (PCR) in LUAD cell lines. Knockdown of LINC01572 significantly inhibited cell viability and induced ferroptosis in LUAD cell lines.
Our data provided a risk score system based on ferroptosis-associated lncRNAs with prognostic value in LUAD. Moreover, LINC01572 may serve as a novel ferroptosis suppressor in LUAD.
In recent years, the maturation of microarray technology has allowed the genome-wide analysis of gene expression patterns to identify tissue-specific and ubiquitously expressed ('housekeeping') ...genes. We have performed a functional and topological analysis of housekeeping and tissue-specific networks to identify universally necessary biological processes, and those unique to or characteristic of particular tissues.
We measured whole genome expression in 31 human tissues, identifying 2374 housekeeping genes expressed in all tissues, and genes uniquely expressed in each tissue. Comprehensive functional analysis showed that the housekeeping set is substantially larger than previously thought, and is enriched with vital processes such as oxidative phosphorylation, ubiquitin-dependent proteolysis, translation and energy metabolism. Network topology of the housekeeping network was characterized by higher connectivity and shorter paths between the proteins than the global network. Ontology enrichment scoring and network topology of tissue-specific genes were consistent with each tissue's function and expression patterns clustered together in accordance with tissue origin. Tissue-specific genes were twice as likely as housekeeping genes to be drug targets, allowing the identification of tissue 'signature networks' that will facilitate the discovery of new therapeutic targets and biomarkers of tissue-targeted diseases.
A comprehensive functional analysis of housekeeping and tissue-specific genes showed that the biological function of housekeeping and tissue-specific genes was consistent with tissue origin. Network analysis revealed that tissue-specific networks have distinct network properties related to each tissue's function. Tissue 'signature networks' promise to be a rich source of targets and biomarkers for disease treatment and diagnosis.
Hexavalent chromium contamination in groundwater has become a very serious and challenging problem. Identification of the groundwater chemical characteristics of the sites and their control ...mechanisms for remediation of pollutants is a significant challenge. In this study, a contaminated site in Xinxiang City, Henan Province, was investigated and 92 groundwater samples were collected from the site. Furthermore, the hydrogeochemical characteristics and the distribution patterns of components in the groundwater were analyzed by a combination of multivariate statistical analysis, Piper diagram, Gibbs diagram, ions ratio and hydrogeochemical simulation. The results showed that the HCO3-Cl-Mg-Ca type, SO4-HCO3-Na type, and HCO3-Mg-Ca-Na type characterize the hydrogeochemical composition of shallow groundwater and HCO3-Cl-Mg-Ca type, HCO3-Na-Mg type, and HCO3-SO4-Mg-Na-Ca type characterize the hydrogeochemical composition of deep groundwater. Ion ratios and saturation index indicated that the groundwater hydrogeochemical characteristics of the study area are mainly controlled by water–rock action and evaporative crystallization. The dissolution of halite, gypsum and anhydrite, the precipitation of aragonite, calcite and dolomite, and the precipitation of trivalent chromium minerals other than CrCl3 and the dissolution of hexavalent chromium minerals occurred in groundwater at the site. The minimum value of pH in groundwater at the site is 7.55 and the maximum value is 9.26. The influence of pH on the fugacity state of minerals was further investigated. It was concluded that the saturation index of dolomite, calcite, aragonite and MgCr2O4 increases with the increase of pH, indicating that these minerals are more prone to precipitation, and the saturation index of Na2Cr2O7, K2Cr2O7 and CrCl3 decreases with the increase of pH, implying that Na2Cr2O7, K2Cr2O7 and CrCl3 are more prone to dissolution. The saturation index of the remaining minerals is less affected by pH changes. The study can provide a scientific basis for groundwater remediation.
•CREB activation protected Sb-induced neuronal apoptosis.•JNK pathway activation contributed to Sb-stimulated CREB phosphorylation.•JNK/CREB activation alleviates Sb-induced neuronal apoptosis ...through Bcl-2 regulation.
Antimony (Sb) is a potentially toxic chemical element abundantly found in the environment. We previously reported that Sb promoted neuronal deathvia reactive oxygen species-dependent autophagy. Here, we assessed the role of cyclic adenosine monophosphate response element-binding protein (CREB) in Sb-induced neuronal damage. We found that Sb treatment induced CREB phosphorylation and neuronal apoptosis both in vitro and in vivo. Interestingly, inhibition of CREB’s transcriptional activity with 666−15 dramatically enhanced apoptosis in PC12 cells by downregulating B-cell lymphoma 2 (Bcl-2). Additionally, Sb activated ERK, JNK, and p38 signaling ; however, only JNK promoted CREB phosphorylation. In conclusion, our findings suggest that CREB phosphorylation by JNK attenuates Sb-induced neuronal apoptosis via Bcl-2 upregulation. These data suggest that JNK-dependent CREB activation prevents neurons from Sb-induced apoptosis and guides the development of novel strategies to prevent Sb-induced neurotoxicity.
Coal tar pitch is a product with high carbon content and aromatic compounds. Modified coal tar pitch is a high quality raw material for the preparation of intermediate phase pitch, needle coke, ...carbon microspheres, et al. In this paper, modified coal tar pitch was used as raw material, nitrogen was used as protective gas, and thermal conversion was carried out at constant temperatures (370, 390, 410, 420 °C). Polarized light microscopy, SEM, elemental analysis, FTIR spectroscopy, Raman spectroscopy and XRD diffraction combined with split-peak fitting were used to characterize the microstructures of the thermal transformation products. The results showed that the Iar and CH3/CH2 contents of the products increased with the gradual increase of the thermal conversion temperature, and the aromatic content increased. And the higher the temperature at the same heating rate, the more the ideal graphite microcrystal content, and the defective graphite microcrystals are converted into ideal graphite microcrystals during the thermal conversion process. When the reaction temperature exceeds 390 °C, the microstructure of the thermal transformation products is anisotropic spheres, and the small spheres fuse with each other and tend to be basin-like and mosaic structure as the temperature increases.
As part of the MicroArray Quality Control (MAQC)-II project, this analysis examines how the choice of univariate feature-selection methods and classification algorithms may influence the performance ...of genomic predictors under varying degrees of prediction difficulty represented by three clinically relevant endpoints.
We used gene-expression data from 230 breast cancers (grouped into training and independent validation sets), and we examined 40 predictors (five univariate feature-selection methods combined with eight different classifiers) for each of the three endpoints. Their classification performance was estimated on the training set by using two different resampling methods and compared with the accuracy observed in the independent validation set.
A ranking of the three classification problems was obtained, and the performance of 120 models was estimated and assessed on an independent validation set. The bootstrapping estimates were closer to the validation performance than were the cross-validation estimates. The required sample size for each endpoint was estimated, and both gene-level and pathway-level analyses were performed on the obtained models.
We showed that genomic predictor accuracy is determined largely by an interplay between sample size and classification difficulty. Variations on univariate feature-selection methods and choice of classification algorithm have only a modest impact on predictor performance, and several statistically equally good predictors can be developed for any given classification problem.
•Arsenic trioxide (ATO) decreased the expression of hTERT at mRNA and protein levels.•Arsenic trioxide suppressed the expression of Sp1, c-Myc, NF-κB and USF2.•Inhibiting Sp1, c-Myc, NF-κB and USF2 ...potentiates antitumor activity of ATO.
Acute promyelocytic leukemia (APL) is largely caused by the t(15,17) chromosome translocation, leading to the production of the PML/retinoic acid receptor alpha fusion. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), as a monotherapy or combination therapy, have been successfully used to treat APL primarily by targeting the degradation of the fusion protein. We previously observed that ATO treatment induced cell death in APL cell line HL-60 accompanied by inhibition of the human telomere reverse transcriptase (hTERT) activity, a critical enzyme responsible for the control of cell replication and transformation in cancer cells. In the present study, we investigated the underlying mechanism by which hTERT activity is inhibited by ATO in HL-60 cells. Our results showed that ATO down-regulated the expression of hTERT at both mRNA and protein levels. Further molecular analysis revealed that the expression of four transcription factors Sp1, c-Myc, NF-κB and USF2, which are located in the proximate promoter region (−1126 to −47) of hTERT, was also suppressed by ATO. Notably, we observed that down-regulation of these four factors by their siRNAs potentiates ATO-induced cell growth inhibition and apoptosis. Therefore, our results provide a novel mechanism of action of ATO for the treatment of APL.
Over the past decade, synthetic trees have been engineered to mimic the transpiration cycle of natural plants, but the leaves are prone to dry out beneath a critical relative humidity. Here, we ...create large-area synthetic leaves whose transpiration process is remarkably stable over a wide range of humidities, even without synthetic stomatal chambers atop the nanopores of the leaf. While the water menisci cannot initially withstand the Kelvin stress of the subsaturated air, they self-stabilized by locally concentrating vapor within the top layers of nanopores that have dried up. Transpiration rates were found to vary nonmonotonically with the ambient humidity because of the tradeoff of dry air increasing the retreat length of the menisci. It is our hope that these findings will encourage the development of large-area synthetic trees that exhibit excellent stability and high throughput for water-harvesting applications.
The important role of cholesterol in tumor metastasis has been widely studied in recent years. Ezetimibe is currently the only selective cholesterol uptake inhibitor on the market. Here, we explored ...the effect of ezetimibe on breast cancer metastasis by studying its impact on breast cancer cell migration, invasion, and epithelial‐mesenchymal transition (EMT). Differential gene expression analysis and validation were also carried out to compare ezetimibe‐treated and untreated breast cancer cells. Finally, breast cancer cells overexpressing TGFβ2 were constructed, and the effect of TGFβ2 on the migration and invasion of ezetimibe‐treated breast cancer cells was examined. Our results show that ezetimibe treatment of breast cancer cells inhibited cell migration, invasion, and EMT, and it significantly suppressed the expression of TGFβ2. Overexpression of TGFβ2 reversed the inhibitory effect of ezetimibe on the migration and invasion of breast cancer cells. Taken together, our results suggest that ezetimibe might be a potential candidate for the treatment of breast cancer metastasis.
The important role of cholesterol in tumor metastasis has been widely studied recently. Ezetimibe, the only selective cholesterol uptake inhibitor on the market, inhibits the migration and invasion of triple‐negative breast cancer cells by targeting TGFβ2 and EMT without relying on inhibiting cholesterol uptake. Overall, our findings suggest a unique mechanism by which ezetimibe prevents breast cancer metastasis.
During COVID-19, personal protective equipment such as face masks was in urgent demand in the daily life. As the pandemic may have withdrawn from public attention, the disposal of face masks is a ...significant issue, especially plastic pollution. To address the degradation of the polymers in the marine environment, seven commercial masks were investigated via artificial weathering procedures in substitute ocean water. A suite of structural and chemical characterization techniques was employed, including scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray diffraction (XRD), and contact angle goniometry, to probe the treatment impact on commercially available N95, surgical, polyurethane, polyester, nylon, silk, and cotton masks. This work provides insights into the comprehensive analysis of material degradation in nature and raises public awareness of environmental issues post-pandemic.
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