Inhibition of Murine Breast Cancer Metastases by Hydrophilic As4S4 Nanoparticles Is Associated With Decreased ROS and HIF-1α Downregulation

Arsenic sulfide (As4S4) is a mineral drug that can be administrated orally and has been applied in the treatment of myeloid leukemia. The aim of this work is to investigate the therapeutic effect of As4S4 in highly metastatic triple-negative breast cancer (TNBC) animal model, as As4S4 has not been applied in the treatment of breast cancer yet. To overcome the poor solubility of original As4S4, a formulation of hydrophilic As4S4 nanoparticles (e-As4S4) developed previously was applied to mouse breast cancer cells as well as the tumor-bearing mice. It was shown that e-As4S4 was much more cytotoxic than r-As4S4, strongly inhibiting the proliferation of the cells and scavenging intracellular reactive oxygen species (ROS). The oral administration of e-As4S4 significantly increased the accumulation of arsenic in the tumor tissue and eliminated ROS in tumor tissues. Besides, e-As4S4 could also inhibit the activation of hypoxia-inducible factor-1α (HIF-1α) and NLRP3 inflammasomes. Consequently, the angiogenesis was reduced, the metastasis to lung and liver was inhibited and the survival of tumor-bearing mice was prolonged. In conclusion, e-As4S4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment

MAL2 drives immune evasion in breast cancer by suppressing tumor antigen presentation

Immune evasion is a pivotal event in tumor progression. To eliminate human cancer cells, current immune checkpoint therapy is set to boost CD8+ T cell-mediated cytotoxicity. However, this action is eventually dependent on the efficient recognition of tumor-specific antigens via T cell receptors. One primary mechanism by which tumor cells evade immune surveillance is to downregulate their antigen presentation. Little progress has been made toward harnessing potential therapeutic targets for enhancing antigen presentation on the tumor cell. Here, we identified MAL2 as a key player that determines the turnover of the antigen-loaded MHC-I complex and reduces the antigen presentation on tumor cells. MAL2 promotes the endocytosis of tumor antigens via direct interaction with the MHC-I complex and endosome-associated RAB proteins. In preclinical models, depletion of MAL2 in breast tumor cells profoundly enhanced the cytotoxicity of tumor-infiltrating CD8+ T cells and suppressed breast tumor growth, suggesting that MAL2 is a potential therapeutic target for breast cancer immunotherapy

Automated EEG Pathology Detection Based on Significant Feature Extraction and Selection

Neurological diseases are a significant health threat, often presenting through abnormalities in electroencephalogram (EEG) signals during seizures. In recent years, machine learning (ML) technologies have been explored as a means of automated EEG pathology diagnosis. However, existing ML-based EEG binary classification methods largely focus on extracting EEG-related features, which may lead to poor performance in classifying EEG signals by overlooking potentially redundant information. In this paper, we propose a novel Kruskal–Wallis (KW) test-based framework for EEG pathology detection. Our framework first divides EEG data into frequency sub-bands using wavelet packet decomposition and then extracts statistical characteristics from each selected coefficient. Next, the piecewise aggregation approximation technique is used to obtain the aggregated feature vectors, followed by the KW statistical test methodology to select significant features. Finally, three ensemble learning classifiers, random forest, categorical boosting (CatBoost), and light gradient boosting machine, are used to classify the extracted significant features into normal or abnormal classes. Our proposed framework achieves an accuracy of 89.13%, F1-score of 87.60%, and G-mean of 88.60%, respectively, outperforming other competing techniques on the same dataset, which shows the great promise in EEG pathology detection

High-pressure experimental verification of rutile-ilmenite oxybarometer: Implications for the redox state of the subduction zone

The more oxidized mantle peridotites above subducting slabs than stable continental areas have been attributed to the infiltration of some oxidizing fluids released from the subducting slabs. However, knowledge for the redox states of the slabs itself is very limited. Until now, few oxybarometers can be directly used to constrain the redox states of the subducting slabs. The rutile-ilmenite oxybarometer was proposed and successfully applied to constrain the oxygen fugacity of mantle assemblages. However, its application to rocks equilibrated at crustal P-T conditions has been hampered by some uncertainties in an early solid solution model of ilmenite. With a newly-released solid solution model for the ilmenite, we have conducted high-P experiments (at 3 and 5 GPa, and 900–1300°C) to test the accuracy of this oxybarometer. The experiments were performed with their oxygen fugacities controlled by the CCO buffer (i.e., C+O2=CO2). We demonstrated that the oxygen fugacities calculated for our high-P experimental products by using the rutile-ilmenite oxybarometer were in excellent agreement with the fO2 dictated by the CCO buffer, suggesting a wide applicability of this oxybarometer to crust rocks. As examples, the rutile-ilmenite oxybarometer has been used to constrain the oxygen fugacities of some metamorphic rocks such as eclogite, granulite and amphibolite usually observed from the subduction zone

Comparative analysis of microRNA profiles between adult Ascaris lumbricoides and Ascaris suum

[Background] The parasitic nematodes Ascaris lumbricoides and A. suum are of great public health and economic significance, and the two taxa were proposed to represent a single species. miRNAs are known with functions of gene regulations at post-transcriptional level.[Results] We herein compared the miRNA profiles of A. lumbricoides and A. suum female adults by Solexa deep sequencing combined with bioinformatics analysis and stem-loop real-time PCR. Using the A. suum genome as the reference genome, we obtained 171 and 494 miRNA candidates from A. lumbricoides and A. suum, respectively. Among which, 74 miRNAs were shared between the two taxa, 97 and 420 miRNAs were A. lumbricoides and A. suum specific. Target and function prediction revealed a significant set of targets which are related to ovarian message protein, vitellogenin and chondroitin proteoglycan of the two nematodes. Enrichment analysis revealed that the percentages of most predicted functions of the miRNA targets were similar, with some taxon specific or taxon enhanced functions, such as different target numbers, specific functions (NADH dehydrogenase and electron carrier functions), etc.[Conclusions] This study characterized comparatively the miRNAs of adult A. lumbricoides and A. suum, and the findings provide additional evidence that A. lumbricoides and A. suum represent a single species. Due to the fast evolution nature of miRNAs and the different parasitic living conditions of humans and pigs, the phenomenon above might indicate a fast evolution of miRNAs of Ascaris in humans and pigs.This work was supported in part by the International Science & Technology Cooperation Program of China (Grant No. 2013DFA31840), the Science Fund for Creative Research Groups of Gansu Province (Grant No. 1210RJIA006) to XQZ, and the China Postdoctoral Science Foundation (Grant No. 201104363) to MJX.Peer Reviewe

Experimental study on snow melting and deicing of carbon fiber heating roads considering thermal insulation conditions

The electrothermal method for snow melting and deicing in road engineering provides efficient deicing. To improve the ice melting efficiency of carbon fiber heating cables, employing extruded polystyrene foam board (XPS)、polyethylene foam cotton (PEF) as insulation materials under the carbon fiber heating wire could reduce heat transfer to the lower layers of the road structure. Road model tests were conducted under various conditions to analyze how different heat insulation conditions、environmental temperatures affect road snow melting and ice melting. The results indicate that the placement of the heat insulation layer significantly affects the temperature fluctuation range between its upper and lower layers.The ice melting rate increases by 25∼50 % compared to pavement structures with no heat insulation layer. When heat insulation material is incorporated into the road structure layer, under preheated conditions, snow with a thickness of 0.2 cm on the surface of the plate heat insulation model can completely melt within 2.5 h, reducing the effective ice-melting time by 40∼51.7 %. A comparison of the thermal performance of the two insulation materials under various conditions reveals that the XPS plate is more suitable as an insulation layer compared to other materials