Pan-cancer analysis identifies EMC6 as a potential target for lung adenocarcinoma.

Endoplasmic reticulum membrane protein complex subunit 6 (EMC6) plays an important function in both physiological and pathological states of cells. Nevertheless, there are few studies focused on the role of EMC6 in tumors. At first, we performed a series of bioinformatics analyses on 33 kinds of cancers, including differential expression analysis, tumor mutational burden analysis, prognostic analysis, and clinicopathological staging analysis. Then, we corroborated the important role of EMC6 in lung cancer by cytological and in vivo experiments. We found that the reduction of EMC6 expression did effectively inhibit the proliferation, invasion, and metastasis of A549. Finally, EMC6 is indeed involved in the regulation of ferroptosis, cuproptosis, and immune response in LUAD. In a word, our study not only comprehensively analyzed the functional mechanisms of EMC6 in all cancers but also validated the regulatory role of EMC6 in lung cancer for the first time.

Recent Advancements of Monotherapy, Combination, and Sequential Treatment of EGFR/ALK-TKIs and ICIs in Non-Small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths with high morbidity and mortality. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 85% of all cases. Fortunately, the development of molecular oncology provides a promising and effective therapeutic strategy for lung cancers, including specific gene mutations/translocations and immune checkpoints, with epidermal growth factor receptor (EGFR) common mutations first and anaplastic lymphoma kinase (ALK) translocations later as the targeted therapy and immune checkpoint inhibitors (ICIs) as immunotherapy. This review summarized the recent therapy advancements of TKIs and ICIs in NSCLC and focused on the clinical effect of combination or sequential treatment so as to provide the effective advice for the treatment of NSCLC.

MiR-323a regulates ErbB3/EGFR and blocks gefitinib resistance acquisition in colorectal cancer.

The rapid onset of resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) limits its clinical utility in colorectal cancer (CRC) patients, and pan-erb-b2 receptor tyrosine kinase (ErbB) treatment strategy may be the alternative solution. The aim of this study was to develop a possible microRNA multi-ErbB treatment strategy to overcome EGFR-TKI resistance. We detect the receptor tyrosine kinase activity in gefitinib-resistant colorectal cancer cells, ErbB3/EGFR is significantly activated and provides a potential multi-ErbB treatment target. MiR-323a-3p, a tumor suppressor, could target both ErbB3 and EGFR directly. Apoptosis is the miR-323a-3p inducing main biological process by functional enrichment analysis, and The EGFR and ErbB signaling are the miR-323a-3p inducing main pathway by KEGG analysis. MiR-323a-3p promotes CRC cells apoptosis by targeting ErbB3-phosphoinositide 3-kinases (PI3K)/PKB protein kinase (Akt)/glycogen synthase kinase 3 beta (GSK3ß)/EGFR-extracellular regulated MAP kinase (Erk1/2) signaling directly. And miR-323a-3p, as a multi-ErbBs inhibitor, increase gefitinib sensitivity of the primary cell culture from combination miR-323a-3p and gefitinib treated subcutaneous tumors. MiR-323a-3p reverses ErbB3/EGFR signaling activation in gefitinib-resistant CRC cell lines and blocks acquired gefitinib resistance.

Cardiovascular syphilis treated with transcatheter aortic valve replacement.

Cardiovascular syphilis presented with concomitant aortic regurgitation (AR) and left coronary ostial stenosis is rare, usually treated with on-pump aortic valve replacement and coronary artery bypass graft. We report a critical case of AR and left coronary ostial stenosis due to cardiovascular syphilis treated with emergent salvage transcatheter aortic valve replacement and percutaneous coronary intervention.

Graphene oxide enhanced the endocrine disrupting effects of bisphenol A in adult male zebrafish: Integrated deep learning and metabolomics studies.

In our previous studies, it was found that graphene oxide (GO) reduced the endocrine disruption of bisphenol A (BPA) in zebrafish embryo and larvae, but through different mechanisms. In this study, adult male zebrafish were selected to further understand the interactions between GO and BPA considering that adult zebrafish have different uptake pathways and metabolism from embryo and larvae. BPA was predicted to bind with the estrogen receptor α (ERα) with a probability of 98.1% by training a directed-message passing deep neural network model, and was confirmed by molecular docking analysis. The results were in accordance with the significantly increased vitellogenin (VTG) and estradiol (E2) levels, while decreased testosterone (T) and follicle-stimulating hormone (FSH) levels in the adult male zebrafish after 7 d exposure to 500 µg/L BPA. Compared to BPA single exposure group, the presence of GO led to significantly lower T and FSH levels and fewer spermatozoa, indicating that GO enhanced the endocrine disruption effects of BPA in the adult zebrafish. Metabolomics analysis revealed that 5 µg/L BPA could elicit changes in the metabolome, and the responses were correlated with BPA concentrations. Metabolic pathway analysis revealed more disturbance was caused by the mixture of GO and BPA compared to BPA alone, including three additional pathways and stronger perturbations on carbohydrate, lipid, and amino acid metabolism, fortifying that GO exaggerated the toxic effects of BPA. This was opposite to the depression effect observed in zebrafish embryo and larvae, magnifying that the joint effects of exposure to nanomaterials and endocrine disrupting chemicals are relevant to the life stages of organisms.

MiR-103a promotes tumour growth and influences glucose metabolism in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common and high-mortality cancer worldwide. Numerous microRNAs have crucial roles in the progression of different cancers. However, identifying the important microRNAs and the target biological function of the microRNA in HCC progression is difficult. In this study, we selected highly expressed microRNAs with different read counts as candidate microRNAs and then tested whether the microRNAs were differentially expressed in HCC tumour tissues, and we found that their expression was related to the HCC prognosis. Then, we investigated the effects of microRNAs on the cell growth and mobility of HCC using a real-time cell analyser (RTCA), colony formation assay and subcutaneous xenograft models. We further used deep-sequencing technology and bioinformatic analyses to evaluate the main functions of the microRNAs. We found that miR-103a was one of the most highly expressed microRNAs in HCC tissues and that it was upregulated in HCC tissue compared with the controls. In addition, high miR-103a expression was associated with poor patient prognosis, and its overexpression promoted HCC cell growth and mobility. A functional enrichment analysis showed that miR-103a mainly promoted glucose metabolism and inhibited cell death. We validated this analysis, and the data showed that miR-103a promoted glucose metabolism-likely function and directly inhibited cell death via ATP11A and EIF5. Therefore, our study revealed that miR-103a may act as a key mediator in HCC progression.

New insights into the enhanced transport of uncoated and polyvinylpyrrolidone-coated silver nanoparticles in saturated porous media by dissolved black carbons.

Silver nanoparticles (AgNPs) are among the most applied nanomaterials and have great potential to be present in the environment. Dissolved black carbon (DBC) is ubiquitous in soil as a result of large-scale application of biomass-derived black carbon as soil amendments, while its impacts on the transport of AgNPs remain unclear. In this study, two DBCs with different functional groups were prepared at 300 and 500 °C (DBC300 and DBC500), and their impacts on the transport of uncoated AgNPs (Bare-AgNP) and polyvinylpyrrolidone-coated AgNPs (PVP-AgNP) in saturated quartz sand were investigated. The transport of PVP-AgNP was much higher than Bare-AgNP under the same conditions because of the increased steric hindrance provided by PVP surface coating. The transport of two kinds of AgNPs was both enhanced by the DBCs under all the experimental conditions. DBC500 displayed a stronger enhancement effect than DBC300 on PVP-AgNP transport, but DBC300 facilitated the migration of Bare-AgNP more significantly than DBC500. The higher aromaticity and stronger hydrophobicity of DBC500 drove it to be adsorbed on the surface of PVP-AgNP, thus providing stronger steric hindrance and promotion effect on PVP-AgNP transport. However, DBC300 contained surface sulfhydryl groups, which bound with the Bare-AgNP tightly, therefore it greatly promoted Bare-AgNP transport via enhanced steric hindrance. (X)DLVO calculations indicated DBCs generally increased the energy barrier between the AgNPs and sand grains. The results shed light on the vital roles of both the properties of AgNPs and DBCs on the fate and environmental behaviors of silver nanomaterials in complex environments.

Obg-Like ATPase 1 Enhances Chemoresistance of Breast Cancer via Activation of TGF-ß/Smad Axis Cascades.

Understanding the molecular mechanism of drug resistance helps to identify an effective target for breast cancer therapy. In this study we investigated the regulatory role of Obg-like ATPase 1 which is involved in multiple uses of drug resistance against breast cancer. Paclitaxel resistant cell line (MCF-7-PTR) was developed by a continuous increasing paclitaxel concentration. MTT assay was used to validate either acquired resistant or OLA1 modified cell lines. qRT-PCR, western blotting, apoptosis, and cell cycle assays were executed to evaluate gene and protein expression in cell lines. A series of in vitro assays was performed in the cells with RNAi-mediated knockdown to expound the regulatory function of OLA1 in breast cancer. We demonstrated that OLA1 was highly correlated with either acquired or intrinsic resistance of breast cancer. Further study showed that escalated expression of OLA1 promoted the EMT process in tumor cells through TGF-ß/Smad signaling cascades, resulting in the enhanced expression of anti-apoptosis-related proteins (cleaved caspase3, Bax, Bcl-2) and the strengthening depolymerization of microtubules in tumor cells. Our findings revealed that OLA1 enhanced the anti-apoptotic ability and elucidated a regulatory role of OLA1 in promoting chemotherapy resistance of breast cancer. Chemo-sensitivity of the disease can be thus enhanced significantly by knocked down OLA1, which led to the inactivation of the TGF-ß/Smad signaling cascades, polymerized microtubules, and promoted cell apoptosis. Our data suggest that OLA1 may be developed as a potential target to improve chemotherapy of patients with breast cancer.

Metabolomics Reveals Antioxidant Stress Responses of Wheat (Triticum aestivum L.) Exposed to Chlorinated Organophosphate Esters.

In this study, wheat (Triticum aestivum L.) was exposed to three of the most typical chlorinated organophosphate esters (OPEs), which are widely present in farmland soil, at environmental concentrations to assess their accumulation, disruption on metabolism, and oxidative stress in wheat. The three OPEs accumulated distinctly in the root and then translocated to the shoot. After exposure for 7 days, the content of chlorophyll b decreased, while the levels of carotenoid and activities of antioxidases, malonaldehyde, and reactive oxygen species increased significantly in both the root and shoot, indicating that the target OPEs caused significant oxidative stresses and affected photosynthesis in wheat. Untargeted metabolomics revealed concentration- and species-dependent metabolic responses of the three OPEs. Saccharides were downregulated, which might be due to the reduced photosynthesis activities. On the other hand, the chlorinated OPEs induced increases in respiration and antioxidative metabolites, revealing that the antioxidant system of wheat was active in scavenging ROS. The disturbance of tris(1,3-dichloro-2-propyl)phosphate on the metabolisms in wheat tissues was the strongest. These results contribute to the food safety and crop quality assessment of chlorinated OPEs and clarify the underlying mechanisms of their phytotoxicities.

What causes growth of global greenhouse gas emissions? Evidence from 40 countries.

With the growing attention on global warming, understanding the main drivers of greenhouse gas (GHG) emissions is important. This paper investigated the contribution of intrinsic reasons for consumption-based GHG emissions growth using structural decomposition analysis based on world input-output database from 1995 to 2009. The drivers are decomposed into five sub-effects at both country-level and industry-level. The results are as follows: (1) The rapid global economic growth is the dominating driving force. However, a decreasing emission intensity caused by the improvement of energy efficiency and technology innovation can contribute significantly to emission reduction; (2) Key factors contributing to GHG emissions vary in different country groups. The investment effects in developing countries are overwhelming those in developed countries. Instead, the net export effects in developed countries are greater than them in developing countries, which means that developing countries are becoming pollution haven; (3) China and India are still the key contributors of CO2 growth and CH4 growth. In developing countries, the total effects of N2O emissions changes are positive, which is mainly because agriculture plays an important role in these countries; (4) Cluster analysis depicts the relationship between growth of GHG emissions and gross domestic outputs in different countries.