Identification of potential biomarkers to differentially diagnose solid pseudopapillary tumors and pancreatic malignancies via a gene regulatory network

Additional file 1: In-degree distribution for GRN. X-axis represents the in-degree for a certain node. A node of in-degree x means that this node is regulated by a total number of x other nodes. Y-axis represents the total number of network nodes which has an in-degree of x. The red curve was the fitting to the power law distribution. (A): The in-degree distribution for sub-GRN in which only miRNAs are included as regulators and the in-degree for each node (miRNAs and protein coding genes) was calculated in this sub-GRN. The in-degree ranges from 0 to 27. (B): In-degree distribution for sub-GRN in which only TFs are included as regulators

LINC01133 can induce acquired ferroptosis resistance by enhancing the FSP1 mRNA stability through forming the LINC01133-FUS-FSP1 complex

Abstract Due to a lack of research on the critical non-coding RNAs in regulating ferroptosis, our study aimed to uncover the crucial ones involved in the process. We found that LINC01133 could make pancreatic cancer cells more resistant to ferroptosis. A higher expression of LINC01133 was associated with a higher IC50 of sorafenib in clinical samples. Furthermore, we discovered that LINC01133 induced this process through enhancing the mRNA stability of FSP1. CEBPB was the transcription factor to increase the expression of LINC01133. A higher CEBPB could also indicate a higher IC50 of sorafenib in patients with cancer. Moreover, we confirmed that LINC01133 could form a triple complex with FUS and FSP1 to increase the mRNA stability of FSP1

The Correlation of Chloride Diffusion Coefficient and Concrete Maturity Value and Its Application in Hong Kong–Zhuhai–Macao Bridge Engineering

The correlation of chloride diffusion coefficient and concrete maturity value within 56 days of curing was investigated by the chemically combined water content method, rapid chloride migration (RCM) test, and concrete maturity test. The experimental results showed that chloride diffusion coefficient of concretes decreased not only with increasing curing ages but also with increasing curing temperature, which can promote the hydration degree of cementitous materials. There is a significant correlation between the chloride diffusion coefficient of indoor cured specimens and the concrete maturity value when expressed as a power function (R2 = 0.976). In addition, the calculated values of concrete maturity for outdoor specimens, obtained using the power function, agree well with the measured values. As a result, the measured concrete maturity values can be used to predict the chloride diffusion coefficient of concrete. And then in this project, when the immersed tube tunnels were placed in seawater, the recommended value and the control values of concrete maturity were 21,064 and 13,926°C h-1, respectively. Furthermore, the ages of the tunnels placed in seawater can be appropriately adjusted by calculation when considering the external curing temperature and heat of hydration of cementitous materials

Phosphogypsum-Based Ultra-Low Basicity Cementing Material

Traditional Portland cement is widely used in the preparation of various hydraulic concrete. However, the high alkalinity produced by cement hydration threatens the survival of aquatic animals and plants. In this paper, a new eco-friendly, ultra-low alkalinity, cementitious material was prepared with industrial waste phosphogypsum, granulated ground blast slag (GGBS) and sulphoaluminate cement. When appropriate proportions are used, the pH value of the test blocks’ pore solutions at different ages were all less than 9, showing the remarkable characteristic of ultra-low alkalinity. The XRD and SEM analyses showed that the 56 d hydration products were mainly ettringite and hydrated calcium silicate, and the content of Ca(OH)2 was not detected. The new cementitious material also has the advantages of short setting time, low heat of hydration, high strength of cement mortar and the ability to fix harmful substances in phosphogypsum, such as phosphate, fluoride and Cr and Ba elements. It has a broad application prospect in the construction of island and reef construction, river restoration and so on

Influence of the Coupling Action of Flexural Load and Freezing–Thawing on the Chloride Diffusion of Marine High-Performance Concrete

The chloride diffusion of marine high-performance concrete under a couple of actions, flexural load and freezing–thawing, was investigated by a fast freezing and thawing test in NaCl solution. Concrete specimens of 100 × 100 × 515 mm were tested under bending load and 300 freeze–thaw cycles under the stress levels of 15%, 30%, and 50% of the ultimate fracture modulus. The change in the microstructure of the concrete was analyzed by SEM and MIP. The results indicated that the chloride diffusion coefficient of concrete under the coupling effect of flexural load and freezing–thawing or simple flexural load increased with the increasing in the flexural stress level, and the chloride diffusion coefficient was approximately exponential to the flexural stress level, as D = 0.8777e1.668σ for a couple of actions of flexural load and freezing–thawing, and D = 0.8336e1.3231σ for a simple flexural load. The resistance ability of concrete to chloride diffusion was reduced by the freezing–thawing procedures, the resisted ability dropped more severely under a couple of actions of flexural load and freezing–thawing than simple flexural load at the same stress level. Micro-cracks at the interfacial transition zone between the aggregate and the paste matrix in concrete was induced under a couple of actions of flexural load and freezing–thawing, which increased the average pore size and total pore volume, resulting in the modification of the pore size distribution in the concrete. The influence of a couple of actions of flexural load and freezing–thawing on the concrete was greater than that of simple flexural load

Transfer Parameter Analysis of Chloride Ingress into Concrete Based on Long-Term Exposure Tests in China’s Coastal Region

Chloride penetration resistance is one of the most important performance measures for the evaluation of the durability of concrete under a chloride environment. Due to differences in theory and experimental conditions, the durability index (chloride diffusion coefficient) obtained from laboratory accelerated migration tests cannot reflect the real process of chloride ingress into concrete in the natural environment. The difference in test methods must be considered and the transfer parameter kt should be introduced into the service life prediction model when the test results of accelerated methods are used. According to the test data of coastal exposure in South China, the attenuation rule of the chloride diffusion coefficient of different cement-based materials changed with time and was analyzed in this paper. Based on the diffusion coefficient–time curve, the theoretical natural diffusion coefficients of 28 d and 56 d were deduced, which were compared with the chloride diffusion coefficients obtained from the non-steady-state rapid migration method (RCM) at the same age. Therefore, the transfer parameter kt that expounds the relationship between concrete resistance to chloride permeability under a non-stationary electrical accelerated state and natural diffusion in the marine environment can be calculated; thus, the RCM testing index can be used to evaluate the long-term performance of the concrete structure in the marine environment. The results show that the value of kt was related to environmental conditions, test methods, and binder systems

An Integrating Approach for Genome-Wide Screening of MicroRNA Polymorphisms Mediated Drug Response Alterations

MicroRNAs (miRNAs) are a class of evolutionarily conserved small noncoding RNAs, ~22 nt in length, and found in diverse organisms and play important roles in the regulation of mRNA translation and degradation. It was shown that miRNAs were involved in many key biological processes through regulating the expression of targets. Genetic polymorphisms in miRNA target sites may alter miRNA regulation and therefore result in the alterations of the drug targets. Recent studies have demonstrated that SNPs in miRNA target sites can affect drug efficiency. However, there are still a large number of specific genetic variants related to drug efficiency that are yet to be discovered. We integrated large scale of genetic variations, drug targets, gene interaction networks, biological pathways, and seeds region of miRNA to identify miRNA polymorphisms affecting drug response. In addition, harnessing the abundant high quality biological network/pathways, we evaluated the cascade distribution of tarSNP impacts. We showed that the predictions can uncover most of the known experimentally supported cases as well as provide informative candidates complementary to existing methods/tools. Although there are several existing databases predicting the gain or loss of targeting function of miRNA mediated by SNPs, such as PolymiRTS, miRNASNP, MicroSNiPer, and MirSNP, none of them evaluated the influences of tarSNPs on drug response alterations. We developed a user-friendly online database of this approach named Mir2Drug

Image_1_Construction of disulfidptosis-based immune response prediction model with artificial intelligence and validation of the pivotal grouping oncogene c-MET in regulating T cell exhaustion.png

BackgroundGiven the lack of research on disulfidptosis, our study aimed to dissect its role in pan-cancer and explore the crosstalk between disulfidptosis and cancer immunity.MethodsBased on TCGA, ICGC, CGGA, GSE30219, GSE31210, GSE37745, GSE50081, GSE22138, GSE41613, univariate Cox regression, LASSO regression, and multivariate Cox regression were used to construct the rough gene signature based on disulfidptosis for each type of cancer. SsGSEA and Cibersort, followed by correlation analysis, were harnessed to explore the linkage between disulfidptosis and cancer immunity. Weighted correlation network analysis (WGCNA) and Machine learning were utilized to make a refined prognosis model for pan-cancer. In particular, a customized, enhanced prognosis model was made for glioma. The siRNA transfection, FACS, ELISA, etc., were employed to validate the function of c-MET.ResultsThe expression comparison of the disulfidptosis-related genes (DRGs) between tumor and nontumor tissues implied a significant difference in most cancers. The correlation between disulfidptosis and immune cell infiltration, including T cell exhaustion (Tex), was evident, especially in glioma. The 7-gene signature was constructed as the rough model for the glioma prognosis. A pan-cancer suitable DSP clustering was made and validated to predict the prognosis. Furthermore, two DSP groups were defined by machine learning to predict the survival and immune therapy response in glioma, which was validated in CGGA. PD-L1 and other immune pathways were highly enriched in the core blue gene module from WGCNA. Among them, c-MET was validated as a tumor driver gene and JAK3-STAT3-PD-L1/PD1 regulator in glioma and T cells. Specifically, the down-regulation of c-MET decreased the proportion of PD1+ CD8+ T cells.ConclusionTo summarize, we dissected the roles of DRGs in the prognosis and their relationship with immunity in pan-cancer. A general prognosis model based on machine learning was constructed for pan-cancer and validated by external datasets with a consistent result. In particular, a survival-predicting model was made specifically for patients with glioma to predict its survival and immune response to ICIs. C-MET was screened and validated for its tumor driver gene and immune regulation function (inducing t-cell exhaustion) in glioma.</p

miRNA Mediated Noise Making of 3′UTR Mutations in Cancer

Somatic mutations in 3&#8242;-untranslated regions (3&#8242;UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA&#8315;mRNA interactions. We identified 67,159 somatic mutations located in the 3&#8242;UTRs of messenger RNAs (mRNAs) which can alter miRNA&#8315;mRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change &gt; 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3&#8242;UTR mutations may play an important role in tumor development