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Abstract Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein–protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS.

Abstract Ventilation door are commonly found in tunnels and other underground engineering ventilation structures, disaster periods using its explosion isolation, explosion relief, wind regulation characteristics for disaster prevention and mitigation is of great significance. This paper numerically simulates the propagation characteristics of the gas explosion shock wave in the nearby tunnel when the ventilation door are opened at different degrees, and analyzes the influence mechanism of the opening degree on the change law of the shock wave overpressure distribution in the nearby tunnel. The results show that the shock wave forms a strong turbulence area (high pressure area) on both sides in front of the ventilation door, and the area range and the overpressure value decrease with the increase of the opening degree; the ventilation door reduce the intensity of the shock wave, so that the overpressure behind the ventilation door decreases, and the smaller the opening degree, the lower the overpressure behind the ventilation door. The secondary explosion formed shock wave and the ventilation door reflected shock wave meet to form a stronger shock wave, which leads to different opening degrees of ventilation door, its before, after the roadway and after the bifurcation of the main roadway in the measured points of the overpressure change curve is different, the main difference is that the peak overpressure for the first wave or the second wave peak. The peak overpressure in the tunnel before and after the ventilation door decreases and increases respectively with the increase of the opening length, and the overall decay of the peak overpressure at 5 m and 10 m before the ventilation door is 49.56% and 4.04% respectively and only has an effect on the peak overpressure in main tunnel within 20 m from the bifurcation.

Abstract Cervical carcinoma (CC) has been associated with high morbidity, poor prognosis, and high intratumor heterogeneity. Necroptosis is the significant cellular signal pathway in tumors which may overcome tumor cells’ apoptosis resistance. To investigate the relationship between CC and necroptosis, we established a prognostic model based on necroptosis-related genes for predicting the overall survival (OS) of CC patients. The gene expression data and clinical information of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients were obtained from The Cancer Genome Atlas (TCGA). We identified 43 differentially expressed necroptosis-related genes (NRGs) in CESC by examining differential gene expression between CESC tumors and normal tissues, and 159 NRGs from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Gene ontology (GO) and KEGG enrichment analysis illustrated that the genes identified were mainly related to cell necrosis, extrinsic apoptosis, Influenza A, I − kappaB kinase/NF − kappaB, NOD − like receptor, and other signaling pathways. Subsequently, least absolute shrinkage and selection operator (LASSO) regression and univariate and multivariate Cox regression analyses were used to screen for NRGs that were correlated with patient prognosis. A prognostic signature that includes CAMK2A, CYBB, IL1A, IL1B, SLC25A5, and TICAM2 was established. Based on the prognostic model, patients were stratified into either the high-risk or low-risk subgroups with distinct survival. Receiver operating characteristic (ROC) curve analysis was used to identify the predictive accuracy of the model. In relation to different clinical variables, stratification analyses were performed to demonstrate the associations between the expression levels of the six identified NRGs and the clinical variables in CESC. Immunohistochemical (IHC) validation experiments explored abnormal expressions of these six NRGs in CESC. We also explored the relationship between risk score of this necroptosis signature and expression levels of some driver genes in TCGA CESC database and Gene Expression Omnibus (GEO) datasets. Significant relationships between the six prognostic NRGs and immune-cell infiltration, chemokines, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoints in CESC were discovered. In conclusion, we successfully constructed and validated a novel NRG signature for predicting the prognosis of CC patients and might also play a crucial role in the progression and immune microenvironment in CC.

Abstract Breast cancer (BC) is considered the second commonest human carcinoma and the most incident and mortal in the female population. Despite promising treatments for breast cancer, mortality rates of metastatic disease remain high. Gasdermin C (GSDMC) is an affiliate of the gasdermin (GSDM) family, which is involved in the process of pyroptosis. Pyroptosis is implicated in tumorigenesis, but the role of GSDMC in cancer cells is yet to be fully elucidated. In this study, we investigated the role and mechanism of GSDMC in breast cancer. We conducted a pan-cancer analysis of the expression and prognosis of GSDMC utilizing multidimensional data from The Cancer Genome Atlas (TCGA). We investigated GSDMC expression levels in 15 BC tissues and matched adjacent normal tissues by immunohistochemistry (IHC). Further verification was performed in the Gene Expression Omnibus (GEO) database. We discovered that elevated GSDMC expression was considerably linked to a worse prognosis in breast invasive carcinoma (BRCA). Next, we identified noncoding RNAs (ncRNAs) which contributing to higher expression of GSDMC by a series of expression, survival, and correlation analysis. We finally identified LINC00511/hsa-miR-573 axis to be the most promising ncRNA-associated pathways that account for GSDMC in BRCA. Furthermore, we demonstrated the significant correlations between GSDMC expression and immune infiltrates, immune checkpoints, and immune markers in BRCA. This study illustrated that ncRNAs-mediated upregulation of GSDMC linked to dismal prognosis and also exhibited a correlation with tumor immune cell infiltration in BRCA. It is anticipated to offer novel ideas for the link between pyroptosis and tumor immunotherapy.

Abstract Background Esophageal carcinoma (ESCA) is a common malignancy with a poor prognosis. Previous research has suggested that necroptosis is involved in anti-tumor immunity and promotes oncogenesis and cancer metastasis, which in turn affects tumor prognosis. However, the role of necroptosis in ESCA is unclear. This study aimed to investigate the relationships between necroptosis-related genes (NRGs) and ESCA. Methods and results The clinical data and gene expression profiles of ESCA patients were extracted from The Cancer Genome Atlas (TCGA), and 159 NRGs were screened from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We then identified 52 differentially expressed NRGs associated with ESCA and used them for further analysis. Gene ontology (GO) and KEGG functional enrichment analyses showed that these NRGs were mostly associated with the regulation of necroptosis, Influenza A, apoptosis, NOD-like receptor, and NF-Kappa B signaling pathway. Next, univariate and multivariate Cox regression and LASSO analysis were used to identify the correlation between NRGs and the prognosis of ESCA. We constructed a prognostic model to predict the prognosis of ESCA based on SLC25A5, PPIA, and TNFRSF10B; the model classified patients into high- and low-risk subgroups based on the patient’s risk score. Furthermore, the receiver operating characteristic (ROC) curve was plotted, and the model was affirmed to perform moderately well for prognostic predictions. In addition, Gene Expression Omnibus (GEO) datasets were selected to validate the applicability and prognostic value of our predictive model. Based on different clinical variables, we compared the risk scores between the subgroups of different clinical features. We also analyzed the predictive value of this model for drug sensitivity. Moreover, Immunohistochemical (IHC) validation experiments explored that these three NRGs were expressed significantly higher in ESCA tissues than in adjacent non-tumor tissues. In addition, a significant correlation was observed between the three NRGs and immune-cell infiltration and immune checkpoints in ESCA. Conclusions In summary, we successfully constructed and validated a novel necroptosis-related signature containing three genes (SLC25A5, PPIA, and TNFRSF10B) for predicting prognosis in patients with ESCA; these three genes might also play a crucial role in the progression and immune microenvironment of ESCA.

Abstract Background Lysophosphatidic acid (LPA) and its receptors play a key role in regulating cancer progression. Upregulation of LPA receptor 2 (LPAR2) plays a role in carcinogenesis; however, the exact role of LPAR2 in tumors remains elusive. This study aims to explore the correlation between LPAR2 expression with tumor prognosis and immune infiltration in pan-cancers. Materials and methods The expression of LPAR2 in pan-cancers was analyzed using the Online Cancer Microarray Database (Oncomine), Tumor Immune Estimation Resource (TIMER), and UALCAN databases. The effects of LPAR2 on the clinical prognosis in pan-cancer were examined using the Kaplan–Meier plotter (KM plotter) as well as Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Human Protein Atlas (HPA) databases. Moreover, the R software program was applied for validation of expression and prognostic value of LPAR2 in tumor patients in the Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. The relationship between the expression level of LPAR2 and the clinical and molecular criteria of head and neck squamous cell carcinoma (HNSC) and kidney renal clear cell carcinoma (KIRC) was analyzed using UALCAN, whereas the relationship between LPAR2 expression and prognosis in patients with HNSC and KIRC with different clinical characteristics was examined using the KM plotter. Furthermore, the correlation between LPAR2 expression and tumor immune infiltration was examined using TIMER. The correlation between LPAR2 expression and gene markers of tumor immune infiltrates was analyzed using TIMER and GEPIA. In addition, the cBioPortal for Cancer Genomics was used to calculate the mutations, methylations, and altered neighbor genes of LPAR2. Results The expression of LPAR2 was significantly correlated with the outcome of multiple types of cancer, especially HNSC and KIRC. Furthermore, high expression of LPAR2 was significantly associated with various immune markers in the immune cell subsets of HNSC and KIRC. Conclusions High expression of LPAR2 plays significantly different prognostic roles in HNSC and KIRC possibly owing to its association with different immune markers. LPAR2 is correlated with tumor immune cell infiltration and is a valuable prognostic biomarker for HNSC and KIRC. However, further experiments are required to validate these findings.

Our aim was to perform an initial assessment of the polymorphic patterns of the PIN1 gene in patients with coronary heart disease (CHD). The PIN1-encoded protein (Pin1) suppresses eNOS-NO signaling and may impair cardiovascular function. Blood collection, DNA extraction, PCR amplification and gene sequencing were performed for thirty CHD participants living in central China, focusing on nine single nucleotide polymorphisms (SNPs). Their genetic linkages were revealed and their allele frequencies were compared with SNP data from the NCBI. Three major linkage patterns were identified: [1.rs2287839-5.rs2233682], [3.rs2233679-4.rs1077220–8.rs2287838] and [6.rs889162-7.rs2010457], suggesting correlated involvement in CHD and possible simultaneous genetic origin in ancient times. The frequencies of six SNPs are consistent with the NCBI data, while the frequencies of three SNPs (2.rs2233678, 4.rs1077220 and 9.rs4804461) are not consistent with the NCBI. Especially, the 3.rs2233679–4.rs1077220 linkage is different from other populations worldwide and may be an interesting genetic characteristic of Chinese CHD patients. Predictably, 1.rs2287839, 2.rs2233678, 3.rs2233679 and 5.rs2233682 may be strongly associated with CHD risk, although this requires future verification. The PIN1 SNP linkages lay a new genetic foundation for discovering novel molecular mechanisms of CHD and for exploring PIN1-based targeted treatment of CHD with nitric oxide regulatory therapies in clinical practice. Resumo: O objetivo deste estudo é avaliar os polimorfismos do gene PIN1 em doentes com doença arterial coronária (DAC). A proteína codificada pelo gene PIN1 (Pin1) suprime a sinalização eNOS-NO e pode afetar a função cardiovascular. Foram incluídos 30 indivíduos com DAC, residentes na China central, a quem foi recolhido sangue, extraído e amplificado o DNA por PCR. Foram estudados nove polimorfismos de nucleótidos únicos (SNPs) do gene PIN1. As suas associações genéticas foram estudadas e as frequências de alelo foram comparadas com os dados de SNPs do NCBI. Foram identificados três grandes padrões de linkage: [1.rs2287839-5.rs2233682], [3.rs2233679-4.rs107220-8.rs2287838] e [6.rs889162-7.rs2010457], sugerindo o seu envolvimento na DAC e possível origem genética simultânea histórica. As frequências de seis dos SNPs foram consistentes com os dados do NCBI, enquanto as frequências de três dos SNPs (2.rs2233678, 4.rs1077220 e 9.rs4804461) não foram consistentes com o NCBI. Especificamente, a ligação 3.rs2233679-4.rs1077220 é diferente de outras populações mundiais e poderá constituir uma característica genética específica dos doentes chineses com DAC. Previsivelmente, 1.rs2287839, 2.rs2233678, 3.rs2233679 e 5.rs2233682 podem estar particularmente associados ao risco de DAC, requerendo validação ulterior. As ligações PIN1-SNP estabelecem uma nova base genética para a descoberta de novos mecanismos moleculares da DAC e para explorar o tratamento de precisão da DAC com medicamentos reguladores do óxido nítrico, baseado nos polimorfismos do gene PIN1.

To study the decompression effects of shaft explosion-proof door at different lifting heights, this paper designed the gas explosion testing system. Based on the test results, this paper made a numeric analysis of the change regularities of the shock wave overpressure when the shaft explosion-proof door was lifted at different heights. Finally, this paper determined the proper lifting height of the shaft explosion-proof door and put forward the active decompression concept. The research showed that (1) the shock wave overpressure at the explosion-proof door decreased in a power exponential relationship as the lifting height increased. When the lifting height increased from 0 cm to 5 cm, the peak overpressure at the explosion-proof door decreased from 36.06 kPa to 22.47 kPa, dropping by 37.7%. When it was lifted at a height of 40 cm, the overpressure dropped to 11.20 kPa and the decompression reached 68.9%. (2) The overpressure at the ventilator decreased in a power exponential relationship as the lifting height increased. When the lifting height of the explosion-proof door increased from 0 cm to 5 cm, the decompression ratio reached the maximum 18.4%. After that, the decompression effect became worse and worse. (3) The explosion-proof door could depressurize and protect the ventilator at gas explosion but with limited effects. To protect the ventilator and the explosion-proof door to the maximum, it was suggested that the pressure sensor was set up somewhere in the mine where the gas explosion is likely to occur. In this way, the explosion was sensed in time and the explosion-proof door could be actively lifted for decompression. This paper was of great guiding significance in optimizing the design of the explosion-proof door equipment, reducing the loss of gas explosion accidents as well as carrying out the emergency rescue.

In order to accurately grasp the characteristics and influencing factors of gas explosion in heading face, the mathematical model of gas explosion was determined. According to the actual size of a heading face of a coal mine, a 3D geometric model with a length of 100 m was established, and the effects of ignition energy and gas explosion equivalent on the gas explosion characteristics of the heading face were analyzed. The results show the following. (1) The mathematical models for numerical simulation of gas explosion can accurately simulate the gas explosion and its propagation process. The time-space step size has a great influence on the simulation results. The grid spacing for numerical simulation of mine gas explosion is determined to be 0.1 m and the time step length is determined to be 0.001 s. (2) The ignition energy has a limited effect on gas explosion characteristics. It only has a certain influence on the gas explosion process, but has little influence on the overpressure of shock wave. The larger the ignition energy is, the faster the explosion reaction speed is, and the maximum overpressure increases slightly. When the ignition energy increases to a certain value, the time of peak shock wave and the maximum overpressure both tend to be stable. The ignition energy has little effect on gas explosion characteristics when an explosion accident occurs underground with a large amount of gas accumulation. (3) The gas explosion equivalent has a great influence on the overpressure of gas explosion shock wave. The higher the explosion equivalent is, the greater the pressure is, and the peak value of the shock wave overpressure increases with the explosion equivalent as a power function. The research results have important guiding significance for the research and development of new technology for prevention and control of gas explosion.

Purpose: This research explores the key factors that contribute to the success of Black students in a predominantly White institution (PWI). Two measures of success are examined: cumulative grade point average (GPA) and graduation status. Design/methodology/approach: Using student-level data from a southeastern university, this research estimates education production functions using ordinary least squares regression. Findings: While the negative effect of being Black is significant for both cumulative GPA and graduation status, the effect becomes overshadowed when peer effects are added. The authors also found the critical effect of institutional support on student success. Research limitations/implications: The student-level data are restricted to a single institution over a relatively short period of time, which limits the authors' ability to analyze institution-level factors. Practical implications: This research provides a broad view of many significant factors for student success with particular highlights on the importance of encouraging Black students to utilize institutional support. Originality/value: This study is an extension of the education production function model in the field of student success. The study identified peer effects and institutional support as more powerful determinants of student success than race.

Objective: A novel genetic and molecular basis of nonalcoholic fatty liver disease (NAFLD) was explored. Study design: A 38-year-old male, who has no bad living and dietary habits, was diagnosed as NAFLD. The potential pathogenic role of Pin1 was evaluated by enzyme-linked immunosorbent (ELISA) assay and single nucleotide polymorphism (SNP) sequencing. Results: ELISA determined a six-time higher concentration of plasma Pin1 compared to our previous data. Nine PIN1 SNPs were sequenced and classified according to their NAFLD-pathogenic risks, suggesting that rs2233678 and rs2287839 may be the most important genotypes that result in Pin1 overexpression and NAFLD development. Conclusion: In summary, this work explores a novel basis for early-onset NAFLD and highlights that elevated plasma Pin1 may predict NAFLD risk at early stage. Hypothetically, inhibiting Pin1 may benefit NAFLD prevention in the future. Keywords: Nonalcoholic fatty liver disease, Early diagnosis, Pin1, Genetic basis, Plasma biomarker