Upregulation of Glutamic-Oxaloacetic Transaminase 1 Predicts Poor Prognosis in Acute Myeloid Leukemia

One of the key features of acute myeloid leukemia (AML), a group of very aggressive myeloid malignancies, is their strikingly heterogenous outcomes. Accurate biomarkers are needed to improve prognostic assessment. Glutamate oxaloacetate transaminase 1 (GOT1) is essential for cell proliferation and apoptosis by regulating cell's metabolic dependency on glucose. It is unclear whether the expression level of GOT1 has clinical implications in AML. Therefore, we analyzed the data of 155 AML patients with GOT1 expression information from The Cancer Genome Atlas (TCGA) database. Among them, 84 patients were treated with chemotherapy alone, while 71 received allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both treatment groups, high GOT1 expression was associated with shorter event-free survival (EFS) and overall survival (OS) (all P = 60 years, white blood cell count >= 15 x 10(9)/L, bone marrow blasts >= 70%, and DNMT3A, RUNX1 or TP53 mutations (all P <0.05); but in the allo-HSCT group, the only independent risk factor for survival was high GOT1 expression (P <0.05 for both EFS and OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the genes related to GOT1 expression were mainly concentrated in "hematopoietic cell lineage" and "leukocyte transendothelial migration" signaling pathways. Collectively, GOT1 expression may be a useful prognostic indicator in AML, especially in patients who have undergone allo-HSCT

Enhanced expression of FCER1G predicts positive prognosis in multiple myeloma

Background: Multiple myeloma (MM) is the second most common hematologic malignancy worldwide and does not have sufficient prognostic indicators. FCER1G (Fc fragment Of IgE receptor Ig) is located on chromosome 1q23.3 and is involved in the innate immunity. Early studies have shown that FCER1G participates in many immune-related pathways encompassing multiple cell types. Meanwhile, it is associated with many malignancies. However, the relationship between MM and FCER1G has not been studied. Methods: In this study, we integrated nine independent gene expression omnibus (GEO) datasets and analyzed the associations of FCER1G expression and myeloma progression, ISS stage, 1q21 amplification and survival in 2296 myeloma patients and 48 healthy donors. Results: The expression of FCER1G showed a decreasing trend with the advance of myeloma. As ISS stage and 1q21 amplification level increased, the expression of FCER1G decreased (P = 0.0012 and 0.0036, respectively). MM patients with high FCER1G expression consistently had longer EFS and OS across three large sample datasets (EFS: P = 0.0057, 0.0049, OS: P = 0.0014, 0.00065, 0.0019 and 0.0029, respectively). Meanwhile, univariate and multivariate analysis indicated that high FCER1G expression was an independent favorable prognostic factor for EFS and OS in MM patients (EFS: P = 0.006, 0.027, OS: P =0.002,0.025, respectively). Conclusions: The expression level of FCER1G negatively correlated with myeloma progression, and high FCER1G expression may be applied as a favorable biomarker in MM patients

Prognostic value of the FUT family in acute myeloid leukemia

Genetic abnormalities are more frequently viewed as prognostic markers in acute myeloid leukemia (AML) in recent years. Fucosylation, catalyzed by fucosyltransferases (FUTs), is a post-translational modification that widely exists in cancer cells. However, the expression and clinical implication of the FUT family (FUT1-11) in AML has not been investigated. From the Cancer Genome Atlas database, a total of 155 AML patients with complete clinical characteristics and FUT1-11 expression data were included in our study. In patients who received chemotherapy alone showed that high expression levels of FUT3, FUT6, and FUT7 had adverse effects on event-free survival (EFS) and overall survival (OS) (all P <0.05), whereas high FUT4 expression had favorable effects on EFS and OS (all P <0.01). However, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group, we only found a significant difference in EFS between the high and low FUT3 expression subgroups (P = 0.047), while other FUT members had no effect on survival. Multivariate analysis confirmed that high FUT4 expression was an independent favorable prognostic factor for both EFS (HR = 0.423, P = 0.001) and OS (HR = 0.398, P <0.001), whereas high FUT6 expression was an independent risk factor for both EFS (HR = 1.871, P = 0.017) and OS (HR = 1.729, P = 0.028) in patients who received chemotherapy alone. Moreover, we found that patients with low FUT4 and high FUT6 expressions had the shortest EFS and OS (P <0.05). Our study suggests that high expressions of FUT3/6/7 predict poor prognosis, high FUT4 expression indicates good prognosis in AML; FUT6 and FUT4 have the best prognosticating profile among them, but their effects could be neutralized by allo-HSCT

Up-regulation of DDIT4 predicts poor prognosis in acute myeloid leukaemia

The mammalian target of rapamycin (mTOR) inhibitor, DNA damage inducible transcript 4 (DDIT4), has inducible expression in response to various cellular stresses. In multiple malignancies, studies have shown that DDIT4 participates in tumorigenesis and impacts patient survival. We aimed to study the prognostic value of DDIT4 in acute myeloid leukaemia (AML), which is currently unclear. Firstly, The Cancer Genome Atlas was screened for AML patients with complete clinical characteristics and DDIT4 expression data. A total of 155 patients were included and stratified according to the treatment modality and the median DDIT4 expression levels. High DDIT4 expressers had shorter overall survival (OS) and event-free survival (EFS) than the low expressers among the chemotherapy-only group (all P <.001); EFS and OS were similar in the high and low DDIT4 expressers of the allogeneic haematopoietic stem cell transplantation (allo-HSCT) group. Furthermore, in the DDIT4(high) group, patients treated with allo-HSCT had longer EFS and OS than those who received chemotherapy alone (all P <.01). In the DDIT4(low) group, OS and EFS were similar in different treatment groups. Secondly, we analysed two other cytogenetically normal AML (CN-AML) cohorts derived from the Gene Expression Omnibus database, which confirmed that high DDIT4 expression was associated with poorer survival. Gene Ontology (GO) enrichment analysis showed that the genes related to DDIT4 expression were mainly concentrated in the acute and chronic myeloid leukaemia signalling pathways. Collectively, our study indicates that high DDIT4 expression may serve as a poor prognostic factor for AML, but its prognostic effects could be outweighed by allo-HSCT

High expression of chaperonin-containing TCP1 subunit 3 may induce dismal prognosis in multiple myeloma

The prognosis role of CCT3 in MM and the possible pathways it involved were studied in our research. By analyzing ten independent datasets (including 48 healthy donors, 2220 MM, 73 MGUS, and 6 PCL), CCT3 was found to express higher in MM than healthy donors, and the expression level was gradually increased from MGUS, SMM, MM to PCL (all P <0.01). By analyzing three independent datasets (GSE24080, GSE2658, and GSE4204), we found that CCT3 was a significant indicator of poor prognosis (all P <0.01). KEGG and GSEA analysis showed that CCT3 expression was associated with JAK-STAT3 pathway, Hippo signaling pathway, and WNT signaling pathway. In addition, different expressed genes analysis revealed MYC, which was one of the downstream genes regulated by JAK-STAT3 pathway, was upregulated in MM. This confirms that JAK-STAT3 signaling pathway may promote the progress of disease which was regulated by CCT3 expression. Our study revealed that CCT3 may play a supporting role at the diagnosis of myeloid, and high expression of CCT3 suggested poor prognosis in MM. CCT3 expression may promote the progression of MM mainly by regulating MYC through JAK-STAT3 signaling pathway

Prognostic role of SCAMP family in acute myeloid leukemia

Acute myeloid leukemia (AML) is a malignant disease of myeloid hematopoietic stem or progenitor cells characterized by abnormal proliferation of primary and immature myeloid cells in bone marrow and peripheral blood. Gene mutation and expression profiles can be used as prognosis predictors for different prognostic subgroups. Secretory carrier-associated membrane proteins (SCAMPs) are a multigenic family with five members and act as cell surface vectors in the post-Golgi recycling pathways in mammals. Nevertheless, the prognostic and clinical influence of SCAMP family has hardly ever been illustrated in AML. In our study, expression patterns of SCAMP family (SCAMP1-5) were analyzed in 155 AML patients which were extracted from the Cancer Genome Atlas database. In chemotherapy, only subgroup, higher SCAMP1 level was significantly associated with longer EFS and OS (all P = 0.002), and SCAMP1 was confirmed to be an independent favorable factor in un-transplanted patients by Multivariate analysis (all P <0.05). Nevertheless, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment subgroup, none of the SCAMP genes had any effect on the clinical survival. Our study found that high expression level of SCAMP1 is a favorable prognostic factor in AML, but allo-HSCT may neutralize its prognostic effect

Interface bond degradation and damage characteristics of full-length grouted rock bolt in tunnels with high temperature

Full-length grouted bolts play a crucial role in geotechnical engineering thanks to their excellent stability. However, few studies have been concerned with the degrading performance of grouted rock bolts caused by extensive and continuous heat conduction from surrounding rocks in high-geothermal tunnels buried more than 100 m (temperature from 28 °C to 100 °C). To investigate the damage mechanism, we examined the time-varying behaviors of grouted rock bolts in both constant and variable temperature curing environments and their damage due to the coupling effects of high temperature and humidity through mechanical and micro-feature tests, including uniaxial compression test, pull-out test, computed tomography (CT) scans, X-ray diffraction (XRD) test, thermogravimetric analysis (TGA), etc., and further analyzed the relationship between grout properties and anchorage capability. In order to facilitate a rapid assessment and control of the anchorage performance of anchors in different conditions, results of the interface bond degradation tests were correlated to environment parameters based on the damage model of interfacial bond stress proposed. Accordingly, a thermal hazard classification criterion for anchorage design in high-geothermal tunnels was suggested. Based on the reported results, although high temperature accelerated the early-stage hydration reaction of grouting materials, it affected the distribution and quantity of hydration products by inhibiting hydration degree, thus causing mechanical damage to the anchorage system. There was a significant positive correlation between the strength of the grouting material and the anchoring force. Influenced by the changes in grout properties, three failure patterns of rock bolts typically existed. Applying a hot-wet curing regime results in less reduction in anchorage force compared to the hot-dry curing conditions. The findings of this study would contribute to the design and investigations of grouted rock bolts in high-geothermal tunnels

Taming Charge Transport and Mechanical Properties of Conjugated Polymers with Linear Siloxane Side Chains

A series of conjugated polymers on the basis of diketopyrrolopyrrole and thienothiophene with different lengths of linear hybrid siloxane-terminal side chains were designed and synthesized. The number of silicon atoms in the side chains was 3, 5, and 7 (PTDPPTT-Si-3, PTDPPTT-Si-5, and PTDPPTT-Si-7, respectively, with two accompanying reference polymers, PTDPPTT-Ref-1 and PTDPPTT-Ref-2). Compared with PTDPPTT-Si-3, PTDPPTT-Si-5 and PTDPPTT-Si-7 had longer siloxane-terminal groups, which allowed them to maintain higher solution processability and excellent mobilities of 2.44 and 2.18 cm–2 V–1 s–1, respectively. In addition, the extended siloxane segment has high flexibility, which provides a good opportunity to improve the mechanical properties of rigid conjugated polymers. PTDPPTT-Si-7 exhibited excellent ductility and a low tensile modulus of 108 ± 21 MPa and retained 80% of its initial electrical properties under 100% stretching, indicating that long linear siloxane side chain-modified semiconductor polymers have great potential for wearable electronics. Our research provides an important guiding principle concerning the molecular engineering of semiconductor polymers with siloxane side chains

Taming Charge Transport and Mechanical Properties of Conjugated Polymers With Linear Siloxane Side Chains

A series of conjugated polymers on the basis of diketopyrrolopyrrole and thienothiophene with different lengths of linear hybrid siloxane-terminal side chains were designed and synthesized. The number of silicon atoms in the side chains was 3, 5, and 7 (PTDPPTT-Si-3, PTDPPTT-Si-5, and PTDPPTT-Si-7, respectively, with two accompanying reference polymers, PTDPPTT-Ref-1 and PTDPPTT-Ref-2). Compared with PTDPPTT-Si-3, PTDPPTT-Si-5 and PTDPPTT-Si-7 had longer siloxane-terminal groups, which allowed them to maintain higher solution processability and excellent mobilities of 2.44 and 2.18 cm–2 V–1 s–1, respectively. In addition, the extended siloxane segment has high flexibility, which provides a good opportunity to improve the mechanical properties of rigid conjugated polymers. PTDPPTT-Si-7 exhibited excellent ductility and a low tensile modulus of 108 ± 21 MPa and retained 80% of its initial electrical properties under 100% stretching, indicating that long linear siloxane side chain-modified semiconductor polymers have great potential for wearable electronics. Our research provides an important guiding principle concerning the molecular engineering of semiconductor polymers with siloxane side chains

Morphological classification method and data-driven estimation of the joint roughness coefficient by consideration of two-order asperity

The roughness of the joint surface plays a significant role in evaluating the shear strength of rock. The waviness (first-order) and unevenness (second-order) of natural joints have different effects on the characterization of joint surface roughness. To accurately quantify the influence of the two-order asperity on the joint roughness coefficient (JRC) prediction of joint surface profile curve, the optimal sampling interval of the asperity was determined through the change of the Rp{R}_{{\rm{p}}} value of the joint surface profile curve. The separation of the two-order asperity of 48 joint surface profile curves was completed at the optimal sampling interval, and morphological parameters of the asperity such as iave{i}_{{\rm{ave}}}, Rmax{R}_{{\rm{\max }}}, and Rp{R}_{{\rm{p}}} were counted from three aspects: asperity angle of the profile curve, asperity degree, and the trace length. Based on the statistical results of the morphological parameters considering the two-order asperity, the new nonlinear prediction models were proposed. The results showed that the curve slope mutation point SI = 2 mm is the optimal separation distance of the two-order asperity of the joint surface profile curve. The refined separation method that considers the waviness and unevenness of morphological parameters can characterize the detailed morphological features of the joint surface in more dimensions. The support vector regression (SVR) and random forest (RF) models that take into account a two-order asperity separated results have higher accuracy than traditional models. The prediction accuracy has improved by 7–8% in SVR model compared with SVR(SO) and RF(SO). The SVR nonlinear model that considering separation of two-orders of joint surface roughness is more suitable for the prediction of JRC