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Purpose: Patients with pancreatic cancer (PC) can be classified into various molecular subtypes and benefit from some precise therapy. Nevertheless, the interaction between metabolic and immune subtypes in the tumor microenvironment (TME) remains unknown. We hope to identify molecular subtypes related to metabolism and immunity in pancreatic cancer Methods: Unsupervised consensus clustering and ssGSEA analysis were utilized to construct molecular subtypes related to metabolism and immunity. Diverse metabolic and immune subtypes were characterized by distinct prognoses and TME. Afterward, we filtrated the overlapped genes based on the differentially expressed genes (DEGs) between the metabolic and immune subtypes by lasso regression and Cox regression, and used them to build risk score signature which led to PC patients was categorized into high- and low-risk groups. Nomogram were built to predict the survival rates of each PC patient. RT-PCR, in vitro cell proliferation assay, PC organoid, immunohistochemistry staining were used to identify key oncogenes related to PC Results: High-risk patients have a better response for various chemotherapeutic drugs in the Genomics of Drug Sensitivity in Cancer (GDSC) database. We built a nomogram with the risk group, age, and the number of positive lymph nodes to predict the survival rates of each PC patient with average 1-year, 2-year, and 3-year areas under the curve (AUCs) equal to 0.792, 0.752, and 0.751. FAM83A, KLF5, LIPH, MYEOV were up-regulated in the PC cell line and PC tissues. Knockdown of FAM83A, KLF5, LIPH, MYEOV could reduce the proliferation in the PC cell line and PC organoids Conclusion: The risk score signature based on the metabolism and immune molecular subtypes can accurately predict the prognosis and guide treatments of PC, meanwhile, the metabolism-immune biomarkers may provide novel target therapy for PC [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to examine the correlation between right posteroinferior bile duct (RPBD) angulation and the occurrence of bile duct stones in patients with hepatolithiasis. Methods: Patients presenting with hepatolithiasis in our hospital from January 2011 to July 2016 were divided into two groups according to whether their RPBD was affected by stones. A statistical analysis for the relevant factors associated with bile duct stone formation in the RPBD was performed. Results: The binary logistic regression results showed that stenosis of the right hepatic duct [odds ratio (OR): 7.313; 95% confidence interval (CI) 4.131–12.945)] and the angle of the RPBD (OR 0.896; 95%CI 0.877–0.916) were risk factors associated with the formation of RPBD stones. Further, the receiver operating characteristic curve indicated that, when the angle of the RPBD was less than 44.58°, stones were able to form more easily in the RPBD. Conclusion: The occurrence of bile duct stones is well correlated with sharp bile duct angulation. [ABSTRACT FROM AUTHOR]

Abstract—Defects in the grouting layer are hidden problems of underground engineering quality, while it plays an important role in the stability of the overall structure of the tunnel segment, the earth pressure transmission and impermeability. There is no accurate means for the detection of the grouting layer so far. As a non-destructive testing method with single detection surface, the impact-echo method is widely used in the detection of cracks, delamination, voids, etc. in concrete structures. In this paper, the impact-echo method was used to detect the grouting defect in grouting-segment structure. Combined with the finite element and the test structure, the signal was analyzed in the time-frequency domain. The results show that the finite element results are in good agreement with the experimental results and the accuracy of frequency distribution characteristics results meets the engineering needs. The time-frequency analysis can provide a foundation for the qualitative judgment of defects. [ABSTRACT FROM AUTHOR]

Water-soluble salt core materials have high bending strength at room temperature. During high-pressure casting, water-soluble salt cores must withstand high temperatures and impact loads. To obtain a composite water-soluble salt core suitable for high-pressure casting components, sodium chloride and sodium carbonate are used as base salt materials. Ceramic particles of alumina are used as reinforcement materials in the preparation of a water-soluble composite salt core with excellent high-temperature strength via gravity casting. The microstructures of the salt core and fracture surface are observed and characterized. The use of alumina to enhance the sensitivity of the binary salt cores results in a low thermal crack sensitivity coefficient. The alumina particles dispersed in the matrix prevent crack propagation. Simulation results show that sodium aluminate has strong interfacial bonding abilities with other components in the salt core, affecting its high-temperature strength. Further results confirm that sodium aluminate formation enhances the high-temperature strength of salt cores. [ABSTRACT FROM AUTHOR]

The secondary prevention trials of Alzheimer's disease (AD) require an enrichment strategy to recruit individuals with imminent cognitive decline at the preclinical stage. Previously, we demonstrated a variant neural correlates of episodic memory (EM) function in apolipoprotein E (APOE) ε4 carriers. Herein, we investigated whether this variation was associated with longitudinal EM performance. This 3-year longitudinal study included 88 normal elderly subjects with EM assessment and resting-state functional MRI data at baseline; 48 subjects (27 ε3 homozygotes and 21 ε4 carriers) underwent follow-up EM assessment. In the identified EM neural correlates, multivariable regression models examined the association between hippocampal functional connectivity (HFC) and longitudinal EM change. Independent validation was performed using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. At baseline, the EM neural correlates were characterized in the Papez circuit regions in the ε3 homozygotes, but in the sensorimotor cortex and cuneus in the ε4 carriers. Longitudinally, the ε4 carriers exhibited a negative association of the baseline HFC strength in the EM neural correlates with annual rate of EM change (R2 = 0.25, p = 0.05). This association also showed a trend in the ADNI dataset (R2 = 0.42, p = 0.06). These results indicate that hippocampal hyperconnectivity in the variant EM neural correlates is associated with imminent EM decline in ε4 carriers, which may serve as a promising enrichment strategy for secondary prevention trials of AD. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. Cell-cycle-related and expression-elevated protein in tumor (CREPT) plays an important role in the phosphorylation of RNA Pol II, and has been implicated in the development of several types of cancer. As yet, however, there have been no reports on its role in PDAC. Here, we aimed to explore the value of CREPT as a prognostic biomarker in PDAC. Methods: CREPT expression was assessed by immunohistochemistry (IHC) on a tissue microarray containing samples from 375 PDAC patients. Kaplan-Meier and Cox regression analyses were performed to explore the independent prognostic value of CREPT expression for the disease-free survival (DFS) and overall survival (OS) of PDAC patients. A Cell Counting Kit-8 (CCK8) assay was used to determine the growth rates and gemcitabine sensitivities of PDAC cells, while a Transwell assay was used to determine the migration and invasion abilities of PDAC cells. Subcutaneous xenografts were used to explore the effect of CREPT expression on tumor growth in vivo. Results: We found that CREPT is highly expressed in tumor tissues and may serve as an independent prognostic biomarker for DFS and OS of PDAC patients. In vitro assays revealed that CREPT expression promotes the proliferation, migration, invasion and gemcitabine resistance of PDAC cells, and in vivo assays showed that CREPT expression knockdown led to inhibition of PDAC tumor growth. Conclusions: We conclude that high CREPT expression enhances the proliferation, migration, invasion and gemcitabine resistance of PDAC cells. In addition, we conclude that CREPT may serve as an independent prognostic biomarker and therapeutic target for PDAC patients. [ABSTRACT FROM AUTHOR]

In this paper, the ability of the CFSv2 model to forecast the polar vortex displacements in the stratosphere of the Northern hemisphere is evaluated. We use the ERA-I reanalysis daily data of the potential vortex (pv) and the horizontal wind; vertical wind in the 430, 475, 530, and 600 K in the potential temperature field; and the temperature in the geopotential height at 50 hPa. And the 1–850 hPa isobaric surface temperature and u, v wind field daily data from the 9-month business forecast data of the Climate Forecast System Version 2 (CFSv2). The two polar vortex displacement events shift to Eurasia that occurred in Feb 2008 and Jan 2012. The results show that the polar vortex displacement events in February 2008 and January 2012 shifted toward the European region. During the polar vortex displacements, the westerly wind at 60°N latitude decreases, the temperature gradient reverses at the north polar and 60°N latitudes at 50 hPa, and a weaker stratospheric warming occurs in this process. For two of the polar vortex displacement events, the CFSv2 predictions of the start, largest, and end times of the polar vortex displacement are accurate at forecast lead times of 0 and 5 days, and the prediction results for the westerly winds and temperature gradients are also excellent. However, the CFSv2 prediction ability at forecast lead times exceeding 20 days is poor. For the polar vortex displacement event in February 2008, the CFSv2 predictions are good for the start and largest times but are not consistent with the actual situation for the end time at a forecast lead time of 10 days. The CFSv2 predictions are good for the end time but are not accurate for the start and largest times at a forecast lead time of 15 days. For the polar vortex displacement event in January 2012, the CFSv2 predictions are poor for the start, largest and end times and for the zonal wind, but are good for the temperature gradient during the displacement at forecast lead times of 10 days. The change in the polar vortex boundary and zonal wind and temperature gradients cannot be predicted at forecast lead times of 15 days. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma is prone to distant metastasis and is expected to become the second leading cause of cancer-related death. In an extremely nutrient-deficient and hypoxic environment resulting from uncontrolled growth, vascular disturbances and desmoplastic reactions, pancreatic cancer cells utilize "metabolic reprogramming" to satisfy their energy demand and support malignant behaviors such as metastasis. Notably, pancreatic cancer cells show extensive enhancement of glycolysis, including glycolytic enzyme overexpression and increased lactate production, and this is caused by mitochondrial dysfunction, cancer driver genes, specific transcription factors, a hypoxic tumor microenvironment and stromal cells, such as cancer-associated fibroblasts and tumor-associated macrophages. The metabolic switch from oxidative phosphorylation to glycolysis in pancreatic cancer cells regulates the invasion–metastasis cascade by promoting epithelial–mesenchymal transition, tumor angiogenesis and the metastatic colonization of distant organs. In addition to aerobic glycolysis, oxidative phosphorylation also plays a critical role in pancreatic cancer metastasis in ways that remain unclear. In this review, we expound on the intracellular and extracellular causes of the enhancement of glycolysis in pancreatic cancer and the strong association between glycolysis and cancer metastasis, which we expect will yield new therapeutic approaches targeting cancer metabolism. [ABSTRACT FROM AUTHOR]

The regional climate of the Tibetan Plateau (TP) was simulated by dynamically downscaling reanalysis data and the Community Climate System Model version 4 (CCSM4) and comparing trends of temperature and precipitation with gridded observations. Then, future CCSM4 projections under high and low emission scenarios were downscaled and compared with CCSM4 projections. Observations showed a marked upward trend in temperature and precipitation since 1979. The spatiotemporal distribution of temperature and precipitation in the TP were well represented by the reanalysis data. Downscaled simulations of ERA-Interim and CCSM4 were able to reproduce the spatial distribution of temperature in the TP; however, a cold bias was apparent in the central and western regions. Compared with precipitation observations, the downscaled CCSM4 simulation showed markedly different precipitation trends. Future climate projections indicated that temperatures will increase markedly in the TP, especially under the high emission RCP8.5 scenario. Under RCP4.5, both CCSM4 and the downscaled simulation projected a 1.5 °C increase in annual temperatures during 2006–2050, while under RCP8.5, the downscaled simulation projected an increase greater than 2.5 °C, and CCSM4 projected an increase of 2.0 °C. Emission scenarios had no apparent impact on projections of future precipitation. Therefore, to mitigate warming over the TP, reducing greenhouse gas emission should be a priority. [ABSTRACT FROM AUTHOR]

The garden asparagus stem blight caused by filamentous fungus Phomopsis asparagi exposes a serious threat on asparagus production globally. However, to present, we understand poorly about the molecular mechanisms of fungal pathogenicity. To facilitate functional genomics research of P. asparagi, here we developed a highly efficient and stable Agrobacterium tumefaciens-mediated transformation approach which yielded 150-200 transformants per 1 × 10 conidia. Our results indicated that 25 °C, acetosyringone concentration of 150 μmol/L, and 72 h were recommended as optimal co-cultivation conditions for the transformation. Using this transformation approach, we constructed a T-DNA insertion mutant library containing 1253 strains. Twenty randomly selected T-DNA insertion mutants were able to grow on 0.2 × PDA selective media after five successive subcultures without selective pressure, indicating that the exogenous T-DNA was stably integrated into the P. asparagi genome. We confirmed several randomly selected mutants using PCR with primers specific to the hph gene. Southern blots suggested that three out of the five selected mutants have a single T-DNA insertion. Interestingly, multiple mutant candidates with growth defects were obtained from the growth assay. Moreover, several mutants were selected for further analysis on the T-DNA flanking sequences through TAIL-PCR analysis. A sequence comparison of total junction fragments implied that the insertion of T-DNA within P. asparagi genome appeared to be a random event. The transformation technology and genetic resources developed here will facilitate studies of pathogenic mechanisms in this devastating filamentous fungal pathogen of garden asparagus. [ABSTRACT FROM AUTHOR]

Cell membrane proteins are believed to play a critical role in the pathogenesis of autoimmune diseases. However, few membrane autoantigens have been linked with Behçet's disease. Here, a cell-chip was performed to identify autoantibody target cells, and the suspected autoantigens were detected using immunoblotting. The amino acid sequences of the detected proteins were determined using LC-MALDI-TOF/TOF. Putative proteins were recombinantly expressed and purified, and a corresponding ELISA was developed and clinically validated using real clinical samples. It was found that a 36-kDa membrane protein - annexin A2 - was detected in approximately one-third of the patients' blood circulation. The immunohistochemistry results showed that annexin A2 was highly expressed in vascular endothelial cells. Moreover, vascular involvement was significantly higher in the anti-annexin A2 antibody-positive group versus the anti-annexin A2 antibody-negative group among all the clinical samples analyzed, indicating that annexin A2 is a novel endothelial cell membrane antigen involved in Behçet's disease. [ABSTRACT FROM AUTHOR]