TPD52L2 as a potential prognostic and immunotherapy biomarker in clear cell renal cell carcinoma

BackgroundTumor Protein D52-Like 2 (TPD52L2) is a tumor-associated protein that participates in B-cell differentiation. However, the role of TPD52L2 in the pathological process of clear cell renal cell carcinoma (ccRCC) is unclear.MethodsMultiple omics data of ccRCC samples were obtained from public databases, and 5 pairs of ccRCC tissue samples were collected from the operating room. Wilcox, chi-square test, Kaplan-Meier method, receiver operating characteristic curve, regression analysis, meta-analysis, and correlation analysis were used to clarify the relationship of TPD52L2 with clinical features, prognosis, and immune microenvironment. Functional enrichment analysis was performed to reveal the potential pathways in which TPD52L2 participates in the progression of ccRCC. The siRNA technique was used to knockdown in the expression level of TPD52L2 in 786-O cells to verify its effect on ccRCC progression.ResultsFirst, TPD52L2 was found to be upregulated in ccRCC at both mRNA and protein levels. Second, TPD52L2 was significantly associated with poor prognosis and served as an independent prognostic factor. Moreover, TPD52L2 expression was regulated by DNA methylation, and some methylation sites were associated with ccRCC prognosis. Third, TPD52L2 overexpression may participate in the pathological process through various signaling pathways such as cytokine-cytokine receptor interactions, PI3K-Akt, IL-17, Wnt, Hippo signaling pathway, and ECM-receptor interactions. Interestingly, TPD52L2 expression level was also closely related to the abundance of various immune cells, immune checkpoint expression, and TMB. Finally, in vitro experiments confirmed that knocking down TPD52L2 can inhibit the proliferation, migration, and invasion abilities of ccRCC cells.ConclusionThis study for the first time revealed the upregulation of TPD52L2 expression in ccRCC, which is closely associated with poor prognosis of patients and is a potentially valuable therapeutic and efficacy assessment target for immunotherapy

Exploring the relationship between abnormally high expression of NUP205 and the clinicopathological characteristics, immune microenvironment, and prognostic value of lower-grade glioma

Nuclear pore complex (NPC) is a major transport pivot for nucleocytoplasmic molecule exchange. Nucleoporin 205 (NUP205)—a main component of NPC—plays a key regulatory role in tumor cell proliferation; however, few reports document its effect on the pathological progression of lower-grade glioma (LGG). Therefore, we conducted an integrated analysis using 906 samples from multiple public databases to explore the effects of NUP205 on the prognosis, clinicopathological characteristics, regulatory mechanism, and tumor immune microenvironment (TIME) formation in LGG. First, multiple methods consistently showed that the mRNA and protein expression levels of NUP205 were higher in LGG tumor tissue than in normal brain tissue. This increased expression was mainly noted in the higher WHO Grade, IDH-wild type, and 1p19q non-codeleted type. Second, various survival analysis methods showed that the highly expressed NUP205 was an independent risk indicator that led to reduced survival time of patients with LGG. Third, GSEA analysis showed that NUP205 regulated the pathological progress of LGG via the cell cycle, notch signaling pathway, and aminoacyl-tRNA biosynthesis. Ultimately, immune correlation analysis suggested that high NUP205 expression was positively correlated with the infiltration of multiple immune cells, particularly M2 macrophages, and was positively correlated with eight immune checkpoints, particularly PD-L1. Collectively, this study documented the pathogenicity of NUP205 in LGG for the first time, expanding our understanding of its molecular function. Furthermore, this study highlighted the potential value of NUP205 as a target of anti-LGG immunotherapy

TRPV1 Activation Attenuates High-Salt Diet-Induced Cardiac Hypertrophy and Fibrosis through PPAR- δ

High-salt diet-induced cardiac hypertrophy and fibrosis are associated with increased reactive oxygen species production. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, exerts a protective role in cardiac remodeling that resulted from myocardial infarction, and peroxisome proliferation-activated receptors δ (PPAR-δ) play an important role in metabolic myocardium remodeling. However, it remains unknown whether activation of TRPV1 could alleviate cardiac hypertrophy and fibrosis and the effect of cross-talk between TRPV1 and PPAR-δ on suppressing high-salt diet-generated oxidative stress. In this study, high-salt diet-induced cardiac hypertrophy and fibrosis are characterized by significant enhancement of HW/BW%, LVEDD, and LVESD, decreased FS and EF, and increased collagen deposition. These alterations were associated with downregulation of PPAR-δ, UCP2 expression, upregulation of iNOS production, and increased oxidative/nitrotyrosine stress. These adverse effects of long-term high-salt diet were attenuated by chronic treatment with capsaicin. However, this effect of capsaicin was absent in TRPV1−/− mice on a high-salt diet. Our finding suggests that chronic dietary capsaicin consumption attenuates long-term high-salt diet-induced cardiac hypertrophy and fibrosis. This benefit effect is likely to be caused by TRPV1 mediated upregulation of PPAR-δ expression

Membrane-associated signaling and sensing in Rhizobium etli - Analysisof c-di-GMP-related proteins and the osmoprotective Opp ABC transporter

The Alpha-proteobacterium Rhizobium etli is a soil bacterium able to establish root nodules in a symbiotic interaction with the common bean plant Phaseolus vulgaris. Within the root nodules, R. etli reduces atmospheric nitrogen gas to ammonia which can be assimilated by the plant. In return, the plant provides R. etli with carbon nutrients during the symbiosis. Besides having a symbiotic relationship with the plant, R. etli encounters different environmental stresses when living in the soil. To adapt to the unfavorable conditions either in the symbiotic root nodules or in the free-living state, R. etli has evolved sophisticated strategies. In this dissertation, we investigated two systems for their involvement in symbiosis and free-living stress survival, i.e. cyclic di-GMP mediated signaling pathways and an ATP binding cassette (ABC) transport system in R. etli. First, we systematically analyzed the presence of c-di-GMP related proteins in different rhizobial species and specifically focused on dissecting the functional and transcriptional profiles of two c-di-GMP related proteins in R. etli. In order to examine the distributions of c-di-GMP metabolizing proteins and their domain arrangement in the genomes of six rhizobial type species, we aligned the c-di-GMP proteins from online databases with the known enzymatically active c-di-GMP proteins and then compiled an inventory of c-di-GMP related proteins in these rhizobial species. We found that c-di-GMP signaling is prevalent in rhizobia, while the degree to which different rhizobial species rely on c-di-GMP signaling might vary. In addition, we identified many c-di-GMP metabolizing proteins that possess degenerate GGDEF or EAL domains in these rhizobial species. Secondly, we selected two c-di-GMP related genes, cdgA and cdgB, located on the symbiotic plasmid of R. etli, for further investigation of the functional roles and expression profiles during symbiosis and free-living conditions. Inactivation of these two genes did not affect R. etli symbiotic phenotypes (e.g. plant root colonization and nitrogen fixation ability) nor exopolysaccharides production, biofilm formation and motility. We confirmed that the proteins encoded both by cdgA and cdgB are bifunctional proteins with diguanylate cyclase (DGC) and phosphodiesterase (PDE) activities. Additionally, by using gusA as reporter, we found that cdgB is significantly expressed during plant root colonization as well as in the free-living state, while cdgA expression is low in the free-living state and undetectable on the root surface. Furthermore, we revealed that the stringent response alarmone (p)ppGpp inhibits expression of both cdgA and cdgB. Secondly, we characterized a novel ABC oligopeptide transporter designated the Opp transporter in R. etli. Firstly, we found that the Opp transporter is essential for establishing effective nitrogen fixation during the R. etli-P. vulgaris symbiosis. Microscopic observation of bacteroids morphology of opp mutants demonstrated that the Opp transporter is crucial for bacteroid development. Secondly, by performing growth tests of opp mutants under high salinity condition, we proved that the Opp transporter is involved in protection of R. etli cells against hyper-osmotic stress in the free-living state. However, expression of opp genes is not induced under hyper-osmotic conditions. Thirdly, we found that R. etli opp mutants displayed increased sensitivity to cell-envelope damaging agents. This effect was reversed in the presence of divalent cations, which are known to stabilize the cell envelope. In agreement with this observation, fatty acid composition differed between opp mutants and wild type. We therefore propose that the Opp transporter is required for maintenance of the structural integrity of the cell envelope of R. etli and fulfills an essential role in bacteroid differentiation.status: publishe

Extraction of Temperature-Dependent Thermoelectric Material Parameters of a Thermoelectric Cooler by the Non-Linear Least Squares Method

This paper presents a method of extracting temperature-dependent parameters of thermoelectric material from the operating conditions of thermoelectric cooler (TEC). Based on the finite element method of calculating TEC’s performance, non-linear least squares method is used for extracting temperature-dependent material parameters including the seebeck coefficient, electrical resistivity and thermal conductivity (α, ρ, κ) as operating current, thermal load and hot end temperature are taken as inputs and cooling temperature is taken as output. To further improve the voltage calculation accuracy, the electric resistance error factor which includes electrical contact resistance and the calculation model error is extracted with the voltage being output on the basis of extracted material parameters. The cooling temperature and voltage of another TEC with the same thermoelectric material are recalculated by the extracted parameters and the exact parameters provided by manufacturer respectively. Compared with the experimental results, the extracted material parameters have the advantages of high accuracy, wide application ranges and easily implementing in evaluating TECs’ performance

Experimental Study of Extracting Weak Infrared Signals of Rock Induced by Cyclic Loading under the Strong Interference Background

To understand the possibility of monitoring the crustal stress and tectonic activities via satellite remote sensing technology, an experimental study focused on the thermal infrared variation was performed for cyclic loaded rock in the outdoor condition with two types of strong interference background. The stress-induced infrared radiation was extracted using wavelet analysis. The results showed that due to the significant effect of the ambient temperature, the weak stress-induced infrared signal was indistinguishable from the original infrared radiation. However, after wavelet decomposition, the infrared radiation concurrent with the change in stress became clear, and the correlation coefficient with the stress increased significantly with the value of 0.91 after decomposition. Additionally, the amplitude of the extracted stress-induced infrared signal was close to the theoretical result, indicating that the wavelet analysis method can extract the weak infrared signals induced by cyclic loading in the background of strong interference to some degree. The results provide an experimental basis and ideas for monitoring crustal stress and tectonic activities using thermal infrared remote sensing

Experimental Study of the Thermal Infrared Emissivity Variation of Loaded Rock and Its Significance

Previous studies have shown that thermal infrared radiation (TIR) changes with stress for loaded rocks. TIR changes were mainly attributed to temperature change without considering the change in surface emissivity. And it remains unclear whether there was a change in emissivity during the rock loading process. Therefore, based on the spectral radiance observations in this paper, an experimental study involving the emissivity variation in the 8.0–13.0 μm range for elastic loaded quartz sandstone under outdoor conditions was conducted. The experiments yield the following results. First, a variation in the stress condition led to the emissivity change in addition to the temperature change. The spectral radiance change was the combined result of the temperature changes and emissivity changes. Second, the emissivity changes linearly with the stress change, and the amplitude is relatively large in the 8.0–10.0 μm range. The waveband features of emissivity variation are the main factor leading to the waveband features of stress-induced radiance change. Third, the explanations for the changes in temperature and emissivity during loading process are analyzed. And the significance and difficulty for further satellite remote sensing purpose is discussed. The experimental results provide an experimental foundation for crustal stress field monitoring