Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB

ObjectivesTo identify the molecular subtypes and develop a scoring system for the tumor immune microenvironment (TIME) and prognostic features of bladder cancer (BLCA) based on the platinum-resistance-related (PRR) genes analysis while identifying P4HB as a potential therapeutic target.MethodsIn this study, we analyzed gene expression data and clinical information of 594 BLCA samples. We used unsupervised clustering to identify molecular subtypes based on the expression levels of PRR genes. Functional and pathway enrichment analyses were performed to understand the biological activities of these subtypes. We also assessed the TIME and developed a prognostic signature and scoring system. Moreover, we analyzed the efficacy of immune checkpoint inhibitors. Then we conducted real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) experiments to detect the expression level of prolyl 4-hydroxylase subunit beta (P4HB) in BLCA cell lines. Transfection of small interference ribonucleic acid (siRNA) was performed in 5637 and EJ cells to knock down P4HB, and the impact of P4HB on cellular functions was evaluated through wound-healing and transwell assays. Finally, siRNA transfection of P4HB was performed in the cisplatin-resistant T24 cell to assess its impact on the sensitivity of BLCA to platinum-based chemotherapy drugs.ResultsIn a cohort of 594 BLCA samples (TCGA-BLCA, n=406; GSE13507, n=188), 846 PRR-associated genes were identified by intersecting BLCA expression data from TCGA and GEO databases with the PRR genes from the HGSOC-Platinum database. Univariate Cox regression analysis revealed 264 PRR genes linked to BLCA prognosis. We identified three molecular subtypes (Cluster A-C) and the PRR scoring system based on PRR genes. Cluster C exhibited a better prognosis and lower immune cell infiltration compared to the other Clusters A and B. The high PRR score group was significantly associated with an immunosuppressive tumor microenvironment, poor clinical-pathological features, and a poor prognosis. Furthermore, the high PRR group showed higher expression of immune checkpoint molecules and a poorer response to immune checkpoint inhibitors than the low PRR group. The key PRR gene P4HB was highly expressed in BLCA cell lines, and cellular functional experiments in vitro indicate that P4HB may be an important factor influencing BLCA migration and invasion.ConclusionOur study demonstrates that the PRR signatures are significantly associated with clinical-pathological features, the TIME, and prognostic features. The key PRR gene, P4HB, s a biomarker for the individualized treatment of BLCA patients

Prognostic biomarker DARS2 correlated with immune infiltrates in bladder tumor

BackgroundDARS2 is a pivotal member of the Aminoacyl-tRNA synthetases family that is critical for regulating protein translation. However, the biological role of DARS2 in bladder cancer remains elusive.MethodsWe analyzed the correlation between DARS2 expression and prognosis, tumor stage, and immune infiltration in bladder cancer using The Cancer Genome Atlas (TCGA) database. We validated findings in clinical samples from The First Affiliated Hospital of Nanchang University and explored the biological functions of DARS2 using cell and animal models.ResultsWe found DARS2 to be upregulated in bladder cancer, associated with tumor progression and poor prognosis. Immune infiltration analysis suggested that DARS2 may facilitate immune evasion by modulating PD-L1. Cell and animal experiments validated that DARS2 knockdown and overexpress can inhibit or increase cancer cell proliferation, metastasis, tumorigenesis, immune escape, and PD-L1 levels.ConclusionsOur study reveals DARS2 as a potential prognostic biomarker and immunotherapy target in BLCA

Photoelectrochemical water splitting under visible light over anti-photocorrosive In2O3-coupling ZnO nanorod arrays photoanode

In2O3 quantum dots with a high crystallinity were deposited on the surface of ZnO nanorods through a chemistry bath method. The resulting In2O3-sensitizing ZnO nanorod arrays not only exhibited enhanced photoelectrochemical activity for water splitting under visible-light irradiation, but also possessed anti-photocorrosion property. The photo-induced charge-transfer property of In2O3 could be improved greatly by coupling with ZnO. This observation demonstrated that the heterojunction at the interface between In2O3 and ZnO could efficiently reduce the recombination of photo-induced electron–hole pairs and increase the lifetime of charge carriers and therefore enhance the photo-to-current efficiency of the In2O3–ZnO nanocrystalline arrays. It reveals that the heterojunction construction between two different semiconductors plays a very important role in determining the dynamic properties of their photo- generated charge carriers and their photo-to-currentconversion efficiency

Comparative Study Of Complex Network Community Structure Algorithms In network Pharmacology Analysis

Community structure is an extremely important characteristic of complex networks composed of network pharmacology. The mining of network community structure is of great importance in many fields such as biology, computer science and sociology. In recent years, for different types of large-scale complex networks, researchers had proposed many algorithms for finding community structures. This paper reviewed some of the most representative algorithms in the field of network pharmacology, and focused on the analysis of the improved algorithms based on the modularity index and the new algorithms that could reflect the level and overlap of the community. Finally, a benchmark was established to measure the quality of the community classification algorithm

Effect of correlation time of the colored noise in negative differential thermal resistance in Frenkel-Kontorova lattices

Negative differential thermal resistance (NDTR) in Frenkel-Kontorova lattices with colored noise is investigated by means of numerical calculations. The results indicate that: (i) as the system has less atoms and is symmetric, the thermal current and heat conductivity becomes bigger with the decrease of correlation time. (ii) As the system with less atoms is asymmetric, the NDTR phenomenon only exists in some specific values of correlation time. (iii) When the lattice has the same on-site potential and different lattice period, NDTR phenomenon can also occur when with colored noise bath. Our results have the implication that the correlation time plays a crucial role in the designs of thermal devices

Effect of lattice period on thermal current of Frenkel-Kontorova lattices

Effect of lattice period on thermal current of Frenkel-Kontorova (FK) lattices in the underdamped case is investigated by means of numerical calculations. The results indicate that: (i) the negative differential thermal resistance (NDTR) effect completely depends on the period of the FK lattice in the case of fixed amplitude of on-site potential. With the increment of the lattice period, the NDTR effect is gradually disappearing. (ii) For the specific lattice period (a = 0.15), the system’s symmetry greatly affects the NDTR phenomenon. The NDTR effect becomes more and more obvious with the increment of VR. (iii) If the lattice periods of the two segments of coupled FK nonlinear lattices are not equal, the NDTR phenomenon can also occur even though the on-site potential is in symmetry (VL = VR = 1). Meanwhile, with the increment of the average environmental reference temperature, the NDTR gradually disappears. Our results indicate that the lattice period of nonlinear lattices plays a crucial role in the design of thermal devices

Study On The Remote Monitoring System For Medical Insurance Prescription Of Chinese Patent Medicine

Chinese patent medicine was the preparation and integration of traditional Chinese medicine in traditional Chinese medicine. It was a continuation of traditional Chinese medicine in modern society. China's hospital information construction was at a stage of development. The implementation of the medical insurance prescription monitoring system had significantly improved the level of medical insurance service management in hospitals. Based on the Eclipse platform and MYSQL database, this paper constructed a prescription insurance monitoring system for Chinese patent medicines. A visual graph of drug monitoring and medication recording was formed to determine whether there is any unreasonable phenomenon. At the same time, auxiliary diagnosis needed to input common symptoms of disease into database. According to the search, it could respond quickly, assist doctors to diagnose and improve the speed of seeking medical treatment. Prescription management recorded the prescribed prescriptions to achieve the visualization of prescription management, and achieved maximum maintainability and operability

Negative differential thermal resistance phenomenon in the FK-

Negative differential thermal resistance (NDTR) was investigated in a system consisting of two dissimilar anharmonic lattices exemplified by Frenkel–Kontorova (FK) lattices and ϕ4 lattices (FK-ϕ4). The results indicate that: (i) For appropriate periodic on-site potentials of FK lattice, as the system is asymmetric, an NDTR phenomenon will appear. (ii) The NDTR phenomenon also depends on the quartic on-site potentials of ϕ4 lattice as the other parameters remain unchanged. With the increment of the quartic on-site potential, the NDTR phenomenon will gradually disappear. (iii) As the system is asymmetric, the averaged environmental reference temperature and coupling displacement cannot only enhance NDTR phenomenon but also regulate thermal rectifier of the system as a thermal switch. (IV) Along with an increasing atomic number of the system, the NDTR phenomenon gradually disappears. Our results indicate that the on-site potential of nonlinear lattices plays a crucial role in the design of thermal devices

Study On The Remote Monitoring System For Medical Insurance Prescription Of Chinese Patent Medicine

Chinese patent medicine was the preparation and integration of traditional Chinese medicine in traditional Chinese medicine. It was a continuation of traditional Chinese medicine in modern society. China's hospital information construction was at a stage of development. The implementation of the medical insurance prescription monitoring system had significantly improved the level of medical insurance service management in hospitals. Based on the Eclipse platform and MYSQL database, this paper constructed a prescription insurance monitoring system for Chinese patent medicines. A visual graph of drug monitoring and medication recording was formed to determine whether there is any unreasonable phenomenon. At the same time, auxiliary diagnosis needed to input common symptoms of disease into database. According to the search, it could respond quickly, assist doctors to diagnose and improve the speed of seeking medical treatment. Prescription management recorded the prescribed prescriptions to achieve the visualization of prescription management, and achieved maximum maintainability and operability