Exploring a ferroptosis and oxidative stress-based prognostic model for clear cell renal cell carcinoma

BackgroundFerroptosis is a newly defined cell death process triggered by increased iron load and tremendous lipid reactive oxygen species (ROS). Oxidative stress-related ferroptosis is of great important to the occurrence and progression of clear cell renal cell carcinoma (ccRCC), which is particularly susceptibility to ferroptosis agonist. Therefore, exploring the molecular features of ferroptosis and oxidative stress might guide the clinical treatment and prognosis prediction for ccRCC patients.MethodsThe differentially expressed ferroptosis and oxidative stress-associated genes (FPTOSs) between normal renal and ccRCC tissues were identified based on The Cancer Genome Atlas (TCGA) database, and those with prognostic significances were applied to develop a prognostic model and a risk scoring system (FPTOS_score). The clinical parameter, miRNA regulation, tumor mutation burden (TMB), immune cell infiltration, immunotherapy response, and drug susceptibility between two FPTOS-based risk stratifications were determined.ResultsWe have identified 5 prognosis-associated FPTOSs (ACADSB, CDCA3, CHAC1, MYCN, and TFAP2A), and developed a reliable FPTOS_socre system to distinguish patients into low- and high-risk groups. The findings implied that patients from the high-risk group performed poor prognoses, even after stratified analysis of various clinical parameters. A total of 30 miRNA-FPTOS regulatory pairs were recognized to identify the possible molecular mechanisms. Meanwhile, patients from the high-risk group exhibited higher TMB levels than those from the low-risk groups, and the predominant mutated driver genes were VHL, PBRM1 and TTN in both groups. The main infiltrating immune cells of high- and low-risk groups were CD8+ T cells and resting mast cells, respectively, and patients from the high-risk groups showed preferable drug responsiveness to anti-PD-1 immunotherapy. Eventually, potential sensitive drugs (cisplatin, BI-D1870, and docetaxel) and their enrichment pathways were identified to guide the treatment of ccRCC patients with high-risk.ConclusionOur study comprehensively analyzed the expression profiles of FPTOSs and constructed a scoring system with considerable prognostic value, which would supply novel insights into the personalized treatment strategies and prognostic evaluation of ccRCC patient

Effect of pore structure on slippage effect in unsaturated tight formation using pore network model

ACKNOWLEDGMENTS We acknowledge the Beijing Natural Science Foundation of China (No. 2204093), Science Foundation of China University of Petroleum, Beijing (No.2462018YJRC033) and financial support from China Scholarship Council ((No. 201906440134)Peer reviewedPostprin

Microstructure and mechanical properties of aluminum-steel dissimilar metal welded using arc and friction stir hybrid welding

In this study, arc and friction stir hybrid welding (AFSHW) was proposed to weld aluminum-steel dissimilar metals in attempt to realize high quality joining. Firstly, an interlayer was produced on galvanized steel by using bypass current-metal inert gas welding (BC-MIG), and then an aluminium plate was jointed via Friction stir lap welding (FSLW). The effects of tool pin length and FSLW times on the microstructure and mechanical properties of dissimilar joints were fully investigated by means of Optical Microscopy (OM), Scanning Electron Microscope (SEM), Electron Backscatter Diffraction (EBSD), and mechanical testing. The results show that as pin length increased, joint strength tended to increase and then decrease, and the tensile failure partially occurred at aluminium base metal. However, with additional number of FSLW, joint strength would be reduced, which was attributed to attenuated dislocation density and strain concertation in dissimilar joint. The research outcomes will provide a new welding method to obtain sound Al-Fe dissimilar metal joint, and benefit to a better understanding of Al-Fe joining mechanism

Mitigation of thermal distortion in wire arc additively manufactured Ti6Al4V part using active interpass cooling

In this study, active interpass cooling using compressed CO2 was innovatively employed in the wire arc additively manufactured Ti6Al4V process with the aim of mitigating part distortion. A comparative analysis between simulation and experimental results was performed to explore the effects of active interpass cooling on the thermal behaviours, geometric features and distortion levels of deposit. The results show that active interpass cooling with CO2 gas is an effective means of reducing Wire arc additive manufacturing (WAAM)-part distortion by increasing heat dissipation and reducing heat accumulation within the deposition. It can contribute to a maximum reduction of 81% in longitudinal distortion and 69% in transverse distortion for the wall structures produced in this study. Compared to the cooling gas flow rate, cooling time alternation is more effective in mitigating WAAM-part distortion due to more effective heat dissipation per unit time. The findings reveal that using active interpass cooling in WAAM can offer significant cost and build-time savings, as well as providing conditions for the improvement of WAAM-part quality

Identification of the Functions and Prognostic Values of RNA Binding Proteins in Bladder Cancer

Post-transcriptional regulation plays a leading role in gene regulation and RNA binding proteins (RBPs) are the most important posttranscriptional regulatory protein. RBPs had been found to be abnormally expressed in a variety of tumors and is closely related to its occurrence and progression. However, the exact mechanism of RBPs in bladder cancer (BC) is unknown. We downloaded transcriptomic data of BC from the Cancer Genome Atlas (TCGA) database and used bioinformatics techniques for subsequent analysis. A total of 116 differentially expressed RBPs were selected, among which 61 were up-regulated and 55 were down-regulated. We then identified 12 prognostic RBPs including CTIF, CTU1, DARS2, ENOX1, IGF2BP2, LIN28A, MTG1, NOVA1, PPARGC1B, RBMS3, TDRD1, and ZNF106, and constructed a prognostic risk score model. Based on this model we found that patients in the high-risk group had poorer overall survival (P < 0.001), and the area under the receiver operator characteristic curve for this model was 0.677 for 1 year, 0.697 for 3 years, and 0.709 for 5 years. Next, we drew a nomogram based on the risk score and other clinical variables, which showed better predictive performance. Our findings contribute to a better understanding of the pathogenesis, progression and metastasis of BC. The model of these 12 genes has good predictive value and may have good prospects for improving clinical treatment regimens and patient prognosis

Development of an Individualized Ubiquitin Prognostic Signature for Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is a common tumor type in genitourinary system and has a poor prognosis. Ubiquitin dependent modification systems have been reported in a variety of malignancies and have influenced tumor genesis and progression. However, the molecular characteristics and prognostic value of ubiquitin in ccRCC have not been systematically reported. In our study, 204 differentially expressed ubiquitin related genes (URGs) were identified from The Cancer Genome Atlas (TCGA) cohort, including 141 up-regulated and 63 down-regulated URGs. A total of seven prognostic related URGs (CDCA3, CHFR, CORO6, RNF175, TRIM72, VAV3, and WDR72) were identified by Cox regression analysis of differential URGs and used to construct a prognostic signature. Kaplan-Meier analysis confirmed that high-risk patients had a worse prognosis (P = 1.11e-16), and the predicted area under the receiver operating characteristic (ROC) curves were 0.735 at 1 year, 0.702 at 3 years, and 0.744 at 5 years, showing good prediction accuracy. Stratified analysis showed that the URGs-based prognostic signature could be used to evaluate tumor progression in ccRCC. Further analysis confirmed that the signature is an independent prognostic factor related to the prognosis of ccRCC patients, which may help to reveal the molecular mechanism of ccRCC and provide potential diagnostic and prognostic markers for ccRCC

Quality improvement in wire arc additive manufacturing

In recent years, significant progress has been made in the development of the Wire Arc Additive Manufacturing (WAAM) processes due to its economically produced large-scale metal components with relatively high deposition rate. As WAAM has evolved, a wide range of materials have become associated with the processes and applications. Today, producing high-quality WAAM products and improving their potential service life are still a challenge. This dissertation focuses primarily on critical issues and methodologies to improve quality performance of component fabricated by WAAM technique. The research was the first attempt to study the WAAM process from complex thermal behaviour point of view. It is found that due to the influences of thermal accumulation, the interlayer’s surface oxidation, bead geometry, microstructural evolution, grain size, and crystalline phase vary along the building direction of the as-fabricated wall, which creates variations in arc shape, metal transfer behaviour, mechanical properties and fracture features. Additionally, the corrosion behaviour within the WAAM-processed part is anisotropic due to corresponding anisotropy in microstructure, phase structure, grain size and orientation. The research provides a better understanding of the effects of heat accumulation behaviour on deposition stability and material properties during WAAM process, which benefits future process control, improvement, and optimization

The effects of forced interpass cooling on the material properties of wire arc additively manufactured Ti6Al4V alloy

To achieve improved microstructure and mechanical properties, an innovative wire arc additive manufacturing (WAAM) process with forced interpass cooling using compressed CO2 was employed in this study to fabricate Ti6Al4V thin-walled structures. The effects of various interpass temperatures and rapid forced cooling on deposition geometry, surface oxidation, microstructural evolution, and mechanical properties of the fabricated part were investigated by laser profilometry, optical microscopy (OM), scanning electron microscopy (SEM), hardness testing and mechanical tensile testing. Results show that the microstructural evolution and mechanical properties of the deposited metal are not greatly affected by an increasing interpass temperature, however, the deposited wall tends to be widened, flattened and exhibit increased surface oxidation through visible coloration. When rapid forced cooling using CO2 is used between deposited layers, slightly higher hardness values and increased strength can be obtained. This is mainly attributed to the combined effects of less surface oxide and high density dislocation caused by the generation of large amounts of fine-grained acicular α within the microstructure. Furthermore, forced interpass cooling not only improves deposition properties, but also promotes geometrical repeatability and also improved manufacturing efficiency through the reduction of dwell time between deposited layers

Switchable Photonic Nanojet by Electro-Switching Nematic Liquid Crystals

This paper first presents a switchable photonic nanojet (PNJ) generated by a polystyrene (PS) microsphere immersed in nematic liquid crystals (NLCs). The PNJ is switched by applying external voltage, which originates from the refractive index change in the surrounding medium caused by the field-induced realignment of liquid crystal molecules. By tuning the refractive index of NLCs larger or smaller than that of the PS microsphere, the PNJ can be switched off or on. Moreover, we present an optimization study to seek a better electric energy focusing property of the PNJ. Our results reveal that the switchability of PNJ can be optimized by applying a shorter incident wavelength, a double-layer microsphere, and a PS ellipsoid. The full width at half-maximum (FWHM) generated by the PS ellipsoid is narrower than that generated by the microsphere with a shorter incident wavelength. The intensity contrast of the PS ellipsoid is higher than that of the double-layer microsphere. As a whole, the switchability of PNJ can be best optimized by a PS ellipsoid. This should open the way for the development of integrated photonic devices