The beneficial effects of Rosuvastatin in inhibiting inflammation in sepsis.

Microbial infection-induced sepsis causes excessive inflammatory response and multiple organ failure. An effective strategy for the treatment of sepsis-related syndromes is still needed. Rosuvastatin, a typical ß-hydroxy ß-methylglutaryl-CoA reductase inhibitor licensed for reducing the levels of low-density lipoprotein cholesterol in patients with hyperlipidemia, has displayed anti-inflammatory capacity in different types of organs and tissues. However, its effects on the development of sepsis are less reported. Here, we found that the administration of Rosuvastatin reduced the mortality of sepsis mice and prevented body temperature loss. Additionally, it inhibited the production of inflammatory cytokines such as tumor necrosis factor (TNF-α), Interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and migration inhibitory factor (MIF) in peritoneal lavage supernatants of animals. The increased number of mononuclear cells in the peritoneum of sepsis mice was reduced by Rosuvastatin. Interestingly, it ameliorated lung inflammation and improved the hepatic and renal function in the sepsis animals. Further in vitro experiments show that Rosuvastatin inhibited lipopolysaccharide (LPS)-induced production of proinflammatory cytokines in RAW 264.7 macrophages by preventing the activation of nuclear factor kappa-B (NF-κB). Our findings demonstrate that the administration of Rosuvastatin hampered organ dysfunction and mitigated inflammation in a relevant model of sepsis.

Pan-cancer analysis for the prognostic and immunological role of CD47: interact with TNFRSF9 inducing CD8 + T cell exhaustion.

PURPOSE: The research endeavors to explore the implications of CD47 in cancer immunotherapy effectiveness. Specifically, there is a gap in comprehending the influence of CD47 on the tumor immune microenvironment, particularly in relation to CD8 + T cells. Our study aims to elucidate the prognostic and immunological relevance of CD47 to enhance insights into its prospective utilities in immunotherapeutic interventions. METHODS: Differential gene expression analysis, prognosis assessment, immunological infiltration evaluation, pathway enrichment analysis, and correlation investigation were performed utilizing a combination of R packages, computational algorithms, diverse datasets, and patient cohorts. Validation of the concept was achieved through the utilization of single-cell sequencing technology. RESULTS: CD47 demonstrated ubiquitous expression across various cancer types and was notably associated with unfavorable prognostic outcomes in pan-cancer assessments. Immunological investigations unveiled a robust correlation between CD47 expression and T-cell infiltration rather than T-cell exclusion across multiple cancer types. Specifically, the CD47-high group exhibited a poorer prognosis for the cytotoxic CD8 + T cell Top group compared to the CD47-low group, suggesting a potential impairment of CD8 + T cell functionality by CD47. The exploration of mechanism identified enrichment of CD47-associated differentially expressed genes in the CD8 + T cell exhausted pathway in multiple cancer contexts. Further analyses focusing on the CD8 TCR Downstream Pathway and gene correlation patterns underscored the significant involvement of TNFRSF9 in mediating these effects. CONCLUSION: A robust association exists between CD47 and the exhaustion of CD8 + T cells, potentially enabling immune evasion by cancer cells and thereby contributing to adverse prognostic outcomes. Consequently, genes such as CD47 and those linked to T-cell exhaustion, notably TNFRSF9, present as promising dual antigenic targets, providing critical insights into the field of immunotherapy.

Study on the Effect of the Pre-Forming of 22MnB5 Steel in Indirect Hot Stamping.

Based on the indirect hot-stamping test system, the effect of pre-forming on the microstructure evolution (grain size, dislocation density, martensite phase transformation) and mechanical properties of the blank in indirect hot stamping is systematically studied using ultra-high-strength steel 22MnB5. It is found that the average austenite grain size slightly decreases with the increase in pre-forming. After quenching, the martensite also becomes finer and more uniformly distributed. Although the dislocation density after quenching slightly decreases with the increase in pre-forming, the overall mechanical properties of the quenched blank are not greatly affected by pre-forming under the combined effect of the grain size and dislocation density. Then, this paper discusses the effect of the pre-forming volume on part formability in indirect hot stamping by manufacturing a typical beam part. According to the numerical simulations and experimental results, when the pre-forming volume increases from 30% to 90%, the maximum thickness thinning rate of the beam part decreases from 30.1% to 19.1%, and the final beam part has better formability and more uniform thickness distribution results when the pre-forming volume is 90%.

Investigation of the Hot Stamping-in-Die Quenching Composite Forming Process of 5083 Aluminum Alloy Skin.

Aluminum alloy has been used as the skin material for rail vehicles and automobiles to meet the requirements of environmental protection. The hot stamping-in-die quenching composite forming (HFQ) process is a promising technology to compensate for the poor formability of the aluminum alloy sheet at room temperature. In this paper, the high-temperature mechanical properties of 5083 aluminum alloy under various temperature (200 °C, 300 °C, 400 °C, 450 °C) and strain rate conditions (0.01 s-1, 0.10 s-1, 1.00 s-1) were investigated by uniaxial tensile tests. The finite element software of PAM-STAMP was employed to simulate the forming process of high-speed train skin. The effects of forming method and process parameters on the minimum thickness and springback of the skin were analyzed using the Response Surface Methodology (RSM). After parameter optimization, the forming experiment verified the simulation results and the test part met the quality requirements: the thickness above 3.84 mm and the springback within 1.1 mm. Mechanical properties of the sheet before and after HFQ were examined by uniaxial tensile tests at room temperature. It can be inferred from the comparison that the yield strength of the Al5083 sheet increases, but the elongation decreases from the HFQ process.

Theoretical Investigation of Forming Process of Aluminum Alloy Rail Vehicle Side Window.

With the vigorous development of rail transit trains around the world and the emergence of global environmental pollution and energy shortages, the world has an urgent need for manufacturing technology for lightweight aluminum alloy rail transit train components. This paper mainly studied the superplastic forming law of 5083Al for rail transit. Through the high-temperature tensile test and blowing forming experiments, the superplastic properties of 5083Al were determined. Based on this, the die design, finite element simulation, and forming experiment of the rail vehicle side window were carried out. In order to study the superplastic deformation behavior of industrial 5083Al under complex stress conditions, the influence of the depth, area ratio, and friction coefficient of the pre-forming die on the part thickness distribution is simulated. The side window is made of a high-strength 5083Al sheet in the form of bending at both ends to ensure the strength of the connection between the overall side window and the side wall skeleton. The variation law of the side wall forming height of 5083Al box-shaped parts was studied. The efficient manufacture of parts that meet quality standards was made possible by the optimization of the pressure profile. The microstructure changes of the material after superplastic forming were studied by Energy Dispersive Spectrometer (EDS) and Electron Backscattered Diffraction (EBSD).