Severe Hypothermia Induces Ferroptosis in Cerebral Cortical Nerve Cells.

Abnormal shifts in global climate, leading to extreme weather, significantly threaten the safety of individuals involved in outdoor activities. Hypothermia-induced coma or death frequently occurs in clinical and forensic settings. Despite this, the precise mechanism of central nervous system injury due to hypothermia remains unclear, hindering the development of targeted clinical treatments and specific forensic diagnostic indicators. The GEO database was searched to identify datasets related to hypothermia. Post-bioinformatics analyses, DEGs, and ferroptosis-related DEGs (FerrDEGs) were intersected. GSEA was then conducted to elucidate the functions of the Ferr-related genes. Animal experiments conducted in this study demonstrated that hypothermia, compared to the control treatment, can induce significant alterations in iron death-related genes such as PPARG, SCD, ADIPOQ, SAT1, EGR1, and HMOX1 in cerebral cortex nerve cells. These changes lead to iron ion accumulation, lipid peroxidation, and marked expression of iron death-related proteins. The application of the iron death inhibitor Ferrostatin-1 (Fer-1) effectively modulates the expression of these genes, reduces lipid peroxidation, and improves the expression of iron death-related proteins. Severe hypothermia disrupts the metabolism of cerebral cortex nerve cells, causing significant alterations in ferroptosis-related genes. These genetic changes promote ferroptosis through multiple pathways.

Response Surface of Speed-Loading Path to Grain Refinement during Current-Heating Compression at SAE 5137H Steel.

In thermal deformation of materials, grain refinement induced by dynamic recrystallization (DRX) is often pursued to obtain excellent mechanical properties. Here, the thermal deformation behaviors of SAE 5137H steel were investigated and characterized at temperature and strain rate range of 1123-1483 K and 0.01-10 s-1. Meanwhile, a design approach in speed-loading paths for grain refinement during current-heating compression was proposed, and these paths are linked to a typical three-dimensional (3D) response surface. Depending on the acquired stress-strain curves, the flow behaviors of this steel were analyzed and the typical 3D processing map was constructed to clarify the stable processing parameter domains during the continuous deformation process. Then, by the typical 3D processing map and microstructure observation, the 3D deformation mechanism map was constructed to connect the processing parameters and microstructural mechanisms. Subsequently, the 3D activation energy map was constructed to evaluate these deformation mechanisms, and the enhanced deformation mechanism map was constructed. Eventually, based on the enhanced deformation mechanism map, the speed-loading paths for SAE 5137H steel during current-heating compression were designed and they are mapped in a 3D response surface.

Uncovering the relationship and mechanisms of Tartary buckwheat (Fagopyrum tataricum) and Type II diabetes, hypertension, and hyperlipidemia using a network pharmacology approach.

BACKGROUND: Tartary buckwheat (TB), a crop rich in protein, dietary fiber, and flavonoids, has been reported to have an effect on Type II diabetes (T2D), hypertension (HT), and hyperlipidemia (HL). However, limited information is available about the relationship between Tartary buckwheat and these three diseases. The mechanisms of how TB impacts these diseases are still unclear. METHODS: In this study, network pharmacology was used to investigate the relationship between the herb as well as the diseases and the mechanisms of how TB might impact these diseases. RESULTS: A total of 97 putative targets of 20 compounds found in TB were obtained. Then, an interaction network of 97 putative targets for these compounds and known therapeutic targets for the treatment of the three diseases was constructed. Based on the constructed network, 28 major nodes were identified as the key targets of TB due to their importance in network topology. The targets of ATK2, IKBKB, RAF1, CHUK, TNF, JUN, and PRKCA were mainly involved in fluid shear stress and the atherosclerosis and PI3K-Akt signaling pathways. Finally, molecular docking simulation showed that 174 pairs of chemical components and the corresponding key targets had strong binding efficiencies. CONCLUSION: For the first time, a comprehensive systemic approach integrating drug target prediction, network analysis, and molecular docking simulation was developed to reveal the relationships and mechanisms between the putative targets in TB and T2D, HT, and HL.