Finite Element Analysis of Dynamic Recrystallization Model and Microstructural Evolution for GCr15 Bearing Steel Warm-Hot Deformation Process.

Warm deformation is a plastic-forming process that differs from traditional cold and hot forming techniques. At the macro level, it can effectively reduce the problem of high deformation resistance in cold deformation and improve the surface decarburization issues during the hot deformation process. Microscopically, it has significant advantages in controlling product structure, refining grain size, and enhancing product mechanical properties. The Gleeble-1500D thermal-mechanical physical simulation system was used to conduct isothermal compression tests on GCr15 bearing steel. The tests were conducted at temperatures of 600-1050 °C and strain rates of 0.01-5 s-1. Based on the experimental data, the critical strain model and dynamic recrystallization model for the warm-hot forming of GCr15 bearing steel were established in this paper. The model accuracy is evaluated using statistical indicators such as the correlation coefficient (R). The dynamic recrystallization model exhibits high predictive accuracy, as indicated by an R-value of 0.986. The established dynamic recrystallization model for GCr15 bearing steel was integrated into the Forge® 3.2 numerical simulation software through secondary program development to simulate the compression process of GCr15 warm-hot forming. The dynamic recrystallization fraction was analyzed in various deformation regions. The grain size of the severe deformation zone, small deformation zone, and difficult deformation zone was compared based on simulated compression specimens under the conditions of 1050 °C and 0.1 s-1 with the corresponding grain size obtained with measurement based on metallographic photos; the relative error between the two is 5.75%. This verifies the accuracy of the established dynamic recrystallization and critical strain models for warm-hot deformation of GCr15 bearing steel. These models provide a theoretical basis for the finite element method analysis and microstructure control of the warm-hot forming process in bearing races.

Modular snapshot multispectral-panchromatic imager (MSPI) with customized filter arrays.

As one of the simplest methods to construct snapshot spectral imagers, multispectral filter array (MSFA) has been applied to commercial miniatured spectral imagers. While most of them have fixed configurations of spectral channels, lacking flexibility and replaceability. Moreover, conventional MSFA only comprises filtering channels but lacks the panchromatic channel which is essential in detecting dim and indistinct objects. Here, we propose a modular assembly method for snapshot imager which can simultaneously acquire the object's multispectral and panchromatic information based on a customized filter array. The multispectral-panchromatic filter array is batch fabricated and integrated with the imaging senor through a modular mode. Five-band spectral images and a broadband intensity image can be efficiently acquired in a single snapshot photographing. The efficacy and accuracy of the imager are experimentally verified in imaging and spectral measurements. Owing to the modular architecture, our proposed assembly method owns the advantages of compactness, simple assembling, rapid replacement, and customized designing, which overcomes the expensiveness and complexity of scientific-level snapshot spectral imaging systems.

Construction of chlorogenic acid-containing liposomes with prolonged antitumor immunity based on T cell regulation.

As a potential cancer immunotherapeutic agent, chlorogenic acid (CHA) has entered phase II clinical trials in China as a lyophilized powder formulation for treating glioma. However, the in vivo instability of CHA necessitates daily intramuscular injections, resulting in patient noncompliance. In this study, CHA-phospholipid complex (PC)-containing PEGylated liposomes (CHA-PC PEG-Lipo, named as CPPL), with CHA-PC as the drug intermediate, were prepared to lower the administration frequency. CPPL demonstrated excellent physicochemical properties, enhanced tumor accumulation, and inhibited tumor growth even when the administration interval was prolonged to 4 days when compared to a CHA solution and CHA-PC loaded liposomes (CHA-PC Lipo, labeled as CPL), both of which only demonstrated antitumor efficacy with once-daily administration. Further evaluation of the in vivo antitumor immune mechanism suggested that the extended antitumor immune efficacy of CPPL could be attributed to its distinct immune-stimulating mechanism when compared with CHA solution and CPL, such as stimulating both CD4+ and CD8+ T cell infiltration, inhibiting myeloid-derived suppressor cell expression, reducing the expression of Th2 related factors, and notably, increasing the memory T cells in tumor tissues. This CHA-containing formulation could reduce the frequency of in vivo CHA administration during cancer treatment via T cells, especially memory T cell regulation.

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein.

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein-phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.

Wenyang Huoxue Jiedu formula inhibits thin-cap fibroatheroma plaque formation via the VEGF/VEGFR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: For many years, Guangzhou University of Chinese Medicine has been successfully using the empirical Wenyang Huoxue Jiedu formula (WHJF) to treat coronary heart disease. Modern theories of acute coronary syndrome mainly focus on rupture of thin-cap fibroatheromas (TCFAs), which is closely related to the release of vascular endothelial growth factor and its receptor (VEGF/VEGFR). AIM OF STUDY: We investigated the effects of WHJF on the formation of TCFA plaques and the potential mechanism (VEGF/VEGFR signaling pathway). MATERIALS AND METHODS: For the in vivo experiments, WHJF was administered to ApoE-/- mice, as a model of TCFA plaque formation. Aortic sections of the mice were obtained, and the vulnerability index and new vessel density of plaques were calculated by the Movat staining assay and immunohistochemistry kit, respectively. Protein and mRNA expression levels of VEGF/VEGFR in aortas were assayed by capillary electrophoresis immunoassay and quantitative real-time polymerase chain reaction analyses. In vitro, WHJF serum was produced in rats on the fourth day 2 h after the first administration of different concentrations of WHJF. Proliferation, migration, and lumen formation ability of human umbilical vein endothelial cells (HUVECs) treated with sera from these rats were assayed by the CKK-8 kit, Transwell plates, and Matrigel assay, respectively. Protein and mRNA expression levels of signaling molecules in the VEGF/VEGFR pathways were also examined. RESULTS: In vivo, the vulnerability index and new vessel density of plaques in the WHJF group were lower than those values in the blank control group (P < 0.05). No differences were found between the groups in the expression levels of VEGF/VEGFR (P > 0.05). In vitro, the proliferation, migration, and tube formation of HUVECs in the high-dose WHJF group were reduced compared to the control group (P < 0.05). This finding was in agreement with the downregulation of VEGFR-2 and pERK (P < 0.05). The mRNA expression of signaling molecules showed no difference between the groups (P > 0.05). CONCLUSIONS: WHJF inhibits TCFA formation by influencing the VEGF/VEGFR signaling pathway.

A novel matrix dispersion based on phospholipid complex for improving oral bioavailability of baicalein: preparation, in vitro and in vivo evaluations.

Phospholipid complex is one of the most successful approaches for enhancing oral bioavailability of poorly absorbed plant constituents. But the sticky property of phospholipids results in an unsatisfactory dissolution of drugs. In this study, a matrix dispersion of baicalein based on phospholipid complex (BaPC-MD) was first prepared by a discontinuous solvent evaporation method, in which polyvinylpyrrolidone-K30 (PVP-K30) was employed for improving the dispersibility of baicalein phospholipid complex (BaPC) and increasing dissolution of baicalein. The combination ratio of baicalein and phospholipids in BaPC-MD was 99.39% and baicalein was still in a complete complex state with phospholipid in BaPC-MD. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier Transform Infrared (FTIR) analyzes demonstrated that baicalein was fully transformed to an amorphous state in BaPC-MD and phospholipid complex formed. The water-solubility and n-octanol solubility of baicalein in BaPC-MD significantly increased compared with those of pure baicalein. Compared with baicalein and BaPC, the cumulative dissolution of BaPC-MD at 120 min increased 2.77- and 1.23-fold, respectively. In vitro permeability study in Caco-2 cells indicated that the permeability of BaPC-MD was remarkably higher than those of baicalein and BaPC. Pharmacokinetic study showed that the average Cmax of BaPC-MD was significantly increased compared to baicalein and BaPC. AUC0-14 h of BaPC-MD was 5.01- and 1.91-fold of baicalein and BaPC, respectively. The novel BaPC-MD significantly enhanced the oral bioavailability of baicalein by improving the dissolution and permeability of baicalein without destroying the complexation state of baicalein and phospholipids. The current drug delivery system provided an optimal strategy to significantly enhance oral bioavailability for poorly water-soluble drugs.