Novel hypoxia-induced HIF-1αactivation in asthma pathogenesis

Abstract Background Asthma’s complexity, marked by airway inflammation and remodeling, is influenced by hypoxic conditions. This study focuses on the role of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) and P53 ubiquitination in asthma exacerbation. Methods High-throughput sequencing and bioinformatics were used to identify genes associated with asthma progression, with an emphasis on GO and KEGG pathway analyses. An asthma mouse model was developed, and airway smooth muscle cells (ASMCs) were isolated to create an in vitro hypoxia model. Cell viability, proliferation, migration, and apoptosis were assessed, along with ELISA and Hematoxylin and Eosin (H&E) staining. Results A notable increase in HIF-1α was observed in both in vivo and in vitro asthma models. HIF-1α upregulation enhanced ASMCs’ viability, proliferation, and migration, while reducing apoptosis, primarily via the promotion of P53 ubiquitination through MDM2. In vivo studies showed increased inflammatory cell infiltration and airway structural changes, which were mitigated by the inhibitor IDF-11,774. Conclusion The study highlights the critical role of the HIF-1α-MDM2-P53 axis in asthma, suggesting its potential as a target for therapeutic interventions. The findings indicate that modulating this pathway could offer new avenues for treating the complex respiratory disorder of asthma

A comprehensive characterization of virgin and recycled 316L powders during laser powder bed fusion

The primary constraints hindering the widespread adoption of laser powder bed fusion (LPBF) are expensive raw materials, internal defects, difficulty in controlling the quality and stability, and lack of consistency in the powder feedstock. The spatters induced by the violent interaction between the laser and powder can be deposited on the unmelted powder bed, and if not effectively separated by sieving, they would pose a significant detriment to the characteristics and consistency of the recycled powders. In this work, a systematic investigation of the evolution mechanism of 316L powders after 10 and 30 successive recycling in the LPBF process was presented. Firstly, the variation mechanism of particle size distribution and morphology of 316L powder and the generation mechanism of heterogeneous particles were studied. Then, changes in microstructure and hardness trends were characterized. Finally, we emphasized the changes of chemical composition, phase composition, magnetic properties, and the formation mechanism of oxide spots. The results show that the circulation had significant effects on the physical properties, phase transformation, mechanical properties, and magnetic properties of the 316L powders, but had minor effects on the chemical composition, surface and cross-sectional microstructure. In addition, a large number of oddly shaped, large-diameter spatters were identified in the recycled powders, which could not be separated effectively by sieving, and the formation mechanism of the spatters were elaborated. Based on the comprehensive high temperature oxidation thermodynamics and experimental results, it was concluded that the circular oxide spots on the spatter surface were a composite of multiple oxides of Mn and Si. Further, it was also shown that the ferrite content, XRD peak characteristics, and magnetic properties in the recycled powders were governed by the droplet solidification modes, which in turn is determined by the chemical composition and cooling rates. (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

An investigation on the oxidation behavior of spatters generated during the laser powder bed fusion of 316L stainless steel

The characterization of the oxide islands on the surface of the spatter contributes to a fundamental understanding of the formation and oxidation of spatter in laser powder bed fusion (LPBF). In the present study, the surface and cross-section characteristics of spatters with oxide islands are investigated using high resolution scanning electron microscopy combined with energy dispersive spectroscopy, scanning transmission electron microscopy and selected area electron diffraction. The oxide islands with different configurations on the spatter surface are divided into three main categories: hemispherical, disc-like and film-like. Moreover, the primary component of oxide islands is an amorphous SiO2, which may also contain MnO, MnSiO3, and Mn2SiO4. Furthermore, a transition layer (enriched in Si, Mn, and O) is found at the oxide islands || spatter substrate interface, and the width of which is 4 mu m and 20 nm on the spatter surface and within the spatter cross-section, respectively. Besides, the composition and sources of the circular oxide nano-inclusions (50-600 nm) internal to the spatters are also discussed in detail. Eventually, the driving forces affecting the formation of oxide islands on the surface of spatters are summarized, and a schematic diagram of the formation procedure is developed

A comprehensive characterization of virgin and recycled 316L powders during laser powder bed fusion

The primary constraints hindering the widespread adoption of laser powder bed fusion (LPBF) are expensive raw materials, internal defects, difficulty in controlling the quality and stability, and lack of consistency in the powder feedstock. The spatters induced by the violent interaction between the laser and powder can be deposited on the unmelted powder bed, and if not effectively separated by sieving, they would pose a significant detriment to the characteristics and consistency of the recycled powders. In this work, a systematic investigation of the evolution mechanism of 316L powders after 10 and 30 successive recycling in the LPBF process was presented. Firstly, the variation mechanism of particle size distribution and morphology of 316L powder and the generation mechanism of heterogeneous particles were studied. Then, changes in microstructure and hardness trends were characterized. Finally, we emphasized the changes of chemical composition, phase composition, magnetic properties, and the formation mechanism of oxide spots. The results show that the circulation had significant effects on the physical properties, phase transformation, mechanical properties, and magnetic properties of the 316L powders, but had minor effects on the chemical composition, surface and cross-sectional microstructure. In addition, a large number of oddly shaped, large-diameter spatters were identified in the recycled powders, which could not be separated effectively by sieving, and the formation mechanism of the spatters were elaborated. Based on the comprehensive high temperature oxidation thermodynamics and experimental results, it was concluded that the circular oxide spots on the spatter surface were a composite of multiple oxides of Mn and Si. Further, it was also shown that the ferrite content, XRD peak characteristics, and magnetic properties in the recycled powders were governed by the droplet solidification modes, which in turn is determined by the chemical composition and cooling rates. (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Regulatory role of interleukin-10 and interferon-gamma in severe hepatic central and peripheral fibrosis in humans infected with Schistosoma japonicum

Schistosoma japonicum is the most pathogenic agent of hepatosplenic schistosomiasis. It causes fibrosis of the central (CentF) and peripheral (PerF) portal areas. We investigated whether CentF and PerF in Chinese fishermen infected with S. japonicum were associated with an abnormal production of cytokines and chemokines that, in experimental models, have been implicated in the regulation of fibrosis. METHODS: Cytokines were measured by enzyme-linked immunosorbent assay in cultures of peripheral blood mononuclear cells from 127 patients, after stimulation with S. japonicum egg antigens. Data were analyzed by logistic regression that included age, sex, number of treatment episodes, alcohol use, and exposure as covariates. RESULTS: CentF was associated with low levels of interleukin (IL)-10 (P= .0004), regulated on activation normally T cell expressed and secreted (P= .0004), and macrophage inflammatory protein-1alpha (P= .007). In a multivariate analysis, only IL-10 was associated with CentF (odds ratio [OR], 10.8; 95% confidence interval [CI], 3.2-38; P= .0004). Splenomegaly was also associated with low IL-10 production and, independently, with CentF. In multivariate analysis, PerF was associated with low production of interferon (IFN)-gamma (OR, 8.2; 95% CI, 2-33; P= .0035) but not with production of IL-10. CONCLUSIONS: IL-10 is associated with protection against central fibrosis, because of its anti-inflammatory and antifibrosis effects. IFN-gamma is associated with protection against PerF, which depends more on egg load and egg-associated toxicity