Microstructure and Solute Segregation around the Melt-Pool Boundary of Orientation-Controlled 316L Austenitic Stainless Steel Produced by Laser Powder Bed Fusion

For this article, we studied the microstructure and solute segregation seen around the melt pool boundary of orientation-controlled 316L austenitic stainless steel produced by laser powder bed fusion, using transmission electron microscopy and energy-dispersive x-ray spectroscopy. We found that the solidification cellular microstructures could be visualized with the aid of solute segregation (Cr and Mo) during solidification. Mn–Si–O inclusions (10–15 nm in diameter) were distributed along the lamellar boundaries, as well as in the dislocation cell walls. It is believed that the grain growth of the inclusions can be effectively suppressed by rapid quenching during the laser powder-bed fusion process. A thin region without cellular microstructures was observed at the melt-pool boundary. The cellular spacing widened near the bottom of the melt-pool boundary, owing to the decrease in the cooling rate. Atomic-structure analysis at the lamellar boundary by high-resolution transmission electron microscopy revealed a local interfacial structure, which is complementary to the results of electron back-scatter diffraction.Sato K., Takagi S., Ichikawa S., et al. Microstructure and Solute Segregation around the Melt-Pool Boundary of Orientation-Controlled 316L Austenitic Stainless Steel Produced by Laser Powder Bed Fusion. Materials 16, 218 (2023); https://doi.org/10.3390/ma16010218

Local valence analysis of 316L austenitic stainless steel produced by laser powder bed fusion

Sato K., Takagi S., Ichikawa S., et al. Local valence analysis of 316L austenitic stainless steel produced by laser powder bed fusion. Materials Letters 372, 136978 (2024); https://doi.org/10.1016/j.matlet.2024.136978.Ultra-rapid cooling of laser powder bed fusion (LPBF) generates a cellular solidification microstructure with submicron-sized periodicity accompanied by non-negligible segregation. In 316L austenitic stainless steel, an important corrosion-resistant alloy, the effect of segregation, particularly variations in Cr concentration, on the corrosion resistance of the LPBF product is unknown. Local valence analysis of the LPBF-produced 316L by electron energy-loss spectroscopy revealed no obvious changes in the energy-loss near-edge structures of Cr and Fe measured within the solidification cellular microstructure, at the cell boundary, or at the melt-pool boundary. This result indicates that solidification segregation in the LPBF-produced 316L is unlikely to affect the corrosion resistance of the material

Design and development of a novel non-equiatomic Ti-Nb-Mo-Ta-W refractory high entropy alloy with a single-phase body-centered cubic structure

Kim Y.S., Ozasa R., Sato K., et al. Design and development of a novel non-equiatomic Ti-Nb-Mo-Ta-W refractory high entropy alloy with a single-phase body-centered cubic structure. Scripta Materialia 252, 116260 (2024); https://doi.org/10.1016/j.scriptamat.2024.116260.Element segregation and consequent phase separation are challenging problems in refractory high entropy alloys (RHEAs). In this study, thermodynamic parameters and calculation of phase diagrams (CALPHAD) were implemented for RHEA design to suppress segregation and phase separation. A novel non-equiatomic RHEA, Ti1(NbMoTa)2W0.5 alloy, was designed with a minimized difference between liquidus and solidus temperatures (ΔTl−s) and a wide temperature range between solidus temperature and transformation temperature (ΔTsingle) and compared with equiatomic RHEA. As-cast Ti1(NbMoTa)2W0.5 alloy maintained a single-phase body-centered cubic (BCC) structure, corresponding to the Scheil–Gulliver model, and segregation of constituent elements was suppressed owing to the minimized ΔTl−s. Ti1(NbMoTa)2W0.5 alloy showed excellent strength (approximately 1100 MPa) and ductility (1.6 times higher than TiNbMoTaW alloy). This study demonstrated a novel approach for obtaining single-phase BCC-structured RHEAs with suppressed elemental segregation and phase separation by utilizing combined use of ΔTl−s and ΔTsingle as alloy design indexes

Excellent strength–ductility balance of Sc-Zr-modified Al–Mg alloy by tuning bimodal microstructure via hatch spacing in laser powder bed fusion

The bimodal microstructure, which comprises ultrafine grains (UFGs) forming along the melt pool boundary and relatively coarse grains inside the melt pool, is a characteristic of the Sc-Zr-modified Al–Mg-based alloy (Scalmalloy) microstructure manufactured using laser powder bed fusion (LPBF). Focusing on this microstructural feature, we investigated the improvement in the mechanical properties of LPBF-fabricated Scalmalloy by tailoring the volume fraction of UFGs. Our approach was to decrease the laser hatch spacing (d) from 0.1 to 0.04 mm, while the volume fraction of UFGs increased from 34.6 ± 0.6 % (d = 0.1 mm) to 59.5 ± 0.5 % (d = 0.06 mm). The tensile yield stress increased from 296 ± 9 (d = 0.1 mm) to 380 ± 6 MPa (d = 0.06 mm), while maintaining a large elongation (14.8 % ± 1.2 %). The yield stress and elongation were superior to those of the cast counterparts by 2.9 and 4.0 times, respectively. In the sample with d = 0.04 mm, pores formed owing to excessive thermal energy input. Additionally, we investigated multiple strengthening mechanisms of the as-fabricated alloy. This is the first study to improve the mechanical properties of LPBF-fabricated Scalmalloy by optimizing the track-to-track interval and tuning the UFG fraction.Ekubaru Y., Gokcekaya O., Ishimoto T., et al. Excellent strength–ductility balance of Sc-Zr-modified Al–Mg alloy by tuning bimodal microstructure via hatch spacing in laser powder bed fusion. Materials and Design, 221, 110976. https://doi.org/10.1016/j.matdes.2022.110976

Periodontal Tissue as a Biomaterial for Hard-Tissue Regeneration following bmp-2 Gene Transfer

The application of periodontal tissue in regenerative medicine has gained increasing interest since it has a high potential to induce hard-tissue regeneration, and is easy to handle and graft to other areas of the oral cavity or tissues. Additionally, bone morphogenetic protein-2 (BMP-2) has a high potential to induce the differentiation of mesenchymal stem cells into osteogenic cells. We previously developed a system for a gene transfer to the periodontal tissues in animal models. In this study, we aimed to reveal the potential and efficiency of periodontal tissue as a biomaterial for hard-tissue regeneration following a bmp-2 gene transfer. A non-viral expression vector carrying bmp-2 was injected into the palate of the periodontal tissues of Wistar rats, followed by electroporation. The periodontal tissues were analyzed through bone morphometric analyses, including mineral apposition rate (MAR) determination and collagen micro-arrangement, which is a bone quality parameter, before and after a gene transfer. The MAR was significantly higher 3–6 d after the gene transfer than that before the gene transfer. Collagen orientation was normally maintained even after the bmp-2 gene transfer, suggesting that the bmp-2 gene transfer has no adverse effects on bone quality. Our results suggest that periodontal tissue electroporated with bmp-2 could be a novel biomaterial candidate for hard-tissue regeneration therapy.Kawai M.Y., Ozasa R., Ishimoto T., et al. Periodontal Tissue as a Biomaterial for Hard-Tissue Regeneration following bmp-2 Gene Transfer. Materials, 15, 3, 993. https://doi.org/10.3390/ma15030993

Lenvatinib for Anaplastic Thyroid Cancer

Background: Lenvatinib has been approved by regulatory agencies in Japan, the United States, and the European Union for treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thyroid cancer, however, is a clinically diverse disease that includes anaplastic thyroid cancer (ATC), the subtype associated with the highest lethality. Effective therapy for ATC is an unmet need. Patients and methods: This phase 2, single-arm, open-label study in patients with thyroid cancer, including ATC, RR-DTC, and medullary thyroid cancer was conducted from 3 September 2012 to 9 July 2015. Patients received lenvatinib 24 mg daily until disease progression or development of unacceptable toxicity. The primary endpoint was safety, and the secondary endpoint was efficacy, as assessed by progression-free survival (PFS), overall survival (OS), and objective response rate. Results: At data cutoff, 17 patients with ATC were enrolled. All experienced >= 1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were decreased appetite (82%), hypertension (82%), fatigue (59%), nausea (59%), and proteinuria (59%). Of note, only one patient required lenvatinib withdrawal because of a TEAE, and this TEAE was considered unrelated to lenvatinib. The median PFS was 7.4 months [95% confidence interval (CI): 1.7-12.9], the median OS was 10.6 months (95% CI: 3.8-19.8), and the objective response rate was 24%. Conclusion: In this study, lenvatinib demonstrated manageable toxicities with dose adjustments and clinical activity in patients with ATC. This clinical activity of lenvatinib warrants further investigation in ATC

Th22 Cells Promote Osteoclast Differentiation via Production of IL-22 in Rheumatoid Arthritis

T helper (Th) cells can differentiate into functionally distinct subsets and play a pivotal role in inflammatory and autoimmune diseases such as rheumatoid arthritis (RA). Th22 cells have been identified as a new subset secreting interleukin (IL)-22. Although elevated levels of IL-22 in the synovial fluids of RA patients were reported, its pathological roles remain unclear. Here, we demonstrated that IL-22 was characteristically produced from CD3+CD4+CC-chemokine receptor (CCR)4+CCR6+CCR10+ cells and their ability of the production of IL-22 markedly exceeded that of other Th subsets and the subset, thereby, designated Th22 cells. Th22 cells were efficiently induced by the stimulation with tumor necrosis factor-α, IL-6, and IL-1β. Th22 cells were markedly infiltrated in synovial tissue in patients with active RA, but not in patients with osteoarthritis (OA). CCL17, CCL20, and CCL28, which are chemokine ligands of CCR4, CCR6, and CCR10, respectively, were abundantly expressed in RA synovial tissue compared to OA. By in vitro Trans-well migration assay, Th22 cells efficiently migrated toward CCL28. Co-culture of Th22 cells, which were sorted from peripheral blood, with monocytes in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor (NF)-κB ligand induced osteoclasts formation more efficiently than that of either Th1 cells or Th17 cells. Furthermore, IL-22 markedly augmented osteoclast differentiation by promoting nuclear factor of activated T cells c1 expression in CD14+ monocytes. Contrarily, the addition of IFN-γ to the culture significantly decreased osteoclasts number, whereas IL-17 had marginal effects. IL-22 neutralizing antibody inhibited osteoclast formation in the co-culture of Th22 cells with CD14+ monocytes. Collectively, the results indicated that Th22 cells, which co-express chemokine receptors CCR4, CCR6, and CCR10, possess strong potency of tissue migration and accumulate into inflamed synovial tissues where the ligands such as CCL28 are highly expressed. Thus, Th22 cells have the capacity to promote osteoclast differentiation through production of IL-22 and thus play a pivotal role in bone destruction in patients with RA

Immunological and Regenerative Aspects of Hepatic Mast Cells in Liver Allograft Rejection and Tolerance

The precise roles of mast cells in liver allograft rejection and tolerance are still unknown. This study aimed to explore the roles of mast cells in immune regulation and liver regeneration for tolerance induction by using rat models of orthotopic liver transplantation (OLT).Stem cell factor (SCF) and its receptor c-Kit, which are critical to the migration and development of not only stem cells but also mast cells, significantly increased in the tolerogenic livers as compared with rejected livers. The significant elevation of mast cell tryptase, high-affinity IgE receptor, and histamine suggested the activation of mast cells in liver allografts at the tolerogenic phase after OLT. Immunohistochemical analysis using confocal microscope clearly showed colocalization of mast cells, Foxp3(+) Tregs, gamma delta T cells, and recipient-derived hepatic progenitor cells with higher expression of SCF, IL-9, IL-10, TGF-beta 1, and IL-17 related to immunoregulation and liver regeneration in the donor grafts of a tolerogenic OLT model. Cross-talk among mast cells and other cells was evaluated by in vitro studies demonstrating that syngeneic bone marrow-derived mast cells (BMMCs) co-cultured with naive splenocytes or primary hepatocytes significantly increased the population of splenic gamma delta T cells by mitogen stimulation or by mast cell degranulation, and also significantly induced the hepatocyte proliferation, respectively. Our results suggested that mast cells in the donor grafts may play important roles in the induction/maintenance of immune tolerance and liver regeneration resulting in the replacement of hepatic cells from donor to recipient

Effect of Heart Failure on Long‐Term Clinical Outcomes After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Severe Coronary Artery Disease

[Background] Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long‐term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). [Methods and Results] Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO‐Kyoto PCI/CABG registry Cohort‐3, we identified the current study population of 3380 patients with three‐vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow‐up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P=0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28–2.42; P<0.001) and no excess mortality risk in patients without heart failure (HR, 1.04; 95% CI, 0.80–1.34; P=0.77). [Conclusions] There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure