Manipulating Stacking Fault Energy to Achieve Crack Inhibition and Superior Strength-Ductility Synergy in an Additively Manufactured High-Entropy Alloy.

Additive manufacturing (AM) is a revolutionary technology that heralds a new era in metal processing, yet the quality of AM-produced parts is inevitably compromised by cracking induced by severe residual stress. In this study, a novel approach is presented to inhibit cracks and enhance the mechanical performances of AM-produced alloys by manipulating stacking fault energy (SFE). A high-entropy alloy (HEA) based on an equimolar FeCoCrNi composition is selected as the prototype material due to the presence of microcracks during laser powder bed fusion (LPBF) AM process. Introducing a small amount (≈2.4 at%) of Al doping can effectively lower SFE and yield the formation of multiscale microstructures that efficiently dissipate thermal stress during LPBF processing. Distinct from the Al-free HEA containing visible microcracks, the Al-doped HEA (Al0.1CoCrFeNi) is crack free and demonstrates ≈55% improvement in elongation without compromising tensile strength. Additionally, the lowered SFE enhances the resistance to crack propagation, thereby improving the durability of AM-printed products. By manipulating SFE, the thermal cycle-induced stress during the printing process can be effectively consumed via stacking faults formation, and the proposed strategy offers novel insights into the development of crack-free alloys with superior strength-ductility synergy for intricate structural applications.

The Characteristic Microstructures and Properties of Steel-Based Alloy via Additive Manufacturing.

Differing from metal alloys produced by conventional techniques, metallic products prepared by additive manufacturing experience distinct solidification thermal histories and solid-state phase transformation processes, resulting in unique microstructures and superior performance. This review starts with commonly used additive manufacturing techniques in steel-based alloy and then some typical microstructures produced by metal additive manufacturing technologies with different components and processes are summarized, including porosity, dislocation cells, dendrite structures, residual stress, element segregation, etc. The characteristic microstructures may exert a significant influence on the properties of additively manufactured products, and thus it is important to tune the components and additive manufacturing process parameters to achieve the desired microstructures. Finally, the future development and prospects of additive manufacturing technology in steel are discussed.

Genome-wide Analysis of Histone H3 Lysine 27 Trimethylation Profiles in Sciatic Nerve of Chronic Constriction Injury Rats.

The histone H3 lysine 27 trimethylation (H3K27me3) is one of the most important chromatin modifications, which is associated with injury-activated gene expression in Schwann cells (SCs). However, the alteration of genome-wide H3K27me3 enrichments in the development of neuropathic pain is still unknown. Here, we applied the chromatin immunoprecipitation sequencing (ChIP-seq) approach to identify the alteration of differential enrichments of H3K27me3 in chronic constriction injury (CCI) sciatic nerve of rats and potential molecular mechanisms underlying the development of neuropathic pain. Our results indicated that CCI increased the numbers of SCs displaying H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) and H3K27me3 in the sciatic nerve. ChIP-seq data showed that CCI significantly changed H3K27me3 enrichments on gene promoters in the sciatic nerve. Bioinformatics analyses exhibited that genes gaining H3K27me3 were mostly associated with regulation of cell proliferation, response to stress and oxidation-reduction process. Genes losing this mark were enriched in neuronal generation, and MAPK, cAMP as well as ERBB signaling pathways. Importantly, IL1A, CCL2, NOS2, S100A8, BDNF, GDNF, ERBB3 and C3 were identified as key genes in neuropathic pain. CCI led to significant upregulation of key genes in the sciatic nerve. EZH2 inhibitor reversed CCI-induced increases of H3K27me3 and key gene protein levels, which were accompanied by relieved mechanical allodynia and thermal hyperalgesia in CCI rats. These results indicate that genes with differential enrichments of H3K27me3 in SCs function in various cellular processes and pathways, and many are linked to neuropathic pain after peripheral nerve injury.

Laser-Directed Energy Deposition of Fe-Mn-Si-Based Shape Memory Alloy: Microstructure, Mechanical Properties, and Shape Memory Properties.

Fe-Mn-Si shape memory alloys (SMAs) have gained significant attention due to their unique characteristics. However, there remains a gap in the literature regarding the fabrication of these alloys using laser-directed energy deposition (LDED). This study fills this void, investigating the properties of Fe-Mn-Si SMAs produced by LDED. The shape memory performance of as-deposited Fe-Mn-Si SMAs was studied using a tensile method. Alloys underwent different degrees of deformation to assess their shape memory effect. Microstructural evaluations were conducted post-deformation to observe the internal structures of the alloys. The tensile tests revealed that shape recovery rates for deformation levels of 3%, 7%, 11%, and 15% were 68.1%, 44.2%, 31.7%, and 17.6%, respectively. Notably, the maximum recoverable deformation of the LDED-formed Fe-Mn-Si-based shape memory alloy reached 3.49%, surpassing the traditional deformation processing SMAs (<3%). The presence of a significant number of stacking faults was linked to the enhanced shape memory performance. The LDED technique demonstrates promising potential for the fabrication of Fe-Mn-Si SMAs, producing alloys with enhanced shape memory performance compared to traditionally processed SMAs. The study's findings offer new insights and broaden the applicability of LDED in the field of SMAs.

Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome.

The activation of mast cells (MCs) and mediator release are closely related to the pathophysiology of irritable bowel syndrome (IBS). However, the exact underlying mechanisms are still not completely understood. The nuclear receptor subfamily 4a (Nr4a) is a family of orphan nuclear receptors implicated in regulating MC activation, degranulation, cytokine/chemokine synthesis and release. Acute and chronic stress trigger hypothalamic-pituitaryadrenal axis (HPA) activation to induce the release of corticotropin-releasing hormone (CRH), resulting in MC activation and induction of the Nr4a family. Our newest data showed that Nr4a members were specially over-expressed in colonic MCs of the chronic water-avoidance stress (WAS)-induced visceral hyperalgesia mice, suggesting that Nr4a members might be involved in the pathophysiology of visceral hypersensitivity. In this review, we highlight the present knowledge on roles of Nr4a members in the activation of MCs and the pathophysiology of IBS, and discuss signaling pathways that modulate the activation of Nr4a family members. We propose that a better understanding of Nr4a members and their modulators may facilitate the development of more selective and effective therapies to treat IBS patients.

Calcitonin gene-related peptide induces the histone H3 lysine 9 acetylation in astrocytes associated with neuroinflammation in rats with neuropathic pain.

AIMS: Calcitonin gene-related peptide (CGRP) as a regulator of astrocyte activation may facilitate spinal nociceptive processing. Histone H3 lysine 9 acetylation (H3K9ac) is considered an important regulator of cytokine and chemokine gene expression after peripheral nerve injury. In this study, we explored the relationship between CGRP and H3K9ac in the activation of astrocytes, and elucidated the underlying mechanisms in the pathogenesis of chronic neuropathic pain. METHODS: Astroglial cells (C6) were treated with CGRP and differentially enrichments of H3K9ac on gene promoters were examined using ChIP-seq. A chronic constriction injury (CCI) rat model was used to evaluate the role of CGRP on astrocyte activation and H3K9ac signaling in CCI-induced neuropathic pain. Specific inhibitors were employed to delineate the involved signaling. RESULTS: Intrathecal injection of CGRP and CCI increased the number of astrocytes displaying H3K9ac in the spinal dorsal horn of rats. Treatment of CGRP was able to up-regulate H3K9ac and glial fibrillary acidic protein (GFAP) expression in astroglial cells. ChIP-seq data indicated that CGRP significantly altered H3K9ac enrichments on gene promoters in astroglial cells following CGRP treatment, including 151 gaining H3K9ac and 111 losing this mark, which mostly enriched in proliferation, autophagy, and macrophage chemotaxis processes. qRT-PCR verified expressions of representative candidate genes (ATG12, ATG4C, CX3CR1, MMP28, MTMR14, HMOX1, RET) and RTCA verified astrocyte proliferation. Additionally, CGRP treatment increased the expression of H3K9ac, CX3CR1, and IL-1ß in the spinal dorsal horn. CGRP antagonist and HAT inhibitor attenuated mechanical and thermal hyperalgesia in CCI rats. Such analgesic effects were concurrently associated with the reduced levels of H3K9ac, CX3CR1, and IL-1ß in the spinal dorsal horn of CCI rats. CONCLUSION: Our findings highly indicate that CGRP is associated with the development of neuropathic pain through astrocytes-mediated neuroinflammatory responses via H3K9ac in spinal dorsa horn following nerve injury. This study found that CGRP act on their astrocytic receptors and lead to H3K9 acetylation (H3K9ac), which are mainly associated with proliferation-, autophagy-, and inflammation-related gene expression. The number of astrocytes with H3K9ac expression is increased after nerve injury. Inhibition of CGRP attenuates the development of neuropathic pain, which was accompanied by the suppression of H3K9ac, CX3CR1, and IL-1ß expression in CCI rats.

Calcitonin gene-related peptide regulates spinal microglial activation through the histone H3 lysine 27 trimethylation via enhancer of zeste homolog-2 in rats with neuropathic pain.

BACKGROUND: Calcitonin gene-related peptide (CGRP) as a mediator of microglial activation at the transcriptional level may facilitate nociceptive signaling. Trimethylation of H3 lysine 27 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that regulates inflammatory-related gene expression after peripheral nerve injury. In this study, we explored the relationship between CGRP and H3K27me3 in microglial activation after nerve injury, and elucidated the underlying mechanisms in the pathogenesis of chronic neuropathic pain. METHODS: Microglial cells (BV2) were treated with CGRP and differentially enrichments of H3K27me3 on gene promoters were examined using ChIP-seq. A chronic constriction injury (CCI) rat model was used to evaluate the role of CGRP on microglial activation and EZH2/H3K27me3 signaling in CCI-induced neuropathic pain. RESULTS: Overexpressions of EZH2 and H3K27me3 were confirmed in spinal microglia of CCI rats by immunofluorescence. CGRP treatment induced the increased of H3K27me3 expression in the spinal dorsal horn and cultured microglial cells (BV2) through EZH2. ChIP-seq data indicated that CGRP significantly altered H3K27me3 enrichments on gene promoters in microglia following CGRP treatment, including 173 gaining H3K27me3 and 75 losing this mark, which mostly enriched in regulation of cell growth, phagosome, and inflammation. qRT-PCR verified expressions of representative candidate genes (TRAF3IP2, BCL2L11, ITGAM, DAB2, NLRP12, WNT3, ADAM10) and real-time cell analysis (RTCA) verified microglial proliferation. Additionally, CGRP treatment and CCI increased expressions of ITGAM, ADAM10, MCP-1, and CX3CR1, key mediators of microglial activation in spinal dorsal horn and cultured microglial cells. Such increased effects induced by CCI were suppressed by CGRP antagonist and EZH2 inhibitor, which were concurrently associated with the attenuated mechanical and thermal hyperalgesia in CCI rats. CONCLUSION: Our findings highly indicate that CGRP is implicated in the genesis of neuropathic pain through regulating microglial activation via EZH2-mediated H3K27me3 in the spinal dorsal horn.

Striped Non-Uniform Corrosion Behavior of Non-Equiatomic FeMnCoCr High-Entropy Alloy Prepared by Laser Melting Deposition in 0.1 M H2SO4 Solution.

The corrosion behavior of the Fe50Mn30Co10Cr10 high-entropy alloy (HEA) manufactured via laser melting deposition (LMD) was investigated using open circuit potential, potentiodynamic polarization, and electrochemical impedance spectroscopy measurements. The microstructure and morphology of LMD samples before and after the electrochemical tests were compared using X-ray diffraction, optical microscopy, scanning electron microscopy, and electron backscatter diffraction techniques. After the corrosion tests, a striped morphology was observed on the surface of the LMD HEA, which is mainly caused by the interval distribution of high-density and low-density grain-boundary regions. The corrosion performances varied with different planes of the LMD HEA sample, which is mainly controlled by the grain size at each plane. Local corrosion in this HEA is concentrated at the melt pool boundary, which may be due to the abundant metallurgical defects and stress concentration at this location.

Densification, Microstructure, and Mechanical Properties of Additively Manufactured 2124 Al-Cu Alloy by Selective Laser Melting.

Owing to its high specific strength and low density, Al-Cu alloys have been extensively used in aerospace for lightweight components. Additive manufacturing techniques such as selective laser melting, which offers geometric freedom, is suitable for topology-optimized designs. In this study, the effect of processing parameters on the densification, microstructure, and mechanical properties of additively manufactured Al-Cu alloy 2124 by selective laser melting was investigated. Parameters such as laser power, scanning speed, hatch spacing, and use of a support were studied. The results revealed that a grille support with a hollow structure played a resistant role in the transfer of heat to the base plate, thus reducing the temperature gradient and lessening cracks in the building part. Smaller hatch spacing was beneficial for the achievement of a higher relative density and strength due to track re-melting and liquid phase backflow, which could fill cracks and pores during the building process. An ultimate tensile strength as high as 300 MPa of the vertically built sample was obtained at optimized processing parameters, while the elongation was relatively limited. Moreover, columnar grains were found to be responsible for the anisotropy of the mechanical properties of the as-printed 2124 alloy.

Microstructure and mechanical properties of additive manufactured porous Ti-33Nb-4Sn scaffolds for orthopaedic applications.

Customized porous titanium alloys have become the emerging materials for orthopaedic implant applications. In this work, diamond and rhombic dodecahedron porous Ti-33Nb-4Sn scaffolds were fabricated by selective laser melting (SLM). The phase, microstructure and defects characteristics were investigated systematically and correlated to the effects of pore structure, unit cell size and processing parameter on the mechanical properties of the scaffolds. Fine ß phase dendrites were obtained in Ti-33Nb-4Sn scaffolds due to the fast solidification velocity in SLM process. The compressive and bending strength of the scaffolds decrease with the decrease of strut size and diamond structures showed both higher compressive and bending strength than the dodecahedron structures. Diamond Ti-33Nb-4Sn scaffold with compressive strength of 76 MPa, bending strength of 127 MPa and elastic modulus of 2.3 GPa was achieved by SLM, revealing the potential of Ti-33Nb-4Sn scaffolds for applications on orthopaedic implant.