Advance on rock-breaking cutter steels: A review of characteristics, failure modes, molding processes and strengthening technology

Rock breaking has always been a challenging problem that must be solved in projects such as excavating mountains, drilling wells, and constructing railways. Among the rock-breaking cutter steels, AISI H13 steel and wear-resistant high manganese steel have become the best choices. From the characteristics and failure modes of the two, rock-breaking cutter steels should simultaneously have high strength, high toughness and high wear resistance to avoid short-term fracture/damage and cost increase. Analyzing the problems existing in the molding process of rock-breaking cutter steels such as die casting, forging, and hot stamping, traditional strengthening technologies such as alloying optimization, heat treatment, and surface treatment can achieve certain performance enhancement. After reaching the limits of traditional strengthening technologies, a series of nanoparticle strengthening technologies came into being. The selection, addition amount, and addition method of nanoparticles all affect the microstructure, mechanical properties and wear. To this end, this article summarizes the research progress and challenges of rock-breaking cutter steels, and discusses traditional strengthening technologies and mainstream nanoparticle strengthening technologies. It provides a reference for the future development of high-quality and high-performance rock-breaking cutter steels, with aim to simultaneously expand their application potentials to other fields

Ceramic particles reinforced copper matrix composites manufactured by advanced powder metallurgy: Preparation, performance, and mechanisms

Copper matrix composites doped with ceramic particles are known to effectively enhance the mechanical properties, thermal expansion behavior and high-temperature stability of copper while maintaining high thermal and electrical conductivity. This greatly expands the applications of copper as a functional material in thermal and conductive components, including electronic packaging materials and heat sinks, brushes, integrated circuit lead frames. So far, endeavors have been focusing on how to choose suitable ceramic components and fully exert strengthening effect of ceramic particles in the copper matrix. This article reviews and analyzes the effects of preparation techniques and the characteristics of ceramic particles, including ceramic particle content, size, morphology and interfacial bonding, on the diathermancy, electrical conductivity and mechanical behavior of copper matrix composites. The corresponding models and influencing mechanisms are also elaborated in depth. This review contributes to a deep understanding of the strengthening mechanisms and microstructural regulation of ceramic particle reinforced copper matrix composites. By more precise design and manipulation of composite microstructure, the comprehensive properties could be further improved to meet the growing demands of copper matrix composites in a wide range of application fields

The role of lithium in the aging precipitation process of al-zn-mg-cu alloys and its effect on the properties

It is well known that the development of lightweight alloys with improved comprehensive performance and application value are the future development directions for the ultra-high-strength 7xxx series Al-Zn-Mg-Cu alloys used in the aircraft field. As the lightest metal element in nature, lithium (Li) has outstanding advantages in reducing the density and increasing the elastic modulus in aluminum alloys, so Al-Zn-Mg-Cu alloys containing Li have gained widespread attention. Furthermore, since the Al-Zn-Mg-Cu alloy is usually strengthened by aging treatment, it is crucial to understand how Li addition affects its aging precipitation process. As such, in this article, the effects and mechanism of Li on the aging precipitation behavior and the impact of Li content on the aging precipitation phase of Al-Zn-Mg-Cu alloys are briefly reviewed, and the influence of Li on the service properties, including mechanical properties, wear resistance, and fatigue resistance, of Al-Zn-Mg-Cu alloys are explained. In addition, the corresponding development prospects and challenges of the Al-Zn-Mg-Cu-Li alloy are also proposed. This review is helpful to further understand the role of Li in Al-Zn-Mg-Cu alloys and provides a reference for the development of high-strength aluminum alloys containing Li with good comprehensive properties

IgG Fc-binding motif-conjugated HIV-1 fusion inhibitor exhibits improved potency and in vivo half-life: Potential application in combination with broad neutralizing antibodies

The clinical application of conventional peptide drugs, such as the HIV-1 fusion inhibitor enfuvirtide, is limited by their short half-life in vivo. To overcome this limitation, we developed a new strategy to extend the in vivo half-life of a short HIV-1 fusion inhibitory peptide, CP24, by fusing it with the human IgG Fc-binding peptide (IBP). The newly engineered peptide IBPCP24 exhibited potent and broad anti-HIV-1 activity with IC50 values ranging from 0.2 to 173.7 nM for inhibiting a broad spectrum of HIV-1 strains with different subtypes and tropisms, including those resistant to enfuvirtide. Most importantly, its half-life in the plasma of rhesus monkeys was 46.1 h, about 26- and 14-fold longer than that of CP24 (t1/2 = 1.7 h) and enfuvirtide (t1/2 = 3 h), respectively. IBP-CP24 intravenously administered in rhesus monkeys could not induce significant IBP-CP24-specific antibody response and it showed no obvious in vitro or in vivo toxicity. In the prophylactic study, humanized mice pretreated with IBPCP24 were protected from HIV-1 infection. As a therapeutic treatment, coadministration of IBP-CP24 and normal human IgG to humanized mice with chronic HIV-1 infection resulted in a significant decrease of plasma viremia. Combining IBP-CP24 with a broad neutralizing antibody (bNAb) targeting CD4-binding site (CD4bs) in gp120 or a membrane proximal external region (MPER) in gp41 exhibited synergistic effect, resulting in significant dose-reduction of the bNAb and IBP-CP24. These results suggest that IBP-CP24 has the potential to be further developed as a new HIV-1 fusion inhibitor-based, long-acting anti-HIV drug that can be used alone or in combination with a bNAb for treatment and prevention of HIV-1 infection

SDC1 and ITGA2 As Novel Prognostic Biomarkers for PDAC Related to IPMN

The existing biomarkers are insufficient for predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary mucinous neoplasm (IPMN) is a precursor to PDAC; therefore, identifying biomarkers from differentially expressed genes (DEGs) of PDAC and IPMN is a new and reliable strategy for predicting the prognosis of PDAC. In this study, four datasets were downloaded from the Gene Expression Omnibus database and standardized using the R package \u27limma.\u27 A total of 51 IPMN and 81 PDAC samples were analyzed, and 341 DEGs in PDAC and IPMN were identified; DEGs were involved in the extracellular matrix and tumor microenvironment. An acceptable survival prognosis was demonstrated by SDC1 and ITGA2, which were highly expressed during in vitro PDAC cell proliferation, apoptosis, and migration. SDC1high was enriched in interferon alpha (IFN-α) response and ITGA2high was primarily detected in epithelial-mesenchymal transition (EMT), which was verified using western blotting. We concluded that SDC1 and ITGA2 are potential prognostic biomarkers for PDAC associated with IPMN. Downregulation of SDC1 and ITGA2 expression in PDAC occurs via a mechanism involving possible regulation of IFN-α response, EMT, and immunity, which may act as new targets for PDAC therapy

CLDN5 affects lncRNAs acting as ceRNA dynamics contributing to regulating blood-brain barrier permeability in tumor brain metastasis

The blood‑brain barrier (BBB) constitutes an efficient organization of tight junctions that limits the delivery of tumor to the brain. The principal tight junction protein in BBB is claudin‑5 (CLDN5), but its mechanism of action remains largely unknown. Long non‑coding RNAs (lncRNAs) are aberrantly expressed in many cancers, some lncRNAs play key roles in regulating BBB permeability and are involved in tumor brain metastasis. In particular, lncRNAs can function as competing endogenous RNAs (ceRNAs). Herein, we investigated whether ceRNA dysregulation is associated with alterations of the level of CLDN5 in human brain vascular endothelial hCMEC/D3 cells. The Affymetrix Human Transcriptome Array 2.0 and Affymetrix GeneChip miRNA 4.0 Array were used to detect the expression levels of 2,578 miRNAs, 22,829 lncRNAs, and 44,699 mRNAs in pLL3.7‑CLDN5‑transfected and pLL3.7 control hCMEC/D3 cells. The distinctly expressed miRNAs, lncRNAs, and mRNAs were subjected to construction of miRNA‑lncRNA‑mRNA interaction network. A total of 41 miRNAs, 954 lncRNAs, and 222 mRNAs were found to be differentially expressed between the CLDN5‑overexpressing and control group. 148 lncRNA acting as ceRNAs were identified based on the miRNA‑lncRNA‑mRNA interaction network. The function of differential mRNA in the network was determined by GO and pathway analysis. The potential roles of the 27 ceRNAs were revealed, the possible biology functions of these regulatory ceRNAs mainly included tight junction, focal adhesion, cell‑cell adhesion, cell growth and apoptosis. The identified sets of miRNAs, lncRNAs and mRNAs specific to CLDN5‑overexpressing hCMEC/D3 cells were verified by quantitative real‑time RT‑PCR experiment. Our study predicts the biological functions of a multitude of ceRNAs associated with the alteration of CLDN5 in brain vascular endothelial cells. Our data suggest that these dysregulated ceRNAs, in conjunction with the high CLDN5 levels, could serve as useful targets of prevention of brain metastasis formation. Further studies are warranted to determine the role of these ceRNAs in facilitating the function of CLDN5 in brain‑tumor barrier