The microstructures and mechanical properties of CoNiCrx medium-entropy alloys

The CoNiCrx (x = 1, 1.4, 1.8, and 2) medium-entropy alloys were synthesized by vacuum arc-melting method to systematically investigate the roles of Cr on microstructures and mechanical properties. The results of microstructural characteristics indicated that both CoNiCr and CoNiCr1.4 alloys have a single face-centered cubic (FCC) structure, while CoNiCr1.8 and CoNiCr2 alloys consist of FCC plus body-centered cubic (BCC) hypoeutectic and eutectic. The formation of FCC and BCC phases could be probably evaluated using the VEC criteria. The tested mechanical properties demonstrated that CoNiCr1.8 alloy exhibited the best comprehensive properties at room and liquid nitrogen temperatures (RT and LNT), whereas the yield strength and hardness of CoNiCr2 alloy were higher than those of other alloys, which may be mainly attributed to the second-phase strengthening and the fine and lamellar microstructure. The yield strength of CoNiCr2 alloy at RT and LNT was 3.8 and 1.9 times (514 MPa and 825 MPa) that of CoNiCr alloy. In addition, the precipitation of dense and ordered FCC (L12) phase could primarily contribute to the enhance of yield strength of CoNiCr1.4 alloy

Specific Blood Cells Derived from Pluripotent Stem Cells: An Emerging Field with Great Potential in Clinical Cell Therapy

Widely known for self-renewal and multilineage differentiation, stem cells can be differentiated into all specialized tissues and cells in the body. In the past few years, a number of researchers have focused on deriving hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) as alternative sources for clinic. Existing findings demonstrated that it is feasible to obtain HSCs and certain mature blood lineages from PSCs, except for several issues to be addressed. This short review outlines the technologies used for hematopoietic differentiation in recent years. In addition, the therapeutic value of PSCs as a potential source of various blood cells is also discussed as well as its challenges and directions in future clinical applications

Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis

Cancer cells display phenotypic equilibrium between the stem-like and differentiated states during neoplastic homeostasis. The functional and mechanistic implications of this subpopulation plasticity remain largely unknown. Herein, it is demonstrated that the breast cancer stem cell (BCSC) secretome autonomously compresses the stem cell population. Co-implantation with BCSCs decreases the tumor-initiating capacity yet increases metastasis of accompanying cancer cells, wherein DKK1 is identified as a pivotal factor secreted by BCSCs for such functions. DKK1-promotes differentiation is indispensable for disseminated tumor cell metastatic outgrowth. In contrast, DKK1 inhibitors substantially relieve the metastatic burden by restraining metastatic cells in the dormant state. DKK1 increases the expression of SLC7A11 to protect metastasizing cancer cells from lipid peroxidation and ferroptosis. Combined treatment with a ferroptosis inducer and a DKK1 inhibitor exhibits synergistic effects in diminishing metastasis. Hence, this study deciphers the contribution of CSC-regulated phenotypic plasticity in metastatic colonization and provides therapeutic approaches to limit metastatic outgrowth

Enhanced HSC-like cell generation from mouse pluripotent stem cells in a 3D induction system cocultured with stromal cells

Abstract Background Decades of efforts have attempted to differentiate the pluripotent stem cells (PSCs) into truly functional hematopoietic stem cells (HSCs), yet the problems of low differentiation efficiency in vitro and poor hematopoiesis reconstitution in vivo still exist, mainly attributing to the lack of solid, reproduced, or pursued differentiation system. Methods In this study, we established an in vitro differentiation system yielding in vivo hematopoietic reconstitution hematopoietic cells from mouse PSCs through a 3D induction system followed by coculture with OP9 stromal cells. The in vivo hematopoietic reconstitution potential of c-kit+ cells derived from the mouse PSCs was evaluated via m-NSG transplantation assay. Flow cytometry analysis, RNA-seq, and cell cycle analysis were used to detect the in vitro hematopoietic ability of endothelial protein C receptor (EPCR, CD201) cells generated in our induction system. Results The c-kit+ cells from 3D self-assembling peptide induction system followed by the OP9 coculture system possessed apparently superiority in terms of in vivo repopulating activity than that of 3D induction system followed by the 0.1% gelatin culture. We interestingly found that our 3D+OP9 system enriched a higher percentage of CD201+c-kit+cells that showed more similar HSC-like features such as transcriptome level and CFU formation ability than CD201-c-kit+cells, which have not been reported in the field of mouse PSCs hematopoietic differentiation. Moreover, CD201+ hematopoietic cells remained in a relatively slow cycling state, consistent with high expression levels of P57 and Ccng2. Further, we innovatively demonstrated that notch signaling pathway is responsible for in vitro CD201+ hematopoietic cell induction from mouse PSCs. Conclusions Altogether, our findings lay a foundation for improving the efficiency of hematopoietic differentiation and generating in vivo functional HSC-like cells from mouse PSCs for clinical application