Lethal and sublethal effects of programmed cell death pathways on hematopoietic stem cells.

Programmed cell death is an evolutionally conserved cellular process in multicellular organisms that eliminates unnecessary or rogue cells during development, infection, and carcinogenesis. Hematopoietic stem cells (HSCs) are a rare, self-renewing, and multipotent cell population necessary for the establishment and regeneration of the hematopoietic system. Counterintuitively, key components necessary for programmed cell death induction are abundantly expressed in long-lived HSCs, which often survive myeloablative stress by engaging a prosurvival response that counteracts cell death-inducing stimuli. Although HSCs are well known for their apoptosis resistance, recent studies have revealed their unique vulnerability to certain types of programmed necrosis, such as necroptosis and ferroptosis. Moreover, emerging evidence has shown that programmed cell death pathways can be sublethally activated to cause nonlethal consequences such as innate immune response, organelle dysfunction, and mutagenesis. In this review, we summarized recent findings on how divergent cell death programs are molecularly regulated in HSCs. We then discussed potential side effects caused by sublethal activation of programmed cell death pathways on the functionality of surviving HSCs.

Medial-lateral translational malalignment of the prosthesis on tibial stress distribution in total knee arthroplasty: A finite element analysis.

Background: Poor prosthesis alignment during total knee arthroplasty could cause problems such as polyethylene spacer wear, leading to surgical failure and revision surgery. The problems caused by the malalignment of the tibial plateau prosthesis in the medial and lateral planes are unclear. We aimed to investigate the stress distribution and micromotion of the tibia when the tibial plateau prosthesis is translated 1 and 2 mm medially and laterally, respectively, using finite element analysis (FEA). Method: A non-homogeneous tibia model was created and load conditions when standing on two legs were applied using FEA to simulate the misaligned prosthesis. The stresses, stress distribution, and micromotion of the proximal tibia were analyzed in five positions of the tibial plateau prosthesis: Lateral-2 mm; Lateral-1 mm; Medium; Medial-2 mm; Medial-1 mm. Result: The maximum stress in the five groups with different misalignments of the platform was 47.29 MPa (Lateral-2 mm). The maximum micromotion among the five groups in different positions was 7.215 µm (Lateral-2 mm). Conclusion: When placing the tibial plateau prosthesis during total knee arthroplasty, an error of 2 mm or less is acceptable as long as it does not overhang.

C-scheme electron transfer mechanism: An efficient ternary heterojunction photocatalyst carbon quantum dots/Bi/BiOBr with full ohmic contact.

With a facile one-pot solvothermal method, an efficient ternary heterojunction photocatalyst carbon quantum dots (CQDs)/Bi/BiOBr is firstly prepared. Ethylene glycol (EG) is used as the solvent and carbon source for the first time. At 190 °C for 3 h, while BiOBr is synthesized, EG is employed to prepare CQDs through bottom-up method. CQDs are grafted by a large number of functional groups with reducibility, which reduce some neighboring BiO+ to metal Bi. By modifying the solvothermal temperature and time, CQDs and Bi are in-situ controllably deposited on the surface of BiOBr microspheres. Due to different Fermi levels and work functions, the interfaces of CQDs, BiOBr and Bi are connected through ohmic junctions with low contact impedance. The hot electrons from Bi with surface plasmon resonance (SPR) properties, and electrons in the CB of BiOBr flow to CQDs, forming a C-scheme electron transfer mechanism. O2- from CQDs and h+ in the VB of BiOBr respectively attack the sites with higher and lower electron density in methyl orange (MO) molecule, resulting in its photodegradation into small molecular products.

CD244 expression represents functional decline of murine hematopoietic stem cells after in vitro culture.

Isolation of long-term hematopoietic stem cell (HSC) is possible by utilizing flow cytometry with multiple cell surface markers. However, those cell surface phenotypes do not represent functional HSCs after in vitro culture. Here we show that cultured HSCs express mast cell-related genes including Cd244. After in vitro culture, phenotypic HSCs were divided into CD244- and CD244+ subpopulations, and only CD244- cells that have low mast cell gene expression and maintain HSC-related genes sustain reconstitution potential. The result was same when HSCs were cultured in an efficient expansion medium containing polyvinyl alcohol. Chemically induced endoplasmic reticulum (ER) stress signal increased the CD244+ subpopulation, whereas ER stress suppression using a molecular chaperone, TUDCA, decreased CD244+ population, which was correlated to improved reconstitution output. These data suggest CD244 is a potent marker to exclude non-functional HSCs after in vitro culture thereby useful to elucidate mechanism of functional decline of HSCs during ex vivo treatment.