In sporadic age-related forms of Alzheimer’s disease (AD), it is unclear why amyloid-β (Aβ) peptides accumulate. Here, we show that soluble amyloid precursor protein-α (sAPP-α) decreases Aβ generation by directly associating with BACE1; thereby modulating APP processing. Whereas specifically targeting sAPP-α using antibodies enhances Aβ production, in transgenic mice with AD-like pathology, sAPP-α overexpression decreases β-amyloid plaques and soluble Aβ. In support, immunoneutralization of sAPP-α increases APP amyloidogenic processing in these mice. Given our current findings, and because a number of risk factors for sporadic AD serve to lower levels of sAPP-α in brains of AD patients, inadequate sAPP-α levels may be sufficient to polarize APP processing toward the amyloidogenic, Aβ-producing route. Therefore, restoration of sAPP-α or enhancement of its association with BACE may be viable strategies to ameliorate imbalances in APP processing that can lead to AD pathogenesis.

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Mesenchymal stem cells (MSCs) are derived from the mesoderm and have the self-renewal capacity and multi-directional differentiation potential of adult stem cells. Stem cells from different sources have different molecular and growth characteristics; therefore, the mechanisms and effects of stem cell-mediated repair and tissue regeneration may be different. The aim of the present study was to compare the biological characteristics of MSCs derived from the umbilical cord (UC-MSCs) and MSCs derived from the decidua parietalis (DP-MSCs), and to provide new evidence for the selection of seed cells in regenerative medicine. Growth curves, cell doubling times, colony formation rates, immunophenotypes, differentiation capacities and secretion-factor levels of MSCs derived from the two sources were analysed. UC-MSCs and DP-MSCs exhibited similar properties with regards to morphology, spiral growth, immunophenotype, and potential to differentiate into osteoblasts and adipocytes. For each cell type, the positive rates of the cell surface markers CD73, CD90 and CD105 were >95%, whereas CD34 and CD45 positive rates were <1%. Analyses of in vitro growth kinetics revealed shorter cell-doubling times, and higher proliferative rates and colony formation rates of UC-MSCs compared with DP-MSCs (P<0.05). The concentration of basic fibroblast growth factor in the supernatant from UC-MSCs was higher compared with that from DP-MSCs (P<0.05). However, UC-MSC supernatants exhibited lower levels of of keratinocyte growth factor, vascular endothelial growth factor and stem cell factor compared with DP-MSCs (P<0.05). In conclusion, in vitro characterization of MSCs from these tissue sources revealed a number of common biological properties. However, the results also demonstrated clear biological distinctions and suggested that UC-MSCs may have more effective application prospects.

Embryo implantation is essential to the successful establishment of pregnancy. A previous study has demonstrated that actinomycin D (ActD) could initiate the activation of mouse delayed implantation. However, the mechanism underlying this activation remains to be elucidated. A low dose of ActD is an inducer of nucleolar stress. This study was to examine whether nucleolar stress is involved in embryo implantation. We showed that nucleolar stress occurred when delayed implantation was activated by ActD in mice. ActD treatment also stimulated the Lif-STAT3 pathway. During early pregnancy, nucleolar stress was detected in the luminal epithelial cells during the receptive phase. Blastocyst-derived lactate could induce nucleolar stress in cultured luminal epithelial cells. The inhibition of nucleophosmin1 (NPM1), which was a marker of nucleolar stress, compromised uterine receptivity and decreased the implantation rates in pregnant mice. To translate these mouse data into humans, we examined nucleolar stress in human endometrium. Our data demonstrated that ActD-induced nucleolar stress had positive effects on the embryo attachment by upregulating IL32 expression in non-receptive epithelial cells rather than receptive epithelial cells. Our data should be the first to demonstrate that nucleolar stress is present during early pregnancy and is able to induce embryo implantation in both mice and humans.

Hydrogel dressings have significant advantages such as absorption of tissue exudate, maintenance of proper moist environment, and promotion of cell proliferation. However, facile preparation method and high‐efficient antibacterial hydrogel dressings are still a great challenge. In this study, a facile approach to prepare antibacterial nanocomposite hydrogel dressing to accelerate healing was explored. The hydrogels consisted of quaternized chitosan and chemically cross‐linked polyacrylamide, as well as silver nanoparticles (AgNPs) stabilized by chitosan. The synthesis of the hydrogels including the formation of AgNPs and polymerization of acrylamide was accomplished simultaneously under UV irradiation in 1 hour without adding initiator. The hydrogels showed favorable tensile strength of ∼100 kPa with elongation at break over 1000% and shear modulus of ∼104 Pa as well as suitable swelling ratio, which were appropriate for wound dressing. The combination of quaternized chitosan and AgNPs exhibited high‐efficient and synergetic antibacterial performance with low cytotoxicity. In vivo animal experiments showed that the hydrogel can effectively prevent wound infection and promote wound healing. This study provides a facile method to produce antibacterial hydrogel wound dressing materials.