Background: Previous studies have established that estrogen is capable of accelerating cutaneous wound healing through multiple mechanisms, one of which involves affecting keratinocytes biological properties, such as migration, proliferation, etc. This study aims to reveal the underlying molecular mechanisms of estrogen promoting epidermal keratinocytes proliferation. Method & Results: We found that compared with female mice with a normal estrous cycle, female mice with their ovaries removed before puberty exhibited a delayed cutaneous wound healing, thinner epidermis, and significantly fewer proliferating cell nuclear antigen (PCNA)-positive keratinocytes. Moreover, a significant increase in HaCaT proliferation was detected by a CCK8 assay when treated with 17 β-estradiol compared with those treated with control vehicle. Consistent with the results of the CCK8 assay, flow cytometry indicated a high proportion of 17 β-estradiol-treated HaCaT cells in S phase compared with vehicle-treated cells. Western blot analysis demonstrated the activation of Akt, Erk and upregulation of PCNA in HaCaT cells treated with 17 β-estradiol. Interestingly, Erk activation occurred prior to Akt activation. Upregulation of PCNA expression, elevated proliferation and high S phase fraction of HaCaT cell by 17 β-estradiol could be reversed by an Akt or Erk inhibitor. Moreover, Erk inhibition reversed 17 β-estradiol-induced Akt activation, whereas an Akt inhibitor exhibited no effect on Erk, further suggesting that Erk was on the upstream while Akt on the downstream of the signaling pathway. Conclusion: This study demonstrates that one of the critical mechanisms underlying 17 β-estradiol promoting skin wound healing is through regulation of keratinocyte proliferation via Erk/Akt signaling pathway.

MXenes are emerging rapidly as promising electrode materials for energy storage due to their high electronic conductivity and rich surface chemistry, but their potassium storage performance is unsatisfactory because of the large size of K+ and irreversible interfacial reaction. Here, a developed 3D foam‐like MXene scaffold (3D‐FMS) is constructed via an electrostatic neutralization of Ti3C2Tx with positive‐charged melamine followed with calcination, which offers massive surface‐active sites and facilitates fast K+ transfer for boosting the potassium‐ion storage capacity and dynamics. In addition, using KFSI‐based electrolyte, the formation of a robust solid electrolyte interface layer with more inorganic components on MXene anode is revealed for enhancing the Coulombic efficiency. Consequently, the 3D‐FMS with KFSI‐based electrolyte delivers enhanced potassium‐ion storage performance in terms of capacity (161.4 mAh g−1 at 30 mA g−1), rate capability (70 mAh g−1 at 2 A g−1), and cycling stability (80.5 mAh g−1 at 1 A g−1 after 2000 cycles). Moreover, the assembled 3D‐FMS//activated carbon potassium‐ion hybrid supercapacitor delivers a high energy density of 57 Wh kg−1 at a power density of 290 W kg−1. These excellent performances demonstrate the great superiority of 3D‐FMS in KFSI‐based electrolyte and may accelerate the development of MXene‐based materials for potassium storage systems.

CTLA4Ig has been successfully used in the clinic for suppression of T cell activation. However, patients treated with CTLA4Ig experienced reduced incidence of tumors than predicted, but the underlying mechanism remains unknown. In this paper, we showed that brief administration of CTLA4Ig significantly reduced tumor metastasis and prolonged the survival of host mice bearing B16 melanoma. Depletion of NK cells prior to CTLA4Ig administration eliminated the CTLA4Ig-mediated anti-tumor activity. CTLA4Ig enhanced NK cell cytotoxicity to tumor cells via up-regulation of NK cell effecter molecules CD107a and perforin in vivo. In addition, we demonstrated that, upon activation, NK cells could significantly increase the expression of CD86 both in vitro and in vivo, and ligation of CD86 with CTLA4Ig significantly increased the ability of NK cells to kill tumor cells. Furthermore, a human NK cell line that expressed high level of CD86 was directly activated by CTLA4Ig so that killing of tumor targets was enhanced; this enhanced killing could be inhibited by blocking CD86. Our findings uncover a novel function of CTLA4Ig in tumor immunity and suggest that CD86 on NK cells is an activating receptor and closely involved in the CTLA4Ig-mediated anti-tumor response.

Dendritic cells are specialized antigen-presenting cells that regulate immunity and tolerance. Chemokine receptor 7 (CCR7), which is expressed by mature dendritic cells, mediates the migration of the cells to secondary lymphoid organs and thus regulates immune responses. It has been demonstrated that immature dendritic cells can induce immune tolerance, but they do not express CCR7 and cannot migrate to secondary lymphoid organs. We transfected immature dendritic cells with a recombinant adenovirus carrying the CCR7 gene to obtain immature dendritic cells with the ability to migrate. The maturity of the cells was monitored by scanning electron microscopy and flow cytometry. In addition, we assessed the ability of cells to migrate and the function of the cells using in vitro chemotactic and mixed leukocyte reaction assays. The results showed that immature dendritic cells became semi-mature, exhibiting a mild upregulation of co-stimulatory molecular expression and a few dendritic processes. Immunofluorescence assay and Western blotting indicated that CCR7 protein expression increased significantly in immature dendritic cells following CCR7 gene transfection. The in vitro chemotactic assay showed a significantly enhanced ability to migrate in response to CCL19 following CCR7 gene transfection. Moreover, transfected cells showed an enhanced ability to stimulate allogeneic T cell proliferation in vitro, but their ability was significantly weaker than that of mature dendritic cells. Interleukin-10 inhibited the differentiation and maturation of immature dendritic cells. It is concluded that, following CCR7 gene transfection, immature dendritic cells exhibit an enhanced ability to migrate and some of the characteristics of mature cells. Thus, these cells are of potential clinical significance in studies of immune tolerance induction during skin grafting after severe burns.