L1CAM overexpression promotes tumor progression through recruitment of regulatory T cells in esophageal carcinoma

Objective:L1 cell adhesion molecule(L1 CAM)exhibits oncogenic activity in tumors.However,the link between L1 CAM and the tumor microenvironment remains poorly understood in patients with esophageal squamous cell carcinoma(ESCC).In this study,we investigated how L1 CAM expression in ESCC affects the oncogenic characteristics of tumor cells and the tumor microenvironment.Methods:Human ESCC samples were collected,and the m RNA and protein levels of L1 CAM were examined by real-time PCR and immunohistochemistry.Overexpression and knockdown gene expression assays were used for mechanistic studies.The cell proliferation and cell cycle were measured with CCK-8 assays and flow cytometry.Cell migration and invasion ability were measured with Transwell assays.Multiplex bead-based assays were performed to identity the factors downstream of L1 CAM.Xenograft studies were performed in nude mice to evaluate the effects of L1 CAM on tumor growth and regulatory T cell(Treg)recruitment.Results:L1 CAM expression was significantly elevated in ESCC tissues(P<0.001)and correlated with poorer prognosis(P<0.05).Ablation of L1 CAM in ESCC cells inhibited tumor growth and migration,and increased tumor cell apoptosis(P<0.05).In the tumor microenvironment,L1 CAM expression correlated with Treg infiltration in ESCC by affecting CCL22 secretion.Mechanistically,L1 CAM facilitated CCL22 expression by activating the PI3 K/Akt/NF-κB signaling pathway.Furthermore,CCL22 promoted Treg recruitment to the tumor site;the Tregs then secreted TGF-β,which in turn promoted L1 CAM expression via Smad2/3 in a positive feedback loop.Conclusions:Our findings provide new insight into the mechanism of immune evasion mediated by L1 CAM,suggesting that targeting L1 CAM-CCL22-TGF-βcrosstalk between tumor cells and Tregs may offer a unique means to improve treatment of patients with ESCC.

An energy harvester combining a piezoelectric cantilever and a single degree of freedom elastic system

This paper presents a type of vibration energy harvester combining a piezoelectric cantilever and a single degree of freedom (SDOF) elastic system. The main function of the additional SDOF elastic system is to magnify vibration displacement of the piezoelectric cantilever to improve the power output. A mathematical model of the energy harvester is developed based on Hamilton's principle and Rayleigh-Ritz method. Furthermore, the effects of the structural parameters of the SDOF elastic system on the electromechanical outputs of the energy harvester are analyzed numerically. The accuracy of the output performance in the numerical solution is identified from the finite element method (FEM). A good agreement is found between the numerical results and FEM results. The results show that the power output can be increased and the frequency bandwidth can be improved when the SDOF elastic system has a larger lumped mass and a smaller damping ratio. The numerical results also indicate that a matching load resistance under the short circuit resonance condition can obtain a higher current output, and so is more suitable for application to the piezoelectric energy harvester.