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Background: Tumor microenvironment actually reduces antitumor effect against the immune attack by exclusion of CD8+T cells. Progranulin (PGRN) is a multifunctional growth factor with significant pathological effects in multiple tumors; however, its role in immunity evasion of breast cancer (BCa) is not completely understood. Methods: We depleted GRN (PGRN gene) genetically in mice or specifically in PY8119 murine BCa cell line, and mouse models of orthotopic or subcutaneous transplantation were used. Chimeric mice-deficient of PGRN (Grn−/−) in bone marrow (BM) compartment was also generated. Association of PGRN expression with chemokine production or BCa development was investigated by histological and immunological assays. Results: We found PGRN was involved in exhaustion of cytotoxic CD8+T cell in BCa with the increasing expressions of M2 markers and intercellular cell adhesion molecule-1 (ICAM-1) on macrophages. Specifically, ablation of PGRN in PY8119 cells reduced tumor burden, accompanied by the infiltrating of cytotoxic CD8+T cells into tumor nests. Moreover, our result revealed that blockade of PD-1 in PGRN-depleted tumors exhibited better antitumor effect in vivo and significantly decreased tumor burden. Conclusion: These findings suggest that inhibition of PGRN may act as a potential immune-therapeutic strategy by recovering infiltration of CD8+T cell in BCa tissue and thereby enhancing the response to anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

Using density functional theory calculation and rigid band model, we investigate the electronic structure and magnetostrictive properties of transition heavy-metal doped Fe-based (Fe–Al, Fe–Si, Fe–B, and Fe–Be) alloys. It is found that a small amount of addition of 4d/5d heavy-metal atoms greatly enhances the coefficient of tetragonal magnetostriction of Fe-based alloys, reaching up to about 1000 ppm in Fe87.5Al6.25Pt6.25 and Fe75Al18.75Rh6.25 alloys. The underlying mechanism is mainly ascribed to combined factors of band narrowing induced by non-bonded states in pure Fe layer, strong spin–orbit coupling effect by heavy metals, and improved mechanical properties, through analysis of the electronic density of states near Fermi level and k-mesh resolved magnetocrystalline anisotropy energy in momentum space. These results provide useful guidance for optimizing the magnetostrictive performance of Fe-based alloys for practical application. [ABSTRACT FROM AUTHOR]

In this paper, a second-order operator splitting method combined with the barycentric Lagrange interpolation collocation method is proposed for the nonlinear Schrödinger equation. The equation is split into linear and nonlinear parts: the linear part is solved by the barycentric Lagrange interpolation collocation method in space combined with the Crank–Nicolson scheme in time; the nonlinear part is solved analytically due to the availability of a closed-form solution, which avoids solving the nonlinear algebraic equation. Moreover, the consistency of the fully discretized scheme for the linear subproblem and error estimates of the operator splitting scheme are provided. The proposed numerical scheme is of spectral accuracy in space and of second-order accuracy in time, which greatly improves the computational efficiency. Numerical experiments are presented to confirm the accuracy, mass and energy conservation of the proposed method. [ABSTRACT FROM AUTHOR]

Magnetic units with large magnetic anisotropy energy (MAE) and high Curie temperature (Tc) are crucial for spintronic and quantum computing devices, which are a persisting demand for miniaturization of magnetic units. Using first-principles calculations and Monte Carlo simulation, it is found that monolayer 1T-CrTe2 exhibits strong perpendicular magnetic anisotropy with a MAE of approximately 5.29 meV and high Tc of ∼136 K. Interestingly, we find that the MAE and Tc of monolayer 1T-CrTe2 are tunable through electron/hole doping, strain, and heterostructure engineering. The magnetic easy-axis can be adjusted from out of plane to in plane, which is mainly attributed to the coupling between Te atomic orbitals ( p x , p y ). Second-order perturbation theory reveals that the spin–orbit coupling interaction between the occupied p x and unoccupied p y orbitals in opposite spin channel near Fermi level gives rise to negative contribution of MAE. Moreover, Tc can be enhanced to ∼230 K through super–superexchange mechanism of heterostructure due to the electron hopping between t 2 g / e g orbitals of Cr4+ ions and e 1 / a 1 orbitals of Fe2+ ions. Importantly, we find that Tc can be boosted above room temperature by applying moderate strain (6%), ascribing to significant enhancement of MAE and exchange coupling constant. The present work indicates that monolayer 1T-CrTe2-based two-dimensional materials are very promising for room temperature application in magnetic storage and information processing. [ABSTRACT FROM AUTHOR]

The electronic structures, charge mobility, and optical properties of the CsXBr3 (X = Ge and Sn) perovskite cells and blue phosphorus (BP) van der Waals heterojunctions have been investigated by using the first-principles method based on density functional theory. We found that the electronic band structures of layered BP and perovskite cells are still retained, a type II band arrangement can be observed in the heterojunctions, and the bandgaps of the heterojunctions gradually decrease with the increase in the number of perovskite layers. Additionally, electrons and holes are gathered at the BP and the perovskite interface of the heterojunctions, respectively. The potential difference formed by net charge aggregation at the BP and perovskite interface can result in a built-in electric field, which promotes the separation of electrons and holes. The maximum carrier mobility of the CsGe(Sn)Br3/BP heterojunctions can reach up to 7.364 × 103 (7.815 × 103) cm2 V−1 s−1 along the y direction of the electron in the CG(S)B/BP heterojunctions by the Boltzmann transport method. Moreover, due to the retention of the high absorption coefficient of monolayer BP, the light absorption spectra of the heterojunctions are obviously increased in the visible and purple light regions, and the absorption coefficient is as high as 105 cm−1, indicating that the heterojunctions could be potentially applied to various optoelectronic devices and solar cells. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of progranulin (PGRN) on the invasion and migration of mouse breast cancer 4T1 cells and its mechanism. Methods After treated with PGRN (1 μg/mL) for 24 hours, the invasion ability of breast cancer 4T1 cells was detected by Transwell TM invasion assay, the migration ability was detected by scratch test, and the epithelial cadherin (E-cadherin), vimentin mRNA expression was detected by real-time fluorescent quantitative PCR. Western blot assay was used to detect the expression of E-cadherin, vimentin, extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2). After treated with 1 μg/mL PGRN and ERK1/2 signaling pathway inhibitor U0126 (10 μmol/L) simultaneously, the migration and invasion ability of 4T1 cells and the changes in the expression of E-cadherin, vimentin and p-ERK proteins were detected again. Results After treated with PGRN, the migration and invasion capabilities of breast cancer 4T1 cells were significantly enhanced; E-cadherin expression decreased; vimentin and p-ERK1/2 expression increased. After treated with ERK1/2 signaling pathway inhibitor, the ability of PGRN to promote breast cancer 4T1 cell migration, invasion and epithelial-mesenchymal transition (EMT) was significantly inhibited. Conclusion PGRN can promote the migration and invasion of breast cancer 4T1 cells by promoting EMT and activating the ERK1/2 pathway.

Objective To explore the functions and mechanisms of macrophages derived from PGRN gene knockout (PGRN -/- ) C57BL/6 mice in the invasion and migration of breast cancer cells. Methods Breast cancer cells were cultured in conditioned medium of macrophages derived from WT and PGRN -/- mice. Transwell TM assay and scratch assay were used to detect the invasion and migration ability of cancer cells. Western blot analysis was used to detect the expression of E-cadherin and N-cadherin in cancer cells. Cytokine array, real-time quantitative PCR and ELISA were performed to investigate the differences of cytokines secreted by macrophages derived from WT and PGRN -/- mice. Breast cancer cells were treated by the differentially expressed cytokine interleukin-6 (IL-6), and then the above methods were used to investigate its effect on cancer cells. Western blot analysis was used to verify the roles of NF-κB and JAK/STAT3 signaling pathways. Results The macrophages derived from PGRN -/- mice blocked NF-κB signaling pathway, reduced IL-6 secretion, and inhibited the invasion and migration of breast cancer cells. IL-6 activated JAK/STAT3 signaling pathway to promote the invasion and migration of breast cancer cells. Conclusion The macrophages derived from PGRN -/- mice can block the NF-κB and JAK/STAT3 signaling pathways, down-regulate IL-6 expression, and inhibit the invasion and migration of breast cancer cells.