Triggering receptor expressed on myeloid cells 2 (TREM-2) is a cell surface receptor abundantly expressed on myeloid lineage cells such as macrophages and dendritic cells. It is reported that TREM-2 functions as an inflammatory inhibitor in macrophages and dendritic cells. However, the role of TREM-2 in bacterial killing remains unclear. This study explored the role of TREM-2 in bacterial eradication of Pseudomonas aeruginosa (PA), a Gram-negative bacterium which causes various opportunistic infections. Phagocytosis assay assessed by flow cytometry suggested that TREM-2 was not involved in the uptake of PA by macrophages, while bacterial plate count data showed that TREM-2 was required for macrophage-mediated intracellular killing of PA. Moreover, our results demonstrated that TREM-2 promoted macrophage killing by enhancing reactive oxygen species (ROS), but not nitric oxygen (NO) production. Treatment with N-acetylcysteine, a ROS scavenger, diminished the TREM-2-mediated intracellular killing of PA. To further investigate the underlined mechanisms of TREM-2-promoted bacterial killing, we examined the activation of downstream mitogen-activated protein kinases and PI3K/Akt pathway. Western blot data showed that silencing of TREM-2 inhibited phosphorylation of Akt, but not ERK, JNK or P38. In addition, pretreatment with PI3K active product PIP3 DiC16 reversed the elevation of intracellular bacterial load in TREM-2-silenced macrophages, while PI3K inhibitor wortmannin restored the decline of bacterial load in TREM-2-overexpressed macrophages. These data together suggested that the TREM-2-mediated bacterial killing is dependent on the activation of PI3K/Akt signalling, which may provide a better understanding of the host antibacterial immune defence.
BackgroundCongenital absence of vas deferens (CAVD) is a major cause of obstructive azoospermia. Mutations in CFTR and ADGRG2 are responsible for this disease. However, until now the genetic spectrum of the CFTR and ADGRG2 genes in Chinese population and the reasons of the differences from Caucasian cohorts were not clear.Objectives(i) To study the characteristic and functional consequences of CFTR and ADGRG2 mutations in Chinese CAVD patients. (ii) To describe the genetic spectrum of Chinese CAVD patients and explain the reasons of the differences from Caucasian cohorts and Chinese cystic fibrosis (CF) patients.Materials and MethodsPatients were screened for mutations in CFTR by Sanger sequencing. Patients with only one or no mutations were further investigated by multiplex ligation‐dependent probe amplification analysis and direct sequencing of ADGRG2 gene. Bioinformatic analysis and structural modeling of proteins were performed.ResultsA total of 28 mutations in CFTR were identified in 72 patients, of which five mutations were novel. Fifty‐five patients (76.39%) had CFTR mutations but no indels, among which 80.00% CBAVD patients have at least one CFTR mutation and 66.67% CUAVD have at least one CFTR mutation. Two novel mutations (p.Lys818* and p.Arg1008Gln) in ADGRG2 were detected. These novel mutations were predicted to be damaging by bioinformatics and were absent or extremely low frequency among our controls and databases. The genetic spectrum of Chinese CAVD patients revealed that the most common mutations were c.1210‐12T[5], p.Ile556Val and p.Gln1352His, the last two of which were predicted to reduce the domains’ contacts and weaken adenosine triphosphate binding.Discussion and ConclusionThis study illustrates the significance of all exon sequencing in CFTR and ADGRG2. A picture of the genetic spectrum of Chinese CAVD patients and the most common mutations can be described, which are different from Caucasian cohorts and Chinese CF patients.
Topological Hall effect (THE) as one of spin-related effects originates from scalar spin chirality formed by non-coplanar spin structures, being a promising tool for probing the change of electron spin. Single-phase (022) Mn4N films with coplanar spin structures were prepared on unpoled ferroelectric [Pb(Mg1/3Nb2/3)O3]0.67-[PbTiO3]0.33 (PMN-PT) substrates. The transport properties of Mn4N/PMN-PT have been investigated. The decreased magnetization and anomalous resistivity imply that the spin states of Mn4N are influenced by ferroelectric polarization of the substrate. The observation of THE in the Mn4N/PMN-PT heterostructure strongly supports that the spin states of Mn4N are modified. After poling PMN-PT, the enhanced THE peak magnitude verifies that the spin states of Mn4N are tuned by ferroelectric polarization. This study provides a non-magnetic method for manipulation of spin states, which could avoid the external magnetic field perturbations.
The anomalous Hall effect (AHE) in the Mn4N/Au bilayers with various Au thicknesses has been investigated. The new scaling including multiple competing mechanisms is employed to analyze the contributions to the AHE. The obvious variations in the skew scattering coefficient α and the two scattering coefficients (β0 + β1 − γ) and (γ − 2β1) in the bilayers reveal that the skew scattering term and the side-jump contribution are dramatically modified, implying that the mechanisms in the bilayers are different from those in the single Mn4N. On further analysis, we find that the coefficient β0 involving the intrinsic mechanism and side-jump contribution also varies, which confirms the experimental results. It is proposed that the modification of the AHE is induced by the spin-orbital coupling from the heavy metal, providing a practical way to tune the AHE.
This paper deals with the problem of time-varying (TV) channel estimation for multiple-input multiple-output/orthogonal frequency-division multiplexing (MIMO/OFDM) systems based on superimposed training (ST). The time-varying coefficients of the TV channel are firstly modeled by truncated discrete Fourier bases, and then optimally estimated both in one OFDM symbols and over multiple OFDM symbols by judiciously designing the superimposed pilots. In addition, an iterative symbol detection based channel estimation scheme with analytical performance analysis, is provided to mitigate the interference due to the unknown information sequences (thus to further improve channel estimation performance as well as SER levels). Simulations confirm that the proposed estimator achieves a considerable gain in estimating TV channels, and exhibits a nearly indistinguishable symbol error rate performance from the OFDM systems of frequency-division multiplexed trainings. 1 .
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