Cross-talk has been shown to occur between the immune system and bone metabolism pathways. In the present study, we investigated the impact of CD4 1 CD25 1 Foxp3 1 regulatory T (Treg) cells on osteoclastogenesis and bone resorption. Treg cells that were isolated and purified from peripheral blood mononuclear cells (PBMCs) of healthy adults inhibited both the differentiation of osteoclasts (OCs) from human embryo bone marrow cells (BMCs) and the pit formation in a dose-dependent manner. In cell cocultures, the production levels of both interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-b1) were proportionally upregulated as the ratio of Treg cells to BMCs was increased, and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-b1 antibodies. Treatment of BMC and Treg cell cocultures with 17b-estradiol (E2) at concentrations between 10 27 and 10 29 mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone; this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-b1 expression. These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-b1. E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-b1 secretion from these cells. Therefore, Treg cell-derived IL-10 and TGF-b1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis (PMO).

Physiological pregnancy requires the maternal immune system to recognize and tolerate embryonic Ags. Although multiple mechanisms have been proposed, it is not yet clear how the fetus evades the maternal immune system. In this article, we demonstrate that trophoblast-derived thymic stromal lymphopoietin (TSLP) instructs decidual CD11c+ dendritic cells (dDCs)with increased costimulatory molecules; MHC class II; and Th2/3-type, but not Th1-type, cytokines. TSLP-activated dDCs induce proliferation and differentiation of decidual CD4+CD25− T cells into CD4+CD25+FOXP3+ regulatory T cells (Tregs) through TGF-β1. TSLP-activated dDC–induced Tregs display immunosuppressive features and express Th2-type cytokines. In addition, decidual CD4+CD25+FOXP3+ Tregs promote invasiveness and HLA-G expression of trophoblasts, resulting in preferential production of Th2 cytokines and reduced cytotoxicity in decidual CD56brightCD16− NK cells. Of interest, decreased TSLP expression and reduced numbers of Tregs were observed at the maternal–fetal interface during miscarriage. Our study identifies a novel feedback loop between embryo-derived trophoblasts and maternal decidual leukocytes, which induces a tolerogenic immune response to ensure a successful pregnancy.

In awake rodents, the neural representation of olfactory information in the olfactory bulb is largely dependent on brain state and behavioral context. Learning-modified neural plasticity has been observed in mitral/tufted cells, the main output neurons of the olfactory bulb. Here, we propose that the odor information encoded by mitral/tufted cell responses in awake mice is highly dependent on the behavioral task demands. We used fiber photometry to record calcium signals from the mitral/tufted cell population in awake, head-fixed male mice under different task demands. We found that the mitral/tufted cell population showed similar responses to two distinct odors when the odors were presented in the context of a go/go task, in which the mice received a water reward regardless of the identity of the odor presented. However, when the same odors were presented in a go/no-go task, in which one odor was rewarded and the other was not, then the mitral cell population responded very differently to the two odors, characterized by a robust reduction in the response to the nonrewarded odor. Thus, the representation of odors in the mitral/tufted cell population depends on whether the task requires discrimination of the odors. Strikingly, downstream of the olfactory bulb, pyramidal neurons in the posterior piriform cortex also displayed a task-demand-dependent neural representation of odors, but the anterior piriform cortex did not, indicating that these two important higher olfactory centers use different strategies for neural representation.

The unique properties of two dimensional (2D) materials make them promising candidates for chemical and biological sensing applications. However, most 2D nanomaterial sensors suffer very long recovery time due to slow molecular desorption at room temperature. Here, we report a highly sensitive molybdenum ditelluride (MoTe 2 ) gas sensor for NO 2 and NH 3 detection with greatly enhanced recovery rate. The effects of gate bias on sensing performance have been systematically studied. It is found that the recovery kinetics can be effectively adjusted by biasing the sensor to different gate voltages. Under the optimum biasing potential, the MoTe 2 sensor can achieve more than 90% recovery after each sensing cycle well within 10 min at room temperature. The results demonstrate the potential of MoTe 2 as a promising candidate for high-performance chemical sensors. The idea of exploiting gate bias to adjust molecular desorption kinetics can be readily applied to much wider sensing platforms based on 2D nanomaterials.

We have previously shown that poly(I:C) activates murine hepatic cells to produce interferon (IFN) and suppresses hepatitis B virus (HBV) replication in vitro. Therefore, we addressed whether poly(I: C

Aim Leptin is an important peptide hormone that regulates food intake and plays a crucial role in modulating olfactory function. Although a few previous studies have investigated the effect of leptin on odor perception and discrimination in rodents, research on the neural basis underlying the behavioral changes is lacking. Here we study how leptin affects behavioral performance during a go/no‐go task and how it modulates neural activity of mitral/tufted cells in the olfactory bulb, which plays an important role in odor information processing and representation. Methods A go/no‐go odor discrimination task was used in the behavioral test. For in vivo studies, single unit recordings, local field potential recordings and fiber photometry recordings were used. For in vitro studies, we performed patch clamp recordings in the slice of the olfactory bulb. Results Behaviorally, leptin affects performance and reaction time in a difficult odor‐discrimination task. Leptin decreases the spontaneous firing of single mitral/tufted cells, decreases the odor‐evoked beta and high gamma local field potential response, and has bidirectional effects on the odor‐evoked responses of single mitral/tufted cells. Leptin also inhibits the population calcium activity in genetically identified mitral/tufted cells and granule cells. Furthermore, in vitro slice recordings reveal that leptin inhibits mitral cell activity through direct modulation of the voltage‐sensitive potassium channel. Conclusions The behavioral reduction in odor discrimination observed after leptin administration is likely due to decreased neural activity in mitral/tufted cells, caused by modulation of potassium channels in these cells.

Toll-like receptors (TLRs) are important in mediating immune responses against various pathogens during pregnancy. However, uncontrolled TLR-triggered inflammation will endanger normal pregnancy, resulting in pregnancy loss. Therefore, maintenance of a moderate inflammatory response is crucial for successful pregnancy under conditions of infection. Here, we demonstrated significantly lowered expression of T-cell immunoglobulin and mucin domain 3 (Tim-3) in miscarried decidual stromal cells (DSCs), indicating that Tim-3 might play important roles in maintaining successful pregnancies. Activation of TLR signaling induced pro-inflammatory cytokine production and apoptosis of DSCs, which was accompanied by up-regulated Tim-3 expression. Tim-3, in turn, protected DSCs from TLR-mediated apoptosis in an ERK1/2 pathway-dependent manner. In addition, Tim-3 inhibited TLR signaling-induced inflammatory cytokine production by DSCs through suppressing NF-κB activation. Tim-3 increased production of T helper 2 (Th2)-type cytokines by DSCs and reversed the inhibitory effect of LPS on Th2 cytokine generation by up-regulation of interferon regulatory factor 4 expression. Tim-3 blockade abolished the effect of Tim-3 on the inflammatory response to LPS stimulation. Thus, Tim-3 signaling could represent a “self-control” mechanism in TLR-triggered inflammation during pregnancy. These findings identify Tim-3 as a key regulator of DSCs and suggest its potential as a target for the treatment of spontaneous abortion.

We report on a new chemical sensor based on black phosphorus/molybdenum diselenide van der Waals hetero-junctions. Due to the atomically thin nature of two-dimensional (2D) materials, surface adsorption of gas molecules can effectively modulate the band alignment at the junction interface, making the device a highly sensitive detector for chemical adsorptions. Compared to sensors made of homogeneous nanomaterials, the hetero-junction demonstrates considerably lower detection limit and higher sensitivity toward nitrogen dioxide. Kelvin probe force microscopy and finite element simulations have provided experimental and theoretical explanations for the enhanced performance, proving that chemical adsorption can induce significant changes in band alignment and carrier transport behaviors. The study demonstrates the potential of van der Waals hetero-junction as a new platform for sensing applications, and provides more insights into the interaction between gaseous molecules and 2D hetero-structures.