Beyond Immune Balance: The Pivotal Role of Decidual Regulatory T Cells in Unexplained Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is defined as two or more consecutive pregnancy failures, which brings tremendous stress to women of childbearing age and seriously affects family well-being. However, the reason in about 50% of cases remains unknown and is defined as unexplained recurrent spontaneous abortion (URSA). The immunological perspective in URSA has attracted widespread attention in recent years. The embryo is regarded as a semi-allogeneic graft to the mother. A successful pregnancy requires transition to an immune environment conducive to embryo survival at the maternal-fetal interface. As an important member of regulatory immunity, regulatory T (Treg) cells play a key role in regulating immune tolerance at the maternal-fetal interface. This review will focus on the phenotypic plasticity and lineage stability of Treg cells to illustrate its relationship with URSA.

Role of macrophage polarization in periodontitis promoting atherosclerosis.

Periodontitis is a chronic inflammatory destructive disease occurring in periodontal supporting tissues. Atherosclerosis(AS) is one of the most common cardiovascular diseases. Periodontitis can promote the development and progression of AS. Macrophage polarization is closely related to the development and progression of the above two diseases, respectively. The purpose of this animal study was to evaluate the effect of periodontitis on aortic lesions in atherosclerotic mice and the role of macrophage polarization in this process. 45 ApoE-/-male mice were randomly divided into three groups: control (NC), atherosclerosis (AS), and atherosclerosis with periodontitis (AS + PD). Micro CT, serological testing and pathological testing(hematoxylin-eosin staining, oil red O staining and Masson staining) were used for Evaluate the modeling situation. Immunohistochemistry(IHC) and immunofluorescence(IF) were performed to evaluate macrophage content and macrophage polarization in plaques. Cytokines associated with macrophage polarization were analyzed using quantitative real-time polymerase chain reaction(qRT-PCR) and enzyme-linked immunosorbent assay(Elisa). The expression of macrophages in plaques was sequentially elevated in the NC, AS, and AS + PD groups(P < 0.001). The expression of M1 and M1-related cytokines showed the same trend(P < 0.05). The expression of M2 and M2-related cytokines showed the opposite trend(P < 0.05). The rate of M1/M2 showed that AS + PD > AS > NC. Our preliminary data support that experimental periodontitis can increase the content of macrophage in aortic plaques to exacerbate AS. Meanwhile, experimental periodontitis can increase M1 macrophages, and decrease M2 macrophages, increasing M1/M2 in the plaque.

Optimizing Molecular Crystallinity and Suppressing Electron-Phonon Coupling in Completely Non-Fused Ring Electron Acceptors for Organic Solar Cells.

High open-circuit voltage (Voc) organic solar cells (OSCs) have received increasing attention because of their promising application in tandem devices and indoor photovoltaics. However, the lack of a precise correlation between molecular structure and stacking behaviors of wide band gap electron acceptors has greatly limited its development. Here, we adopted an asymmetric halogenation strategy (AHS) and synthesized two completely non-fused ring electron acceptors (NFREAs), HF-BTA33 and HCl-BTA33. The results show that AHS significantly enhances the molecular dipoles and suppresses electron-phonon coupling, resulting in enhanced intramolecular/intermolecular interactions and decreased nonradiative decay. As a result, PTQ10 : HF-BTA33 realizes a power conversion efficiency (PCE) of 11.42 % with a Voc of 1.232 V, higher than that of symmetric analogue F-BTA33 (PCE=10.02 %, Voc=1.197 V). Notably, PTQ10 : HCl-BTA33 achieves the highest PCE of 12.54 % with a Voc of 1.201 V due to the long-range ordered π-π packing and enhanced surface electrostatic interactions thereby facilitating exciton dissociation and charge transport. This work not only proves that asymmetric halogenation of completely NFREAs is a simple and effective strategy for achieving both high PCE and Voc, but also provides deeper insights for the precise molecular design of low cost completely NFREAs.

Effects of Ni Content and Heat Treatment on the Properties, Microstructures, and Precipitates of Cu-0.2 wt% Be-x wt% Ni Alloys.

Cu-Be alloys exhibit excellent comprehensive performance in electrics, thermotics, and mechanics, and hence, they attract much attention. Among them, low-Be copper alloys are more environmentally friendly and promising. This study explores the effects of different Ni contents and heat treatment parameters on the properties, microstructures, and precipitates of Cu-0.2 wt% Be-x wt% Ni (0 < x < 2.0) alloys. The experimental results demonstrate that the fast cooling rate of cast alloys during solidification contributes to retention of the solute atoms in the copper matrix, which is beneficial for subsequent solid solution treatment. Furthermore, solid solution treatment slightly reduces the electrical conductivities, microhardness values, and compressive yield strengths of Cu-0.2 wt% Be-1.0/1.6 wt% Ni alloys. The optimal solution temperature and time are about 925 ℃ and 60 min, respectively. Aging treatment significantly increases the electrical conductivities, microhardness values, and compressive yield strengths of Cu-0.2 wt% Be-1.0/1.6 wt% Ni alloys. The best aging temperature is around 450 ℃. However, the properties of Cu-0.2 wt%Be-0.4 wt%Ni alloys remain unaffected by solution and aging treatments. Around x = 1.0, Cu-0.2 wt% Be-x wt% Ni alloys possess the best comprehensive properties, which are about 72%IACS of electrical conductivity, 241 HV of microhardness, and 281MPa of compressive yield strength, respectively. TEM and EDS analyses reveal that the precipitate evolution of Cu-0.2 wt% Be-1.0 wt% Ni alloys with aging time is GP zones → γ″ → γ'. Notably, a distinct double-peak age strengthening phenomenon emerges with Cu-0.2 wt% Be-1.0/1.6 wt% Ni alloys. The precipitation of plenty of GP zones at the early stage of aging should account for the first strengthening peak, and the strengthening mechanism transformation of the γ″ or γ' phase from shear to Orowan should induce the second strengthening peak. This work may help to design new low-Be copper alloys and their preparation processes.

Efficient CsPbBr3 Perovskite Light-Emitting Diodes via Novel Multi-Step Ligand Exchange Strategy Based on Zwitterionic Molecules.

Perovskite nanocrystals have absorbed increasing interest, especially in the field of optoelectronics, owing to their unique characteristics, including their tunable luminescence range, robust solution processability, facile synthesis, and so on. However, in practice, due to the inherent instability of the traditional long-chain insulating ligands surrounding perovskite quantum dots (PeQDs), the performance of the as-fabricated QLED is relatively disappointing. Herein, the zwitterion 3-(decyldimethylammonio)propanesulfonate (DLPS) with the capability of double passivating perovskite quantum dots could effectively replace the original long-chain ligand simply through a multistep post-treatment strategy to finally inhibit the formation of defects. It was indicated from theexperimental results that the DLPS, as one type of ligand with the bimolecular ion, was very adavntageous in replacing long-chain ligands and further suppressing the formation of defects. Finally, the perovskite quantum dots with greatly enhanced PLQY as high as 98% were effectively achieved. Additionally, the colloidal stability of the corresponding PeQDs has been significantly enhanced, and a transparent colloidal solution was obtained after 45 days under ambient conditions. Finally, the as-fabricated QLEDs based on the ligand-exchanged PeQDs exhibited a maximum brightness of 9464 cd/m2 and an EQE of 12.17%.

Bipolaris fujianensis sp. nov., an Emerging Pathogen of Sapling Shoot Blight on Chinese Fir, and Its Sensitivity to Fungicides.

Chinese fir is an extremely important economic tree species in southern China. In recent years, 74.5% of Chinese fir saplings suffered from shoot blight in Shunchang County, Nanping City, Fujian Province, China. Seventeen isolates were collected from rotten shoots, and their pathogenicity was confirmed following Koch's postulates. The five pathogenic isolates were identified as belonging to the genus Bipolaris based on morphological characteristics, including septate and geniculate conidiophores, smooth to slightly verruculose conidiogenous nodes, dematiaceous phragmospore conidia, oblong or fusiform conidia, and slightly protruding or truncate hilum on conidia, but the number of pseudosepta (3 to 11, mostly 5 to 8) and the size of conidia ([22.81 to 116.13] × [9.16 to 26.58] µm) are different from those of the known species of Bipolaris. A phylogenetic analysis based on ITS, GAPDH, and Tef1-α sequences determined that the five strains belong to a new species of Bipolaris, and the name Bipolaris fujianensis sp. nov. is proposed. The fungicide sensitivity of the pathogen strain Cfsb3 was further evaluated using eight fungicides. Flusilazole, difenoconazole, tebuconazole, and propiconazole exhibited high toxicity to Cfsb3, and the effective concentration inhibiting 50% (EC50) of mycelial growth was 0.08, 0.20, 0.34, and 0.36 µg/ml, respectively, for these four fungicides. Flusilazole, difenoconazole, and iprodione inhibited B. fujianensis by 100% on detached Chinese fir shoots at their recommended concentrations, but azoxystrobin and thiram were ineffective. In conclusion, this study reported an emerging pathogen of Chinese fir sapling shoot blight and proposed triazole and dicarboximide fungicides for disease control.

The interrelation of galectins and autophagy.

Autophagy is a vital physiological process that maintains intracellular homeostasis by removing damaged organelles and senescent or misfolded molecules. However, excessive autophagy results in cell death and apoptosis, which will lead to a variety of diseases. Galectins are a type of animal lectin that binds to ß-galactosides and can bind to the cell surface or extracellular matrix glycans, affecting a variety of immune processes in vivo and being linked to the development of many diseases. In many cases, galectins and autophagy both play important regulatory roles in the cellular life course, yet our understanding of the relationship between them is still incomplete. Galectins and autophagy may share common etiological cofactors for some diseases. Hence, we summarize the relationship between galectins and autophagy, aiming to draw attention to the existence of multiple associations between galectins and autophagy in a variety of physiological and pathological processes, which provide new ideas for etiological diagnosis, drug development, and therapeutic targets for related diseases.

Placental exosomal miR-125b triggered endothelial barrier injury in preeclampsia.

INTRODUCTION: Preeclampsia (PE) is an elusive life-threatening complication of pregnancy, and maternal endothelial dysfunction induced by components from the impaired placenta is a key hallmark of PE. Placenta-derived exosomes in maternal circulation have been correlated with risk of PE, however, the role of exosomes in PE remains to be determined. We hypothesized that placenta-released exosomes link the placental abnormalities with maternal endothelial dysfunction in PE. METHODS: Circulating exosomes were collected from plasma samples of preeclamptic patients and normal pregnancies. Endothelial barrier function was examined by transendothelial electrical resistance (TEER) and cell permeability to FITC-dextran assays in human umbilical vein endothelial cells (HUVECs). miR-125b and VE-cadherin gene expression in exosomes and endothelial cells were assessed by qPCR and Western, and the possible post-transcriptional regulation of miR-125b on VE-cadherin was detected by luciferase assay. RESULTS: We isolated placenta-derived exosomes in the maternal circulation and found that placenta-derived exosomes from preeclamptic patients (PE-exo) leads to endothelial barrier dysfunction. We then identified decreased expression of VE-cadherin in endothelial cells contribute to the breakdown of the endothelial barrier. Further investigations revealed increased exosomal miR-125b in PE-exo directly inhibited VE-cadherin in HUVECs, thereby mediating the adverse effect of PE-exo on endothelial barrier function. DISCUSSION: Placental exosomes link impaired placentation and endothelial dysfunction, thus providing new insight into the pathophysiology of preeclampsia. Exosomal miRNAs derived from placenta contribute to the endothelial dysfunction in PE and could be a promising therapeutic target for PE.

RANKL up-regulated by progesterone aggravates lipopolysaccharide-induced acute lung injury during pregnancy.

Acute lung injury (ALI) is a common acute respiratory disease with high morbidity and mortality rate in pregnant women. Receptor activator of NF-κB ligand (TNFSF11, also known as RANKL) exerts either pro-inflammatory or anti-inflammatory effects on the immune response. LPS administration reduced the survival time (n = 10, p < 0.01), increased wet/dry ratio (n = 10, p < 0.001) and lung injury score (n = 10, p < 0.001), the elevated proportions of plasmacytoid dendritic cells (pDCs) (n = 10, p < 0.0001), tissue-resident DCs (resDCs) (n = 10, p < 0.0001), macrophages (n = 10, p < 0.0001), and neutrophils (n = 10, p < 0.0001), and the expressions of costimulatory molecules and inflammation cytokines (n = 10, p < 0.05) in lungs of pregnant mice, compared with non-pregnant mice. In vitro, progesterone up-regulated the expression of RANKL (n > 6, p < 0.05) on pulmonary fibroblasts. The results of cytokine arrays showed that the cytokines associated with inflammatory response and leukocyte differentiation were decreased in pulmonary fibroblasts after treatment with anti-RANKL neutralizing antibody, compared with control pulmonary fibroblasts. More notably, we found that Tnfsf11-/- pregnant mice had longer survival durations (n = 10, p < 0.01), lower lung injury scores (n = 10, p < 0.05), and lower immune cell infiltration (n = 10, p < 0.05). These data imply that the RANKL/RANK axis plays an essential role in LPS-induced ALI during pregnancy possibly through a variety of pathways.

Decidual macrophages in recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is defined as two or more pregnancy loss, affecting the happiness index of fertility couples. The mechanisms involved in the occurrence of RSA are not clear to date. The primary problem for the maternal immune system is how to establish and maintain the immune tolerance to the semi-allogeneic fetuses. During the pregnancy, decidual macrophages mainly play an important role in the immunologic dialogue. The purpose of this study is to explore decidual macrophages, and to understand whether there is a connection between these cells and RSA by analyzing their phenotypes and functions. Pubmed, Web of Science and Embase were searched. The eligibility criterion for this review was evaluating the literature about the pregnancy and macrophages. Any disagreement between the authors was resolved upon discussion and if required by the judgment of the corresponding author. We summarized the latest views on the phenotype, function and dysfunction of decidual macrophages to illuminate its relationship with RSA.

Astrocyte-specific loss of lactoferrin influences neuronal structure and function by interfering with cholesterol synthesis.

Growing evidence indicates that circulating lactoferrin (Lf) is implicated in peripheral cholesterol metabolism disorders. It has emerged that the distribution of Lf changes in astrocytes of aging brains and those exhibiting neurodegeneration; however, its physiological and/or pathological role remains unknown. Here, we demonstrate that astrocyte-specific knockout of Lf (designated cKO) led to decreased body weight and cognitive abnormalities during early life in mice. Accordingly, there was a reduction in neuronal outgrowth and synaptic structure in cKO mice. Importantly, Lf deficiency in the primary astrocytes led to decreased sterol regulatory element binding protein 2 (Srebp2) activation and cholesterol production, and cholesterol content in cKO mice and/or in astrocytes was restored by exogenous Lf or a Srebp2 agonist. Moreover, neuronal dendritic complexity and total dendritic length were decreased after culture with the culture medium of the primary astrocytes derived from cKO mice and that this decrease was reversed after cholesterol supplementation. Alternatively, these alterations were associated with an activation of AMP-activated protein kinase (AMPK) and inhibition of SREBP2 nuclear translocation. These data suggest that astrocytic Lf might directly or indirectly control in situ cholesterol synthesis, which may be implicated in neurodevelopment and several neurological diseases.

Carboxylate-Containing Wide-Bandgap Polymers for High-Voltage Non-Fullerene Organic Solar Cells.

As one of the polymer modification strategies, carboxylate functionalization has proved effective in downshifting the energy levels and enhancing polymer crystallinity and aggregation. However, high-performance carboxylate-containing polymers are still limited for organic solar cells (OSCs), especially with open-circuit voltage (VOC) above 1.0 V. Herein, we utilize two carboxylate-functionalized wide-band gap (WBG) donor polymers (TTC-F and TTC-Cl) to pair with two WBG electron acceptors (BTA5 and F-BTA5) for high-voltage OSCs. Due to the deeper molecular energy levels, chlorinated polymer TTC-Cl shows higher VOC than fluorinated polymer TTC-F. Furthermore, because of the stronger aggregation in the film, the TTC-Cl-based devices attain suppressed energetic disorders and trap-assisted recombination, decreasing voltage loss and JSC loss. Finally, the TTC-Cl: F-BTA5 blend achieves a higher VOC of 1.17 V and an excellent PCE of 10.98%, one of the best results for high-voltage carboxylate-containing polymers. In addition, the TTC-Cl: BTA5 combination demonstrates the highest VOC of 1.25 V with an ultralow nonradiative energy loss of 0.17 eV. Our results indicate that the carboxylate-containing polymer donors have significant application potential for high-voltage OSCs due to reduced energy loss and improved charge transport and dissociation. Furthermore, the matched absorption spectra with the indoor light sources and low voltage loss promote these material combinations to construct high-performance indoor photovoltaics.

Ginsenoside Compound K Protects against Obesity through Pharmacological Targeting of Glucocorticoid Receptor to Activate Lipophagy and Lipid Metabolism.

(1) Background: The glucocorticoid receptor (GR) plays a key role in lipid metabolism, but investigations of GR activation as a potential therapeutic approach have been hampered by a lack of selective agonists. Ginsenoside compound K (CK) is natural small molecule with a steroid-like structure that offers a variety of therapeutic benefits. Our study validates CK as a novel GR agonist for the treatment of obesity. (2) Methods: By using pulldown and RNA interference, we determined that CK binds to GR. The anti-obesity potential effects of CK were investigated in obese mice, including through whole-body energy homeostasis, glucose and insulin tolerance, and biochemical and proteomic analysis. Using chromatin immunoprecipitation, we identified GR binding sites upstream of lipase ATGL. (3) Results: We demonstrated that CK reduced the weight and blood lipids of mice more significantly than the drug Orlistat. Proteomics data showed that CK up-regulated autophagy regulatory proteins, enhanced fatty acid oxidation proteins, and decreased fatty acid synthesis proteins. CK induced lipophagy with the initial formation of the phagophore via AMPK/ULK1 activation. However, a blockade of autophagy did not disturb the increase in CK on lipase expression, suggesting that autophagy and lipase are independent pathways in the function of CK. The pulldown and siRNA experiments showed that GR is the critical target. After binding to GR, CK not only activated lipophagy, but also promoted the binding of GR to the ATGL promoter. (4) Conclusions: Our findings indicate that CK is a natural food candidate for reducing fat content and weight.

Uterine natural killer cells and recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA), termed as two or more consecutive pregnancy loss is a great problem for some women of childbearing age. A large number of evidence confirm that there may be an immune background of RSA. As a member of the innate immune system, uterine natural killer (uNK) cells account for about 70% of total lymphocytes during pregnancy and play a critical role in the establishment and maintenance of pregnancy. This review mainly introduces the phenotype, origin, receptor, and function of uNK cells to illuminate its relationship with RSA.

Recombinant human lactoferrin attenuates the progression of hepatosteatosis and hepatocellular death by regulating iron and lipid homeostasis in ob/ob mice.

Lactoferrin (Lf), an iron-binding glycoprotein, has been shown to possess antioxidant and anti-inflammatory properties and exert modulatory effects on lipid homeostasis and non-alcoholic fatty liver disease (NAFLD), but our understanding of its regulatory mechanisms is limited and inconsistent. We used leptin-deficient (ob/ob) mice as the rodent model of NAFLD, and administered recombinant human Lf (4 mg per kg body weight) or control vehicle by intraperitoneal injection to evaluate the hepatoprotective effects of Lf. After 40 days of treatment with Lf, insulin sensitivity and hepatic steatosis in ob/ob mice were significantly improved with the down-regulation of sterol regulatory element binding protein-2 (SREBP2), indicating an improvement in hepatic lipid metabolism and function. We further explored the mechanism, and found that Lf may increase the hepatocellular iron output by targeting the hepcidin-ferroportin (FPn) axis, and then maintains the liver oxidative balance through a nonenzymatic antioxidant system, ultimately suppressing the death of hepatocytes. In addition, the cytoprotective role of Lf may be associated with the inhibition of endoplasmic reticulum (ER) stress and inflammation, promotion of autophagy of damaged hepatocytes and induction of up-regulation of hypoxia inducible factor-1α/vascular endothelial growth factor (HIF-lα/VEGF) to facilitate liver function recovery. These findings suggest that recombinant human Lf might be a potential therapeutic agent for mitigating or delaying the pathological process of NAFLD.

Elevated microRNA-125b inhibits cytotrophoblast invasion and impairs endothelial cell function in preeclampsia.

Preeclampsia (PE) is a life-threatening disorder of human pregnancy affecting 5-8% of all pregnancies. Currently, PE remains an elusive complicated and heterogenous medical condition with no early marker or symptoms is recognized for this serious pregnancy complications. Here, we profiled the plasma miRNA expression patterns associated with preeclampsia and found 16 miRNAs were deregulated (p < 0.01) in patients who later developed PE. Circulating hsa-miR-125b was aberrantly upregulated in early pregnancy and significantly reduced after delivery in preeclampsia. We then investigated the underlying molecular mechanisms between miR-125b and PE in vitro. We found that upregulated miR-125b can target KCNA1 to inhibit trophoblast invasion in human trophoblast cells. Moreover, overexpression of miR-125b in HUVECs impaired endothelial cell function through GPC1. The findings indicated that upregulated miR-125b leads to impaired placentation, and an increased risk of preeclampsia, Our studies provide novel insights into the underlying mechanisms on the association of miR-125b in early pregnancy and risk of PE, miR-125b might be a more specific predictive marker and a safe therapeutic target for treating patients with PE.

The bioflavonoid quercetin improves pathophysiology in a rat model of preeclampsia.

Preeclampsia (PE) is a pregnancy-specific hypertensive syndrome and is a leading risk of thousands of patient and offspring's deaths worldwide with no effective therapies but early delivery. Quercetin is associated with multiple pathways that link placental dysfunction with the maternal system phenotypes in the pathogenesis of PE, however, whether quercetin can be used to treat preeclampsia is not known. We employed a preeclampsia animal model induced by ultra-low-dose endotoxin infusion and monitored angiogenic factors, inflammatory response and oxidative stress changes after quercetin treatment. We showed that quercetin attenuated multi-pathophysiology changes induced by LPS and ameliorated the symptoms. We concluded that quercetin significantly improved the pathophysiology in PE and could be developed as candidates for preeclampsia treatment.

ADATMS-7 regulates the focal adhesion kinase signaling and promotes invasiveness of trophoblasts in early pregnancy.

INTRODUCTION: ADAMTS-7, a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, was recently identified to be associated with cell migration and invasion. However, its function on trophoblasts remains unknown. In this study, we are aimed to investigate the role of ADAMTS-7 on trophoblasts in human first trimester gestation. METHODS: The expression of ADAMTS-7 in trophoblasts and HTR8/SVneo cells is examined by immunohistochemistry and quantitative real-time PCR. BrdU incorporation and Annexin V/PI staining are utilized to measure the effect of ADAMTS-7 on the proliferation and apoptosis of HTR8/SVneo cells, respectively. In addition, we detect the role of ADAMTS-7 on the invasion ability of HTR8/SVneo cells using matrigel invasion assays. The activation of focal adhesion kinase (FAK) and integrinß1 induced by ADAMTS-7 were determined by Western blot. RESULTS: ADAMTS-7 and its substrate cartilage oligomeric matrix protein (COMP) were expressed in both primary human trophoblasts and human trophoblast cell lines. TGF-ß1 induced a continuous and significant decrease of ADAMTS-7. Inversely, IL-1ß up-regulated the ADAMTS-7 level in a dosage dependent manner. In addition, knockdown of ADAMTS-7 inhibited the growth and invasion of HTR8/SVneo cells. To the contrary, ADAMTS-7 overexpression promoted the growth and invasion of HTR8/SVneo cells. ADAMTS-7 knockdown led to a decreased level of FAK Tyr-397 phosphorylation. DISCUSSION: Our results suggest that ADAMTS-7 may regulate trophoblasts invasion through focal adhesion kinase (FAK) signaling.

Negative regulation of AMPKα1 by PIM2 promotes aerobic glycolysis and tumorigenesis in endometrial cancer.

Endometrial cancer (EC) is one of the most common gynecologic malignancies. However, the molecular mechanisms underlying the development and progression of EC remain unclear. Here, we demonstrated that the protein proviral insertion in murine lymphomas 2 (PIM2) was necessary for maintaining EC tumorigenesis in vivo and in vitro, and could inhibit AMPKα1 kinase activity in EC cells. Specifically, we found that PIM2 bound to AMPKα1, and directly phosphorylated it on Thr467. Phosphorylation of AMPKα1 by PIM2 led to decreasing AMPKα1 kinase activity, which in turn promoted aerobic glycolysis and tumor growth. In addition, PIM2 expression positively correlated with AMPKα1 Thr467 phosphorylation in EC tissues. Further, treatment with a combination of the PIM2 inhibitor SMI-4a and the AMPKα1 activator AICAR could effectively inhibit tumor growth. Thus, our findings provide insight into the role of PIM2 and AMPKα1 in EC and suggest that combination targeting of these proteins may represent a new strategy for EC treatment.

Decidual RANKL/RANK interaction promotes the residence and polarization of TGF-ß1-producing regulatory γδ T cells.

ABSTACT: Decidual Î³Î´Τ (dγδΤ) cells play an essential role during successful pregnancy; however, the residence and polarization of Î³Î´Τ cells in decidua remain unclear. In this study, we observed higher levels of receptor activator for nuclear factor-κ B ligand (RANKL) on decidual stromal cells (DSCs), and its receptor RANK on dÎ³Î´Τ cells in decidua from normal pregnancy compared with patients with recurrent spontaneous abortion (RSA). RANKL expressed by DSCs can induce the polarization of peripheral blood Î³Î´Τ (pγδΤ) and dÎ³Î´Τ cells to Foxp3 + Î³Î´Τ cells, and upregulate the expression of transforming growth factor (TGF)-ß1. This process is mediated through activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In addition, RANKL promotes the adhesion of dÎ³Î´Τ cells to DSCs in vitro, which is associated with the upregulation of ICAM-1 and VCAM-1 on DSCs and integrins on dÎ³Î´Τ cells. RANKL knockout leads to the decreased numbers of uterus total Î³Î´Τ cells, Foxp3+Î³Î´Τ cells and the expression of TGF-ß1, and the increased pregnancy loss in mice. These results suggest that RANKL is a pivotal regulator of maternal-fetal tolerance by triggering the polarization and residence of TGF-ß1-producing Foxp3+Î³Î´Τ cells in early pregnancy. The abnormal low level of RANKL/RANK results in pregnancy loss because of the dialogue disorder between DSCs and dÎ³Î´Τ cells. This observation provides a scientific basis on which a potential marker can be detected to early warning of pregnancy loss.