Abstract Background: A successful pregnancy is a complicated process that builds upon two aspects of the maternal immune system that needs to be balanced. As one of the dominant groups of cells at the maternal fetal interface, the decidual γδ T cells have attracted great research attention in normal pregnancy or miscarriage. However, the role of γδ T cells in fetal growth still remains poorly studied. Results: In this study, we identified γδ T cells were enriched and resident in decidua during early pregnancy, and early decidual γδ T cells were involved in the secretion of growth factors, including growth differentiation factor 15 (GDF15) and bone morphogenetic protein 1 (BMP1). Decrease of these growth factors could impaire fetal development, resulting in fetal growth restriction. We also observed that the early decidual γδ T cells exhibited stronger cytokine secretion characteristic, but its cytotoxicity against A549 cells was weaker, when compared with the γδ T cells in peripheral blood mononuclear cells (PBMCs). In addition, the functional abilities of early decidual γδ T cells in promoting trophoblast cell proliferation, migration, invasion and tube formation were also significantly stronger than those in γδ T cells of PBMCs. Conclusions: These findings highlighted the importance of γδ T cells in fetal growth and maternal immune tolerance during pregnancy, which is different from γδ T cells in PBMCs, and encouraged further research in this field.
Neoadjuvant chemotherapy (NAC) has shown promising results in patients with locally advanced penile cancer. However, no consensus exists on its applications for locally advanced penile cancer. Thus, it is unclear which kind of chemotherapy regimen is the best choice. Consequently, a systematic search of PubMed, Web of Science, and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer. The Newcastle-Ottawa Scale was used to assess the risk of bias in each study. This study synthesized 14 published studies. The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response. In addition, the objective response rates (ORRs) and pathological complete response (pCR) rates were 0.57 and 0.11, respectively. The incidence of grade ≥3 toxicity was 0.36. Subgroup analysis found that the ORR and pCR of the taxane-platinum (TP) regimen group performed better than those of the nontaxane-platinum (NTP) regimen group (0.57 vs 0.54 and 0.14 vs 0.07, respectively). Moreover, the TP regimen group had more frequent toxicity than the NTP regimen group (0.41 vs 0.26). However, further studies were warranted to confirm the findings.
Abstract MucA and MucB are critical negative modulators of sigma factor AlgU and regulate the mucoid conversion of Pseudomonas aeruginosa . Previous studies have revealed that lipid signals antagonize MucA-MucB binding. Here we report the crystal structure of MucB in complex with the periplasmic domain of MucA and polyethylene glycol (PEG), which unveiled an intermediate state preceding the MucA-MucB dissociation. Based on the biochemical experiments, the aliphatic side chain with a polar group was found to be of primary importance for inducing MucA cleavage. These results provide evidence that the hydrophobic cavity of MucB is a primary site for sensing lipid molecules and illustrates the detailed control of conformational switching within MucA-MucB in response to lipophilic effectors.
Abstract Disorganized maternal–fetal immune tolerance contributes to the occurrence of unexplained recurrent pregnancy loss (RPL). AHNAK is a scaffolding protein participating in the regulation of Ca2+ entry into T cells and the pathophysiology of diverse diseases. We performed differential gene expression analysis in decidual immune cells (DICs) isolated from three patients with RPL and from three healthy controls via RNA-sequencing (RNA-seq), which revealed 407 differentially expressed genes (DEGs). Among these DEGs, we underscored the clinical significance of elevated AHNAK mRNA and protein levels in DICs, peripheral blood mononuclear cells (PBMCs), and decidua of the patients with RPL, suggesting its potential use as a biomarker for the diagnosis of RPL. Especially, the ratios of decidual and blood AHNAK+CD4+ T cells in the CD4+ T cell population were significantly increased in patients with RPL, and the loss of AHNAK was further shown to inhibit interleukin (IL)-6 secretion in the CD4+ Jurkat cell line. Similar patterns were also observed in the clinical decidual and blood specimens. We uncovered that the AHNAK+CD4+ T cells could secrete more IL-6 than that the corresponding AHNAK-CD4+ T cells. Moreover, the frequencies of decidual and blood IL-6+CD4+ T cells in the CD4+ T-cell population were also increased in patients with RPL and showed significant positive correlations with the frequencies of AHNAK+CD4+ T cells. Our findings suggest that the elevated AHNAK expressed by CD4+ T cells may be involved in the immune dysregulation of RPL by increasing IL-6 production, illustrating its potential as a novel intervention target for RPL.
The immunomodulatory properties of human chorionic gonadotrophin (hCG) have been identified to be critical for successful pregnancy. However, the effects of hCG on peripheral γδT cells during early pregnancy have not been reported previously.
To investigate the characteristic functional changes of the decidual natural killer (NK) cells and γδ T cells, two immunocytes in the decidua, at the maternal-fetal interface in in vitro fertilization-embryo transfer (IVF-ET) pregnancy.Decidual samples were collected from 12 women of natural pregnancy (NP) and 32 women of IVF-ET pregnancy, who were enrolled in the NP group and the IVF-ET group, respectively. Then part of the decidual samples were paraffin-embedded for HE staining and immunofluorescence staining, while the rest of the samples were digested and Percoll was used for isolating decidual immunocytes (DICs) by gradient centrifugation. Flow cytometry was used to determine the cell counts of decidual NK cells and γδ T cells and the expression levels of their surface activation markers, CD69 and NKG2D in the NP and the IVF-ET groups. In addition, the expression levels of IFN-γ, TNF-α, IL-17A, and IL-10, the intracellular cytokines, and granzyme B, perforin, and granulysin, the cytolytic granules, were measured. The characteristic changes in the relevant immunological indicators were compared and analyzed.HE staining of the tissue specimens showed that the typical structure of decidua was observed, and that lymphocytes were enriched in the decidua. Immunofluorescence staining showed that the percentage of decidual NK (dNK) cells in nucleated cells of the IVF-ET group was significantly lower than that of the NP group ( P<0.05). Flow cytometry analysis of DICs showed that, compared with those of the NP group, the percentage of dNK cells of the IVF-ET group was decreased ( P<0.05) and the expression levels of IL-10 and perforin were significantly decreased in the IVF-ET group ( P<0.05). However, there was no significant difference in the decidual γδ T (dγδT) cell count between the two groups. The expression of IL-10, IL-17A, and perforin was downregulated in the IVF-ET group ( P<0.05). There was no significant difference in the expression of IFN-γ, TNF-α, granzyme B, and granulysin, the cellular function indicators ( P>0.05).The dNK cell count and the secretion of some intracellular cytokines of dNK and dγδT cells of women of IVF-ET pregnancy decreased to some degree, which suggests that certain changes may have taken place in the immunological microenvironment at the maternal-fetal interface. The specific effect of these changes on pregnancy outcomes needs further investigation.
Abstract BackgroundPre-eclampsia affects around 2-10% pregnancies in the world. In vitro fertilization embryo transfer (IVF) pregnancies are associated with a 2.7-fold risk of pre-eclampsia. MethodsIn our retrospective study, 20 pre-eclampsia patients with IVF treatment (PE with IVF group) and 20 matched pre-eclampsia controls with spontaneous conception (PE group) were enrolled. We also collected several fresh decidua tissue and cord blood specimens to determine functional changes of innate immune cells at maternal-fetal interface using flow cytometry assays. ResultsThere were no obvious differences in pregnancy outcomes between 2 groups. However, maternal prealbumin (PA) level was significantly decreased while creatinine (Cr) and uric acid (UA) levels were significantly elevated in PE with IVF group. Although levels of maternal alkaline phosphatase (ALP) and cystatin C (CysC) did not differ between 2 groups, they were both abnormally elevated, exceeding the normal reference range. Moreover, significant elevations of IFN-γ and TNF-α secretions were observed in both decidual NK cells and γδT cells of pre-eclampsia patients with IVF treatment. In cord blood, productions of IFN-γ and TNF-α were only increased in the NK cells of pre-eclampsia patients with IVF treatment. ConclusionThe close surveillance for clinical features of this special pre-eclampsia population is strongly warranted.
Low-carbon economy is one of the important tasks of economic and social development in the world, but the carbon reduction effect of industrial agglomeration has not been fully studied. It is necessary to explore the relationship between China's industrial agglomeration and carbon intensity and put forward some insightful policy implications for China to promote green industrial agglomeration and speed up the process of green technological innovation. This paper incorporates technological progress into the analysis framework of industrial agglomeration and carbon emissions and employs a dynamic panel model and a mediation effect model to confirm the influence mechanism of industrial agglomeration on carbon emissions. The main findings are as follows: (1) There is an inverted U relationship between industrial agglomeration and carbon emissions; (2) Industrial agglomeration enhances the reduction of carbon emissions through technological progress.
The objectives of this study were to determine reliability of Chinese version of Acceptance and Action Questionnaire-II (AAQ-II), the relationship between psychological acceptance (PA), and burnout syndrome and their risk factors among nurses in China. The reliability of AAQ-II in Chinese was evaluated first by testing on 111 doctors and 108 nurses in China. On the number of 845 nurses selected from nine city hospitals by using stratified cluster sampling method, the Maslach Burnout Inventory-General Survey was administered to establish the presence of burnout, and the AAQ-II was used to measure their PA. Results showed that the AAQ-II in Chinese had a good test-retest reliability. PA was statistically significantly negatively correlated to the three dimensionalities of burnout among nurses in China. Male and female nurses had a significant difference in PA. Risk factors for burnout were age (25-44 years), marital status (married), gender (male), hospital department (emergency) and position (primary title) as well as PA. The findings provide insights into the risk factors of burnout in Chinese nurses and may have clinical implications in preventing burnout in Chinese nurses.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
'/%3e%3cuse xlink:href='%23a' transform='rotate(144 450 300)'/%3e%3cuse xlink:href='%23a' transform='rotate(216 450 300)'/%3e%3cuse xlink:href='%23a' transform='rotate(288 450 300)'/%3e%3c/svg%3e)
