Breathing process involves inhalation and exhalation of different gases in animals. The gas exchange of the breathing process plays a critical role in maintaining the physiological functions of living organisms. Although artificial breathing materials exhibiting volume expansion and contraction upon alternate exposure to different gases have been well explored, those being able to realize the gas exchange remain elusive. Herein, we report breathing micelles (BM) capable of inhaling nitric oxide (NO) and exhaling carbon monoxide (CO), both of which are endogenous gaseous signaling molecules. We demonstrate that BM can simultaneously scavenge overproduced NO and attenuate proinflammatory cytokines in lipopolysaccharide (LPS)‐challenged macrophage cells. In vivo studies revealed that BM outperformed conventional nonsteroidal anti‐inflammatory drugs such as dexamethasone (Dexa) in treatment of rheumatoid arthritis (RA) in adjuvant‐induced arthritis (AIA) rats, likely due to the combinatorial effect of NO depletion, CO‐mediated deactivation of inducible NO synthase (iNOS) and activation of heme oxygenase‐1 (HO‐1). This work provides new insights into artificial BM for potential biomedical applications.

| INTRODUC TI ONAs a member of an integrin family, CD49a is expressed on a variety of immune cells including T cells, natural killer T cells (NKT), and NK cells. CD49a plays important roles in innate and adaptive immunemediated responses as well as in inflammation, regulation of growth, differentiation, 1 and liver cirrhosis. 2,3 CD8 + CD49a + Trm (Tissue-resident memory T cells) cells and CD8 + CD49a − Trm cells exert significantly different immune effects. 4 CD49a also regulates the migration, retention, and preservation of immune cells. Interaction of CD49a with collagen promotes immune cells proliferation and the secretion of inflammatory cytokines, which upregulate the expression of CD49a on endothelial cells and mesangial cells, promoting the formation of blood vessels. 2,3 In normal pregnancy, embryonic trophoblast cells and maternal decidual stromal cells comprise the maternal-fetal interface. NK cells, components of the innate immune system, are concentrated within the decidual tissue of the maternal-fetal interface. 5,6 A recent study has shown integrin, αvβ3, to regulate adhesion between villous trophoblastic cells. When a small molecule inhibitor (SB-273005) was used to inhibit the expression of Problem: The function of CD49a on human decidual natural killer (dNK) cells is unknown. Method of study: The expression of CD49a on dNK cells from human patients with recurrent spontaneous abortions or age-matched healthy controls was analyzed by flow cytometry. DNK cells were treated with CD49a neutralizing antibody and analyzed for function (cytokines production and cytotoxic activity). Long non-coding RNA (lncRNA) microarray analysis was used to identify a potential regulator of CD49a. Results: DNK cells from human patients who underwent recurrent spontaneous abortions had lower levels of CD49a and increased perforin, granzyme B, and IFN-r expression, when compared to dNK cells from age-matched healthy controls. Perforin, granzyme B, and IFN-r expression levels in dNK cells were upregulated, while the migration and adhesion of dNK cells were downregulated by CD49a-neutralizing antibody. By the 51 Cr release assay, the killing activity of dNK cells also increased with CD49a neutralizing antibody. Further, lnc-49a, a newly identified lncRNA, was shown to be a positive regulator of CD49a in primary human NK cells. Conclusion: CD49a is involved in the regulation of dNK cells functions, including cytotoxic activity, migration, and adhesion. Further, lnc-49a is a positive regulator of CD49a in human primary dNK cells. K E Y W O R D S adhesion, CD49a, long non-coding RNAs, migration, natural killer cells S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Li H, Hou Y, Zhang S, et al. CD49a regulates the function of human decidual natural killer cells. Am J Reprod Immunol. 2019;81:e13101. https://doi.

PurposePRDX (Peroxiredoxin) family has involved in breast cancer tumorigenesis from the evidence obtained from cell lines, human tissues and mouse models. Nonetheless, the diversified expression patterns, coupled with the prognostic values of PRDX family, still require explanation. This study aimed at investigating the clinical importance and biological of PRDXs in breast cancer.Patients and methodsSpecimens of paraffin sections used for immunohistochemistry were collected from the hospital and the remaining patient information was retrieved from online databases. The expression and survival data of PRDXs in patients with breast cancer were from ONCOMINE, GEPIA, Kaplan–Meier Plotter. cBioPortal, Metascape, String, Cytoscape and DAVID were used to predict functions and pathways of the changes in PRDXs and their frequently altered neighbor genes. Immunohistochemistry was used to detect the expression of PRDXs in breast cancer.ResultsWe discovered the expression levels of PRDX1-5 were higher in breast cancer tissues than in normal tissues, whereas the expression level of PRDX6 was observed as lower in the former one in comparison with that of the latter one. There existed a correlation between the expression levels of PRDX4, 5 and the advanced tumor stage. Survival analysis revealed that the expression of PRDXs were all associated with relapse-free survival (RFS) in all of the patients with breast cancer. Eventually, we discovered significant regulation of the cellular oxidant detoxification and detoxification of ROS by the PRDX changes, together with obtaining the core modules of genes (TXN, TXN2, TXNRD1, TXNRD2, GPX1 and GPX2) linked to the PRDX family of genes in breast cancer.ConclusionThe PRDX family is widely involved in the development of breast cancer and affects the prognosis of patients. The functions and pathways of the changes in PRDXs and their frequently altered neighbor genes can be further verified by wet experiments.

Background As an inflammatory factor and oncogenic driver protein, the pleiotropic cytokine macrophage migration inhibitory factor (MIF) plays a crucial role in the osteosarcoma microenvironment. Although 4‐iodo‐6‐phenylpyrimidine (4‐IPP) can inactivate MIF biological functions, its anti‐osteosarcoma effect and molecular mechanisms have not been investigated. In this study, we identified the MIF inhibitor 4‐IPP as a specific double‐effector drug for osteosarcoma with both anti‐tumour and anti‐osteoclastogenic functions. Methods The anti‐cancer effects of 4‐IPP were evaluated by wound healing assay, cell cycle analysis, colony formation assay, CCK‐8 assay, apoptosis analysis, and Transwell migration/invasion assays. Through the application of a luciferase reporter, chromatin immunoprecipitation assays, and immunofluorescence and coimmunoprecipitation analyses, the transcriptional regulation of the NF‐κB/P‐TEFb complex on c‐Myb‐ and STUB1‐mediated proteasome‐dependent MIF protein degradation was confirmed. The effect of 4‐IPP on tumour growth and metastasis was assessed using an HOS‐derived tail vein metastasis model and subcutaneous and orthotopic xenograft tumour models. Results In vitro, 4‐IPP significantly reduced the proliferation and metastasis of osteosarcoma cells by suppressing the NF‐κB pathway. 4‐IPP hindered the binding between MIF and CD74 as well as p65. Moreover, 4‐IPP inhibited MIF to interrupt the formation of downstream NF‐κB/P‐TEFb complexes, leading to the down‐regulation of c‐Myb transcription. Interestingly, the implementation of 4‐IPP can mediate small molecule‐induced MIF protein proteasomal degradation via the STUB1 E3 ligand. However, 4‐IPP still interrupted MIF‐mediated communication between osteosarcoma cells and osteoclasts, thus promoting osteoclastogenesis. Remarkably, 4‐IPP strongly reduced HOS‐derived xenograft osteosarcoma tumourigenesis and metastasis in an in vivo mouse model. Conclusions Our findings demonstrate that the small molecule 4‐IPP targeting the MIF protein exerts an anti‐osteosarcoma effect by simultaneously inactivating the biological functions of MIF and promoting its proteasomal degradation. Direct destabilization of the MIF protein with 4‐IPP may be a promising therapeutic strategy for treating osteosarcoma.