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Mycobacterium tuberculosis is a hard-to-eradicate intracellular pathogen that infects one-third of the global population. It can live within macrophages owning to its ability to arrest phagolysosome biogenesis. Autophagy has recently been identified as an effective way to control the intracellular mycobacteria by enhancing phagosome maturation. In the present study, we demonstrate a novel role of miR-155 in regulating the autophagy-mediated anti-mycobacterial response. Both in vivo and in vitro studies showed that miR-155 expression was significantly enhanced after mycobacterial infection. Forced expression of miR-155 accelerated the autophagic response in macrophages, thus promoting the maturation of mycobacterial phagosomes and decreasing the survival rate of intracellular mycobacteria, while transfection with miR-155 inhibitor increased mycobacterial survival. However, macrophage-mediated mycobacterial phagocytosis was not affected after miR-155 overexpression or inhibition. Furthermore, blocking autophagy with specific inhibitor 3-methyladenine or silencing of autophagy related gene 7 (Atg7) reduced the ability of miR-155 to promote autophagy and mycobacterial elimination. More importantly, our study demonstrated that miR-155 bound to the 3′-untranslated region of Ras homologue enriched in brain (Rheb), a negative regulator of autophagy, accelerated the process of autophagy and sequential killing of intracellular mycobacteria by suppressing Rheb expression. Our results reveal a novel role of miR-155 in regulating autophagy-mediated mycobacterial elimination by targeting Rheb, and provide potential targets for clinical treatment.

BackgroundDNA methylation is an important biological form of epigenetic modification, playing key roles in plant development and environmental responses.ResultsIn this study, we examined single-base resolution methylomes of Populus under control and drought stress conditions using high-throughput bisulfite sequencing for the first time. Our data showed methylation levels of methylated cytosines, upstream 2kp, downstream 2kb, and repeatitive sequences significantly increased after drought treatment in Populus. Interestingly, methylation in 100 bp upstream of the transcriptional start site (TSS) repressed gene expression, while methylations in 100-2000bp upstream of TSS and within the gene body were positively associated with gene expression. Integrated with the transcriptomic data, we found that all cis-splicing genes were non-methylated, suggesting that DNA methylation may not associate with cis-splicing. However, our results showed that 80% of trans-splicing genes were methylated. Moreover, we found 1156 transcription factors (TFs) with reduced methylation and expression levels and 690 TFs with increased methylation and expression levels after drought treatment. These TFs may play important roles in Populus drought stress responses through the changes of DNA methylation.ConclusionsThese findings may provide valuable new insight into our understanding of the interaction between gene expression and methylation of drought responses in Populus.

A simple approach to wafer-scale self-cleaning antireflective hierarchical silicon structures is demonstrated. By employing the KOH etching and silver catalytic etching, pyramidal hierarchical structures were generated on the crystalline silicon wafer, which exhibit strong antireflection and superhydrophobic properties after fluorination. Furthermore, a flexible superhydrophobic substrate was fabricated by transferring the hierarchical Si structure to the NOA 63 film with UV-assisted imprint lithography. This method is of potential application in optical, optoelectronic, and wettability control devices.

Objective: To investigate whether chronic endometritis (CE) affects the immune status of peripheral blood and endometrium in patients with recurrent reproductive failure (RRF). Design: Retrospective study. Setting: Private fertility center. Patients(s): A total of 524 RRF patients, including 324 women with recurrent miscarriage (RM) and 200 women with recurrent implantation failure (RIF). Intervention(s): Peripheral blood and endometrium samples were collected in the midluteal phase before in vitro fertilization treatment or pregnancy. The number of peripheral T, natural killer (NK), and B cells, as well as cytotoxicity of NK cells and expression of T H 1 cytokines were analyzed with the use of flow cytometry, and uterine immune cells were subjected to immunohistochemistry. Main Outcome Measure(s): Peripheral immune cells, cytokines, NK cytotoxicity, and endometrial immune cells were compared in RRF patients with versus without CE. Result(s): The proportion and function of the analyzed immune cell subsets in peripheral blood as well as the percentages of CD56 þ NK cells, CD163 þ M2 macrophages, and CD1a þ immature dendritic cells in the endometrium were not significantly altered between non-CE and CE patients, whereas the proportions of uterine CD68 þ macrophages, CD83 þ mature dendritic cells, CD8 þ T cells, and Foxp3 þ regulatory T cells were significantly elevated in CE patients. After antibiotic treatment, the percentage of CD68 þ macrophages, CD83 þ mature dendritic cells, CD8 þ T cells, and Foxp3 þ regulatory T cells in endometrium were significantly reduced in patients with cured CE. Conclusion(s): CE contributes to elevated endometrial infiltration levels of immune cells. The excessive presence of endometrial immune cells in CE patients may be involved in reduced endometrial receptivity and recurrent pregnancy failures. (Fertil Steril Ò 2020;113: 187-96. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.