Increased miR-3074-5p expression promotes M1 polarization and pyroptosis of macrophages via ERα/NLRP3 pathway and induces adverse pregnancy outcomes in mice.

Decidual macrophages (dMϕs) play critical roles in regulation of immune-microhomeostasis at maternal-fetal interface during pregnancy, but the underlying molecular mechanisms are still unclear. In this study, it was found that litter size and fetal weight were significantly reduced, whereas the rate of embryo resorption was increased in miR-3074-5p knock-in (3074-KI) pregnant mice, compared to that of wild-type (WT) pregnant mice. Plasma levels of pro-inflammatory cytokines in 3074-KI pregnant mice were also significantly elevated compared to WT pregnant mice at GD7.5. The quantity of M1-Mϕs in uterine tissues of 3074-KI pregnant mice was significantly increased compared to WT pregnant mice at GD13.5. Estrogen receptor-α (ERα) was validated to be a target of miR-3074-5p. Either miR-3074-5p overexpression or ERα knockdown promoted transcriptional activity of NF-κB/p65, induced M1-polarization and pyroptosis of THP1-derived Mϕs, accompanied with increased intracellular levels of cleaved Caspase-1, cleaved IL-1ß, NLRP3, cleaved GSDMD and ASC aggregation. Furthermore, ERα could not only bind to NLRP3 or ASC directly, but also inhibit the interaction between NLRP3 and ASC. The endometrial miR-3074-5p expression level at the middle secretory stage of repeated implantation failure (RIF) patients was significantly decreased compared to that of control fertile women. These data indicated that miR-3074-5p could promote M1 polarization and pyroptosis of Mϕs via activation of NLRP3 inflammasome by targeting ERα, and the dysregulation of miR-3074-5p expression in dMϕs might damage the embryo implantation and placentation by interfering with inflammatory microenvironment at the maternal-fetal interface during early pregnancy.

Sperm-specific protein ACTL7A as a biomarker for fertilization outcomes of assisted reproductive technology.

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.

Next-Generation Sequencing Technologies and Neurogenetic Diseases.

Next-generation sequencing (NGS) technology has led to great advances in understanding the causes of Mendelian and complex neurological diseases. Owing to the complexity of genetic diseases, the genetic factors contributing to many rare and common neurological diseases remain poorly understood. Selecting the correct genetic test based on cost-effectiveness, coverage area, and sequencing range can improve diagnosis, treatments, and prevention. Whole-exome sequencing and whole-genome sequencing are suitable methods for finding new mutations, and gene panels are suitable for exploring the roles of specific genes in neurogenetic diseases. Here, we provide an overview of the classifications, applications, advantages, and limitations of NGS in research on neurological diseases. We further provide examples of NGS-based explorations and insights of the genetic causes of neurogenetic diseases, including Charcot-Marie-Tooth disease, spinocerebellar ataxias, epilepsy, and multiple sclerosis. In addition, we focus on issues related to NGS-based analyses, including interpretations of variants of uncertain significance, de novo mutations, congenital genetic diseases with complex phenotypes, and single-molecule real-time approaches.

[Analysis of major QTL for Fusarium head blight resistance on the short arm of chromosome 3B in wheat].

Three recombinant inbred populations, Ning894037/Alondra, Wangshuibai/Alondra and Sumai3/Alondra, were analyzed for QTLs associated with Fusarium head blight resistance by interval mapping and composite interval mapping in this study. The result showed that the major QTLs were detected on the short arm of chromosome 3B of all three resistant parents using the data of FHB resistance evaluated in greenhouse or field. They were located in the interval of 5.0 cM between BARC133 and Xgwm493 in Ning894037, 11.5 cM between BARC147 and Xgwm493 in Wangshuibai, and 13.0 cM between Xgwm533a and Xgwm493 in Sumai3, explaining 42.8%, 15.1% and 10.6% of the phenotypic variance for Type II resistance (spread within the spike), respectively. Some of the SSR markers linking to the major QTLs tightly can be used directly in marker-assisted breeding to improve FHB resistance in wheat.