Hypoxia-sensitive cells trigger NK cell activation via the KLF4-ASH1L-ICAM-1 axis, contributing to impairment in the rat epididymis.

Male infertility is a global health problem especially prevalent in high-altitude regions. The epididymis is essential for sperm maturation, but the influence of environmental cues on its reshaping remains poorly understood. Here, we use single-cell transcriptomics to track the cellular profiles of epidydimal cells in rats raised under normoxia or extended hypoxia. The results show that hypoxia impairs epididymal function, evident in reduced epithelial cells, compromised blood-epididymis barrier integrity, and increased natural killer cells. Through combined analysis of gene-regulatory networks and cell-cell interaction maps, we identify epididymal hypoxia-sensitive cells that communicate with natural killer (NK) cells via increased intercellular adhesion molecule 1 (ICAM-1) driven by KLF4 recruitment of the histone methyltransferase ASL1L to the Icam1 promoter. Taken together, our study offers a detailed blueprint of epididymal changes during hypoxia and defines a KLF4-ALSH1L-ICAM-1 axis contributing to NK cell activation, yielding a potential treatment targeting hypoxia-induced infertility.

Quantitative Analysis Using Consecutive Time Window for Unobtrusive Atrial Fibrillation Detection Based on Ballistocardiogram Signal.

Atrial fibrillation (AF) is the most common clinically significant arrhythmia; therefore, AF detection is crucial. Here, we propose a novel feature extraction method to improve AF detection performance using a ballistocardiogram (BCG), which is a weak vibration signal on the body surface transmitted by the cardiogenic force. In this paper, continuous time windows (CTWs) are added to each BCG segment and recurrence quantification analysis (RQA) features are extracted from each time window. Then, the number of CTWs is discussed and the combined features from multiple time windows are ranked, which finally constitute the CTW-RQA features. As validation, the CTW-RQA features are extracted from 4000 BCG segments of 59 subjects, which are compared with classical time and time-frequency features and up-to-date energy features. The accuracy of the proposed feature is superior, and three types of features are fused to obtain the highest accuracy of 95.63%. To evaluate the importance of the proposed feature, the fusion features are ranked using a chi-square test. CTW-RQA features account for 60% of the first 10 fusion features and 65% of the first 17 fusion features. It follows that the proposed CTW-RQA features effectively supplement the existing BCG features for AF detection.

Inhibin α-subunit inhibits BMP9-induced osteogenic differentiation through blocking BMP/Smad signal and activating NF-κB signal in mesenchymal stem cells.

Inhibin-α, a member of the transforming growth factor (TGF-ß) superfamily, has been involved in bone turnover during the menopausal transition via endocrine effects, and it was previously reported that inhibins may antagonize the function of BMPs. Certainly, one of the most important functions of BMPs is to induce osteogenic differentiation. BMP9 as one of the most potent BMPs to induce osteogenic differentiation has gotten more and more attentions. Nonetheless, the effects of inhibin-α on osteogenesis remain unknown. Besides, mesenchymal stem cells (MSCs) with the ability to differentiate into multiple mesenchymal lineages, including osteoblasts, adipocyte, chondrocytes, and myoblasts in vitro, have become the promising seed cells for bone tissue engineering. Here, we investigated the role of inhibin-α on BMP9-induced osteogenic differentiation in MSCs and tried to discover the mechanism underlying this process. We found inhibin-α apparently reduced the classical osteogenic markers and the ectopic bone formation induced by BMP9. In addition, the ratio of OPG to RANKL is declined also in the presence of inhibin-α. For mechanism, we found that exogenous expression of inhibin-α inhibits BMP9-induced osteogenic differentiation through blocking BMP/Smad signal transduction and activating NF-κB signal which is repressed by BMP9. Thus, our findings indicated that inhibin-α has a negative effect on BMP9-induced osteogenic differentiation in MSCs, which may provide a novel insight into the regulation of skeletal development and new strategy for bone tissue engineering.