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BackgroundImmune checkpoints are a set of costimulatory and inhibitory molecules that maintain self-tolerance and regulate immune homeostasis. The expression of immune checkpoints on T cells in malignancy, chronic inflammation, and neurodegenerative diseases has gained increasing attention.ResultsTo characterize immune checkpoints in neurodegenerative diseases, we aimed to examine the expression of the immune checkpoint PD-1/PD-L1 in peripheral T cells in different Alzheimer’s disease (AD) patients. To achieve this aim, sixteen AD patients and sixteen age-matched healthy volunteers were enrolled to analyze their CD3+T cells, CD3+CD56+(neural cell adhesion molecule, NCAM) T cells, CD4+/CD8+T cells, and CD4+/CD8+CD25+(interleukin-2 receptor alpha, IL-2RA) T cells in this study. The expression of PD-1 on T cells was similar between the AD patients and healthy volunteers, but increased expression of PD-L1 on CD3+CD56+T cells (natural killer T cells, NKT-like), CD4+T cells (helper T cells, Th), CD4+CD25+T cells, and CD8+T cells (cytotoxic T lymphocytes, CTL) was detected in the AD patients. In addition, we found negative correlations between the AD patients’ cognitive performance and both CD8+T cells and CD8+CD25+T cells. To identify CD8+T-cell phenotypic and functional characteristic differences between the healthy volunteers and AD patients in different stages, a machine learning algorithm, t-distributed stochastic neighbor embedding (t-SNE), was implemented. Using t-SNE enabled the above high-dimensional data to be visualized and better analyzed. The t-SNE analysis demonstrated that the cellular sizes and densities of PD-1/PD-L1 on CD8+T cells differed among the healthy, mild AD, and moderate AD subjects.ConclusionsOur results suggest that changes in PD-1/PD-L1-expressing T cells in AD patients’ peripheral blood could be a potential biomarker for monitoring disease and shed light on the AD disease mechanism. Moreover, these findings indicate that PD-1/PD-L1 blockade treatment could be a novel choice to slow AD disease deterioration.

Orchestrated control of multiple overlapping and sequential processes is required for the maintenance of epidermal homeostasis and the response to and recovery from a variety of skin insults. Previous studies indicate that membrane-associated serine protease matriptase and prostasin play essential roles in epidermal development, differentiation, and barrier formation. The control of proteolysis is a highly regulated process, which depends not only on gene expression but also on zymogen activation and the balance between protease and protease inhibitor. Subcellular localization can affect the accessibility of protease inhibitors to proteases and, thus, also represents an integral component of the control of proteolysis. To understand how membrane-associated proteolysis is regulated in human skin, these key aspects of matriptase and prostasin were determined in normal and injured human skin by immunohistochemistry. This staining shows that matriptase is expressed predominantly in the zymogen form at the periphery of basal and spinous keratinocytes, and prostasin appears to be constitutively activated at high levels in polarized organelle-like structures of the granular keratinocytes in the adjacent quiescent skin. The membrane-associated proteolysis appears to be elevated via an increase in matriptase zymogen activation and prostasin protein expression in areas of skin recovering from epidermal insults. There was no noticeable change observed in other regulatory aspects, including the expression and tissue distribution of their cognate inhibitors HAI-1 and HAI-2. This study reveals that the membrane-associated proteolysis may be a critical epidermal mechanism involved in responding to, and recovering from, damage to human skin.

The purpose of this quasi-experimental study was to examine whether attention cueing can assist learners in learning the structure and functions of the brain. This study investigated the interactive effects of the experimental treatment and learners’ prior knowledge on their test results and cognitive load. Self-regulatory, mobile-phone-based animations depicting the brain comprised the instrument. A total of 55 English as a foreign language learners from two sections of a linguistics course were recruited. First, the participants’ prior knowledge concerning the functions of the brain was assessed. Next, they were randomly assigned into two modes—animation-only or animation-plus-cueing. Immediately, after the treatment period, the participants were administered retention, matching, organization, and transfer test along with cognitive load questionnaire. Experimental treatment and prior knowledge were the independent variables, while comprehension tests, cognitive load, and study time were the dependent variables. The results demonstrated that the learners in the cueing condition outperformed the non-cueing condition for matching and organization test, but not for transfer test. No differences were observed between the cueing and non-cueing condition concerning the cognitive load. The results stressed the importance of presenting relation cueing emphasizing cause–effect relationship on dynamic external representations can facilitate learners’ selection and organization of information so as to enhance general comprehension of external representations.