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Intracellular metabolic adaptations help define the function and homeostasis of memory CD8+ T cells. These cells, which promote protection against infections or cancer, undergo consecutive metabolic shifts, ultimately relying on mitochondrial-related pathways. Vismodegib Past CD8+ T cell metabolism studies focused on circulating memory cells, which are exclusive to secondary lymphoid organs or recirculate between lymphoid and non-lymphoid organs. Yet, now there is unequivocal evidence that memory CD8+ T cells reside in many non-lymphoid organs and mediate protective immunity in barrier tissues. The metabolic adaptations occurring in forming and established tissue-resident memory CD8+ T cells are currently subject of intense research. In this review, we discuss the latest breakthroughs on the transcriptional and protein control of tissue-resident memory CD8+ T cell metabolism.

Physical function is a strong predictor of the adverse outcomes of cardiovascular disease in older populations. However, studies of healthy older people on the prevention of coronary heart disease (CHD) are very limited.

We prospectively examined the association of walking speed and handgrip strength with CHD in the community-dwelling older populations.

The study cohort in Japan included 1272 older people free from heart disease at the baseline. Physical function was identified based on walking speed and handgrip strength assessment at the survey site. Any new case of CHD was identified based on a self-reported doctor's diagnosis. Cox-proportion hazard models were adjusted for covariate factors to examine the CHD risk.

During the 7-year follow-up, 45 new cases of CHD (25 men and 20 women) were documented. Slow walking speed was strongly associated with CHD risk after adjusting for all confounding factors in the total participants and women (hazard ratio (HR)= 2.53, 95%confidence interval (CI), 1.20-5.33, p=0.015, and HR= 4.78, 95% CI,1.07-21.35, p=0.040, respectively), but not in men. Weak grip strength was associated with CHD after age-adjustment (HR= 2.45, 95%CI, 1.03-5.81, p=0.043) only in men. However, after additional multivariate adjustment, the associations were getting weaker.

During the 7-year follow-up, 45 new cases of CHD (25 men and 20 women) were documented. Slow walking speed was strongly associated with CHD risk after adjusting for all confounding factors in the total participants and women (hazard ratio (HR)= 2.53, 95%confidence interval (CI), 1.20-5.33, p=0.015, and HR= 4.78, 95% CI,1.07-21.35, p=0.040, respectively), but not in men. Weak grip strength was associated with CHD after age-adjustment (HR= 2.45, 95%CI, 1.03-5.81, p=0.043) only in men. However, after additional multivariate adjustment, the associations were getting weaker.Sensory organs are not only involved in passively transmitting sensory input, but are also involved in actively seeking it. Some sensory organs move dynamically to allow highly prioritized input to be detected by their most sensitive parts. Such 'active sensing' systems engage in pursuing relevant input, relying on attentional prioritizations. However, pursuing input may not always be advantageous. Task-irrelevant input may be distracting and interfere with task performance. We hypothesize that an efficient 'active sensing' mechanism should be able to not only pursue relevant input but also to predict irrelevant input and avoid it. Moreover, we hypothesize that this mechanism should be evident even when the task is non-visual and all visual information acts as a distractor. In this study, we demonstrate the existence of a predictive 'overt avoidance' mechanism in vision. In two experiments, participants were asked to perform a continuous mental-arithmetic task while occasionally being presented with task-irrelevant crowded displays limited to one quadrant of a screen. The locations of these visual stimuli were constant within a block but varied between blocks. Results show that gaze was consistently shifted away from the predicted location of distraction, even prior to its appearance, confirming the existence of a predictive 'overt avoidance' mechanism in vision. Based on these findings, we propose a conceptual model to explain how an 'active sensing' system, hardwired to explore, can overcome this drive when presented with distracting information. According to the model, distraction is handled through a dual mechanism of suppression and avoidance processes that are causally linked. This framework demonstrates how perception and motion work together to approach relevant information while avoiding irrelevant distraction.Previous studies have demonstrated that silica nanoparticle (SiNP) exposure induces pulmonary and cardiovascular diseases, yet their transportation and degradation in vivo have not been fully elucidated. From the perspective of reproduction, this study was implemented to examine the uterine accumulation of SiNP and explore its reproductive toxicity and pathogenic mechanisms. First, we coupled FITC onto SiNPs and intratracheally instilled them into pregnant mice on the fifth gestational day, and the toxic effect of SiNP was evaluated in vitro and in vivo. It was found that SiNP penetrated the trophoblast membrane, leading to apoptosis and suppression of cell proliferation, tube formation, and invasion in a dose-dependent manner. Mechanistically, SiNP dysregulated the expression of Scd1, Slc27a1, and Cpt1a, and induced over synthesis and efflux obstruction of fatty acid through the PPARγ signaling pathway. The downregulation of Caspase-3 triggered apoptosis of trophoblast, which was causally associated with intracellular fatty acid accumulation as revealed by the correlation analysis. Besides, SiNP induced uterine inflammation in vivo, which aggravated with the observation prolongation within 24 h. Overall, SiNPs were visualized by coupling with FITC, and the uterine accumulation of SiNP induced fatty acid metabolic disorder, biological dysfunction, and trophoblast apoptosis, which were mediated in part by the PPARγ signaling pathway. These findings would contribute to understanding the environmental impacts of SiNP better, as well as the development of control measures for environmental pollution.

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