Individuals often predict consequences, particularly emotional consequences, according to emotional or non-emotional signals conveyed by environmental cues (i.e., emotional and non-emotional cues, respectively). Some of these cues signify the consequences with certainty (i.e., certain cues), whereas others do not (i.e., uncertain cues). Several event-related potential (ERP) studies regarding non-emotional cues have suggested that the effects of cue uncertainty on attention to emotional events occur in both perception and evaluation processes. However, due to the limitations of previous studies, it is unclear what the effects of cue uncertainty would be in an emotional cue condition. Moreover, it is uncertain whether the effects of cue uncertainty are affected by cue valence (i.e., emotional and non-emotional cues). To address these questions, we asked participants to view cues and then to view emotional (positive or negative) pictures. The cues either did or did not indicate the emotional content of the picture. In the emotional cue condition, happy and fearful faces were used as certain cues indicating upcoming positive and negative pictures, respectively, and neutral faces were used as uncertain cues. In the non-emotional cue condition, scrambled faces outlined in red and blue indicated upcoming positive and negative pictures, respectively, and scrambled faces outlined in green served as uncertain cues. The results showed that for negative pictures, ERP responses in a time range between 60 and 1,000 ms were shifted to a more negative direction in a certain condition than in the uncertain condition when the cues were emotional. However, the effect was the reverse for positive pictures. This effect of cue uncertainty was similar in the non-emotional cue-negative condition. In contrast, there was no effect of cue uncertainty in the non-emotional cue-positive condition. Therefore, the findings indicate that cue uncertainty modulates attention toward emotional events when the events are signified by emotional cues. The findings may also suggest that cue valence modulates the effects of cue uncertainty on attention to emotional events.

Results showed that 1) the ReHo values of right V3 and bilateral MT/V5 for older adults were significantly lower than that of younger adults, as well as the ALFF of bilateral MT/V5, and these functional metrics were significantly negatively correlated with individuals' MCT; 2) The FCs between V2 and left primary motor cortex, V3 and left secondary visual cortex, MT/V5 and left premotor cortex, as well as the FCs between V1, V2, V3 and MT/V5 regions for the older adults were significantly stronger than that of younger adults, and these FCs were correlated with individuals' MCT; 3) Older adults' K, E nodal and b of most nodes in temporal lobe were significantly lower than younger adults, and the E nodal of the right temporal cortex were significantly negatively correlated with individuals' MCT; 4) Older adults' global network properties including small-world parameters (C p , γ, L p , λ, and σ) and network efficiency (E glob and E loc) were all significantly lower than younger adults', with C P and E loc significantly negatively correlated with their MCT. These findings suggested that the decline of GMS for the elderly was associated not only with functional changes in the dorsal visual pathway, especially in the MT/V5, but may also with functional changes in broader areas of the whole brain, which supported the theory of "dedifferentiation".

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Nonsteroidal anti-inflammatory drugs (NSAIDs), such as sulindac, have been reported for striking chemopreventive activity in various types of human cancer, including breast cancer. However, few studies have reported that sulindac is able to prevent tumor metastasis. In this study, we aim to study anti-metastatic activity of sulindac in breast cancer and explore the mechanistic basis responsible for this activity, which we hypothesize may involve a cyclooxygenase (COX) independent mechanism. Numerous studies have reported that the anticancer properties of sulindac might involve, at least partially, a non-COX mediated mechanism, which provides an insight into development of safer and more efficacious new derivatives. We have previously described a chemical derivative of sulindac, referred to as sulindac sulfide amide (SSA), which lacks inhibitory effect on COX-1 or -2, yet shows greater potency to inhibit tumor cell growth compared with sulindac sulfide (SS). Our results showed that SSA treatment at a sub-cytotoxic concentration (4μM) for 36 h significantly inhibits both migration and invasion of highly aggressive MDA-MB-231, BT-20 and SK-BR-3 breast tumor cells. When treating non-invasive breast MCF-7 cells with TGF-β1 to induce their motility, we found that SSA could significantly counteract the induced motility of these cells. These results indicate that SSA can suppress breast tumor cell invasion by modulation of TGF-β1 signaling. We further studied Smad-2/3 that are important downstream components in the TGF-β1 signaling pathway and found that SSA could inhibit Smad-2/3 phosphorylation and reduce their translocation to the nucleus. In addition, Smad-2/3 knockdown could mimic the anti-invasive effect of SSA in MDA-MB-231 cells, regardless of the presence of TGF-β1. In summary, we demonstrate that the non-COX inhibitory derivative, SSA can suppress breast cancer cell invasion and migration. These observations suggest that inhibition of TGF-β1/Smad signaling is responsible for the inhibitory effect of SSA on breast tumor cell invasion and migration. Citation Format: Bin Yi, Xingling Feng, Ruixia Ma, Xiaoguo Zhang, Hong Chang, Hongyou Zhao, Ziping Liang, Xi Chen, Xiuhua Hu, Gary Piazza, Yaguang Xi. SSA, a novel sulindac derivative, inhibits breast cancer cell invasion and migration. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4125. doi:10.1158/1538-7445.AM2015-4125