Neural correlates of confidence during decision formation in a perceptual judgment task.

When we make a decision, we also estimate the probability that our choice is correct or accurate. This probability estimate is termed our degree of decision confidence. Recent work has reported event-related potential (ERP) correlates of confidence both during decision formation (the centro-parietal positivity component; CPP) and after a decision has been made (the error positivity component; Pe). However, there are several measurement confounds that complicate the interpretation of these findings. More recent studies that overcome these issues have so far produced conflicting results. To better characterise the ERP correlates of confidence we presented participants with a comparative brightness judgment task while recording electroencephalography. Participants judged which of two flickering squares (varying in luminance over time) was brighter on average. Participants then gave confidence ratings ranging from "surely incorrect" to "surely correct". To elicit a range of confidence ratings we manipulated both the mean luminance difference between the brighter and darker squares (relative evidence) and the overall luminance of both squares (absolute evidence). We found larger CPP amplitudes in trials with higher confidence ratings. This association was not simply a by-product of differences in relative evidence (which covaries with confidence) across trials. We did not identify postdecisional ERP correlates of confidence, except when they were artificially produced by pre-response ERP baselines. These results provide further evidence for neural correlates of processes that inform confidence judgments during decision formation.

Structural characterization of Russula griseocarnosa polysaccharide and its improvement on hematopoietic function.

The hematopoietic function of a polysaccharide derived from Russula griseocarnosa was demonstrated in K562 cells, and subsequently purified through chromatography to obtain RGP1. RGP1 is a galactan composed of 1,6-α-D-Galp as the main chain, with partial substitutions. A -CH3 substitution was detected at O-3 of 1,6-α-D-Galp. The possible branches at O-2 of 1,6-α-D-Galp was α-L-Fucp. In mice with cyclophosphamide (CTX)-induced hematopoietic dysfunction, RGP1 alleviated bone marrow damage and multinucleated giant cell infiltration of the spleen, increased the number of long-term hematopoietic stem cells, and regulated the levels of myeloid cells in the peripheral blood. Furthermore, RGP1 promoted the differentiation of activated T cells and CD4+ T cells without affecting natural killer cells and B cells. Proteomic analysis, detection of cytokines, and western blotting revealed that RGP1 could alleviate hematopoietic dysfunction by promoting the activation of CD4+ T cells and the Janus kinase/ signal transducer and activator of transcription 3 pathway. The present study provides experimental evidence to support the application of RGP1 in CTX-induced hematopoietic dysfunction.

Cloning, Expression, Purification, and Characterization of a Novel ß-Galactosidase/α-L-Arabinopyranosidase from Paenibacillus polymyxa KF-1.

Glycosidases are essential for the industrial production of functional oligosaccharides and many biotech applications. A novel ß-galactosidase/α-L-arabinopyranosidase (PpBGal42A) of the glycoside hydrolase family 42 (GH42) from Paenibacillus polymyxa KF-1 was identified and functionally characterized. Using pNPG as a substrate, the recombinant PpBGal42A (77.16 kD) was shown to have an optimal temperature and pH of 30 °C and 6.0. Using pNPαArap as a substrate, the optimal temperature and pH were 40 °C and 7.0. PpBGal42A has good temperature and pH stability. Furthermore, Na+, K+, Li+, and Ca2+ (5 mmol/L) enhanced the enzymatic activity, whereas Mn2+, Cu2+, Zn2+, and Hg2+ significantly reduced the enzymatic activity. PpBGal42A hydrolyzed pNP-ß-D-galactoside and pNP-α-L-arabinopyranoside. PpBGal42A liberated galactose from ß-1,3/4/6-galactobiose and galactan. PpBGal42A hydrolyzed arabinopyranose at C20 of ginsenoside Rb2, but could not cleave arabinofuranose at C20 of ginsenoside Rc. Meanwhile, the molecular docking results revealed that PpBGal42A efficiently recognized and catalyzed lactose. PpBGal42A hydrolyzes lactose to galactose and glucose. PpBGal42A exhibits significant degradative activity towards citrus pectin when combined with pectinase. Our findings suggest that PpBGal42A is a novel bifunctional enzyme that is active as a ß-galactosidase and α-L-arabinopyranosidase. This study expands on the diversity of bifunctional enzymes and provides a potentially effective tool for the food industry.

SIRT1-dependent deacetylation of Txnip H3K9ac is critical for exenatide-improved diabetic kidney disease.

Glucagon-like peptide 1 receptor agonist exenatide (exendin-4) has potential protective capabilities against diabetic kidney disease (DKD). However, the underlying mechanism has not been fully elucidated. The expression of thioredoxin-interacting protein (Txnip) is upregulated during DKD progression by histone acetylation. Sirtuin 1 (SIRT1) is a deacetylase and is decreased in DKD, which indicates that it may regulate Txnip in this disease. Here, we used whole-body heterozygous Sirt1 knockout (Sirt1+/-) and kidney-specific Sirt1 knockout (KSK) mice to investigate whether SIRT1 regulates Txnip via histone deacetylation in DKD and exenatide-alleviated DKD. Exenatide substantially improved renal pathological damage, decreased the albumin-to-creatinine ratio (ACR), upregulated SIRT1 expression, and downregulated Txnip expression in kidneys of high-fat diet-treated C57BL/6J mice. However, these effects diminished in Sirt1+/- and KSK mice under exenatide treatment. The downregulation of Txnip expression by exendin-4 in high-glucose-treated SV40 MES13 cells was hampered during Sirt1 knockdown. These results demonstrate that kidney SIRT1 is indispensable in exenatide-improved DKD and downregulation of Txnip expression. Exendin-4 mechanistically downregulated Txnip histone 3 lysine 9 acetylation (H3K9ac) in a SIRT1-dependent manner and decreased spliced X-box binding protein 1 (XBP1s) recruitment to the Txnip promoter. These findings provide epigenetic evidence elucidating the specific mechanism for exenatide-mediated DKD alleviation and highlight the importance of Txnip as a promising therapeutic target for DKD.

Stimulus expectations do not modulate visual event-related potentials in probabilistic cueing designs.

Humans and other animals can learn and exploit repeating patterns that occur within their environments. These learned patterns can be used to form expectations about future sensory events. Several influential predictive coding models have been proposed to explain how learned expectations influence the activity of stimulus-selective neurons in the visual system. These models specify reductions in neural response measures when expectations are fulfilled (termed expectation suppression) and increases following surprising sensory events. However, there is currently scant evidence for expectation suppression in the visual system when confounding factors are taken into account. Effects of surprise have been observed in blood oxygen level dependent (BOLD) signals, but not when using electrophysiological measures. To provide a strong test for expectation suppression and surprise effects we performed a predictive cueing experiment while recording electroencephalographic (EEG) data. Participants (n=48) learned cue-face associations during a training session and were then exposed to these cue-face pairs in a subsequent experiment. Using univariate analyses of face-evoked event-related potentials (ERPs) we did not observe any differences across expected (90% probability), neutral (50%) and surprising (10%) face conditions. Across these comparisons, Bayes factors consistently favoured the null hypothesis throughout the time-course of the stimulus-evoked response. When using multivariate pattern analysis we did not observe above-chance classification of expected and surprising face-evoked ERPs. By contrast, we found robust within- and across-trial stimulus repetition effects. Our findings do not support predictive coding-based accounts that specify reduced prediction error signalling when perceptual expectations are fulfilled. They instead highlight the utility of other types of predictive processing models that describe expectation-related phenomena in the visual system without recourse to prediction error signalling.

Neuroprotection of low-molecular-weight galactan obtained from Cantharellus cibarius Fr. against Alzheimer's disease.

The large molecular weight of polysaccharides limits their absorption and utilization by organisms, affecting their biological activities. In this study, we purified α-1,6-galactan from Cantharellus cibarius Fr. (chanterelle) and reduced its molecular weight from approximately 20 kDa to 5 kDa (named CCP) to increase its solubility and absorption. In APP/PS1 mice, CCP improved both spatial and non-spatial memory loss in Alzheimer's disease (AD) mice, as confirmed by the Morris water maze, step-down, step-through, and novel object recognition tests, and dampened the deposition of amyloid-ß plaques, as assessed by immunohistochemical analysis. Proteomic analysis suggested that the neuroprotective effects of CCP are related to anti-neuroinflammation. Immunofluorescence analysis and western blotting confirmed that CCP attenuated AD-like symptoms partly by inhibiting neuroinflammation, which was related to the blocking of complement component 3. Our study provides theoretical support and experimental evidence for the future application of chanterelle-extracted polysaccharides in AD treatment, promoting the modern development of traditional medicines originating from natural polysaccharides.

Cloning, Expression, Purification and Characterization of the ß-galactosidase PoßGal35A from Penicillium oxalicum.

Galactosidases are industrially important enzymes that hydrolyze galactosidic bonds in carbohydrates. Identifying new galactosidases with distinct functional characteristics is of paramount importance. In this study, we report the finding of a novel ß-galactosidase PoßGal35A from the fungus Penicillium oxalicum. PoßGal35A belongs to the glycoside hydrolase family 35 (GH35), functions optimally at 70 °C and pH 5.0, and exhibits a specific high activity (191 ± 6.2 U/mg) towards pNPßgal. Ca2+, Fe3+and Ba2+ ions enhance the activity of the enzyme, whereas Cu2+ and Hg2+ significantly reduce it. This enzyme releases galactose from ß-1,3-galactan, ß-1,4-galactan, ß-1,6-galactan, as well as arabinogalactan from larchwood (LWAG). In addition, PoßGal35A acts synergistically with arabinosidase to degrade LWAG. These results suggest that PoßGal35A is a high activity exo-ß-1,3/4/6-galactanase that can be used to establish glycan blocks in glycoconjugates, and thus provides a new tool for biotechnological applications.

Combined spinal-epidural anesthesia with acupoint injection for labor anesthesia reduces IL-1ß/IL-10 ratio in maternal peripheral blood, umbilical cord blood and improves the labor outcomes: A prospective randomized controlled trial.

BACKGROUND: This study aimed to investigate the effects of combined spinal-epidural anesthesia (CSEA) with acupoint injection (AI) on the maternal-fetal expression of interleukin-1ß (IL-1ß), interleukin-10 (IL-10), analgesia effect, and labor outcomes. METHODS: A total of 360 healthy primiparas were randomized into the CSEA+AI group, the CSEA group, the AI group, and the control group (n = 90, each group) according to the labor analgesia methods. RESULTS: Compared to the CSEA group, the CSEA+AI group had significantly lower visual analog scale (VAS) scores, adverse events, dose of ropivacaine/sufentanil, and shorter labor durations. The IL-1ß/IL-10 ratio in maternal peripheral blood and umbilical cord blood was reduced in the CSEA+AI group compared with the CSEA group. CONCLUSION: The combination of CSEA and AI can reduce the ratio of IL-1ß/ IL-10 in maternal peripheral blood and umbilical cord blood, which can effectively relieve labor pain.

Macrophage NFATc3 prevents foam cell formation and atherosclerosis: evidence and mechanisms.

AIMS: Our previous study demonstrated that Ca2+ influx through the Orai1 store-operated Ca2+ channel in macrophages contributes to foam cell formation and atherosclerosis via the calcineurin-ASK1 pathway, not the classical calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Moreover, up-regulation of NFATc3 in macrophages inhibits foam cell formation, suggesting that macrophage NFATc3 is a negative regulator of atherogenesis. Hence, this study investigated the precise role of macrophage NFATc3 in atherogenesis. METHODS AND RESULTS: Macrophage-specific NFATc3 knockout mice were generated to determine the effect of NFATc3 on atherosclerosis in a mouse model of adeno-associated virus-mutant PCSK9-induced atherosclerosis. NFATc3 expression was decreased in macrophages within human and mouse atherosclerotic lesions. Moreover, NFATc3 levels in peripheral blood mononuclear cells from atherosclerotic patients were negatively associated with plaque instability. Furthermore, macrophage-specific ablation of NFATc3 in mice led to the atherosclerotic plaque formation, whereas macrophage-specific NFATc3 transgenic mice exhibited the opposite phenotype. NFATc3 deficiency in macrophages promoted foam cell formation by potentiating SR-A- and CD36-meditated lipid uptake. NFATc3 directly targeted and transcriptionally up-regulated miR-204 levels. Mature miR-204-5p suppressed SR-A expression via canonical regulation. Unexpectedly, miR-204-3p localized in the nucleus and inhibited CD36 transcription. Restoration of miR-204 abolished the proatherogenic phenotype observed in the macrophage-specific NFATc3 knockout mice, and blockade of miR-204 function reversed the beneficial effects of NFATc3 in macrophages. CONCLUSION: Macrophage NFATc3 up-regulates miR-204 to reduce SR-A and CD36 levels, thereby preventing foam cell formation and atherosclerosis, indicating that the NFATc3/miR-204 axis may be a potential therapeutic target against atherosclerosis.

Design, synthesis and biological evaluation of novel indolin-2-ones as potent anticancer compounds.

The indolin-2-one core is a privileged structure for antitumor agents, especially kinase inhibitors. Twenty-three novel indolin-2-ones were designed by molecular dissection of the anticancer drug indirubin. Seventeen of them exhibited significant inhibition against the tested cell lines, and two of them (1c and 1h) showed IC50 values at the submicromolar level against HCT-116 cells. Compounds 1c and 2c were also potent inhibitors of the triple-negative breast cancer (TNBC) cell line MDA-MB-231. Flow cytometry was utilized to explore the antitumor mechanism of 1c and 2c with MDA-MB-231 cells, and distinct effects were observed on 2c. Furthermore, immunocytochemical examination of 1c suggested a destabilization of microtubules, which was significantly different from the effect of IM, an indirubin derivative.