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Reward has been known to render the reward-associated stimulus more salient to block effective attentional orienting in space. However, whether and how reward influences goal-directed attention in time remains unclear. Here, we used a modified attentional cueing paradigm to explore the effect of reward on temporal attention, in which the valid targets were given a low monetary reward and invalid targets were given a high monetary reward. The results showed that the temporal cue validity effect was significantly smaller when the competitive reward structure was employed (Experiment 1), and we ruled out the possibility that the results were due to the practice effect (Experiment 2a) or a reward-promoting effect (Experiment 2b). When further strengthening the intensity of the reward from 1:10 to 1:100 (Experiment 3), we found a similar pattern of results to those in Experiment 1. These results suggest that reward information which was based on relative instead of absolute values can weaken, but not reverse, the orienting attention in time. [ABSTRACT FROM AUTHOR]

Background: Panax notoginseng saponins (PNS) are commonly used first-line drugs for treating cerebral thrombosis and stroke in China. However, the synchronized and targeted delivery of active ingredients in traditional Chinese medicine (TCM) poses a significant challenge for modern TCM formulations. Methods: Bovine serum albumin (BSA) was modified using 2-methacryloyloxyethyl phosphorylcholine (MPC), an analog of acetylcholine, and subsequently adsorbed the major PNS onto the modified albumin to produce MPC-BSA@PNS nanoparticles (NPs). This novel delivery system facilitated efficient and synchronized transport of PNS across the blood–brain barrier (BBB) through active transport mediated by nicotinic acetylcholine receptors. Results: In vitro experiments demonstrated that the transport rates of R1, Rg1, Rb1, and Rd across the BBB were relatively synchronous in MPC-BSA@PNS NPs compared to those in the PNS solution. Additionally, animal experiments revealed that the brain-targeting efficiencies of R1 + Rg1 + Rb1 in MPC-BSA@PNS NPs were 2.02 and 7.73 times higher than those in BSA@PNS NPs and the free PNS group, respectively. Conclusions: This study presents a simple and feasible approach for achieving the targeted delivery of complex active ingredient clusters in TCM. [ABSTRACT FROM AUTHOR]

Background: Daily activities are associated with affective experiences. A 24-h day can be separated into five mutually exclusive activity types: sleep, awake in bed, moderate-to-vigorous physical activity (MVPA), light-intensity physical activity (LIPA), and sedentary behavior (SB). Most research has examined these activities independently and not collectively, yet increased time in one activity must be offset by decreasing other activities. Using compositional isotemporal substitution analyses, this study examined the associations between time spent in daily activities and affect, including both high and low arousal positive and negative affect. Method: Across three separate studies, daily activities and affect were measured throughout 7–15 days (Mdays = 10) in 361 healthy community adults (72.5% females, Mage = 22.79 years). Activities were objectively assessed using accelerometry and self-reported affect was assessed using repeated ecological momentary assessments. Minutes spent in each activity and affect values across the three studies were averaged for each participant. Results: Longer sleep duration at the expense of time awake in bed was associated with lower high arousal negative affect (e.g., nervousness, b = − 0.24, p =.007). More MVPA at the expense of LIPA or SB was associated with higher high arousal positive affect (e.g., happiness, b = 0.35, p =.027). Activity composition was not associated with low arousal positive or negative affect (all p ≥.06). Conclusion: Associations between 24-h activity composition and affect differed based on types of activities, types of affect, and the interrelationships between activities within the composition. Findings can aid interventions to develop integrated guidance on the optimal activity patterns for mental health. [ABSTRACT FROM AUTHOR]

This study examined whether resilience capacity moderates the association of daily perceived stress and affect with cortisol diurnal slope among relocated emerging adults. Relocated undergraduates (N = 98; aged 18–25 years) were recruited from three groups: Resilient, Vulnerable, and Control. The Resilient group required Risky Family Questionnaire (RFQ) scores ≥ 29 and Brief Resilience Scale (BRS) scores ≥ 3.6. The Vulnerable group required RFQ scores ≥ 29 and BRS scores ≤ 3. The comparison Control group required RFQ scores ≤ 21 and T-scores < 60 on PROMIS anxiety and depression symptoms. Mixed-effects models were used to test the unique associations of perceived stress, negative affect, and positive affect x group interactions (predictors) on diurnal cortisol slope (outcome) across 14 consecutive days. The Resilient group did not moderate the associations between daily stress or affect on cortisol diurnal slope. Instead, both the Resilient and Vulnerable groups with early family risk, showed a steeper diurnal slope unique to higher stress and a flatter slope unique to higher negative affect. Results suggest that riskier early family life was significantly associated with altered cortisol diurnal slope outcomes to stress (i.e., demand) and negative affect (i.e., distress). These associations were not attenuated by current resilience capacity. [ABSTRACT FROM AUTHOR]

Acquired resistance to BRAF/MEK-targeted therapy occurs in the majority of melanoma patients that harbor BRAF mutated tumors, leading to relapse or progression and the underlying mechanism is unclear in many cases. Using multiplex immunohistochemistry and spatial imaging analysis of paired tumor sections obtained from 11 melanoma patients prior to BRAF/MEK-targeted therapy and when the disease progressed on therapy, we observed a significant increase of tumor cellularity in the progressed tumors and the close association of SOX10+ melanoma cells with CD8+ T cells negatively correlated with patient's progression-free survival (PFS). In the TCGA-melanoma dataset (n = 445), tumor cellularity exhibited additive prognostic value in the immune score signature to predict overall survival in patients with early-stage melanoma. Moreover, tumor cellularity prognoses OS independent of immune score in patients with late-stage melanoma. [ABSTRACT FROM AUTHOR]

Lung cancer remains the leading cause of cancer deaths worldwide. Although low-dose spiral computed tomography (LDCT) screening is used for the detection of lung cancer in a high-risk population, false-positive results of LDCT remain a clinical problem. Here, we developed a blood test of a novel panel of three established lung cancer methylation biomarkers for lung cancer detection. Short stature homeobox 2 gene (SHOX2), ras association domain family 1A gene (RASSF1A), and prostaglandin E receptor 4 gene (PTGER4) methylation was analyzed in a training cohort of 351 individuals (197 controls, 154 cases) and validated from an independent cohort of 149 subjects (89 controls, 60 cases). The novel panel biomarkers distinguished between malignant and benign lung disease at high sensitivity and specificity: 87.0% sensitivity [95% CI 80.2–91.5%], 98.0% specificity [95% CI 94.9–99.4%]. Sensitivity in adenocarcinoma, squamous cell carcinoma, small cell lung cancer, and other lung cancer was 89.0%, 87.5%, 85.7%, and 77.8%, respectively. Notably, cancer patients in stage I and II showed high diagnostic sensitivity at 82.5% and 90.5%, respectively. Moreover, the diagnostic efficiency did not show bias toward age, gender, smoking, and the presence of other (nonlung) cancers. The performance of the panel in the validation cohort confirmed the diagnostic value. These findings clearly showed that this panel of DNA methylation biomarkers was effective in detecting lung cancer noninvasively and may provide clinical utility in stand-alone or in combination with current imaging techniques to improve the diagnosis of lung cancer. [ABSTRACT FROM AUTHOR]

Purpose: Patients with localized breast cancer have a 5-year survival rate > 99% compared to patients with metastatic breast cancer (MBC) that have a 5-year survival rate of ~ 27%. Unregulated PI3K/AKT signaling is a common characteristic of MBC, making it a desirable therapeutic target for tumors with activating mutations in this pathway. Interestingly, inhibition of the PI3K/AKT pathway can affect signaling in immune cells, which could potentially alter the immune phenotype of patients undergoing therapy with these drugs. The purpose of this study is to evaluate how PI3K inhibition affects the immune cells of MBC patients during treatment. Methods: We investigated the effects of PI3K inhibition on the immune cell populations in peripheral blood of MBC patients enrolled in 4 different clinical trials utilizing PI3K inhibitors. Peripheral blood was drawn at different points in patient treatment cycles to record immune cell fluctuations in response to therapy. Results: MBC patients who responded to treatment with a positive fold-change in cytotoxic T cell population, had an average duration of treatment response of 31.4 months. In contrast, MBC patients who responded to treatment with a negative fold-change in cytotoxic T-cell population, had an average duration of therapeutic response of 5 months. These data suggest that patients with a more robust, initial anti-tumor T cell response may have a longer therapeutic response compared to patients who do not have a robust, initial anti-tumor T cell response. Conclusions: These results highlight the potential for PI3K inhibition to sensitize tumors to immune checkpoint inhibitors, thus providing additional therapeutic options for patients with MBC. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is an invasive subtype of breast cancer but paradoxically associated with increased tumor-infiltrating leukocytes. The molecular and cellular mechanisms underlying TNBC immunobiology are incompletely understood. Interleukin (IL)-17A is a pro-inflammatory cytokine that has both pro- and anti-tumor effects and found in 40–80% of TNBC samples. We report here that IL-17A mRNA and protein are detectable in some human TNBC cell lines and further upregulated by IL-23 and LPS stimulation. Furthermore, the impact of tumor-derived IL-17A in host immune response and tumor growth was examined using murine TNBC 4T1 mammary carcinoma cells transduced with an adenoviral vector expressing IL-17A (AdIL-17A) or control vector (Addl). Compared to Addl-transduction, AdIL-17A-transduction enhanced 4T1 tumor growth and lung metastasis in vivo, which was associated with a marked expansion of myeloid-derived suppressor cells (MDSCs). However, AdIL-17A-transduction also induced strong organ-specific and time-dependent immune activation indicated by dynamic changes of NK cells, B cells, CD4, and CD8 T cells in peripheral blood, lung, and tumor site, as well as the plasma levels of IFNγ. Such findings highlight that tumor-associated IL-17A induces concurrent immune activation and immune suppression. Administration of anti-Gr1 or anti-G-CSF antibody effectively depleted MDSCs in vivo, markedly reducing the growth of AdIL-17A-transduced 4T1 tumors, and eliminating lung metastasis. Collectively, our study demonstrates that MDSC depletion is an effective and practical approach for treating IL-17A-enriched mammary carcinomas. [ABSTRACT FROM AUTHOR]

The effects of heat treatment on the microstructure and mechanical properties of Mg-containing (7 ppm), low-carbon commercial steel (SS400) were investigated. Twenty different heat treatment paths were performed using a Gleeble 1500 thermomechanical simulator. It was observed by using an optical microscope that as the cooling rate increased and holding temperature decreased, the volume fractions of pearlite, Widmanstätten ferrite, and grain boundary allotriomorphs ferrite fell, whereas that of acicular ferrite (AF) increased. Quantifying the fractions of AF and other phases by using electron backscatter diffraction shows that the heat treatment path with a cooling rate of 20 K/s and holding temperature of 723 K (450 °C) induced the highest volume fraction (44 pct) of AF. As such, the toughness of the sample was increased 12.4 times compared with that observed in the sample containing 4 pct AF. Typical inclusions were analyzed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy. The results showed that the magnesium-based complex inclusions could act as nucleation sites of AF. Inclusions with a size of about 5 μm can serve as heterogeneous nucleation sites for AF. Mg-containing SS400 steel also has excellent hot-ductility in the temperature range of 973 K to 1273 K (700 °C to 1000 °C), and the minimum percentage reduction in area (R.A pct) value of around 63 pct at 1073 K (800 °C). [ABSTRACT FROM AUTHOR]

Mobile learning, with its features of ubiquitousness and flexibility, enables users to learn in any appropriate place and at any appropriate time. This emerging way of digital learning will be the future trend. Therefore, the technology acceptance model (TAM) proposed by Davis was extended with extrinsic motivation, perceived convenience, and intrinsic motivation, perceived playfulness, for examining the factors that affect continuance intention to use the English mobile learning system (EMLS) and the relationships among these factors. Participating in the study were 158 technical college students from the middle part of Taiwan who were studying English via EMLS using PDAs for 4 weeks. Data were collected by questionnaires and were analyzed by SmartPLS as an SEM analysis tool. The results revealed that perceived convenience, perceived playfulness, perceived ease of use, and perceived usefulness were antecedent factors that affected continuance intention to use the EMLS. Perceived usefulness had a greater impact on continuance intention than perceived playfulness. Overall, the extended TAM in the present study was effective at predicting and explaining the continuance intention to use the EMLS. [ABSTRACT FROM AUTHOR]

Abstract  The endophytic fungus Nodulisporium sylviforme produces taxol, a diterpene alkaloid compound that has unique anti-neoplastic activity. In this study, suppression subtractive hybridization was performed to identify genes in N. sylviforme that were involved in the up-regulation of taxol production. A total of 91 clones represented the differentially expressed genes were selected based on reverse blotting results. These clones were then sequenced and analyzed using BLAST-X comparisons that revealed that about 37.8% of the ESTs were homologous to 17 different proteins with known function, 20.7% were homologous to nine hypothetical proteins and the remaining 41.5% had no identifiable homology; these may be novel genes. Two enzymatic genes involved in taxol production were found. The data presented in this study provide the first primary overview of a set of genes that are differentially expressed in N. sylviforme during taxol biosynthesis and form a solid foundation for the construction of high taxol-yielding genetically engineered strains. [ABSTRACT FROM AUTHOR]