The dynamic cell–cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are ...extracellular vesicles that actively participate in cell–cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the β‐catenin/Tcf‐4‐activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA‐146a‐5p (miR‐146a) is the major miRNA in CRCSC exosomes and exosomal miR‐146a promotes stem‐like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR‐146a expression in serum exhibits higher miR‐146aHigh/NumbLow CRCSC traits, an increased number of tumor‐filtrating CD66(+) neutrophils and a decreased number of tumor‐infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome‐mediated stemness expansion.
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The tumor microenvironment (TME) is composed of heterogeneous tumor cells and host cells interacting with each other to promote disease progression. However, diagnostic and prognostic biomarkers to monitor the cancer stem cells (CSCs)‐host interplay are lacking. Here, the authors explore the role of tumor exosomes in cancer stemness and demonstrate that RAB27B‐assisted secretion of miRNA‐dominant exosomes is one critical feature of CSCs. Importantly, they show that colorectal cancer stem cells release miR‐146a‐loaded oncogenic exosomes for reprogramming non‐CSC cells and demonstrate the clinical relevance of exosomal miR‐146a in predicting the TME of CRC patients.
Loihi is a 60-mm2 chip fabricated in Intels 14-nm process that advances the state-of-the-art modeling of spiking neural networks in silicon. It integrates a wide range of novel features for the ...field, such as hierarchical connectivity, dendritic compartments, synaptic delays, and, most importantly, programmable synaptic learning rules. Running a spiking convolutional form of the Locally Competitive Algorithm, Loihi can solve LASSO optimization problems with over three orders of magnitude superior energy-delay-product compared to conventional solvers running on a CPU iso-process/voltage/area. This provides an unambiguous example of spike-based computation, outperforming all known conventional solutions.
The aim of this study was to investigate the effect of outdoor activity during class recess on myopia changes among elementary school students in a suburban area of Taiwan.
Prospective, comparative, ...consecutive, interventional study.
Elementary school students 7 to 11 years of age recruited from 2 nearby schools located in a suburban area of southern Taiwan.
The children of one school participated in the interventions, whereas those from the other school served as the control group. The interventions consisted of performing a recess outside the classroom (ROC) program that encouraged children to go outside for outdoor activities during recess. The control school did not have any special programs during recess.
Data were obtained by means of a parent questionnaire and ocular evaluations that included axial length and cycloplegic autorefraction at the beginning and after 1 year.
Five hundred seventy-one students were recruited for this study, of whom 333 students participated in the interventional program, and 238 students were in the control school. At the beginning of the study, there were no significant differences between these 2 schools with regard to age, gender, baseline refraction, and myopia prevalence (47.75% vs. 49.16%). After 1 year, new onset of myopia was significantly lower in the ROC group than in the control group (8.41% vs. 17.65%; P<0.001). There was also significantly lower myopic shift in the ROC group compared with the control group (-0.25 diopter D/year vs. -0.38 D/year; P = 0.029). The multivariate analysis demonstrated that the variables of intervention of the ROC program and higher school year proved to be a protective factor against myopia shift in nonmyopic subjects (P = 0.020 and P = 0.017, respectively). For myopic subjects, school year was the only variable significantly associated with myopia progression (P = 0.006).
Outdoor activities during class recess in school have a significant effect on myopia onset and myopic shift. Such activities have a prominent effect on the control of myopia shift, especially in nonmyopic children.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
To investigate the effectiveness of a school-based program promoting outdoor activities in Taiwan for myopia prevention and to identify protective light intensities.
Multi-area, cluster-randomized ...intervention controlled trial.
A total 693 grade 1 schoolchildren in 16 schools participated. Two hundred sixty-seven schoolchildren were in the intervention group and 426 were in the control group.
Initially, 24 schools were randomized into the intervention and control groups, but 5 and 3 schools in the intervention and control groups, respectively, withdrew before enrollment. A school-based Recess Outside Classroom Trial was implemented in the intervention group, in which schoolchildren were encouraged to go outdoors for up to 11 hours weekly. Data collection included eye examinations, cycloplegic refraction, noncontact axial length measurements, light meter recorders, diary logs, and questionnaires.
Change in spherical equivalent and axial length after 1 year and the intensity and duration of outdoor light exposures.
The intervention group showed significantly less myopic shift and axial elongation compared with the control group (0.35 diopter D vs. 0.47 D; 0.28 vs. 0.33 mm; P = 0.002 and P = 0.003) and a 54% lower risk of rapid myopia progression (odds ratio, 0.46; 95% confidence interval CI, 0.28-0.77; P = 0.003). The myopic protective effects were significant in both nonmyopic and myopic children compared with controls. Regarding spending outdoor time of at least 11 hours weekly with exposure to 1000 lux or more of light, the intervention group had significantly more participants compared with the control group (49.79% vs. 22.73%; P < 0.001). Schoolchildren with longer outdoor time in school (≥200 minutes) showed significantly less myopic shift (measured by light meters; ≥1000 lux: 0.14 D; 95% CI, 0.02-0.27; P = 0.02; ≥3000 lux: 0.16 D; 95% CI, 0.002-0.32; P = 0.048).
The school-based outdoor promotion program effectively reduced the myopia change in both nonmyopic and myopic children. Outdoor activities with strong sunlight exposure may not be necessary for myopia prevention. Relatively lower outdoor light intensity activity with longer time outdoors, such as in hallways or under trees, also can be considered.
Partial least squares structural equation modeling (PLS‐SEM) has become a key multivariate statistical modeling technique that educational researchers frequently use. This paper reviews the uses of ...PLS‐SEM in 16 major e‐learning journals, and provides guidelines for improving the use of PLS‐SEM as well as recommendations for future applications in e‐learning research. A total of 53 articles using PLS‐SEM published in January 2009–August 2019 are reviewed. We assess these published applications in terms of the following key criteria: reasons for using PLS‐SEM, model characteristics, sample characteristics, model evaluations and reporting. Our results reveal that small sample size and nonnormal data are the first two major reasons for using PLS‐SEM. Moreover, we have identified how to extend the applications of PLS‐SEM in the e‐learning research field.
Summary Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from ...Asian countries. With a high mortality-to-incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries.
Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis ...factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.
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•TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation•Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization•CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination•Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy
Lim et al. show that inflammation increases PD-L1 expression in tumors through TNF-α-mediated activation of NF-κB, leading to transactivation of CSN5. CSN5 reduces PD-L1 ubiquitination and stabilizes it. Inhibition of CSN5 cooperates with anti-CTLA4 to enhance anti-tumor T cell function and reduce tumor growth.
Triple-negative breast cancer (TNBC), which lacks estrogen receptor α (ERα), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression, is closely related to basal-like ...breast cancer. Previously, we and others report that cyclin E/cyclin-dependent kinase 2 (CDK2) phosphorylates enhancer of zeste homolog 2 (EZH2) at T416 (pT416-EZH2). Here, we show that transgenic expression of phospho-mimicking EZH2 mutant EZH2
in mammary glands leads to tumors with TNBC phenotype. Coexpression of EZH2
in mammary epithelia of HER2/Neu transgenic mice reprograms HER2-driven luminal tumors into basal-like tumors. Pharmacological inhibition of CDK2 or EZH2 allows re-expression of ERα and converts TNBC to luminal ERα-positive, rendering TNBC cells targetable by tamoxifen. Furthermore, the combination of either CDK2 or EZH2 inhibitor with tamoxifen effectively suppresses tumor growth and markedly improves the survival of the mice bearing TNBC tumors, suggesting that the mechanism-based combination therapy may be an alternative approach to treat TNBC.
The contribution of retailing to total airport revenue is becoming more important. This study examines the relationship between passengers' shopping motivations and their commercial activities at ...airports, as well as the moderating effects of time pressure and impulse buying on this relationship. A sample of passenger survey data was collected at Taiwan's Taoyuan International Airport. Three shopping motivations, namely, “favorable price and quality”, “environment and communication”, and “culture and atmosphere,” are identified based on the results of factor analysis. The results reveal that passenger shopping motivations have positive impacts on commercial activities at the airport, and furthermore both time pressure and impulse buying tendency moderate the relationship between shopping motivations and commercial activities.
► The paper examines shoppers motives and their impacts on airport commercial activities. ► Data are derived from a sample of shoppers at Taiwan's Taoyuan International Airport. ► Three key factors were found impacting airport commercial activities. ► Two moderating variables of time pressure and predisposition to impulse buying were found.
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