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Graphene is a single-layer crystal of carbon, the thinnest two-dimensional material. It has unique electronic and photonic properties.

GLP-1 (glucagon-like peptide-1) has been reported to play a vital role in neuroprotection. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model widely used to study human multiple sclerosis, a chronic demyelination disease in the central nervous system (CNS). Recently, important studies have designated that the signaling axis of GLP-1 and its receptor controls the clinical manifestations and pathogenesis of EAE. However, it is elusive whether GLP-1 receptor signaling regulates the phenotype of autoreactive T cells in the CNS. We administered dulaglutide, a well-established GLP-1 receptor agonist (GLP-1 RA), to treat EAE mice prophylactically or semi-therapeutically and subsequently analyzed the mononuclear cells of the CNS. In this study, dulaglutide treatment significantly alleviates the clinical manifestations and histopathological outcomes of EAE. Dulaglutide decreases incidences of encephalitogenic Th1/Th17 cells and Th1 granulocyte-macrophage-colony-stimulating factor (GM-CSF) expression in the CNS. Administration of dulaglutide failed to control the chemotactic abilities of encephalitogenic Th1 and Th17 cells; however, prophylactic treatment considerably decreased the populations of dendritic cells and macrophages in the CNS parenchyma. These results obtained indicate that dulaglutide modulates the differentiation of encephalitogenic Th1/Th17 and the pathogenicity of Th1 cells by influencing antigen presenting cells quantities, providing mechanism insight on T cells regulation in ameliorating EAE by GLP-1.

Covalent organic frameworks (COFs), which are a new type of carbonaceous polymeric material, have attracted great interest because of their large surface area and high chemical and thermal stability. However, to the best of our knowledge, no work has reported the use of magnetic COFs as adsorbents for magnetic solid-phase extraction (MSPE) to enrich and determine environmental pollutants. This work aims to investigate the feasibility of using covalent triazine-based framework (CTF)/Fe2O3 composites as MSPE adsorbents to enrich and analyze perfluorinated compounds (PFCs) at trace levels in water samples. Under the optimal conditions, the method developed exhibited low limits of detection (0.62–1.39 ng·L-1), a wide linear range (5–4000 ng L-1), good repeatability (1.12–9.71%), and good reproducibility (2.45–7.74%). The new method was successfully used to determine PFCs in actual environmental water samples. MSPE based on CTF/Fe2O3 composites exhibits potential for analysis of PFCs at trace levels in environmental water samples.Graphical abstractMagnetic covalent triazine-based frameworks (CTFs) were used as magnetic solid-phase extraction adsorbents for the sensitive determination of perfluorinated compounds in environmental water samples. PFBA perfluorobutyric acid, PFBS perfluorobutane sulfonate, PFDA perfluorodecanoic acid, PFDoA perfluorododecanoic acid, PFHpA perfluoroheptanoic acid, PFHxA perfluorohexanoic acid, PFHxS perfluorohexane sulfonate, PFNA perfluorononanoic acid, PFOA perfluorooctanoic acid, PFPeA perfluoropentanoic acid, PFUdA Perfluoroundecanoic acid

Metalenses consist of an array of optical nanoantennas on a surface capable of manipulating the properties of an incoming light wavefront. Various flat optical components, such as polarizers, optical imaging encoders, tunable phase modulators and a retroreflector, have been demonstrated using a metalens design. An open issue, especially problematic for colour imaging and display applications, is the correction of chromatic aberration, an intrinsic effect originating from the specific resonance and limited working bandwidth of each nanoantenna. As a result, no metalens has demonstrated full-colour imaging in the visible wavelength. Here, we show a design and fabrication that consists of GaN-based integrated-resonant unit elements to achieve an achromatic metalens operating in the entire visible region in transmission mode. The focal length of our metalenses remains unchanged as the incident wavelength is varied from 400 to 660 nm, demonstrating complete elimination of chromatic aberration at about 49% bandwidth of the central working wavelength. The average efficiency of a metalens with a numerical aperture of 0.106 is about 40% over the whole visible spectrum. We also show some examples of full-colour imaging based on this design.

Background The six core competencies of ACGME - patient care (PC), medical knowledge (MK), system s -based practice (SBP), practice-based learning and improvement (PBLI), professionalism (PROF), and interpersonal and communication skills (ICS) - represent domains in which physicians must ultimately demonstrate competence. Although the ACGME’s six core competencies have been applied in Taiwan with the milestone project, the application of the six core competences in the Family Medicine milestones for residency training have not yet been established. Methods We recruited 61 family medicine physicians from 25 hospitals from four major geographic areas for a Delphi round one survey and 72 physicians from 27 hospitals for a Delphi round two survey. With 5-point scales, the Cronbach’s alphas for both importance and fitness were 0.98 in round one. In round two, the Cronbach’s alphas were 0.86 and 0.83 for importance and fitness. The mode and quartile deviation in Delphi method, importance-performance analysis (IPA), and importance-performance matrix analysis (IPMA) were used for three stages IPA process. Results In IPA, a total of 72.7% (16/22) of the sub-competencies exhibited high importance and fitness, with a mean score ≥ 4.7; the exceptions were PC-1 (cares for acutely ill or injured patients), MK-2 (critical thinking skills in patient care), SBP-1 (cost-conscious medical care), PBLI-3 (improves systems), PROF-3 (humanism/cultural proficiency), and ICS-4 (utilizes technology). In IPMA, the performance value of six core competencies for FMM-Taiwan was 92.6 when considering the importance and fitness indices of the 22 sub-competencies. Conclusions The accordance of the ACGME’s milestones to Taiwan was acceptable to good and related milestones could been developed for residency training.

ObjectiveAlthough mass eradication of Helicobacter pylori has been proposed as a means to eliminate gastric cancer, its long-term effects remain unclear.DesignMass eradication of H. pylori infection was launched in 2004 and continued until 2018 for a high-risk Taiwanese population aged 30 years or older dwelling on Matsu Islands with prevalent H. pylori infection. Test positives for the 13C-urea breath test underwent eradication therapy. We evaluated the effectiveness of the mass eradication in reducing two main outcomes, incidence and mortality rates of gastric cancer, until the end of 2016 and 2018, respectively.ResultsAfter six rounds of mass screening and eradication, the coverage rate reached 85.5% (6512/7616). The referral rate for treatment was 93.5% (4286/4584). The prevalence rates of H. pylori fell from 64.2% to 15.0% with reinfection rates of less than 1% per person-year. The presence and severity of atrophic gastritis and intestinal metaplasia also decreased with time. Compared with the historical control period from 1995 to 2003, the effectiveness in reducing gastric cancer incidence and mortality during the chemoprevention period was 53% (95% CI 30% to 69%, p<0.001) and 25% (95% CI −14% to 51%, p=0.18), respectively. No significant changes were noted in the incidence rates of other digestive tract cancers or the antibiotic resistance rate of H. pylori.ConclusionPopulation-based eradication of H. pylori has significantly reduced gastric cancer incidence with no increase in the likelihood of adverse consequences. A significant reduction in mortality is likely to be achieved with a longer follow-up period.Trial registration number NCT00155389

Overweight and obesity are important risk factors of gestational diabetes mellitus (GDM). Clustering of metabolic risk factors in early pregnancy may be a potential pathogenesis between the link of overweight/obesity and GDM. Since it remains unexplored, we investigated if overweight and obesity are associated with clustering of metabolic risk factors in early pregnancy and the risk of GDM in this cohort study. Total 527 women who visited National Taiwan University Hospital for prenatal care in between November 2013 to April 2018 were enrolled. Risk factors of GDM in the first prenatal visit (FPV) were recorded. Overweight/obesity was defined if body mass index ≥24 kg/m2. GDM was diagnosed from the result of a 75g oral glucose tolerance test in 24-28 gestational weeks. Overweight/obesity was associated with clustering of metabolic risk factors of GDM, including high fasting plasma glucose, high HbA1c, insulin resistance, high plasma triglyceride and elevated blood pressure in FPV (p<0.05). There was a positive relationship between the number of metabolic risk factors and the incidence of GDM (p <0.05). The odds ratios of HbA1c and diastolic blood pressure were higher in overweight/obese women, compared with those in normal-weight women. Overweight/obesity is associated with clustering of metabolic risk factors in early pregnancy, which is correlated with higher risk of GDM. Our findings suggest that metabolic risk factors during early pregnancy should be evaluated in overweight/obese women.

Background:In the modern society when intelligent mobile devices become popular, the Internet breaks through the restrictions on time and space and becomes a ubiquitous learning tool. Designing teaching activity for digital learning and flexibly applying technology tools are the key issues for current information technology integrated education.Material and methods:In this study, students are tested and proceeded questionnaire survey to understand the opinions about digital learning. To effectively achieve the research objectives and test the research hypotheses, quasi-experimental research is applied in this study. Total 116 students in 4 classes are selected as the research subjects for the instructional research.Results:The research results conclude that 1.digital learning presents better positive effects on learning motivation than traditional teaching does, 2.digital learning shows better positive effects on learning outcome than traditional teaching does, 3.learning motivation reveals significantly positive effects on learning effect in learning outcome, and 4.learning motivation appears remarkably positive effects on learning gain in learning outcome.Conclusions:It is expected to combine with current teaching trend and utilize the advantages of digital learning to develop practicable teaching strategies for the teaching effectiveness.

Anaplastic thyroid carcinoma (ATC) and squamous thyroid carcinoma (STC) are both rare and advanced thyroid malignancies with a very poor prognosis and an average median survival time of 5 months and less than 20% of affected patients are alive 1 year after diagnosis. The clinical management of both ATC and STC is very similar because they are not particularly responsive to radiotherapy and chemotherapy. This inspired us to explore a novel and effective clinically approved therapy for ATC treatment. Histone deacetylase inhibitor (HDACi) drugs are recently FDA-approved drug for malignancies, especially for blood cell cancers. Therefore, we investigated whether an HDACi drug acts as an effective anticancer drug for advanced thyroid cancers. Cell viability analysis of panobinostat treatment demonstrated a significant IC50 of 0.075 µM on SW579 STC cells. In addition, panobinostat exposure activated histone acetylation and triggered cell death mainly through cell cycle arrest and apoptosis-related protein activation. Using CRISPR/Cas9 to knock out HDAC1 and HDAC2 genes in SW579 cells, we observed that the histone acetylation level and cell cycle arrest were enhanced without any impact on cell growth. Furthermore, HDAC1 and HDAC2 double knockout (KO) cells showed dramatic cell apoptosis activation compared to HDAC1 and HDAC2 individual KO cells. This suggests expressional and biofunctional compensation between HDAC1 and HDAC2 on SW579 cells. This study provides strong evidence that panobinostat can potentially be used in the clinic of advanced thyroid cancer patients.

Background Lung cancer is the most common and deadliest cancer worldwide, and approximately 90% of all lung cancer deaths are caused by tumor metastasis. Tumor-derived exosomes could potentially promote tumor metastasis through the delivery of metastasis-related molecules. However, the function and underlying mechanism of exosomal long noncoding RNA (lncRNA) in lung cancer metastasis remain largely unclear. Methods Cell exosomes were purified from conditioned media by differential ultracentrifugation and observed using transmission electron microscopy, and the size distributions were determined by nanoparticle tracking analysis. Exosomal lncRNA sequencing (lncRNA-seq) was used to identify long noncoding RNAs. Cell migration and invasion were determined by wound-healing assays, two-chamber transwell invasion assays and cell mobility tracking. Mice orthotopically and subcutaneously xenografted with human cancer cells were used to evaluate tumor metastasis in vivo. Western blot, qRT‒PCR, RNA-seq, and dual-luciferase reporter assays were performed to investigate the potential mechanism. The level of exosomal lncRNA in plasma was examined by qRT‒PCR. MS2-tagged RNA affinity purification (MS2-TRAP) assays were performed to verify lncRNA-bound miRNAs. Results Exosomes derived from highly metastatic lung cancer cells promoted the migration and invasion of lung cancer cells with low metastatic potential. Using lncRNA-seq, we found that a novel lncRNA, lnc-MLETA1, was upregulated in highly metastatic cells and their secreted exosomes. Overexpression of lnc-MLETA1 augmented cell migration and invasion of lung cancer. Conversely, knockdown of lnc-MLETA1 attenuated the motility and metastasis of lung cancer cells. Interestingly, exosome-transmitted lnc-MLETA1 promoted cell motility and metastasis of lung cancer. Reciprocally, targeting lnc-MLETA1 with an LNA suppressed exosome-induced lung cancer cell motility. Mechanistically, lnc-MLETA1 regulated the expression of EGFR and IGF1R by sponging miR-186-5p and miR-497-5p to facilitate cell motility. The clinical datasets revealed that lnc-MLETA1 is upregulated in tumor tissues and predicts survival in lung cancer patients. Importantly, the levels of exosomal lnc-MLETA1 in plasma were positively correlated with metastasis in lung cancer patients. Conclusions This study identifies lnc-MLETA1 as a critical exosomal lncRNA that mediates crosstalk in lung cancer cells to promote cancer metastasis and may serve as a prognostic biomarker and potential therapeutic target for lung cancer diagnosis and treatment.