Uniform, Strain-Free, Large-Scale Graphene and h-BN Monolayers Enabled by Hydrogel Substrates.

Translation of the unique properties of 2D monolayers from non-scalable micron-sized samples to macroscopic scale is a longstanding challenge obstructed by the substrate-induced strains, interface nonuniformities, and sample-to-sample variations inherent to the scalable fabrication methods. So far, the most successful strategies to reduce strain in graphene are the reduction of the interface roughness and lattice mismatch by using hexagonal boron nitride (h-BN), with the drawback of limited uniformity and applicability to other 2D monolayers, and liquid water, which is not compatible with electronic devices. This work demonstrates a new class of substrates based on hydrogels that overcome these limitations and excel h-BN and water substrates at strain relaxation enabling superiorly uniform and reproducible centimeter-sized sheets of unstrained monolayers. The ultimate strain relaxation and uniformity are rationalized by the extreme structural adaptability of the hydrogel surface owing to its high liquid content and low Young's modulus, and are universal to all 2D materials irrespective of their crystalline structure. Such platforms can be integrated into field effect transistors and demonstrate enhanced charge carrier mobilities in graphene. These results present a universal strategy for attaining uniform and strain-free sheets of 2D materials and underline the opportunities enabled by interfacing them with soft matter.

Intra-Articular Lactate Dehydrogenase A Inhibitor Oxamate Reduces Experimental Osteoarthritis and Nociception in Rats via Possible Alteration of Glycolysis-Related Protein Expression in Cartilage Tissue.

Osteoarthritis (OA) is the most common form of arthritis and joint disorder worldwide. Metabolic reprogramming of osteoarthritic chondrocytes from oxidative phosphorylation to glycolysis results in the accumulation of lactate from glycolytic metabolite pyruvate by lactate dehydrogenase A (LDHA), leading to cartilage degeneration. In the present study, we investigated the protective effects of the intra-articular administration of oxamate (LDHA inhibitor) against OA development and glycolysis-related protein expression in experimental OA rats. The animals were randomly allocated into four groups: Sham, anterior cruciate ligament transection (ACLT), ACLT + oxamate (0.25 and 2.5 mg/kg). Oxamate-treated groups received an intra-articular injection of oxamate once a week for 5 weeks. Intra-articular oxamate significantly reduced the weight-bearing defects and knee width in ACLT rats. Histopathological analyses showed that oxamate caused significantly less cartilage degeneration in the ACLT rats. Oxamate exerts hypertrophic effects in articular cartilage chondrocytes by inhibiting glucose transporter 1, glucose transporter 3, hexokinase II, pyruvate kinase M2, pyruvate dehydrogenase kinases 1 and 2, pyruvate dehydrogenase kinase 2, and LHDA. Further analysis revealed that oxamate significantly reduced chondrocyte apoptosis in articular cartilage. Oxamate attenuates nociception, inflammation, cartilage degradation, and chondrocyte apoptosis and possibly attenuates glycolysis-related protein expression in ACLT-induced OA rats. The present findings will facilitate future research on LDHA inhibitors in prevention strategies for OA progression.

Unique interface reflection phenomena tailored by nanoscale electromagnetic boundary conditions.

Local interface response effects are neglected based on the traditional electromagnetic boundary conditions (EMBCs) in an abrupt interface model. In this study, generalized nanoscale EMBCs are derived with interface response functions (IRFs) representing field inhomogeneity across the interface based on integral Maxwell's equations. They are rewritten in two different forms that correspond to the equivalent abrupt interface models with interface-induced dipoles or charges and currents. Interesting behaviors of Brewster angle shifting, non-extinction at Brewster angle, and unique absorption or gain effects are revealed based on the advanced Fresnel formula. IRFs-controlled GH-shift and angular GH-shift of a Gaussian beam near the Brewster angles are generated by the gradient interface. These unique phenomena provide some guidance for measuring the IRFs and expanding interface photonics at the nanoscale.

Tooth extraction within 2 weeks before radiotherapy and osteoradionecrosis: A nationwide cohort study.

OBJECTIVES: The theory of at least 2-week waiting period between tooth extraction and head and neck radiotherapy could reduce osteoradionecrosis remains controversial. Thus, this study examined the theory and associated factors. MATERIALS AND METHODS: Data were retrieved from the National Health Insurance Research Database, Taiwan Cancer Registry Database, and Cause of Death Statistics. We included 24,353 patients with head and neck cancer who received radiotherapy from 2011 to 2017 and were followed up until 2019. The patients were divided into three groups: those undergoing tooth removal 2-8 weeks before radiotherapy, those undergoing tooth removal within 2 weeks before radiotherapy, and others. Confounding factors were clinical information, physical conditions, and risky habits. We used the Cox regression model to assess osteoradionecrosis risk. RESULTS: No significant difference in osteoradionecrosis risk was observed between those undergoing tooth extraction within 2 weeks before radiotherapy and the other groups. An irradiation dose of ≥60 Gy, chemotherapy, tumor excision, post-radiotherapy tooth extraction, mandibulectomy, hyperlipidemia, and oral cavity as the tumor subsite were significantly positively associated with osteoradionecrosis risk. CONCLUSION: A waiting period of ≥2 weeks between tooth extraction and radiotherapy did not significantly reduce osteoradionecrosis risk.

Microtubule-severing protein Fidgetin-like 1 promotes spindle organization during meiosis of mouse oocytes.

Microtubule-severing proteins (MTSPs) play important roles in mitosis and interphase. However, to the best of our knowledge, no previous studies have evaluated the role of MTSPs in female meiosis in mammals. It was found that FIGNL1, a member of MTSPs, was predominantly expressed in mouse oocytes and distributed at the spindle poles during meiosis in the present study. FIGNL1 was co-localized and interacted with γ-tubulin, an important component of the microtubule tissue centre (MTOC). Fignl1 knockdown by specific small interfering RNA caused spindle defects characterized by an abnormal length:width ratio and decreased microtubule density, which consequently led to aberrant chromosome arrangement, oocyte maturation and fertilization obstacles. In conclusion, the present results suggested that FIGNL1 may be an essential factor in oocyte maturation by influencing the meiosis process via the formation of spindles.

Design and Validation of an Augmented Reality Teaching System for Primary Logic Programming Education.

Programming is a skill that requires high levels of logical thinking and problem-solving abilities. According to the Curriculum Guidelines for the 12-Year Basic Education currently implemented in Taiwan, programming has been included in the mandatory courses of middle and high schools. Nevertheless, the guidelines simply recommend that elementary schools conduct fundamental instructions in related fields during alternative learning periods. This may result in the problem of a rough transition in programming learning for middle school freshmen. To alleviate this problem, this study proposes an augmented reality (AR) logic programming teaching system that combines AR technologies and game-based teaching material designs on the basis of the fundamental concepts for seventh-grade structured programming. This system can serve as an articulation curriculum for logic programming in primary education. Thus, students are able to develop basic programming logic concepts through AR technologies by performing simple command programming. This study conducted an experiment using the factor-based quasi-experimental research design and questionnaire survey method, with 42 fifth and sixth graders enrolled as the experimental subjects. The statistical analysis showed the following results: In terms of learning effectiveness, both AR-based and traditional learning groups displayed a significant performance. However, of the two groups, the former achieved more significant effectiveness in the posttest results. Regarding learning motivation, according to the evaluation results of the Attention, Relevance, Confidence, and Satisfaction (ARCS) motivation model, the AR-based learning group manifested significantly higher levels of learning motivation than the traditional learning group, with particularly significant differences observed in the dimension of Attention. Therefore, the experimental results validate that the proposed AR-based logic programming teaching system has significant positive effects on enhancing students' learning effectiveness and motivation.

Stellettin B-Induced Oral Cancer Cell Death via Endoplasmic Reticulum Stress-Mitochondrial Apoptotic and Autophagic Signaling Pathway.

Oral squamous cell carcinoma (OSCC) affects tens of thousands of people worldwide. Despite advances in cancer treatment, the 5-year survival rate of patients with late-stage OSCC is low at 50-60%. Therefore, the development of anti-OSCC therapy is necessary. We evaluated the effects of marine-derived triterpene stellettin B in human OC2 and SCC4 cells. Stellettin B dose-dependently decreased the viability of both cell lines, with a significant reduction in OC2 cells at ≥0.1 µM at 24 and 48 h, and in SCC4 cells at ≥1 µM at 24 and 48 h. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells were significantly observed at 20 µM of stellettin B at 48 h, with the overexpression of cleaved caspase3 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, mitochondrial respiratory functions were ablated by stellettin B. Autophagy-related LC3-II/LC3-I ratio and Beclin-1 proteins were increased, whereas p62 was decreased. At 20 µM at 48 h, the expression levels of the endoplasmic reticulum (ER) stress biomarkers calnexin and BiP/GRP78 were significantly increased and mitogen-activated protein kinase (MAPK) signaling pathways were activated. Further investigation using the autophagy inhibitor 3-methyladenine (3-MA) demonstrated that it alleviated stellettin B-induced cell death and autophagy. Overall, our findings show that stellettin B induces the ER stress, mitochondrial stress, apoptosis, and autophagy, causing cell death of OSCC cells.

Health literacy and cancer screening behaviors among community-dwelling female adults in Taiwan.

This study was designed to explore the association among health literacy and cancer screening behaviors in Taiwanese females. A total of 353 community-dwelling females were recruited in this cross-sectional study from February to October 2015. Demographic, socioeconomic and personal behavior variables including physical activity, community activity, smoking, alcohol consumption, and betel nut chewing were recorded. Health literacy was evaluated using the Mandarin version of the European Health Literacy Survey Questionnaire. Data on screening behaviors for cervical, breast and colorectal cancers were confirmed by the Taiwanese National eHealth Database. Most respondents with inadequate or problematic general health literacy had no or irregular screening behaviors for cervical, breast and colorectal cancers. In multivariable regression analysis, women with inadequate health literacy were at a greater risk (Odds ratio = 5.71; 95% CI: 1.40-23.26) of having no previous Pap smear screening or >3 years screening interval regardless of education level. However, this association was not detected for breast or colorectal cancer. Women with inadequate health literacy were more likely to have irregular cervical cancer screening, however no associations among health literacy and breast or colorectal cancer were detected. The impact of health literacy on cancer screening behavior warrants further attention and research.

Chondroprotective Effects of a Histone Deacetylase Inhibitor, Panobinostat, on Pain Behavior and Cartilage Degradation in Anterior Cruciate Ligament Transection-Induced Experimental Osteoarthritic Rats.

Osteoarthritis (OA) is the most common articular degenerative disease characterized by chronic pain, joint inflammation, and movement limitations, which are significantly influenced by aberrant epigenetic modifications of numerous OA-susceptible genes. Recent studies revealed that both the abnormal activation and differential expression of histone deacetylases (HDACs) might contribute to OA pathogenesis. In this study, we investigated the chondroprotective effects of a marine-derived HDAC inhibitor, panobinostat, on anterior cruciate ligament transection (ACLT)-induced experimental OA rats. The intra-articular administration of 2 or 10 µg of panobinostat (each group, n = 7) per week from the 6th to 17th week attenuates ACLT-induced nociceptive behaviors, including secondary mechanical allodynia and weight-bearing distribution. Histopathological and microcomputed tomography analysis showed that panobinostat significantly prevents cartilage degeneration after ACLT. Moreover, intra-articular panobinostat exerts hypertrophic effects in the chondrocytes of articular cartilage by regulating the protein expressions of HDAC4, HDAC6, HDAC7, runt-domain transcription factor-2, and matrix metalloproteinase-13. The study indicated that HDACs might have different modulations on the chondrocyte phenotype in the early stages of OA development. These results provide new evidence that panobinostat may be a potential therapeutic drug for OA.

A case report and literature review of vaginal bleeding in prepubertal girl.

Vaginal bleeding in the prepubertal girl is an uncommon condition with complex aetiological factors. We report a case of a 6-year-old girl brought to hospital when vaginal bleeding was noticed after defecation. Various common causes were excluded by genital and auxiliary examinations. Serial vaginoscopy revealed increasing petechiae within the non-oestrogenised cervix and vaginal wall. The aetiology of these petechiae was considered to result from ruptured small blood vessels or submucosal capillaries due to an increase in abdominal pressure. CONCLUSION: This case report and review of literature has shed new light on the aetiology of prepubertal bleeding, which details challenging clinical characteristics of use to gynaecologists in the evaluation of related conditions and formulation of appropriate treatment regimens.

Risk factors and clinical characteristics of recurrent ectopic pregnancy: A case-control study.

OBJECTIVE: To compare signs and symptoms between patients with recurrent ectopic pregnancies (REP) and primary ectopic pregnancies (PEP) and to identify potential risk factors of REP. MATERIALS AND METHODS: Data from 2014 to 2016 were analyzed. The study included 81 women each diagnosed with REP and PEP with no recurrence of ectopic pregnancy (EP) before January 2019. Information, including historical factors and findings at presentation of both group were collected. Data were compared between the two groups. Associations between REP and the risk factors were analyzed by logistic regression. RESULTS: The findings revealed that compared to the patients in the PEP group, REP patients had significantly lower education (P = 0.001), higher proportion of previous infertility (P < 0.001) and different methods of PEP treatment (P = 0.001). Clinical data of the last operation revealed significantly higher occurrences of pelvic and peritubal adhesions (P < 0.05). Further multiple regression analysis showed that lower educational background (odds ratio [OR] = 4.183 95% confidence interval [CI] 1.311-13.344 P = 0.016), nulliparity (OR = 12.312 95% CI 3.382-44.824 P < 0.001), history of salpingotomy (OR = 7.129 95% CI 1.022-49.748 P < 0.05) and abortion (OR for one abortion = 21.576, P = 0.001; OR for two abortions =36.794, P < 0.001; OR for three abortions or more = 119.013, P < 0.001) were significant risk factors for REP. CONCLUSION: Active education on contraception is required for patients with lower educational level and history of abortion. Different plans should be formulated for patients with EP. For EP patients wanting fertility, the risk between fertility preservation and REP needs to be evaluated as reproductive function cannot be pursued blindly while ignoring the risk of recurrence.

Factors associated with low health literacy among community-dwelling women in Taiwan.

The present study investigated factors associated with health literacy in community-dwelling Taiwanese women, particularly focusing on those associated with prevalent unhealthy behaviors. This cross-sectional study recruited 353 community-dwelling women aged 39-89 years from February to October 2015 in urban, suburban, and rural areas. Variables investigated included physical activity, community activity, tobacco usage, alcohol consumption, and betel-nut chewing. Degree of health literacy was evaluated using the Chinese-language version of the European Health Literacy Survey Questionnaire. Most respondents had inadequate (17.6%), or problematic (49.3%), general health literacy. Multiple logistic regression analyses showed that low educational attainment was closely associated with inadequate or problematic general health literacy. Women who did not engage in regular physical activity or direct community activity were more likely to have inadequate and problematic general health literacy, respectively. Selected unhealthy behaviors (tobacco usage, alcohol consumption, betel-nut chewing) were not associated with health literacy. Low health literacy was prevalent among participants. Lower educational attainment and a lack of physical or community activity were associated with low health literacy. Health literacy should be considered during the process of delivering health information, and health education programs must enhance health literacy tailored to address individuals' lifestyles.

Rhodoptilometrin, a Crinoid-Derived Anthraquinone, Induces Cell Regeneration by Promoting Wound Healing and Oxidative Phosphorylation in Human Gingival Fibroblast Cells.

Gingival recession (GR) potentially leads to the exposure of tooth root to the oral cavity microenvironment and increases susceptibility to dental caries, dentin hypersensitivity, and other dental diseases. Even though many etiological factors were reported, the specific mechanism of GR is yet to be elucidated. Given the species richness concerning marine biodiversity, it could be a treasure trove for drug discovery. In this study, we demonstrate the effects of a marine compound, (+)-rhodoptilometrin from crinoid, on gingival cell migration, wound healing, and oxidative phosphorylation (OXPHOS). Experimental results showed that (+)-rhodoptilometrin can significantly increase wound healing, migration, and proliferation of human gingival fibroblast cells, and it does not have effects on oral mucosa fibroblast cells. In addition, (+)-rhodoptilometrin increases the gene and protein expression levels of focal adhesion kinase (FAK), fibronectin, and type I collagen, changes the intracellular distribution of FAK and F-actin, and increases OXPHOS and the expression levels of complexes I~V in the mitochondria. Based on our results, we believe that (+)-rhodoptilometrin might increase FAK expression and promote mitochondrial function to affect cell migration and promote gingival regeneration. Therefore, (+)-rhodoptilometrin may be a promising therapeutic agent for GR.

Factors Associated with Functional Performance among Patients on Hemodialysis in Taiwan.

BACKGROUND/AIMS: We investigated factors associated with functional performance in hemodialysis (HD) patients as well as their relationships with mortality. METHODS: We enrolled 790 HD patients who were followed up from 2009 to 2013. Functional performance was evaluated by Karnofsky Performance Status Scale (KPSS) scores. We examined the associations of clinical variables and all-cause mortality with KPSS scores. RESULTS: Of the participants, 460 had high KPSS scores (range 90-100) and 330 had low KPSS scores (below 80). On multivariate analysis, age and weekly HD sessions were associated with significantly increased odds of a lower KPSS score (age: OR 1.05, 95% CI 1.04-1.07, p < 0.001; weekly HD: OR 2.10, 95% CI 1.37-3.21, p = 0.001). A low KPSS score was a significant predictor of increased all-cause mortality (hazard ratio 1.49; 95% CI 1.02-2.16, p = 0.037), as determined using Cox regression analysis. CONCLUSION: Functional performance was associated with clinical variables and all-cause mortality in HD patients.

Worse outcome in breast cancer with higher tumor-infiltrating FOXP3+ Tregs : a systematic review and meta-analysis.

BACKGROUND: Forkhead box P3(FOXP3) is known as the optimum maker for regulatory T cells(Tregs), which are conventionally thought to induce immune tolerance to disturb the antitumor immunity. However, the research on the prognostic significance of tumor-infiltrating FOXP3+ Tregs in breast cancer is still limited and the results are controversial. METHODS: We searched for studies in PubMed, EMBASE and Web of Science prior to January 2015. The correlation between FOXP3+ tumor-infiltrating lymphocytes(TILs) and breast cancer prognosis was analyzed. The meta-analysis was performed using STATA 11.0. Pooled hazard ratios (HRs) with 95 % confidence intervals (CIs) were used to estimate the degree of the association between FOXP3+ TILs and prognosis of breast cancers, while relative ratios (RRs) were used to evaluate the relationship between FOXP3+ TILs and clinicopathological features of breast cancers. RESULT: A total of 15 studies comprising 8666 breast cancer patients met the inclusion criteria. Our results showed that higher FOXP3+ TILs level was significantly associated with poor prognosis in terms of overall survival (OS) (pooled HR:1.60, 95 % CI:1.06-2.42; P < 0.05). We found that breast cancer with higher FOXP3+ TILs level was positively correlated with c-erbB-2 positive status (pooled RR:1.52, 95 % CI:1.32-1.75; P < 0.05), lymph node positive status(pooled RR:1.17, 95 % CI:1.04-1.32; P < 0.05) while there was a negative association with ER positive status(pooled RR:0.65, 95 % CI:0.56-0.76; P < 0.05) and PR positive status(pooled RR:0.66, 95 % CI:0.51-0.87; P < 0.05). CONCLUSION: The present results of meta-analysis showed that higher FOXP3+ TILs level in patients with breast cancer led to poor overall survival (OS) and was significantly associated with c-erbB-2 status, lymph node status, ER status and PR status. FOXP3+ TILs level is a promising prognostic factor in breast cancer.

Impact of subtropical climate on frequency of ambulance use for trauma patients in a coastal area of China.

PURPOSE: To explore the impact of subtropical maritime monsoon climate on the frequency of ambulance use for trauma patients in a coastal region in China. METHOD: Statistical analysis of data on ambulance use from the 120 Emergency Command Center in Shantou City, Guangdong Province, from January to December 2012 as well as daily meteorological data from a Shantou observatory was performed to determine how climatic factors (seasons, time, and weather) affect the frequency of ambulance use for trauma patients. RESULTS: The daily ambulance use for trauma patients differed between spring and summer or autumn (p<0.05), between sunny and rainy days (p<0.05), and between cloudy and lightly or moderately rainy days (p<0.05).We found a linear correlation between daily maximum temperature and daily ambulance use for trauma patients (R² =0.103, p<0.05). In addition, there was significant difference in ambulance use between good and bad weather (p<0.05). CONCLUSION: Frequency of ambulance use for trauma patients is affected by the subtropical maritime monsoon climate in the coastal region. Better weather contributes to increased daily frequency of ambulance use, which is the highest in autumn and lowest in spring.

Toward functional screening of cardioactive and cardiotoxic drugs with zebrafish in vivo using pseudodynamic three-dimensional imaging.

Given the high mortality in patients with cardiovascular diseases and the life-threatening consequences of drugs with unforeseen adverse effects on hearts, a critical evaluation of the pharmacological response of cardiovascular function on model animals is important especially in the early stages of drug development. We report a proof-of-principle study to demonstrate the utility of zebrafish as an analytical platform to predict the cardiac response of new drugs or chemicals on human beings. With pseudodynamic 3D imaging, we derive individual parameters that are central to the cardiac function of zebrafish, including the ventricular stroke volume, ejection fraction, cardiac output, heart rate, diastolic filling function, and ventricular mass. We evaluate both inotropic and chronotropic responses of the heart of zebrafish treated with drugs that are commonly prescribed and possess varied known cardiac activities. We reveal deranged cardiac function of a zebrafish model of cardiomyopathy induced with a cardiotoxic drug. The cardiac function of zebrafish exhibits a pharmacological response similar to that of human beings. We compare also cardiac parameters obtained in this work with those derived with conventional 2D approximation and show that the latter tends to overestimate the cardiac parameters and produces results of greater variation. In view of the growing interest of using zebrafish in both fundamental and translational biomedical research, we envisage that our approach should benefit not only contemporary pharmaceutical development but also exploratory research such as gene, stem cell, or regenerative therapies targeting congenital or acquired heart diseases.