Universal Platform for Robust Dual-Atom Doped 2D Catalysts with Superior Hydrogen Evolution in Wide pH Media.

Layered 2D transition metal dichalcogenides (TMDs) have been suggested as efficient substitutes for Pt-group metal electrocatalysts in the hydrogen evolution reaction (HER). However, poor catalytic activities in neutral and alkaline electrolytes considerably hinder their practical applications. Furthermore, the weak adhesion between TMDs and electrodes often impedes long-term durability and thus requires a binder. Here, a universal platform is reported for robust dual-atom doped 2D electrocatalysts with superior HER performance over a wide pH range media. V:Co-ReS2 on a wafer scale is directly grown on oxidized Ti foil by a liquid-phase precursor-assisted approach and subsequently used as highly efficient electrocatalysts. The catalytic performance surpasses that of Pt group metals in a high current regime (≥ 100 mA cm-2) at pH ≥ 7, with a high durability of more than 70 h in all media at 200 mA cm-2. First-principles calculations reveal that V:Co dual doping in ReS2 significantly reduces the water dissociation barrier and simultaneously enables the material to achieve the thermoneutral Gibbs free energy for hydrogen adsorption.

Smoothed quantile residual life regression analysis with application to the Korea HIV/AIDS cohort study.

BACKGROUND: The residual life of a patient with human immunodeficiency virus (HIV) is of major interest to patients and their physicians. While existing analyses of HIV patient survival focus mostly on data collected at baseline, residual life analysis allows for dynamic analysis based on additional data collected over a period of time. As survival times typically exhibit a right-skewed distribution, the median provides a more useful summary of the underlying distribution than the mean. In this paper, we propose an efficient inference procedure that fits a semiparametric quantile regression model assessing the effect of longitudinal biomarkers on the residual life of HIV patients until the development of dyslipidemia, a disease becoming more prevalent among those with HIV. METHODS: For estimation of model parameters, we propose an induced smoothing method that smooths nonsmooth estimating functions based on check functions. For variance estimation, we propose an efficient resampling-based estimator. The proposed estimators are theoretically justified. Simulation studies are used to evaluate their finite sample performances, including their prediction accuracy. We analyze the Korea HIV/AIDS cohort study data to examine the effects of CD4 (cluster of differentiation 4) cell count on the residual life of HIV patients to the onset of dyslipidemia. RESULTS: The proposed estimator is shown to be consistent and normally distributed asymptotically. Under various simulation settings, our estimates are approximately unbiased. Their variances estimates are close to the empirical variances and their computational efficiency is superior to that of the nonsmooth counterparts. Two measures of prediction performance indicate that our method adequately reflects the dynamic character of longitudinal biomarkers and residual life. The analysis of the Korea HIV/AIDS cohort study data shows that CD4 cell count is positively associated with residual life to the onset of dyslipidemia but the effect is not statistically significant. CONCLUSIONS: Our method enables direct prediction of residual lifetimes with a dynamic feature that accommodates data accumulated at different times. Our estimator significantly improves computational efficiency in variance estimation compared to the existing nonsmooth estimator. Analysis of the HIV/AIDS cohort study data reveals dynamic effects of CD4 cell count on the residual life to the onset of dyslipidemia.

Association Between Individual Air Pollution (PM10, PM2.5) Exposure and Adverse Pregnancy Outcomes in Korea: A Multicenter Prospective Cohort, Air Pollution on Pregnancy Outcome (APPO) Study.

BACKGROUND: Prenatal exposure to ambient air pollution is linked to a higher risk of unfavorable pregnancy outcomes. However, the association between pregnancy complications and exposure to indoor air pollution remains unclear. The Air Pollution on Pregnancy Outcomes research is a hospital-based prospective cohort research created to look into the effects of aerodynamically exposed particulate matter (PM)10 and PM2.5 on pregnancy outcomes. METHODS: This prospective multicenter observational cohort study was conducted from January 2021 to June 2023. A total of 662 women with singleton pregnancies enrolled in this study. An AirguardK® air sensor was installed inside the homes of the participants to measure the individual PM10 and PM2.5 levels in the living environment. The time-activity patterns and PM10 and PM2.5, determined as concentrations from the time-weighted average model, were applied to determine the anticipated exposure levels to air pollution of each pregnant woman. The relationship between air pollution exposure and pregnancy outcomes was assessed using logistic and linear regression analyses. RESULTS: Exposure to elevated levels of PM10 throughout the first, second, and third trimesters as well as throughout pregnancy was strongly correlated with the risk of pregnancy problems according to multiple logistic regression models adjusted for variables. Except for in the third trimester of pregnancy, women exposed to high levels of PM2.5 had a high risk of pregnancy complications. During the second trimester and entire pregnancy, the risk of preterm birth (PTB) increased by 24% and 27%, respectively, for each 10 µg/m3 increase in PM10. Exposure to high PM10 levels during the second trimester increased the risk of gestational diabetes mellitus (GDM) by 30%. The risk of GDM increased by 15% for each 5 µg/m3 increase in PM2.5 during the second trimester and overall pregnancy, respectively. Exposure to high PM10 and PM2.5 during the first trimester of pregnancy increased the risk of delivering small for gestational age (SGA) infants by 96% and 26%, respectively. CONCLUSION: Exposure to high concentrations of PM10 and PM2.5 is strongly correlated with the risk of adverse pregnancy outcomes. Exposure to high levels of PM10 and PM2.5 during the second trimester and entire pregnancy, respectively, significantly increased the risk of PTB and GDM. Exposure to high levels of PM10 and PM2.5 during the first trimester of pregnancy considerably increased the risk of having SGA infants. Our findings highlight the need to measure individual particulate levels during pregnancy and the importance of managing air quality in residential environment.

Identification of Short-Chain Fatty Acids for Predicting Preterm Birth in Cervicovaginal Fluid Using Mass Spectrometry.

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, predicting and preventing PTB are important. In this study, we investigated the potential of using short-chain fatty acid (SCFA) levels, specific vaginal microbiota-derived metabolites, as a biomarker in predicting PTB using gas chromatography/mass spectrometry. Cervicovaginal fluid (CVF) was collected from 89 pregnant women (29 cases of PTB vs. 60 controls) without evidence of other clinical infections, and SCFA levels were measured. Furthermore, the PTB group was divided into two subgroups based on birth timing after CVF sampling: delivery ≤ 2 days after sampling (n = 10) and ≥2 days after sampling (n = 19). The concentrations of propionic acid, isobutyric acid, butyric acid, valeric acid, hexanoic acid, and heptanoic acid were significantly higher in the PTB group than in the term birth (TB) group (p < 0.05). In particular, the concentrations of propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid were continuously higher in the PTB group than in the TB group (p < 0.05). In the delivery ≤ 2 days after sampling group, the propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid levels were significantly higher than those in the other groups (p < 0.05). This study demonstrated a significant association between specific SCFAs and PTB. We propose these SCFAs as potential biomarkers for the prediction of PTB.

Assessment of oral hypofunction and its association with age among Korean community-dwelling older adults.

BACKGROUND: Due to the increasing proportion of older adults in Korea and growing interest in aging, the concepts of oral aging and oral hypofunction have recently been introduced. Thus, it is necessary to investigate the age-specific oral function levels of Korean older adults and develop expert intervention methods for healthy aging. METHODS: Dysphagia, independence of daily living, and oral hypofunction were assessed in 206 older adults living in Wonju, Gangwon State, South Korea. Subjective dysphagia was assessed through self-report questionnaires using the Dysphagia Handicap Index (DHI), the Korean version of Eating Assessment Tool-10, and the Korean version of the Modified Barthel Index. In addition, the oral hypofunction assessment items included decreased chewing ability, occlusal pressure, tongue pressure, oral dryness, and oral cleanliness. RESULTS: DHI increased significantly with age, with those in their 80 s reporting the most difficulty swallowing. Oral function in terms of chewing ability (maximum occlusal pressure and number of remaining teeth), maximum occlusal pressure, and maximum tongue pressure also declined with increasing age. While there was no significant difference in oral dryness by age, those in their 80 s had dry mouth according to the criteria of the oral moisture checking device. CONCLUSIONS: In an assessment of oral function in community-dwelling, independent Korean older adults, the number of items that were assessed as oral hypofunction increased with age. The findings can be used to standardize the oral hypofunction assessment item and develop age-based individualized intervention plans for the early management of oral health and individual oral myofunctional rehabilitation in Korean community-dwelling older adults.

Differences in Korean adult inpatients' oral care behaviour in daily life and hospitals.

OBJECTIVES: The objectives of the study were to identify the differences in oral care methods between current and past hospitalizations and to investigate the need for inpatient oral care education for South Korean adults who have been hospitalized for more than 24 h. METHODS: This study employed a cross-sectional design. Between 23 December 2019 and 4 May 2020, a questionnaire was administered to 200 adult inpatients awaiting treatment and their guardians at university hospitals or clinics. Of these, the data of 195 patients were analysed. Frequency analysis, descriptive statistics and chi-square tests were used for data analysis. RESULTS: In daily life, the participants reported brushing their teeth thrice a day (52.3%) for 2 min (60%). A single product was the most used (51.3%). During hospitalization, 40% of the participants brushed their teeth thrice or more a day, 84.1% brushed for <1 min, and 83.6% did not use additional oral care products. CONCLUSIONS: Differences were observed between South Korean adults' oral care behaviours in daily life and those performed in hospitals. Oral hygiene habits, the frequency and duration of tooth brushing, and the use of oral care products decreased during hospitalization. Our findings can be applied to the development of oral care interventions for inpatients, while considering changes in the hospitalization environment and physical activity levels during hospitalization.

Fabrication of a surface-enhanced Raman spectroscopy-based analytical method consisting of multifunctional DNA three-way junction-conjugated porous gold nanoparticles and Au-Te nanoworm for C-reactive protein detection.

C-Reactive protein (CRP) is a biomarker of inflammatory responses and an index for assessing the risk of cardiovascular disease and estimating prognosis. In this study, we constructed a surface-enhanced Raman spectroscopy (SERS) biosensor composed of a multifunctional DNA three-way junction (DNA 3WJ), porous gold nanoplates (pAuNPs), and an Au-Te nanoworm structure for detection of CRP. The pAuNP and Au-Te nanostructures were synthesized by galvanic replacement reactions, and the morphology was confirmed by transmission electron microscopy, scanning electron microscopy, and dynamic light scattering (DLS). To generate the SERS signal, the Au-Te nanostructure was immobilized on an indium-tin oxide substrate, and the thiol-modified CRP aptamer was then self-assembled onto the modified substrate for CRP recognition. To amplify the SERS signal and identify the Raman tag, the multifunctional DNA 3WJ was conjugated with the pAuNPs, and each fragment of 3WJ was functionalized to biotin (pAuNP conjugation), methylene blue (Raman reporter), and CRP aptamer (target binding). The results were confirmed by gel electrophoresis. For conjugation between pAuNPs and DNA 3WJ, avidin was encapsulated in pAuNPs, and the conjugation structure was confirmed by DLS. The fabricated SERS biosensor showed detection limits of 2.23 pM in phosphate-buffered saline and 3.11 pM in diluted human serum. Overall, the proposed biosensor may have potential applications as a SERS biosensor platform.

Fabrication of MERS-nanovesicle biosensor composed of multi-functional DNA aptamer/graphene-MoS2 nanocomposite based on electrochemical and surface-enhanced Raman spectroscopy.

Middle East respiratory syndrome coronavirus (MERS-CoV) is one of the most harmful viruses for humans in nowadays. To prevent the spread of MERS-CoV, a valid detection method is highly needed. For the first time, a MERS-nanovesicle (NV) biosensor composed of multi-functional DNA aptamer and graphene oxide encapsulated molybdenum disulfide (GO-MoS2) hybrid nanocomposite was fabricated based on electrochemical (EC) and surface-enhanced Raman spectroscopy (SERS) techniques. The MERS-NV aptamer was designed for specifically binding to the spike protein on MERS-NVs and it is prepared using the systematic evolution of ligands by exponential enrichment (SELEX) technique. For constructing a multi-functional MERS aptamer (MF-aptamer), the prepared aptamer was connected to the DNA 3-way junction (3WJ) structure. DNA 3WJ has the three arms that can connect the three individual functional groups including MERS aptamer (bioprobe), methylene blue (signal reporter) and thiol group (linker) Then, GO-MoS2 hybrid nanocomposite was prepared for the substrate of EC/SERS-based MERS-NV biosensor construction. Then, the assembled multifunctional (MF) DNA aptamer was immobilized on GO-MoS2. The proposed biosensor can detect MERS-NVs not only in a phosphate-buffered saline (PBS) solution (SERS LOD: 0.176 pg/ml, EIS LOD: 0.405 pg/ml) but also in diluted 10% saliva (SERS LOD: 0.525 pg/ml, EIS LOD: 0.645 pg/ml).

Silica-Enveloped 2D-Sheet-to-Nanocrystals Conversion for Resilient Catalytic Dry Reforming of Methane.

Here, lamellar confinement strategy is introduced for "sheet-to-nanocrystals (NCs)" conversion within a 2D-SiO2 envelope, which constructs a catalytic nanocartridge holding a platoon of isolated and in-plane-aligned ultrasmall Ni-NCs, performing as a robust and coking-resistant catalytic system for dry reforming of methane. Overcoming the problem of unavoidable bulk crystal growth from multiple sheets-stack or sheet-on-open-support, silica bilayer-encasing tightly clamps the atomic-thin Ni(OH)2 -nanosheet during thermal conversion and further hinders the migratory fusion of the resultant Ni-NCs. Upon heating-cooling cycle, the flapping silica envelope clutches the Ni-NCs like "eggs in a carton," subsequently, ensuring their thermal stability. Owing to the unique 2D-enveloped rigid architecture, Ni-NCs can circumvent sintering and coke deposition while tolerating the high temperatures (>700 °C) for long operation (>100 h), affording high conversions to syngas.

Tissue-remodelling M2 Macrophages Recruits Matrix Metallo-proteinase-9 for Cryotherapy-induced Fibrotic Resolution during Keloid Treatment.

Cryotherapy is used to treat keloid scars; however, the molecular and pathological mechanisms are not clearly understood. This study retrospectively evaluated the efficacy of combined treatment with cryotherapy and intralesional triamcinolone injection (Cryo+TA) or intralesional TA monotherapy (TA) in 40 Asian patients with keloid scars. Scar improvement was assessed using the Vancouver Scar Scale and Global Improvement Scale. Clinical improvement in scars, especially reduced vascularity and redness, was significantly greater in the Cryo+TA group than in the TA group. Cryotherapy-treated and untreated keloid tissue was collected from six patients for analysis. Histo-logically, collagen bundles from cryotherapy-treated keloid tissue were more fibrillar and abnormal thickness was reduced. Immunohistochemical staining showed a reduced number of dermal vessels after cryotherapy. Moreover, CD163+ M2 macrophages and matrix metalloproteinase-9 (MMP-9) were significantly increased in cryotherapy-treated tissue. Double immunofluorescence staining revealed co-expression of CD163 and MMP-9. These data indicate that cryotherapy recruits tissue-remodelling M2 macrophages with accompanying MMP-9, suggesting that cryotherapy-recruited M2 macrophages function in fibrotic resolution during keloid treatment.

Maternal Malnutrition Affects Hepatic Metabolism through Decreased Hepatic Taurine Levels and Changes in HNF4A Methylation.

Fetal programming implies that the maternal diet during pregnancy affects the long-term health of offspring. Although maternal diet influences metabolic disorders and non-alcoholic fatty liver disease in offspring, the hepatic mechanisms related to metabolites are still unknown. Here, we investigated the maternal diet-related alterations in metabolites and the biological pathway in male offspring at three months of age. Pregnant rats were exposed to 50% food restriction during the prenatal period or a 45% high-fat diet during the prenatal and postnatal periods. The male offspring exposed to food restriction and high-fat diets had lower birth weights than controls, but had a catch-up growth spurt at three months of age. Hepatic taurine levels decreased in both groups compared to controls. The decreased hepatic taurine levels in offspring affected excessive lipid accumulation through changes in hepatocyte nuclear factor 4 A methylation. Moreover, the alteration of gluconeogenesis in offspring exposed to food restriction was observed to a similar extent as that of offspring exposed to a high fat diet. These results indicate that maternal diet affects the dysregulation in hepatic metabolism through changes in taurine levels and HNF4A methylation, and predisposes the offspring to Type 2 diabetes and non-alcoholic fatty liver disease in later life.

Exposure to cigarette smoke via respiratory system may induce abnormal alterations of reproductive organs in female diabetic rats.

Cigarette smoke (CS) has harmful effects on human fertility, reproduction, and development as well as on patients suffering from metabolic diseases such as diabetes than on healthy individuals. This study was conducted to investigate the relationship between CS exposure and histological alterations of reproductive organs in female diabetic rats. We evaluated the histology of uteruses and ovaries obtained from female rats exposed to smoke from standard cigarettes for 4 weeks (28 hours a week). After CS exposure, tissue slides were made from uterine and ovarian samples and examined after hematoxylin and eosin staining. Immunohistochemistry was used for detection of matrix metallopeptidase 9 (MMP9), C-X-C chemokine receptor type 4 (CXCR4), and estrogen receptor (ER)α in the uterus and ovary. MMP9 is an inflammatory biomarker that increases during progression to endometriosis. As a chemokine receptor, CXCR4 is involved in development of the inner wall of the uterus and cell adhesion. In the uterus, the occurrence of MMP9, CXCR4, and ERα and the number of endometrial glands were increased by CS exposure, while in the ovary, occurrence of MMP9, CXCR4, ERα, proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Collectively, this study indicates that CS induced abnormal development of the uterus and ovary under induced diabetes, leading to adverse effects on normal function of reproductive organs in female rats. HIGHLIGHTS: Cigarette smoke (CS) exposure adversely affected reproductive organs of diabetic female rats. In the uterus, expression of matrix metallopeptidase 9 (MMP9), C-X-C chemokine receptor type 4 (CXCR4), estrogen receptor (ER)α, and the number of endometrial glands were increased by CS exposure, In the ovary, the expression of MMP9, CXCR4, ERα, and proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Exposure to CS via the respiratory system exerted a harmful impact on the uterus and ovary in female rats with diabetes.

Diagnostic Accuracy and Financial Implications of Age-Adjusted D-Dimer Strategies for the Diagnosis of Deep Venous Thrombosis in the Emergency Department.

BACKGROUND: Multiple D-dimer cutoffs have been suggested for older patients to improve diagnostic specificity for venous thromboembolism. These approaches are better established for pulmonary embolism. OBJECTIVES: We evaluated the diagnostic performance and compared the health system cost for previously suggested cutoffs and a new D-dimer cutoff for low-risk emergency department (ED) deep venous thrombosis (DVT) patients. METHODS: We conducted a retrospective cohort study in two large EDs involving patients aged > 50 years who had low pretest probability for DVT and had a D-dimer performed. The outcome was a diagnosis of DVT at 30 days. We evaluated the diagnostic accuracy and estimated the difference in cost for cutoffs of 500 ng/mL and the age-adjusted (age × 10) rule. A derived cutoff of 1000 ng/mL was also assessed. RESULTS: Nine hundred and seventy-two patients were included (median age 66 years; 59.5% female); 63 (6.5%) patients were diagnosed with DVT. The conventional cutoff of < 500 ng/mL demonstrated a sensitivity of 100% (95% confidence interval [CI] 94.3-100%) and a specificity of 35.6% (95% CI 32.5-38.8%). The age-adjusted approach increased specificity while maintaining high sensitivity. A new cutoff of 1000 ng/mL demonstrated improved performance: sensitivity 100% (95% CI 94.3-00%) and specificity 66.3% (95% CI 63.2-69.4%). Compared to the conventional approach, both the 1000 ng/mL cutoff and the age-adjusted cutoffs could save healthcare dollars. A cutoff of 1000 ng/mL could have saved 310 ED length of stay hours and $166,909 (Canadian dollars) in our cohort, or an average savings of 0.32 h and $172 per patient. CONCLUSIONS: Among patients aged > 50 years with suspected DVT, the age-adjusted D-dimer and a cutoff of 1000 ng/mL improved specificity without compromising sensitivity, and lowered the health care system cost compared to that for the conventional approach.

Hypoxia-Induced Epithelial-To-Mesenchymal Transition Mediates Fibroblast Abnormalities via ERK Activation in Cutaneous Wound Healing.

Previous studies described the involvement of extracellular signal-related kinase (ERK) in systemic fibrotic diseases, but the role of ERK in cutaneous scarring is unknown. Although hypoxia drives tissue fibrosis by activating hypoxia-inducible factor-1α (HIF-1α), the specific roles of hypoxia and associated ERK phosphorylation in abnormal fibroblast activity during cutaneous scarring are unclear. Here, we investigated whether pathologic myofibroblast-like keloid fibroblast activity is promoted by hypoxia-induced epithelial-mesenchymal transition mediated by ERK activation. ERK phosphorylation was significantly increased in keloid tissue and fibroblasts. Human dermal fibroblasts cultured under hypoxia (1% O2) expressed phosphorylated ERK and exhibited activation of p38 mitogen-activated protein kinase signaling. Hypoxic human dermal fibroblasts showed increased protein and mRNA levels of epithelial-mesenchymal transition markers. Furthermore, administration of an ERK inhibitor (SCH772984) reduced the hypoxia-induced elevation of collagen type I levels in human dermal fibroblasts. Therefore, ERK may be a promising therapeutic target in profibrogenic diseases.

Investigation of the Phase Transition Mechanism in LiFePO4 Cathode Using In Situ Raman Spectroscopy and 2D Correlation Spectroscopy during Initial Cycle.

The phase transition of the LiFePO4 and FePO4 in Li-ion cell during charging-discharging processes in the first and second cycles is elucidated by Raman spectroscopy in real time. In situ Raman spectroscopy showed the sudden phase transition between LiFePO4 and FePO4. Principal component analysis (PCA) results also indicated that the structural changes and electrochemical performance (charge-discharge curve) are correlated with each other. Phase transition between LiFePO4 and FePO4 principally appeared in the second charging process compared with that in the first charging process. 2D correlation spectra provided the phase transition mechanism of LiFePO4 cathode which occurred during the charging-discharging processes in the first and second cycles. PCA and 2D correlation spectroscopy are very helpful methods to understand in situ Raman spectra for the Li-ion battery.

Application of outpatient cardiac testing among emergency department patients with syncope.

OBJECTIVES: 2.6% of ED syncope patients will suffer cardiac serious adverse events (SAEs) within 30 days of disposition, and outpatient cardiac testing can improve patient safety. The objective is to determine whether outpatient cardiac testing for ED syncope patients is being appropriately ordered after discharge. To this end, we describe the proportion of high-risk and non-high (low and medium)-risk ED syncope patients as per the Canadian Syncope Risk Score (CSRS) who have a SAE after ED discharge, and the proportion referred for outpatient cardiac testing. METHODS: Our multicentre prospective cohort study enrolled adult syncope patients between 2010 and 2014 in five academic EDs. We collected patient characteristics, disposition, CSRS predictors, outpatient referrals and testing results (Holter, echocardiography), and 30-day adjudicated SAE (death due to unknown/cardiac cause, myocardial infarction, arrhythmia and structural heart disease). We used descriptive statistics (mean, SD) to report our results. RESULTS: Of 3584 enrolled patients (mean age 50.9 years, 57.7% women), 800 patients (22.3%) received an outpatient referral. Of these 800 patients, 40.3% of the non-high-risk patients (305/756) and 54.5% of the high-risk patients (24/44) received outpatient cardiac testing. Of all patients who received cardiac testing, five (1.5%; 95% CI 0.6% to 3.5%) suffered outpatient SAE (60.0% arrhythmias). Of all patients who did not receive cardiac testing, four patients (0.9%; 95% CI 0.3% to 2.2%) suffered SAE (all arrhythmias). Of the 20 (45.5%) high-risk patients who did not receive testing, two patients (10.0%; 95% CI 2.8% to 30.1%) suffered arrhythmias outside the hospital, while among the 451 (59.7%) non-high-risk patients, only two (0.4%; 95% CI 0.1% to 1.6%) suffered outpatient arrhythmias. CONCLUSION: Outpatient cardiac testing is largely underused, especially among high-risk ED syncope patients. Better guidelines for outpatient cardiac testing are needed, as the practice is highly variable and mismatched with patient risk.

3,3'-Diindolylmethane Suppressed Cyprodinil-Induced Epithelial-Mesenchymal Transition and Metastatic-Related Behaviors of Human Endometrial Ishikawa Cells via an Estrogen Receptor-Dependent Pathway.

Cyprodinil (CYP) is a pyrimidine amine fungicide that has been extensively used in agricultural areas. 3,3'-Diindolylmethane (DIM) is a derivative of the dietary phytoestrogen, indole-3-carbinol (I3C), which is derived from cruciferous vegetables and considered to be a cancer-preventive phytonutrient agent. In this study, the effects of CYP and DIM were examined on the cell viability, invasion, and metastasis of human endometrial cancer cells, Ishikawa, via epithelial mesenchymal transition (EMT). CYP increased the level of cell viability of Ishikawa cells compared to DMSO as a control, as did E2. Ishikawa cells lost cell-to-cell contact and obtained a spindle-shaped or fibroblast-like morphology in response to the application of E2 or CYP by the cell morphology assay. In the cell migration and invasion assay, CYP enhanced the ability of migration and invasion of Ishikawa cells, as did E2. E2 and CYP increased the expressions of N-cadherin and Snail proteins, while decreasing the expression of E-cadherin protein as EMT-related markers. In addition, E2 and CYP increased the protein expressions of cathepsin D and MMP-9, metastasis-related markers. Conversely, CYP-induced EMT, cell migration, and invasion were reversed by fulvestrant (ICI 182,780) as an estrogen receptor (ER) antagonist, indicating that CYP exerts estrogenic activity by mediating these processes via an ER-dependent pathway. Similar to ICI 182,780, DIM significantly suppressed E2 and CYP-induced proliferation, EMT, migration, and invasion of Ishikawa cancer cells. Overall, the present study revealed that DIM has an antiestrogenic chemopreventive effect to withdraw the cancer-enhancing effect of E2 and CYP, while CYP has the capacity to enhance the metastatic potential of estrogen-responsive endometrial cancer.

A Novel and Facile Route to Synthesize Atomic-Layered MoS2 Film for Large-Area Electronics.

High-quality and large-area molybdenum disulfide (MoS2 ) thin film is highly desirable for applications in large-area electronics. However, there remains a challenge in attaining MoS2 film of reasonable crystallinity due to the absence of appropriate choice and control of precursors, as well as choice of suitable growth substrates. Herein, a novel and facile route is reported for synthesizing few-layered MoS2 film with new precursors via chemical vapor deposition. Prior to growth, an aqueous solution of sodium molybdate as the molybdenum precursor is spun onto the growth substrate and dimethyl disulfide as the liquid sulfur precursor is supplied with a bubbling system during growth. To supplement the limiting effect of Mo (sodium molybdate), a supplementary Mo is supplied by dissolving molybdenum hexacarbonyl (Mo(CO)6 ) in the liquid sulfur precursor delivered by the bubbler. By precisely controlling the amounts of precursors and hydrogen flow, full coverage of MoS2 film is readily achievable in 20 min. Large-area MoS2 field effect transistors (FETs) fabricated with a conventional photolithography have a carrier mobility as high as 18.9 cm2 V-1 s-1 , which is the highest reported for bottom-gated MoS2 -FETs fabricated via photolithography with an on/off ratio of ≈105 at room temperature.

Chemically Conjugated Carbon Nanotubes and Graphene for Carrier Modulation.

Nanocarbons such as fullerene and carbon nanotubes (CNT) in late 20th century have blossomed nanoscience and nanotechnology in 21st century, which have been further proliferated by the new finding of graphene and have indeed opened a new carbon era. Several new branches of research, for example, zero-dimensional nanoparticles, one-dimensional nanowires, and two-dimensional insulating hexagonal boron nitride, and semiconducting and metallic transition metal dichalcogenides including the recently emerging black phosphorus, have been explored and numerous unprecedented quantum mechanical features have been revealed, that have been hardly accessible otherwise. Extensive research has been done on devices and applications related to such materials. Many experimental instruments have been developed with high sensitivity and improved spatial and temporal resolution to detect such tiny objects. The need for multidisciplinary research has been growing stronger than ever, which will be the tradition in the next few decades. In this Account, we will demonstrate an example of multidisciplinary effort of utilizing CNTs and graphene for electronics by modulating electronic structures. While there are several methods of modifying electronic structures of nanocarbons such as gate bias, contact metal, and conventional substitutional doping, we focus on chemical doping approaches here. We first introduce the concept of chemical doping on CNTs and graphene in terms of electronegativity of molecules and electrochemical potential of CNTs and graphene. To understand the relationship of electrochemical potential of CNTs and graphene to electronegativity of molecules, we propose a simple water bucket model: how to fill or drain water (electrons in CNTs or graphene) in the bucket (density of states) by the chemical dopants. The doping concept is then demonstrated experimentally by tracking the absorption spectroscopy, X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, Raman spectroscopy, transmittance, and transport measurements and by relating them to the reduction potential of molecules relative to that of CNTs or graphene. Two effects of chemical doping in electronics, transparent conducting films, and field effect transistors are extensively discussed. One critical issue, the stability of chemical dopants under ambient conditions, is further discussed. We believe that the presented doping concept will be useful tools for other low dimensional materials such as recently emerging transition metal dichalcogenides and black phosphorus.