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Background: Exposure to air pollution has been associated with a wide range of adverse health effects; however, few studies addressed the relationship between ambient particulate matter as well as the compositions in particulate matter such as lead and the risk of small for gestational age (SGA) in offspring. The aim of this study is to investigate the effect of maternal exposure to criteria air pollutants and the lead in total suspended particulate matter during pregnancy on SGA births in Taiwan. Methods: This population study consisted of 322,513 singleton live births in Taiwan between 1996 and 2002. Daytime (7 AM–7 PM) exposure to particulate matter ≤10 μm (PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3), and monthly exposure to lead in total suspended particles (TSP) during each trimester were estimated. Generalized additive model (GAM) was used to assess the association between maternal exposure to particulate air pollutants and SGA births, taking into account potential confounders and gaseous air pollutants. Results: We found significant association between the highest quartile (≥75th) of maternal PM10 exposure and SGA and demonstrated a significant exposure–response relationship. Furthermore, the highest quartile (≥75th) of maternal lead exposure was also associated with SGA during the second and third trimester of pregnancy, and there was a significant exposure–response relationship between maternal lead exposure and SGA during pregnancy. Conclusion: Maternal exposure to PM10 and lead in total suspended particulate matter during pregnancy was associated with an increased risk of SGA in offspring. Key Words: air pollution, lead, pregnancy, small for gestational age

analysis of fashion trends is crucial. However, existing predictive algorithms of fashion popularity are restricted to be feasible on the coarse style level but not a finer item level. That is, they are only predictive in the future popularity of a given type of fashion styles (e.g., Rocker), but cannot be precisely down to a particular outfit look chosen by individuals. This paper thus proposes the first solution directly aimed at predicting the fine-grained fashion popularity of an outfit look by taking social media as the learning source. Particularly, a deep temporal sequence learning framework is developed and the proposed framework is evaluated on a real dataset of 380,000 street fashion images collected from the fashion website lookbook.nu. The experimental results show that our proposed framework outperforms the state-of-the-art approaches, with a relative increase of 11.51% to 27.62% (MSE metric) and 7.02% to 32.61% (CSE metric) in the prediction accuracy.

Background The relationship between the use of benzodiazepine-receptor agonists (BZRAs) and the risk of hospitalization for pneumonia remains inconclusive. This study aimed to explore the association between BZRA use and hospitalization for pneumonia in a general population. Methods This population-based nested case-control study used Taiwan's National Health Insurance Research Database between 2002 and 2012. We included only new users who did not have any BZRA prescriptions on record in the preceding 2 years and identified 12,002 subjects who were hospitalized for pneumonia (International Classification of Diseases, Ninth Revision codes 480-486, and 507) and 12,002 disease risk score-matched control subjects. A logistic regression model was used to determine the association of BZRA use and hospitalization for pneumonia. The exposure date, dose-response relationship, and class of BZRAs were comprehensively assessed. Results Current BZRA exposure was associated with hospitalization for pneumonia (adjusted OR [aOR],1.86; 95% CI, 1.75-1.97). Benzodiazepine hypnotic agents (aOR, 2.42; 95% CI, 2.16-2.71) had a higher risk of pneumonia than did benzodiazepine anxiolytic agents (aOR, 1.53; 95% CI, 1.44-1.63) or nonbenzodiazepine hypnotic agents (aOR, 1.60; 95% CI, 1.46-1.76). The pneumonia risk was increased with ultrashort-acting and short- to intermediate-acting agents, a higher defined daily dose, and the number of BZRAs used. Among individual BZRAs examined, midazolam had a higher risk (aOR, 5.77; 95% CI, 4.31-7.73) of hospitalization for pneumonia than did the others. Conclusions This study suggests that there is a dose-response relationship between current BZRA use and the risk of hospitalization for pneumonia. In addition, benzodiazepine hypnotic agents, especially midazolam, present a greater risk of hospitalization for pneumonia. These findings reinforce the importance of a careful analysis of the benefits vs the risks of BZRA use.

Three novel anthracene-based organic dyes, denoted as AN-11, AN-12 and AN-14, were synthesized for outdoor and indoor dye-sensitized solar cell studies. Laboratory-fabricated small cells, as well as rigid and flexible modules, were prepared and analyzed for their photovoltaic performance under simulated outdoor and indoor conditions. Owing to the panchromatic absorption of visible light, the AN-11 module gives rise to a very black color and superior photovoltaic performance. Significantly, the AN-11 rigid module with a large active area of 26.80 cm2 outperforms its Z907 counterpart under indoor conditions, reaching an overall efficiency of 11.94% under 1000 lux of T5 fluorescent light. In addition, the AN-11 module exhibits good stability during weather stress tests. Finally, the AN-11 dye is cost-effective and our studies show that the photovoltaic performance of the solar cells is not affected upon lowering the synthetic cost and increasing the synthetic scale.

We herein report the synthesis, UV–vis absorption, fluorescence emission, and redox properties of three novel meso-diphenylbacteriochlorins. Significantly, we show that substituents at the meso-positions of an air-stable bacteriochlorin can be manipulated for the first time. With proper design, this allows tailor-made bacteriochlorins to exhibit suitable properties for a chosen application. As an example, photovoltaic properties of two such bacteriochlorins in dye-sensitized solar cells are investigated. The results show that the bacteriochlorin dyes outperform a reference porphyrin dye. Intriguingly, the anodes sensitized with the new dyes display rare colors—blue and pink.

A tobacco-specific component, 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK), is a major risk factor for many cancers. Recent reports have demonstrated that NNK exposure may be associated with tumor progression and chemoresistance in certain cancers. However, the underlying NNK-induced mechanism contributing to the aggressiveness of colorectal cancer (CRC) has not been thoroughly studied. In this study, we used HT29 cells treated with NNK to simulate the long-term exposure of cigarette smoke. A comparative analysis was performed to evaluate cell proliferation, migration, and invasion as well as epithelial-mesenchymal transition (EMT) markers and drug-resistance genes expression, cancer stem cell (CSC) properties, and anti-apoptotic activity. Signaling pathways related to chemoresistance were also investigated. As a result, NNK exposure dose-dependently stimulates cell proliferation, enhance abilities of migration and invasion, induce EMT phenomenon, and attenuate apoptosis. Furthermore, NNK exposure also promotes the capabilities of sphere formation, upregulation of Snail, and overexpression of CD133, Nanog, OCT4, and the drug-resistant genes. Knockdown of Snail results in upregulation of Raf kinase inhibitor protein (RKIP), increased apoptosis, reversal of EMT phenomenon, and reducation of expression of CSC markers, all of which contribute to a decrease of chemoresistance. Our study demonstrates a number of related mechanisms that mediate the effect of NNK exposure on increasing CRC therapeutic resistance via the Snail signaling pathway. Targeting Snail may provide a feasible strategy for the treatment of CRC.

// Chia-Lin Liu 1 , Su-Feng Chen 2, * , Min-Zu Wu 3 , Shu-Wen Jao 4 , Yaoh-Shiang Lin 5 , Chin-Yuh Yang 6 , Tsai-Yu Lee 4 , Lian-Wu Wen 7 , Guo-Lun Lan 7 , Shin Nieh 1, 7, * 1 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan 2 Department of Dental Hygiene, China Medical University, Taichung, Taiwan 3 Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA 4 Institute of Environmental and Occupational Health Sciences, School of Medicine & Division of Colon and Rectum Surgery, Department of Surgery, National Yang-Ming University & National Defense Medical Center, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan 5 Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 6 Department of Dentistry, Cheng Hsin Hospital & Taipei Medical University, Taipei, Taiwan 7 Department of Pathology, National Defense Medical Center & Tri-Service General Hospital, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Shin Nieh, e-mail: niehshin1014@yahoo.com.tw Su-Feng Chen, e-mail: su374065@gmail.com Keywords: cisplatin-based chemotherapy, drug-resistant sphere, lung cancer, heat shock protein 27, treatment strategy Received: November 17, 2015 Accepted: January 29, 2016 Published: February 10, 2016 ABSTRACT Treatment failure followed by relapse and metastasis in patients with non-small cell lung cancer is often the result of acquired resistance to cisplatin-based chemotherapy. A cancer stem cell (CSC)-mediated anti-apoptotic phenomenon is responsible for the development of drug resistance. The underlying molecular mechanism related to cisplatin resistance is still controversial, and a new strategy is needed to counteract cisplatin resistance. We used a nonadhesive culture system to generate drug-resistant spheres (DRSPs) derived from cisplatin-resistant H23 lung cancer cells. The expressions of drug-resistance genes, properties of CSCs, and markers of anti-apoptotic proteins were compared between control cells and DRSPs. DRSPs exhibited upregulation of cisplatin resistance-related genes. Gradual morphological alterations showing epithelial-to-mesenchymal transition phenomenon and increased invasion and migration abilities were seen during induction of DRSPs. Compared with control cells, DRSPs displayed increased CSC and anti-apoptotic properties, greater resistance to cisplatin, and overexpression of p-Hsp27 via activation of p38 MAPK signaling. Knockdown of Hsp27 or p38 decreased cisplatin resistance and increased apoptosis in DRSPs. Clinical studies confirmed that the expression of p-Hsp27 was closely associated with prognosis. Overexpression of p-Hsp27 was usually detected in advanced-stage patients with lung cancer and indicated short survival. Summary: DRSPs were useful for investigating drug resistance and may provide a practical model for studying the crucial role of p-Hsp27 in the p38 MAPK–Hsp27 axis in CSC-mediated cisplatin resistance. Targeting this axis using siRNA Hsp27 may provide a treatment strategy to improve prognosis and prolong survival in lung cancer patients.

Three porphyrin dyes with different electron-donating groups were prepared to compare their photovoltaic performance in dye-sensitized solar cells. LWP12 is based on LD31 which has a complicated, piece-together electron-donating group, whereas LWP13 and LWP14 have merged substituents with electron-donating and absorption-broadening abilities. The results in this work suggest that consolidated anthryl donors may be used to design highly efficient photosensitizers.

Although many studies have shown the association between smoking and the increased incidence and adverse prognosis of head and neck squamous cell carcinoma (HNSCC), the mechanisms and pharmaceutical targets involved remain unclear. Here, we integrated gene expression signatures, genetic alterations, and survival analyses to identify prognostic indicators and therapeutic targets for smoking HNSCC patients, and we discovered that the FDA-approved drug varenicline inhibits the target for cancer cell migration/invasion. We first identified 18 smoking-related and prognostic genes for HNSCC by using RNA-Seq and clinical follow-up data. One of these genes, CHRNB4 (neuronal acetylcholine receptor subunit beta-4), increased the risk of death by approximately threefold in CHRNB4-high expression smokers compared to CHRNB4-low expression smokers (log rank, p = 0.00042, hazard ratio, 2.82, 95% CI, 1.55&ndash, 5.14), former smokers, and non-smokers. Furthermore, we examined the functional enrichment of co-regulated genes of CHRNB4 and its 246 frequently occurring copy number alterations (CNAs). We found that these genes were involved in promoting angiogenesis, resisting cell death, and sustaining proliferation, and contributed to much worse outcomes for CHRNB4-high patients. Finally, we performed CHRNB4 gene editing and drug inhibition assays, and the results validate these observations. In summary, our study suggests that CHRNB4 is a prognostic indicator for smoking HNSCC patients and provides a potential new therapeutic drug to prevent recurrence or distant metastasis.

Background Recent studies suggest that long-term exposure of the carcinogen 4-methylnitrosamino-1–3-pyridyl-1-butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine-mediated mechanism remains unclear. Methods An analysis of SCC-25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial–mesenchymal transition, drug-resistance-related genes, properties of cancer stem cells (CSCs), and anti-apoptosis was performed. Results Long-term NNK exposure enhances migration and invasion with morphological alterations in a dose-dependently manner. Furthermore, NNK exposure also upregulates Snail, promotes sphere-forming ability, and overexpresses aldehyde dehydrogenase 1 (ALDH1), Nanog, OCT4, ABCG2, and MDR1. Conclusion The current study confirmed that long-term NNK exposure plays a role in HNSCC by increasing anti-apoptosis and therapeutic resistance via the Snail-RKIP signaling pathway. Our data also suggest that α7 nicotinic acetylcholine receptor (α7-nAChR) inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 37: 1712–1721, 2015

The relationship between the use of benzodiazepine-receptor agonists (BZRAs) and the risk of hospitalization for pneumonia remains inconclusive. This study aimed to explore the association between BZRA use and hospitalization for pneumonia in a general population.This population-based nested case-control study used Taiwan's National Health Insurance Research Database between 2002 and 2012. We included only new users who did not have any BZRA prescriptions on record in the preceding 2 years and identified 12,002 subjects who were hospitalized for pneumonia (International Classification of Diseases, Ninth Revision codes 480-486, and 507) and 12,002 disease risk score-matched control subjects. A logistic regression model was used to determine the association of BZRA use and hospitalization for pneumonia. The exposure date, dose-response relationship, and class of BZRAs were comprehensively assessed.Current BZRA exposure was associated with hospitalization for pneumonia (adjusted OR [aOR],1.86; 95% CI, 1.75-1.97). Benzodiazepine hypnotic agents (aOR, 2.42; 95% CI, 2.16-2.71) had a higher risk of pneumonia than did benzodiazepine anxiolytic agents (aOR, 1.53; 95% CI, 1.44-1.63) or nonbenzodiazepine hypnotic agents (aOR, 1.60; 95% CI, 1.46-1.76). The pneumonia risk was increased with ultrashort-acting and short- to intermediate-acting agents, a higher defined daily dose, and the number of BZRAs used. Among individual BZRAs examined, midazolam had a higher risk (aOR, 5.77; 95% CI, 4.31-7.73) of hospitalization for pneumonia than did the others.This study suggests that there is a dose-response relationship between current BZRA use and the risk of hospitalization for pneumonia. In addition, benzodiazepine hypnotic agents, especially midazolam, present a greater risk of hospitalization for pneumonia. These findings reinforce the importance of a careful analysis of the benefits vs the risks of BZRA use.

The mechanisms by which hypoxic tumours evade immunological pressure and anti-tumour immunity remain elusive. Here, we report that two hypoxia-responsive microRNAs, miR-25 and miR-93, are important for establishing an immunosuppressive tumour microenvironment by downregulating expression of the DNA sensor cGAS. Mechanistically, miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS during hypoxia. This allows hypoxic tumour cells to escape immunological responses induced by damage-associated molecular pattern molecules, specifically the release of mitochondrial DNA. Moreover, restoring cGAS expression results in an anti-tumour immune response. Clinically, decreased levels of cGAS are associated with poor prognosis for patients with breast cancer harbouring high levels of miR-25/93. Together, these data suggest that inactivation of the cGAS pathway plays a critical role in tumour progression, and reveal a direct link between hypoxia-responsive miRNAs and adaptive immune responses to the hypoxic tumour microenvironment, thus unveiling potential new therapeutic strategies.

Purpose Diabetes mellitus (DM) is a global pandemic metabolic disorder. In recent years, the amount of medical resources required for the treatment of diabetes has increased as diabetes rates have gradually risen. The combined effects of individual and neighbourhood socio-economic status (SES) on DM survival rates are still not clear, especially in patients of working age. In this paper, we aim to analyze the combined effects of neighbourhood and individual SES on DM survival rates in patients of working age in Taiwan. Methods The study of 23,781 people who were diagnosed with DM by using population—based study between 2002 and 2006. Each sample was followed up for 4 years or as a sensor case. We defined Individual SES and neighbourhood SES by each patient’s job category and household income which characterized as advantaged or disadvantaged. Then we compared the survival rates by SES group used Cox proportional hazards model for adjust risk factors. Results The 4-year overall survival rates of diabetic patients were worst for those with low individual SES who living in advantaged neighbourhoods. After adjustment for patient characteristics, DM patients with high individual SES living in disadvantaged neighbourhoods had the same risk of mortality as those patients with high individual SES living in advantaged neighbourhoods (hazard ratio: 1.11; 95% confidence interval [CI]: 0.81–1.51). The study found that DM patients with low individual SES who live in disadvantaged areas had a greater risk of mortality than those with high SES (odds ratio: 2.57; 95% CI: 2.04–3.24). There were significant differences in survival rates between patients with high individual SES and patients with low individual SES. In contrast, the results did not statistically significant differences in survival rates between advantaged and disadvantaged neighbourhood SES groups. Conclusion DM patients with low individual SES had the worst survival rate, regardless of whether they were living in a high or low SES neighbourhood area. The competitive cause of death, i.e., the fact that complications, rather than DM itself, are often the cause of death, may be the reason for the inverse relationship found between the effects of individual SES and neighbourhood SES on DM survival. We conclude that the socio-economic gradient in survival among DM patients may be the result of differences in access to medical treatment and attributes related to individual SES.

Background Recent studies have shown that use of angiotensin-converting enzyme (ACE) inhibitors may decrease pneumonia risk in various populations. We investigated the effect of ACE inhibitors and angiotensin II receptor blockers (ARBs) on pneumonia hospitalization in the general population of Taiwan. Methods We conducted a case-crossover study using the Taiwan Longitudinal Health Insurance Database for the year 2005. Data from patients hospitalized for the first time for pneumonia during 1997-2007 were analyzed. The case period was defined as the 30 days before admission; the periods 90 to 120 days and 180 to 210 days before admission were used as control periods. Prescribing status of ACE inhibitors and ARBs during the 3 periods was assessed for each patient. Conditional logistic regression was used to estimate the odds ratio (OR) for pneumonia associated with use of ACE inhibitors and ARBs. Results We identified 10 990 cases of hospitalization for new pneumonia. After adjustment for time-variant confounding factors, pneumonia was not associated with use of ACEI or ARBS: the ORs were 0.99 (95% CI, 0.81-1.21) and 0.96 (0.72-1.28), respectively. No association was seen for cumulative defined daily doses (DDDs), as compared with nonusers, for 0 to 30, 31 to 60, or more than 60 DDDs. The results were found to be robust in sensitivity analysis. Conclusions Neither the use nor cumulative dose of ACE inhibitors or ARBs was associated with pneumonia among the Taiwanese general population.

A new uranyl silicate, K2Ca4[(UO2)(Si2O7)2], with a 1D chain structure has been synthesized from a solution of mixed alkali- and alkaline-earth-metal cations under hydrothermal conditions at 550 °C and 1400 bar and characterized by single-crystal X-ray diffraction and photoluminescence spectroscopy. It crystallizes in the triclinic space group P1̅ (No. 2) with a = 6.6354(2) Å, b = 6.6791(2) Å, c = 9.6987(3) Å, α = 98.324(2)°, β = 93.624(2)°, γ = 112.310(2)°, and Z = 1. Its crystal structure consists of a 1D chain of uranyl disilicate formed of corner-sharing UO6 tetragonal bipyramids and Si2O7 double groups. The adjacent chains are separated by K(+) and Ca(2+) cations. It is the first example of uranyl silicate with a 1D chain structure.

Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related death worldwide. The prognosis of HNSCC is usually poor because of its propensity for extensive invasion, local recurrence and frequent regional lymph node metastasis, even at initial diagnosis. Carcinoma-associated fibroblasts (CAFs), a major type of tumour-surrounding stromal cell, generate mediators through which they interact with tumours and contribute to cancer progression. The orchestration between CAFs and cancer cells is complex. Despite recent studies demonstrating the paracrine effect of stromal cells in the tumour microenvironment on initiation and progression of cancer cells, the major mediator related to CAFs and its underlying mechanism remain unknown. In the present study, we used organotypic culture to investigate CAFs that promote aggressive behaviour of HNSCC cells. Using microarray analysis, we detected abundant expression of interleukin-33 (IL-33) in CAFs and identified IL-33 as a critical mediator in CAF-induced invasiveness. Counteracting IL-33 activity diminished the aggressive phenotype of cancer cells induced by CAFs. Administration of IL-33 promoted cancer cell migration and invasion through induction of epithelial-to-mesenchymal transdifferentiation and increased IL-33 gene expression in cancer cells. In 40 patients with HNSCC, IL-33 expression in CAFs correlated with IL-33 expression in cancer cells. Most cases with a low invasion pattern grading score (IPGS) showed low or no expression of IL-33, whereas most HNSCC cases with high IPGS displayed over-expression of IL-33 in CAFs and cancer cells. High IL-33 expression associated with poor prognosis in terms of nodal metastasis-free survival. These results indicate that CAFs promote cancer invasiveness via paracrine and autocrine effects on microenvironmental IL-33 signalling, and suggest that IL-33 is a potential prognostic biomarker that could be considered in therapeutic strategies for the treatment of patients with HNSCC.

Background Despite increased experience in therapy, the overall outcome of oral squamous cell carcinoma (OSCC) has not improved because of the relative resistance to chemotherapeutic drugs in addition to local invasion and frequent regional lymph node metastases. Quercetin (Qu) is a principal flavonoid compound and an excellent free-radical-scavenging antioxidant that promotes apoptosis. Limited reports regarding the molecular or cellular role of Qu in anticancer properties on OSCC have been presented. This study was conducted to clarify the efficacy of Qu on OSCC in vitro and further to evaluate the possible mechanism(s). Methods Cultured OSCC cells (SCC-25) and human gingival fibroblasts (HGFs) were treated with different concentrations of Qu. Cell viability and cell colony-forming potential were detected with the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and colony growth assays. Cell-cycle analysis and apoptosis were measured by flow cytometry. Cell migration and invasion were tested using the micropore chamber assay. Results Cell viability and colony-forming potential were decreased in a dose-dependent manner following Qu treatment. Qu also dose-dependently inhibited the proliferation of SCC-25 cells via both G1 phase cell cycle arrest and mitochondria-mediated apoptosis. In addition, Qu also decreased the abilities of migration and invasion of SCC-25 cells in a dose-dependent manner. Conclusion Qu effectively inhibits cell growth and invasion/migration of SCC-25 cells in vitro . The cellular and molecular mechanisms are via cell cycle arrest accompanied by mitochondria-mediated apoptosis. Our findings suggest that Qu may have potential as a new chemopreventive agent or serve as a therapeutic adjuvant for OSCC.

Nucleoprotein (NP) is the most abundant type of RNA-binding viral protein in influenza A virus–infected cells and is necessary for viral RNA transcription and replication. Recent studies demonstrated that influenza NP is a valid target for antiviral drug development. The surface of the groove, covered with numerous conserved residues between the head and body domains of influenza A NP, plays a crucial role in RNA binding. To explore the mechanism by which NP binds RNA, we performed a series of site-directed mutagenesis in the RNA-binding groove, followed by surface plasmon resonance (SPR), to characterize the interactions between RNA and NP. Furthermore, a role of Y148 in NP stability and NP-RNA binding was evaluated. The aromatic residue of Y148 was found to stack with a nucleotide base. By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP’s RNA-binding affinity and hindered viral replication. Our findings will be useful for the development of new drugs that disrupt the interaction between RNA and viral NP in the influenza virus.

This paper presents an adaptive residential renewable energy management scheme considering end-users' life style to optimize electricity consumption including renewable resources in the smart homes. The proposed scheme generates smart residential power schedules dynamically according to the real-time stock of renewable resources and user-specific life style in home energy management. Experimental results show that the proposed work is more effectively, efficiently and user friendly in terms of electricity cost, CO2 emission and user's life style.

The new title compound is hydrothermally synthesized from a mixture of Ca(OH)2, UO3, SiO2, KOH, and H2O in a molar ratio of K:Ca:U:Si = 75:1:1:4 (gold ampule, 1400 bar, 550 °C, 4 d; 45% yield).

J Oral Pathol Med (2012) 41: 322–331 Background: To clarify the efficacy of grape seed procyanidin (GSP) on antiproliferative effects related to p53 functional status of oral squamous cell carcinoma (OSCC) for its chemoadjuvant potential. Methods: We used GSP to investigate SCC-25 cells with wild-type p53 gene and OEC-M1 cells with mutant p53 gene for the assessment of antiproliferative effects including cell viability, cell cycle, apoptosis, migration and invasion potential, and alterations of associated oncoproteins involved in cellular and molecular events. Results: The findings suggest that GSP on OEC-M1 cells leads to cell cycle arrest by increasing the expression of p21Cip1/p27Kip1 protein without functioning mitochondria-mediated apoptosis, whereas GSP on SCC-25 cells inhibits cell proliferation via both G1-phase arrest and mitochondria-mediated apoptosis in a dose-dependent manner as a result of alterations of Bcl-2. GSP also inhibits the migration and invasion of both cells, which are associated with the suppression of matrix metalloproteinases (MMPs), MMP-2 and MMP-9. Conclusion: Antiproliferative effectiveness of GSP is closely associated with the p53 status of OSCC cells. GSP displays chemoadjuvant potential via cell cycle blockage and apoptotic induction. Our findings clearly suggest that GSP may play a role as a novel chemopreventive or therapeutic agent for OSCC.

Architecture of a digital-input driving circuit for RGB-LED Backlight is proposed. By combining such a digital interface of RGB-LED driving circuit, matrix-arranged RGB-LEDs and the corresponding DC-DC conversion circuit, improvement for a backlight system, which is area color-controllable, scanning type and is for color sequential display can be achieved. Instead of using those sophisticated traditional LED driving techniques, such as constant current control, constant voltage control, charge pump, etc., an alternative employing software-controlled RGB-LED backlight system may help perform superior image quality on LCD screen.

Objectives To determine whether there is a bidirectional association between sleep apnea and diabetes mellitus. Methods We conducted longitudinal analyses of a population-based cohort over 12 years using Taiwan's national universal health insurance database. In analysis I, we included 102 355 individuals without type 2 diabetes mellitus at baseline and estimated the hazard ratio of incident diagnosis of type 2 diabetes mellitus for patients with and those without sleep apnea. In analysis II, we included 258 053 participants without sleep apnea at baseline and calculated the hazard ratio of developing sleep apnea for patients with and those without type 2 diabetes. Results In analysis I, the incidence rates of type 2 diabetes were 17.7 and 11.1 per 1000 person-years for patients with and those without sleep apnea, respectively. Patients with sleep apnea had an increased risk for diabetes (adjusted hazard ratio [aHR] = 1.33; 95% confidence interval [CI], 1.22 to 1.46). In analysis II, the risk for sleep apnea with diabetes was not statistically significant (aHR = 1.06; 95% CI, 0.98 to 1.16). These associations in both analyses did not substantively change after accounting for various latent periods. Conclusions Baseline sleep apnea is associated with incident type 2 diabetes; however, the presence of type 2 diabetes cannot predict the development of sleep apnea.

Recent studies suggest that long-term exposure of the carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine-mediated mechanism remains unclear.An analysis of SCC-25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial-mesenchymal transition, drug-resistance-related genes, properties of cancer stem cells (CSCs), and anti-apoptosis was performed.Long-term NNK exposure enhances migration and invasion with morphological alterations in a dose-dependently manner. Furthermore, NNK exposure also upregulates Snail, promotes sphere-forming ability, and overexpresses aldehyde dehydrogenase 1 (ALDH1), Nanog, OCT4, ABCG2, and MDR1.The current study confirmed that long-term NNK exposure plays a role in HNSCC by increasing anti-apoptosis and therapeutic resistance via the Snail-RKIP signaling pathway. Our data also suggest that α7 nicotinic acetylcholine receptor (α7-nAChR) inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC.

An architecture of H.265/HEVC video decoder for next generation video applications is presented. By exploiting near-lossless data compression and Sharing Above Line Buffer (SALB) schemes, both memory bandwidth and on-chip storage can be reduced. Moreover, cross-stage scheduling is applied to the 4-stage decoding pipeline to minimize idle computations. Fabricated in 90nm 1P9M CMOS process, the test chip of the proposed H.265/HEVC video decoder occupies an area of 1.60×1.98mm2 to achieve 1080p@30fps and 720p@30fps realtime decoding with power consumption of 36.90 and 9.57mW.

Pregnancy-specific glycoproteins (PSGs) are primarily expressed in the placenta and become the major glycoproteins at term. To understand the regulation of PSG expression, we characterized the promoter elements of a rodent PSG gene, rnCGM3, and delineated three nuclear protein binding sites: FPI, -II, and -III in the 5'-flanking region of the gene. The FPII-binding factor is shown to be C/EBPbeta, which positively regulates rnCGM3 expression [Chen, H., et al. (1995) DNA Cell Biol. 14, 681-688]. In the current study, we used the yeast one-hybrid system to isolate transcription factors binding to the FPIII site and demonstrated that a rodent J kappa recombination signal sequence binding protein, rRBPJ kappa-2N, bound to the FPIII site. Electrophoretic mobility shift assay with rat placental nuclear proteins revealed a constitutive occupancy of the FPIII site by RBPJ kappa. By transient expression analyses, we demonstrated that rRBPJ kappa-2N repressed the expression from an FPIII-driven SV40 promoter. However, this repression effect was counteracted by the active intracellular domain of Notch (NotchIC). Using the native rnCGM3 promoter construct, we demonstrated that the promoter activity stimulated by C/EBP beta was also repressed by rRBPJ kappa-2N but enhanced by NotchIC. Additionally, we found that NotchIC can stimulate expression through another RBPJkappa site within the FPI site. A functional interaction between factors binding to the FPI, FPII, and FPIII sites is proposed.

Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related death worldwide. The prognosis of HNSCC is usually poor because of its propensity for extensive invasion, local recurrence and frequent regional lymph node metastasis, even at initial diagnosis. Carcinoma-associated fibroblasts (CAFs), a major type of tumour-surrounding stromal cell, generate mediators through which they interact with tumours and contribute to cancer progression. The orchestration between CAFs and cancer cells is complex. Despite recent studies demonstrating the paracrine effect of stromal cells in the tumour microenvironment on initiation and progression of cancer cells, the major mediator related to CAFs and its underlying mechanism remain unknown. In the present study, we used organotypic culture to investigate CAFs that promote aggressive behaviour of HNSCC cells. Using microarray analysis, we detected abundant expression of interleukin-33 (IL-33) in CAFs and identified IL-33 as a critical mediator in CAF-induced invasiveness. Counteracting IL-33 activity diminished the aggressive phenotype of cancer cells induced by CAFs. Administration of IL-33 promoted cancer cell migration and invasion through induction of epithelial-to-mesenchymal transdifferentiation and increased IL-33 gene expression in cancer cells. In 40 patients with HNSCC, IL-33 expression in CAFs correlated with IL-33 expression in cancer cells. Most cases with a low invasion pattern grading score (IPGS) showed low or no expression of IL-33, whereas most HNSCC cases with high IPGS displayed over-expression of IL-33 in CAFs and cancer cells. High IL-33 expression associated with poor prognosis in terms of nodal metastasis-free survival. These results indicate that CAFs promote cancer invasiveness via paracrine and autocrine effects on microenvironmental IL-33 signalling, and suggest that IL-33 is a potential prognostic biomarker that could be considered in therapeutic strategies for the treatment of patients with HNSCC.

Background Metastasis occurs in a series of discrete steps involving invasion, angiogenesis, lymphovascular space permeation, and establishment of secondary tumors. Malignant pleural effusion (MPE), a type of tumor metastasis, is usually a poor prognostic sign for patients with pulmonary adenocarcinoma, although its underlying mechanism has received less attention than other types of metastases have. The objective of the current study was to confirm whether cancer stem cells (CSCs) in MPE contribute to the “metastatic cascade” through the epithelial – mesenchymal transition (EMT), anoikis, and adaptation in the microenvironment. Methods Pulmonary tissue and corresponding cell blocks of MPE samples from 20 patients with primary adenocarcinoma were analyzed by immunohistochemical staining with CSC-representative markers (CD133, Nanog, and OCT-4) and EMT-associated markers (E-cadherin and vimentin). Correlations between these variables and clinico-pathological parameters were analyzed. Primary cultures from eight cases of MPE were investigated to characterize the CSC properties, including marker expression, sphere formation, and differentiation. Results Expressions of CSC-representative markers for 20 cases of MPE cell blocks were quite diverse and variable ranging from 15% to 90%. Stronger expression of CSC-representative markers and alteration of EMT-associated markers were found at the invasive fronts and in MPEs compared with the expression in primary pulmonary tumor tissues. The expression of OCT-4 in MPEs significantly related to distant metastasis and stage, as well as inversely correlated with patient survival. Primary cultures confirmed the CSC properties in MPE. Five of eight cases of MPE yielded adequate cell clusters, which also showed variable expressions of CSC markers in addition to sphere formation and the ability for differentiation and metastasis. Conclusion This pilot study offers a better understanding of the metastatic cascade. Establishing a model of MPE will provide further insight into the role of CSCs in metastasis and may explain the high therapeutic failure rates for patients with MPE.

In the hardware architecture of the H.264/AVC video coding systems, the storage size of the intra predictor and de-blocking filter occupies a great portion of the internal memory size in the video coding. However, the higher resolution video costs huge internal memory size to store pixels to predict block data and eliminate the blocking effect, especially for the next-generation video applications which target resolution is Ultra-HD (8Kx4K). In this article, a memory-efficient architecture for intra predictor and de-blocking filter has been proposed which can roughly reduce up to 19% internal memory usage to efficiently reduce the decoder size and power consumption, and the sequential-interleaving memory architecture has also been adopted in the proposed architecture to solve the memory access conflict during video decoding. A test module is designed for the proposal and operates at 200 MHz for real-time processing with 85.1 K gates and 8.4 KB SRAM in 90nm CMOS technology.

OBJECTIVE To investigate the effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on pneumonia hospitalization in patients with stroke history in Taiwan. METHODS We conducted a case-crossover study using the National Health Insurance Research Database in Taiwan during the period from 1998 to 2007. Patients who had stroke history and were subsequently admitted for pneumonia were enrolled for analysis. The status of exposure to angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers 1-30 days prior to admission (case period) was compared to that during 91-120 days and 181-210 days before admission (control periods) for each patient. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between pneumonia and use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. RESULTS In this study, 13 832 patients with incident pneumonia from the stroke patient population were enrolled. After adjustment for time-varying confounding factors, angiotensin-converting enzyme inhibitor use was associated with a decreased pneumonia risk (OR 0.70; 95% CI 0.68-0.87) and a significant dose-response relationship (P

Background Cancer stem cells (CSCs) play an important role in tumor initiation, progression, and metastasis and are responsible for high therapeutic failure rates. Identification and characterization of CSC are crucial for facilitating the monitoring, therapy, or prevention of cancer. Great efforts have been paid to develop a more effective methodology. Nevertheless, the ideal model for CSC research is still evolving. In this study, we created a nonadhesive culture system to enrich CSCs from human oral squamous cell carcinoma cell lines with sphere formation and to characterize their CSC properties further. Methods A nonadhesive culture system was designed to generate spheres from the SAS and OECM-1 cell lines. A subsequent investigation of their CSC properties, including stemness, self-renewal, and chemo- and radioresistance in vitro, as well as tumor initiation capacity in vivo, was also performed. Results Spheres were formed cost-effectively and time-efficiently within 5 to 7 days. Moreover, we proved that these spheres expressed putative stem cell markers and exhibited chemoradiotherapeutic resistance, in addition to tumor-initiating and self-renewal capabilities. Conclusions Using this nonadhesive culture system, we successfully established a rapid and cost-effective model that exhibits the characteristics of CSCs and can be used in cancer research.

Two common drinking water earthy/musty odorants, 2-methyl-isoborneol (2-MIB) and trans-1,10-dimethyl-trans-9-decalol (geosmin), were monitored and analyzed for their correlation with environmental conditions in Feng-Shen Reservoir (FSR), Taiwan. Long-term monitoring results, from December 2000 to July 2003, indicated that 2-MIB was present in the reservoir at concentrations between 10 and 200 ng L(-1), and those of geosmin were always smaller than 10 ng L(-1). The 2-MIB concentrations followed a trend of higher concentrations during the warm seasons. After being analyzed with 10 water quality and three meteorological parameters, 2-MIB concentration was found to correlate with corresponding air and water temperatures. An analysis of air temperature history versus 2-MIB concentration in FSR suggested that 2-MIB concentration was best correlated with the mean of average daily temperature from 1 to 9 days before sampling, with R (2) = 0.90. This correlation was further employed to predict the 2-MIB concentration observed during another sampling period in FSR. A similar degree of fit was observed between predictions and experimental data, suggesting the potential applicability of the approach. In addition to the effect of temperature, heavy rainfalls that occurred before the sampling time may also reduce the 2-MIB concentration in the reservoir. A short-term continuous monitoring of the odorants for 32 h showed that both geosmin and 2-MIB concentrations in the reservoir remained almost constant, with only about a 10% difference during the sampling period. This may suggest that the odorants were uniformly distributed in the water near the sampling location in the reservoir.