Search

Photopatternable perovskite quantum dot–polymer composites with feature sizes as small as 3.86 μm are prepared for light-emitting applications.

BackgroundThe retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration.MethodsA retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insurance Research Database (NHIRD) during 2012–2016. We included 9149 and 11 112 MMT patients as the short and long groups according to the length of their cumulative MMT duration, 1–364 and ⩾365 days, respectively. The risk of mortality was calculated by Cox proportional hazards regression model with time-dependent exposure to MMT, and the survival probability was plotted with the Kaplan-Meier curve.ResultsThe mortality rates were 2.51 and 1.51 per 100 person-years in the short and long cumulative MMT duration groups, respectively. After adjusting for on or off MMT, age, sex, marital status, education level, maximum methadone dose, and comorbidities (human immunodeficiency virus, depression, hepatitis C virus, hepatitis B virus, alcoholic liver disease, and cardiovascular disease), the long group had a lower risk of death (hazard ratio = 0.67; 95% confidence interval 0.60–0.75) than the short group. Increased risk was observed in patients with advanced age, being male, unmarried, infected by HIV, HCV, and HBV, and diagnosed with depression, ALD, and CVD. Causes of death were frequently related to drug and injury.ConclusionsLonger cumulative MMT duration is associated with lower all-cause and drug-related mortality rate.

The health benefits of entering methadone maintenance treatment (MMT) for opioid-dependent persons may not be merely limited to therapy of opioid use disorder. We aimed to compare the healthcare utilization of MMT patients before and after MMT. A retrospective analysis was performed using the Taiwan Illicit Drug Issue Database and the National Health Insurance Research Database (NHIRD) between 2014 and 2016. We included 1255 newly enrolled MMT patients in 2015 and randomly selected 5020 patients from NHIRD matched by age and gender as the comparison group. Changes in healthcare utilization 1 year before and 1 year after the date of the index date (MMT initiation) were compared within and between MMT and comparison groups. During the 1-year period following MMT, the hospitalization length was considerably decreased, while the number of outpatient visits, emergency department (ED) visits, and ED expenditure significantly increased in MMT patients. Multivariable linear regression with the difference-in-difference approach revealed that all the categories of healthcare utilization increased, except for a minor increase of outpatient expenditure and a slight decrease of hospitalization length for the MMT group relative to the comparison group. Increases in utilization of the departments of psychiatry and infectious diseases of the MMT patients were considerable. MMT is associated with increased healthcare utilization, and departments of psychiatry and infectious diseases play substantial roles. Policy-makers should warrant access for all who need healthcare by ensuring the availability of the treatment for drug dependence.

Glioblastoma (GBM) is the most aggressive brain tumor and relapses after chemo- or radiotherapy in a short time. The anticancer drug temozolamide (TMZ) is commonly used for GBM treatment, but glioma stem-like cells (GSCs) often lead to drug resistance and therapeutic failure. To date, the mechanism of GSC formation in TMZ-treated GBM remains largely unknown. CCAAT/Enhancer-binding protein delta (CEBPD) is an inflammation-responsive transcription factor and is proposed to be oncogenic in the context of drug resistance, prompting us to clarify its role in TMZ-resistant GBM. In this study, we first found that the CEBPD protein levels in GBM patients were significantly increased and further contributed to TMZ resistance by promoting GSC formation. Accordingly, the protein levels of stemness transcription factors, namely, SRY-box transcription factor 2 (SOX2), octamer-binding transcription factor 4 (OCT4), NANOG, and ATP-binding cassette subfamily A member 1 (ABCA1), were increased in GSCs and TMZ-treated GBM cells. Increased binding of CEBPD to promoter regions was observed in GSCs, indicating the direct regulation of these GSC-related genes by CEBPD. In addition, an ABCA1 inhibitor increased the caspase 3/7 activity of TMZ-treated GSCs, suggesting that TMZ efflux is controlled by ABCA1 activity and that the expression levels of the ABCA1 gene are an indicator of the efficiency of TMZ treatment. Together, we revealed the mechanism of CEBPD-mediated GSC drug resistance and proposed ABCA1 inhibition as a potential strategy for the treatment of TMZ-resistant GBM.

BACKGROUND Animal models of trauma have shown that females have better posttraumatic survival; however, results of previous studies on the influence of gender on major trauma patients have been controversial. This study aimed to evaluate the association between gender and survival in major trauma patients. METHODS We retrospectively analyzed patients registered in Taiwan's National Health Insurance Research Database between 2008 and 2012 with the diagnosis codes 800-939 and 950-957 (International Classification of Diseases, ninth revision, clinical modification). Data on gender, age, catastrophic illness, and new injury severity score (NISS) ≥16 were collected for comparing patients' mortality after trauma. Propensity score matching (PSM) was performed to eliminate dissimilarities in age, comorbidities, NISS, and primary traumatic regions between the genders. RESULTS Among 10 012 major trauma patients included in the study cohort, 28.8% (n = 2880) were women. The PSM patient group consisted of 50% (2876 of 5752) women. Women had a higher 30-day (15.4% of women vs 13.8% of men; p < 0.05) and hospital (16.1% of women vs 14.5% of men; p < 0.05) mortality and lower incidence rates of acute respiratory dysfunction (62.5% of women vs 65.9% of men; p < 0.005) and acute hepatic dysfunction (0.8% of women vs 2.1% of men; p < 0.001). However, the analysis of PSM patient groups showed lower mortality rates in women with moderate trauma (NISS 16-24) in the acute phase within three days (1.4% of women vs 2.7% of men, p = 0.03). Analysis of patients with an NISS of 16-24 who died within three days showed a higher NISS in women than in men (19.7 ± 2.3 vs 18.0 ±1.9, respectively, p

This article proposes a scenario-based, self-taught and collaborative system to assist an innovation team to perform design projects robustly. This system transforms the innovation process into a collection of screen-based storyboards consist of the facilitator, design method-induced tools, environment and activities. This system also includes: 1) a set of modular courses that follow the design process of start-adapt-evolve-conclude, based on narrative in Chinese literature, 2) a modular space that is constructed the same scene as in the storyboard, and 3) a quantitative and qualitative evaluation mechanism. Through this system, the innovation team can engage in the collaborative activities and innovate together seamlessly. This method has been used by nearly 100 persons, and the users’ evaluation feedback of the innovation output is exceedingly positive, and the evaluation mechanism also provides new insights for continuous improvemens. This modular system has been proven effective in helping design teams more freely use proper methods to explore different innovative touch points, and to further inquire more human-centered design realms in the future.

The health benefits of entering methadone maintenance treatment (MMT) for opioid-dependent persons may not be merely limited to therapy of opioid use disorder. We aimed to compare the healthcare utilization of MMT patients before and after MMT.A retrospective analysis was performed using the Taiwan Illicit Drug Issue Database and the National Health Insurance Research Database (NHIRD) between 2014 and 2016. We included 1255 newly enrolled MMT patients in 2015 and randomly selected 5020 patients from NHIRD matched by age and gender as the comparison group. Changes in healthcare utilization 1 year before and 1 year after the date of the index date (MMT initiation) were compared within and between MMT and comparison groups.During the 1-year period following MMT, the hospitalization length was considerably decreased, while the number of outpatient visits, emergency department (ED) visits, and ED expenditure significantly increased in MMT patients. Multivariable linear regression with the difference-in-difference approach revealed that all the categories of healthcare utilization increased, except for a minor increase of outpatient expenditure and a slight decrease of hospitalization length for the MMT group relative to the comparison group. Increases in utilization of the departments of psychiatry and infectious diseases of the MMT patients were considerable.MMT is associated with increased healthcare utilization, and departments of psychiatry and infectious diseases play substantial roles. Policy-makers should warrant access for all who need healthcare by ensuring the availability of the treatment for drug dependence.

Leakage of lead and other heavy metals into drinking water is a significant health risk and one that is not easily detected. We have developed simple sensors containing only platinum electrodes for the detection of heavy metal contamination in drinking water. The two-electrode sensor can identify the existence of a variety of heavy metals in drinking water, and the four-electrode sensor can distinguish lead from other heavy metals in solution. No false-positive response is generated when the sensors are placed in simulated and actual tap water contaminated by heavy metals. Lead detection on the four-electrode sensor is not affected by the presence of common ions in tap water. Experimental results suggest the sensors can be embedded in water service lines for long-time use until lead or other heavy metals are detected. With its low cost (∼$0.10/sensor) and the possibility of long-term operation, the sensors are ideal for heavy metal detection of drinking water.

Globally, pangolins are overt for poaching and illegal trade, but Taiwan projects totally a contrary image where their population is stable and increasing. This paper illustrated the factors responsible for causing mortality and morbidity in free ranging Formosan pangolin (M. pentadactyla pentadactyla). Results from radio-tracking showed that Formosan pangolins are highly susceptible to stuck in tree hallows or ground burrows despite being proficient burrowers, and killed by gin traps, especially during the dryer season. Whilst the data consolidated from the Pingtung Rescue Center for Endangered Wild Animals illustrated the trauma (73.0%) was the major reason of causing morbidity in Formosan pangolin. The gin traps were the leading cause of trauma (77.8%) along with tail injuries caused by dog attack (20.4%). Despite all the pressing data about the injuries Taiwan, it is able to establish substantial success rate in rescuing and releasing pangolins through consolidating and applying valuable information among the rescue centers in the span of two decades. Taiwan has made a phenomenal progress in sustaining a salubrious population of pangolin but the situation requires continuous examination to ensure the existence of this species on the island.

Globally, pangolins are threatened by poaching and illegal trade. Taiwan presents a contrary situation, where the wild pangolin population has stabilized and even begun to increase in the last two decades. This paper illustrates the factors responsible for causing mortality and morbidity in the wild Taiwanese pangolin (Manis pentadactyla pentadactyla) based on radio-tracking data of wild pangolins and records of sick or injured pangolins admitted to a Taiwanese wildlife rehabilitation center. Despite being proficient burrowers, results from radio-tracking show that Taiwanese pangolins are highly susceptible to getting trapped in tree hollows or ground burrows. Data from Pingtung Rescue Center for Endangered Wild Animals showed that trauma (73.0%) was the major reason for morbidity in the Taiwanese pangolin with trauma from gin traps being the leading cause (77.8%), especially during the dry season, followed by tail injuries caused by dog attacks (20.4%). Despite these threats, Taiwan has had substantial success in rehabilitating and releasing injured pangolins, primarily due to the close collaboration of Taiwanese wildlife rehabilitation centers over the last twenty years.

We have constructed micro-fabricated flow sensors that can measure water flow rates of 0.1 to 2.0 gallons per minute (GPM), and the experimental results we obtained are in good agreement with those from COMSOL simulations. Two identical sensors were fabricated on each device with an upstream sensor functioning as a temperature sensor, and the voltage difference between the two sensors indicating the water flow rate. The sensors were constructed on glass substrates, chosen for their low price, efficient thermal isolation, and compatibility with current water supply systems. The variation of water temperature of the flowing fluid from 10 to 50 °C was accounted for by normalizing the voltage readings. The dimensions of the sensors ranged from 71 μm by 80 μm to 430 μm by 480 μm with the smaller sensors having a higher sensitivity. Sensitivity also increased with increasing input power up to the point when boiling occurred. The optimized sensor, which was 71 μm by 80 μm on a 3 mm by 3 mm glass substrate, could be operated with only 2.75 mW of power in 10 to 50 °C water, providing an economic and energy efficient method to measure large water flow rates of 0.1–0.5 GPM.

Inspiratory flow limitation (IFL) is a critical symptom of sleep breathing disorders. A characteristic flattened flow-time curve indicates the presence of highest resistance flow limitation. This study involved investigating a real-time algorithm for detecting IFL during sleep. Three categories of inspiratory flow shape were collected from previous studies for use as a development set. Of these, 16 cases were labeled as non-IFL and 78 as IFL which were further categorized into minor level (20 cases) and severe level (58 cases) of obstruction. In this study, algorithms using polynomial functions were proposed for extracting the features of IFL. Methods using first- to third-order polynomial approximations were applied to calculate the fitting curve to obtain the mean absolute error. The proposed algorithm is described by the weighted third-order (w.3rd-order) polynomial function. For validation, a total of 1,093 inspiratory breaths were acquired as a test set. The accuracy levels of the classifications produced by the presented feature detection methods were analyzed, and the performance levels were compared using a misclassification cobweb. According to the results, the algorithm using the w.3rd-order polynomial approximation achieved an accuracy of 94.14% for IFL classification. We concluded that this algorithm achieved effective automatic IFL detection during sleep.

Article history:Received 2 April 2013Received in revised form 28 August 2013Accepted 30 August 2013Available online 7 September 2013Keywords:LMX1ASp1EZH2Histone modificationDNA methylationCervical cancer WehavereportedpreviouslythatLIMhomeoboxtranscriptionfactor1α(LMX1A)ishypermethylatedandfunc-tionsasa metastasissuppressor incervical cancer cells. However, the regulation of LMX1A incarcinogenesis hasnotbeenreported.Weaimtoclarifywhetherspecificityprotein1(Sp1)andenhancerofzestehomolog2(EZH2)are involved in the regulation of LMX1A in cervical cancer. First we characterizedthe LMX1A promoter and usedoverexpression, knockdown, and reporter assaysto show that Sp1 increasedLMX1A promoter activity. Next, weused site-directed mutagenesis and electrophoresis mobility shift assays (EMSAs) to demonstrate that Sp1-binding siteswereimportant forSp1-mediatedactivationoftheLMX1A promoter.Chromatinimmunoprecipita-tiondatademonstratedthatSp1couldbinddirectlytotheLMX1ApromoterandactivateendogenousLMX1Aex-pression in cellspretreated with 5-aza-2′-deoxycytidine (5-aza-dC). Knockdown of EZH2 decreasedH3K27me3histone modification but was insufficient to restore LMX1A expression. To explore the effect of EZH2 on the en-dogenous LMX1A promoter, we treated EZH2-knockdown cells with 5-aza-dC and trichostatin A (TSA) andthen depleted the cells of drugs for 3 days. H3K14ac was enriched at the LMX1A promoter in EZH2-knockdown cells and LMX1A mRNA was still expressed. Taken together, these data imply that Sp1 may activateLMX1A expression upon oncogenic stress during cervical cancer development. Moreover, suppression of EZH2may delay resilencing of LMX1A after the removal of 5-aza-dC and TSA.© 2013 Elsevier B.V. All rights reserved.

Drug resistance is an obstacle to the treatment of ovarian cancer. Using a unique cell model, we have proven previously that a subpopulation of ovarian cancer cells is more resistant to cisplatin than are the original cells. MicroRNAs (miRNAs), small noncoding RNAs, are involved in many biological events in cancer cells. In our study, we explored whether miRNAs are involved in cisplatin resistance of ovarian cancer cells. Cisplatin-resistant cells expressed a lower level of miR-29a/b/c. Manipulation of microRNA-29 (miR-29) expression modulated cisplatin sensitivity of CP70, HeyC2, SKOV3 and A2780 ovarian cancer cells. Knockdown of miR-29a/b/c increased the ability of cells to escape cisplatin-induced cell death partly through upregulation of collagen type I alpha 1 (COL1A1) and increased the activation of extracellular signal-regulated kinase 1/2 and inactivation of glycogen synthase kinase 3 beta. When combined with cisplatin treatment, knockdown of miR-29 decreased the amount of the active form of caspase-9 and caspase-3. Ectopic expression of miR-29 alone or in combination with cisplatin treatment efficaciously reduced the tumorigenicity of CP70 cells in vivo. Our data show that downregulation of miR-29 increases cisplatin resistance in ovarian cancer cells. Taken together, these data suggest that overexpression of miR-29 is a potential sensitizer to cisplatin treatment that may have therapeutic implications.

Optical properties of histamine and l-histidine have been analyzed by using surface-enhanced Raman scattering (SERS). A silver film over nanosphere (AgFON) structure with 120-nm-thick silver film on polystyrene nanospheres 1,000 nm in diameter is fabricated by nanosphere lithography to enhance the Raman signal excited at the laser wavelength of 532 nm. Normal Raman spectrum and the SERS spectrum of histamine and l-histidine were compared. Further, vibration modes of these molecules were calculated by using density functional method. In the SERS experiment, we were able to measure the Raman spectrum with a histamine concentration as less as 100 pM. This sensitivity is higher than that from high-performance liquid chromatography.

The tidal volume and breath frequency had demonstrated to have respective effect on respiratory sinus arrhythmia. This study was designed to mimic the oscillatory breath pattern as periodic breathing by healthy subjects. We aimed to determine the impacts of breathing frequency and tidal volume on the respiratory modulation on heart rate. The components of heart rate variability were calculated in the time and frequency domain. The increase of SDNN or VLF in heart rate variability was observed during breathing manipulation.

The dependence of nanoparticle size on surface-enhanced Raman scattering (SERS) from silver film over nanospheres substrate is studied. For a range of nanosphere sizes from 430 to 1,500 nm, optimum SERS signal is obtained with a nanosphere size of 1,000 nm at an excitation wavelength of 532 nm. We have clarified the physical origin of this optimization in an unambiguious way as due to resonant plasmonic excitations from 3D finite-difference time-domain simulations, as well as with the assistance of UV-visible reflectance spectrum.

miRNAs are a class of non-coding RNAs, which bind to the 3'-untranslated regions of their target mRNAs to repress translation. However, the details of miRNA-mediated epigenetic regulation targeting genomic DNA remained largely unknown. Here, we demonstrated that transcription factor CCAAT/enhancer binding protein delta (CEBPD) was responsive to the anticancer drug bortezomib, is a highly selective reversible inhibitor for leukemia treatment, and resulting in caspase activation and apoptosis. Interestingly, following the identification of CEBPD-induced miRNAs, we found that miR-744, miR-3154 and miR-3162 feedback to suppress the transcription of CEBPD itself and genes adjacent to its 5'-flanking region, including protein kinase DNA-activated catalytic polypeptide (PRKDC), minichromosome maintenance-deficient 4 (MCM4) and ubiquitin-conjugating enzyme E2 variant 2 (UBE2V2), upon bortezomib treatment. Additionally, we previously demonstrated that the Yin Yang 1 (YY1)/polycomb group (PcG) protein/DNA methyltransferase (DNMT) complex is important for mediating epigenetic silencing of the CEBPD gene; we further found that Argonaute 2 (Ago2) interacts with YY1 and binds to the CEBPD promoter. Moreover, we revealed that miRNA binding plays a key role for YY1/PcG group protein/DNMT complex-mediated epigenetic gene silencing and is associated with bortezomib-induced methylation on genomic DNA. Altogether, we provided new insights for miRNA-mediated epigenetic regulation in the case of bortezomib-induced cell death in leukemia. Citation Format: Ju-Ming Wang, Yu-Yi Chu, Chiung-Yuan Ko, Shao-Ming Wang, Pin-I Lin, Han-Ying Wang, Wen-Chi Lin, Dong-Yu Wu. miRNAs/Ago2/YY1/PcG protein/DNMT complex mediates epigenetic silencing of locus genes and associates with bortezomib-induced apoptosis of leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 358.

It is demonstrated that the surface-enhanced Raman scattering (SERS) intensity of R6G molecules adsorbed on a Ag nanoparticle array can be controlled by tuning the size and height of the nanoparticles. A firm Ag nanoparticle array was fabricated on glass substrate by using nanosphere lithography (NSL) combined with reactive ion etching (RIE). Different sizes of Ag nanoparticles were fabricated with seed polystyrene nanospheres ranging from 430 nm to 820 nm in diameter. By depositing different thicknesses of Ag film and lifting off nanospheres from the surface of the substrate, the height of the Ag nanoparticles can be tuned. It is observed that the SERS enhancement factor will increase when the size of the Ag nanoparticles decreases and the deposition thickness of the Ag film increases. An enhancement factor as high as 2×106 can be achieved when the size of the polystyrene nanospheres is 430 nm in diameter and the height of the Ag nanoparticles is 96 nm. By using a confocal Raman mapping technique, we also demonstrate that the intensity of Raman scattering is enhanced due to the local surface plasmon resonance (LSPR) occurring in the Ag nanoparticle array.

Oncogenic activation of the Wnt signaling pathway is common in cancers, but mutation of beta-catenin in ovarian cancer is rare. In addition to genetic events, epigenetic modification of secreted frizzled-related protein (SFRP) family has been shown to be important in regulating Wnt signaling. Although high degree of homology is observed in the same family, different SFRPs may have opposing effects on the same process. We reported recently that a Wnt antagonist, SFRP5, is downregulated frequently through promoter hypermethylation and that this hypermethylation is associated with overall survival in ovarian cancer. The aim of this study was to analyze the function of SFRP5 in ovarian cancer. Functional assays including measuring cell proliferation, invasion, colony formation and xenograft were performed using ovarian cancer cell lines with overexpression of SFRP5 or a short hairpin RNA silencing. The methylation status of SFRP5 in relation to cisplatin resistance in ovarian cancer patients was analyzed. Restoration of the expression of SFRP5 attenuated Wnt signaling in ovarian cancer cells and suppressed cancer cell growth, invasion of cells and tumorigenicity in mice. These effects were independent of the canonical pathway. The expression of SFRP5 inhibited epithelial-mesenchymal transition (EMT). The restoration of SFRP5 downregulated AKT2 and sensitized ovarian cancer cells to chemotherapy. These effects are consistent with the poor response to platinum-based chemotherapy in patients with methylation of SFRP5. Our data suggested that epigenetic silencing of SFRP5 leads to oncogenic activation of the Wnt pathway and contributes to ovarian cancer progression and chemoresistance through the TWIST-mediated EMT and AKT2 signaling.

Intravenous immunoglobulin (IVIG) has emerged as a promising treatment that interrupts the progression of Stevens-Johnson syndrome (SJS). Our patient experienced an uncommon adverse effect, non-eczematous, vesiculobullous eruptions, after treatment with IVIG. These new lesions developed rapidly on the palms while most previous SJS bullous lesions subsided. A skin biopsy of these new lesions showed an intracorneal vesicle, without epidermal necrosis, with inflammatory cell infiltration. IVIG-induced, vesiculobullous eruptions are discussed, along with their possible pathogenesis. With the increasing use of IVIG for treatment of bullous dermatoses, recognition of this rare adverse effect is important for prompt differential diagnosis.

T cell-mediated immunodestruction of pancreatic β cells is the key process responsible for both the development of autoimmune diabetes and the induction of rejection during islet transplantation. In this study, we investigate the hypothesis that transgenic expression of an agonistic, membrane-bound single-chain anti-CTLA-4 Fv (anti-CTLA-4 scFv) on pancreatic β cells can inhibit autoimmune processes by selectively targeting CTLA-4 on pathogenic T cells. Strikingly, transgenic expression of anti-CTLA-4 scFv on pancreatic β cells significantly protected NOD mice from spontaneous autoimmune diabetes. Interestingly, local expression of this CTLA-4 agonist did not alter the diabetogenic properties of systemic lymphocytes, because splenocytes from transgenic mice or their nontransgenic littermates equally transferred diabetes in NOD/SCID recipients. By analyzing the T cell development in anti-CTLA-4 scFv/Th1/Th2 triple transgenic mice, we found that β cell-specific expression of CTLA-4 agonist did not affect the development of Th1/Th2 or CD4+CD25+ regulatory T cells. Most strikingly, islets from transgenic mice inhibited T cell response to immobilized anti-CD3 in a T cell-islet coculture system, suggesting a trans-mediated inhibition provided by transgenic islets. Finally, transgenic islets implanted in diabetic recipients survived much longer than did wild-type islets, indicating a therapeutic potential of this genetically modified islet graft in autoimmune diabetes.

The optical properties of tetrodotoxin (TTX), a scarce toxin with anesthetic properties, were studied using nanoparticle arrays-assisted surface-enhanced Raman scattering (SERS). The nanoparticles arrays were fabricated using nanosphere lithography and a metallic lift-off process to control the particle size, shape, and spacing in the arrays. Using density functional methods, the Raman spectrum of TTX was also calculated with Gaussian03 software. The main peaks of the spectrum are originated from the vibration of the NH2 molecule group. In the SERS experiment, we were able to measure the Raman spectrum with a TTX concentration as less as 0.9 ng/mL. This sensitivity is comparable to that from high performance liquid chromatography.

Using optical sensors to transform light-matter interaction into optical signal has become more and more popular. This is especially true for the fields that require ultrafast responsibility and remote sensing, such as environmental monitoring, food analysis and medical diagnosis. Among numerous optical sensors, plasmonic nanosensors are of great promise due to their spectral tunability and good adaptability to modern nanobiotechnologies. Localized surface plasmon resonance (LSPR) is the electromagnetic resonance of conducting electrons on metal surface, and it is very sensitive to the variation of environmental refractive index. The LSPR is considered as a useful sensing parameter that provides very good biochemical information. The SPR absorption peak also can be adjusted by changing the nano structure on the LSPR biological sensor chip. In this study, Finite-Difference Time- Domain (FDTD) was applied to simulate the LSPR absorption peak. Four model parameters were modified to study the LSPR sensing sensitivity: (a) the incident light wavelength, (b) the diameter of nanoparticle, (c) the spacing among nanoparticles, and (d) the height of nanoparticle. The simulation results show that 860nm is the best wavelength for the LSPR adsorption measurement. The optimal diameter of nanoparticle is 150nm, and the nanoparticle spacing is 90nm. Higher nanoparticle height provides higher sensitivity, but it also depends on the process capability. The FDTD simulation can be a useful tool to design a LSPR nanoparticle biosensor.

In this study, we investigated the use of humor in college classrooms. We examined how students perceived professors' uses of various types of humor during class and the types of humor that students and faculty recommend for use in class. We also correlated the way professors incorporated humor into their class lectures with their perceived competence and effectiveness, and we investigated whether students felt their learning experience improved when their teachers used humor. We also discussed topics such as ''scarcasm,'' professor gender, student and faculty support of humor, and humor in classrooms, tests, and the rest of life. Humor appropriately used has the potential to humanize, illustrate, defuse, encourage, reduce anxiety, and keep people thinking.

With utilization of a transparent medaka fish (Oryzias latipes) and fluorescent confocal microscopy, essential knowledge about biodistribution of fluorescein isothiocyanate (FITC)-functionalized me...

Drug resistance is an obstacle to the treatment of ovarian cancer. Using a unique cell model, we have proven previously that a subpopulation of ovarian cancer cells is more resistant to cisplatin than are the original cells. MicroRNAs (miRNAs), small noncoding RNAs, are involved in many biological events in cancer cells. In our study, we explored whether miRNAs are involved in cisplatin resistance of ovarian cancer cells. Cisplatin-resistant cells expressed a lower level of miR-29a/b/c. Manipulation of microRNA-29 (miR-29) expression modulated cisplatin sensitivity of CP70, HeyC2, SKOV3 and A2780 ovarian cancer cells. Knockdown of miR-29a/b/c increased the ability of cells to escape cisplatin-induced cell death partly through upregulation of collagen type I alpha 1 (COL1A1) and increased the activation of extracellular signal-regulated kinase 1/2 and inactivation of glycogen synthase kinase 3 beta. When combined with cisplatin treatment, knockdown of miR-29 decreased the amount of the active form of caspase-9 and caspase-3. Ectopic expression of miR-29 alone or in combination with cisplatin treatment efficaciously reduced the tumorigenicity of CP70 cells in vivo. Our data show that downregulation of miR-29 increases cisplatin resistance in ovarian cancer cells. Taken together, these data suggest that overexpression of miR-29 is a potential sensitizer to cisplatin treatment that may have therapeutic implications.

Oncogenic activation of the Wnt/β-catenin signaling pathway is common in hepatocellular carcinoma (HCC). Our recent studies have demonstrated that SRY (sex determining region Y)-box 1 (SOX1) and secreted frizzled-related proteins are concomitantly promoter-hypermethylated, and this might lead to abnormal activation of the Wnt signaling pathway in HCC. SOX1 encodes a transcription factor involved in the regulation of embryonic development and cell fate determination. However, the expression and functional role of SOX1 in HCC remains unclear. In this study, we confirmed via quantitative methylation-specific polymerase chain reaction that SOX1 was frequently downregulated through promoter hypermethylation in HCC cells and tissues. Overexpression of SOX1 by a constitutive or inducible approach could suppress cell proliferation, colony formation, and invasion ability in HCC cell lines, as well as tumor growth in nonobese diabetic/severe combined immunodeficiency mice. Conversely, knockdown of SOX1 by withdrawal of doxycycline could partially restore cell proliferation and colony formation in HCC cells. We used a T cell factor (TCF)-responsive luciferase reporter assay and western blot analysis to prove that SOX1 could regulate TCF-responsive transcriptional activity and inhibit the expression of Wnt downstream genes. Furthermore, we used glutathione S-transferase pull-down, co-immunoprecipitation, and confocal microscopy to demonstrate that SOX1 could interact with β-catenin but not with the β-catenin/TCF complex. Moreover, restoration of the expression of SOX1 induces significant cellular senescence in Hep3B cells. Conclusion: Our data show that a developmental gene, SOX1, may function as a tumor suppressor by interfering with Wnt/β-catenin signaling in the development of HCC. (HEPATOLOGY 2012;56:2142–2153)

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, regulates immune responses through competing with receptors of Fas ligand (FasL), LIGHT and TNF-like molecule 1A (TL1A). We have previously demonstrated that transgenic expression of DcR3 in a β cell-specific manner significantly protects non-obese diabetic (NOD) mice from autoimmune diabetes. In this study, we further investigated the systemic effect of DcR3 in regulating lymphocytes and dendritic cells in NOD mice. Our results demonstrated that both DcR3 plasmid and protein treatments significantly inhibited insulitis and diabetes. Lymphocytes from DcR3.Fc-treated mice revealed less proliferative potential and transferred ameliorated diabetes. By administration of DcR3.Fc in T1 and T2 double transgenic NOD mice expressing human Thy1 or murine Thy1.1 surface marker under IFN-γ or IL-4 promoter control respectively, we observed a remarkable reduction of Th1 and an increase of Th2 immune responses in vivo. Strikingly, in vitro polarization experiments exhibited that not only Th1 but also Th17 cell differentiation was significantly inhibited in splenocytes treated with DcR3.Fc protein. However, this phenomenon was only observed in splenocytes, not in purified CD4(+) T cells, suggesting that DcR3-mediated inhibition of Th1 and Th17 differentiation is not T cell-autonomous and maybe through other cell types such as dendritic cells. Finally, our results demonstrated that DcR3 directly modulates the differentiation and maturation of dendritic cells and subsequently regulates the differentiation and effector function of T cells.

The optical properties of tetrodotoxin (TTX), a scarce toxin with anesthetic properties, were studied using nanoparticle arrays-assisted surface-enhanced Raman scattering (SERS). The nanoparticles arrays were fabricated using nanosphere lithography and a metallic lift-off process to control the particle size, shape, and spacing in the arrays. In the SERS experiment, we were able to measure the Raman spectrum with a TTX concentration as less as 0.9 ng/mL. This sensitivity is comparable to that from high performance liquid chromatography.