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Background: Psoriasis is an inflammatory skin disease characterized by the hyperproliferative epidermal keratinocytes and significant immune cells infiltration, leading to cytokines production such as IL-1β, TNF-α, IL-23, and IL-17. Recent study highlights the critical role of IL-1β in the induction and activation of pathogenic Th17 and IL-17-producing γδ T cells, contributing to psoriasis. However, the mechanism underlying IL-1β dysregulation in psoriasis pathogenesis is unclear. Autophagy regulates IL-1β production and has a pleiotropic effect on inflammatory disorders. Previous studies showed controversial role of autophagy in psoriasis pathogenesis, either pro-inflammatory in autophagy-deficient keratinocyte or anti-inflammatory in pharmacologically autophagy-promoting macrophages. Thus, the direct role of autophagy and its therapeutic potential in psoriasis remains unclear. Methods: We used myeloid cell-specific autophagy-related gene 7 (Atg7)-deficient mice and determined the effect of autophagy deficiency in myeloid cells on neutrophilia and disease pathogenesis in an imiquimod-induced psoriasis mouse model. We then assessed the pathogenic mechanism focusing on immune cells producing IL-1β and IL-17 along with gene expression profiles associated with psoriasis in mouse model and public database on patients. Moreover, therapeutic potential of IL-1β blocking in such context was assessed. Results: We found that autophagy deficiency in myeloid cells exacerbated neutrophilic inflammation and disease pathogenesis in mice with psoriasis. This autophagy-dependent effect was associated with a significant increase in IL-1β production from myeloid cells, particularly macrophages, Cxcl2 expression, and IL-17 A producing T cells including γδ T cells. Supporting this, treatment with systemic IL-1 receptor blocking antibody or topical saccharin, a disaccharide suppressing pro-IL-1β expression, led to the alleviation of neutrophilia and psoriatic skin inflammation linked to autophagy deficiency. The pathophysiological relevance of this finding was supported by dysregulation of autophagy-related genes and their correlation with Th17 cytokines in psoriatic skin lesion from patients with psoriasis. Conclusions: Our results suggest that autophagy dysfunction in myeloid cells, especially macrophages, along with IL-1β dysregulation has a causal role in neutrophilic inflammation and psoriasis pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic inflammation is a hallmark of refractory chronic rhinosinusitis (CRS) and considered a major therapeutic target. Autophagy deficiency in myeloid cells plays a causal role in eosinophilic CRS (ECRS) via macrophage IL‐1β overproduction, thereby suggesting autophagy regulation as a potential therapeutic modality. Trehalose is a disaccharide sugar with known pro‐autophagy activity and effective in alleviating diverse inflammatory diseases. We sought to investigate the therapeutic potential of autophagy‐enhancing agent, trehalose, or related sugar compounds, and the underlying mechanism focusing on macrophage IL‐1β production in ECRS pathogenesis. Methods: We investigated the therapeutic effects of trehalose and saccharin on macrophage IL‐1β production and eosinophilia in the mouse model of ECRS with myeloid cell‐specific autophagy‐related gene 7 (Atg7) deletion. The mechanisms underlying their anti‐inflammatory effects were assessed using specific inhibitor, genetic knockdown or knockout, and overexpression of cognate receptors. Results: Unexpectedly, trehalose significantly attenuated eosinophilia and disease pathogenesis in ECRS mice caused by autophagy deficiency in myeloid cells. This autophagy‐independent effect was associated with reduced macrophage IL‐1β expression. Various sugars recapitulated the anti‐inflammatory effect of trehalose, and saccharin was particularly effective amongst other sugars. The mechanistic study revealed an involvement of sweet taste receptor (STR), especially T1R3, in alleviating macrophage IL‐1β production and eosinophilia in CRS, which was supported by genetic depletion of T1R3 or overexpression of T1R2/T1R3 in macrophages and treatment with the T1R3 antagonist gurmarin. Conclusion: Our results revealed a previously unappreciated anti‐inflammatory effect of STR agonists, particularly trehalose and saccharin, and may provide an alternative strategy to autophagy modulation in the ECRS treatment. [ABSTRACT FROM AUTHOR]

Despite the promising anticancer effects of kinesin spindle protein (KSP) inhibition, functional plasticity of kinesins induced resistance against KSP inhibitors in a variety of cancers, leading to clinical failure. Additionally, paclitaxel is a widely used anticancer agent, but drug resistance has limited its use in the recurrent cancers. To overcome resistance against KSP inhibitors, we paired KSP inhibition with microtubule stabilization using KSP siRNA and paclitaxel. To enable temporal co-localization of both drugs in tumor cells in vivo , we exploited PEGylated cationic liposomes carrying both simultaneously. Drug synergism study shows that resistance against KSP inhibition can be suppressed by the action of microtubule-stabilizing paclitaxel, because microtubule stabilization prevents a different kinesin Kif15 from replacing all essential functions of KSP when KSP is inhibited. Our combination therapy showed more effective antiproliferative activity in vitro and in vivo than either paclitaxel or KSP siRNA alone. Ultimately, we could observe significantly improved therapeutic effects in the drug-resistant in vivo models, including cell line and patient-derived xenografts. Taken together, our combination therapy provides a potential anticancer strategy to overcome resistance against KSP inhibitors. Particularly, this strategy also provides an efficient approach to improve the therapeutic effects of paclitaxel in the drug-resistant cancers. Unlabelled Image • We prepared KSP siRNA/paclitaxel-loaded liposomes and paired KSP inhibition with microtubule stabilization. • Paclitaxel prevented a different kinesin Kif15 from replacing all essential functions of KSP when KSP was inhibited. • Our combination therapy shows more effective antiproliferative activity than either paclitaxel or KSP siRNA alone. • This work provides a potential anticancer strategy to overcome resistance against KSP inhibitors. [ABSTRACT FROM AUTHOR]

A red-emitting and ratiometric fluorescence probe 1 for detecting H 2 O 2 , based on a styrylnaphthalimide-boronate ester was developed. Upon a H 2 O 2 -mediated hydrolysis of boronate ester, probe 1 was transformed to 2 with a ratiometric fluorescence change, decrease at 535 and increase at 640 nm. It was also found that the fluorescent reaction of 1 with H 2 O 2 in solution could be completed within 10 min and the detection limit was estimated to be 0.30 μM. Moreover, this ratiometric change was highly selective for H 2 O 2 over other redox species, metal ions, and anions. Also, this system was found to be capable of detecting H 2 O 2 in the pH range of 6–9. Furthermore, probe 1 was preferentially accumulated into the endoplasmic reticulum (ER) in the live HeLa cells, and an increased H 2 O 2 level in the presence of an ER stress inducer, thapsigargin was revealed. Image 1 • A red-emitting and ratiometric fluorescence probe for detecting H 2 O 2 was developed. • This probe is based on H 2 O 2 -mediated hydrolysis of styrylnaphthalimide-boronate ester. • This probe can show a selective fluorescence change between 535 and 640 nm to H 2 O 2. • The probe can detect H 2 O 2 within 10 min with the detection limit of 0.30 μM. • This probe can be utilized to monitor H 2 O 2 in the ER of the live cells. [ABSTRACT FROM AUTHOR]

Duration of gene silencing due to the short-term silencing effects induced by exogenous siRNA have limited the therapeutic applications of RNAi and the development of RNAi-based therapeutics. We here generated Eg5 shRNA-expressing plasmids using the inverted terminal repeats (ITRs) sequences to produce Eg5 hairpin RNA under the control of U6 promoter. Using PEGylated DC-Chol/DOPE cationic liposomes, we demonstrated that a single systemic administration of Eg5 shRNA-expressing plasmid/liposome lipoplexes induced the long-term Eg5 silencing in the tumor sites of tumor-bearing mice, and ultimately lead to more sustained anticancer effects than standard synthetic siEg5/liposome lipoplexes. This non-viral Eg5 shRNA expression system had no risk of immunogenicity anticipated in the use of viral vectors, and could reduce the potential of off-target effects by scaling down the administration dose of RNAi therapeutics in patient. Therefore, the sustainable shRNA expression properties in the tumor sites suggest an efficient strategy to overcome the limitations caused by chemically synthesized siRNA methods such as short-term silencing effects and off-target effects. Herein, this study provides a non-viral silencing strategy for inducing long-term Eg5 silencing in vivo and suggests the great potential of Eg5 shRNA-expressing lipoplexes as a DNA-based RNAi therapeutics for cancer treatment. [ABSTRACT FROM AUTHOR]

Although siRNA-mediated downregulation technology has been highly successful in suppressing the expression of any disease-related gene, systemic delivery of siRNA for the clinical applications remains challenging, especially in the use of cancer therapy. DC-Chol/DOPE cationic liposomes as one of the most attractive vehicles for gene delivery have been widely exploited for transfection of siRNA into cells, but complexity of systemic delivery has allowed only their direct injection into local targets due to the formation of aggregations with negatively-charged blood components. Herein, we demonstrate the effects of PEGylation on DC-Chol/DOPE cationic liposomes for systemic siRNA delivery in cancer therapy. In contrast to non-PEGylated DC-Chol/DOPE-siRNA lipoplexes, PEGylated DC-Chol/DOPE-siRNA lipoplexes reduce the excretion by kidneys and scavenging in liver, prolonging the circulation time in vivo , and ultimately increase their preferential tumor accumulation. Therefore, systemic injection of PEGylated DC-Chol/DOPE liposomes loaded with siRNA against kinesin spindle protein (KSP) gene exhibited a high level of target gene silencing at tumor sites and substantial suppression of tumor growth. Furthermore, systemically administered PEGylated lipoplexes did not lead to any activation of innate immune responses in the immunocompetent mice. These results suggest the potential of PEGylated DC-Chol/DOPE liposomes as a systemic delivery carrier for siRNA-mediated cancer therapy. [ABSTRACT FROM AUTHOR]

A pyrene-appended naphthalimide-dipicolylamine was developed as a ratiometric fluorescent probe for Zn 2+ ions. This probe displayed a ratiometric change in the fluorescent intensities at 385 and 530 nm corresponding to the emissions of pyrene and naphthalimide units for Zn 2+ over other metal ions, allowing for a precise quantitative analysis of the Zn 2+ ion. The fluorescent color change was also visualized from blue to green. We demonstrated that probe recognized Zn 2+ ions based on a 1:1 stoichiometric binding event and it showed a high sensitivity (limit of detection: 10.5 nM) and a rapid detection time for the Zn 2+ ion. In addition, the ratiometric change was found to be highly selective for the Zn 2+ ions even in the existence of other competitive metal ions including Cd 2+ , Pb 2+ , Hg 2+ , Ni 2+ , Co 2+ and Cu 2+ ions. Moreover, this probe was able to detect Zn 2+ ion in a wide pH range of 4–11 and it could be efficiently recycled by treating ethylenediaminetetraacetic acid (EDTA). Furthermore, this probe was successfully utilized for measurement of Zn 2+ concentration contained in drug commercially available zinc supplement. [ABSTRACT FROM AUTHOR]

A naphthalimide-indoline hybrid ( 1 ) was developed as a pH-sensitive turn-on fluorescent probe. Probe 1 displays a weak fluorescence intensity in pH span of 2.5–11.0 owing to a photo-induced electron transfer (PET) from the indoline moiety to the naphthalimide. However, the PET process is suppressed under the pH of 2.5, showing a strong fluorescence signal at 430 nm. The turn-on fluorescent change of 1 is selective for the acidity (H + ) over other anions, metal ions, redox species and it displays a good reversibility. Moreover, glass TLC plates coated with probe 1 can readily detect acid vapors at an ambient atmosphere. [ABSTRACT FROM AUTHOR]

An oxyfluoride glass-ceramic containing Eu2+-doped nepheline and LaF 3 crystals was synthesized with varying compositions to modify its color conversion and quantum efficiency under ultra-violet light emitting diode (UV-LED) excitation. Glass composing elements such as SiO 2 , Na 2 O and Al 2 O 3 were exchanged with LaF 3 to influence the formation of nepheline crystals within the glass matrix. Among the various combinations, when Al 2 O 3 was replaced by LaF 3 there was improvement in the observed emission intensity and photo-luminescence quantum yield (PL-QY). The optimum composition of Al 2 O 3 and LaF 3 content was investigated to improve PL-QY. X-ray diffractometer (XRD) was used to monitor structural changes in the crystals within the glass-ceramic. A white LED, with a high color rendering index (CRI) comparable to commercial white LEDs, was successfully demonstrated using the modified glass-ceramic as a color converter in structures of phosphor in silicone and phosphor in glass. • Oxyfluoride glass ceramic containing Eu2+-doped nepheline was fabricated. • PL-QY was improved by the modification of glass ceramic composition. • Phosphor in glass and phosphor in silicone were composed with the glass ceramic. • White LED with high CRI up to 85 was successfully achieved. [ABSTRACT FROM AUTHOR]

BaF 2 –Al 2 O 3 –B 2 O 3 –SiO 2 glasses and glass-ceramics doped with Eu3+-Tb3+ were fabricated as an inorganic color converter for white LEDs. The BaF 2 –Al 2 O 3 –B 2 O 3 glass composition was modified by adding SiO 2 , and thermal and mechanical stability improved with increasing SiO 2 content while maintaining a quantum yield (QY) as high as 91%. To realize white color coordinates, Tm3+ was additionally introduced at varying contents, and Eu3+ content was also controlled. Excellent chromatic properties, such as a pure white color coordinates (x = 0.33, y = 0.33) with a co-related color temperature of 5772K, and a color rendering index (CRI) of 91 under 370 nm excitation, were successfully achieved. After the glass was heat-treated at 600 °C to fabricate a glass ceramic, the glass-ceramics were mounted on top of a 370 nm UV-LED, successfully demonstrating a white LED with nearly pure white color coordinates and a high CRI of 86. The increased emission intensity in the glass-ceramic was attributed to the formation of BaF 2 crystals which were investigated by X-ray diffractometer (XRD) and a transmission electron microscope with energy dispersive spectroscopy (TEM-EDS). • Glass composition was modified to improve mechanical and thermal properties. • Tm3+ ions were additionally doped for blue emission under UV light. • Tb-Eu-Tm contents were adjusted to make a white color coordinate. • Emission intensity was improved with heat treatment at 600 °C for 10hrs due to form the BaF 2 crystal. • White color coordinate (0.36, 0.36) was successfully achieved with high CRI of 85 under 370 nm UV LED chip. [ABSTRACT FROM AUTHOR]

• Academic resilience of a previous time point affects resilience at a later time • Emotional engagement of a previous time point affects engagement at a later time • Academic resilience predicted emotional engagement of EWPS Project participants • Emotional engagement did not predict academic resilience Rapid economic growth in Korean society has widened the social and educational gaps among children. This study examines the reciprocal relationship between academic resilience and emotional engagement and the effect of participation in Korea's Educational Welfare Priority Project from a longitudinal perspective. Elementary and middle schools were studied for three years (2015–2017), with 820 students involved in the first year, 911 in the second, and 837 in the third. The results show that academic resilience predicted emotional engagement at a later time point only for project participants, but emotional engagement did not predict academic resilience. This study reveals the importance of psychological resources, such as academic resilience, for disadvantaged students and has implications for educational welfare policies. [ABSTRACT FROM AUTHOR]

A method based on the hydrogen/deuterium isotope effect is proposed to separate and quantify the effects of interface trap creation and oxide charge trapping on hot-carrier-induced degradation in n-channel metal-oxide-semiconductor field-effect transistors (MOSFETs). Hydrogenated and deuterated transistors were subjected to hot-carrier stress with a fixed drain voltage V[sub ds] and various gate voltages V[sub gs]. The threshold voltage V[sub t] and interface trap density N[sub it] were recorded as a function of stress time. It is found that at low V[sub gs] stress when equal numbers of interface traps are created, the shift of V[sub t] is larger in hydrogenated transistors than in deuterated transistors. Increasing V[sub gs] to 1/3V[sub ds] produces no noticeable difference of V[sub t] shift in these two kinds of transistors. However, further increasing V[sub gs] results in larger V[sub t] shift in deuterated transistors than in hydrogenated ones. From a quantitative analysis, the contribution of oxide charge trapping to V[sub t] shift is separated from the contribution of interface trap creation. The results suggest that interface trap creation is the dominant mechanism for hot-carrier-induced degradation in n-channel MOSFETs. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Although gas chromatography is the gold standard for detecting the persistent organic pollutant dichlorodiphenyltrichloroethane (DDT), a quick and easy alternative is needed to detect this highly toxic pesticide in food and household products. Therefore, we developed a monoclonal antibody (mAb)-based assay for the sensitive detection of DDT. The mAb used in our assay demonstrated favourable binding affinity in the nanomolar range against 2,2-bis(4-chlorophenyl)acetic acid (DDA), a DDT analogue, which is considered higher than commercially developed antibodies. By optimizing the assay conditions, we were able to detect DDT and its closely related compounds, including dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyldichloroethane (DDD), and isomeric impurities. Our dot blotting assay demonstrated a detection limit of 0.9 ng/mL for DDT. Using computational modelling, we predicted the structure of the mAb and its interaction with DDT. Overall, this study provides insights for engineering mAb with improved sensitivity, facilitates point-of-care detection of toxic chemicals, including DDT, and offers a vital method for food safety monitoring and environmental protection. [Display omitted] • A sensitive monoclonal Ab-based assay detecting DDT and its derivatives is reported. • A detection limit of 0.9 ng/mL was demonstrated for DDT. • DDT spiked in milk and various juice samples was successfully quantified. • The antibody structure and its interaction with DDT were predicted. • This assay can be practically used to monitor potential DDT contamination in food. [ABSTRACT FROM AUTHOR]

Drawing on various studies, we provide a holistic view incorporating different nested cultural contexts, organizational shame, and health outcomes. We introduce the concept of organizational shame and explain its two key domains: conformity and status/competition. Then, we comprehensively review prior studies on cultural approaches to shame and propose our cultural variance model of organizational shame. Our model illustrates an equilibrium, exhibiting dominant and stable patterns of shame domains formed by reinforcing relationships among three key nested contextual layers: individuals (workers), organizations (firms), and the labor market. We apply our model to discuss general and occupational implications and outline future research directions. Thus, we hope to conceptualize organizational shame within the dynamic contexts of organizations and cultures. [ABSTRACT FROM AUTHOR]

Deals with a study which proposed an alternative interpretation of hot electron interface degradation in n-metal-oxide semiconductor (NMOS) field-effect transistors. Background information on NMOS degradation; Focus of other studies; Experimental results; Conclusion.

Provides information on a study which investigated the effect of deuterium sintering for reliability lifetime improvement of complementary metal oxide semiconductors transistors with nitride sidewall spacers. Experimental framework of the study; Results and discussion; Conclusions.

Compared to the significant development of creativity studies, individual creativity research has not reached a meaningful consensus regarding the most valid and reliable method for assessing individual creativity. This study revisited 2 of the most popular methods for assessing individual creativity: subjective and objective methods. This study analyzed 1,500 individuals to investigate whether the methods for assessing individual creativity affect the measurement outcomes of individual creativity. Findings indicated that subjective assessments have a smaller variance a higher mean and a moderate but significant correlation with objective assessment methods. Such differences can be motivated by social desirability, consistency motif, illusory superiority, and leniency biases. Based on these findings, this study highlighted the need to acknowledge how subjective and objective assessment methods may affect individual creativity assessment outcomes. [ABSTRACT FROM PUBLISHER]

Precise switchover of numerous resistance states is desirable to achieve repeatable multilevel data storage memory windows. However, this could be hindered by the inherent random nature of oxygen vacancy creation. In this study, oxygen-deficient CeO 2− x thin films were fabricated on indium tin oxide (ITO)-coated/glass substrates using radio-frequency magnetron sputtering at room temperature to obtain simple Ni/CeO 2− x /ITO/glass devices. Multilevel bipolar resistive switching characteristics were investigated by controlling the RESET voltage and current compliance. The device could be regarded as four-level switching memory, controlled by the RESET voltage. An increase in the RESET-stop voltage from −1.5 to −2.0 V increased the Schottky barrier height, leading to an improvement in the ON/OFF ratio. The multilevel resistive switching behavior could be attributed to the formation and partial rupture of conductive filaments owing to interfacial oxygen ion migration. This study shows the potentials of the Ni/CeO 2− x /ITO/glass devices for multilevel data storage resistive random-access memory applications. Unlabelled Image • Oxygen deficient CeO 2-x film is deposited on ITO coated/glass substrate using rf-magnetron sputtering at room temperature. • Multilevel bipolar resistive switching are investigated by controlling the RESET-voltage and current compliance. • Device demonstrated four level switching memory that could be determined by controlling RESET-voltage. • By increasing the RESET-stop voltage from −1.5 to −2.0 V will increases the Schottky barrier height. [ABSTRACT FROM AUTHOR]

By introducing a thin non-stoichiometric CeO2-x switching layer between the high oxygen affinity metal TaN top electrode and the TiO2 layer in a TaN/CeO2-x/TiO2/Pt bilayer (BL) device, it is possible to enhance the endurance characteristics and overcome the reliability issue. Compared with a single layer device, a BL device significantly enhances the number of direct current overswitching cycles to >1.2 × 104, non-destructive retention (>104 s), and switching uniformity. A TaON interface layer is formed which served as a reservoir of oxygen ions (O2−) in the SET-process and acts as an O2− supplier to refill the oxygen vacancies in the RESET-process and so plays a key role in the formation and rupture of conductive filaments. This study demonstrates that simply introducing a thin non-stoichiometric CeO2-x switching layer into TiO2-based devices can facilitate the enhancement of the endurance property for future nonvolatile memory applications. [ABSTRACT FROM AUTHOR]

In this letter, we report the coexistence of unipolar and bipolar switching in a solution-based nanocrystalline spinel ferrite ZnFe2O4 thin film prepared by the sol-gel method. It is seen that the Au/ZnFe2O4/Pt device could be activated between unipolar and bipolar switching modes just by choosing RESET-voltage polarity. Conversions between unipolar to bipolar switching modes are reversible and controllable. The results show that the SET-voltage of unipolar switching is smaller than that of bipolar switching, while memory windows (ON/OFF ratio) are identical. Furthermore, filaments are induced by the migration of oxygen vacancies (VOs), which are responsible for reducing variations in SET voltages of unipolar switching. By analyzing the current transport conduction mechanism, the electrode-limited Schottky emission mechanism is dominated in the high field region. Temperature dependence of low and high resistance states indicates that conductive filaments are composed of VOs and metallic Zn atoms, involving Joule heating and electrochemical redox reaction effects. Investigation on coexisting both unipolar and bipolar switching modes in a single Au/ZnFe2O4/Pt memory cell would open a pathway for spinel ferrite based low-cost nonvolatile memory. [ABSTRACT FROM AUTHOR]

Theranostic systems are receiving ever-increasing attention due to their potential therapeutic utility, imaging enhancement capability, and promise for advancing the field of personalized medicine, particularly as it relates to the diagnosis, staging, and treatment of cancer. In this Tutorial Review, we provide an introduction to the concepts of theranostic drug delivery effected via use of conjugates that are able to target cancer cells selectively, provide cytotoxic chemotherapeutics, and produce readily monitored imaging signals in vitro and in vivo. The underlying design concepts, requiring the synthesis of conjugates composed of imaging reporters, masked chemotherapeutic drugs, cleavable linkers, and cancer targeting ligands, are discussed. Particular emphasis is placed on highlighting the potential benefits of fluorogenic reaction-based targeted systems that are activated for both imaging and therapy by cellular entities, e.g., thiols, reactive oxygen species and enzymes, which are present at relatively elevated levels in tumour environments, physiological characteristics of cancer, e.g., hypoxia and acidic pH. Also discussed are systems activated by an external stimulus, such as light. The work summarized in this Tutorial Review will help define the role fluorogenic reaction-based, cancer-targeting theranostics may have in advancing drug discovery efforts, as well as improving our understanding of cellular uptake and drug release mechanisms. [ABSTRACT FROM AUTHOR]

Hydrazide-linked naphthalimides undergo copper ion-selective hydrolysis with concomitant ratiometric fluorescence change. In addition, probe 1 is biocompatible and mainly localized to the endoplasmic reticulum (ER) in live HeLa cells. It thus can be used for imaging copper accumulation in the ER of live cells, as implied in copper-overloaded situations. [ABSTRACT FROM AUTHOR]

Despite the high potency of bilirubin as an endogenous anti-inflammatory compound, its clinical translation has been hampered because of its insolubility in water. Bilirubin-based nanoparticles that may overcome this critical issue are presented. A polyethylene glycol compound (PEG) was covalently attached to bilirubin, yielding PEGylated bilirubin (PEG-BR). The PEG-BR self-assembled into nanoscale particles with a size of approximately 110 nm, termed bilirubin nanoparticles (BRNPs). BRNPs are highly efficient hydrogen peroxide scavengers, thereby protecting cells from H2O2-induced cytotoxicity. In a murine model of ulcerative colitis, intravenous injection of BRNPs showed preferential accumulation of nanoparticles at the sites of inflammation and significantly inhibited the progression of acute inflammation in the colon. Taken together, BRNPs show potential for use as a therapeutic nanomedicine in various inflammatory diseases. [ABSTRACT FROM AUTHOR]

Despite the high potency of bilirubin as an endogenous anti-inflammatory compound, its clinical translation has been hampered because of its insolubility in water. Bilirubin-based nanoparticles that may overcome this critical issue are presented. A polyethylene glycol compound (PEG) was covalently attached to bilirubin, yielding PEGylated bilirubin (PEG-BR). The PEG-BR self-assembled into nanoscale particles with a size of approximately 110 nm, termed bilirubin nanoparticles (BRNPs). BRNPs are highly efficient hydrogen peroxide scavengers, thereby protecting cells from H2O2-induced cytotoxicity. In a murine model of ulcerative colitis, intravenous injection of BRNPs showed preferential accumulation of nanoparticles at the sites of inflammation and significantly inhibited the progression of acute inflammation in the colon. Taken together, BRNPs show potential for use as a therapeutic nanomedicine in various inflammatory diseases. [ABSTRACT FROM AUTHOR]

Due to paleoparasitology's relatively late beginnings, the fundamental data necessary for any reasonably complete understanding of parasitic infection patterns in Korean history remains insufficient. Especially with respect to ancient samples dating to before the Joseon Dynasty (1392–1910 CE), few cases have been analyzed by parasitological techniques. In the present study, we therefore undertook a series of paleoparasitological examinations of archaeological samples from the ancient Silla Kingdom (57 BCE–935 CE). Specifically, in soil samples obtained from shell midden and mountain top fortress sites, we observed Ascaris lumbricoides , Trichuris trichiura , Dicrocoelid and Taenia sp. eggs. The results of our current investigation of strata and samples from the prosperous first-millennium era of the Silla Kingdom are encouraging for a comprehensive understanding of the parasitic infection patterns in the earlier days of Korean history that could not be obtained by any previous studies. [ABSTRACT FROM AUTHOR]

Abstract: Targeted delivery of anticancer drugs to tumors has attracted considerable research interest because of its potential to reduce adverse toxicity while improving therapeutic efficacy. In this study, we synthesized and evaluated the therapeutic efficacy of a conjugate of a high-affinity peptide (aptide) and the anticancer drug docetaxel (DTX). A fibronectin extra domain B (EDB)-specific aptide (APTEDB) was used as a cancer-specific targeting ligand. An APTEDB–DTX conjugate was synthesized from an alkyne-modified aptide and azide-modified DTX via click chemistry. A microscopy study revealed selective binding of dye-labeled APTEDB to EDB-overexpressing cancer cells. The cytotoxicity of the conjugate toward EDB-overexpressing murine lung carcinoma (LLC) and human glioblastoma (U87MG) was similar to that of free DTX. In a pharmacokinetic study, APTEDB–DTX formulated with PEG400/ethanol(5%) exhibited a circulation half-life similar to that of a Tween-80/ethanol formulation of parent DTX. Finally, an evaluation of intravenously injected APTEDB–DTX in mice bearing EDB-positive tumors showed that APTEDB–DTX inhibited the growth of both LLC allograft and U87MG xenograft tumors with an efficacy better than the parent-DTX formulation but with much lower toxicity, as evidenced by reduced body weight loss. Taken together, these results indicate that the aptide–drug conjugate system described here may hold potential as a targeted therapy regimen. [Copyright &y& Elsevier]

The threshold energy barrier for hydrogen desorption from the SiO[sub 2]-Si interface has been assumed to be the Si-H bond energy with the value of 3.6 eV. Based on the uniform Si-H bond energy and diffusion-limited degradation, the time-dependent hot-carrier degradation of metal-oxide-semiconductor (MOS) devices has been described by the so-called power law. In this letter, by investigating the degradation of submicron n-channel MOS devices at various stress conditions and over a large time scale (0.01-10000 s), we present experimental evidence that contradicts the uniform bond energy theory and supports the bond energy variation theory proposed recently by Hess and co-workers [Appl. Phys. Lett. 75, 3147 (1999); Physica B 272, 527 (1999)]. We find that, instead of a constant power factor of n=0.5 predicted by the uniform bond/diffusion-limited energy theory, n varies from ∼0.8 at the initial stress stage to ∼0.2 at the final stress stage consistent with the bond energy variation theory. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The deuterium isotope effect has been widely demonstrated to improve hot-carrier reliability in metal-oxide-semiconductor transistors. Most of the interface traps, however, may have been passivated by hydrogen before the final deuterium anneal due to the ubiquitous presence of hydrogen in modern complementary metal-oxide-semiconductor processing technology. Therefore, effective deuteration requires both deuterium diffusion to the SiO[sub 2]-Si interface and displacement of the previously bonded hydrogen. We have introduced a "prestress" process in which hydrogen is depassivated before deuterium annealing. We found that the prestressed transistors are more robust to hot-carrier stress than control transistors without the prestress. We have also found that the replacement of hydrogen with deuterium is the rate-limiting step for deuterium incorporation at the SiO[sub 2]-Si interface. With the prestress, a lower deuterium annealing temperature can be applied without compromising the reliability improvement. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

• A mitochondria-targetable fluorogenic quinone dehydrogenase chemosensor was developed. • Probe consists of the mitochondria-targetable trimethyl lock quinone (TLQ)-linked hemicyanine. • This exhibited fluorescence Off-On and visual color change from yellow to orange. • Probe underwent a fluorogenic reaction through a quinone reduction-sensitive electron transport chain (ETC). • Probe could be used to detect the mitochondrial ETC in the live cells. A trimethyl lock quinone (TLQ)-linked hemicyanine (probe 1) is developed for imaging mitochondrial dehydrogenase activity in the live human cells. In aqueous environment, the system underwent a fluorogenic reduction of TLQ moiety upon incubation with human recombinant NQO1, providing a fluorescence Off-On with a concomitant visual color change from yellow to orange. In contrast to other TLQ-based fluorescent probes, probe 1 is localized to the mitochondria of living cells where little NQO1 exist. And, it can provide a fluorescence turn-on response which was selectively modulated by antimycin A and myxothiazol, a potent inhibitor of the complex III in the electron transfer chain and showed poor response to dicoumarol, a potent inhibitor of NQO1. Likely, probe 1 acts as a fluorogenic chemosensor for the mitochondrial electron transferring reaction in the live cells. [ABSTRACT FROM AUTHOR]

We investigated the effects of the Gibbs free energy difference (∆G o ) and distribution of oxygen vacancies in a bilayer ZnO/ZrO 2 structure. The device exhibited high endurance characteristics of up to 1000 DC repetitive resistive cycles, long retention (104), and a low coefficient of variation of SET and RESET-voltages (6% and 5%, respectively). In addition, X-ray photoelectron spectroscopy (XPS) analysis of the ZnO and ZrO 2 layers indicated that the oxygen vacancies/defects in the ZnO layer (44.13%) were larger than in the ZrO 2 layer (34.11%), and that the oxygen ions of O Zr (65.89%) were larger than those of O Zn (55.87). This XPS analysis confirmed that the differing oxygen vacancy distributions in the ZnO/ZrO 2 layer are responsible for improving the switching performance. The switching behavior, endurance, and retention time strongly depend on the types of electrode and switching materials used. We obtained qualitative and quantitative evidence that ∆G o of the oxide materials plays a significant role in determining the resistive switching characteristics. Bipolar switching mechanisms are explained by considering ∆G o in the ZnO and ZrO 2 layers, where the formation and rupture of conductive filaments are caused by oxygen vacancies. Our findings suggest that a bilayer ZnO/ZrO 2 structure is promising for application to non-volatile memory. • Effects of Gibbs free energy difference and oxygen vacancies distribution in a bilayer ZnO/ZrO 2 structure are studied. • High endurance characteristics of up to 1000 cycles, long data retention (104), and a lower variation are demonstrated • XPS conforms the different oxygen vacancies distribution in two layers are responsible for improving the switching. • Bipolar resistive switching mechanisms are explained by considering Gibbs free energy of ZnO and ZrO 2 layers. [ABSTRACT FROM AUTHOR]